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1. Use of oral moist tobacco (snus) in puberty and its association with asthma in the population-based RHINESSA study

Author

Torben Sigsgaard, Vivi Schlünssen, Mathias Holm, Cecilie Svanes, Christer Janson, Simone Accordini, Andrei Malinovschi, Anna Oudin, Randi Jacobsen Bertelsen, Francisco Javier Callejas, Nils Oskar Jõgi, Juan Pablo López-Cervantes, Elin Helga Thorarinsdottir, Chamara Senaratna, and Karl A Franklin

Subjects
Medicine, Diseases of the respiratory system, RC705-779
Abstract

Objectives To investigate the association of early snus use initiation (≤15 years of age) with asthma and asthma symptoms.Design Cross-sectional analysis of a population-based cohort.Setting Study centres in Norway, Sweden, Iceland, Denmark and Estonia, from 2016 to 2019.Participants 9002 male and female participants above 15 years of age of the Respiratory Health in Northern Europe, Spain and Australia study.Main outcome measures Current asthma and asthma symptoms.Results The median age of study participants was 28 years (range 15–53) and 58% were women. 20% had used snus, 29% men and 14% women. Overall, 26% of males and 14% of females using snus started ≤15 years of age. Early snus use initiation was associated with having three or more asthma symptoms (OR 2.70; 95% CI 1.46 to 5.00) and a higher asthma symptom score (β-coefficient (β) 0.35; 95% CI 0.07 to 0.63) in women. These associations were weak in men (OR 1.23; 95% CI 0.78 to 1.94; β 0.16; 95% CI −0.06 to 0.38, respectively). There was evidence for an association of early snus initiation with current asthma (OR 1.72; 95% CI 0.88 to 3.37 in women; OR 1.31; 95% CI 0.84 to 2.06 in men). A sensitivity analysis among participants without smoking history showed stronger estimates for all three outcomes, in both men and women, statistically significant for three or more asthma symptoms in women (OR 3.28; 95% CI 1.18 to 9.10). Finally, no consistent associations with asthma outcomes were found for starting snus after age 15 years.Conclusions Snus initiation in puberty was associated with higher likelihood of asthma and asthma symptoms, with the highest estimates in females and those without smoking history. These results raise concerns about the health adversities of early snus initiation and emphasise the need for public health initiatives to protect young people from this tobacco product.

Published
2024
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2. Early life exposures contributing to accelerated lung function decline in adulthood – a follow-up study of 11,000 adults from the general populationResearch in context

Author

Jorunn Kirkeleit, Trond Riise, Mathias Wielscher, Simone Accordini, Anne-Elie Carsin, Julie Dratva, Karl A. Franklin, Judith Garcia-Aymerich, Deborah Jarvis, Benedicte Leynaert, Caroline J. Lodge, Francisco Gomez Real, Vivi Schlünssen, Angelo Guido Corsico, Joachim Heinrich, Matthias Holm, Christer Janson, Bryndis Benediktsdóttir, Rain Jogi, Shyamali C. Dharmage, Marjo-Riitta Järvelin, and Cecilie Svanes

Subjects
Lung function, FVC, FEV1, FEV1/FVC ratio, Accelerated decline, Early life risk factors, Medicine (General), R5-920
Abstract

Summary: Background: We aimed to assess whether exposure to risk factors in early life from conception to puberty continue to contribute to lung function decline later in life by using a pooled cohort comprising approx. 11,000 adults followed for more than 20 years and with up to three lung function measurements. Methods: Participants (20–68 years) in the ECRHS and NFBC1966 cohort studies followed in the periods 1991–2013 and 1997–2013, respectively, were included. Mean annual decline in maximum forced expired volume in 1 s (FEV1) and forced vital capacity (FVC) were main outcomes. Associations between early life risk factors and change in lung function were estimated using mixed effects linear models adjusted for sex, age, FEV1, FVC and height at baseline, accounting for personal smoking. Findings: Decline in lung function was accelerated in participants with mothers that smoked during pregnancy (FEV1 2.3 ml/year; 95% CI: 0.7, 3.8) (FVC 2.2 ml/year; 0.2, 4.2), with asthmatic mothers (FEV1 2.6 ml/year; 0.9, 4.4) (FEV1/FVC 0.04 per year; 0.04, 0.7) and asthmatic fathers (FVC 2.7 ml/year; 0.5, 5.0), and in women with early menarche (FVC 2.4 ml/year; 0.4, 4.4). Personal smoking of 10 pack-years contributed to a decline of 2.1 ml/year for FEV1 (1.8, 2.4) and 1.7 ml/year for FVC (1.3, 2.1). Severe respiratory infections in early childhood were associated with accelerated decline among ever-smokers. No effect-modification by personal smoking, asthma symptoms, sex or cohort was found. Interpretation: Mothers’ smoking during pregnancy, parental asthma and early menarche may contribute to a decline of FEV1 and FVC later in life comparable to smoking 10 pack-years. Funding: European Union's Horizon 2020; Research Council of Norway; Academy of Finland; University Hospital Oulu; European Regional Development Fund; Spanish Ministry of Science and Innovation; Generalitat de Catalunya.

Published
2023
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3. Impact of long-term exposure to ambient ozone on lung function over a course of 20 years (The ECRHS study): a prospective cohort study in adultsResearch in context

Author

Tianyu Zhao, Iana Markevych, Elaine Fuertes, Kees de Hoogh, Simone Accordini, Anne Boudier, Lidia Casas, Bertil Forsberg, Judith Garcia Aymerich, Marco Gnesi, Mathias Holm, Christer Janson, Deborah Jarvis, Ane Johannessen, Rudolf A. Jörres, Stefan Karrasch, Benedicte Leynaert, José Antonio Maldonado Perez, Andrei Malinovschi, Jesús Martínez-Moratalla, Lars Modig, Dennis Nowak, James Potts, Nicole Probst-Hensch, José Luis Sánchez-Ramos, Valerie Siroux, Isabel Urrutia Landa, Danielle Vienneau, Simona Villani, Bénédicte Jacquemin, and Joachim Heinrich

Subjects
Air pollution, NDVI, Spirometry, Vital capacity, Forced expiratory volume, Middle aged, Public aspects of medicine, RA1-1270
Abstract

Summary: Background: While the adverse effects of short-term ambient ozone exposure on lung function are well-documented, the impact of long-term exposure remains poorly understood, especially in adults. Methods: We aimed to investigate the association between long-term ozone exposure and lung function decline. The 3014 participants were drawn from 17 centers across eight countries, all of which were from the European Community Respiratory Health Survey (ECRHS). Spirometry was conducted to measure pre-bronchodilation forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) at approximately 35, 44, and 55 years of age. We assigned annual mean values of daily maximum running 8-h average ozone concentrations to individual residential addresses. Adjustments were made for PM2.5, NO2, and greenness. To capture the ozone-related change in spirometric parameters, our linear mixed effects regression models included an interaction term between long-term ozone exposure and age. Findings: Mean ambient ozone concentrations were approximately 65 μg/m³. A one interquartile range increase of 7 μg/m³ in ozone was associated with a faster decline in FEV1 of −2.08 mL/year (95% confidence interval: −2.79, −1.36) and in FVC of −2.86 mL/year (−3.73, −1.99) mL/year over the study period. Associations were robust after adjusting for PM2.5, NO2, and greenness. The associations were more pronounced in residents of northern Europe and individuals who were older at baseline. No consistent associations were detected with the FEV1/FVC ratio. Interpretation: Long-term exposure to elevated ambient ozone concentrations was associated with a faster decline of spirometric lung function among middle-aged European adults over a 20-year period. Funding: German Research Foundation.

Published
2023
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4. Residential greenspace and lung function decline over 20 years in a prospective cohort: The ECRHS study

Author

Iana Markevych, Tianyu Zhao, Elaine Fuertes, Alessandro Marcon, Payam Dadvand, Danielle Vienneau, Judith Garcia Aymerich, Dennis Nowak, Kees de Hoogh, Deborah Jarvis, Michael J. Abramson, Simone Accordini, Andre FS Amaral, Hayat Bentouhami, Randi Jacobsen Bertelsen, Anne Boudier, Roberto Bono, Gayan Bowatte, Lidia Casas, Shyamali C Dharmage, Bertil Forsberg, Thorarinn Gislason, Marco Gnesi, Mathias Holm, Benedicte Jacquemin, Christer Janson, Rain Jogi, Ane Johannessen, Dirk Keidel, Benedicte Leynaert, José Antonio Maldonado Perez, Pierpaolo Marchetti, Enrica Migliore, Jesús Martínez-Moratalla, Hans Orru, Isabelle Pin, James Potts, Nicole Probst-Hensch, Andrea Ranzi, José Luis Sánchez-Ramos, Valerie Siroux, David Soussan, Jordi Sunyer, Isabel Urrutia Landa, Simona Villani, and Joachim Heinrich

Subjects
Green space, Nature, Spirometry, FEV1, FVC, ECRHS, Environmental sciences, GE1-350
Abstract

Background: The few studies that have examined associations between greenspace and lung function in adulthood have yielded conflicting results and none have examined whether the rate of lung function decline is affected. Objective: We explored the association between residential greenspace and change in lung function over 20 years in 5559 adults from 22 centers in 11 countries participating in the population-based, international European Community Respiratory Health Survey. Methods: Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were measured by spirometry when participants were approximately 35 (1990–1994), 44 (1999–2003), and 55 (2010–2014) years old. Greenness was assessed as the mean Normalized Difference Vegetation Index (NDVI) in 500 m, 300 m, and 100 m circular buffers around the residential addresses at the time of lung function measurement. Green spaces were defined as the presence of agricultural, natural, or urban green spaces in a circular 300 m buffer. Associations of these greenspace parameters with the rate of lung function change were assessed using adjusted linear mixed effects regression models with random intercepts for subjects nested within centers. Sensitivity analyses considered air pollution exposures. Results: A 0.2-increase (average interquartile range) in NDVI in the 500 m buffer was consistently associated with a faster decline in FVC (−1.25 mL/year [95% confidence interval: −2.18 to −0.33]). These associations were especially pronounced in females and those living in areas with low PM10 levels. We found no consistent associations with FEV1 and the FEV1/FVC ratio. Residing near forests or urban green spaces was associated with a faster decline in FEV1, while agricultural land and forests were related to a greater decline in FVC. Conclusions: More residential greenspace was not associated with better lung function in middle-aged European adults. Instead, we observed slight but consistent declines in lung function parameters. The potentially detrimental association requires verification in future studies.

Published
2023
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5. Risk factors for colonization with multidrug-resistant Gram-negative bacteria and Clostridioides difficile in Long Term Care Facilities (LTCFs) residents: the evidence from 27 facilities in a high endemic setting

Author

Anna Maria Azzini, Giorgia Be, Laura Naso, Lorenza Lambertenghi, Nicola Duccio Salerno, Ilaria Coledan, Alda Bazaj, Massimo Mirandola, Jessica Miotti, Fulvia Mazzaferri, Simone Accordini, Giuliana Lo Cascio, and Evelina Tacconelli

Subjects
LTCF, colonization, ESBL, carbapenem-resistant, carbapenemase, C. difficile, Microbiology, QR1-502
Abstract

IntroductionResidency in LTCFs increases the likelihood of colonization with multidrug resistant Gram-negative bacteria (MDR-GNB). We assessed the prevalence and risk factors for enteric colonization by III-generation cephalosporins-resistant and carbapenem-resistant (CR) GNB in a large group of LTCFs in a high endemic setting. We also assessed the prevalence and risk factors for C. difficile colonization.MethodsA point prevalence survey with rectal screening (RS) was conducted in 27 LTCFs in north Italy. Epidemiological and clinical variables on the survey day, history of hospitalization and surgery within one year, and antibiotics within three months, were collected. The presence of III-generation cephalosporin resistant and CR GNB was assessed using a selective culture on chromogenic medium and PCR for carbapenemase detection. The presence of C. difficile was assessed using ELISA for GDH and RT-PCR to identify toxigenic strains. Multi-variable analyses were performed using two-level logistic regression models.ResultsIn the study period 1947 RSs were performed. The prevalence of colonization by at least one GNB resistant to III-generation cephalosporin was 51% (E. coli 65%, K. pneumoniae 14% of isolates). The prevalence of colonization by CR GNB was 6%. 6% of all isolates (1150 strains) resulted in a carbapenem-resistant K. pneumoniae, and 3% in a carbapenem-resistant E. coli. KPC was the most frequent carbapenemase (73%) identified by PCR, followed by VIM (23%). The prevalence of colonization by C. difficile was 11.7%. The presence of a medical device (OR 2.67) and previous antibiotic use (OR 1.48) were significantly associated with III-generation cephalosporin resistant GNB colonization. The presence of a medical device (OR 2.67) and previous hospitalization (OR 1.80) were significantly associated with CR GNB. The presence of a medical device (OR 2.30) was significantly associated with C. difficile colonization. Main previously used antibiotic classes were fluoroquinolones (32% of previously treated subjects), III-generation cephalosporins (21%), and penicillins (19%).ConclusionAntimicrobial stewardship in LTCFs is a critical issue, being previous antibiotic treatment a risk factor for colonization by MDR-GNB. The prevalence of colonization by III-generation cephalosporin and CR GNB among LTCF residents also underlines the importance to adhere to hand hygiene indications, infection prevention and control measures, and environmental hygiene protocols, more achievable than rigorous contact precautions in this type of social setting.

Published
2023
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6. Subjects who developed SARS-CoV-2 specific IgM after vaccination show a longer humoral immunity and a lower frequency of infectionResearch in context

Author

Chiara Piubelli, Alessandra Ruggiero, Lucia Calciano, Cristina Mazzi, Concetta Castilletti, Natalia Tiberti, Sara Caldrer, Matteo Verzè, Silvia Stefania Longoni, Simone Accordini, Zeno Bisoffi, and Donato Zipeto

Subjects
SARS-CoV-2, COVID-19, BTN162b2 vaccine, IgG, IgM, Spike, Medicine, Medicine (General), R5-920
Abstract

Summary: Background: We have previously shown that eliciting SARS-CoV-2-specific IgM after vaccination is associated with higher levels of SARS-CoV-2 neutralizing IgG. This study aims to assess whether IgM development is also associated with longer-lasting immunity. Methods: We analysed anti-SARS-CoV-2 spike protein IgG and IgM (IgG-S, IgM-S), and anti-nucleocapsid IgG (IgG-N) in 1872 vaccinees at different time points: before the first dose (D1; w0), before the second dose (D2; w3) at three (w6) and 23 weeks (w29) after D2; moreover, 109 subjects were further tested at the booster dose (D3, w44), at 3 weeks (w47) and 6 months (w70) after D3. Two-level linear regression models were used to evaluate the differences in IgG-S levels. Findings: In subjects who had no evidence of a previous infection at D1 (non-infected, NI), IgM-S development after D1 and D2 was associated with higher IgG-S levels at short (w6, p

Published
2023
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7. Health impact assessment to predict the impact of tobacco price increases on COPD burden in Italy, England and Sweden

Author

Elaine Fuertes, Alessandro Marcon, Laura Potts, Giancarlo Pesce, Stefan K. Lhachimi, Virjal Jani, Lucia Calciano, Alex Adamson, Jennifer K. Quint, Debbie Jarvis, Christer Janson, Simone Accordini, and Cosetta Minelli

Subjects
Medicine, Science
Abstract

Abstract Raising tobacco prices effectively reduces smoking, the main risk factor for chronic obstructive pulmonary disease (COPD). Using the Health Impact Assessment tool “DYNAMO-HIA”, this study quantified the reduction in COPD burden that would occur in Italy, England and Sweden over 40 years if tobacco prices were increased by 5%, 10% and 20% over current local prices, with larger increases considered in secondary analyses. A dynamic Markov-based multi-state simulation modelling approach estimated the effect of changes in smoking prevalence states and probabilities of transitioning between smoking states on future smoking prevalence, COPD burden and life expectancy in each country. Data inputs included demographics, smoking prevalences and behaviour and COPD burden from national data resources, large observational cohorts and datasets within DYNAMO-HIA. In the 20% price increase scenario, the cumulative number of COPD incident cases saved over 40 years was 479,059 and 479,302 in Italy and England (populous countries with higher smoking prevalences) and 83,694 in Sweden (smaller country with lower smoking prevalence). Gains in overall life expectancy ranged from 0.25 to 0.45 years for a 20 year-old. Increasing tobacco prices would reduce COPD burden and increase life expectancy through smoking behavior changes, with modest but important public health benefits observed in all three countries.

Published
2021
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8. Cohort profile: the multigeneration Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) cohort

Author

Thorarinn Gislason, Torben Sigsgaard, Vivi Schlünssen, Joachim Heinrich, Jesús Martínez-Moratalla, Øistein Svanes, Mathias Holm, Bertil Forsberg, Dan Norbäck, Rain Jogi, Kjell Torén, Deborah Jarvis, Magnus Ekström, Adrian Lowe, Caroline J Lodge, Michael Abramson, Shyamali Dharmage, Kathrine Pape, Cecilie Svanes, Gita Mishra, Caroline Lodge, Lyle Gurrin, Bruce Thompson, Eva Lindberg, Christer Janson, Simone Accordini, Ane Johannessen, Bryndis Benediktsdottir, Karl Franklin, Andrei Malinovschi, Anna Oudin, Francisco Gómez Real, José Luis Sánchez-Ramos, Lennart Bråbäck, Torgeir Storaas, Shanshan Xu, Julia Dratva, John Holloway, Jorunn Kirkeleit, Christine Cramer, Gro Tjalvin, Anne Mette Lund Würtz, Randi Jacobsen Bertelsen, Oskar Jõgi, Signe Timm, Francisco Javier Callejas, Raúl Godoy, Trude Duelien Skorge, Christine Drengenes, Nils Oskar Jõgi, Maryia Khomich, Toril Mørkve Knudsen, Ingrid Kuiper, Juan Pablo López-Cervantes, Marianne Lønnebotn, Shokouh Makvandi-Nejad, Antonio Pérez, Anders Røsland, Rajesh Shigdel, Svein Magne Skulstad, Kai Triebner, Hilde Vindenes, Jose Luis Sanchez, Jose Maldonado, David Martino, Jennifer Perret, Lucia Calciano, William Horsnell, and Susanne Krauss-Etchmann

Subjects
Medicine
Published
2022
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9. SARS-CoV-2 vaccination elicits unconventional IgM specific responses in naïve and previously COVID-19-infected individuals

Author

Alessandra Ruggiero, Chiara Piubelli, Lucia Calciano, Simone Accordini, Maria Teresa Valenti, Luca Dalle Carbonare, Gabriel Siracusano, Nigel Temperton, Natalia Tiberti, Silvia Stefania Longoni, Massimo Pizzato, Silvia Accordini, Tobia Fantoni, Lucia Lopalco, Alberto Beretta, Zeno Bisoffi, and Donato Zipeto

Subjects
SARS-CoV-2, COVID-19, BTN162b2 vaccine, IgG, IgM, Spike, Medicine, Medicine (General), R5-920
Abstract

Summary: Background: Currently, evaluation of the IgG antibodies specific for the SARS-CoV-2 Spike protein following vaccination is used worldwide to estimate vaccine response. Limited data are available on vaccine-elicited IgM antibodies and their potential implication in immunity to SARS-CoV-2. Methods: We performed a longitudinal study to quantify anti-S SARS-CoV-2 IgG and IgM (IgG-S and IgM-S) in health care worker (HCW) recipients of the BNT162b2 vaccine. Samples were collected before administration (T0), at the second dose (T1) and three weeks after T1 (T2). The cohort included 1584 immunologically naïve to SARS-CoV-2 (IN) and 289 with history of previous infection (PI). Findings: IN showed three patterns of responses: (a) IgG positive/IgM negative (36.1%), (b) coordinated IgM-S/IgG-S responses appearing at T1 (37.4%) and (c) IgM appearing after IgG (26.3%). Coordinated IgM-S/IgG-S responses were associated with higher IgG titres. In IgM-S positive PI, 64.5% were IgM-S positive before vaccination, whereas 32% and 3.5% developed IgM-S after the first and second vaccine dose, respectively. IgM-S positive sera had higher pseudovirus neutralization titres compared to the IgM-S negative. Interpretation: Coordinated expression of IgG-S and IgM-S after vaccination was associated with a significantly more efficient response in both antibody levels and virus-neutralizing activity. The unconventional IgG-S positive/IgM-S negative responses may suggest a recruitment of cross coronaviruses immunity by vaccination, warranting further investigation. Funding: Italian Ministry of Health under “Fondi Ricerca Corrente”- L1P5 and “Progetto Ricerca Finalizzata COVID-2020-12371675”; FUR 2020 Department of Excellence 2018-2022, MIUR, Italy; The Brain Research Foundation Verona.

Published
2022
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10. Bronchodilator response and lung function decline: Associations with exhaled nitric oxide with regard to sex and smoking status

Author

Elisabet Nerpin, Diogenes Seraphim Ferreira, Joost Weyler, Vivi Schlunnsen, Rain Jogi, Chantal Raherison Semjen, Thorainn Gislasson, Pascal Demoly, Joachim Heinrich, Dennis Nowak, Angelo Corsico, Simone Accordini, Alessandro Marcon, Giulia Squillacioti, Mario Olivieri, Rune Nielsen, Ane Johannessen, Francisco Gómez Real, Judith Garcia -Aymerich, Isabel Urrutia, Antonio Pereira-Vega, Jose Antonio Gullón, Anna-Carin Olin, Bertil Forsberg, Össur Ingi Emilsson, Isabelle Pin, Deborah Jarvis, Christer Janson, and Andrei Malinovschi

Subjects
Bronchodilatation, Epidemiology, FeNO, Lung function, Immunologic diseases. Allergy, RC581-607
Abstract

Background: Fractional exhaled nitric oxide (FeNO) is a marker of type-2 inflammation used both to support diagnosis of asthma and follow up asthma patients. The associations of FeNO with lung function decline and bronchodilator (BD) response have been studied only scarcely in large populations. Objectives: To study the association between FeNO and a) retrospective lung function decline over 20 years, and b) lung function response to BD among asthmatic subjects compared with non-asthmatic subjects and with regards to current smoking and sex. Methods: Longitudinal analyses of previous lung function decline and FeNO level at follow-up and cross-sectional analyses of BD response and FeNO levels in 4257 participants (651 asthmatics) from the European Community Respiratory Health Survey. Results: Among asthmatic subjects, higher percentage declines of FEV1 and FEV1/FVC were associated with higher FeNO levels (p = 0.001 for both) at follow-up. These correlations were found mainly among non-smoking individuals (p = 0.001) and females (p = 0.001) in stratified analyses.Percentage increase in FEV1 after BD was positively associated with FeNO levels in non-asthmatic subjects. Further, after stratified for sex and smoking separately, a positive association was seen between FEV1 and FeNO levels in non-smokers and women, regardless of asthma status. Conclusions: We found a relationship between elevated FeNO and larger FEV1 decline over 20 years among subjects with asthma who were non-smokers or women. The association between elevated FeNO levels and larger BD response was found in both non-asthmatic and asthmatic subjects, mainly in women and non-smoking subjects.

Published
2021
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11. Lifelong exposure to air pollution and greenness in relation to asthma, rhinitis and lung function in adulthood

Author

Ingrid Nordeide Kuiper, Cecilie Svanes, Iana Markevych, Simone Accordini, Randi J. Bertelsen, Lennart Bråbäck, Jesper Heile Christensen, Bertil Forsberg, Thomas Halvorsen, Joachim Heinrich, Ole Hertel, Gerard Hoek, Mathias Holm, Kees de Hoogh, Christer Janson, Andrei Malinovschi, Alessandro Marcon, Roy Miodini Nilsen, Torben Sigsgaard, and Ane Johannessen

Subjects
Air pollution, Greenness, Asthma, Lung function, Rhinitis, Environmental sciences, GE1-350
Abstract

Objectives: To investigate if air pollution and greenness exposure from birth till adulthood affects adult asthma, rhinitis and lung function. Methods: We analysed data from 3428 participants (mean age 28) in the RHINESSA study in Norway and Sweden. Individual mean annual residential exposures to nitrogen dioxide (NO2), particulate matter (PM10 and PM2.5), black carbon (BC), ozone (O3) and greenness (normalized difference vegetation index (NDVI)) were averaged across susceptibility windows (0–10 years, 10–18 years, lifetime, adulthood (year before study participation)) and analysed in relation to physician diagnosed asthma (ever/allergic/non-allergic), asthma attack last 12 months, current rhinitis and low lung function (lower limit of normal (LLN), z-scores of forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and FEV1/FVC below 1.64). We performed logistic regression for asthma attack, rhinitis and LLN lung function (clustered with family and study centre), and conditional logistic regression with a matched case-control design for ever/allergic/non-allergic asthma. Multivariable models were adjusted for parental asthma and education. Results: Childhood, adolescence and adult exposure to NO2, PM10 and O3 were associated with an increased risk of asthma attacks (ORs between 1.29 and 2.25), but not with physician diagnosed asthma. For rhinitis, adulthood exposures seemed to be most important. Childhood and adolescence exposures to PM2.5 and O3 were associated with lower lung function, in particular FEV1 (range ORs 2.65 to 4.21). No associations between NDVI and asthma or rhinitis were revealed, but increased NDVI was associated with lower FEV1 and FVC in all susceptibility windows (range ORs 1.39 to 1.74). Conclusions: Air pollution exposures in childhood, adolescence and adulthood were associated with increased risk of asthma attacks, rhinitis and low lung function in adulthood. Greenness was not associated with asthma or rhinitis, but was a risk factor for low lung function.

Published
2021
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12. Physical activity and lung function-Cause or consequence?

Author

Annabelle Bédard, Anne-Elie Carsin, Elaine Fuertes, Simone Accordini, Shyamali C Dharmage, Vanessa Garcia-Larsen, Joachim Heinrich, Christer Janson, Ane Johannessen, Bénédicte Leynaert, José Luis Sánchez-Ramos, Gabriela P Peralta, Isabelle Pin, Giulia Squillacioti, Joost Weyler, Deborah Jarvis, and Judith Garcia-Aymerich

Subjects
Medicine, Science
Abstract

Concerns exist that the positive association of physical activity with better lung function, which has been suggested in previous longitudinal studies in smokers, is due to reverse causation. To investigate this, we applied structural equation modeling (SEM), an exploratory approach, and marginal structural modeling (MSM), an approach from the causal inference framework that corrects for reverse causation and time-dependent confounding and estimates causal effects, on data from participants in the European Community Respiratory Health Survey (ECRHS, a multicentre European cohort study initiated in 1991-1993 with ECRHS I, and with two follow-ups: ECRHS II in 1999-2003, and ECRHS III in 2010-2014). 753 subjects who reported current smoking at ECRHS II, with repeated data on lung function at ECRHS I, II and III, physical activity at ECRHS II and III, and potential confounders at ECRHS I and II, were included in the analyses. SEM showed positive associations between physical activity and lung function in both directions. MSM suggested a protective causal effect of physical activity on lung function (overall difference in mean β (95% CI), comparing active versus non-active individuals: 58 mL (21-95) for forced expiratory volume in one second and 83 mL (36-130) for forced vital capacity). Our results suggest bi-directional causation and support a true protective effect of physical activity on lung function in smokers, after accounting for reverse causation and time-dependent confounding.

Published
2020
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13. Pharmacological treatment of asthma in a cohort of adults during a 20-year period: results from the European Community Respiratory Health Survey I, II and III

Author

Christer Janson, Simone Accordini, Lucia Cazzoletti, Isa Cerveri, Sebastien Chanoine, Angelo Corsico, Diogenes Seraphim Ferreira, Judith Garcia-Aymerich, David Gislason, Rune Nielsen, Ane Johannessen, Rain Jogi, Andrei Malinovschi, Jesús Martinez-Moratalla Rovira, Alessandro Marcon, Isabelle Pin, Jennifer Quint, Valerie Siroux, Enrique Almar, Valeria Bellisario, Karl A. Franklin, José A. Gullón, Mathias Holm, Joachim Heinrich, Dennis Nowak, José Luis Sánchez-Ramos, Joost J. Weyler, Deborah Jarvis, The members of the ECRHS I scientific team., P. Burney, S. Chinn, C. Luczynska, D. Jarvis, E. Lai, P. Vermeire, H. Kesteloot, J. Bousquet, D. Nowak, J. Prichard, R. de Marco, B. Rijcken, J.M. Anto, J. Sunyer, J. Alves, G. Boman, N. Nielsen, P. Paoletti, M. Abramson, J. Kutin, F. van Bastelaer, R. Jõgi, A. Taytard, I. Pin, C. Pison, F. Neukirch, R. Liard, J. Knani, H-E. Wichmann, J. Heinrich, H. Magnussen, T. Gislason, D. Gislason, A. Marinoni, I. Cerveri, M. Bugiani, C. Bucca, C. Romano, L. Cascio, C. Campello, J. Droste, M. Kerkhof, A. Gulsvik, E. Omenaas, J. Martinez-Moratalla, E. Almar, A. Mateos, M. Arévalo, A. Sánchez, M. Vizcaya, X. Aguilar, A. Teixidó, J.M. Antó, M. Kogevinas, F. Burgos, J. Castellsagué, J. Roca, JB. Soriano, A. Tobías, N. Muiñozguren, J. Ramos González, A. Capelastegui, J. Maldonado Pérez, A. Pereira, J. Sánchez, J. Quiros, I. Huerta, F. Payo, N. Lindholm, P. Plaschke, C. Janson, E. Björnsson, L. Rosenhall, E. Norrman, B. Lundbäck, U. Ackermann-Liebrich, N. Küenzli, A. Perruchoud, M. Burr, J. Layzell, R. Hall, B. Harrison, The members of the ECRHS II scientific team., J. Knox, M. Wjst, N. Kuenzli, E.H. Walters, J. Raven, J. Weyler, M. van Sprundel, V. Nelen, A. Soon, C. Raherison, J. Ferran-Quentin, B. Leynaert, M. Zureik, P.J. Bousquet, C. Frye, I. Meyer, E. Bjornsson, K.B. Jörundsdóttir, S. Villani, M. Ponzio, F. Frigerio, M. Comelli, M. Grassi, A. Corsico, R. Bono, P. Piccioni, E. Caria, A. Carosso, E. Migliore, G. Castiglioni, G. Verlato, E. Zanolin, S. Accordini, A. Poli, V. Lo Cascio, M. Ferrari, I. Cazzoletti, C. Svanes, B. Laerum, J. Martinez-Moratalla Rovira, C. Boix, G. González, J.M. Ignacio García, J. Solera, J. Damián, J.P. Zock, X. Basagaña, A. Jaen, C. Acosta, N. Muñozguren, J. Ramos, I. Urrutia, U. Aguirre, J. Maldonado, J.L. Sanchez, A. de la Vega, L. Palenciano, J. Azofra, A. Cañada, K. Toren, L. Lillienberg, A.C. Olin, B. Balder, A. Pfeifer-Nilsson, R. Sundberg, D. Norback, G. Wieslander, M. Gunnbjornsdottir, M. Soderberg, K.A. Franklin, B. Lundback, B. Forsberg, L. Nystrom, B. Dibbert, M. Hazenkamp, M. Brutsche, D. Seaton, The members of the ECRHS III scientific team., M. Tumilty, J. Potts, T. Gislasson, T. Rochat, B. Leyneart, G. Benke, S. Dharmage, B. Thompson, S. Kaushik, M. Matheson, H. Bentouhami, H. Orru, P.O. Girodet, V. Siroux, J. Ferran, J.L. Cracowski, P. Demoly, A. Bourdin, I. Vachier, D. Soussan, D. Courbon, C. Neukirch, L. Alavoine, X. Duval, I. Poirier, E. Becker, G. Woelke, O. Manuwald, A-M. Kirsten, B. Benediktsdottir, E.S. Arnardottir, M. Clausen, G. Gudmundsson, L. Gudmundsdottir, H. Palsdottir, K. Olafsdottir, S. Sigmundsdottir, K. Bara-Jörundsdottir, A. Grosso, F. Albicini, E. Gini, E.M. Di Vincenzo, V. Ronzoni, F. Campanella, M. Gnesi, F. Manzoni, L. Rossi, O. Ferraro, R. Tassinari, V. Bellisario, G. Trucco, L. Calciano, L. Cazzoletti, A.M. Fratta Pasini, F. Locatelli, P. Marchetti, A. Marcon, E. Montoli, G. Nguyen, M. Olivieri, C. Papadopoulou, C. Posenato, G. Pesce, P. Vallerio, H.M. Boezen, A. Johannessen, T. Skorge, F. Gomez Real, S. García, A. Núñez, P. López, R. Sánchez, E. Mancebo, J-M. Antó, J. Garcia-Aymerich, A.E. Carsin, C. Sanjuas, S. Guerra, B. Jacquemin, P. Davdand Galdakao, S. Pascual, J. Antonio Maldonado, J.L. Sánchez, L. Palacios, N. Sánchez, M. Fernández, B. Robles, K. Torén, M. Holm, J-L. Kim, A-C. Olin, A. Dahlman-Höglund, L. Braback, L. Modig, B. Järvholm, K.A. Bertilsson, H. Franklin, C. Wahlgreen, B. Andersson, U. Spetz Nystrom, G.M. Bodinaa Lund, K. Nisser, N.M. Probst-Hensch, N. Künzli, D. Stolz, C. Schindler, J.M. Gaspoz, E. Zemp Stutz, M. Adam, C. Autenrieth, I. Curjuric, J. Dratva, A. Di Pasquale, R. Ducret-Stich, E. Fischer, L. Grize, A. Hensel, D. Keidel, A. Kumar, M. Imboden, N. Maire, A. Mehta, H. Phuleria, M. Ragettli, M. Ritter, E. Schaffner, G.A. Thun, A. Ineichen, T. Schikowski, M. Tarantino, M. Tsai, S. Kapur, R. Newson, N. Innes, and A. Wilson

Subjects
Medicine
Abstract

Asthma often remains uncontrolled, despite the fact that the pharmacological treatment has undergone large changes. We studied changes in the treatment of asthma over a 20-year period and identified factors associated with the regular use of inhaled corticosteroid (ICS) treatment. Changes in the use of medication were determined in 4617 randomly selected subjects, while changes in adults with persistent asthma were analysed in 369 participants. The study compares data from three surveys in 24 centres in 11 countries. The use of ICSs increased from 1.7% to 5.9% in the general population and the regular use of ICSs increased from 19% to 34% among persistent asthmatic subjects. The proportion of asthmatic subjects reporting asthma attacks in the last 12 months decreased, while the proportion that had seen a doctor in the last 12 months remained unchanged (42%). Subjects with asthma who had experienced attacks or had seen a doctor were more likely to use ICSs on a regular basis. Although ICS use has increased, only one-third of subjects with persistent asthma take ICSs on a regular basis. Less than half had seen a doctor during the last year. This indicates that underuse of ICSs and lack of regular healthcare contacts remains a problem in the management of asthma.

Published
2019
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14. The role of C-reactive protein levels on the association of physical activity with lung function in adults.

Author

Elaine Fuertes, Anne-Elie Carsin, Vanessa Garcia-Larsen, Stefano Guerra, Isabelle Pin, Bénédicte Leynaert, Simone Accordini, Jesús Martinez-Moratalla, Josep M Antó, Isabel Urrutia, Audrey Le Gouellec, Joachim Heinrich, Thorarinn Gislason, Rain Jõgi, Christer Janson, Debbie Jarvis, and Judith Garcia-Aymerich

Subjects
Medicine, Science
Abstract

ObjectiveRegular physical activity may be associated with improved lung function via reduced systemic inflammation, although studies exploring this mechanism are rare. We evaluated the role of C-reactive protein in blood, which is a common marker of systemic inflammation, on the association of physical activity with forced expiratory volume in one second and forced vital capacity.MethodsCross-sectional data on spirometry, C-reactive protein levels and self-reported physical activity (yes/no; ≥2 times and ≥1hr per week of vigorous physical activity) were available in the European Community Respiratory Health Survey (N = 2347 adults, 49.3% male, 28-56 years-old). A subsample was also assessed 10 years later using the International Physical Activity Questionnaire, and tertiles of Metabolic Equivalent of Task-minutes per week spent in vigorous, moderate and walking activities were calculated (N = 671, 49.6% male, 40-67 years-old). Adjusted cross-sectional mixed linear regression models and the "mediate" package in "R" were used to assess the presence of mediation.ResultsDespite positive significant associations between nearly all physical activity metrics with forced expiratory volume in one second and forced vital capacity, there was no evidence that C-reactive protein levels played a role. An influence of C-reactive protein levels was only apparent in the smaller subsample when comparing the medium to low tertiles of moderate activity (mean difference [95% CIs]: 21.1ml [5.2, 41.9] for forced expiratory volume in one second and 17.3ml [2.6, 38.0] for forced vital capacity).ConclusionsIn a population of adults, we found no consistent evidence that the association of physical activity with forced expiratory volume in one second or forced vital capacity is influenced by the level of C-reactive protein in blood.

Published
2019
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15. Time and age trends in smoking cessation in Europe.

Author

Giancarlo Pesce, Alessandro Marcon, Lucia Calciano, Jennifer L Perret, Michael J Abramson, Roberto Bono, Jean Bousquet, Alessandro G Fois, Christer Janson, Deborah Jarvis, Rain Jõgi, Bénédicte Leynaert, Dennis Nowak, Vivi Schlünssen, Isabel Urrutia-Landa, Giuseppe Verlato, Simona Villani, Torsten Zuberbier, Cosetta Minelli, Simone Accordini, and Ageing Lungs in European Cohorts (ALEC) study

Subjects
Medicine, Science
Abstract

BackgroundSmoking is the main risk factor for most of the leading causes of death. Cessation is the single most important step that smokers can take to improve their health. With the aim of informing policy makers about decisions on future tobacco control strategies, we estimated time and age trends in smoking cessation in Europe between 1980 and 2010.MethodsData on the smoking history of 50,228 lifetime smokers from 17 European countries were obtained from six large population-based studies included in the Ageing Lungs in European Cohorts (ALEC) consortium. Smoking cessation rates were assessed retrospectively, and age trends were estimated for three decades (1980-1989, 1990-1999, 2000-2010). The analyses were stratified by sex and region (North, East, South, West Europe).ResultsOverall, 21,735 subjects (43.3%) quit smoking over a total time-at-risk of 803,031 years. Cessation rates increased between 1980 and 2010 in young adults (16-40 years), especially females, from all the regions, and in older adults (41-60 years) from North Europe, while they were stable in older adults from East, South and West Europe. In the 2000s, the cessation rates for men and women combined were highest in North Europe (49.9 per 1,000/year) compared to the other regions (range: 26.5-32.7 per 1,000/year). A sharp peak in rates was observed for women around the age of 30, possibly as a consequence of pregnancy-related smoking cessation. In most regions, subjects who started smoking before the age of 16 were less likely to quit than those who started later.ConclusionsOur findings suggest an increasing awareness on the detrimental effects of smoking across Europe. However, East, South and West European countries are lagging behind North Europe, suggesting the need to intensify tobacco control strategies in these regions. Additional efforts should be made to keep young adolescents away from taking up smoking, as early initiation could make quitting more challenging during later life.

Published
2019
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16. Trends in smoking initiation in Europe over 40 years: A retrospective cohort study.

Author

Alessandro Marcon, Giancarlo Pesce, Lucia Calciano, Valeria Bellisario, Shyamali C Dharmage, Judith Garcia-Aymerich, Thorarinn Gislasson, Joachim Heinrich, Mathias Holm, Christer Janson, Deborah Jarvis, Bénédicte Leynaert, Melanie C Matheson, Pietro Pirina, Cecilie Svanes, Simona Villani, Torsten Zuberbier, Cosetta Minelli, Simone Accordini, and Ageing Lungs In European Cohorts study

Subjects
Medicine, Science
Abstract

BackgroundTobacco consumption is the largest avoidable health risk. Understanding changes of smoking over time and across populations is crucial to implementing health policies. We evaluated trends in smoking initiation between 1970 and 2009 in random samples of European populations.MethodsWe pooled data from six multicentre studies involved in the Ageing Lungs in European Cohorts consortium, including overall 119,104 subjects from 17 countries (range of median ages across studies: 33-52 years). We estimated retrospectively trends in the rates of smoking initiation (uptake of regular smoking) by age group, and tested birth cohort effects using Age-Period-Cohort (APC) modelling. We stratified all analyses by sex and region (North, East, South, West Europe).ResultsSmoking initiation during late adolescence (16-20 years) declined for both sexes and in all regions (except for South Europe, where decline levelled off after 1990). By the late 2000s, rates of initiation during late adolescence were still high (40-80 per 1000/year) in East, South, and West Europe compared to North Europe (20 per 1000/year). Smoking initiation rates during early adolescence (11-15 years) showed a marked increase after 1990 in all regions (except for North European males) but especially in West Europe, where they reached 40 per 1000/year around 2005. APC models supported birth cohort effects in the youngest cohorts.ConclusionSmoking initiation is still unacceptably high among European adolescents, and increasing rates among those aged 15 or less deserve attention. Reducing initiation in adolescents is fundamental, since youngsters are particularly vulnerable to nicotine addiction and tobacco adverse effects.

Published
2018
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18. Body silhouettes as a tool to reflect obesity in the past.

Author

Marianne Lønnebotn, Cecilie Svanes, Jannicke Igland, Karl A Franklin, Simone Accordini, Bryndís Benediktsdóttir, Hayat Bentouhami, José A G Blanco, Roberto Bono, Angelo Corsico, Pascal Demoly, Shyamali Dharmage, Sandra Dorado Arenas, Judith Garcia, Joachim Heinrich, Mathias Holm, Christer Janson, Debbie Jarvis, Bénédicte Leynaert, Jesús Martinez-Moratalla, Dennis Nowak, Isabelle Pin, Chantal Raherison-Semjen, Jose Luis Sánchez-Ramos, Vivi Schlünssen, Svein Magne Skulstad, Julia Dratva, and Francisco Gómez Real

Subjects
Medicine, Science
Abstract

Life course data on obesity may enrich the quality of epidemiologic studies analysing health consequences of obesity. However, achieving such data may require substantial resources. We investigated the use of body silhouettes in adults as a tool to reflect obesity in the past. We used large population-based samples to analyse to what extent self-reported body silhouettes correlated with the previously measured (9-23 years) body mass index (BMI) from both measured (European Community Respiratory Health Survey, N = 3 041) and self-reported (Respiratory Health In Northern Europe study, N = 3 410) height and weight. We calculated Spearman correlation between BMI and body silhouettes and ROC-curve analyses for identifying obesity (BMI ≥30) at ages 30 and 45 years. Spearman correlations between measured BMI age 30 (±2y) or 45 (±2y) and body silhouettes in women and men were between 0.62-0.66 and correlations for self-reported BMI were between 0.58-0.70. The area under the curve for identification of obesity at age 30 using body silhouettes vs previously measured BMI at age 30 (±2y) was 0.92 (95% CI 0.87, 0.97) and 0.85 (95% CI 0.75, 0.95) in women and men, respectively; for previously self-reported BMI, 0.92 (95% CI 0.88, 0.95) and 0.90 (95% CI 0.85, 0.96). Our study suggests that body silhouettes are a useful epidemiological tool, enabling retrospective differentiation of obesity and non-obesity in adult women and men.

Published
2018
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19. Assessment of asthma severity in adults with ever asthma: A continuous score.

Author

Lucia Calciano, Angelo Guido Corsico, Pietro Pirina, Giulia Trucco, Deborah Jarvis, Christer Janson, and Simone Accordini

Subjects
Medicine, Science
Abstract

In epidemiological studies, continuous measures of asthma severity should be used to catch the heterogeneity of phenotypes. This study aimed at developing and validating continuous measures of asthma severity in adult patients with ever asthma from the general population, to be used in epidemiological studies.Respiratory symptoms, anti-asthmatic treatment and lung function were measured on 520 patients with ever asthma aged 20-64 years from the general Italian population (GEIRD study; 2007/2010). The variables that represent the same dimension of asthma severity were identified through an exploratory factor analysis and were summarized through a multiple factor analysis.Only respiratory symptoms and anti-asthmatic treatment were summarized in a continuous score (STS). STS ranges from 0 (no symptoms/treatment) to 10 (maximum symptom frequency and treatment intensity). STS was positively correlated with the Global Initiative for Asthma classification of asthma severity computed on the 137 cases with a doctor's diagnosis (Spearman's coefficient = 0.61, p-value

Published
2017
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20. An Interleukin 13 Polymorphism Is Associated with Symptom Severity in Adult Subjects with Ever Asthma.

Author

Simone Accordini, Lucia Calciano, Cristina Bombieri, Giovanni Malerba, Francesca Belpinati, Anna Rita Lo Presti, Alessandro Baldan, Marcello Ferrari, Luigi Perbellini, and Roberto de Marco

Subjects
Medicine, Science
Abstract

Different genes are associated with categorical classifications of asthma severity. However, continuous outcomes should be used to catch the heterogeneity of asthma phenotypes and to increase the power in association studies. Accordingly, the aim of this study was to evaluate the association between single nucleotide polymorphisms (SNPs) in candidate gene regions and continuous measures of asthma severity, in adult patients from the general population. In the Gene Environment Interactions in Respiratory Diseases (GEIRD) study (www.geird.org), 326 subjects (aged 20-64) with ever asthma were identified from the general population in Verona (Italy) between 2007 and 2010. A panel of 236 SNPs tagging 51 candidate gene regions (including one or more genes) was analysed. A symptom and treatment score (STS) and pre-bronchodilator FEV1% predicted were used as continuous measures of asthma severity. The association of each SNP with STS and FEV1% predicted was tested by fitting quasi-gamma and linear regression models, respectively, with gender, body mass index and smoking habits as potential confounders. The Simes multiple-test procedure was used for controlling the false discovery rate (FDR). SNP rs848 in the IL13 gene region (IL5/RAD50/IL13/IL4) was associated with STS (TG/GG vs TT genotype: uncorrected p-value = 0.00006, FDR-corrected p-value = 0.04), whereas rs20541 in the same gene region, in linkage disequilibrium with rs848 (r(2) = 0.94) in our sample, did not reach the statistical significance after adjusting for multiple testing (TC/CC vs TT: uncorrected p-value = 0.0003, FDR-corrected p-value = 0.09). Polymorphisms in other gene regions showed a non-significant moderate association with STS (IL12B, TNS1) or lung function (SERPINE2, GATA3, IL5, NPNT, FAM13A) only. After adjusting for multiple testing and potential confounders, SNP rs848 in the IL13 gene region is significantly associated with a continuous measure of symptom severity in adult subjects with ever asthma.

Published
2016
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21. Early Life Origins of Lung Ageing: Early Life Exposures and Lung Function Decline in Adulthood in Two European Cohorts Aged 28-73 Years.

Author

Julia Dratva, Elisabeth Zemp, Shyamali C Dharmage, Simone Accordini, Luc Burdet, Thorarinn Gislason, Joachim Heinrich, Christer Janson, Deborah Jarvis, Roberto de Marco, Dan Norbäck, Marco Pons, Francisco Gómez Real, Jordi Sunyer, Simona Villani, Nicole Probst-Hensch, and Cecilie Svanes

Subjects
Medicine, Science
Abstract

OBJECTIVES:Early life environment is essential for lung growth and maximally attained lung function. Whether early life exposures impact on lung function decline in adulthood, an indicator of lung ageing, has scarcely been studied. METHODS:Spirometry data from two time points (follow-up time 9-11 years) and information on early life exposures, health and life-style were available from 12862 persons aged 28-73 years participating in the European population-based cohorts SAPALDIA (n = 5705) and ECRHS (n = 7157). The associations of early life exposures with lung function (FEV1) decline were analysed using mixed-effects linear regression. RESULTS:Early life exposures were significantly associated with FEV1 decline, with estimates almost as large as personal smoking. FEV1 declined more rapidly among subjects born during the winter season (adjusted difference in FEV1/year of follow-up [95%CI] -2.04ml [-3.29;-0.80]), of older mothers, (-1.82 ml [-3.14;-0.49]) of smoking mothers (-1.82ml [-3.30;-0.34] or with younger siblings (-2.61ml [-3.85;-1.38]). Less rapid FEV1-decline was found in subjects who had attended daycare (3.98ml [2.78;5.18]), and indicated in subjects with pets in childhood (0.97ml [-0.16;2.09]). High maternal age and maternal smoking appeared to potentiate effects of personal smoking. The effects were independent of asthma at any age. CONCLUSION:Early life factors predicted lung function decline decades later, suggesting that some mechanisms related lung ageing may be established early in life. Early life programming of susceptibility to adult insults could be a possible pathway that should be explored further.

Published
2016
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22. Seventy Years of Asthma in Italy: Age, Period and Cohort Effects on Incidence and Remission of Self-Reported Asthma from 1940 to 2010.

Author

Giancarlo Pesce, Francesca Locatelli, Isa Cerveri, Massimiliano Bugiani, Pietro Pirina, Ane Johannessen, Simone Accordini, Maria Elisabetta Zanolin, Giuseppe Verlato, and Roberto de Marco

Subjects
Medicine, Science
Abstract

BackgroundIt is well known that asthma prevalence has been increasing all over the world in the last decades. However, few data are available on temporal trends of incidence and remission of asthma.ObjectiveTo evaluate the rates of asthma incidence and remission in Italy from 1940 to 2010.MethodsThe subjects were randomly sampled from the general Italian population between 1991 and 2010 in the three population-based multicentre studies: ECRHS, ISAYA, and GEIRD. Individual information on the history of asthma (age at onset, age at the last attack, use of drugs for asthma control, co-presence of hay-fever) was collected on 35,495 subjects aged 20-84 and born between 1925-1989. Temporal changes in rates of asthma incidence and remission in relation to age, birth cohort and calendar period (APC) were modelled using Poisson regression and APC models.ResultsThe average yearly rate of asthma incidence was 2.6/1000 (3,297 new cases among 1,263,885 person-years). The incidence rates have been linearly increasing, with a percentage increase of +3.9% (95%CI: 3.1-4.5), from 1940 up to the year 1995, when the rates begun to level off. The stabilization of asthma incidence was mainly due to a decrease in the rates of atopic asthma after 1995, while non-atopic asthma has continued to increase. The overall rate of remission was 43.2/1000person-years, and it did not vary significantly across generations, but was associated with atopy, age at asthma onset and duration of the disease.ConclusionsAfter 50 years of a continuous upward trend, the rates of asthma incidence underwent a substantial stabilization in the late 90s. Despite remarkable improvements in the treatment of asthma, the rate of remission did not change significantly in the last seventy years. Some caveats are required in interpreting our results, given that our estimates are based on self-reported events that could be affected by the recall bias.

Published
2015
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23. Correction to: Socioeconomic inequalities in smoking habits are still increasing in Italy

Author

Giuseppe Verlato, Simone Accordini, Giang Nguyen, Pierpaolo Marchetti, Lucia Cazzoletti, Marcello Ferrari, Leonardo Antonicelli, Francesco Attena, Valeria Bellisario, Roberto Bono, Lamberto Briziarelli, Lucio Casali, Angelo Guido Corsico, Alessandro Fois, Maria Grazia Panico, Pavilio Piccioni, Pietro Pirina, Simona Villani, Gabriele Nicolini, and Roberto de Marco

Subjects
Public aspects of medicine, RA1-1270
Published
2017
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24. The coexistence of asthma and chronic obstructive pulmonary disease (COPD): prevalence and risk factors in young, middle-aged and elderly people from the general population.

Author

Roberto de Marco, Giancarlo Pesce, Alessandro Marcon, Simone Accordini, Leonardo Antonicelli, Massimiliano Bugiani, Lucio Casali, Marcello Ferrari, Gabriele Nicolini, Maria Grazia Panico, Pietro Pirina, Maria Elisabetta Zanolin, Isa Cerveri, and Giuseppe Verlato

Subjects
Medicine, Science
Abstract

BACKGROUND: The joint distribution of asthma and chronic obstructive pulmonary disease (COPD) has not been well described. This study aims at determining the prevalence of self-reported physician diagnoses of asthma, COPD and of the asthma-COPD overlap syndrome and to assess whether these conditions share a common set of risk factors. METHODS: A screening questionnaire on respiratory symptoms, diagnoses and risk factors was administered by mail or phone to random samples of the general Italian population aged 20-44 (n = 5163) 45-64 (n = 2167) and 65-84 (n = 1030) in the frame of the multicentre Gene Environment Interactions in Respiratory Diseases (GEIRD) study. RESULTS: A physician diagnosis of asthma or COPD (emphysema/chronic bronchitis/COPD) was reported by 13% and 21% of subjects aged

Published
2013
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25. Long-term air pollution exposure, greenspace and health-related quality of life in the ECRHS study

Author

Anne, Boudier, Iana, Markevych, Bénédicte, Jacquemin, Michael J, Abramson, Simone, Accordini, Bertil, Forsberg, Elaine, Fuertes, Judith, Garcia-Aymerich, Joachim, Heinrich, Ane, Johannessen, Bénédicte, Leynaert, Isabelle, Pin, Valérie, Siroux, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), CHU Grenoble, Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Monash university, Università degli studi di Verona = University of Verona (UNIVR), Umeå University, Imperial College London, Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Universitat Pompeu Fabra [Barcelona] (UPF), Ludwig-Maximilians University [Munich] (LMU), University of Bergen (UiB), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre Hospitalier Universitaire [Grenoble] (CHU), The present analyses are part of the NEVADA project funded by the French Direction Générale de l'Offre de Soin (DGOS), call PHRC-2012.The local investigators and funding agencies for the European Community Respiratory Health Survey (ECRHS I, ECRHS II and ECRHS III) are reported in the online supplementary file.Coordination of the ECRHS I was supported by the European Commission as part of the 'Quality of Life' program and the authors and participants are grateful to the late C. Baya and M. Hallen for their help during the study and K. Vuylsteek and the members of the COMAC for their support. Coordination of the ECRHS II was supported by the European Commission as part of the 'Quality of Life' program (Grant: QLK4-CT-1999-01237). The coordination of the ECRHS 3 was funded through the Medical Research Council (Grant: 92091). NDVI calculations were conducted within the framework of the Ageing Lungs In European Cohorts study that was funded by the European Union's Horizon 2020 research and innovation program under (Grant: 633212). Iana Markevych is currently supported from the 'NeuroSmog: Determining the impact of air pollution on the developing brain' (Nr. POIR.04.04.00-1763/18-00) which is implemented as part of the TEAM-NET programme of the Foundation for Polish Science, co-financed from EU resources, obtained from the European Regional Development Fund under the Smart Growth Operational Programme. ISGlobal acknowledges support from the Spanish Ministry of Science and Innovation through the 'Centro de Excelencia Severo Ochoa 2019–2023' Program (CEX2018-000806-S), and the Generalitat de Catalunya through the CERCA Program., and Jonchère, Laurent

Subjects
Adult, Male, Environmental Engineering, greenness, PM, Epidemiology, Parks, Recreational, [SDV]Life Sciences [q-bio], Nitrogen Dioxide, Well-being, NO(2), NO2, rhinitis, well-being, Air Pollution, Humans, Environmental Chemistry, European Union, Waste Management and Disposal, Rhinitis, Air Pollutants, asthma, greenness, NO2, PM, well-being, Environmental Exposure, asthma, Health Surveys, Pollution, Asthma, [SDV] Life Sciences [q-bio], Greenness, Quality of Life, Female, Particulate Matter, epidemiology
Abstract

International audience; BACKGROUND: Associations of long-term exposure to air pollution and greenspace with health-related quality of life (HRQOL) are poorly studied and few studies have accounted for asthma-rhinitis status. OBJECTIVE: To assess the associations of air pollution and greenspace with HRQOL and whether asthma and/or rhinitis modify these associations. METHODS: The study was based on the participants in the second (2000-2002, n = 6542) and third (2011-2013, n = 3686) waves of the European Community Respiratory Health Survey (ECRHS) including 19 centres. The mean follow-up time was 11.3 years. HRQOL was assessed by the SF-36 Physical and Mental Component Summary scores (PCS and MCS). NO(2), PM(2.5) and PM(10) annual concentrations were estimated at the residential address from existing land-use regression models. Greenspace around the residential address was estimated by the (i) mean of the Normalized Difference Vegetation Index (NDVI) and by the (ii) presence of green spaces within a 300 m buffer. Associations of each exposure variable with PCS and MCS were assessed by mixed linear regression models, accounting for the multicentre design and repeated data, and adjusting for potential confounders. Analyses were stratified by asthma-rhinitis status. RESULTS: The mean (SD) age of the ECRHS-II and III participants was 43 (7.1) and 54 (7.2) years, respectively, and 48 % were men. Higher NO(2), PM(2.5) and PM(10) concentrations were associated with lower MCS (regression coefficients [95%CI] for one unit increase in the inter-quartile range of exposures were -0.69 [-1.23; -0.15], -1.79 [-2.88; -0.70], -1.80 [-2.98; -0.62] respectively). Higher NDVI and presence of forests were associated with higher MCS. No consistent associations were observed for PCS. Similar association patterns were observed regardless of asthma-rhinitis status. CONCLUSION: European adults who resided at places with higher air pollution and lower greenspace were more likely to have lower mental component of HRQOL. Asthma or rhinitis status did not modify these associations.

Published
2022
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26. Long-term effect of asthma on the development of obesity among adults: an international cohort study, ECRHS

Author

Subhabrata Moitra, Anne-Elie Carsin, Michael J Abramson, Simone Accordini, Andre F S Amaral, Josep Anto, Roberto Bono, Lidia Casas Ruiz, Isa Cerveri, Leda Chatzi, Pascal Demoly, Sandra Dorado-Arenas, Bertil Forsberg, Frank Gilliland, Thorarinn Gislason, Jose A Gullón, Joachim Heinrich, Mathias Holm, Christer Janson, Rain Jogi, Francisco Gómez Real, Debbie Jarvis, Bénédicte Leynaert, Dennis Nowak, Nicole Probst-Hensch, José Luis Sánchez-Ramos, Chantal Raherison-Semjen, Valerie Siroux, Stefano Guerra, Manolis Kogevinas, Judith Garcia-Aymerich, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), RS: NUTRIM - R3 - Respiratory & Age-related Health, and Complexe Genetica

Subjects
Pulmonary and Respiratory Medicine, NATIONAL-HEALTH, Respiratory Medicine and Allergy, Asthma Epidemiology, NUTRITION EXAMINATION, ASSOCIATION, SMOKING-CESSATION, GENERAL-PRACTITIONERS, Asthma, WEIGHT-GAIN, BODY-MASS INDEX, COMMUNITY, LUNG-FUNCTION, PHYSICAL-ACTIVITY, Clinical Epidemiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Human medicine, Lungmedicin och allergi
Abstract

IntroductionObesity is a known risk factor for asthma. Although some evidence showed asthma causing obesity in children, the link between asthma and obesity has not been investigated in adults.MethodsWe used data from the European Community Respiratory Health Survey (ECRHS), a cohort study in 11 European countries and Australia in 3 waves between 1990 and 2014, at intervals of approximately 10 years. We considered two study periods: from ECRHS I (t) to ECRHS II (t+1), and from ECRHS II (t) to ECRHS III (t+1). We excluded obese (body mass index≥30 kg/m2) individuals at visitt. The relative risk (RR) of obesity att+1associated with asthma attwas estimated by multivariable modified Poisson regression (lag) with repeated measurements. Additionally, we examined the association of atopy and asthma medication on the development of obesity.ResultsWe included 7576 participants in the period ECRHS I-II (51.5% female, mean (SD) age of 34 (7) years) and 4976 in ECRHS II-III (51.3% female, 42 (8) years). 9% of participants became obese in ECRHS I-II and 15% in ECRHS II—III. The risk of developing obesity was higher among asthmatics than non-asthmatics (RR 1.22, 95% CI 1.07 to 1.38), and particularly higher among non-atopic than atopic (1.47; 1.17 to 1.86 vs 1.04; 0.86 to 1.27), those with longer disease duration (1.32; 1.10 to 1.59 in >20 years vs 1.12; 0.87 to 1.43 in ≤20 years) and those on oral corticosteroids (1.99; 1.26 to 3.15 vs 1.15; 1.03 to 1.28). Physical activity was not a mediator of this association.ConclusionThis is the first study showing that adult asthmatics have a higher risk of developing obesity than non-asthmatics, particularly those non-atopic, of longer disease duration or on oral corticosteroids.

Published
2022
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27. Parental Prepuberty Overweight and Offspring Lung Function

Author

Marianne Lønnebotn, Lucia Calciano, Ane Johannessen, Deborah L. Jarvis, Michael J. Abramson, Bryndís Benediktsdóttir, Lennart Bråbäck, Karl A. Franklin, Raúl Godoy, Mathias Holm, Christer Janson, Nils O. Jõgi, Jorunn Kirkeleit, Andrei Malinovschi, Antonio Pereira-Vega, Vivi Schlünssen, Shyamali C. Dharmage, Simone Accordini, Francisco Gómez Real, and Cecilie Svanes

Subjects
Adult, Male, Parents, Respiratory Medicine and Allergy, men, ECRHS, lung function, overweight, nutrition, prepuberty, father/paternal/male/men, causal inference, intergenerational, counterfactual-based mediation analysis, RHINE, RHINESSA, Fathers, male, father, Humans, Lung, Lungmedicin och allergi, Nutrition and Dietetics, Overweight, respiratory system, respiratory tract diseases, Adult Children, Female, paternal, Food Science
Abstract

In a recent study we found that fathers’ but not mothers’ onset of overweight in puberty was associated with asthma in adult offspring. The potential impact on offspring’s adult lung function, a key marker of general and respiratory health, has not been studied. We investigated the potential causal effects of parents’ overweight on adult offspring’s lung function within the paternal and maternal lines. We included 929 offspring (aged 18–54, 54% daughters) of 308 fathers and 388 mothers (aged 40–66). Counterfactual-based multi-group mediation analyses by offspring’s sex (potential moderator) were used, with offspring’s prepubertal overweight and/or adult height as potential mediators. Unknown confounding was addressed by simulation analyses. Fathers’ overweight before puberty had a negative indirect effect, mediated through sons’ height, on sons’ forced expiratory volume in one second (FEV1) (beta (95% CI): −144 (−272, −23) mL) and forced vital capacity (FVC) (beta (95% CI): −210 (−380, −34) mL), and a negative direct effect on sons’ FVC (beta (95% CI): −262 (−501, −9) mL); statistically significant effects on FEV1/FVC were not observed. Mothers’ overweight before puberty had neither direct nor indirect effects on offspring’s lung function. Fathers’ overweight starting before puberty appears to cause lower FEV1 and FVC in their future sons. The effects were partly mediated through sons’ adult height but not through sons’ prepubertal overweight.

Published
2022
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28. The coexistence of asthma and COPD: risk factors, clinical history and lung function trajectories

Author

Peter Burney, Rain Jõgi, Giuseppe Verlato, Theodore Lytras, Angelo Corsico, Gulser Caliskan, Judith Garcia-Aymerich, Lidia Casas, Thorarinn Gislason, Christer Janson, Nicole Probst-Hensch, Shyamali C. Dharmage, Francesca Locatelli, Alessandro Marcon, Bénédicte Leynaert, Andrei Malinovschi, Kjell Torén, Lucia Calciano, Cecilie Svanes, Deborah Jarvis, Simone Accordini, Joachim Heinrich, and Ageing Lungs European Cohorts ALEC

Subjects
Pulmonary and Respiratory Medicine, Adult, medicine.medical_specialty, Vital capacity, Respiratory Medicine and Allergy, Vital Capacity, Cumulative Exposure, 03 medical and health sciences, FEV1/FVC ratio, Pulmonary Disease, Chronic Obstructive, Young Adult, 0302 clinical medicine, Risk Factors, Internal medicine, Forced Expiratory Volume, Original Research Articles, health trajectories, medicine, longitudinal studies, Humans, COPD, 030212 general & internal medicine, Respiratory system, Lung, Asthma-COPD overlap, Disease burden, Asthma, Lungmedicin och allergi, Aged, business.industry, lung function, Asthma-COPD overlap, longitudinal studies, health trajectories, risk factors, lung function, Middle Aged, medicine.disease, 3. Good health, respiratory tract diseases, 030228 respiratory system, Spirometry, Concomitant, Human medicine, business
Abstract

Patients with concomitant features of asthma and chronic obstructive pulmonary disease (COPD) have a heavy disease burden. Using data collected prospectively in the European Community Respiratory Health Survey, we compared the risk factors, clinical history and lung function trajectories from early adulthood to late sixties of middle-aged subjects with asthma+COPD (n=179), past (n=263) or current (n=808) asthma alone, COPD alone (n=111) or none of these (n=3477). Interview data and pre-bronchodilator forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were obtained during three clinical examinations in 1991–1993, 1999–2002 and 2010–2013. Disease status was classified in 2010–2013, when the subjects were aged 40–68 years, according to the presence of fixed airflow obstruction (post-bronchodilator FEV1/FVC below the lower limit of normal), a lifetime history of asthma and cumulative exposure to tobacco or occupational inhalants. Previous lung function trajectories, clinical characteristics and risk factors of these phenotypes were estimated. Subjects with asthma+COPD reported maternal smoking (28.2%) and respiratory infections in childhood (19.1%) more frequently than subjects with COPD alone (20.9% and 14.0%, respectively). Subjects with asthma+COPD had an impairment of lung function at age 20 years that tracked over adulthood, and more than half of them had asthma onset in childhood. Subjects with COPD alone had the highest lifelong exposure to tobacco smoking and occupational inhalants, and they showed accelerated lung function decline during adult life. The coexistence between asthma and COPD seems to have its origins earlier in life compared to COPD alone. These findings suggest that prevention of this severe condition, which is typical at older ages, should start in childhood., The coexistence of asthma and COPD is generally diagnosed in older persons. Nonetheless, prevention of this condition should start in childhood. As a priority, maternal and personal smoking avoidance should be encouraged. https://bit.ly/3uQCmIX

Published
2021

29. Long-term air pollution exposure, greenness and health-related quality of life (HRQOL) in ECRHS

Author

Bénédicte Jacquemin, Bénédicte Leynaert, Joachim Heinrich, Elaine Fuertes, Anne Boudier, Iana Markevych, Michael J. Abramson, Ane Johanessen, Judith Garcia-Aymerich, Isabelle Pin, Valérie Siroux, Simone Accordini, Bertil Forsberg, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École des Hautes Études en Santé Publique [EHESP] (EHESP), Monash University [Melbourne], Università degli studi di Verona = University of Verona (UNIVR), Umeå University, Imperial College London, Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Helmholtz Zentrum München = German Research Center for Environmental Health, University of Bergen (UiB), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, and Centre Hospitalier Universitaire [Grenoble] (CHU)

Subjects
Quality of life, Health related quality of life, business.industry, [SDV]Life Sciences [q-bio], Environmental health, Air pollution exposure, Medicine, Environment, business, ComputingMilieux_MISCELLANEOUS, Asthma, Term (time)
Abstract

International audience

Published
2021
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30. Exposures during the prepuberty period and future offspring's health:Evidence from human cohort studies

Author

Petur Benedikt Juliusson, Francisco Gómez-Real, Svein Magne Skulstad, Eistine Boateng, Simone Accordini, John W. Holloway, Randi Jacobsen Bertelsen, Vivi Schlünssen, Susanne Krauss-Etchmann, and Cecilie Svanes

Subjects
Male, obesity, puberty, non-genetic heredity, father’s overweight, father’s smoking, Physiology, Disease, Overweight, Epigenesis, Genetic, Cohort Studies, Mice, Beyond Genes Special Issue, 0302 clinical medicine, Risk Factors, Epidemiology, prepuberty, pre-puberty, 0303 health sciences, anthropometry, Smoking, Child Health, General Medicine, AcademicSubjects/SCI01070, Spermatozoa, Paternal Exposure, Cohort, AcademicSubjects/MED00773, medicine.symptom, medicine.medical_specialty, Offspring, Biology, 03 medical and health sciences, father's smoking, Prepuberty, medicine, Animals, Humans, 030304 developmental biology, allergies, Cell Biology, asthma, medicine.disease, Obesity, nongenetic heredity, RHINESSA, sex-specific, Reproductive Medicine, adolescence, Adolescence, Allergies, Anthropometry, Asthma, Father’s overweight, Father’s smoking, Nongenetic heredity, Puberty, Sex-specific, 030217 neurology & neurosurgery, father's overweight
Abstract

Emerging evidence suggests that exposures in prepuberty, particularly in fathers-to-be, may impact the phenotype of future offspring. Analyses of the RHINESSA cohort find that offspring of father’s exposed to tobacco smoking or overweight that started in prepuberty demonstrate poorer respiratory health in terms of more asthma and lower lung function. A role of prepuberty onset smoking for offspring fat mass is suggested in the RHINESSA and ALSPAC cohorts, and historic studies suggest that ancestral nutrition during prepuberty plays a role for grand-offspring’s health and morbidity. Support for causal relationships between ancestral exposures and (grand-)offspring’s health in humans has been enhanced by advancements in statistical analyses that optimize the gain while accounting for the many complexities and deficiencies in human multigeneration data. The biological mechanisms underlying such observations have been explored in experimental models. A role of sperm small RNA in the transmission of paternal exposures to offspring phenotypes has been established, and chemical exposures and overweight have been shown to influence epigenetic programming in germ cells. For example, exposure of adolescent male mice to smoking led to differences in offspring weight and alterations in small RNAs in the spermatozoa of the exposed fathers. It is plausible that male prepuberty may be a time window of particular susceptibility, given the extensive epigenetic reprogramming taking place in the spermatocyte precursors at this age. In conclusion, epidemiological studies in humans, mechanistic research, and biological plausibility, all support the notion that exposures in the prepuberty of males may influence the phenotype of future offspring., Emerging research from human multigeneration cohorts, historic studies, and mechanistic research indicates that prepuberty is an important window of susceptibility with regard to health and disease of future offspring.

Published
2021
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31. Bronchodilator response and lung function decline:Associations with exhaled nitric oxide with regard to sex and smoking status

Author

Thorainn Gislasson, Angelo Corsico, Simone Accordini, Dennis Nowak, Joost Weyler, Rune Nielsen, Össur Ingi Emilsson, Isabelle Pin, Deborah Jarvis, Vivi Schlunnsen, Elisabet Nerpin, Francisco Gómez Real, Christer Janson, José Antonio Gullón, Diogenes S. Ferreira, Giulia Squillacioti, Andrei Malinovschi, Joachim Heinrich, Rain Jõgi, Ane Johannessen, Anna-Carin Olin, Bertil Forsberg, Chantal Raherison Semjen, Antonio Pereira-Vega, Alessandro Marcon, Pascal Demoly, Isabel Urrutia, Judith Garcia-Aymerich, Mario Olivieri, Commission of the European Communities, Uppsala University, Dalarna University, School of Public Health and Preventive Medicine [Melbourne, Australia], Universidade Federal do Parana [Curitiba] (UFPR), Universidade Federal do Paraná (UFPR), University of Antwerp (UA), Aarhus University [Aarhus], Tartu University Hospital [Tartu, Estonia], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Landspitali National University Hospital of Iceland, University of Iceland [Reykjavik], CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Arnaud de Villeneuve [CHRU Montpellier], Université de Montpellier (UM), Epidemiology of Allergic and Respiratory Diseases Department [Paris] (EPAR), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Ludwig-Maximilians University [Munich] (LMU), German Research Center for Environmental Health - Helmholtz Center München (GmbH), University of Melbourne, German Center for Lung Research, Foundation IRCCS Policlinico San Matteo, University of Pavia, University of Verona (UNIVR), University of Turin, Haukeland University Hospital, University of Bergen (UiB), Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Galdakao Hospital, Hospital Juan Ramón Jiménez, University of Gothenburg (GU), Umeå University, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), and Imperial College London

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, medicine.drug_class, Bronchodilatation, Epidemiology, FeNO, Lung function, Respiratory Medicine and Allergy, Immunology, Article, 03 medical and health sciences, FEV1/FVC ratio, 0302 clinical medicine, Bronchodilator, Internal medicine, medicine, Immunology and Allergy, 030223 otorhinolaryngology, Respiratory health, Asthma, Lungmedicin och allergi, business.industry, 1103 Clinical Sciences, RC581-607, respiratory system, medicine.disease, 3. Good health, respiratory tract diseases, 030228 respiratory system, Feno, Lung Function, Exhaled nitric oxide, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Smoking status, Human medicine, Immunologic diseases. Allergy, business
Abstract

Background: Fractional exhaled nitric oxide (FeNO) is a marker of type-2 inflammation used both to support diagnosis of asthma and follow up asthma patients.The associations of FeNO with lung function decline and bronchodilator (BD) response have been studied only scarcely in large populations. Objectives: To study the association between FeNO and a) retrospective lung function decline over 20 years, and b) lung function response to BD among asthmatic subjects compared with non-asthmatic subjects and with regards to current smoking and sex. Methods: Longitudinal analyses of previous lung function decline and FeNO level at follow-up and cross-sectional analyses of BD response and FeNO levels in 4257 participants (651 asthmatics) from the European Community Respiratory Health Survey. Results: Among asthmatic subjects, higher percentage declines of FEV1 and FEV1/FVC were associated with higher FeNO levels (p¼0.001 for both) at follow-up. These correlations were found mainly among non-smoking individuals (p ¼ 0.001) and females (p ¼ 0.001) in stratified analyses. Percentage increase in FEV1 after BD was positively associated with FeNO levels in non-asthmatic subjects. Further, after stratified for sex and smoking separately, a positive association was seen between FEV1 and FeNO levels in non-smokers and women, regardless of asthma status. Conclusions: We found a relationship between elevated FeNO and larger FEV1 decline over 20 years among subjects with asthma who were non-smokers or women. The association between elevated FeNO levels and larger BD response was found in both non-asthmatic and asthmatic subjects, mainly in women and non-smoking subjects. The coordination of ECRHS III was supported by the Medical Research Council (Grant Number 92091).We acknowledge support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program.

Published
2021
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32. Health Impact assessment to predict the impact of tobacco price increases on COPD burden in Italy, England and Sweden

Author

Lucia Calciano, Simone Accordini, Alessandro Marcon, Laura Potts, Deborah Jarvis, Jennifer K Quint, Giancarlo Pesce, Virjal Jani, Elaine Fuertes, Stefan K. Lhachimi, Alex Adamson, Cosetta Minelli, Christer Janson, European Union's Horizon 2020 research and innovation programme, Commission of the European Communities, HAL-SU, Gestionnaire, Imperial College London, Università degli studi di Verona = University of Verona (UNIVR), King‘s College London, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Epidemiology of Allergic and Respiratory Diseases Department [iPlesp] (EPAR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), University of Bremen, Uppsala University, University of Verona (UNIVR), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Epidemiology of Allergic and Respiratory Diseases Department [Paris] (EPAR), and Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
medicine.medical_specialty, Epidemiology, Science, 010501 environmental sciences, 01 natural sciences, Article, COPD burden, 03 medical and health sciences, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Environmental health, tobacco prices, Tobacco, Medicine, Humans, 030212 general & internal medicine, Risk factor, chronic obstructive pulmonary disease (COPD), Tobacco price, 0105 earth and related environmental sciences, Sweden, COPD, Public health, Multidisciplinary, business.industry, chronic obstructive pulmonary disease (COPD), COPD burden, tobacco prices, Health Impact Assessment, Chronic obstructive pulmonary disease, Smoking, Public Health, Global Health, Social Medicine and Epidemiology, medicine.disease, Markov Chains, 3. Good health, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, England, Italy, Risk factors, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Life expectancy, Observational study, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Health Impact Assessment, business, Health impact assessment
Abstract

Raising tobacco prices effectively reduces smoking, the main risk factor for chronic obstructive pulmonary disease (COPD). Using the Health Impact Assessment tool “DYNAMO-HIA”, this study quantified the reduction in COPD burden that would occur in Italy, England and Sweden over 40 years if tobacco prices were increased by 5%, 10% and 20% over current local prices, with larger increases considered in secondary analyses. A dynamic Markov-based multi-state simulation modelling approach estimated the effect of changes in smoking prevalence states and probabilities of transitioning between smoking states on future smoking prevalence, COPD burden and life expectancy in each country. Data inputs included demographics, smoking prevalences and behaviour and COPD burden from national data resources, large observational cohorts and datasets within DYNAMO-HIA. In the 20% price increase scenario, the cumulative number of COPD incident cases saved over 40 years was 479,059 and 479,302 in Italy and England (populous countries with higher smoking prevalences) and 83,694 in Sweden (smaller country with lower smoking prevalence). Gains in overall life expectancy ranged from 0.25 to 0.45 years for a 20 year-old. Increasing tobacco prices would reduce COPD burden and increase life expectancy through smoking behavior changes, with modest but important public health benefits observed in all three countries.

Published
2021
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33. Communication of personalised disease risk by general practitioners to motivate smoking cessation in England: a cost-effectiveness and research prioritisation study

Author

Deborah Jarvis, Gianluca Baio, Laura Portas, Simone Accordini, Cosetta Minelli, Alessandro Marcon, and Alexander Adamson

Subjects
Adult, medicine.medical_specialty, Cost effectiveness, medicine.medical_treatment, Cost-Benefit Analysis, Medicine (miscellaneous), Disease, tobacco, State Medicine, Value of information, General Practitioners, cost-effectiveness analysis, general practitioner, personalised disease risk, smoking cessation, tobacco, value of information, Credible interval, medicine, Humans, Stroke, business.industry, Communication, cost-effectiveness analysis, personalised disease risk, Bayes Theorem, Odds ratio, Middle Aged, medicine.disease, value of information, Psychiatry and Mental health, England, general practitioner, Family medicine, Population study, Smoking cessation, Smoking Cessation, business
Abstract

BACKGROUND AND AIMS Communication of personalised disease risk can motivate smoking cessation. We assessed whether routine implementation of this intervention by general practitioners (GPs) in England is cost-effective or whether we need further research to better establish its effectiveness. DESIGN Cost-effectiveness analysis (CEA) with value of information (VoI) analysis from the UK National Health Service perspective, using GP communication of personalised disease risk on smoking cessation versus usual care. SETTING GP practices in England. STUDY POPULATION Healthy smokers aged 35-60 attending the GP practice. MEASUREMENTS Effectiveness of GP communication of personalised disease risk on smoking cessation was estimated through systematic review and meta-analysis. A Bayesian CEA was then performed using a lifetime Markov model on smokers aged 35-60 that measured lifetime costs and quality-adjusted life-years (QALYs) assigned to the four diseases contributing the most to smoking-related morbidity, mortality and costs: chronic obstructive pulmonary disease, lung cancer, myocardial infarction, and stroke. Costs and QALYs for each disease state were obtained from the literature. VoI analysis identified sources of uncertainty in the CEA and assessed how much would be worth investing in further research to reduce this uncertainty. FINDINGS The meta-analysis odds ratio for the effectiveness estimate of GP communication of personalised disease risk was 1.48 (95% credibility interval (CrI): 0.91-2.26), an absolute increase in smoking cessation rates of 3.84%. The probability of cost-effectiveness ranged from 89-94% depending on sex and age. VoI analysis indicated that: 1) uncertainty in the effectiveness of the intervention was the driver of the overall uncertainty in the CEA and 2) a research investment to reduce this uncertainty is justified if lower than £27.6million (£7 per smoker). CONCLUSIONS Evidence to date shows that, in England, incorporating disease risk communication into general practitioners' practices to motivate smoking cessation is likely to be cost-effective compared with usual care.

Published
2021

34. SARS-CoV-2 Vaccination Elicits Unconventional IgM Specific Responses in Naïve and Previously COVID19-Infected Individuals

Author

Alessandra Ruggiero, Chiara Piubelli, Lucia Calciano, Simone Accordini, Maria Teresa Valenti, Luca Dalle Carbonare, Gabriel Siracusano, Lucia Lopalco, Nigel Temperton, Natalia Tiberti, Silvia Stefania Longoni, Massimo Pizzato, Silvia Accordini, A.M.S.L.V. Group, Tobia Fantoni, Alberto Beretta, Zeno Bisoffi, and Donato Zipeto

Subjects
History, COVID-19 Vaccines, IgM, Polymers and Plastics, IgG, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Spike, Antibodies, Viral, General Biochemistry, Genetics and Molecular Biology, Industrial and Manufacturing Engineering, Neutralization, Immunity, Humans, Medicine, Longitudinal Studies, Business and International Management, BTN162b2 vaccine, COVID-19, IgG, IgM, SARS-CoV-2, Spike, BNT162 Vaccine, QR355, biology, SARS-CoV-2, business.industry, Vaccination, Antibody titer, COVID-19, General Medicine, Titer, Immunoglobulin M, Spike Glycoprotein, Coronavirus, Immunology, Cohort, biology.protein, BTN162b2 vaccine, Antibody, business
Abstract

Background: IgG antibodies specific for the SARS-CoV-2 Spike protein are under intensive investigation for the urgent need to identify a correlate of protective immunity in individuals vaccinated with licensed and candidate COVID-19 vaccines. Limited data are available on vaccine-elicited IgM antibodies and their potential implication in immunity to SARS-CoV-2. Methods: We performed a longitudinal study to quantify IgG and IgM antibodies specific for the SARS-CoV-2 spike protein (IgG-S and IgM-S) in 1873 health care worker (HCW) recipients of the BNT162b2 (Comirnaty) vaccine. Samples were collected before administration (T0), at the second dose (T1) and three weeks after the second dose (T2). The cohort included 1584 immunologically naive to SARS-CoV-2 (IN) and 289 had a history of previous infection (PI). Findings: In IN we identified three patterns of responses: (a) IgG positive/IgM negative (36.1%), (b) coordinated IgM-S/IgG-S responses appearing three weeks after the first dose (37.4%) and (c) delayed IgM appearing after IgG (26.3%). Coordinated IgM-S/IgG-S responses were associated with higher IgG titers. Of the 289 PI vaccinees, 64.5% were IgM-S positive before vaccination, whereas 32% and 3.5% developed IgM-S after the first and second vaccine dose respectively. IgM-S positive sera had higher pseudovirus neutralization titers compared to the IgM-S negative. Similar results were observed in individuals who received either Moderna or Astrazeneca. Interpretation: Coordinated expression of IgG-S and IgM-S after vaccination was associated with a significantly more efficient response in both antibody titers and virus-neutralizing activity, representing a potential correlate of protection. Instead, the unconventional IgG-S positive/IgM-S negative responses may be suggestive of a recruitment of cross coronaviruses immunity by vaccination, warranting further investigation. Funding Information: This work was supported by the Italian Ministry of Health under “Fondi Ricerca Corrente”- L1P5 and “Progetto Ricerca Finalizzata COVID-2020-12371675” to IRCCS Sacro Cuore Don Calabria Hospital, by FUR 2020 Department of Excellence 2018-2022, MIUR, Italy and by The Brain Research Foundation Verona.

Published
2021
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35. Lifelong exposure to air pollution and greenness in relation to asthma, rhinitis and lung function in adulthood

Author

Bertil Forsberg, Gerard Hoek, Randi Jacobsen Bertelsen, Cecilie Svanes, Andrei Malinovschi, Joachim Heinrich, Jesper H. Christensen, Thomas Halvorsen, Christer Janson, Lennart Bråbäck, Torben Sigsgaard, Iana Markevych, Alessandro Marcon, Mathias Holm, Simone Accordini, Roy Miodini Nilsen, Kees de Hoogh, Ole Hertel, Ingrid Nordeide Kuiper, and Ane Johannessen

Subjects
Vital capacity, 010504 meteorology & atmospheric sciences, greenness, Respiratory Medicine and Allergy, air pollution, Air pollution, 010501 environmental sciences, medicine.disease_cause, Logistic regression, 01 natural sciences, Medicine, Child, Lung, Lung function, lcsh:Environmental sciences, General Environmental Science, Lungmedicin och allergi, Rhinitis, lcsh:GE1-350, Air Pollutants, Norway, respiratory system, Adult, Adolescent, Nitrogen Dioxide, Air Pollution, Greenness, Asthma, Lung Function, FEV1/FVC ratio, Arbetsmedicin och miljömedicin, rhinitis, Humans, Risk factor, 0105 earth and related environmental sciences, Sweden, business.industry, lung function, Environmental Exposure, Occupational Health and Environmental Health, asthma, medicine.disease, respiratory tract diseases, Particulate Matter, business, Demography
Abstract

OBJECTIVES: To investigate if air pollution and greenness exposure from birth till adulthood affects adult asthma, rhinitis and lung function.METHODS: We analysed data from 3428 participants (mean age 28) in the RHINESSA study in Norway and Sweden. Individual mean annual residential exposures to nitrogen dioxide (NO2), particulate matter (PM10 and PM2.5), black carbon (BC), ozone (O3) and greenness (normalized difference vegetation index (NDVI)) were averaged across susceptibility windows (0-10 years, 10-18 years, lifetime, adulthood (year before study participation)) and analysed in relation to physician diagnosed asthma (ever/allergic/non-allergic), asthma attack last 12 months, current rhinitis and low lung function (lower limit of normal (LLN), z-scores of forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and FEV1/FVC below 1.64). We performed logistic regression for asthma attack, rhinitis and LLN lung function (clustered with family and study centre), and conditional logistic regression with a matched case-control design for ever/allergic/non-allergic asthma. Multivariable models were adjusted for parental asthma and education.RESULTS: Childhood, adolescence and adult exposure to NO2, PM10 and O3 were associated with an increased risk of asthma attacks (ORs between 1.29 and 2.25), but not with physician diagnosed asthma. For rhinitis, adulthood exposures seemed to be most important. Childhood and adolescence exposures to PM2.5 and O3 were associated with lower lung function, in particular FEV1 (range ORs 2.65 to 4.21). No associations between NDVI and asthma or rhinitis were revealed, but increased NDVI was associated with lower FEV1 and FVC in all susceptibility windows (range ORs 1.39 to 1.74).CONCLUSIONS: Air pollution exposures in childhood, adolescence and adulthood were associated with increased risk of asthma attacks, rhinitis and low lung function in adulthood. Greenness was not associated with asthma or rhinitis, but was a risk factor for low lung function.

Published
2021
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36. The Exposome Approach in Allergies and Lung Diseases: Is It Time to Define a Preconception Exposome?

Author

Francisco Gómez-Real, Kathrine Pape, Matthew G. Darby, Jorunn Kirkeleit, Simone Accordini, Lucia Calciano, Cecilie Svanes, Signe Timm, Toril Mørkve Knudsen, Jennifer J. Koplin, Ane Johannessen, Susanne Krauss-Etschmann, Ingrid Nordeide Kuiper, Randi Jacobsen Bertelsen, Gro Tjalvin, Svein Magne Skulstad, Juan Pablo López-Cervantes, Anne Mette Lund Würtz, Barbara Hammer, Shyamali C. Dharmage, Marianne Lønnebotn, Nils Oskar Jõgi, Vivi Schlünssen, Institute of Infectious Disease and Molecular Medicine, and Faculty of Health Sciences

Subjects
Lung Diseases, Exposome, Health, Toxicology and Mutagenesis, Review, Disease, exposome, Reproductive cycle, Intergenerational, Environmental health, Allergies, Hypersensitivity, Humans, Medicine, Lung health, transgenerational, Life Style, Lung function, Organism, Respiratory health, Exposure assessment, epigenetics, allergies, preconception, business.industry, Public Health, Environmental and Occupational Health, Preconception, lung function, Environmental Exposure, asthma, lung health, Asthma, Lifestyle factors, intergenerational, Epigenetics, business, Transgenerational
Abstract

Emerging research suggests environmental exposures before conception may adversely affect allergies and lung diseases in future generations. Most studies are limited as they have focused on single exposures, not considering that these diseases have a multifactorial origin in which environmental and lifestyle factors are likely to interact. Traditional exposure assessment methods fail to capture the interactions among environmental exposures and their impact on fundamental biological processes, as well as individual and temporal factors. A valid estimation of exposure preconception is difficult since the human reproductive cycle spans decades and the access to germ cells is limited. The exposome is defined as the cumulative measure of external exposures on an organism (external exposome), and the associated biological responses (endogenous exposome) throughout the lifespan, from conception and onwards. An exposome approach implies a targeted or agnostic analysis of the concurrent and temporal multiple exposures, and may, together with recent technological advances, improve the assessment of the environmental contributors to health and disease. This review describes the current knowledge on preconception environmental exposures as related to respiratory health outcomes in offspring. We discuss the usefulness and feasibility of using an exposome approach in this research, advocating for the preconception exposure window to become included in the exposome concept.

Published
2021
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37. Prenatal and prepubertal exposures to tobacco smoke in men may cause lower lung function in future offspring : a three-generation study using a causal modelling approach

Author

Francisco Gómez Real, Shyamali C. Dharmage, Christer Janson, Alessandro Marcon, José Luis Sánchez-Ramos, Rain Jõgi, Vivi Schlünssen, Cecilie Svanes, Nils Oskar Jõgi, Ane Johannessen, Jesús Martínez-Moratalla Rovira, Simone Accordini, Andrei Malinovschi, Bryndis Benediktsdottir, Deborah Jarvis, Mathias Holm, Randi Jacobsen Bertelsen, John W. Holloway, Kjell Torén, Lucia Calciano, Bertil Forsberg, and Lennart Bråbäck

Subjects
lung function, tobacco smoking, prepuberty, pregnancy, paternal line, causal inference, multi-level mediation modelling, ALEC, ECRHS, RHINESSA, EPIGENETIC INHERITANCE, Respiratory Medicine and Allergy, Vital Capacity, Tobacco Smoke Pollution/adverse effects, CHILDHOOD, Tobacco smoke, Pregnancy, Original Research Articles, Forced Expiratory Volume, Smoking/adverse effects, Medicine, Child, Lung, Lungmedicin och allergi, NICOTINE EXPOSURE, Smoking, Middle Aged, respiratory system, MEDIATION ANALYSIS, 3. Good health, PREGNANCY, Adult Children, ODDS RATIO, Pulmonary and Respiratory Medicine, Adult, Mediation (statistics), Adolescent, Offspring, FEV1/FVC ratio, Young Adult, Prepuberty, Tobacco, Humans, business.industry, Paediatrics, medicine.disease, Confidence interval, respiratory tract diseases, Causal inference, RISK-FACTORS, ASTHMA, Tobacco Smoke Pollution, CIGARETTE-SMOKING, WEIGHT, business, Demography
Abstract

Mechanistic research suggests that lifestyle and environmental factors impact respiratory health across generations by epigenetic changes transmitted through male germ cells. Evidence from studies on humans is very limited. We investigated multigeneration causal associations to estimate the causal effects of tobacco smoking on lung function within the paternal line. We analysed data from 383 adult offspring (age 18–47 years; 52.0% female) and their 274 fathers, who had participated in the European Community Respiratory Health Survey (ECRHS)/Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) generation study and had provided valid measures of pre-bronchodilator lung function. Two counterfactual-based, multilevel mediation models were developed with: paternal grandmothers’ smoking in pregnancy and fathers’ smoking initiation in prepuberty as exposures; fathers’ forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), or FEV1/FVC z-scores as potential mediators (proxies of unobserved biological mechanisms that are true mediators); and offspring's FEV1 and FVC, or FEV1/FVC z-scores as outcomes. All effects were summarised as differences (Δ) in expected z-scores related to fathers’ and grandmothers’ smoking history. Fathers’ smoking initiation in prepuberty had a negative direct effect on both offspring's FEV1 (Δz-score –0.36, 95% CI −0.63– −0.10) and FVC (−0.50, 95% CI −0.80– −0.20) compared with fathers’ never smoking. Paternal grandmothers’ smoking in pregnancy had a negative direct effect on fathers’ FEV1/FVC (−0.57, 95% CI −1.09– −0.05) and a negative indirect effect on offspring's FEV1/FVC (−0.12, 95% CI −0.21– −0.03) compared with grandmothers’ not smoking before fathers’ birth nor during fathers’ childhood. Fathers’ smoking in prepuberty and paternal grandmothers’ smoking in pregnancy may cause lower lung function in offspring. Our results support the concept that lifestyle-related exposures during these susceptibility periods influence the health of future generations., Fathers’ prepuberty and paternal grandmothers’ pregnancy are vulnerable periods to the adverse effects of smoking on offspring's lung function. Preventing smoking in these susceptibility time windows might improve the next generation's health. https://bit.ly/3vvgjsN

Published
2021
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38. Association of candidate genes with FeNO in asthma: preliminary results from the Gene Environment Interactions in Respiratory Diseases (GEIRD) study

Author

Simone Accordini, Valentina Lando, Lucia Calciano, Mario Olivieri, Giuseppe Verlato, Cristina Bombieri, and Giovanni Malerba

Subjects
Candidate gene, business.industry, Association (object-oriented programming), feno, snp, asthma, medicine.disease, Immunology, Medicine, Respiratory system, snp, feno, asthma, business, Gene, Asthma
Published
2020
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39. Associations of preconception exposure to air pollution and greenness with offspring asthma and hay fever

Author

Joachim Heinrich, Ingrid Nordeide Kuiper, Randi Jacobsen Bertelsen, Christer Janson, Kees de Hoogh, Thomas Halvorsen, Ole Hertel, Lennart Bråbäck, Jesper H. Christensen, Simone Accordini, Cecilie Svanes, Torben Sigsgaard, Alessandro Marcon, Bertil Forsberg, Gerard Hoek, Iana Markevych, Mathias Holm, Ane Johannessen, and A. Malinovschi

Subjects
air pollution, childhood asthma, childhood hay fever, greenness, preconception exposure, Male, Allergy, Health, Toxicology and Mutagenesis, Respiratory Medicine and Allergy, lcsh:Medicine, 010501 environmental sciences, Logistic regression, 01 natural sciences, 0302 clinical medicine, Pregnancy, 030212 general & internal medicine, Child, Lungmedicin och allergi, Air Pollutants, 3. Good health, Europe, Child, Preschool, Paternal Exposure, Hay fever, Female, Maternal Inheritance, Adolescent, Offspring, Nitrogen Dioxide, Environment, Article, 03 medical and health sciences, Arbetsmedicin och miljömedicin, medicine, Humans, 0105 earth and related environmental sciences, Asthma, business.industry, lcsh:R, Public Health, Environmental and Occupational Health, Australia, Infant, Newborn, Infant, Rhinitis, Allergic, Seasonal, Odds ratio, Occupational Health and Environmental Health, Environmental Exposure, medicine.disease, Preconception Injuries, 13. Climate action, Spain, Particulate Matter, business, Demography
Abstract

We investigated if greenness and air pollution exposure in parents&rsquo, childhood affect offspring asthma and hay fever, and if effects were mediated through parental asthma, pregnancy greenness/pollution exposure, and offspring exposure. We analysed 1106 parents with 1949 offspring (mean age 35 and 6) from the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) generation study. Mean particulate matter (PM2.5 and PM10), nitrogen dioxide (NO2), black carbon (BC), ozone (O3) (&micro, g/m3) and greenness (normalized difference vegetation index (NDVI)) were calculated for parents 0&ndash, 18 years old and offspring 0&ndash, 10 years old, and were categorised in tertiles. We performed logistic regression and mediation analyses for two-pollutant models (clustered by family and centre, stratified by parental lines, and adjusted for grandparental asthma and education). Maternal medium PM2.5 and PM10 exposure was associated with higher offspring asthma risk (odds ratio (OR) 2.23, 95%CI 1.32&ndash, 3.78, OR 2.27, 95%CI 1.36&ndash, 3.80), and paternal high BC exposure with lower asthma risk (OR 0.31, 95%CI 0.11&ndash, 0.87). Hay fever risk increased for offspring of fathers with medium O3 exposure (OR 4.15, 95%CI 1.28&ndash, 13.50) and mothers with high PM10 exposure (OR 2.66, 95%CI 1.19&ndash, 5.91). The effect of maternal PM10 exposure on offspring asthma was direct, while for hay fever, it was mediated through exposures in pregnancy and offspring&rsquo, s own exposures. Paternal O3 exposure had a direct effect on offspring hay fever. To conclude, parental exposure to air pollution appears to influence the risk of asthma and allergies in future offspring.

Published
2020
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40. Being overweight in childhood, puberty, or early adulthood : Changing asthma risk in the next generation?

Author

Karl A. Franklin, Vivi Schlünssen, Marianne Lønnebotn, Rain Jõgi, Cecilie Svanes, Thorarinn Gislason, Ane Johannessen, Christer Janson, Antonio Pereira-Vega, Deborah Jarvis, Andrei Malinovschi, Randi Jacobsen Bertelsen, Lennart Bråbäck, Jeong-Lim Kim, Jorunn Kirkeleit, Mathias Holm, Lucia Calciano, Shyamali C. Dharmage, Simone Accordini, Roy Miodini Nilsen, Francisco Gómez Real, Caroline J Lodge, Jesús Martínez-Moratalla, Bryndis Benediktsdottir, Læknadeild (HÍ), Faculty of Medicine (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland, and Commission of the European Communities

Subjects
Male, Parents, Pediatric Obesity, Pediatrics, Allergy, Offita, Respiratory Medicine and Allergy, Ageing Lungs in European Cohorts (ALEC) Study, Overweight, 0302 clinical medicine, Pregnancy, Risk Factors, immune system diseases, Immunology and Allergy, 030212 general & internal medicine, Young adult, Ageing Lungs in European Cohorts study, epidemiology, multilevel mediation model, offspring, parental risk factors, Lungmedicin och allergi, Ageing Lungs in European Cohorts study, Middle Aged, Astmi, 3. Good health, 1107 Immunology, Prenatal Exposure Delayed Effects, Adult Children, Female, epidemiology, medicine.symptom, parental risk factors, Adult, medicine.medical_specialty, Adolescent, Immunology, Young Adult, 03 medical and health sciences, medicine, Humans, multilevel mediation model, Risk factor, Asthma, offspring, Faraldsfræði, business.industry, Immunology in the medical area, nutritional and metabolic diseases, Odds ratio, medicine.disease, Obesity, respiratory tract diseases, 030228 respiratory system, Immunologi inom det medicinska området, Relative risk, business, Body mass index
Abstract

Publisher's version (útgefin grein)., Background: Overweight status and asthma have increased during the last decades. Being overweight is a known risk factor for asthma, but it is not known whether it might also increase asthma risk in the next generation. Objective: We aimed to examine whether parents being overweight in childhood, adolescence, or adulthood is associated with asthma in their offspring. Methods: We included 6347 adult offspring (age, 18-52 years) investigated in the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) multigeneration study of 2044 fathers and 2549 mothers (age, 37-66 years) investigated in the European Community Respiratory Health Survey (ECRHS) study. Associations of parental overweight status at age 8 years, puberty, and age 30 years with offspring's childhood overweight status (potential mediator) and offspring's asthma with or without nasal allergies (outcomes) was analyzed by using 2-level logistic regression and 2-level multinomial logistic regression, respectively. Counterfactual-based mediation analysis was performed to establish whether observed associations were direct or indirect effects mediated through the offspring's own overweight status. Results: We found statistically significant associations between both fathers' and mothers' childhood overweight status and offspring's childhood overweight status (odds ratio, 2.23 [95% CI, 1.45-3.42] and 2.45 [95% CI, 1.86-3.22], respectively). We also found a statistically significant effect of fathers' onset of being overweight in puberty on offspring's asthma without nasal allergies (relative risk ratio, 2.31 [95% CI, 1.23-4.33]). This effect was direct and not mediated through the offspring's own overweight status. No effect on offspring's asthma with nasal allergies was found. Conclusion: Our findings suggest that metabolic factors long before conception can increase asthma risk and that male puberty is a time window of particular importance for offspring's health., This study was funded by the European Union's Horizon 2020 research and innovation program as part of the ALEC study (Ageing Lungs in European Cohorts study, grant no. 633212). The RHINESSA generation study also received funding by the Research Council of Norway (grant nos. 214123 and 228174), the Bergen Medical Research Foundation (Norway), the Western Norwegian Regional Health Authorities (grant nos. 912011, 911892, and 911631), the Norwegian Labour Inspection, the Norwegian Asthma and Allergy Association, the Danish Woods Foundation (grant no. 444508795), the Danish Working Environment Authority (grant no. 20150067134), the Swedish Lung Foundation, the Swedish Asthma and Allergy Association, and the Estonian Research Council (grant no. PUT562). The funding agencies had no direct role in the conduct of the study; the collection, management, statistical analysis, and interpretation of the data; and the preparation or approval of the manuscript.

Published
2020
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41. Regular Physical Activity Levels and Incidence of Restrictive Spirometry Pattern: A Longitudinal Analysis of 2 Population-based Cohorts

Author

Dirk Keidel, Isabelle Pin, Anne-Elie Carsin, Giulia Squillacioti, José Luis Sánchez, Jesús Martínez-Moratalla, Elaine Fuertes, Anna Beckmeyer-Borowko, Bénédicte Leynaert, Joost Weyler, Chantal Raherison, Shyamali C. Dharmage, Stefano Guerra, Thorarinn Gislason, Margareta Emtner, Seraina Caviezel, Christer Janson, Medea Imboden, Nicole Probst-Hensch, Silvia Pascual Erquicia, Pascal Demoly, Rain Jögi, Ismael Huerta, Francisco Gómez Real, Judith Garcia-Aymerich, Kjell Torén, Bertill Forsberg, Isa Cerveri, Simone Accordini, Emmanuel Schaffner, Cecilie Svanes, Deborah Jarvis, Joachim Heinrich, Dennis Nowak, Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Spirometry, Adult, Male, Vital capacity, Epidemiology, Population, Vital Capacity, spirometry, physical activity, Exercici, Overweight, Lower risk, 03 medical and health sciences, FEV1/FVC ratio, BMI, 0302 clinical medicine, Forced Expiratory Volume, medicine, Humans, Longitudinal Studies, education, Exercise, 030304 developmental biology, Aged, Aged, 80 and over, 0303 health sciences, education.field_of_study, medicine.diagnostic_test, business.industry, Incidence, restrictive spirometry, Middle Aged, Respiration Disorders, Confidence interval, FVC, 3. Good health, Europe, 030228 respiratory system, Relative risk, Espirometria, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, Human medicine, medicine.symptom, business, Demography
Abstract

We estimated the association between regular physical activity and the incidence of restrictive spirometry pattern. Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and physical activity were assessed in 2 population-based European cohorts (European Community Respiratory Health Survey: n = 2,757, aged 39-67 years; and Swiss Study on Air Pollution and Lung and Heart Diseases in Adults: n = 2,610, aged 36-82 years) first in 2000-2002 and again approximately 10 years later (2010-2013). Subjects with restrictive or obstructive spirometry pattern at baseline were excluded. We assessed the association of being active at baseline (defined as being physically active at least 2-3 times/week for ≥1 hour) with restrictive spirometry pattern at follow-up (defined as a postbronchodilation FEV1/FVC ratio of at least the lower limit of normal and FVC of

Published
2020
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42. Incidence trends of airflow obstruction among European adults without asthma: a 20-year cohort study

Author

Francesca Locatelli, Nicole Probst-Hensch, Anne-Elie Carsin, Lucia Calciano, Alessandro Marcon, Cecilie Svanes, Simone Accordini, Giancarlo Pesce, Christer Janson, Josep M. Antó, Medea Imboden, Anna Beckmeyer-Borowko, Angelo Corsico, Dirk Keidel, Peter Burney, Deborah Jarvis, Cosetta Minelli, Bodescot, Myriam, Aging Lungs in European Cohorts - ALEC - - H20202015-05-01 - 2019-04-30 - 633212 - VALID, Università degli studi di Verona = University of Verona (UNIVR), Epidemiology of Allergic and Respiratory Diseases Department [iPlesp] (EPAR), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] (UPF)-Catalunya ministerio de salud, Hospital del Mar Medical Research Institute [Barcelone, Espagne] (IMIM), CIBER de Epidemiología y Salud Pública (CIBERESP), Universitat Pompeu Fabra [Barcelona] (UPF), Swiss Tropical and Public Health Institute [Basel], University of Basel (Unibas), Università degli Studi di Pavia = University of Pavia (UNIPV), Uppsala University, University of Bergen (UiB), Haukeland University Hospital, Imperial College London, ALEC has received funding from the European Union’s Horizon 2020 research and innovation programme [Grant Agreement No. 633212]. The co-ordination of the ECRHS was supported by the European Commission (phases 1 and 2) and the Medical Research Council (phase 3). The SAPALDIA cohort was funded by The State Secretariat for Education, Research and Innovation (SERI), Switzerland., European Project: 633212,H2020,H2020-PHC-2014-two-stage,ALEC(2015), University of Verona (UNIVR), Epidemiology of Allergic and Respiratory Diseases Department [Paris] (EPAR), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Pavia, and Commission of the European Communities

Subjects
Male, Respiratory Medicine and Allergy, lcsh:Medicine, Ageing Lungs in European Cohorts (ALEC) Study, airflow obstruction, Rate ratio, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Cohort Studies, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, 030212 general & internal medicine, lcsh:Science, Lungmedicin och allergi, COPD, Multidisciplinary, medicine.diagnostic_test, Chronic obstructive pulmonary disease, Incidence (epidemiology), Smoking, Middle Aged, Bronchodilator Agents, 3. Good health, Europe, trend, Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA), Female, Cohort study, Adult, Spirometry, Article, 03 medical and health sciences, Arbetsmedicin och miljömedicin, Sex Factors, cohort study, medicine, Humans, tobacco smoking, European Community Respiratory Health Survey (ECRHS), Disease burden, Asthma, business.industry, lcsh:R, Occupational Health and Environmental Health, medicine.disease, Risk factors, 030228 respiratory system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, incidence, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, lcsh:Q, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Ageing Lungs in European Cohorts (ALEC) Study, airflow obstruction, cohort study, European Community Respiratory Health Survey (ECRHS), incidence, Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA), tobacco smoking, trend, business, Demography
Abstract

Investigating COPD trends may help healthcare providers to forecast future disease burden. We estimated sex- and smoking-specific incidence trends of pre-bronchodilator airflow obstruction (AO) among adults without asthma from 11 European countries within a 20-year follow-up (ECRHS and SAPALDIA cohorts). We also quantified the extent of misclassification in the definition based on pre-bronchodilator spirometry (using post-bronchodilator measurements from a subsample of subjects) and we used this information to estimate the incidence of post-bronchodilator AO (AOpost-BD), which is the primary characteristic of COPD. AO incidence was 4.4 (95% CI: 3.5-5.3) male and 3.8 (3.1-4.6) female cases/1,000/year. Among ever smokers (median pack-years: 20, males; 12, females), AO incidence significantly increased with ageing in men only [incidence rate ratio (IRR), 1-year increase: 1.05 (1.03-1.07)]. A strong exposure-response relationship with smoking was found both in males [IRR, 1-pack-year increase: 1.03 (1.02-1.04)] and females [1.03 (1.02-1.05)]. The positive predictive value of AO for AOpost-BD was 59.1% (52.0-66.2%) in men and 42.6% (35.1-50.1%) in women. AOpost-BD incidence was 2.6 (1.7-3.4) male and 1.6 (1.0-2.2) female cases/1,000/year. AO incidence was considerable in Europe and the sex-specific ageing-related increase among ever smokers was strongly related to cumulative tobacco exposure. AOpost-BD incidence is expected to be half of AO incidence. ALEC has received funding from the European Union’s Horizon 2020 research and innovation programme [Grant Agreement No. 633212]. The co-ordination of the ECRHS was supported by the European Commission (phases 1 and 2) and the Medical Research Council (phase 3). The SAPALDIA cohort was funded by The State Secretariat for Education, Research and Innovation (SERI), Switzerland. The principal investigators and team members of the ECRHS and SAPALDIA studies, and the national funders who supported data collection in the ECRHS and SAPALDIA studies are listed in the appendix available in the Supplementary Information.

Published
2020
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43. Atopy modifies the association between inhaled corticosteroid use and lung function decline in patients with asthma

Author

Isabelle Pin, Isa Cerveri, Lucia Cazzoletti, Andrei Malinovschi, Josep M. Antó, Simone Accordini, Deborah Jarvis, David Gislason, Ane Johannessen, Bénédicte Leynaert, Pierpaolo Marchetti, Diogenes S. Ferreira, Nicole Probst-Hensch, Alessandro Marcon, Christer Janson, Rain Jögi, Judith Garcia-Aymerich, Angelo Corsico, Joachim Heinrich, Joost Weyler, Vieillissement et Maladies chroniques : approches épidémiologique et de santé publique (VIMA), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), 2610, 4350 97/0035-01, 99/0034-01, 99/0034-02 97/0035, 97/0035-02, 99/0034-04, 99/0034-06, 99/0034-07, 99/350 90MR/10, 91AF/6 SEPAR R01 HL62633-01 018996 911631 Russell Sage Foundation, RSF ResMed Foundation AstraZeneca GlaxoSmithKline, GSK Novartis U.S. Public Health Service, USPHS: R01 HL62633-01 Chiesi Farmaceutici, Chiesi Faculty of Arts and Sciences, Harvard University, FAS Boehringer Ingelheim VÃ¥rdalstiftelsen Freiwillige Akademische Gesellschaft, FAG Commercial Aircraft of China, COMAC Wellcome Trust, WT: WT 084703MA Horizon 2020 Framework Programme, H2020: 633212 Growing Spine Foundation, GSF Gobierno del Principado de Asturias Blond McIndoe Research Foundation, BMRF Asthma and Allergy Foundation of America, AAFA Ministerio de Sanidad, Consumo y Bienestar Social, MISAN Union Chimique Belge, UCB Medical Research Council, MRC: 92091, G0901214 National Institute for Health Research, NIHR British Lung Foundation, BLF European Commission, EC: EU-PEAL PL01237 National Health and Medical Research Council, NHMRC: G.0402.00 Asthma Foundation of Victoria Deutsche Forschungsgemeinschaft, DFG: FR1526/1-1, HE 3294/10-1, MA 711/4-1, MA 711/6-1, NO 262/7-1 Agence Nationale de la Recherche, ANR Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, SNSF: 3100-059302, 3200-042532, 3200-052720, 3247-065896, 3247BO-104283, 3247BO-104284, 3247BO-104288, 33CSCO-108796, 33CSCO-134276/1, 4026-028099, 4026-28099 Eesti Teadusfondi, ETF: 1088 ForskningsrÃ¥det för Arbetsliv och Socialvetenskap, FAS Eesti Teadusagentuur: 562 Bundesamt für Gesundheit, BAG Belgian Federal Science Policy Office, BELSPO Generalitat de Catalunya Consell Català de Recerca i Innovació: 1999SGR 00241 Haridus- ja Teadusministeerium: SF0180060s09 Hjärt-Lungfonden Consiglio Nazionale delle Ricerche, CNR Instituto de Salud Carlos III, ISCIII: C03/011, C03/09 Háskóli Íslands, HI Norges ForskningsrÃ¥d: 101422/310, 214123 Medicinska ForskningsrÃ¥det, MFR Cancéropôle Ile de France Russian Science Foundation, RSF: 381/05.93 Ministeriet Sundhed Forebyggelse SUVA Sociedad Española de Neumología y Cirugía Torácica, SEPAR: FIS 09/01511, FIS PS09/00716, FIS PS09/02185, FIS PS09/03190, SEPAR 1001/2010 Horizon 2020 Universiteit Antwerpen Comité des Maladies Respiratoires de l'Isère Comissió Interdepartamental de Recerca i Innovació Tecnològica, CIRIT: 1997 SGR 00079, 1999 SGR 00214 Servicio Murciano de Salud Regione del Veneto Regione Piemonte Astma- och Allergiförbundet Centre Hospitalier Universitaire de Bordeaux, CHU de Bordeaux Office Fédéral de l'Education et de la Science, OFES Bundesministerium für Bildung, Wissenschaft, Forschung und Technologie, BMBWF Helmholtz Zentrum München Lungenliga Schweiz Ministerio de Medio Ambiente y Medio Rural y Marino, MARM: G03/176 Ministère des Solidarités et de la Santé INCLIVA Instituto de Investigación Sanitaria: 91/0016-060-05/E, 92/0319, 93/0393, PS09/00716, PS09/01511, PS09/02185, PS09/02457, PS09/03190 Fundació Autònoma Solidària, FAS Servicio Andaluz de Salud, SAS, The ALEC study is funded by the European Union's Horizon 2020 Research and Innovation programme under grant agreement number 633212. ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya. National funders who supported data collection in the original studies are listed in Appendix E4 in this article's Online Repository at www.jaci-inpractice.org. The funders had no role in the writing of the manuscript or the decision to submit it for publication.Conflicts of interest: D. S. Ferreira reports grants from the Asthma Foundation of Victoria, Allen and Hanburys, National Health and Medical Research Council. I. Pin reports travel grants and honoraria from Novartis, Zambon, and AstraZeneca, and nonfinancial support from AGIR?dom. R. J?gi reports grants from Estonian Research Council Personal Research (grant no. 562), and consultancy, lecture, and travel fees from GlaxoSmithKline, Boehringer, and Novartis. The rest of the authors report no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years, and no other relationships or activities that could appear to have influenced the submitted work.Financial support for ECRHS I: The coordination of this work was supported by the European Commission, and the authors and participants are grateful to the late C. Baya and M. Hallen for their help during the study and K. Vuylsteek and the members of the COMAC for their support. The following grants helped to fund the local studies: Australia: Asthma Foundation of Victoria, Allen and Hanbury's, Belgium: Belgian Science Policy Office, National Fund for Scientific Research, Estonia: Estonian Science Foundation (grant no. 1088), France: Minist?re de la Sant?, Glaxo France, Institut Pneumologique d'Aquitaine, Contrat de Plan Etat-R?gion Languedoc-Rousillon, Caisse nationale de l'assurance maladie des travailleurs salari?s, Comit? national contre les maladies respiratoires et la tuberculose (90MR/10, 91AF/6), Ministre delegu? de la sant?, R?seau national de sant? publique, France, Germany: Helmholtz Zentrum Munich and Bundesminister f?r Forschung und Technologie, Italy: Ministero dell'Universit? e della Ricerca Scientifica e Tecnologica, Consiglio Nazionale delle Ricerche, Regione Veneto (grant RSF no. 381/05.93), Norway: Norwegian Research Council project no. 101422/310, Portugal: Glaxo Farmac?utica Lda, Sandoz Portugesa, Spain: Fondo de Investigaci?n Sanitaria (nos. 91/0016-060-05/E, 92/0319, and 93/0393), Hospital General de Albacete, Hospital General Juan Ram?n Jim?nez, Direcci?n Regional de Salud P?blica (Consejer?a de Sanidad del Principado de Asturias), Consell Interdepartamental de Recerca i Innovaci? Tecnol?gica (1997 SGR 00079), and Servicio Andaluz de Salud, Sweden: The Swedish Medical Research Council, the Swedish Heart-Lung Foundation, the Swedish Association against Asthma and Allergy, Switzerland: Swiss National Science Foundation (grant no. 4026-28099), and UK: National Asthma Campaign, British Lung Foundation, Department of Health, South Thames Regional Health Authority.Financial support for ECRHS II: Australia: National Health and Medical Research Council, Belgium: Antwerp: Fund for Scientific Research (grant code G.0402.00), University of Antwerp, and Flemish Health Ministry, Estonia: Tartu: Estonian Science Foundation (grant no. 4350), France: (All) Programme Hospitalier de Recherche Clinique?Direction de la Recherche Clinique de Grenoble 2000 number 2610, Ministry of Health, Minist?re de l'Emploi et de la Solidarit?, Direction G?nerale de la Sant?, Centre Hospitalier Universitaire de Grenoble, Bordeaux: Institut Pneumologique d'Aquitaine, Grenoble: Comite des Maladies Respiratoires de l'Isere, Montpellier: Aventis (France), Direction Regionale des Affaires Sanitaires et Sociales Languedoc-Roussillon, Paris: Union Chimique Belge-Pharma (France), Aventis (France), Glaxo France, Germany: Erfurt: GSF?National Research Centre for Environment and Health, Deutsche Forschungsgemeinschaft (grant code FR1526/1-1), Hamburg: GSF?National Research Centre for Environment and Health, Deutsche Forschungsgemeinschaft (grant code MA 711/4-1), Iceland: Reykjavik: Icelandic Research Council and Icelandic University Hospital Fund, Italy: Pavia: GlaxoSmithKline Italy, Italian Ministry of University and Scientific and Technological Research (MURST), and Local University Funding for Research 1998 and 1999, Turin: Azienda Sanitaria Locale 4 Regione Piemonte (Italy), Azienda Ospedaliera Centro Traumatologico Ospedaliero/Centro Traumatologico Ortopedico?Istituto Clinico Ortopedico Regina Maria Adelaide Regione Piemonte, Verona: Ministero dell'Universit? e della Ricerca Scientifica (MURST), Glaxo Wellcome s.p.a., Norway: Bergen: Norwegian Research Council, Norwegian Asthma and Allergy Association, Glaxo Wellcome AS, and Norway Research Fund, Spain: Fondo de Investigacion Santarias (grant codes 97/0035-01, 99/0034-01, and 99/0034-02), Hospital Universitario de Albacete, Consejeria de Sanidad, Barcelona: Sociedad Espanola de Neumolog?a y Cirug?a Toracica, Public Health Service (grant code R01 HL62633-01), Fondo de Investigaciones Santarias (grant codes 97/0035-01, 99/0034-01, and 99/0034-02), Consell Interdepartamentalde Recerca i Innovaci? Tecnol?gica (grant code 1999SGR 00241), Instituto de Salud Carlos III, Red de Centros de Epidemiolog?a y Salud P?blica, C03/09, Red de Bases moleculares y fisiol?gicas de las Enfermedades Respiratorias, C03/011 and Red de Grupos Infancia y Medio Ambiente G03/176, Huelva: Fondo de Investigaciones Santarias (grant codes 97/0035-01, 99/0034-01, and 99/0034-02), Galdakao: Basque Health Department, Oviedo: Fondo de Investigaciones Sanitaria (97/0035-02, 97/0035, 99/0034-01, 99/0034-02, 99/0034-04, 99/0034-06, 99/350, and 99/0034-07), European Commission (EU-PEAL PL01237), Generalitat de Catalunya (CIRIT 1999 SGR 00214), Hospital Universitario de Albacete, Sociedad Espa?ola de Neumolog?a y Cirug?a Tor?cica (SEPAR R01 HL62633-01), Red de Centros de Epidemiolog?a y Salud P?blica (C03/09), Red de Bases moleculares y fisiol?gicas de las Enfermedades Respiratorias (C03/011), and Red de Grupos Infancia y Medio Ambiente (G03/176, 97/0035-01, 99/0034-01, and 99/0034-02), Sweden: G?teborg, Umea, AND Uppsala: Swedish Heart Lung Foundation, Swedish Foundation for Health Care Sciences and Allergy Research, Swedish Asthma and Allergy Foundation, Swedish Cancer and Allergy Foundation, and Swedish Council for Working Life and Social Research (FAS), Switzerland: Basel: Swiss National Science Foundation, Swiss Federal Office for Education and Science, and Swiss National Accident Insurance Fund, UK: Ipswich and Norwich: Asthma UK (formerly known as National Asthma Campaign).Financial support for ECRHS III: Australia: National Health and Medical Research Council, Belgium: Antwerp: South and Antwerp City: Research Foundation Flanders (grant code G.0.410.08.N.10), Estonia: Tartu: the Estonian Ministry of Education (SF0180060s09), France: (All): Minist?re de la Sant?, Programme Hospitalier de Recherche Clinique national 2010, Bordeaux: INSERM U897 Universit? Bordeaux segalen, Grenoble: Comite Scientifique AGIRadom 2011, and Paris: Agence Nationale de la Sant?, R?gion Ile de France, domaine d'int?r?t majeur, Germany: Erfurt: German Research Foundation (HE 3294/10-1), Hamburg: German Research Foundation (MA 711/6-1, NO 262/7-1), Iceland: Reykjavik: The Landspitali University Hospital Research Fund, University of Iceland Research Fund, ResMed Foundation, California, USA, Orkuveita Reykjavikur (Geothermal plant), and Vegager?in (The Icelandic Road Administration, Italy: All Italian centers were funded by the Italian Ministry of Health, Chiesi Farmaceutici SpA, in addition, Verona was funded by Cariverona Foundation and Education Ministry (Ministero dell'Istruzione, dell'Universit? e della Ricerca), Norway: Norwegian Research Council (grant no. 214123), Western Norway Regional Health Authorities (grant no. 911631), and Blond McIndoe Research Foundation, Spain: Fondo de Investigaci?n Sanitaria (PS09/02457, PS09/00716, PS09/01511, PS09/02185, PS09/03190), Servicio Andaluz de Salud, Sociedad Espa?ola de Neumolog?a y Cirurg?a Tor?cica (SEPAR 1001/2010), Fondo de Investigaci?n Sanitaria (PS09/02457), Barcelona: Fondo de Investigaci?n Sanitaria (FIS PS09/00716), Galdakao: Fondo de Investigaci?n Sanitaria (FIS 09/01511), Huelva: Fondo de Investigaci?n Sanitaria (FIS PS09/02185) and Servicio Andaluz de Salud, Oviedo: Fondo de Investigaci?n Sanitaria (FIS PS09/03190), Sweden: All centers were funded by The Swedish Heart and Lung Foundation, The Swedish Asthma and Allergy Association, The Swedish Association against Lung and Heart Disease, Swedish Research Council for health, working life and welfare, G?teborg: also received further funding from the Swedish Council for Working Life and Social Research. Umea: also received funding from Vasterbotten Country Council ALF grant, Switzerland: The Swiss National Science Foundation (grants nos. 33CSCO-134276/1, 33CSCO-108796, 3247BO-104283, 3247BO-104288, 3247BO-104284, 3247-065896, 3100-059302, 3200-052720, 3200-042532, and 4026-028099), The Federal Office for Forest, Environment and Landscape, The Federal Office of Public Health, The Federal Office of Roads and Transport, the canton's government of Aargan, Basel-Stadt, Basel-Land, Geneva, Luzern, Ticino, Valais, and Z?rich, the Swiss Lung League, the canton's Lung League of Basel-Stadt/Basel, Landschaft, Geneva, Ticino, Valais, and Zurich, SUVA, Freiwillige Akademische Gesellschaft, UBS Wealth Foundation, Talecris Biotherapeutics GmbH, Abbott Diagnostics, European Commission 018996 (GABRIEL), Wellcome Trust WT 084703MA, and UK: Medical Research Council (grant no.92091), support also provided by the National Institute for Health Research through the Primary Care Research Network., Financial support for ECRHS III: Australia: National Health and Medical Research Council, Estonia: Tartu: the Estonian Ministry of Education ( SF0180060s09 ), France: (All): Ministère de la Santé, Programme Hospitalier de Recherche Clinique national 2010, Bordeaux: INSERM U897 Université Bordeaux segalen, and Paris: Agence Nationale de la Santé, Région Ile de France, domaine d'intérêt majeur, Germany: Erfurt: German Research Foundation ( HE 3294/10-1 ), Hamburg: German Research Foundation ( MA 711/6-1 , NO 262/7-1 ), Iceland: Reykjavik: The Landspitali University Hospital Research Fund, University of Iceland Research Fund, ResMed Foundation , California, USA , Orkuveita Reykjavikur (Geothermal plant), and Vegagerðin (The Icelandic Road Administration, Italy: All Italian centers were funded by the Italian Ministry of Health , Chiesi Farmaceutici SpA, in addition, Verona was funded by Cariverona Foundation and Education Ministry (Ministero dell'Istruzione, dell'Università e della Ricerca), Norway: Norwegian Research Council (grant no. 214123 ), Western Norway Regional Health Authorities (grant no. 911631 ), and Blond McIndoe Research Foundation, Spain: Fondo de Investigación Sanitaria (PS09/02457, PS09/00716, PS09/01511, PS09/02185, PS09/03190), Servicio Andaluz de Salud, Sociedad Española de Neumología y Cirurgía Torácica ( SEPAR 1001/2010), Fondo de Investigación Sanitaria (PS09/02457), Barcelona: Fondo de Investigación Sanitaria (FIS PS09/00716), Galdakao: Fondo de Investigación Sanitaria (FIS 09/01511), Huelva: Fondo de Investigación Sanitaria (FIS PS09/02185) and Servicio Andaluz de Salud, Oviedo: Fondo de Investigación Sanitaria (FIS PS09/03190), Sweden: All centers were funded by The Swedish Heart and Lung Foundation, The Swedish Asthma and Allergy Association , The Swedish Association against Lung and Heart Disease , Swedish Research Council for health, working life and welfare, Göteborg: also received further funding from the Swedish Council for Working Life and Social Research . Umea: also received funding from Vasterbotten Country Council ALF grant, Switzerland: The Swiss National Science Foundation (grants nos. 33CSCO-134276/1 , 33CSCO-108796 , 3247BO-104283 , 3247BO-104288 , 3247BO-104284 , 3247-065896 , 3100-059302 , 3200-052720 , 3200-042532 , and 4026-028099 ), The Federal Office for Forest, Environment and Landscape, The Federal Office of Public Health, The Federal Office of Roads and Transport, the canton's government of Aargan, Basel-Stadt, Basel-Land, Geneva, Luzern, Ticino, Valais, and Zürich, the Swiss Lung League , the canton's Lung League of Basel-Stadt/Basel, Landschaft, Geneva, Ticino, Valais, and Zurich, SUVA, Freiwillige Akademische Gesellschaft , UBS Wealth Foundation, Talecris Biotherapeutics GmbH, Abbott Diagnostics , European Commission 018996 (GABRIEL), Wellcome Trust WT 084703MA, and UK: Medical Research Council (grant no. 92091 ), support also provided by the National Institute for Health Research through the Primary Care Research Network ., Conflicts of interest: D. S. Ferreira reports grants from the Asthma Foundation of Victoria , Allen and Hanburys , National Health and Medical Research Council . I. Pin reports travel grants and honoraria from Novartis , Zambon , and AstraZeneca , and nonfinancial support from AGIRàdom. R. Jõgi reports grants from Estonian Research Council Personal Research (grant no. 562 ), and consultancy, lecture, and travel fees from GlaxoSmithKline, Boehringer, and Novartis. The rest of the authors report no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years, and no other relationships or activities that could appear to have influenced the submitted work., Financial support for ECRHS II: Australia: National Health and Medical Research Council, Belgium: Antwerp: Fund for Scientific Research (grant code G.0402.00 ), University of Antwerp , and Flemish Health Ministry, Estonia: Tartu: Estonian Science Foundation (grant no. 4350 ), France: (All) Programme Hospitalier de Recherche Clinique—Direction de la Recherche Clinique de Grenoble 2000 number 2610, Ministry of Health , Ministère de l’Emploi et de la Solidarité, Direction Génerale de la Santé, Centre Hospitalier Universitaire de Grenoble, Bordeaux: Institut Pneumologique d’Aquitaine, Grenoble: Comite des Maladies Respiratoires de l’Isere, Germany: Erfurt: GSF— National Research Centre for Environment and Health , Deutsche Forschungsgemeinschaft (grant code FR1526/1-1 ), Hamburg: GSF— National Research Centre for Environment and Health , Deutsche Forschungsgemeinschaft (grant code MA 711/4-1 ), Turin: Azienda Sanitaria Locale 4 Regione Piemonte (Italy), Azienda Ospedaliera Centro Traumatologico Ospedaliero/Centro Traumatologico Ortopedico—Istituto Clinico Ortopedico Regina Maria Adelaide Regione Piemonte, Verona: Ministero dell’Università e della Ricerca Scientifica (MURST), Glaxo Wellcome s.p.a., Norway: Bergen: Norwegian Research Council , Norwegian Asthma and Allergy Association , Glaxo Wellcome AS , and Norway Research Fund, Spain: Fondo de Investigacion Santarias (grant codes 97/0035-01 , 99/0034-01 , and 99/0034-02 ), Hospital Universitario de Albacete, Consejeria de Sanidad, Barcelona: Sociedad Espanola de Neumología y Cirugía Toracica, Public Health Service (grant code R01 HL62633-01 ), Fondo de Investigaciones Santarias (grant codes 97/0035-01 , 99/0034-01 , and 99/0034-02 ), Consell Interdepartamentalde Recerca i Innovació Tecnológica (grant code 1999SGR 00241 ), Instituto de Salud Carlos III, Red de Centros de Epidemiología y Salud Pública, C03/09, Red de Bases moleculares y fisiológicas de las Enfermedades Respiratorias, C03/011 and Red de Grupos Infancia y Medio Ambiente G03/176, Huelva: Fondo de Investigaciones Santarias (grant codes 97/0035-01 , 99/0034-01 , and 99/0034-02 ), Oviedo: Fondo de Investigaciones Sanitaria ( 97/0035-02 , 97/0035 , 99/0034-01 , 99/0034-02 , 99/0034-04 , 99/0034-06 , 99/350 , and 99/0034-07 ), European Commission ( EU-PEAL PL01237 ), Generalitat de Catalunya ( CIRIT 1999 SGR 00214), Hospital Universitario de Albacete, Sociedad Española de Neumología y Cirugía Torácica ( SEPAR R01 HL62633-01 ), Red de Centros de Epidemiología y Salud Pública (C03/09), Red de Bases moleculares y fisiológicas de las Enfermedades Respiratorias (C03/011), and Red de Grupos Infancia y Medio Ambiente (G03/176, Sweden: Göteborg, Umea, AND Uppsala: Swedish Heart Lung Foundation, Swedish Foundation for Health Care Sciences and Allergy Research , Swedish Asthma and Allergy Foundation , Swedish Cancer and Allergy Foundation , and Swedish Council for Working Life and Social Research ( FAS ), Switzerland: Basel: Swiss National Science Foundation , Swiss Federal Office for Education and Science , and Swiss National Accident Insurance Fund, UK: Ipswich and Norwich: Asthma UK (formerly known as National Asthma Campaign)., Financial support for ECRHS I: The coordination of this work was supported by the European Commission , and the authors and participants are grateful to the late C. Baya and M. Hallen for their help during the study and K. Vuylsteek and the members of the COMAC for their support. The following grants helped to fund the local studies: Australia: Asthma Foundation of Victoria , Allen and Hanbury's, Belgium: Belgian Science Policy Office , National Fund for Scientific Research, Estonia: Estonian Science Foundation (grant no. 1088 ), France: Ministère de la Santé, Glaxo France , Institut Pneumologique d'Aquitaine , Contrat de Plan Etat-Région Languedoc-Rousillon , Caisse nationale de l'assurance maladie des travailleurs salariés, Comité national contre les maladies respiratoires et la tuberculose (90MR/10, 91AF/6), Ministre delegué de la santé, Réseau national de santé publique, France, Germany: Helmholtz Zentrum Munich and Bundesminister für Forschung und Technologie, Italy: Ministero dell'Università e della Ricerca Scientifica e Tecnologica, Consiglio Nazionale delle Ricerche, Regione Veneto (grant RSF no. 381/05.93 ), Portugal: Glaxo Farmacêutica Lda, Sandoz Portugesa, Spain: Fondo de Investigación Sanitaria (nos. 91/0016-060-05/E , 92/0319 , and 93/0393 ), Hospital General de Albacete, Hospital General Juan Ramón Jiménez, Dirección Regional de Salud Pública (Consejería de Sanidad del Principado de Asturias), Consell Interdepartamental de Recerca i Innovació Tecnològica (1997 SGR 00079), and Servicio Andaluz de Salud, Sweden: The Swedish Medical Research Council , the Swedish Heart-Lung Foundation , the Swedish Association against Asthma and Allergy, Switzerland: Swiss National Science Foundation (grant no. 4026-28099 ), and UK: National Asthma Campaign , British Lung Foundation , Department of Health , South Thames Regional Health Authority ., The ALEC study is funded by the European Union’s Horizon 2020 Research and Innovation programme under grant agreement number 633212. ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya. National funders who supported data collection in the original studies are listed in Appendix E4 in this article's Online Repository at www.jaci-inpractice.org . The funders had no role in the writing of the manuscript or the decision to submit it for publication., Commission of the European Communities, Medical Research Council (MRC), and Ageing Lungs European Cohorts ALEC

Subjects
Allergy, Epidemiology, Respiratory Medicine and Allergy, Cohort Studies, Atopy, Allergic sensitization, 0302 clinical medicine, Adrenal Cortex Hormones, Immunology and Allergy, Medicine, 030212 general & internal medicine, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, Lung, Sensitization, Lungmedicin och allergi, biology, Inhaled corticosteroids, Lung function decline, Pyroglyphidae, Precision medicine, 3. Good health, PROPENSITY SCORE, medicine.anatomical_structure, IgE, Cohort study, Life Sciences & Biomedicine, Response to corticosteroids, Asthma, Adult, medicine.medical_specialty, Immunology, Allergic inflammation, 03 medical and health sciences, FEV1/FVC ratio, Internal medicine, Administration, Inhalation, Animals, Humans, House dust mite, Science & Technology, business.industry, Ageing Lungs in European Cohorts (ALEC) study, medicine.disease, biology.organism_classification, 030228 respiratory system, Cats, Human medicine, business
Abstract

BACKGROUND: Inhaled corticosteroids (ICSs) are the mainstay of asthma treatment, but response to medication is variable. Patients with allergic inflammation generally show a better short-term response to ICSs; however, studies on predictors of long-term response are few. OBJECTIVE: To assess whether allergic sensitization can modify the association between ICS use and lung function decline over 20 years in adult asthma. METHODS: We used data from the 3 clinical examinations of the European Community Respiratory Health Survey. We measured ICS use (no use, and use for 8 years) and FEV1 decline among subjects with asthma over the 2 periods between consecutive examinations. We conducted a cohort study combining data of the 2 periods (906 observations from 745 subjects) to assess whether the association between ICS use and FEV1 decline was modified by allergic sensitization (IgE > 0.35 kU/L for any of house-dust mite, timothy grass, cat, or Cladosporium). RESULTS: FEV1 decline was similar for non-ICS users, as well as ICS users for less than 1.3 years, with and without allergic sensitization. However, among subjects on ICSs for a longer period, sensitization was associated with an attenuated decline (P-interaction = .006): in the group treated for more than 8 years, FEV1 decline was on average 27 mL/y (95% CIBonferroni-adjusted, 11-42) lower for subjects with sensitization compared with nonsensitized subjects. CONCLUSIONS: Our study suggests that biomarkers of atopy can predict a more favorable long-term response to ICSs. Randomized controlled studies are needed to confirm these findings. (C) 2019 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology.

Published
2020
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44. Body mass index and weight change are associated with adult lung function trajectories:The prospective ECRHS study

Author

Peter Burney, Gayan Bowatte, Torben Sigsgaard, Valérie Siroux, Mathias Holm, Jan Paul Zock, Joachim Heinrich, Isabel Urrutia, Andre F.S. Amaral, Elaine Fuertes, Anne-Elie Carsin, Bénédicte Leynaert, Jesús Martínez-Moratalla Rovira, Nicole Probst-Hensch, Chantal Raherison, Alessandro Marcon, Thorarinn Gislason, Christer Janson, Gabriela P. Peralta, José Antonio Gullón, Judith Garcia-Aymerich, Simone Accordini, Vanessa Garcia-Larsen, Pascal Demoly, Joost Weyler, Deborah Jarvis, José Luis Sánchez-Ramos, Shyamali C. Dharmage, Bertil Forsberg, Michael J. Abramson, Giulia Squillacioti, Angelo Corsico, Josep M. Antó, Dennis Nowak, Rain Jõgi, Ane Johannessen, Læknadeild (HÍ), Faculty of Medicine (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland, Service d'allergologie et de pneumologie [Hôpital Arnaud de Villeneuve], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Vieillissement et Maladies chroniques : approches épidémiologique et de santé publique (VIMA), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Epidemiologie-Biostatistique [Bordeaux], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux Ségalen [Bordeaux 2], Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), European Project: 633212,H2020,H2020-PHC-2014-two-stage,ALEC(2015), Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)

Subjects
Male, obesity, Offita, Respiratory Medicine and Allergy, Vital Capacity, Physiology, Respiratory Epidemiology, Weight Gain, Body Mass Index, Cohort Studies, 0302 clinical medicine, Weight loss, Forced Expiratory Volume, adults, 030212 general & internal medicine, Prospective Studies, Young adult, Prospective cohort study, media_common, Lungmedicin och allergi, 2. Zero hunger, medicine.diagnostic_test, weight change, Age Factors, LUNGNA, EPICENE, respiratory system, 3. Good health, Respiratory Function Tests, Female, epidemiology, medicine.symptom, Pulmonary and Respiratory Medicine, Spirometry, Adult, Risk Assessment, 03 medical and health sciences, Young Adult, BMI, Sex Factors, Predictive Value of Tests, Weight Loss, medicine, lung function, media_common.cataloged_instance, Humans, European Union, European union, Life Style, Aged, business.industry, Weight change, Body Weight, respiratory tract diseases, 030228 respiratory system, Þyngd, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Lungu, Human medicine, business, Weight gain, Body mass index, Follow-Up Studies
Abstract

Publisher's version (útgefin grein), Background: Previous studies have reported an association between weight increase and excess lung function decline in young adults followed for short periods. We aimed to estimate lung function trajectories during adulthood from 20-year weight change profiles using data from the population-based European Community Respiratory Health Survey (ECRHS). Methods: We included 3673 participants recruited at age 20-44 years with repeated measurements of weight and lung function (forced vital capacity (FVC), forced expiratory volume in 1 s (FEV 1)) in three study waves (1991-93, 1999-2003, 2010-14) until they were 39-67 years of age. We classified subjects into weight change profiles according to baseline body mass index (BMI) categories and weight change over 20 years. We estimated trajectories of lung function over time as a function of weight change profiles using population-averaged generalised estimating equations. Results: In individuals with normal BMI, overweight and obesity at baseline, moderate (0.25-1 kg/year) and high weight gain (>1 kg/year) during follow-up were associated with accelerated FVC and FEV 1 declines. Compared with participants with baseline normal BMI and stable weight (±0.25 kg/year), obese individuals with high weight gain during follow-up had -1011 mL (95% CI -1.259 to -763) lower estimated FVC at 65 years despite similar estimated FVC levels at 25 years. Obese individuals at baseline who lost weight (, Funding The present analyses are part of the ageing lungs in european cohorts (alec) study (www.alecstudy.org), which has received funding from the european Union’s horizon 2020 research and innovation programme under grant agreement no. 633212. The local investigators and funding agencies for the european community respiratory health survey are reported in the online supplement. isglobal is a member of the cerca Programme, generalitat de catalunya.

Published
2020
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45. Physical activity and lung function-Cause or consequence?

Author

Gabriela P. Peralta, Simone Accordini, Joost Weyler, Deborah Jarvis, Annabelle Bédard, Elaine Fuertes, José Luis Sánchez-Ramos, Giulia Squillacioti, Vanessa Garcia-Larsen, Judith Garcia-Aymerich, Shyamali C. Dharmage, Ane Johannessen, Bénédicte Leynaert, Joachim Heinrich, Isabelle Pin, Christer Janson, Anne-Elie Carsin, and European Union's Horizon 2020 research and innovation programme

Subjects
Male, Vital capacity, Pulmonology, Physiology, Respiratory Medicine and Allergy, Vital Capacity, Pulmonary function testing, 0302 clinical medicine, Medical Conditions, Forced Expiratory Volume, Medicine and Health Sciences, Public and Occupational Health, 030212 general & internal medicine, Longitudinal Studies, Young adult, Lung, Respiratory Tract Infections, Lungmedicin och allergi, Multidisciplinary, Smokers, Longitudinal studies, Confounding, Smoking, Middle Aged, Respiratory Function Tests, Infectious Diseases, Physiological Parameters, Research Design, Medicine, Female, Engineering sciences. Technology, Cohort study, Research Article, Adult, Computer and Information Sciences, Pulmonary function, Adolescent, General Science & Technology, Science, Research and Analysis Methods, Data management, Structural equation modeling, 03 medical and health sciences, Respiratory Disorders, Young Adult, Physical activity, Pulmonary function, Body weight, Diet, Respiratory infections, Data management, Nutrition, Longitudinal studies, medicine, Humans, Exercise, Asthma, Nutrition, business.industry, Physical activity, Body Weight, Biology and Life Sciences, Respiratory infections, Body weight, medicine.disease, Health Surveys, Diet, 030228 respiratory system, Causal inference, business, Demography
Abstract

Concerns exist that the positive association of physical activity with better lung function, which has been suggested in previous longitudinal studies in smokers, is due to reverse causation. To investigate this, we applied structural equation modeling (SEM), an exploratory approach, and marginal structural modeling (MSM), an approach from the causal inference framework that corrects for reverse causation and time-dependent confounding and estimates causal effects, on data from participants in the European Community Respiratory Health Survey (ECRHS, a multicentre European cohort study initiated in 1991-1993 with ECRHS I, and with two follow-ups: ECRHS II in 1999-2003, and ECRHS III in 2010-2014). 753 subjects who reported current smoking at ECRHS II, with repeated data on lung function at ECRHS I, II and III, physical activity at ECRHS II and III, and potential confounders at ECRHS I and II, were included in the analyses. SEM showed positive associations between physical activity and lung function in both directions. MSM suggested a protective causal effect of physical activity on lung function (overall difference in mean β (95% CI), comparing active versus non-active individuals: 58 mL (21-95) for forced expiratory volume in one second and 83 mL (36-130) for forced vital capacity). Our results suggest bi-directional causation and support a true protective effect of physical activity on lung function in smokers, after accounting for reverse causation and time-dependent confounding. The present analyses are part of the Ageing Lungs in European Cohorts (ALEC) Study (www.alecstudy.org), which has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no 633212.

Published
2020

47. Determinants of fractional exhaled nitric oxide in healthy men and women from the European Community Respiratory Health Survey III

Author

Roberto Bono, Mario Olivieri, Torben Sigsgaard, Anna C. Olin, A. Malinovschi, Deborah Jarvis, Isabelle Pin, Bénédicte Leynaert, Simone Accordini, Joachim Heinric, Jan Paul Zock, Elisabet Nerpin, Angelo Corsico, Bertil Forsberg, Christer Janson, Alessandro Marcon, Lucia Cazzoletti, Pascal Demoly, Joost Weyler, Rune Nielsen, Thorainn Gislason, Diogenes S. Ferreira, Rain Jõgi, Ane Johannessen, Dennis Nowak, Uppsala University Hospital, University of Verona (UNIVR), Landspitali National University Hospital of Iceland, Department of Swedish [Gothenburg], University of Gothenburg (GU), Haukeland University Hospital, University of Bergen (UiB), Monash University [Melbourne], Universidade Federal do Parana [Curitiba] (UFPR), Universidade Federal do Paraná (UFPR), Department of Diagnostics and Public Health [Verona] (UNIVR | DDSP), Centre Hospitalier Universitaire [Grenoble] (CHU), University of Pavia, Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Universiteit Antwerpen [Antwerpen], Ludwig Maximilian University [Munich] (LMU), University of Tartu, Umeå University, Universitat Pompeu Fabra [Barcelona] (UPF), Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), Aarhus University Hospital, Ludwig-Maximilians-Universität München (LMU), Helmholtz-Zentrum München (HZM), Melbourne School of Population and Global Health [Melbourne], University of Melbourne, University of Turin, Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, European Community Resp Hlth Surve, Università degli studi di Verona = University of Verona (UNIVR), Università degli Studi di Pavia = University of Pavia (UNIPV), Universiteit Antwerpen = University of Antwerpen [Antwerpen], Helmholtz Zentrum München = German Research Center for Environmental Health, Università degli studi di Torino = University of Turin (UNITO), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and Salvy-Córdoba, Nathalie

Subjects
Male, 0301 basic medicine, Fractional Exhaled Nitric Oxide, Healthy Population, Ige Sensitization, Smoking, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 0302 clinical medicine, Surveys and Questionnaires, Immunology and Allergy, Medicine, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, Ige sensitization, Healthy population, Middle Aged, respiratory system, 3. Good health, fractional exhaled nitric oxide, Breath Tests, Exhalation, Biomarker (medicine), Female, FENO, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology, Adult, medicine.medical_specialty, European community, Immunology, IgE sensitization, Nitric Oxide, smoking, 03 medical and health sciences, Internal medicine, Humans, European Union, Respiratory health, FENO, healthy population, IgE sensitization, smoking, Aged, Asthma, business.industry, Fractional exhaled nitric oxide, medicine.disease, Health Surveys, respiratory tract diseases, Cross-Sectional Studies, 030104 developmental biology, 030228 respiratory system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Exhaled nitric oxide, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, healthy population, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Human medicine, business, Follow-Up Studies
Abstract

Introduction: The fractional exhaled nitric oxide (FENO) is a marker for type 2 inflammation used in diagnostics and management of asthma. In order to use FENO as a reliable biomarker, it is important to investigate factors that influence FENO in healthy individuals. Men have higher levels of FENO than women, but it is unclear whether determinants of FENO differ by sex. Objective: To identify determinants of FENO in men and women without lung diseases. Method: Fractional exhaled nitric oxide was validly measured in 3881 healthy subjects that had answered the main questionnaire of the European Community Respiratory Health Survey III without airways or lung disease. Results: Exhaled NO levels were 21.3% higher in men compared with women P ENO than subjects in the lowest age quartile (39.7-48.3 years) P = 0.02. Women in the two highest age quartiles (54.6-60.2 and 60.3-67.6 years) had 15.4 ppb (14.7, 16.2), P = 0.03 and 16.4 ppb (15.6, 17.1), P = ENO, compared with the lowest age quartile. Height was related to 8% higher FENO level in men (P ENO levels in women (P = 0.008). Men who smoked had 37% lower FENO levels and women had 30% lower levels compared with never-smokers (P ENO levels compared with non-sensitized subjects 26% and 29%, P ENO started increasing at lower age in women than in men, suggesting that interpretation of FENO levels in adults aged over 50 years should take into account age and sex.

Published
2019
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48. Data-driven adult asthma phenotypes based on clinical characteristics are associated with asthma outcomes twenty years later

Author

Isabelle Pin, Valérie Siroux, Christer Janson, Jordi Sunyer, Bénédicte Leynaert, Raphaëlle Varraso, Anne Boudier, Sébastien Chanoine, Jean Bousquet, Christophe Pison, Régis Matran, Xavier Basagaña, Simone Accordini, Deborah Jarvis, Pascal Demoly, Joachim Heinrich, Judith Garcia-Aymerich, Chantal Raherison, Nino Künzli, Josep M. Antó, Frédéric Gormand, Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Vieillissement et Maladies chroniques : approches épidémiologique et de santé publique (VIMA), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Medical Research Council (MRC), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)

Subjects
0301 basic medicine, Male, Allergy, Asthma phenotypes, [SDV]Life Sciences [q-bio], 0302 clinical medicine, Quality of life, immune system diseases, Risk Factors, Epidemiology, follow-up, Immunology and Allergy, Public Health Surveillance, Registries, Lung function, phenotypes, EPICENE, Middle Aged, 3. Good health, LUNG-FUNCTION, Europe, Phenotype, asthma, clustering, lung function, 1107 Immunology, Female, Symptom Assessment, Life Sciences & Biomedicine, Adult, medicine.medical_specialty, Immunology, Risk Assessment, 03 medical and health sciences, Internal medicine, medicine, Humans, Clinical significance, Asthma, CLUSTER-ANALYSIS, Science & Technology, business.industry, Genetic heterogeneity, medicine.disease, respiratory tract diseases, LIFE, 030104 developmental biology, 030228 respiratory system, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, RESPONSES, Follow-Up Studies
Abstract

European Journal of Allergy and Clinical 2018, in press; BACKGROUND:Research based on cluster analyses led to the identification of particular phenotypes confirming phenotypic heterogeneity of asthma. The long-term clinical course of asthma phenotypes defined by clustering analysis remains unknown, although it is a key aspect to underpin their clinical relevance. We aimed to estimate risk of poor asthma events between asthma clusters identified 20 years earlier.METHODS:The study relied on two cohorts of adults with asthma with 20-year follow-up, ECRHS (European Community Respiratory Health Survey) and EGEA (Epidemiological study on Genetics and Environment of Asthma). Regression models were used to compare asthma characteristics (current asthma, asthma exacerbations, asthma control, quality of life, and FEV1 ) at follow-up and the course of FEV1 between seven cluster-based asthma phenotypes identified 20 years earlier.RESULTS:The analysis included 1325 adults with ever asthma. For each asthma characteristic assessed at follow-up, the risk for adverse outcomes differed significantly between the seven asthma clusters identified at baseline. As compared with the mildest asthma phenotype, ORs (95% CI) for asthma exacerbations varied from 0.9 (0.4 to 2.0) to 4.0 (2.0 to 7.8) and the regression estimates (95% CI) for FEV1 % predicted varied from 0.6 (-3.5 to 4.6) to -9.9 (-14.2 to -5.5) between clusters. Change in FEV1 over time did not differ significantly across clusters.CONCLUSION:Our findings show that the long-term risk for poor asthma outcomes differed between comprehensive adult asthma phenotypes identified 20 years earlier, and suggest a strong tracking of asthma activity and impaired lung function over time.

Published
2019

49. The role of C-reactive protein levels on the association of physical activity with lung function in adults

Author

Stefano Guerra, Rain Jõgi, Bénédicte Leynaert, Isabelle Pin, Jesús Martínez-Moratalla, Josep M. Antó, Anne-Elie Carsin, Joachim Heinrich, Thorarinn Gislason, Isabel Urrutia, Audrey Le Gouellec, Christer Janson, Elaine Fuertes, Vanessa Garcia-Larsen, Judith Garcia-Aymerich, Simone Accordini, Deborah Jarvis, Commission of the European Communities, European Union’s Horizon 2020 research and innovation programme, and Medical Research Council (MRC)

Subjects
Male, Questionnaires, Vital capacity, Pulmonology, Respiratory Medicine and Allergy, Social Sciences, Physiology, Surveys, 030204 cardiovascular system & hematology, Pathology and Laboratory Medicine, Biochemistry, C-reactive proteins, Metabolic equivalent, Pulmonary function testing, Habits, 0302 clinical medicine, Surveys and Questionnaires, Medicine and Health Sciences, Psychology, Medicine, Public and Occupational Health, 030212 general & internal medicine, Immune Response, Lung, Lungmedicin och allergi, education.field_of_study, Multidisciplinary, medicine.diagnostic_test, biology, Professions, Research Design, Female, Research Article, Adult, Spirometry, Pulmonary function, General Science & Technology, Health surveys, Science, Immunology, Population, Research and Analysis Methods, C-reactive protein, 03 medical and health sciences, Signs and Symptoms, Diagnostic Medicine, Humans, Smoking habits, Exercise physiology, education, Exercise, Asthma, Inflammation, Behavior, Survey Research, business.industry, Physical activity, Biology and Life Sciences, Proteins, medicine.disease, Cross-Sectional Studies, People and Places, biology.protein, Population Groupings, business
Abstract

Objective: Regular physical activity may be associated with improved lung function via reduced systemic inflammation, although studies exploring this mechanism are rare. We evaluated the role of C-reactive protein in blood, which is a common marker of systemic inflammation, on the association of physical activity with forced expiratory volume in one second and forced vital capacity. Methods: Cross-sectional data on spirometry, C-reactive protein levels and self-reported physical activity (yes/no; ≥2 times and ≥1hr per week of vigorous physical activity) were available in the European Community Respiratory Health Survey (N = 2347 adults, 49.3% male, 28–56 years-old). A subsample was also assessed 10 years later using the International Physical Activity Questionnaire, and tertiles of Metabolic Equivalent of Task—minutes per week spent in vigorous, moderate and walking activities were calculated (N = 671, 49.6% male, 40–67 years-old). Adjusted cross-sectional mixed linear regression models and the “mediate” package in “R” were used to assess the presence of mediation. Results: Despite positive significant associations between nearly all physical activity metrics with forced expiratory volume in one second and forced vital capacity, there was no evidence that C-reactive protein levels played a role. An influence of C-reactive protein levels was only apparent in the smaller subsample when comparing the medium to low tertiles of moderate activity (mean difference [95% CIs]: 21.1ml [5.2, 41.9] for forced expiratory volume in one second and 17.3ml [2.6, 38.0] for forced vital capacity). Conclusions: In a population of adults, we found no consistent evidence that the association of physical activity with forced expiratory volume in one second or forced vital capacity is influenced by the level of C-reactive protein in blood. The results reported herein correspond to the specific aims of the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Individual Fellowship scheme (H2020-MSCA-IF-2015; proposal number 704268; https://ec.europa.eu/research/mariecurieactions/actions/individual-fellowships_en), awarded to the Principal Investigator EF. These results also correspond to the specific aims of the Ageing Lungs in European Cohorts (ALEC) Study (www.alecstudy.org), awarded to the Principal Investigator DJ, which has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 633212 (https://ec.europa.eu/programmes/horizon2020/). The local investigators and funding agencies for the participating European Community Respiratory Health Survey (ECRHS II and ECRHS III) centres are reported in the Supplementary File. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Published
2019

50. Restrictive spirometry pattern is associated with low physical activity levels. A population based international study

Author

Valeria Bellisario, Anne-Elie Carsin, Cecilie Svanes, Chantal Raherison, Bénédicte Leynaert, Elaine Fuertes, Stefano Guerra, José Luis Sánchez Ramos, Emmanuel Schaffner, Joachim Heinrich, Thorarinn Gislason, Nicole Probst-Hensch, Christer Janson, Medea Imboden, Isabelle Pin, Josep M. Antó, Pascal Demoly, Jesús Martínez-Moratalla, Kjell Torén, José Antonio Gullón, Isa Cerveri, Francisco Gómez Real, Bertil Forsberg, Joost Weyler, Anna Beckmeyer-Borowko, Silvia Pascual, Dirk Keidel, Rain Jõgi, Dennis Nowak, Margareta Emtner, Seraina Caviezel, Simone Accordini, Wasif Raza, Judith Garcia-Aymerich, Shyamali C. Dharmage, Deborah Jarvis, Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), CIBER de Epidemiología y Salud Pública (CIBERESP), IMIM-Hospital del Mar, Generalitat de Catalunya, University Hospital Basel [Basel], Imperial College London, National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, Institute of Epidemiology [Neuherberg] (EPI), German Research Center for Environmental Health - Helmholtz Center München (GmbH), Helmholtz Zentrum München = German Research Center for Environmental Health, German Centre for Lung Research, Partenaires INRAE, School of Medicine [University of Melbourne], University of Melbourne, Haukeland University Hospital, University of Bergen (UiB), Universiteit Antwerpen = University of Antwerpen [Antwerpen], Ludwig Maximilian University [Munich] (LMU), Universidad de Castilla-La Mancha = University of Castilla-La Mancha (UCLM), Respiratory Department, Hospital Universitario San Agustín (HUSA), Universidad de Huelva, Swiss Tropical and Public Health Institute [Basel], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Sorbonne Université (SU), IRCCS 'San Matteo' Hospital Foundation [Pavie, Italie], Università degli Studi di Pavia = University of Pavia (UNIPV), University Hospital of Verona, Landspitali National University Hospital of Iceland, Göteborgs Universitet (GU), Uppsala University Hospital, University of Tartu, Umeå University, Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Galdakao Hospital, University of Arizona, Melbourne School of Population and Global Health [Melbourne], Universitat Pompeu Fabra [Barcelona] (UPF), Salvy-Córdoba, Nathalie, Helmholtz-Zentrum München (HZM), University of Turin, Universiteit Antwerpen [Antwerpen], Universidad de Castilla-La Mancha (UCLM), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), University of Pavia, Department of Pulmonary Medicine, University of Tartu and Lung Clinic, Tartu University Hospital, Tartu, Estonia, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Medical Research Council (MRC), and Commission of the European Communities

Subjects
Male, DISORDER, Cardiac & Cardiovascular Systems, Cross-sectional study, Epidemiology, Vital Capacity, Respiratory System, ACTIVITY QUESTIONNAIRE, Disease, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, DISEASE, 0302 clinical medicine, Forced Expiratory Volume, Prevalence, Prospective Studies, 030212 general & internal medicine, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, Prospective cohort study, Lung, Body mass index, RISK, medicine.diagnostic_test, Middle Aged, IMPAIRMENT, Respiratory Function Tests, 3. Good health, Europe, LUNG-FUNCTION, medicine.anatomical_structure, Lung function, Physical activity, Restrictive spirometry pattern, Female, Life Sciences & Biomedicine, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology, MESH: Exercise / physiology, Lung / physiopathology, Lung Diseases, Obstructive / physiopathology, Obesity / epidemiology, Spirometry / adverse effects, NATIONAL-HEALTH, Pulmonary and Respiratory Medicine, Spirometry, medicine.medical_specialty, Restrictive Spirometry Pattern, Body Mass Index, Lung Function, Physical Activity, 1102 Cardiovascular Medicine And Haematology, EVENTS, 03 medical and health sciences, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, Internal medicine, medicine, Humans, Lung Diseases, Obstructive, Obesity, Exercise, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Science & Technology, business.industry, MORTALITY, 1103 Clinical Sciences, medicine.disease, Cross-Sectional Studies, 030228 respiratory system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Cardiovascular System & Cardiology, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Human medicine, business
Abstract

Introduction: Restrictive spirometry pattern is an under-recognised disorder with a poor morbidity and mortality prognosis. We compared physical activity levels between adults with a restrictive spirometry pattern and with normal spirometry. Methods: Restrictive spirometry pattern was defined as a having post-bronchodilator FEV1/FVC ≥ Lower Limit of Normal and a FVC

Published
2019
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