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Background: Airway inflammation may drive the progression of chronic obstructive pulmonary disease (COPD) associated with alpha-1 antitrypsin deficiency (AATD), but the relationship between airway microbiota and inflammation has not been investigated., Methods: We studied 21 non-treated AATD (AATD-noT) patients, 20 AATD-COPD patients under augmentation therapy (AATD-AT), 20 cigarette smoke-associated COPD patients, 20 control healthy smokers (CS) and 21 non-smokers (CON) with normal lung function. We quantified sputum inflammatory cells and inflammatory markers (IL-27, CCL3, CCL5, CXCL8, LTB 4 , MPO) by ELISA, total bacterial load (16S) and pathogenic bacteria by qRT-PCR., Results: AATD-AT patients were younger but had similar spirometric and DLCO values compared to cigarette smoke-associated COPD, despite a lower burden of smoking history. Compared to cigarette smoke-associated COPD, AATD-noT and AATD-AT patients had lower sputum neutrophil levels ( p =0.0446, p =0.0135), total bacterial load (16S) ( p =0.0081, p =0.0223), M. catarrhalis ( p =0.0115, p =0.0127) and S. pneumoniae ( p =0.0013, p =0.0001). Sputum IL-27 was significantly elevated in CS and cigarette smoke-associated COPD. AATD-AT, but not AATD-noT patients, had IL-27 sputum levels (pg/ml) significantly lower than COPD ( p =0.0297) and these positively correlated with FEV 1 % predicted values ( r =0.578, p =0.0307)., Conclusions: Compared to cigarette smoke-associated COPD, AATD-AT (COPD) patients have a distinct airway inflammatory and microbiological profile. The decreased sputum bacterial load and IL-27 levels in AATD-AT patients suggests that augmentation therapy play a role in these changes., Competing Interests: This study was funded by Istituti Clinici Scientifici Maugeri, IRCCS and by Grifols Inc. Grifols Inc. with a two-year grant. Grifols funding included laboratory supplies, travel expenses for collecting samples around the Country and a fellowship for a Ph.D. The authors report no other conflicts of interest in this work., (© 2019 Balbi et al.)

This longitudinal study investigated whether smoking bans influence passive smoking at work and/or at home in the same subjects. Passive smoking at work and/or at home was investigated in random population samples (European Community Respiratory Health Survey) in 1990-1995, with follow-up interviews in 1998-2003 and 2010-2014. National smoking bans were classified as partial (restricted to public workplaces) or global (extended to private workplaces). Multivariable analysis was accomplished by three-level logistic regression models, where level-1, level-2, and level-3 units were, respectively, questionnaire responses, subjects, and centers. Passive smoking at work was reported by 31.9% in 1990-1995, 17.5% in 1998-2003, and 2.5% in 2010-2014. Concurrently, passive smoking at home decreased from 28.9% to 18.2% and 8.8%. When controlling for sex, age, education, smoking status, and ECHRS wave, the odds of passive smoking at work was markedly reduced after global smoking bans (OR = 0.45, 95% CI 0.25-0.81), particularly among non-smokers, while the protective effect of global smoking bans on passive smoking at home was only detected in non-smokers. Smoking bans both in public and private workplaces were effective in reducing passive smoking at work in Europe. However, given the inefficacy of smoking bans in current smokers' dwellings, better strategies are needed to avoid smoking indoors., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Socioeconomic inequalities in smoking habits have stabilized in many Western countries. This study aimed at evaluating whether socioeconomic disparities in smoking habits are still enlarging in Italy and at comparing the impact of education and occupation., Methods: In the frame of the GEIRD study (Gene Environment Interactions in Respiratory Diseases) 10,494 subjects, randomly selected from the general population aged 20-44 years in seven Italian centres, answered a screening questionnaire between 2007 and 2010 (response percentage = 57.2%). In four centres a repeated cross-sectional survey was performed: smoking prevalence recorded in GEIRD was compared with prevalence recorded between 1998 and 2000 in the Italian Study of Asthma in Young Adults (ISAYA)., Results: Current smoking was twice as prevalent in people with a primary/secondary school certificate (40-43%) compared with people with an academic degree (20%), and among unemployed and workmen (39%) compared with managers and clerks (20-22%). In multivariable analysis smoking habits were more affected by education level than by occupation. From the first to the second survey the prevalence of ever smokers markedly decreased among housewives, managers, businessmen and free-lancers, while ever smoking became even more common among unemployed (time-occupation interaction: p = 0.047). At variance, the increasing trend in smoking cessation was not modified by occupation., Conclusion: Smoking prevalence has declined in Italy during the last decade among the higher socioeconomic classes, but not among the lower. This enlarging socioeconomic inequality mainly reflects a different trend in smoking initiation.

Background: No study has been carried out on the time trend in the prevalence of chronic bronchitis (CB) in recent years, despite its clinical and epidemiological relevance. We evaluated the trend in CB prevalence during the past decade among young Italian adults., Methods: A screening questionnaire was mailed to general population samples of 20-44 year-old subjects in two cross-sectional surveys: the Italian Study on Asthma in Young Adults (ISAYA) (1998/2000; n = 18,873, 9 centres) and the screening stage of the Gene Environment Interactions in Respiratory Diseases (GEIRD) study (2007/2010; n = 10,494, 7 centres). CB was defined as having cough and phlegm on most days for a minimum of 3 months a year and for at least 2 successive years. The prevalence rates and the risk ratios (RRs) for the association between CB and each potential predictor were adjusted for gender, age, season of response, type of contact, cumulative response rate, and centre., Results: CB prevalence was 12.5% (95% CI: 12.1-12.9%) in 1998/2000 and 12.6% (95% CI: 11.7-13.7%) in 2007/2010; it increased among never smokers (from 7.6 to 9.1%, p = 0.003), current light smokers (<15 pack-years; from 15.1 to 18.6%, p < 0.001), and unemployed/retired subjects (from 14.3 to 19.1%, p = 0.001). In this decade, the prevalence of current smoking decreased (from 33.6 to 26.9%, p < 0.001), whereas the prevalence of unemployment/premature retirement (from 5.3 to 6.0%, p = 0.005), asthma (from 5.0 to 6.2%, p = 0.003), and allergic rhinitis (from 19.5 to 24.5%, p < 0.001) increased. In both 1998/2000 and 2007/2010, the likelihood of having CB was significantly higher for women, current smokers, asthmatic patients, and subjects with allergic rhinitis. During this period, the strength of the association between CB and current heavy smoking (≥15 pack-years) decreased (RR: from 4.82 to 3.57, p = 0.018), whereas it increased for unemployment/premature retirement (from 1.11 to 1.53, p = 0.019); no change was observed for gender, asthma, and allergic rhinitis., Conclusions: Despite the significant reduction in current smoking, CB prevalence did not vary among young Italian adults. The temporal pattern of CB prevalence can only be partly explained by the increase of unemployment/premature retirement, asthma and allergic rhinitis, and suggests that other factors could have played a role.

Background: The prevalence rates of smoking in subjects with asthma have frequently been reported as similar to those in the general population; however, available data are not up-to-date. There is only limited and somewhat conflicting information on the long-term effects of smoking on health outcomes among population-based cohorts of subjects with asthma. We aimed to investigate changes in smoking habits and their effects on forced expiratory volume in 1 s (FEV(1)) in subjects with asthma in comparison with the rest of the population, focusing on the healthy smoker effect., Methods: We studied 9,092 subjects without asthma and 1,045 with asthma at baseline who participated in both the European Community Respiratory Health Survey I (20-44 years old in 1991-1993) and II (1999-2002)., Results: At follow-up, smoking was significantly less frequent among subjects with asthma than in the rest of the population (26 vs. 31%; p < 0.001). Subjects with asthma who were already ex-smokers at the beginning of the follow-up in the 1990 s had the highest mean asthma score (number of reported asthma-like symptoms, range 0-5), probably as a result of the healthy smoker effect (2.80 vs. 2.44 in never smokers, 2.19 in quitters and 2.24 in smokers; p < 0.001). The influence of smoking on FEV(1) decline did not depend on asthma status. Smokers had the highest proportion of subjects with chronic cough/phlegm (p < 0.01)., Conclusion: One out of 4 subjects with asthma continues smoking and reports significantly more chronic cough and phlegm than never smokers and ex-smokers. This stresses the importance of smoking cessation in all patients with asthma, even in those with less severe asthma., (Copyright © 2012 S. Karger AG, Basel.)

Background: The association between smoking habits and asthma is complex because subjects with asthma could avoid smoking, whereas smoking could increase asthma severity or incidence., Purpose: The relation between asthma in childhood (0-10 years) and smoking initiation in the second decade (11-20 years) was investigated using the database of the Italian Study on Asthma in Young Adults, performed in 1998-2000 on people aged 20-45 years., Methods: The cumulative incidence of smoking initiation was compared among (1) subjects not reporting asthma attacks in the first 20 years of life (n = 17,384), (2) subjects reporting asthma onset in the first decade and no disease remission by the age of 20 years (n = 305), (3) subjects reporting asthma onset in the first decade and remission in the first and second decades (n = 573)., Results: Among men, the cumulative incidence of smoking onset was higher among nonasthmatics (49%) than among asthmatics (35.6%), and intermediate among asthmatics with disease remission (44.2%) (p = .001). These differences were larger in males born between 1953 and 1965, and tended to decrease in males born between 1966 and 1979: cumulative incidence of smoking onset decreased from 54.3% to 43.8% in nonasthmatics, whereas it remained stable in asthmatics (from 36.8% to 35%). Women, instead, had similar cumulative incidence of smoking initiation, irrespective of asthma onset or remission (p = .849)., Conclusion: Asthma in childhood reduces smoking initiation during the subsequent teenage in men, but not in women. This protective effect tends to fade when asthma remission occurs. In the last decades, smoking initiation has decreased among nonasthmatic males, but not among asthmatic males., (Copyright © 2011 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Rationale and Objectives: Response to mailed epidemiological surveys has decreased in recent decades. Since subjects with respiratory symptoms are usually early responders to surveys performed in Southern Europe, this trend could bias prevalence estimates. The present study aimed at evaluating the impact of non-response bias on prevalence estimates of respiratory symptoms and smoking habits., Methods: In 9 centres, participating in the Italian Study on Asthma in Young Adults (ISAYA), random samples of people aged 20-45 years were administered a mailed questionnaire between 1998 and 2000. Non-responders were contacted again first by mail and then by phone. Cumulative response percentage was 30.5%, 52.4% and 72.7% (18,873/25,969), respectively, after the 1st, 2nd and 3rd contact., Results: The prevalence of self-reported current asthma, asthma-like symptoms, and chronic cough/phlegm was more than halved from the first contact (5.6%, 17.8%, 14.6% respectively) to the third contact (2.7%, 6.4%, 6.9%). This pattern was less pronounced when considering allergic rhinitis and past asthma, whose prevalence decreased, respectively, from 21.5% to 15.6% and from 3.5% to 2.6%. At the same time the proportion of current smokers increased from 29.2% to 38%, while the proportion of ex-smokers decreased from 16.5% to 10.1%. In a multinomial logistic model current asthma, asthma-like symptoms, chronic cough/phlegm and smoking habits, and to a lower extent past asthma and allergic rhinitis, were significant predictors of late response., Conclusions: In Italy when response percentage is low, the prevalence of current asthma, chronic cough/phlegm and ex-smokers is overestimated, while the proportion of current smokers is underestimated.

Background: Little is known about factors associated with lung function decline in asthma., Objective: To identify the determinants of FEV(1) decline in adults with asthma with and without airflow obstruction at baseline., Methods: An international cohort of 638 subjects with asthma (20-44 years old) was identified in the European Community Respiratory Health Survey (1991-1993) and followed up from 1998 to 2002. Spirometry was performed on both occasions. FEV(1) decline was related to potential determinants evaluated at baseline and during the follow-up by random intercept linear regression models. The analyses were stratified by the presence of airflow obstruction (FEV(1)/forced vital capacity < 0.70) at baseline., Results: In the group of individuals without airflow obstruction (n = 544), a faster FEV(1) decline was observed for subjects with intermediate body mass index (BMI) than for lean and obese subjects. FEV(1) decline was associated with weight gain independently of baseline BMI, and this association was stronger in men (20; 95% CI, 10-30, mL/y/kg gained) than in women (6; 95% CI, 1-11, mL/y). In the group of individuals with airflow obstruction (n = 94), the absence of allergen sensitization and a low BMI at baseline were associated with a faster FEV(1) decline, whereas weight gain was not associated with decline., Conclusions: The detrimental effect of weight gain on FEV(1) decline is particularly relevant in subjects with asthma who still do not have an established airflow obstruction. Our findings support the importance of weight management in asthma and recommend weight loss in overweight or obese individuals with asthma.

The current report describes the use of CapLC-ESI-Q/TOF-MS for investigating the proteome profiles of hypertonic saline-induced sputum samples from 56 smokers. The severity of their lung disease ranged from normal (healthy smokers) to chronic bronchitis, chronic obstructive pulmonary disease (COPD), and COPD with emphysema. This pilot study examined the hypothesis that there were distinct differences in protein expression profiles that were related to the phenotype and cigarette smoking illness severity. A total of 203 unique proteins were identified. These may represent the most highly expressed proteins in induced sputum. Our results provide evidence that different proteins are expressed, as the disease progresses from health to more advanced stages, and support our contention that a proteomic approach would be beneficial in discovering selective molecules linked to specific COPD stages.

Background: In most developed countries the prevalence of smoking habits is decreasing in men, while in women the prevalence seems to decline in Northern Europe but to increase in the Mediterranean area. The present research aims at assessing time trends in smoking habits in Italy., Methods: In the frame of the Italian Study on Asthma in Young Adults (ISAYA) a random sample of the Italian population aged 20-45 years was administered a mailed questionnaire in 9 Italian centers between 1998 and 2000. Cumulative response was 72.7% (18873/25969). Kaplan-Meier survival curves and log-rank test were used to compare probability of remaining a life-time non-smoker across birth cohorts (1953-58, 1959-63, 1964-68, 1969-73, 1974-78). Probability to quit smoking was also evaluated among ever-smokers., Results: Probability to persist as a non-smoker significantly increased across subsequent generations in both sexes. At the age of 20 years this probability amounted to 41.7% (95% CI 39.4-44.0%) in men and 52.7% (50.4-54.9%) in women born between 1953 and 1958, and it increased to 57% (54.8-59.1%) in men and 68.7% (66.6-70.7%) in women born in 1969-73, but no further decline in smoking habits was observed in the next birth cohort (1974-78). Also the probability to quit smoking significantly increased from the 1953-58 birth cohort to the 1969-73 one., Conclusions: Smoking has declined among Italian young adults of both genders. Further efforts are necessary to promote active anti-smoking campaign, especially among adolescents, which are at higher risk of starting to smoke.

Background: Gastroesophageal reflux disease (GERD) has been reported to be significantly associated with chronic rhinosinusitis, but the strength of the association is still debated.Aims: To evaluate the strength of the association between gastritis/GERD and non-allergic rhinitis (NAR)/allergic rhinitis (AR)/sinusitis.Methods: We investigated 2887 subjects aged 20-84 years, who underwent a clinical visit in seven Italian centres (Ancona, Palermo, Pavia, Terni, Sassari, Torino, Verona) within the study on Gene Environment Interactions in Respiratory Diseases, a population-based multicase-control study between 2008 and 2014. Subjects were asked if they had doctor-diagnosed "gastritis or stomach ulcer (confirmed by gastroscopy)" or "gastroesophageal reflux disease, hiatal hernia or esophagitis". The association between NAR/AR/sinusitis and either gastritis or GERD was evaluated through relative risk ratios (RRR) by multinomial logistic regression.Results: The prevalence of gastritis/GERD increased from subjects without nasal disturbances (22.8% = 323/1414) to subjects with AR (25.8% = 152/590) and further to subjects with NAR (36.7% = 69/188) or sinusitis (39.9% = 276/691). When adjusting for centre, sex, age, education level, BMI, smoking habits and alcohol intake, the combination of gastritis and GERD was associated with a four-fold increase in the risk of NAR (RRR = 3.80, 95% CI 2.56-5.62) and sinusitis (RRR = 3.70, 2.62-5.23) with respect to controls, and with a much smaller increase in the risk of AR (RRR = 1.79, 1.37-2.35)..Conclusion: The study confirmed the association between gastritis/GERD and nasal disturbances, which is stronger for NAR and sinusitis than for AR. [ABSTRACT FROM AUTHOR]

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 < 0.001. Being in the upper age quartile (60.3‐67.6 years), men had 19.2 ppb (95% CI: 18.3, 20.2) higher FENO 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 = <0.001 higher FENO, compared with the lowest age quartile. Height was related to 8% higher FENO level in men (P < 0.001) and 5% higher FENO 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 < 0.001 for both). Men and women sensitized to both grass and perennial allergens had higher FENO levels compared with non‐sensitized subjects 26% and 29%, P < 0.001 for both. Conclusion and Clinical Relevance: Fractional exhaled nitric oxide levels were higher in men than women. Similar effects of current smoking, height, and IgE sensitization were found in both sexes. FENO 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. [ABSTRACT FROM AUTHOR]

Background: Early identification of patients with COPD and prone to more rapid decline in lung function is of particular interest from both a prognostic and therapeutic point of view. The aim of this study was to identify the clinical, functional and imaging characteristics associated with the rapid FEV1 decline in COPD. Methods: Between 2001 and 2005, 131 outpatients with moderate COPD in stable condition under maximum inhaled therapy underwent clinical interview, pulmonary function tests and HRCT imaging of the chest and were followed for at least 3 years. Results: Twenty-six percent of patients had emphysema detected visually using HRCT. The FEV1 decline was 42 ± 66 mL/y in the total sample, 88 ± 76 mL/y among rapid decliners and 6 ± 54 mL/y among the other patients. In the univariable analysis, the decline of FEV1 was positively associated with pack-years (p < 0.05), emphysema at HRCT (p < 0.001), RV (p < 0.05), FRC (p < 0.05), FEV1 (p < 0.01) at baseline and with number of hospitalizations per year (p < 0.05) during the follow-up. Using multivariable analysis, the presence of emphysema proved to be an independent prognostic factor of rapid decline (p = 0.001). When emphysema was replaced by RV, the model still remained significant. Conclusions: The rapid decline in lung function may be identified by the presence of emphysema at HRCT or increased RV in patients with a long smoking history. [ABSTRACT FROM AUTHOR]

Summary: An unusual case of smoking-related centrilobular emphysema with normal spirometry. A 64-year-old man presented with severe dyspnoea and respiratory failure. Pulmonary function and mechanics were normal except for a marked reduction in diffusing capacity of the lung. High-resolution CT scan showed diffuse centrilobular emphysema also involving lower lobes. Pulmonary embolism, cardiac or pulmonary shunt and immunopathologically based vasculitis were excluded. Pulmonary pressure was at the upper limit of normality but within few months he developed a severe pulmonary hypertension. Although spirometry is the only physiologic measure recommended by the updated Global Initiative for Chronic Obstructive Lung Disease guidelines for confirming the diagnosis it should be recognized that diffuse emphysema may occur with only abnormalities in gas exchange without airflow obstruction. The identification of different phenotypes within COPD is important for understanding disease heterogeneity and progression. [Copyright &y& Elsevier]

Abstract Background Very few studies have examined whether a long-term beneficial effect of physical activity on lung function can be influenced by living in polluted urban areas. Objective We assessed whether annual average residential concentrations of nitrogen dioxide (NO 2) and particulate matter with aerodynamic diameters < 2.5 μm (PM 2.5) and <10 μm (PM 10) modify the effect of physical activity on lung function among never- (N = 2801) and current (N = 1719) smokers in the multi-center European Community Respiratory Health Survey. Methods Associations between repeated assessments (at 27–57 and 39–67 years) of being physically active (physical activity: ≥2 times and ≥1 h per week) and forced expiratory volume in 1 s (FEV 1) and forced vital capacity (FVC) were evaluated using adjusted mixed linear regression models. Models were conducted separately for never- and current smokers and stratified by residential long-term NO 2 , PM 2.5 mass and PM 10 mass concentrations (≤75th percentile (low/medium) versus >75th percentile (high)). Results Among current smokers, physical activity and lung function were positively associated regardless of air pollution levels. Among never-smokers, physical activity was associated with lung function in areas with low/medium NO 2 , PM 2.5 mass and PM 10 mass concentrations (e.g. mean difference in FVC between active and non-active subjects was 43.0 mL (13.6, 72.5), 49.5 mL (20.1, 78.8) and 49.7 mL (18.6, 80.7), respectively), but these associations were attenuated in high air pollution areas. Only the interaction term of physical activity and PM 10 mass for FEV 1 among never-smokers was significant (p-value = 0.03). Conclusions Physical activity has beneficial effects on adult lung function in current smokers, irrespective of residential air pollution levels in Western Europe. Trends among never-smokers living in high air pollution areas are less clear. Highlights • Air pollution may modify associations between physical activity and lung function. • Physical activity was positively associated with lung function in current smokers regardless of air pollution levels. • Results in never smokers were less clear. • Air pollution control policies would ensure maximal benefit of physical activity promotion policies. [ABSTRACT FROM AUTHOR]