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Background: In children, asthma and sleep-disordered breathing (SDB) may affect quality of life (QoL), and SDB may complicate asthma management., Objective: To evaluate the prevalence of SDB, its association with asthma control, and risk factors associated with SDB in a cohort of asthmatic children. The effects of asthma control and SDB on QoL were also investigated., Methods: We consecutively recruited asthmatic children referred to our Pulmonology Service from December 1, 2022 to May 31, 2023. Data on anthropometrics, respiratory function, and allergies were collected. The prevalence of SDB was assessed by the Pediatric Sleep Questionnaire (PSQ). Asthma control status was assessed by the Childhood Asthma Control Test (C-ACT), while QoL was evaluated by the Pediatric Quality of Life Inventory (PedsQL) questionnaire. Factors associated with SDB were analyzed., Results: A total of 78 asthmatic children aged 5-12 years were included. SDB was found in 37.2% of them, with a higher prevalence in children with uncontrolled versus well-controlled asthma (60.1% vs. 27.3%; p-value = 0.005). The C-ACT score was significantly lower in SDB-positive versus SDB-negative group, and uncontrolled asthma (C-ACT ≤19) was associated with a 4.15-fold increased risk of SDB. The PedsQL score was significantly lower in asthmatic children with than without SDB and was associated with lower SDB risk. SDB increased the risk of uncontrolled asthma in children, and asthmatic children with SDB had lower QoL., Conclusion: In asthmatic children, SDB affects both asthma control and QoL. Children with uncontrolled asthma should be referred for polysomnography to identify a possible underlying SDB., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim: To study if individuals with nocturnal gastroesophageal reflux (nGER) and habitual snoring are more likely to develop asthma and respiratory symptoms (i.e. wheeze, cough, chest tightness, breathlessness) than those without these conditions, and if these associations are additive., Methods: We used data from the population-based prospective questionnaire study Respiratory Health in Northern Europe (RHINE) (11,024 participants), with data from 1999 and 2011. Participants with heartburn or belching after going to bed, at least 1 night/week, were considered to have nGER. Participants reporting loud snoring at least 3 nights/week were considered to have habitual snoring. Participants were grouped into four groups by their nGER and snoring status: "never"; "former"; "incident"; "persistent". Incident respiratory symptoms were analyzed among participants without respective symptom at baseline., Results: Snoring and nGER were independently associated with incident asthma and respiratory symptoms. The risk of incident wheeze was increased in subjects with incident or persistent snoring (adjusted odds ratio (95 % CI): 1.44 (1.21-1.72)), nGER (2.18 (1.60-2.98)) and in those with both snoring and nGER (2.59 (1.83-3.65)). The risk of developing asthma was increased in subjects with incident or persistent snoring (1.44 (1.15-1.82)), nGER (1.99 (1.35-2.93)) and in those with both snoring and nGER (1.72 (1.06-2.77)). No significant interaction was found between snoring and nGER. A similar pattern was found for the incidence of all other respiratory symptoms studied, with the highest risk among those with both incident or persistent nGER and snoring., Conclusion: The risk of developing asthma and respiratory symptoms is increased among subjects with nGER and habitual snoring. These associations are independent of each other and confounding factors. Snoring and nGER together are additive on respiratory symptoms., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The small-airway dysfunction (SAD), detected with impulse oscillometry (IOS) methods, has been recently better characterized in patients with asthma. However, little is known about SAD in asthmatic patients with normal spirometry (NS)., Objective: In this study, we aimed to investigate, in an unselected sample of 321 patients with physician-diagnosed asthma and NS, prevalence, clinical characterization, and impact on asthma control of IOS-defined SAD. As a secondary objective of the study, we focused on comparing the difference between IOS- and spirometry-defined SAD., Methods: Consecutive patients with a previous diagnosis of asthma but normal spirometry at the moment of the enrollment were stratified by the presence of IOS-defined SAD (difference in resistance at 5 Hz and at 20 Hz [R5-R20] greater than 0.07 kPa x s x L -1 ). We have also assessed the presence of SAD defined by spirometry, according to FEF 25-75 < 65% of the predicted. Clinical and laboratory features were collected, and univariable and multivariable analyses were used to analyze cross-sectional associations between clinical variables and outcomes (SAD)., Results: IOS-defined SAD was present in 54.1% of the cohort. In contrast, spirometry-defined SAD was present in only 10% of patients. Subjects with IOS-defined SAD showed less well-controlled asthma and a higher mean inhaled corticosteroid dosage use compared with subjects without SAD (both P < .001). Overweight (odds ratio [OR], 1.14; 95% CI, 1.05-1.23), exacerbation history (OR, 3.06; 95% CI, 1.34-6.97), asthma-related night awakenings (OR, 6.88; 95% CI, 2.13-22.23), exercise-induced asthma symptoms (OR, 33.5; 95% CI, 9.51-117.8), and controlled asthma (OR, 0.22; 95% CI, 0.06-0.84) were independently associated with SAD., Conclusions: Asthmatic patients with IOS-defined SAD showed less well-controlled asthma, more severe exacerbations and higher mean inhaled corticosteroid dosage. We confirmed exercise-induced asthma, asthma-related night awakenings, exacerbation history, and overweight as independently associated with SAD, while showing well-controlled asthma as inversely associated. SAD may be overlooked by standard spirometry., Competing Interests: Declaration of competing interest All authors have no conflicts of interest to disclose about this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Patients with asthma often experience sleep disturbances. We assessed the 5-item Asthma Control Questionnaire (ACQ-5) score ≥2.5 as a useful threshold to identify patients with moderate-to-severe type 2 asthma and high sleep disturbance (HSD) and investigated dupilumab efficacy on clinical and sleep-related outcomes among patients with HSD., Methods: QUEST (NCT02414854) data were used in this post hoc analysis. A composite endpoint from validated patient-reported outcomes was developed to identify patients with HSD using sleep-related items from the ACQ-5, Asthma-Related Quality-of-Life Questionnaire, Rhino-Conjunctivitis Quality-of-Life Questionnaire, and Sino-Nasal Outcome Test-22. Impairment in at least 1 item was considered an indication of HSD. Change from baseline to Week 52 in nighttime symptoms, ACQ-5 score, lung function, annualized severe exacerbation rates (AER), and short-acting β-agonists use during treatment was used to assess dupilumab efficacy., Results: In type 2 asthma patients, 64% had HSD at baseline; of those with ACQ-5 ≥2.5 at baseline, 82% had HSD. In this population, dupilumab reduced nighttime symptoms and ACQ-5 score by 0.31 and 0.56 points, respectively, by Week 52 versus placebo, and led to a 66% reduction in AER during QUEST and 0.34 L improvement in pre-bronchodilator (pre-BD) forced expiratory volume in 1 s (FEV 1 ) at Week 52., Conclusion: A majority of patients with moderate-to-severe type 2 asthma with ACQ-5 ≥2.5 at baseline had HSD. Dupilumab reduced nighttime symptoms and exacerbations, and improved lung function, overall asthma control, and quality of life. Further studies are needed to confirm the association between ACQ-5 score ≥2.5 and higher sleep disturbance rates., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: The purpose of this study was to determine how four different definitions of bronchodilator response (BDR) relate to asthma control and asthma symptom burden in a large population of participants with poorly controlled asthma., Procedures: We examined the baseline change in FEV1 and FVC in response to albuterol among 931 participants with poorly controlled asthma pooled from three clinical trials conducted by the American Lung Association - Airways Clinical Research Centers. We defined BDR based on four definitions and analyzed the association of each with asthma control as measured by the Asthma Control Test or Asthma Control Questionnaire, and asthma symptom burden as measured by the Asthma Symptom Utility Index., Main Findings: A BDR was seen in 31-42% of all participants, depending on the definition used. There was good agreement among responses (kappa coefficient 0.73 to 0.87), but only 56% of participants met all four definitions for BDR. A BDR was more common in men than women, in Blacks compared to Whites, in non-smokers compared to smokers, and in non-obese compared to obese participants. Among those with poorly controlled asthma, 35% had a BDR compared to 25% of those with well controlled asthma, and among those with a high symptom burden, 34% had a BDR compared to 28% of those with a low symptom burden. After adjusting for age, sex, height, race, obesity and baseline lung function, none of the four definitions was associated with asthma control or symptom burden., Conclusion: A BDR is not associated with asthma control or symptoms in people with poorly controlled asthma, regardless of the definition of BDR used. These findings question the clinical utility of a BDR in assessing asthma control and symptoms., Competing Interests: Declaration of competing interest DAK – David A. Kaminsky reports article publishing charges and statistical analysis were provided by American Lung Association. David A. Kaminsky reports a relationship with MGC Diagnostics Corporation that includes: speaking and lecture fees. David A. Kaminsky reports a relationship with UptoDate Inc that includes: consulting or advisory. Editor, Netter Respiratory Disease, Elsevier, Inc. - DAK CGI – Charles G Irvin reports a relationship with Medical Graphics Corp that includes: board membership and travel reimbursement. AED – Anne Dixon reports a relationship with American Lung Association that includes: board membership. Anne Dixon reports a relationship with American Board of Internal Medicine that includes: consulting or advisory. Anne Dixon reports a relationship with UptoDate Inc that includes: consulting or advisory. LJS- Lewis Smith reports financial support was provided by American Lung Association. RAW – Consultant: Astra-Zeneca, Boehringer Ingelheim, GlaxoSmithKline, Glenmark Pharmaceuticals, Verona. JH, RH, JM, EAS, JTH – no declarations., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Asthma and inflammatory bowel disease (IBD) are common inflammatory diseases. The aim of this study was to investigate the associations of IBD with asthma and respiratory symptoms., Methods: This study is based on 13,499 participants from seven northern European countries that filled in a postal questionnaire on asthma, respiratory symptoms, IBD including ulcerative colitis and Crohn's disease and various lifestyle variables., Results: There were 195 participants with IBD. The prevalence of asthma (14.5 vs 8.1%, p = 0.001), different respiratory symptoms (range 11.9-36.8% vs range 6.0-18.6%, p < 0.005), non-infectious rhinitis (52.1 vs. 41.6%, p = 0.004) and chronic rhinosinusitis (11.6 vs 6.0%, p = 0.001) were higher in subjects with IBD than in those without IBD. In multivariable regression analysis, the association between IBD and asthma was statistically significant (OR 1.95 (95% CI 1.28-2.96)) after adjusting for confounders such as sex, BMI, smoking history, educational level and physical activity. There was a significant association between asthma and ulcerative colitis (adjusted OR 2.02 (95% CI 1.27-2.19)), and asthma but not Crohn's disease (adjusted OR 1.66 (95% CI 0.69-3.95)). A significant gender interaction was found with a significant association between IBD and asthma in women but not in men ((OR 2.72 (95% CI 1.67-4.46) vs OR 0.87 (95% CI 0.35-2.19), p = 0.038)., Conclusions: Patients with IBD, particularly those with ulcerative colitis and female, have a higher prevalence of asthma and respiratory symptoms. Our findings indicate that it is important to consider respiratory symptoms and disorders when examining patients with manifest or suspected IBD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Asthma and obesity are prevalent conditions that are increasing worldwide. Asthma is characterized by airway inflammation and bronchial variability, while obesity is a complex metabolic disorder that poses significant morbidity and mortality risks. Obesity is a risk factor for asthma and a plethora of other non-communicable diseases., Objective: To compare all-cause and cause-specific mortality between obese, overweight and normal weight adults with asthma in a cohort with long-term follow-up., Methods: Individuals from a population-based adult asthma cohort recruited in Norrbotten county, Sweden, were clinically examined between 1986 and 2001 and grouped into body mass index (BMI) categories. Underlying causes of death until December 31st , 2020 were categorized as cardiovascular, respiratory, cancer and other mortality by linking cohort data to the Swedish National Board of Health and Welfare's National Cause of Death register. Hazard ratios (HR) with 95% confidence intervals (CI) for all-cause and cause-specific mortality associated with overweight and obesity were calculated via Cox proportional hazard models., Results: In total, 940 individuals were normal weight, 689 overweight and 328 obese while only 13 were underweight. Obesity increased the hazard for all-cause (HR 1.26, 95% CI 1.03-1.54) and cardiovascular mortality (HR 1.43, 95% CI 1.03-1.97). Obesity was not significantly associated with respiratory or cancer mortality. Overweight did not increase the hazard of all-cause or any cause-specific mortality category., Conclusion: Obesity, but not overweight, was significantly associated with increased hazard of all-cause and cardiovascular mortality in adults with asthma. Neither obesity nor overweight were associated with increased hazard of respiratory mortality., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To describe the short-term and long-term effects of cesarean section on childhood asthma and wheezing., Method: Firstly, in the cohort study, 6640 infants were included in the cohort baseline from January 2018 to December 2019, in which 6501 children completed the follow-up study for respiratory diseases at age 2 years. The effect of cesarean section on asthma and wheezing was estimated by the logistic regression model. Secondly, we conducted a meta-analysis of studies with outcomes of childhood asthma and wheezing under 2 years of age and over 2 years of age, respectively, to investigate the short-term and long-term effects of cesarean section on asthma and wheezing., Results: In our cohort study, the cumulative incidence of asthma and wheezing was 1.3% (84/6501). 45.5% of children (2961/6501) were born by cesarean section. The adjusted odds ratio for the effect of cesarean section on asthma and wheezing in children under 2 years of age was 1.14 (95%CI 0.73-1.78). Combining previous studies (outcomes of asthma and wheezing under 2 years of age) with our results for a meta-analysis, the odds ratio was 1.15 (95%CI 1.05-1.25, I 2  = 46.82%). Meanwhile, cesarean section had a long-term effect on asthma and wheezing in the child population over 2 years of age (OR = 1.17, 95%CI 1.11-1.24, P < 0.001, I 2  = 79.38%)., Conclusion: Cesarean section had a short-term effect on asthma and wheezing before the age of 2, in addition, the long-term effect of cesarean section on asthma and wheezing persisted in the child population (under 18)., Competing Interests: Declaration of competing interest The authors declared that they have no conflicts of interest to this work., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: MUC5 dysregulation is a hallmark of severe neutrophilic asthmatic patients. This study investigates the expression of MUC5AC and MUC5B at mRNA levels on asthma severity and airway wall thickness in severe neutrophilic asthmatic patients., Method: In this case-control clinical trial, twenty-five severe neutrophilic asthmatic patients and ten control subjects were enrolled. Subjects underwent ACT, pulmonary functions tests, and fractional exhaled nitric oxide (FENO). Also, induced sputum has been obtained to assess the expression of MUC5AC and MUC5B by the real-time PCR. In addition, the thickness of the airway wall was assessed by high-resolution computed tomography (HRCT), and bioinformatic analysis was implemented to approve the selection of the appropriate genes and for further investigations., Result: A significant difference was observed between the asthmatic and control in MUC5AC and MUC5B mRNA expression. Meanwhile, the expression of MUC5AC increased remarkably by asthma severity; also, it is associated with airway wall thickness (WT) (both P-value <0.05). The expression of MUC5B in asthmatic patients was lower than in control. There is no significant correlation between MUC5B mRNA level and WT and asthma severity. Notably, MUC5AC transcription level was correlated to sputum neutrophil percentage, while MUC5B transcription level had a positive correlation with sputum macrophages and a negative one with sputum neutrophils., Conclusion: In severe neutrophilic asthma, airway wall thickness increases with MUC5AC mRNA overexpression, which is probably related to asthma severity and the formation of mucus plugs. However, the expression of MUC5B was decreased, resulting in poor mucociliary clearance in the airways., Trial Registration: IR.IAU.MSHD.REC.1400.124., Competing Interests: Declaration of competing interest On behalf of all authors, the corresponding author states that there is no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: The aim of this study was to determine the impact of hospitalizations on levels of physical activity (PA) and whether other factors were associated with subsequent changes in PA., Methods: Prospective observational cohort study with a nested case-control study, with follow-up 60 days from the index hospital admission. Nine hospitals participated in the study. Patients were recruited consecutively. Several variables and questionnaires of the clinical baseline status of the patients were recorded including: the COPD Assessment Test (CAT), the Hospital Anxiety-Depression scale (HADS), comorbidities and the Yale Physical Activity Survey. Patients' data related to admission and up to two months after discharge were also recorded., Results: 883 patients were studied: 79.7% male; FEV1 48%; Charlson index 2; 28.7% active smokers. The baseline PA level for the total sample was 23 points. A statistically significant difference in PA was found between patients readmitted up to 2 months after the index admission and those not readmitted (17vs. 27, p < 0.0001). Multivariable linear regression analysis identified the following as predictors of the decrease of PA from baseline (index admission) up to 2 months follow-up: admission for COPD exacerbation in the two months prior to the index admission; readmission up to 2 months after the index admission; baseline HAD depressive symptoms, worse CAT score, and patient-reported "need for help"., Conclusions: In a cohort of admitted COPD patients, we identified a strong relationship between hospitalization for exacerbation and PA. In addition, some other potentially modifiable factors were found associated with the change in PA level after an admission., Competing Interests: Declaration of competing interest The study protocol was approved by the Basque Ethics Committee (reference PI2015124). Ninguno de los autores de este original presenta conflicto de interés alguno (directo o indirecto) en relación al mismo., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Children hospitalized for bronchiolitis have increased risk of asthma and low lung function persisting into adulthood, but the underlying mechanisms are poorly understood. Body mass index (BMI) and adipokines are associated with respiratory morbidity. We aimed to investigate if associations between BMI and adipokines and the outcomes asthma, atopy, and lung function differed between young adults previously hospitalized for bronchiolitis and control subjects., Methods: This sub study of a historical cohort enrolled 185 young adults previously hospitalized for bronchiolitis and 146 matched control subjects. Exposures (BMI and the adipokines: adiponectin, leptin, resistin, and ghrelin) and outcomes (asthma, atopy, and lung function) were measured cross-sectionally at 17-20 years of age. Associations were tested in regression models, and differences between the post-bronchiolitis- and control group were tested by including interaction terms., Results: BMI was associated with asthma and lung function, but we did not find that the associations differed between the post-bronchiolitis- and control group. We also found some associations between adipokines and outcomes, but only associations between adiponectin and forced vital capacity (FVC) and between resistin and current asthma differed between the groups (p-value interaction term 0.027 and 0.040 respectively). Adiponectin tended to be positively associated with FVC in the post-bronchiolitis group, with an opposite tendency in the control group. Resistin was positively associated with current asthma only in the control group., Conclusion: The increased prevalence of asthma and impaired lung function observed in young adults previously hospitalized for bronchiolitis do not seem to be related to growth and fat metabolism., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: It is unclear if depression is associated with impaired lung function in subjects with asthma, while few studies evaluated the effect of antidepressants on the relationship between depression and asthma. We designed this study to investigate if subjects with concomitant asthma and depression not taking antidepressants have worse asthma outcomes compared to asthmatic subjects without depression, and to evaluate whether antidepressants modify this association., Methods: This is a cross-sectional study. We included non-smokers with asthma, 18 years old or above. Study subjects attended an appointment with a chest physician, answered study questionnaires and underwent a spirometry test. We performed crude and adjusted binary logistic regression analyses., Results: We enrolled 309 subjects with asthma, of whom 48 with depression taking antidepressants, 52 with depression not taking antidepressants, and 209 without depression (control group). Asthmatic subjects with depression who had not used antidepressants before enrollment were more likely to have uncontrolled symptoms of asthma [adjusted OR 3.10, 95CI (1.56-6.15)] and airway obstruction [adjusted OR 2.41, 95CI (1.24-4.69)] compared to the control group. Subjects who had used antidepressants had higher odds of uncontrolled symptoms of asthma [adjusted OR 3.02, 95CI (1,50-6.07)], but similar odds of airway obstruction [adjusted OR 1.24, 95CI (0.87-1.77)] compared to the control group., Conclusions: Non-treated depression is associated with airway obstruction in subjects with asthma, but antidepressants modify this association. Thus, we recommend regular screening of depression in subjects with asthma, and prescription of antidepressants whenever depression symptoms justify pharmacological therapy., Competing Interests: Declaration of competing interest Authors declare no conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Many studies exploring the factors associated with asthma-specific quality of life (QOL) have shown that asthma control is the main predictor of asthma-related QOL. However, to the best of our knowledge, no study has ever explored the individual impact of the five main symptoms of asthma (wheezing, dyspnea, chest tightness, cough and airway secretion) reported directly by the patient on asthma-related QOL. A cross-sectional study was conducted on untreated adult (≥18 years) asthmatics recruited from the Liege University Hospital Asthma Clinic (Belgium) for asthma diagnosis confirmation between 2018 and 2021 (n = 171). Multiple linear regression analysis demonstrated that dyspnea and chest tightness were the two leading factors associated with asthma-related QOL in a population of mild asthma., Competing Interests: Declaration of competing interest Outside of this submitted work, RL received unrestricted research grants from GSK, AstraZeneca, Novartis and Chiesi and lecture or adboard fees from GSK, AZ, Novartis and Sonafi. Outside of this submitted work, FS received lecture or adboard fees from Chiesi, AZ, GSK, and Novartis. Outside this submitted work, JB reports personal fees (member of advisory boards, consultations, honoraria for meeting lectures) from Cipla, Menarini, Mylan, Novartis, Purina, Sanofi‐Aventis, Teva, Uriach. Shareholder of KYomed Innov and MASK-air-SAS. The rest of the authors declare that they have no relevant conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Competing Interests: Declaration of competing interest The authors certify that none of them have any conflicts of interest.

Over 20 years ago, the concept of asthma control was created and appropriate measurement tools were developed and validated. Loss of asthma control can lead to an exacerbation. Years ago, the term "clinically significant asthma exacerbation" was introduced to define when a loss of control is severe enough to declare it an asthma exacerbation. This term is also used by health insurances to determine when an exacerbation is eligible for reimbursement of biologics in clinical practice, however, it sometimes becomes apparent that a clear separation between loss of "asthma control" and an exacerbation is not always possible. In this review, we attempt to justify why exacerbations in early allergic asthma and adult eosinophilic asthma can differ significantly and why this is important in clinical practice as well as when dealing with health insurers., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Airway wall thickening and excess airway mucus occur in asthma and chronic obstructive pulmonary disease (COPD), but few studies have investigated the relationship between them. Our objective was to determine the association between computed tomography (CT) airway wall thickening in segmental airways proximal to airways with or without mucus plugging in patients with asthma and COPD., Methods: Mucus plugging was scored using a CT bronchopulmonary segment-based scoring system in asthma and COPD patients. For each of the 19 segmental airways, a mucus plug was defined as complete occlusion of one or more of the daughter branches (sub-segmental airways) by mucus. CT airway measurements were generated for each of the 19 segmental airways: wall-area-percentage (WA%), lumen area (LA), and total airway count (TAC) (VIDA Diagnostics Inc.). Multivariable logistic regression models were constructed for the presence of mucus plugs with corresponding CT measurement and adjusted by covariates; each of the 19 segments was treated as a nested variable., Results: A total of 33 participants were evaluated. Participants had a mean age of 60 ± 15yrs and there were n = 14 (42%) males. There were 16 (48%) participants with a diagnosis of asthma and 17 (52%) with a COPD diagnosis. The mean FEV 1 was 53 ± 21%pred and FEV 1 /FVC was 54 ± 15%. The mean mucus score in all participants was 15 ± 4 (min = 0, max = 19). Multivariable logistic regression analysis showed the presence of airway mucus was significantly associated with increased CT WA% (β = 7.30, p = 0.004) and reduced TAC (β = -0.06, p = 0.045)., Conclusions: There was increased airway wall thickness and reduced airway counts on CT in segments where there was a distal mucus plug compared to segments without mucus plugs in asthma and COPD., Competing Interests: Declaration of competing interest TH reports grants from Fisher and Paykel and personal fees from Sanofi, outside the submitted work. PN reports grants from AstraZeneca, Teva, Roche, Novartis, Sanofi and Foresee, and personal fees from AstraZeneca, Teva, Roche, Novartis, Merck and Equillium, outside the submitted work. SS reports grants from Cyclomedica and personal fees from AstraZeneca, Novartis, Polarean, and Arrowhead Pharmaceuticals, all outside the submitted work. All other authors do not have any potential conflicts of interest to declare., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Persistent cough with sputum production is an important clinical trait in chronic obstructive pulmonary disease (COPD). We defined "frequent productive cough" based on 2 questions from the St George's Respiratory Questionnaire (SGRQ) and sought to determine its occurrence and associated outcomes in patients with physician-assigned asthma and/or COPD from the NOVELTY study., Methods: Frequent productive cough was defined as cough and sputum production most or several days/week for the past 3 months (scoring ≥3 for both SGRQ questions). Relationships with baseline disease characteristics and exacerbations over 12 months' follow-up were examined using logistic regression., Results: Baseline SGRQ data were available for 7125 patients, of whom 31.3% had frequent productive cough. It was more common in asthma+COPD (38.8%) and COPD (38.1%) than asthma (25.0%), increasing with physician-assessed severity, and in current versus former and never smokers. Patient-reported symptomatic worsening was more common in patients with versus without frequent productive cough. Reduced post-bronchodilator FEV 1 (odds ratio [OR] per 10% decrement 1.14 [95% confidence interval 1.11-1.16]) and history of pollutant exposure at home/work (OR 1.50 [1.33-1.69]) were associated with frequent productive cough in all diagnoses. Patients with baseline frequent productive cough were more likely to have ≥1 exacerbation over the subsequent 12 months (OR 1.71 [1.52-1.93]), including exacerbations requiring hospital admission and those treated with oral corticosteroids., Conclusions: Frequent productive cough represents an important indicator of adverse clinical outcomes across asthma and/or COPD. Research into the underlying pathologic mechanisms is required to support targeted therapy development., Clinicaltrials: GOV: NCT02760329., Competing Interests: Declaration of competing interest R.H., E.R., C.K., E.L.T., and H.M. are employees of AstraZeneca; C.J. has received personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, and Orion; B.J.M. has received CME personal fees from American College of Chest Physicians, Eastern Pulmonary Society, Integritas Communications, Medscape, National Jewish Health, Novartis, Mt Sinai, Projects in Knowledge, WebMD, and Wolters Kluwer Health; medical advisory board fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Mylan, Novartis, Phillips, Third Pole, and Verona; personal fees for data safety and monitoring board from Quintiles and Spiration; grants from American Lung Association, AstraZeneca, GlaxoSmithKline; personal fees from AstraZeneca, GlaxoSmithKline, Optimum Patient Care Global Limited, Spiration, and Third Pole; funding from the NHLBI for the COPDGene study; P-R.B. has received personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Insmed, Pfizer, Vertex Pharmaceuticals, and Zambon; grants from Boehringer Ingelheim, GlaxoSmithKline and Vertex Pharmaceuticals; H.K.R. has participated in advisory boards for AstraZeneca, Chiesi, GlaxoSmithKline, Novartis, and Sanofi-Genzyme; and has received honoraria from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Sanofi, and Teva Pharmaceuticals for independent medical educational presentations; and independent research funding from AstraZeneca, GlaxoSmithKline and Novartis., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: This study's objectives were to compare the prevalence of mental disorders and consumption of psychiatric medications in asthmatic subjects with non-asthmatic controls and identify risk factors associated with psychiatric conditions., Methods: This was an epidemiological case-control study based on the 2020 European Health Survey in Spain self-reported data. Each asthmatic subject was paired with a non-asthmatic control. Study variables included demographics, use of healthcare services, comorbidities, and risky behaviours were compared., Results: There were 22,072 participants in the survey; 1151 cases and 1151 controls were selected. The prevalence of mental disorders (25.5% versus 13.4%; p < 0.001) and consumption of psychiatric medications (25.8% versus 15.6%; p < 0.001) were higher in cases than controls. In asthmatic subjects, female gender (OR 1.814; p = 0.001), age over 80 years (OR 2.558; p = 0.002), poor self-rated health (OR 2.047; p < 0.001), visits to a psychologist (OR 10.854; p < 0.001) and chronic pain (OR 1.938; p < 0.001) were independently associated with mental disorder diagnoses. Meanwhile, female sex (OR 1.710; p < 0.001), age over 80 years (OR 3.802; p < 0.001), poor self-rated health (OR 2.482; p < 0.001), visits to a psychologist (OR 2.694; p < 0.001) and chronic pain (OR 1.494; p = 0.012) were risk factors independently associated with psychiatric medication consumption., Conclusions: The prevalence of psychiatric conditions were higher in asthmatic subjects. Female gender, older age, worse self-rated health, visits to a psychologist and chronic pain were associated with psychiatric conditions in asthmatic subjects., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Small airway dysfunction (SAD) is an early lesion of chronic respiratory disease that is best detected using impulse oscillometry (IOS). Few studies have investigated risk factors for IOS-defined SAD (IOS-SAD) in a large population. We aimed to explore the clinical features of and risk factors for IOS-SAD in a community-based population., Methods: We divided subjects into IOS-SAD and non-SAD groups based on a cutoff of >0.07 kPa/L/s in the difference between the resistance at 5 Hz versus the resistance at 20 Hz (R5-R20). All participants underwent spirometry, IOS, and completed a questionnaire; some participants underwent computed tomography (CT). We analyzed the risk factors for SAD based on binary logistic regression., Results: The total cohort comprised 1327 subjects. The prevalence of IOS-SAD was 32.9% (437/1327). Compared with the non-SAD group, the IOS-SAD group was older (64.0 ± 7.8 vs. 59.6 ± 7.8 years, p < 0.001), included less never-smokers (30.2% vs. 35.8%, p < 0.001), had greater airway resistance and worse lung function, indicated by a larger R5-R20 (0.15 ± 0.08 vs. 0.03 ± 0.02 kPa/L/s, p < 0.001) and smaller forced expiratory volume in 1 s to forced vital capacity after bronchodilation (60.2 ± 14.4% vs. 72.6 ± 10.0%, p < 0.001); on CT, the IOS-SAD group had higher prevalences of emphysema and gas trapping. Risk factors for SAD were older age, high BMI, smoking, childhood cough, and asthma., Conclusion: Subjects with IOS-SAD had increased airway resistance and visible CT changes. Individuals with smoking exposure, advanced age, high BMI, childhood cough, and asthma were more prone to SAD., Clinical Trial Registration: ChiCTR1900024643., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Increasing evidence shows that environmental factors in childhood play a role in development of irreversible airway obstruction. We evaluated early-life and preschool-age risk factors for irreversible airway obstruction in adolescence after bronchiolitis in infancy., Methods: This study is a secondary analysis of data collected during prospective long-term follow-up of our post-bronchiolitis cohort. Risk factor data were collected during hospitalisation and on follow-up visits at 5-7 and 10-13 years of ages. Lung function was measured from 103 participants with impulse oscillometry at 5-7 years of age and from 89 participants with flow-volume spirometry at 10-13 years of age., Results: Asthma diagnosis at <12 months of age showed a significant association with irreversible airway obstruction at 10-13 years of age independently from current asthma. Irreversible airway obstruction was less frequent in children with variant than wild genotype of the Toll-like receptor 4(TLR4) rs4986790, but the significance was lost in logistic regression adjusted for current asthma and weight status. Higher post-bronchodilator respiratory system resistance at 5 Hz and lower baseline and post-bronchodilator reactance at 5 Hz by impulse oscillometry at 5-7 years of age were associated with irreversible airway obstruction at 10-13 years of age., Conclusion: Asthma diagnosis during the first living year and worse lung function at preschool age increased the risk for irreversible airway obstruction at 10-13 years of age after bronchiolitis. TLR4 rs4986790 polymorphism may be protective for development of irreversible airway obstruction after bronchiolitis., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The association of bronchiectasis (BE) in patients with severe eosinophilic asthma (SEA) is quite frequent. Mepolizumab is a well-recognized treatment for SEA; we aim to evaluate its effectiveness in SEA patients with and without BE in real-life., Methods: We performed a single-center retrospective pilot study, including patients with SEA treated with mepolizumab for one year. Asthma control test (ACT), lung function, annual exacerbations rate, oral corticosteroid dosage, FeNO, chronic mucous secretions, blood and sputum eosinophils were recorded at baseline and after 6 and 12 months., Results: we included 32 patients (mean age: 52.3 ± 10, 59% female). 50% showed co-presence of bronchiectasis, (SEA + BE). Significant improvements were found in ACT [(13.8 ± 4.6 to 20.7 ± 4.1, p = 0.0009) and (13 ± 4.8 to 20.7 ± 4.6, p = 0.0003)], annual exacerbations rate [from 7 (4-12) to 0 (0.00-0.75) and from 8 (4-12) to 0 (0-1), p < 0.0001], and blood eosinophils count [748 cells/μL (400-1250) vs. 84 cells/μL (52.5-100), and from 691 cells/μL (405-798) vs. 60 cells/μL (41-105), p < 0.0001] in SEA and SEA + BE group respectively, already after 6 months of treatment. A reduction in daily oral corticosteroids intake at 12 months was shown [from 15 mg (0-25) to 0 mg (0-0), p = 0.003 and from 8.8 mg (0-25) to 0 mg (0-0) (p = 0.01)] in both SEA and SEA + BE, respectively. Similar results were found, comparing SEA + BE patients based on the severity of bronchiectasis., Conclusions: Mepolizumab effectively improves asthma symptoms control, reducing annual exacerbations and corticosteroid intake in all patients with SEA, even in the subgroup with coexisting bronchiectasis, independently of their severity., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Published data on vitamin D and the quality of life of asthma patients are scarce and disparate. The ACVID clinical trial, published in 2020, showed the efficacy of calcifediol in improving asthma control in asthma patients with vitamin D deficiency. Data on vitamin D and quality of life measured by the Mini-AQLQ questionnaire were analysed: supplemented patients showed improved quality of life compared with a placebo group, and the initial mini-AQLQ scores were improved for both groups., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The effects of chronic inhaled and systemic corticosteroids use on COVID-19 susceptibility and severity are unclear. Since many patients with chronic pulmonary diseases rely on corticosteroids to control disease, it is important to understand the risks of their use during the pandemic. We aim to study if the use of inhaled or systemic corticosteroids affects the likelihood of developing COVID-19 infection., Methods: We used the National Jewish Health electronic medical record research database to identify a cohort of all subjects who were tested for suspected COVID-19 between March 11 - June 23, 2020. Testing results, medication use, and comorbidities were obtained from the medical record. Following a comparison of different propensity score weighting methods, overlap propensity score weighting was used to analyze the association between medication use and COVID-19 diagnosis., Results: The cohort consisted of 928 patients, of which 12% tested positive. The majority (66%) of patients had a history of chronic pulmonary diseases. There was no significant association between inhaled corticosteroid use and testing positive for COVID-19. Interestingly, systemic corticosteroid use was associated with a lower odds ratio (0.95, 95% CI: 0.91-0.99) of testing positive for COVID-19. Similar results were noted when the analysis was restricted to those with any chronic pulmonary diseases, with asthma or with chronic obstructive pulmonary disease (COPD)., Conclusions: Our study supports the recommendation that patients with chronic pulmonary diseases, including asthma and COPD who require treatment with either inhaled or systemic corticosteroids, should continue their use during the COVID-19 pandemic., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: The novel coronavirus disease 2019 (COVID-19) has rapidly spread across the globe. Pre-existing comorbidities have been found to have a dramatic effect on the disease course. We sought to analyze the effect of asthma on the disease progression and outcomes of COVID-19 patients., Methods: We conducted a multi-center retrospective study of positively confirmed COVID-19 patients. The primary outcome of interest was in-hospital mortality. Secondary outcomes were the Intensive Care Unit (ICU) admission, intubation, mechanical ventilation, and length of hospital stay., Results: A total of 502 COVID-19 adult patients (72 asthma and 430 non-asthma cohorts) with mean age of 60.7 years were included in the study. The frequency of asthma in hospitalized cohorts was 14.3%. Univariate analysis revealed that asthma patients were more likely to be obese (75% versus 54.2%, p = 0.001), with a higher frequency of intubation (40.3% versus 27.8%, p = 0.036), and required a longer duration of hospitalization (15.1 ± 12.5 versus 11.5 ± 10.6, p = 0.015). After adjustment, multivariable analysis showed that asthmatic patients were not associated with higher risk of ICU admission (OR = 1.81, 95%CI = 0.98-3.09, p = 0.06), endotracheal intubation (OR = 1.77, 95%CI = 0.99-3.04, p = 0.06) or complications (OR = 1.37, 95%CI = 0.82-2.31, p = 0.23). Asthmatic patients were not associated with higher odds of prolonged hospital length of stay (OR = 1.48, 95%CI = 0.82-2.66, p = 0.20) or with ICU stay (OR = 0.76, 95%CI = 0.28-2.02, p = 0.58). Kaplan-Meier curve showed no significant difference in the overall survival of the two groups (p = 0.65)., Conclusion: Despite the increased prevalence of hospitalization in elder asthmatic COVID-19 patients, after adjustment for other variables, it was neither associated with increased severity nor worse outcomes., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background and Objective: Airway remodeling, as many other factors, may lead to lung function decline and irreversible airflow obstruction (IRAO) in asthma. This study was undertaken in order to highlight predictors of incomplete reversibility of airflow obstruction in adult asthmatics to identify patients with poorer prognosis and improve their care, and decrease morbidity., Methods: A retrospective study was conducted in 973 asthmatics recruited from the University Asthma Clinic of Liege. Patients with IRAO (post-BD FEV 1 /FVC<0.7 & FEV 1 <80% predicted) were compared to patients with reversible airway obstruction (RAO) (post-BD FEV 1 /FVC≥0.7 & FEV 1 ≥80% predicted). TGF-β was measured in sputum supernatant of 85 patients., Results: Seventeen percent of asthmatics presented with IRAO. These patients were significantly older, more smokers, with a lower proportion of female, a longer disease duration, were more poorly controlled with a lower quality of life. This sub-population of asthmatics also showed more often elevated blood and sputum eosinophils and neutrophils, and higher exacerbation and hospitalisation rates in the previous year. The multivariable analysis revealed male gender, longer disease duration, cigarette smoking, ACQ score, sputum eosinophils and neutrophils, ICS dose and OCS maintenance, BMI, and asthma onset as variables independently linked to IRAO. Total TGF-β levels appeared higher in patients with IRAO (n = 38) compared to patients with RAO (n = 47)., Conclusion: These data show that risk factors for IRAO are male gender, smoking, a longer disease duration, uncontrolled asthma, eosinophilic or neutrophilic airway inflammation, lower BMI, and later asthma onset. Moreover, TGF-β levels are higher in IRAO., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Long-term childhood asthma studies that investigate adult outcomes other than lung function are lacking. This study examines the associations of childhood asthma and the occurrence of respiratory events and all-cause mortality in adulthood., Methods: A cohort of 4430 school children (aged to 17 years) who attended the Busselton Health Study between 1967 and 1983 were analysed. Self-reported history of asthma was determined using questionnaires. Participants were followed until 2014 for respiratory disease-related events (hospital admissions or death) and all-cause mortality using the Western Australia Data Linkage System. Cox regression models were used to investigate the impact of childhood asthma on respiratory events and all-cause mortality in adulthood. A subgroup of 2153 participants who re-attended a survey in young adulthood was also analysed., Results: A total of 462 (10%) of the cohort had childhood asthma. During follow-up 791 participants experienced a respiratory event and 140 participants died. Childhood asthma was associated with an increased risk of respiratory events in adulthood (unadjusted HR 1.84, 95% CI 1.52 to 2.23; P < 0.0001). The result remained significant after adjusting for adult-onset asthma, FEV 1 , body mass index, smoking, dusty job, hay fever, and respiratory symptoms (adjusted HR 1.68, 95% CI 1.07 to 2.64; P = 0.0247). Childhood asthma was not associated with all-cause mortality in adulthood (unadjusted HR 1.08, 95% CI 0.63 to 1.84; P = 0.7821)., Conclusion: Childhood asthma is associated with increased risk of respiratory disease-related hospital admissions and death but not all-cause mortality in adulthood., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: It is essential to recognize and treat findings that can simulate or worsen symptoms to improve asthma control and thereby to reduce costs. Guidelines highlight a paranasal (PS) and chest computed tomography (CT) scan as a tool for disease evaluation and, although they suggest its indication in patients whom presentation is atypical, there are not well-defined criteria., Objectives: To describe the most common findings in the PS and chest CT in severe asthma patients and to analyse the characteristics of asthmatics with the finding of nasal polyps or bronchiectasis., Methods: We retrospectively reviewed the medical records of 161 adults with confirmed severe asthma who had undergone to PS and/or chest CT. Clinical data from their electronic health record and the findings from a PS and/or chest CT within the last five years were collected., Results: In the PS CT, 70.5% of patients presented mucous thickening and 46.7% presented nasal polyps. Both findings were associated with male gender and level of blood eosinophils. In chest CT, 28% of individuals showed atelectasis, 16.5% air trapping, 17.7% affectation of the small airway, 11.6% pulmonary infiltrates and 10.4% emphysema. Bronchiectasis were identified in 60.4% of subjects, who were older and had poorer lung function., Conclusion: Paranasal and thoracic computed tomography are important tools in the treatment of severe asthma because they allow us to detect highly prevalent findings in this disease that can lead to poorer control of it., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Cough is a common yet distressing symptom that results in significant health care costs from outpatient visits and related consultations., Objective: The understanding of the pathobiology of cough in recent times has undergone an evolution with Cough hypersensitivity syndrome (CHS) being suggested in most cases of dry cough. However, in the case of productive cough, ancillary mechanisms including impaired Mucociliary clearance, in addition to hypermucosecretory bronchospastic conditions of Smoker's cough, asthma-COPD overlap, bronchiectasis, and allergic bronchopulmonary aspergillosis, need to be critically addressed while optimizing patient care with symptomatic therapy in outpatient settings of India., Methods: In this review, evidence-based graded recommendations on use of antitussives - & protussives as a Position Paper were developed based on the Level and Quality of Scientific evidence as per Agency for Health Care and Quality (AHRQ) criteria listing and Expert opinions offered by a multidisciplinary EMA panel in India., Results: Management of acute or chronic cough involves addressing common issues of environmental exposures and patient concerns before instituting supportive therapy with antitussives or bronchodilatory cough formulations containing mucoactives, anti-inflammatory, or short-acting beta-2 agonist agents., Conclusion: The analyses provides a real world approach to the management of acute or chronic cough in various clinical conditions with pro- or antitussive agents while avoiding their misuse in empirical settings., Competing Interests: Declaration of competing interest The listed authors declare and report no conflict of interest for this work and received no honorarium for the development of this Position Paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Nasal polyps are a significantly associated pathology of chronic rhinosinusitis (CRS) whose mechanisms of pathogenesis are not fully elucidated, especially the interaction of the polyp with its environment that allows its growth on the nasal epithelial lining. Exosomes are nanovesicles that serve important biological functions, including cell-to-cell signaling and communication., Objective: Hence, we sought to explore the roles of the epithelial-derived exosomal proteome obtained from the human nasal epithelium in the modulation of CRS with nasal polyp (CRSwNP) pathogenesis., Methods: We sampled exosomes from nasal lavage fluid and primary human nasal epithelial cells (hNECs) from healthy controls and patients with CRSwNP with and without coexisting asthma. The presence of exosomes was confirmed using a NanoSight assay, transmission electron microscopy and western blotting. The exosomal proteome was profiled with mass spectrometry. The Cell Counting Kit-8 was used to confirm the roles of exosomes in mediating cellular proliferation., Results: The hNEC-derived exosomes from diseased epithelium contained differentially expressed proteins that were mainly involved in epithelial remodeling via pathways such as p53. An in vitro study further demonstrated that epithelial-derived exosomes from patients with CRSwNP (with and without coexisting asthma) significantly reduced the rate of proliferation of control hNECs at an effective concentration of ≥10 μg/ml., Conclusions: Exosomes secreted by hNECs from patients with CRSwNP, regardless of their coexistence with asthma, are laden with proteins that influence cell proliferation pathways, potentially leading to remodeling of the sinonasal mucosa., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Although many studies have highlighted the link between asthma/rhinitis and depression, it is still unclear which characteristics of these diseases are associated with the risk of depression. We aimed to explore the relationship between depression and asthma or rhinitis in a representative sample of the Italian general population., Methods: The data were collected in GEIRD, an Italian multicenter, population-based, multicase-control study. 2227 participants (age 21-86 years, female 50%) underwent standardized interviews, skin prick and lung function tests, and were divided into cases of current asthma (n = 528), rhinitis without asthma (n = 972), and controls (n = 727). Two specific questions from the Patient Health Questionnaire (PHQ-2) were asked to identify symptoms of depressed mood and anhedonia, which were used as a proxy of major depression disorder., Results: The prevalence of depression was 16.7%, 11.9%, and 5.1% in subjects with asthma, rhinitis and controls, respectively. Both in asthma and rhinitis, subjects with depression had worse respiratory-health related quality of life and more frequent disease-related symptoms than their non-depressed counterparts. In asthma, depression was associated with poorer disease control. In rhinitis, depression was significantly associated with a disease-related limitations in daily activities and greater risk of symptom exacerbations and prescriptions of medicines for breathing. Cases of rhinitis with depression were less likely to be atopic., Conclusions: Our results suggest that rhinitis exacerbations, particularly in non-atopic subjects, and low asthma control are strongly related to the presence of depressed mood in adults from the general population., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Severe asthma and bronchiectasis are heterogeneous diseases that contribute to disability beyond the pulmonary system. The magnitude of the impact that these extrapulmonary features has on health-related quality of life (HRQoL) is unknown., Methods: We analysed the cross-sectional relationships between HRQoL (St. George's Respiratory Questionnaire; SGRQ) and extrapulmonary characteristics, including physical activity (steps/day), anxiety and depression, isometric leg strength, systemic inflammation, and several comorbidities in adults with severe asthma (n = 70) and bronchiectasis (n = 61)., Results: Participants with severe asthma and bronchiectasis had similar SGRQ total scores (mean scores 43.7 and 37.8 for severe asthma and bronchiectasis; p > 0.05), and similar pulmonary and extrapulmonary characteristics. The associations between extrapulmonary variables and HRQoL did not differ according to diagnosis (all interactions p > 0.05). Greater anxiety and depressive symptoms, fewer steps/day and greater systemic inflammation were statistically associated with poorer HRQoL in both diseases (p < 0.05). Lower isometric leg strength in severe asthma, and greater Charlson Comorbidity Index in bronchiectasis were also associated with poorer HRQoL (p < 0.05). In the multivariable regression model performed in the combined disease groups, anxiety and depression, steps/day, systemic inflammation and isometric leg strength remained independently associated with HRQoL. Associations between extrapulmonary characteristics and SGRQ domains were stronger for the activity and impact domains, than symptoms., Conclusion: In severe asthma and bronchiectasis, extrapulmonary features including physical activity and leg strength have a significant impact on HRQoL, especially within the activity and impact domains. These features should be considered as part of the assessment of these conditions, and they may represent additional treatment targets to improve HRQoL., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: By definition bronchiectasis (BE) means destructed structure of normal bronchus as a consequence of frequent bacterial infections and inflammation. In many senses, BE is a neglected orphan disease. A recent pan-European registry study, EMBARC, has been set up in order to better understand its pathophysiology, better phenotype patients, and to individualize their management., Aim: To examine the aetiology and co-morbidity of BE in the capital area in Finland., Methods: Two hundred five patients with BE diagnosis and follow up visits between 2016 and 2017 in Helsinki University Hospital were invited to participate in the study. Baseline demographics, lung functions, imaging, microbiological, and therapeutic data, together with co-morbidities were entered into EMBARC database. Clinical characteristics, aetiologic factors, co-morbidities, and risk factors for extensive BE were explored., Results: To the study included 95 adult patients and seventy nine percent of the BE patients were women. The mean age was 69 years (SD ± 13). Asthma was a comorbid condition in 68% of the patients but in 26% it was estimated to be the cause of BE. Asthma was aetiological factor for BE if it had been diagnosed earlier than BE. As 41% BE were idiopathic, in 11% the disorder was postinfectious and others were associated to rheumatic disease, Alpha-1-antitrypsin deficiency, IgG deficiency and Kartagener syndrome. The most common co-morbidities in addition to asthma were cardiovascular disease (30%), gastroesophageal reflux disease (26%), overweight (22%), diabetes (16%), inactive neoplasia (15%), and immunodeficiency (12%). Extensive BE was found in 68% of BE patients in whom four or more lobes were affected. Risk factors for extensive BE were asthma (OR 2.7), asthma as aetiology for BE (OR 4.3), and rhinosinusitis (OR 3.1)., Conclusions: Asthma was associated to BE in 68% and it was estimated as aetiology in every fourth patient. However, retrospectively, it is difficult to exclude asthma as a background cause in patients with asthma-like symptoms and respiratory infections. We propose asthma as an aetiology factor for BE if it is diagnosed earlier than BE. Asthma and rhinosinusitis were predictive for extensive BE., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Asthma is often associated with different comorbidities such as cardiovascular diseases, depression, diabetes mellitus, dyslipidaemia, osteoporosis, rhinosinusitis and mainly gastro-oesophageal reflux disease and allergic rhinitis. Although bronchodilators play an important role in the treatment of asthma, there is no overall description of their impact on comorbid asthma, regardless of whether favourable or negative. This narrative review examines the potential effects of bronchodilators on comorbidities of asthma., (Copyright © 2019. Published by Elsevier Ltd.)

Gastro-oesophageal reflux disease (GORD) has long been associated with poor asthma control without an established cause-effect relationship. 610 asthmatics (421 severe/88 mild-moderate) and 101 healthy controls were assessed clinically and a subset of 154 severe asthmatics underwent proteomic analysis of induced sputum using untargeted mass spectrometry, LC-IMS-MS E . Univariate and multiple logistic regression analyses (MLR) were conducted to identify proteins associated with GORD in this cohort. When compared to mild/moderate asthmatics and healthy individuals, respectively, GORD was three- and ten-fold more prevalent in severe asthmatics and was associated with increased asthma symptoms and oral corticosteroid use, poorer quality of life, depression/anxiety, obesity and symptoms of sino-nasal disease. Comparison of sputum proteomes in severe asthmatics with and without active GORD showed five differentially abundant proteins with described roles in anti-microbial defences, systemic inflammation and epithelial integrity. Three of these were associated with active GORD by multiple linear regression analysis: Ig lambda variable 1-47 (p = 0·017) and plasma protease C1 inhibitor (p = 0·043), both in lower concentrations, and lipocalin-1 (p = 0·034) in higher concentrations in active GORD. This study provides evidence which suggests that reflux can cause subtle perturbation of proteins detectable in the airways lining fluid and that severe asthmatics with GORD may represent a distinct phenotype of asthma., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Age at asthma onset is associated with severity and outcomes of the disease., Objective: We studied if age at asthma diagnosis is related to employment and outcomes in working career., Patients and Methods: A questionnaire was sent to 2613 adults with asthma in Tampere, Finland, and a follow-up questionnaire was sent after six years. Asthmatics were divided into groups based on their employment status: working full-time or work disability. Logistic regression was used to study the association of age at asthma diagnosis with employment status at baseline and with the risk of exiting full-time work during follow-up period., Results: In cross-sectional analysis, asthma diagnosed in late adulthood (50 + years) was associated with higher OR for having work-disability compared to childhood onset asthma (OR [95% CI] 3.60 [1.43-9.06]). During follow-up, asthma diagnosed in late adulthood was associated with higher OR for exiting full time work compared to childhood-onset asthma (OR 10.87 [3.25-36.40])., Conclusions: Asthma diagnosed in late adulthood is a higher risk for poor employment than asthma diagnosed earlier in life. Adult-onset of asthma is an important factor in view of work ability and early rehabilitation procedures., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Individuals with obesity are more likely to develop asthma, but the exact mechanism is still uncertain and several hypotheses have been raised, such as the release of inflammatory mediators secreted by adipose tissue., Objective: To assess the effects of weight loss in patients submitted to bariatric surgery on pulmonary and systemic inflammation., Method: The study evaluated patients undergoing bariatric surgery (Roux-en-Y gastric bypass) with the diagnosis of asthma, except smokers. The patients were evaluated at the time of entry into a preoperative weight loss group (T1), just before bariatric surgery (T2), six months after surgery (T3), and 12 months after surgery (T4). The following were measured: anthropometric data, dosage of systemic inflammatory markers by means of blood collection, pulmonary inflammatory markers obtained by induced sputum collection, pulmonary function parameters, and asthma activity assessed by a Asthma Control Test (ACT) questionnaire., Results: Nineteen patients participated in the study. There were significant reductions in the systemic levels of interleukin (IL)-8 (p = 0.002), C-reactive protein (CRP) (p = 0.003), leptin (p = 0.001) and tumor necrosis factor (TNF)-α (p = 0.007), and significant increase in the systemic levels of IL-6 (p = 0.004) over time and adiponectin in T2 (p = 0.025). In regards to pulmonary inflammation, there were significant reductions in the sputum levels of TNF-α (p < 0.001). There was no significant improvement of the pulmonary function parameters (p > 0.05) and significant improvement in asthma activity scores (p < 0.0001)., Conclusion: Weight loss was associated with significant changes in the systemic and pulmonary inflammatory profiles of individuals with asthma, leading to a better asthma control as a result of an increase in some anti-inflammatory mediators and a reduction of pro-inflammatory mediators., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Chronic Refractory Cough (CRC) is a common condition that significantly impairs patients' quality of life. Unfortunately, in many situations patients continue to experience CRC in spite of following published guidelines for diagnosis and treatment., Methods: 99 patients were referred to National Jewish Health (NJH), a specialty respiratory center for evaluation of CRC (cough ≥ 8 weeks duration). Study duration occurred over 18 months. Intake evaluation for all patients included history, physical examination, spirometry and fiberoptic laryngoscopy. Testing to confirm causes of CRC were performed. Specific therapy for each potential cause was provided. A visual analog cough scale measured cough response., Results: Ten final diagnostic categories were found in the cohort of 99 patients with CRC: Obstructive sleep apnea (apnea/hypoxia index ≥ 5), rhinosinusitis, Tracheobronchomalacia (≥65% collapse of airway with dynamic expiratory imaging), esophageal dysmotility, gastroesophageal reflux, abnormal swallowing with laryngeal penetration, asthma, COPD, bronchiectasis and paradoxical vocal cord movement. In these patients there were 42 incorrect intake diagnoses and 101 new diagnoses established. Patients with CRC have had multiple diagnoses (3.8 ± 1.6) associated with chronic cough. With directed therapy 71/76 (93%) patients had resolution or improvement in cough symptoms., Conclusions: Among patients referred to a specialty respiratory center with CRC multiple concomitant diagnoses for cough were common. Certain diagnoses such as OSA and TBM have not been reported in cough guidelines but in this study are commonly associated diagnoses. Targeted therapy for each recognized diagnosis improves patient response., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Asthma is a common medical condition that impacts the lives of many Canadians; yet the health-related quality of life (HRQoL) in persons with asthma relative to the general population (GP) is poorly studied. In this study, data from the Canadian Community Health Survey (CCHS) 2013 was used to quantify and compare the HRQoL of the asthmatic population (AP) and the GP., Methods: A representative survey sample of Canadians was taken from the CCHS to compare the Health Utilities Index Mark 3 (HUI3) scores, a generic HRQoL measure, between the AP (n = 572) and the GP (n = 6518). The HUI3 multi-attribute utility (MAU) and the single-attribute utility (SAU) scores between the two sample groups were studied. The CCHS 2013 dataset was explored as the primary analysis, while the 2012 dataset was used as the confirmatory analysis to verify the consistency of the results., Results: Clinically important difference was found in the MAU score between the AP and GP (p < 0.001, Effect size = 0.30). MANOVA on the eight SAU scores with post-hoc test revealed that the AP had a lower mean score of vision (p < 0.001, Effect size = 0.36) and pain/disconfort (p < 0.001, Effect size = 0.29). Those findings were consistent with the CCHS 2012 dataset result., Conclusions: These results provided evidence that in Canada, having asthma significantly worsens asthma patients' overall HRQoL and imposes significant impacts on the patients' vision and pain/discomfort. Therefore, there is room for improvement in the currently available asthma therapies so patients could achieve better HRQoL; particular focus should be given to the pain/discomfort and vision health domains., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Asthma and COPD may overlap (ACO) but information about incidence and risk factors are lacking. This study aimed to estimate prevalence, incidence and risk factors of chronic airway obstruction (CAO) in a population-based adult asthma cohort., Methods: During 1986-2001 a large population-based asthma cohort was identified (n = 2055, 19-72y). Subsamples have participated in clinical follow-ups during the subsequent years. The entire cohort was invited to a clinical follow-up including interview, spirometry, and blood sampling in 2012-2014 when n = 983 subjects performed adequate spirometry. CAO was defined as post-bronchodilator FEV 1 /FVC<0.7., Results: At study entry, asthmatics with prevalent CAO (11.4%) reported more respiratory symptoms, asthma medication use, and ischemic heart disease than asthmatics without CAO (asthma only). Subjects who developed CAO during follow-up (17.6%; incidence rate of 16/1000/year) had a more rapid FEV 1 decline and higher levels of neutrophils than asthma only. Smoking, older age and male sex were independently associated with increased risk for both prevalent and incident CAO, while obesity had a protective effect., Conclusions: In this prospective adult asthma cohort, the majority did not develop CAO. Smoking, older age and male sex were risk factors for prevalent and incident CAO, similar to risk factors described for COPD in the general population., (Copyright © 2018. Published by Elsevier Ltd.)

Background: The most common adverse effect of bronchial thermoplasty (BT) is short-term aggravation of asthma immediately following the procedure. However, the magnitude and duration of this deterioration, and its predisposing factors are yet to be quantitated. This information will be particularly important as BT is extended to include more severely obstructed patients., Methods: In this prospective, observational study of 20 consecutive patients with very severe asthma undergoing BT, post bronchodilator FEV 1 was measured in the 30 min prior to surgery, and then 24 h following the 60 procedures. In half the patients, further spirometry was conducted on day 3 and day 7 post procedure., Results: This study enrolled 12 males and 8 females, mean age 59.7 ± 12.8 years, with mean prebronchodilator FEV 1 of 52.3 ± 15.2% predicted, mean forced expiratory ratio of 51.4 ± 12.6%, and mean improvement in FEV 1 post salbutamol of 19.5 ± 15.3%. All patients were taking inhaled corticosteroids, mean beclomethasone equivalent dose 1950 ± 857 mcg, and 7 patients required maintenance oral corticosteroids for control of their asthma. Twenty four hours after BT, the mean deterioration in post bronchodilator FEV 1 was 166 ± 237 mls (CI 102-224, p < 0.001) or 9.1 ± 15.2% of baseline. This deterioration was significantly greater after upper lobe procedures (p < 0.01, ANOVA repeated measures), where a mean fall in FEV 1 of 17.1 ± 12.6% was observed. The change in FEV 1 post procedure was significantly correlated with the number of radiofrequency activations applied, r = -0.376, p < 0.005. By multivariate analysis, the only factor other than activations predictive of the change in FEV 1 was age, which was protective. When the lower lobes were treated, the postbronchodilator FEV 1 had returned to baseline values by day 3, but patients took 7 days to recover after upper lobe treatments. Despite the severity of asthma in these patients, and the measured deterioration post treatment, there was only one instance of readmission in the 60 procedures., Conclusions: The deterioration in lung function after BT is transient and well tolerated, but is greatest after upper lobe treatment, and is significantly related to the number of radiofrequency activations applied., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Bronchial hypersecretion is a poorly studied symptom in asthma. The aim of the study was to determine the specific characteristics of asthmatics with bronchial hypersecretion., Methods: A total of 142 asthmatics (21.8% men; mean age 49.8 years) were prospectively followed for one year. Mucus hypersecretion was clinically classified into two severity categories: daily sputum production and frequent expectoration but not every day. Clinical and pulmonary function variables associated with mucus hypersecretion were assessed by multiple logistic regression analysis., Results: Daily cough was recorded in 28.9% of patients and sputum production daily or most of the days in 52.1%. Patients with mucus hypersecretion had more dyspnoea, poorer asthma control and quality of life, had suffered from more exacerbations and showed anosmia associated with chronic rhinosinusitis and nasal polyposis more frequently. Factors associated to mucus hypersecretion were anosmia, one exacerbation or more in the previous year and FEV1/FVC <70% (AUC 0.75, 95% CI 0.66-0.85) for the first definition of hypersecretion, and anosmia, poor asthma control and age (AUC 0.75, 95% CI 0.67-0.83) for the second definition., Conclusions: Mucus hypersecretion is frequent in patients with asthma, and is associated with chronic upper airways disease, airway obstruction, poor asthma control and more exacerbations., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The weight loss induced by bariatric surgery (BS) improves asthma clinical control evaluated usually after a short time. The long-term effects of weight loss attained by BS on asthma control and health related-quality of life (HRQoL) in patients affected by asthma and obesity are not known., Objective: To investigate the five-year effect of weight reduction induced by BS on asthma control, quality of life and pulmonary functional parameters in severely obese intermittent or mild-to-moderate asthmatic patients., Methods: Twenty-six consecutive severe obese subjects with previous diagnosis of asthma with indication for laparoscopic adjustable gastric banding (LAGB) were enrolled into the study. Fifteen of them agreed to undertake the surgery (treatment group, TG) while the remaining eleven non-operated patients represented the control group (CG). Body mass index (BMI), Asthma Control Test (ACT), Mini Asthma Quality of Life Questionnaire (mini-AQLQ) and spirometric parameters were evaluated at baseline and after one and five years from surgery., Results: Mean BMI of TG significantly decreased at one and five years after the surgery, while it remained unchanged in CG. After surgery, both the overall ACT and the mini-AQLQ score significantly improved in TG after one year, persisting improved after 5-years (p < 0.001), while these outcomes remained unchanged in CG. As compared with the pre-surgery values, the percentage of predicted FEV 1 and FVC significantly increased at five-year follow-up from surgery in TG, while it remained unchanged in CG., Conclusions: In severe obese asthmatic patients, the significant improvement of asthma control test and HRQoL, observed one year after LAGB, persists five years after surgery., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Chronic cough is commonly associated with asthma, gastro-oesophageal reflux disease and postnasal drip, but in a significant proportion, no associated cause can be found. We determined whether examination of bronchial biopsies would be useful in determining the cause associated with chronic cough., Methods: 100 consecutive patients referred to a specialist cough clinic underwent a systematic assessment including a fiberoptic bronchoscopy for bronchial biopsies., Results: In 38 patients, treatment of associated causes led to amelioration of cough ('explained') and in 62, there was no association or improvement ('idiopathic'). The latter group had a longer duration of cough, a lower FeNO levels and a more sensitive capsaicin cough response, with an increase in basement membrane thickness with no differences in goblet cell hyperplasia and seromucinous hyperplasia, and in lymphocyte, neutrophil and eosinophil counts. The duration of cough was inversely correlated with the degree of neutrophil infiltration., Conclusion: We conclude that pathological examination of bronchial biopsies is unlikely to be useful in the diagnosis of chronic cough in non-smokers., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Previous studies demonstrated a high prevalence of cigarette smoking in patients presenting to the emergency department (ED) with acute asthma. Despite the clinical and public health importance, there have been no recent multicenter efforts to characterize this patient population. We aimed to update the prevalence of cigarette smoking among ED patients with asthma exacerbations., Methods: Multicenter chart review study of 48 EDs across 23 US states. We identified ED patients aged 18-54 years with asthma exacerbations during 2011-2012. We classified patients into three groups based on smoking status: never smoker, former smoker, and current smoker. We fit multivariable logistic regression models to examine independent predictors of being a current smoker., Results: Of 1801 enrolled patients, never smokers accounted for 51% (95%CI, 49%-54%), former smokers 13% (95%CI, 11%-14%), and current smokers 36% (95%CI, 34%-38%). The multivariable model demonstrated several independent predictors for current smoking: older age (age 30-39 and 40-54 years), non-Hispanic white or black, having public or no insurance, and not having an asthma specialist (all P < 0.05)., Conclusion: This large multicenter study of ED patients with asthma exacerbations demonstrated that one in three patients were current smokers. This burden of current smokers has not changed from multicenter findings in the late 1990s. The persistently high burden suggests the inadequacy of current measures to manage tobacco use in these high-risk patients., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Although evidence for the heterogeneity of asthma accumulated, consensus for definitions of asthma phenotypes is still lacking. Obesity may have heterogeneous effects on various asthma phenotypes. We aimed to distinguish asthma phenotypes by latent class analysis and to investigate their associations with different obesity parameters in adults using a population-based Swiss cohort (SAPALDIA). We applied latent class analysis to 959 self-reported asthmatics using information on disease activity, atopy, and age of onset. Associations with obesity were examined by multinomial logistic regression, after adjustments for age, sex, smoking status, educational level, and study centre. Body mass index, percent body fat, waist hip ratio, waist height ratio, and waist circumference were used as obesity measure. Four asthma classes were identified, including persistent multiple symptom-presenting asthma (n = 122), symptom-presenting asthma (n = 290), symptom-free atopic asthma (n = 294), and symptom-free non-atopic asthma (n = 253). Obesity was positively associated with symptom-presenting asthma classes but not with symptom-free ones. Percent body fat showed the strongest association with the persistent multiple symptom-presenting asthma. We observed heterogeneity of associations with obesity across asthma classes, indicating different asthma aetiologies., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Objective: Dysfunctional breathing (DB) is a respiratory disorder, which involves a pattern of breathing too deeply, too superficially and/or too rapidly. In asthma patients, DB may lead to an overestimation of the severity of asthma symptoms, and hence potentially to overtreatment. However, it is not known to which degree DB may affect estimates of asthma control, in a specialist clinical setting., Methods: The MAPOut-study examined all patients referred consecutively over a 12-months period for specialist assessment of asthma at the Respiratory Outpatient Clinic at Bispebjerg Hospital in Copenhagen. All patients were examined with the Nijmegen questionnaire with a DB defined as a score ≥23 and the ACQ questionnaire. Linear regression analysis of predictors of ACQ score was performed. Asthma was defined as asthma symptoms and a positive asthma test., Results: Of the 256 patients referred to the lung clinic, data on both the Nijmegen questionnaire and ACQ score was obtained in 127 patients, who were included in the present analysis. Median (range) age: 30 (15-63) years, and 76 (59.8%) were females. DB was found in 31 (24.4%). Asthmatic patients with co-existing DB had a poorer asthma control compared to asthmatics without DB (Median (range) ACQ score: 2.40 (0.20-4.60) vs 1.20 (0.00-4.40); p < 0.001.). A regression analysis showed that the effect of DB on asthma control was independent of airway hyperresponsiveness or airway inflammation in patients with DB., Conclusion: Dysfunctional breathing is common among asthma patients in a specialist setting, and results in a clinically significant underestimation of asthma control, which may potentially lead to overtreatment., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Obesity worsens asthma control partly through enhanced airway neutrophilia, altered lung mechanics and comorbidities, including obstructive sleep apnea syndrome, gastroesophageal reflux disease and depression. Although controversial, obesity may also cause poorer outcomes in acute asthma. IL-17 is associated with neutrophilic inflammation, steroid resistance and severe asthma, but its importance in the association between asthma and obesity is unknown., Objective: To investigate the role of IL-17 in obese asthma in both acute and stable settings., Methods: Both stable (n = 177) and acute (n = 78) asthmatics were recruited and categorized into lean (n = 77 and 39 respectively), overweight (n = 41 and 17 respectively) and obese (n = 59 and 22 respectively) groups and compared for clinical characteristics, including sputum and plasma IL-17 protein concentrations, sputum cellularity, spirometry and comorbidities. Correlations of IL-17 expression with other measures were explored., Results: In stable subjects, airway neutrophilia and IL-17 concentrations were most prominent in the obese, and correlated positively with each other. Significant increase in plasma IL-17 levels was also noted and associated with elevated depressive symptoms in obesity. In acute asthma, IL-17 expression, like most other clinical measures, was similar among lean, overweight and obese groups, but was higher in acute versus stable asthma subjects, with sputum IL-17 correlating positively with sputum neutrophils and negatively with FEV 1 and plasma IL-17 showing a positive connection to airway eosinophilia during exacerbation., Conclusions: IL-17 contributes to worse disease control in obese asthma through enhancing airway neutrophilia and depression, and may implicate in asthma exacerbations. Effects of adiposity on acute asthma remain uncertain., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: The diagnosis of asthma in children is challenging and relies on a combination of clinical factors and biomarkers including methacholine challenge, lung function, bronchodilator responsiveness, and presence of airway inflammation. No single test is diagnostic. We sought to identify a pattern of inflammatory biomarkers that was unique to asthma using a targeted metabolomics approach combined with data science methods., Methods: We conducted a nested case-control study of 100 children living in a peri-urban community in Lima, Peru. We defined cases as children with current asthma, and controls as children with no prior history of asthma and normal lung function. We further categorized enrollment following a factorial design to enroll equal numbers of children as either overweight or not. We obtained a fasting venous blood sample to characterize a comprehensive panel of targeted markers using a metabolomics approach based on high performance liquid chromatography-mass spectrometry., Results: A statistical comparison of targeted metabolites between children with asthma (n = 50) and healthy controls (n = 49) revealed distinct patterns in relative concentrations of several metabolites: children with asthma had approximately 40-50% lower relative concentrations of ascorbic acid, 2-isopropylmalic acid, shikimate-3-phosphate, and 6-phospho-d-gluconate when compared to children without asthma, and 70% lower relative concentrations of reduced glutathione (all p < 0.001 after Bonferroni correction). Moreover, a combination of 2-isopropylmalic acid and betaine strongly discriminated between children with asthma (2-isopropylmalic acid ≤ 13 077 normalized counts/second) and controls (2-isopropylmalic acid > 13 077 normalized counts/second and betaine ≤ 16 47 121 normalized counts/second)., Conclusions: By using a metabolomics approach applied to serum, we were able to discriminate between children with and without asthma by revealing different metabolic patterns. These results suggest that serum metabolomics may represent a diagnostic tool for asthma and may be helpful for distinguishing asthma phenotypes., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: The literature reports a significant association between various mental disorders and asthma, in particular depression and/or anxiety, with some more robust data regarding anxiety disorders. However, the nature of this association remains largely unclear., Objectives: (1) To test the hypothesis of a specific association of anxiety and depressive disorder (according to the DSM-IV) with asthma and (2) to test the bidirectional hypothesis of causality between asthma and psychiatric disorders., Methods: Ninety-six adults were compared with 96 control subjects matched according to main socio-demographic variables (i.e., gender, age, marital status, cohabiting/non-cohabiting, and BMI). Subjects with asthma were divided according to GINA and ACT classifications. All subjects underwent Structured Clinical Interviews for DSM-IV Axis I (SCID-I) diagnosis., Results: Significant association between asthma and lifetime anxiety disorders emerged (OR 3.03; p = 0.003); no significant association with other psychiatric diagnosis emerged. Moreover, lifetime and current anxiety were associated with asthma severity levels (p < 0.01 and p = 0.001 based on age). Asthma preceded anxiety in 48% of cases; in 52% of cases, anxiety preceded asthma, without significant group differences. The risk of asthma, particularly of severe, uncontrolled forms (p < 0.01), resulted higher in lifetime anxiety disorder patients (p = 0.003 and p = 0.001 based on age at onset). Current anxiety increased the risk of asthma, and that of an uncontrolled form (p < 0.05). Asthma increased the risk of lifetime anxiety disorders (p = 0.002 and p = 0.018 using ages). Intermittent asthma increased the risk of lifetime and current anxiety disorders (p < 0.01)., Conclusions: Anxiety disorders, in particular Lifetime Anxiety Disorders, represent the only psychiatric disorder significantly associated with asthma, with a possible bidirectional, anxiety-asthma relationship, each of which can be caused or result from the other., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Asthma may be associated with polycystic ovary syndrome (PCOS), and possibly patients with PCOS have a more severe type of asthma. The purpose of this systematic literature review is to summarize evidence of a coexistense of PCOS and asthma using the available literature. The search was completed on 01.01.2016. English language articles were retrieved using the search terms 'Asthma' AND 'PCOS', 'Asthma' AND 'systemic inflammation', 'Asthma' AND 'metabolic syndrome', 'asthma' AND 'gynaecology', 'PCOS' AND 'systemic inflammation', 'PCOS' AND 'metabolic syndrome', 'PCOS' AND 'allergy'. Five papers meeting prespecified search criteria were found of which two were registry studies of relevance. The current literature supports a coexistense of PCOS and asthma and gives us an indication of the causes for the possible link between PCOS and asthma. Further research in the area must be conducted to determine the exact nature and magnitude of the association., (Copyright © 2016 Elsevier Ltd. All rights reserved.)