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

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

Airway responsiveness to methacholine and incidence of COPD: an international prospective cohort study

Background: It has been debated, but not yet established, whether increased airway responsiveness can predict COPD. Recognising this link may help in identifying subjects at risk. Objective: We studied prospectively whether airway responsiveness is associated with the risk of developing COPD. Methods: We pooled data from two multicentre cohort studies that collected data from three time points using similar methods (European Community Respiratory Health Survey and Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults). We classified subjects (median age 37 years, 1st-3rd quartiles: 29-44) by their level of airway responsiveness using quintiles of methacholine dose-response slope at the first examination (1991-1994). Then, we excluded subjects with airflow obstruction at the second examination (1999-2003) and analysed incidence of COPD (postbronchodilator FEV1/FVC below the lower limit of normal) at the third examination (2010-2014) as a function of responsiveness, adjusting for sex, age, education, body mass index, history of asthma, smoking, occupational exposures and indicators of airway calibre. Results: We observed 108 new cases of COPD among 4205 subjects during a median time of 9 years. Compared with the least responsive group (incidence rate 0.6 per 1000/year), adjusted incidence rate ratios for COPD ranged from 1.79 (95% CI 0.52 to 6.13) to 8.91 (95% CI 3.67 to 21.66) for increasing airway responsiveness. Similar dose-response associations were observed between smokers and non-smokers, and stronger associations were found among subjects without a history of asthma or asthma-like symptoms. Conclusions: Our study suggests that increased airway responsiveness is an independent risk factor for COPD. Further research should clarify whether early treatment in patients with high responsiveness can slow down disease progression.The ALEC Study is funded by the European Union’s Horizon 2020 Research and Innovation programme under grant agreement no. 633212. ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya. The SAPALDIA cohort has been funded since 1991 primarily by the Swiss National Science Foundation (grants no 33CS30-148470/1&2, 33CSCO-134276/1, 33CSCO-108796, 324730_135673, 3247BO-104283, 3247BO-104288, 3247BO-104284, 3247-065896, 3100-059302, 3200-052720, 3200-042532, 4026-028099, PMPDP3_129021/1, PMPDP3_141671/1). Other national funders who supported data collection in the original studies are listed in the supplement

Airway responsiveness to methacholine and incidence of COPD: an international prospective cohort study

Background: It has been debated, but not yet established, whether increased airway responsiveness can predict COPD. Recognising this link may help in identifying subjects at risk. Objective: We studied prospectively whether airway responsiveness is associated with the risk of developing COPD. Methods: We pooled data from two multicentre cohort studies that collected data from three time points using similar methods (European Community Respiratory Health Survey and Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults). We classified subjects (median age 37 years, 1st–3rd quartiles: 29–44) by their level of airway responsiveness using quintiles of methacholine dose–response slope at the first examination (1991–1994). Then, we excluded subjects with airflow obstruction at the second examination (1999–2003) and analysed incidence of COPD (postbronchodilator FEV1/FVC below the lower limit of normal) at the third examination (2010–2014) as a function of responsiveness, adjusting for sex, age, education, body mass index, history of asthma, smoking, occupational exposures and indicators of airway calibre. Results: We observed 108 new cases of COPD among 4205 subjects during a median time of 9 years. Compared with the least responsive group (incidence rate 0.6 per 1000/year), adjusted incidence rate ratios for COPD ranged from 1.79 (95% CI 0.52 to 6.13) to 8.91 (95% CI 3.67 to 21.66) for increasing airway responsiveness. Similar dose–response associations were observed between smokers and non-smokers, and stronger associations were found among subjects without a history of asthma or asthma-like symptoms. Conclusions: Our study suggests that increased airway responsiveness is an independent risk factor for COPD. Further research should clarify whether early treatment in patients with high responsiveness can slow down disease progression