Nasal gene expression differentiates COPD from controls and overlaps bronchial gene expression

© 2017 The Author(s). Background: Nasal gene expression profiling is a promising method to characterize COPD non-invasively. We aimed to identify a nasal gene expression profile to distinguish COPD patients from healthy controls. We investigated whether this COPD-associated gene expression profile in nasal epithelium is comparable with the profile observed in bronchial epithelium. Methods: Genome wide gene expression analysis was performed on nasal epithelial brushes of 31 severe COPD patients and 22 controls, all current smokers, using Affymetrix Human Gene 1.0 ST Arrays. We repeated the gene expression analysis on bronchial epithelial brushes in 2 independent cohorts of mild-to-moderate COPD patients and controls. Results: In nasal epithelium, 135 genes were significantly differentially expressed between severe COPD patients and controls, 21 being up- and 114 downregulated in COPD (false discovery rate < 0.01). Gene Set Enrichment Analysis (GSEA) showed significant concordant enrichment of COPD-associated nasal and bronchial gene expression in both independent cohorts (FDRGSEA < 0.001). Conclusion: We identified a nasal gene expression profile that differentiates severe COPD patients from controls. Of interest, part of the nasal gene expression changes in COPD mimics differentially expressed genes in the bronchus. These findings indicate that nasal gene expression profiling is potentially useful as a non-invasive biomarker in COPD. Trial registration:ClinicalTrials.govregistration number NCT01351792(registration date May 10, 2011), ClinicalTrials.govregistration number NCT00848406(registration date February 19, 2009), ClinicalTrials.govregistration number NCT00807469(registration date December 11, 2008)

Associations of AMP and adenosine induced dyspnea sensation to large and small airways dysfunction in asthma

Abstract Background Bronchial provocation is often used to confirm asthma. Dyspnea sensation, however, associates poorly with the evoked drop in FEV1. Provocation tests only use the large airways parameter FEV1, although dyspnea is associated with both large- and small airways dysfunction. Aim of this study was to explore if adenosine 5′-monophosphate (AMP) and adenosine evoke an equal dyspnea sensation and if dyspnea associates better with large or small airways dysfunction. Methods We targeted large airways with AMP and small airways with dry powder adenosine in 59 asthmatic (ex)-smokers with ≥5 packyears, 14 ± 7 days apart. All subjects performed spirometry, impulse oscillometry (IOS), and Borg dyspnea score. In 36 subjects multiple breath nitrogen washout (MBNW) was additionally performed. We analyzed the association of the change (Δ) in Borg score with the change in large and small airways parameters, using univariate and multivariate linear regression analyses. MBNW was analyzed separately. Results Provocation with AMP and adenosine evoked similar levels of dyspnea. ΔFEV1 was not significantly associated with ΔBorg after either AMP or adenosine provocation, in both univariate and multivariate analyses. In multivariate linear regression, a decrease in FEF25–75 during adenosine provocation was independently associated with an increase in Borg. In the multivariate analyses for AMP provocation, no significant associations were found between ΔBorg and any large or small airways parameters. Conclusion AMP and adenosine induce equally severe dyspnea sensations. Our results suggest that dyspnea induced with dry powder adenosine is related to small airways involvement, while neither large nor small airways dysfunction was associated with AMP-induced dyspnea. Trail registration NCT01741285 at www.clinicaltrials.gov, first registered Dec 4th, 2012

A population analysis of prescriptions for asthma medications during pregnancy

<p>Background: It is important to control asthma during pregnancy. However, some studies indicate that women stop or change their asthma medications when they become pregnant. Objective: We used a population database to analyze changes in prescriptions for asthma medications to patients before, during, and after pregnancy.</p><p>Methods: We collected information from a pregnancy database that is part of the population-based pharmacy prescription InterAction Database from the northern Netherlands. Our study cohort comprised 25,709 pregnancies for which prescription data were available. We collected data over a study period of 1 year before pregnancy until 6 months after birth and analyzed data from pregnant women who received at least 1 prescription for asthma medication during the study period (n = 2072), identifying all prescriptions for asthma medication and oral corticosteroids.</p><p>Results: Prescriptions for asthma medications did not change during pregnancies from 1994-2003. However, during the 2004-2009 period, there was a significant decrease (P = .017) in prescriptions for asthma medications during the first months of pregnancy compared with the months before pregnancy, especially prescriptions of long-acting bronchodilators. Although most asthma prescriptions continued throughout pregnancy, prescriptions for controller therapies were reduced by 30% during the first months of pregnancy.</p><p>Conclusions: Many women stop or reduce their use of asthma medications when they become pregnant. Strategies to safely control asthma during pregnancy are needed. (J Allergy Clin Immunol 2013;131:711-7.)</p>