Nasal epithelial gene expression identifies relevant asthma endotypes in the ATLANTIS study.

Introduction: Asthma is an inflammatory airways disease encompassing multiple phenotypes and endotypes. Several studies suggested gene expression in nasal epithelium to serve as a proxy for bronchial epithelium, being a non-invasive approach to investigate lung diseases. We hypothesised that molecular differences in upper airway epithelium reflect asthma-associated differences in the lower airways and are associated with clinical expression of asthma.

Identification of asthma-associated microRNAs in bronchial biopsies.

Background: Changes in microRNA (miRNA) expression can contribute to the pathogenesis of many diseases, including asthma. We aimed to identify miRNAs that are differentially expressed between asthma patients and healthy controls, and explore their association with clinical and inflammatory parameters of asthma.

Methods: Differentially expressed miRNAs were determined by small RNA sequencing on bronchial biopsies of 79 asthma patients and 82 healthy controls using linear regression models.

Current Smoking Alters Gene Expression and DNA Methylation in the Nasal Epithelium of Patients with Asthma.

Current smoking contributes to worsened asthma prognosis and more severe symptoms and limits the beneficial effects of corticosteroids. As the nasal epithelium can reflect smoking-induced changes in the lower airways, it is a relevant source to investigate changes in gene expression and DNA methylation. This study explores gene expression and DNA methylation changes in current and ex-smokers with asthma.

Identifying a nasal gene expression signature associated with hyperinflation and treatment response in severe COPD.

Hyperinflation contributes to dyspnea intensity in COPD. Little is known about the molecular mechanisms underlying hyperinflation and how inhaled corticosteroids (ICS) affect this important aspect of COPD pathophysiology. To investigate the effect of ICS/long-acting β-agonist (LABA) treatment on both lung function measures of hyperinflation, and the nasal epithelial gene-expression profile in severe COPD.

Current Smoking is Associated with Decreased Expression of miR-335-5p in Parenchymal Lung Fibroblasts.

Cigarette smoking causes lung inflammation and tissue damage. Lung fibroblasts play a major role in tissue repair. Previous studies have reported smoking-associated changes in fibroblast responses and methylation patterns.

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

Background: Bronchial provocation is often used to confirm asthma. Dyspnea sensation, however, associates poorly with the evoked drop in FEV. Provocation tests only use the large airways parameter FEV, although dyspnea is associated with both large- and small airways dysfunction.

Predictors of clinical response to extrafine and non-extrafine particle inhaled corticosteroids in smokers and ex-smokers with asthma.

We performed a post-hoc analysis of the OLiVIA-study investigating whether current and ex-smoking asthmatics with small airways dysfunction (SAD) show a better response in airway hyperresponsiveness (AHR) to small particle adenosine after treatment with extrafine compared to non-extrafine particle inhaled corticosteroids (ICS), and to investigate which clinical parameters predict a favorable response to both treatments. We show that smoking and ex-smoking asthmatics with and without SAD have a similar treatment response with either extrafine or non-extrafine particle ICS. We also found that lower blood neutrophils are associated with a smaller ICS-response in smokers and ex-smokers with asthma, independent from the level of blood eosinophils.

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

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.

Extrafine compared to non-extrafine particle inhaled corticosteroids in smokers and ex-smokers with asthma.

Background: Smoking is as prevalent in asthmatics as in the general population. Asthmatic smokers benefit less from inhaled corticosteroids (ICS) than non-smoking asthmatics, possibly due to more smoking-induced small airways disease. Thus targeting small airways may be important in treating asthmatic (ex-)smokers.

Nocturnal dry cough in the first 7 years of life is associated with asthma at school age.

Background: Childhood wheeze is an important, well-known risk factor for asthma, yet little is known about the contribution of nocturnal dry cough. We investigated the association of nocturnal dry cough at ages 1-7 years with doctor-diagnosed asthma at 8 years of age, both in the presence and absence of wheeze.

Methods: Data of 3,252 children from the PIAMA birth cohort were studied.