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Background: Bronchial provocation is often used to confirm asthma. Dyspnea sensation correlates poorly with the provocative dose that causes the FEV1 to drop ≥20% (PD20). Aim: To explore if dyspnea sensation associates better with small airways then large airways function. Methods: We induced dyspnea with dry powder adenosine and nebulized adenosine 5’‑monophosphate (AMP), targeting the small and large airways, respectively, 14±7 days apart. We obtained spirometry, impulse oscillometry (IOS), and Borg score in all subjects, but multiple breath nitrogen washout (MBNW) was only limited available. Subjects were asthmatic (ex‑)smokers with ≥5 packyears. We analyzed the correlation between the change (Δ) in large and small airways parameters to ΔBorg in univariate and multivariate linear regression analysis. MBNW was analyzed separately. Results: We included 61 subjects of which 36 performed MBNW. Provocation with adenosine and AMP evoked similar levels of dyspnea. The large airways parameter, ΔFEV1 was not significantly correlated with ΔBorg after either adenosine or AMP provocation, in both univariate and multivariate analyses. Multivariate linear regression models for ΔBorg included for adenosine: gender, smoking status, ΔFEV1, ΔFEF25-75, ΔR20, ΔR5‑R20, and ΔScond and for AMP: gender, smoking status, ΔFEV1, ΔFEF25-75, ΔR20, ΔX5, and ΔLCI5%. ΔFEF25-75 during adenosine provocation was independently associated with ΔBorg, but for ΔBorg during AMP provocation no significant associations were found. Conclusion: Our results suggest that dyspnea sensation induced with dry powder adenosine is related to small airways involvement, while neither large nor airways small airways dysfunction was associated with AMP induced dyspnea.

Introduction: Nasal gene expression profiling is a promising method to characterize COPD non-invasively. First, we aimed to identify a nasal gene expression profile that distinguishes COPD patients from healthy controls. Next, we investigated whether this COPD-associated gene expression profile in nasal epithelium is comparable with the profile in the lower airways, i.e. the bronchial epithelium. Methods: Genome wide gene expression analysis was performed on nasal epithelial brushes of 76 COPD patients and 39 healthy controls, using Affymetrix Human Gene 1.0 ST Arrays. To compare findings in nasal and bronchial epithelium, we repeated the gene expression analysis on bronchial epithelial brushes in 2 independent cohorts of COPD patients and controls. Results: We found 2673 genes to be significantly differentially expressed in nasal epithelium between COPD patients and controls, 1158 being up- and 1515 downregulated in COPD (false discovery rate Conclusion: We identified a nasal gene expression profile that differentiates individuals with and without COPD. Of interest, part of the nasal gene expression changes in COPD is comparable to differentially expressed genes in the bronchus. These findings indicate that nasal gene expression has the potential to be developed as a non-invasive biomarker in COPD.

Background: Hyperinflation contributes to dyspnea intensity in COPD. Little is known about the underlying molecular mechanisms of hyperinflation, an important aspect of COPD pathophysiology, and how inhaled corticosteroids (ICS) affect it. Objectives: To investigate the effects of extra-fine and standard sized ICS/long-acting β 2 -agonist (LABA) treatment on both hyperinflation and the upper airway epithelial gene expression profile in severe COPD. Methods: Sixty patients entered a 1-month run-in period on low dose standard sized ICS/LABA, budesonide/formoterol (BUD/F) 200/6 b.i.d. Thereafter, patients were randomly and double-blind assigned to 3-month treatment with higher and BUD-equivalent doses of 1) extra-fine particle ICS/LABA, beclomethasone/formoterol (BDP/F) 100/6 (n=31), or 2) standard sized BUD/F200/6 (n=29), 2 inhalations b.i.d. Lung function and upper airway epithelial gene expression were assessed before and after 1 and 3-month ICS/LABA treatment. Results: Three-month combination treatment with both extra-fine and standard-sized ICS/LABA reduced hyperinflation (RV/TLC%predicted, p Conclusions: ICS/LABA treatment improves RV/TLC%predicted in severe COPD, in association with decreased expression of genes involved in the signal transduction by p53 class mediator resulting in induction of apoptosis pathway.

Background: Although the importance of teaching a correct inhalation technique in patients with asthma or COPD is recognised, the optimal method of inhalation technique education is unknown. To improve this, inhaler-specific visual instruction cards as an adjunct to standard education have been developed. Aim: To evaluate the value of these visual instruction cards in optimising inhalation technique in patients with asthma or COPD. Methods: Randomised controlled trial in 100 outpatients with asthma or COPD (49% male, mean age 63 years). Patients received either usual inhalation technique education (Usual Care) or received the visual instruction card in addition to the usual inhalation technique education (Usual Care + ). At baseline and follow-up (at 6-8 weeks) inhalation technique was assessed using inhaler-specific checklists. Disease control was measured by ACQ or CCQ. Results: In both groups the proportion of patients with an adequate inhalation technique significantly improved. The improvement in the Usual Care + group was significantly higher as compared to the Usual Care group (4% to 85% and 12% to 57% respectively, p + group as compared to the Usual Care group (-0.5 and -0.3 respectively, p + group (–0.5 in the Usual Care + and –0.3 in the Usual Care group, p=0.09). Conclusion: This study emphasises the importance of proper inhalation technique education, and in particular, the value of the newly developed visual instruction cards.