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 β2-agonist (LABA) treatment on both lung function measures of hyperinflation, and the nasal epithelial gene-expression profile in severe COPD. 117 patients were screened and 60 COPD patients entered a 1-month run-in period on low-dose ICS/LABA budesonide/formoterol (BUD/F) 200/6 one inhalation b.i.d. Patients were then randomly assigned to 3-month treatment with either a high dose BDP/F 100/6 two inhalations b.i.d. (n = 31) or BUD/F 200/6 two inhalations b.i.d. (n = 29). Lung function measurements and nasal epithelial gene-expression were assessed before and after 3-month treatment and validated in independent datasets. After 3-month ICS/LABA treatment, residual volume (RV)/total lung capacity (TLC)% predicted was reduced compared to baseline (p < 0.05). We identified a nasal gene-expression signature at screening that associated with higher RV/TLC% predicted values. This signature, decreased by ICS/LABA treatment was enriched for genes associated with increased p53 mediated apoptosis was replicated in bronchial biopsies of COPD patients. Finally, this signature was increased in COPD patients compared to controls in nasal, bronchial and small airways brushings. Short-term ICS/LABA treatment improves RV/TLC% predicted in severe COPD. Furthermore, it decreases the expression of genes involved in the signal transduction by the p53 class mediator, which is a replicable COPD gene expression signature in the upper and lower airways.Trial registration: ClinicalTrials.gov registration number NCT01351792 (registration date May 11, 2011), ClinicalTrials.gov registration number NCT00848406 (registration date February 20, 2009), ClinicalTrials.gov registration number NCT00158847 (registration date September 12, 2005)

Factors influencing adherence to guidelines in general practice

OBJECTIVES: To identify and assess the effects of general practitioner and patient characteristics on global adherence to pharmacotherapeutic guidelines. METHODS: In a cross-sectional study in the northern Netherlands, a two-level multilevel model was applied to patients (n = 269,067) in 190 practices with a total of 251 general practitioners. The dependent variable was the global adherence to pharmacotherapeutic guidelines as a measure of good prescribing in a general practice setting. RESULTS: The mean global adherence was 82%. Two general practice variables, organization form and degree of urbanization influenced the global adherence, whereas all patient variables (age and gender) and the patient-related prescription characteristics (costs, volume, different ATC-codes) were significant predictors for the global adherence. The total explained variance was 28%. CONCLUSIONS: Patient characteristics have a greater influence on prescribing behavior than general practitioner characteristics. Record 21 of 25 - SilverPlatter MEDLINE(R) October Week 2