Theophylline induces a reduction in circulating interleukin-4 and interleukin-5 in atopic asthmatics

Abstract

Mast cells and eosinophils may play a role in the pathophysiology of chronic cough in nonasthmatics. It is unknown, however, whether degranulation of these cells occurs in the airways of such patients.Thirty-five nonsmoking patients referred with a chronic nonproductive cough (mean cough duration 76.2 months) were evaluated using a comprehensive diagnostic protocol. Bronchoalveolar lavage (BAL) cell differentials and BAL histamine, tryptase and eosinophilic cationic protein (ECP) concentrations were determined. Ten nonsmoking healthy volunteers served as controls.Diagnostic subgroups were identified: eight postnasal drip syndrome (PNDS), seven cough variant asthma (CVA), seven gastro-oeseophageal reflux (GOR), seven dual aetiology and six idiopathic. Nonasthmatic coughers (NAC) were characterized as those patients without bronchial hyperresponsiveness on histamine challenge and whose cough had either responded to therapy for PNDS or GOR or failed to improve with antiasthma therapy. There was a significant increase in both eosinophil and mast cell numbers (p<0.05) and in histamine levels (p=0.027) when NAC patients were compared with controls. Tryptase and ECP levels were elevated in 7 of 23 and 6 of 23 NAC patients, respectively.In conclusion, airway inflammatory cell numbers are not only increased but also activated, suggesting an important role for airways inflammation in the pathophysiology of chronic nonproductive cough. Eur Respir J 1999; 13: 59±65.

A framework for applying unfamiliar trial designs in studies of rare diseases

“…Two treatments are given in randomized order over several crossover periods, with masking of both the participant and the researcher [9,18]. Randomized, double-blind, placebo-controlled n-of-1 trials of nebulized recombinant human deoxyribonuclease (DNase) in cystic fibrosis (CF) were well suited to an n-of-1 design given the drug's rapid onset of action (within 5 days) and its short duration and carryover effects (most effects disappear within 10 days of cessation) ( Table 2) [9,15,19]. The study used two consecutive 14-day periods, with placebo or DNase randomly allocated to the first or second period.…”

“…The study used two consecutive 14-day periods, with placebo or DNase randomly allocated to the first or second period. To address disease variability in CF, the 28-day assessments were repeated until two assessments either showed a response or no response (best of three assessments) [19]. Meta-analysis of individual n-of-1 trials can be used to estimate overall population effects [9,20], and effect sizes can approximate those of large RCTs [9].…”

Role of magnesium in the failure of rhDNase therapy in patients with cystic fibrosis

“…[15][16][17] Indeed, different studies have shown a wide variation in the clinical response to rhDNase-I with about 30% of patients-the so-called non-responders-not benefiting from it. [18][19][20] The reason for the failure of rhDNase-I in these patients is not understood. This study was therefore undertaken to elucidate the reason for the failure of rhDNase-I in certain CF patients and to evaluate strategies to overcome this.…”

Inhaled Therapy in Children

“…30,31 ABD'nin KF Derneği, 6 yaş ve üzerindeki orta ve ağır akciğer hastalığı olan KF hastalarında, solunum fonksiyonlarının düzeltilmesi ve alevlenmelerin önlenmesi için dornaz alfanın kronik kullanımını güçlü bir şekilde öner-mektedir. 32 Beş yaş altında da iyi tolere edilmektedir. Dornaz alfa DNA miktarını azaltarak aminoglikozid antibiyotiklerin etkinliğini artırmaktadır.…”