Toll-like receptor 9 dependent interferon-α release is impaired in severe asthma but is not associated with exacerbation frequency.

Patients with asthma and chronic obstructive pulmonary disease (COPD) are susceptible to exacerbations, often caused by microbial pathogens. We hypothesised that intracellular Toll-like receptor (TLR) function in blood mononuclear cells (PBMCs) from these subjects would be impaired and that this impairment is related to exacerbation frequency. PBMCs stimulated with a TLR-9 agonist (but not TLR-3 or 7/8) produced significantly less IFN-α in asthma (26 [3-696]pg/ml) compared to control (943 [164-1651]) and COPD (597 [127-1186]) subjects (p = 0.

A cross-sectional study of patterns of airway dysfunction, symptoms and morbidity in primary care asthma.

Background: Most patients with asthma are managed exclusively in primary care. Little is known about the patterns of airway dysfunction in these patients and how these relate to other aspects of the disease.

Aims: We set out to assess this in a cross-sectional study of 262 patients.

Increased expression of immunoreactive thymic stromal lymphopoietin in patients with severe asthma.

Background: Thymic stromal lymphopoietin (TSLP) is a cytokine implicated in the pathophysiology of asthma through 2 distinct pathways: a TSLP-OX40 ligand (OX40L)-T cell axis and a TSLP-mast cell axis. Whether these pathways are active in human asthma is unknown.

Objective: We sought to investigate whether mucosal TSLP protein expression relates to asthma severity and distinct immunologic pathways.

Association between neutrophilic airway inflammation and airflow limitation in adults with asthma.

Background: There is debate about the mechanisms of persistent airflow limitation in patients with asthma. Chronic inflammation is assumed to be important, although there is limited and contradictory information about the relationship between airway inflammation and postbronchodilator FEV1.

Methods: We have assessed the cross-sectional relationship between prebronchodilator and postbronchodilator FEV1 and measures of airway inflammation after allowing for the effects of potential confounding factors.

Evidence of a role of tumor necrosis factor alpha in refractory asthma.

Background: The development of tumor necrosis factor alpha (TNF-alpha) antagonists has made it feasible to investigate the role of this cytokine in refractory asthma.

Methods: We measured markers of TNF-alpha activity on peripheral-blood monocytes in 10 patients with refractory asthma, 10 patients with mild-to-moderate asthma, and 10 control subjects. We also investigated the effects of treatment with the soluble TNF-alpha receptor etanercept (25 mg twice weekly) in the patients with refractory asthma in a placebo-controlled, double-blind, crossover pilot study.