Treating idiopathic pulmonary fibrosis with the addition of co-trimoxazole: a randomised controlled trial
Idiopathic pulmonary fibrosis (IPF) is a fatal condition with limited treatment options. However, in a previous small study, co-trimoxazole was found to be beneficial.
In a double-blind multicentre study, 181 patients with fibrotic idiopathic interstitial pneumonia (89% diagnosed as definite/probable IPF) were randomised to receive co-trimoxazole 960 mg twice daily or placebo for 12 months in addition to usual care. Measurements were made of forced vital capacity (FVC) (primary endpoint), diffusing capacity of carbon monoxide (D
Co-trimoxazole had no effect on FVC (mean difference 15.5 ml (95% CI –93.6 to 124.6)), D
The addition of co-trimoxazole therapy to standard treatment for fibrotic idiopathic interstitial pneumonia had no effect on lung function but resulted in improved quality of life and a reduction in mortality in those adhering to treatment.
TNF{alpha} antagonists for acute exacerbations of COPD: a randomised double-blind controlled trial
The purpose of this randomised double-blind double-dummy placebo-controlled trial was to investigate whether etanercept, a tumour necrosis factor α (TNFα) antagonist, would provide more effective anti-inflammatory treatment for acute exacerbations of chronic obstructive pulmonary disease (COPD) than prednisone.
We enrolled 81 patients with acute exacerbations of COPD and randomly assigned them to treatment with either 40 mg oral prednisone given daily for 10 days or to 50 mg etanercept given subcutaneously at randomisation and 1 week later. Both groups received levofloxacin for 10 days plus inhaled bronchodilators. The primary endpoint was the change in the patient's forced expiratory volume in 1 s (FEV1) 14 days after randomisation. Secondary endpoints included 90-day treatment failure rates and dyspnoea and quality of life.
At 14 days the mean±SE change in FEV1 from baseline was 20.1±5.0% and 15.2±5.7% for the prednisone and etanercept groups, respectively. The mean between-treatment difference was 4.9% (95% CI –10.3% to 20.2%), p=0.52. Rates of treatment failure at 90 days were similar in the prednisone and etanercept groups (32% vs 40%, p=0.44), as were measures of dyspnoea and quality of life. Subgroup analysis revealed that patients with serum eosinophils >2% at exacerbation tended to experience fewer treatment failures if treated with prednisone compared with etanercept (22% vs 50%, p=0.08).
Etanercept was not more effective than prednisone for treatment of acute exacerbations of COPD. Efficacy of prednisone was most apparent in patients who presented with serum eosinophils >2%.
Airway inflammation in patients with chronic non-asthmatic cough
Chronic non-asthmatic cough (CC) is a clinical challenge and underlying pathophysiological mechanisms remain still not completely understood. One of the most common comorbidities in CC is gastro-oesophageal reflux disease (GORD). Airway epithelium damage can contribute to airway inflammation in CC.
We studied airway inflammation in patients with CC compared to healthy controls. Patients with GORD were treated with proton pump inhibitors (PPI) and cough response to PPI was evaluated.
Sputum was induced in 41 adults with CC and 20 healthy non-smokers who were age and sex matched. We compared sputum differential cell count by cytospin and cytokine and chemokine production at the mRNA and/or protein levels by real-time (RT)-PCR and cytokine bead array (CBA), between patients with CC and healthy subjects. Furthermore we studied airway inflammation in patients with different comorbidities.
No differences in sputum differential cell counts were observed between patients with CC and healthy subjects. Sputum monocyte chemoattractant protein-1 (MCP-1) protein levels were significantly higher in patients when compared to controls. Thymic stromal lymphopoietin (TSLP) mRNA was significantly more often expressed in sputum of patients with CC than from healthy controls. Sputum transforming growth factor (TGF)-β levels did not differ between patients and controls, but were significantly lower in the PPI responders compared to the non-responders; p=0.047. There is no evidence for impaired T helper cell (Th)1/Th2/Th17 balance in CC. Patients with reflux oesophagitis (RO) have significantly more sputum eosinophils than patients without RO.
CC is a condition presenting with different disease phenotypes. High sputum MCP-1 levels are present in a large group of patients with CC and a majority of these patients with CC have increased sputum TSLP levels, most likely produced by damaged airway epithelial cells.
The FDA-mandated trial of safety of long-acting beta-agonists in asthma: finality or futility?
In 2010, in response to a prolonged debate over the safety of long-acting beta-agonists (LABAs), the United States Food and Drugs Administration (FDA) issued guidelines for the use of LABAs in asthma,
Controversy regarding safety has surrounded the use of long-acting beta-agonists in asthma virtually since salmeterol (Serevent, GlaxoSmithKline) was introduced into clinical practice in the UK in 1990 (
Restriction of LABA use to combination ICS/LABA inhaler therapy in asthma
- This represented a revision to the 2009 BTS guidelines in which LABAs were recommended if used with ICS, either as separate inhalers or as a combination ICS/LABA inhaler.
- The revision was based on the evidence that LABAs have the potential to increase the risk of asthma mortality when used by patients with unstable asthma without concomitant ICS therapy or scheduled medical review,
- that there is no evidence of an increased risk of asthma mortality with combination ICS/LABA inhaler therapy in asthma,
- and that it is only with combination ICS/LABA products that it could be guaranteed that LABA monotherapy can be avoided.
- It recognised that the use...