David Hodgson

A randomised controlled trial of small particle inhaled steroids in refractory eosinophilic asthma (SPIRA)

Background Some patients with refractory asthma have evidence of uncontrolled eosinophilic inflammation in the distal airways. While traditional formulations of inhaled steroids settle predominantly in the large airways, newer formulations with an extra-fine particle size have a more peripheral pattern of deposition. Specifically treating distal airway inflammation may improve asthma control. Methods 30 patients with refractory asthma despite high dose inhaled corticosteroids were identified as having persistent airway eosinophilia. Following 2 weeks of prednisolone 30 mg, patients demonstrating an improvement in asthma control were randomised to receive either ciclesonide 320 µg twice daily or placebo in addition to usual maintenance therapy for 8 weeks. The primary outcome measure was sputum eosinophil count at week 8. Alveolar nitric oxide was measured as a marker of distal airway inflammation. Results There was continued suppression of differential sputum eosinophil counts with ciclesonide (median 2.3%) but not placebo (median 4.5%) though the between-group difference was not significant. When patients who had changed their maintenance prednisolone dose during the trial were excluded the difference between groups was significant (1.4% vs 4.5%, p=0.028). Though alveolar nitric oxide decreased with ciclesonide the value did not reach statistical significance. Conclusions These data demonstrate that patients with ongoing eosinophilic inflammation are not truly refractory, and that suppression of airway eosinophilia may be maintained with additional inhaled corticosteroid. Further work is needed with a focus on patient-orientated outcome measures such as exacerbation rate, with additional tests of small airway function. Trial registration number NCT01171365. Protocol available at http://www.clinicaltrials.gov.

Evaluation of the PPAR-γ Agonist Pioglitazone in Mild Asthma: A Double-Blind Randomized Controlled Trial.

Background Peroxisome proliferator-activated receptor gamma (PPAR-γ) is a nuclear receptor that modulates inflammation in models of asthma. To determine whether pioglitazone improves measures of asthma control and airway inflammation, we performed a single-center randomized, double-blind, placebo-controlled, parallel-group trial. Methods Sixty-eight participants with mild asthma were randomized to 12 weeks pioglitazone (30 mg for 4 weeks, then 45 mg for 8 weeks) or placebo. The primary outcome was the adjusted mean forced expiratory volume in one second (FEV1) at 12 weeks. The secondary outcomes were mean peak expiratory flow (PEF), scores on the Juniper Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ), fractional exhaled nitric oxide (FeNO), bronchial hyperresponsiveness (PD20), induced sputum counts, and sputum supernatant interferon gamma-inducible protein-10 (IP-10), vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1), and eosinophil cationic protein (ECP) levels. Study recruitment was closed early after considering the European Medicines Agency’s reports of a potential increased risk of bladder cancer with pioglitazone treatment. Fifty-five cases were included in the full analysis (FA) and 52 in the per-protocol (PP) analysis. Results There was no difference in the adjusted FEV1 at 12 weeks (-0.014 L, 95% confidence interval [CI] -0.15 to 0.12, p = 0.84) or in any of the secondary outcomes in the FA. The PP analysis replicated the FA, with the exception of a lower evening PEF in the pioglitazone group (-21 L/min, 95% CI -39 to -4, p = 0.02). Conclusions We found no evidence that treatment with 12 weeks of pioglitazone improved asthma control or airway inflammation in mild asthma. Trial Registration ClinicalTrials.gov NCT01134835

The Effects of Azithromycin in Treatment-Resistant Cough: A Randomized, Double-Blind, Placebo-Controlled Trial

BACKGROUND Chronic cough is a common clinical problem worldwide. Although many patients have underlying precipitating conditions such as asthma, gastroesophageal reflux, or rhinitis, many remain symptomatic despite treating these conditions. New approaches are needed for the treatment of this group of patients. METHODS We conducted a randomized, double-blind, placebo-controlled trial to determine whether 250 g of azithromycin three times a week for 8 weeks would affect the Leicester Cough Questionnaire (LCQ) score in 44 patients with treatment-resistant cough. Cough severity on a visual analog scale and bronchial exhaled nitric oxide were measured as secondary outcomes. RESULTS There was a clinically important improvement in LCQ score with azithromycin (mean change, 2.4; 95% CI, 0.5 to 4.2) but not placebo (mean change, 0.7; 95% CI, -0.6 to 1.9), but the between-group difference was not statistically significant (P = .12). There were no significant between-group differences for any of the secondary outcome measures. Looking at subgroups of responders, there was a large and significant improvement in LCQ score in patients with chronic cough and a concurrent diagnosis of asthma who were treated with azithromycin (mean, 6.19; 95% CI, 4.06 to 8.32). CONCLUSIONS Treatment with low-dose azithromycin for 8 weeks did not significantly improve LCQ score compared with placebo. The use of macrolides for treatment-resistant cough cannot be recommended from this study, but they may have a place in the treatment of chronic cough associated with asthma; this is worthy of further investigation. TRIAL REGISTRY WHO International Clinical Trials Registry; No.: ISRCTN75749391. URL: http://apps.who.int.

Budesonide/formoterol in the treatment of asthma

Budesonide and formoterol are available in a combined inhaler that offers therapeutic advantages in the treatment of asthma. The rapid onset of bronchodilation seen with formoterol means that budesonide/formoterol can be used as both maintenance and relief therapy. This approach has been shown to reduce exacerbations and overcome the problem of patients who overuse short-acting β-agonists at the expense of inhaled corticosteroids. Concerns regarding safety of long-acting β-agonists have not been confirmed in studies of the budesonide/formoterol combination inhaler, and we believe the benefits of this medication clearly outweigh any possible small increased risk.

Exhaled nitric oxide and inhaled corticosteroid dose reduction in asthma: a cohort study

To the Editor: Inhaled corticosteroids (ICS) reduce airway inflammation; however, guidelines recommend titrating ICS dose based on symptoms [1], which are not closely associated with airway inflammation [2]. Once symptoms are controlled for ≥3 months, ICS reduction is recommended [3] but step-down is often not implemented. Studies suggest that the majority of patients treated with ICS can have their therapy stepped down, although there is no clear evidence on how best to achieve this [4]. We assessed whether exhaled nitric oxide fraction ( F eNO) measurements could predict a loss of symptom control or exacerbation following a reduction in ICS dose in a cohort study of people with well-controlled asthma recruited from primary care. All participants had a recorded asthma diagnosis, were aged 18–75 years, and had received at least one ICS prescription in the last year. The study was restricted to nonsmokers ( 1.5 at visit 1 (indicating poor control) were excluded. Participants were seen at the same time of day on four occasions: days 0, 14, 21 and 110. At each visit, ACQ-5, F eNO (Flex Flow; Aerocrine, Solna, Sweden) and spirometry were performed. Symptoms were assessed using the ACQ-5 [6]. Airway inflammation was measured using F eNO at 50 mL·s−1; participants were blinded to their measurements. Differential …

Thorax in focus: chronic obstructive pulmonary disease

Keeping up to date with scientific developments in any field of medicine is challenging, and chronic obstructive pulmonary disease (COPD) is no exception. Thorax has played an important part in the communication of key developments to its readership. In this article we review original research published in the journal over the last 2-3 years. We consider scientific and clinical developments in the epidemiology, mechanisms and treatment of COPD, placing these articles in the context of other relevant literature in COPD.

Optimising prescription and titration of oxygen for adult inpatients using novel silicone wristbands: results of a pilot project at three centres

Oxygen is the most commonly used drug in the acute hospital setting. Oxygen can be lifesaving but there is increasing evidence that it can cause harm if it is not given correctly. Prescription of oxygen, according to target saturations, has been advocated since 2008 but compliance remains at low levels. This paper describes a novel approach to improve oxygen prescription and titration in three acute hospital trusts using a colour-coded silicone wristband. The project ran for 3 months and covered more than 2,000 emergency admissions to hospital. Data was collected for oxygen prescription and titration rates for 270 patients during the project period. The wristbands showed an improvement in prescription and titration of oxygen in two out of three sites. The results support a wider controlled study of colour-coded wristbands to improve oxygen safety in secondary care.