Jane Lafferty

Effect of low-dose theophylline plus beclometasone on lung function in smokers with asthma: a pilot study

Smoking is common in asthma and is associated with worse asthma control and a reduced therapeutic response to corticosteroids. The present authors hypothesised that treating smokers with asthma with low-dose theophylline added to inhaled corticosteroids would enhance steroid sensitivity and thereby improve lung function and symptoms. In a double-blind, parallel group exploratory trial, 68 asthmatic smokers were randomised to one of three treatments for 4 weeks: inhaled beclometasone (200 μg·day−1), theophylline (400 mg·day−1) or both treatments combined. Outcome measures included change in lung function and Asthma Control Questionnaire (ACQ) scores. At 4 weeks, theophylline added to inhaled beclometasone produced an improvement in peak expiratory flow (39.9 L·min−1, 95% confidence intervals (CI) 10.9–68.8) and ACQ score (-0.47, 95% CI -0.91– -0.04) and a borderline improvement in pre-bronchodilator forced expiratory volume in one second (mean difference 165 mL, 95% CI -13–342) relative to inhaled corticosteroid alone. Theophylline alone improved the ACQ score (-0.55, 95% CI -0.99– -0.11), but not lung function. In the present pilot study, the combination of low-dose theophylline and inhaled beclometasone produced improvements in both lung function and symptoms in a group of smokers with asthma. Larger trials are required to extend and confirm these findings.

Effects of atorvastatin added to inhaled corticosteroids on lung function and sputum cell counts in atopic asthma

Background: Statins have anti-inflammatory properties that may be beneficial in the treatment of asthma. A study was undertaken to test the hypothesis that atorvastatin added to inhaled corticosteroids improves lung function and airway inflammation in atopic adults with asthma. Methods: 54 adults with atopic asthma were recruited to a double-blind randomised controlled crossover trial comparing the effect of oral atorvastatin 40 mg daily with that of a matched placebo on asthma control and airway inflammation. Each treatment was administered for 8 weeks separated by a 6-week washout period. The primary outcome was morning peak expiratory flow (PEF). Secondary outcomes included forced expiratory volume in 1 s, asthma control questionnaire score, airway hyper-responsiveness to methacholine, induced sputum cytology and inflammatory biomarkers. Results: At 8 weeks the change in mean morning PEF compared with baseline did not differ substantially between the atorvastatin and placebo treatment periods (mean difference −0.5 l/min, 95% CI −10.6 to 9.6, p = 0.921). Values for other clinical outcomes were similar between the atorvastatin and placebo treatment periods. The absolute sputum macrophage count was reduced after atorvastatin compared with placebo (mean difference −45.0×104 cells, 95% CI −80.1 to −9.7, p = 0.029), as was the sputum fluid leucotriene B4 (mean difference −88.1 pg/ml, 95% CI −156.4 to −19.9, p = 0.014). Conclusion: The addition of atorvastatin to inhaled corticosteroids results in no short-term improvement in asthma control but reduces sputum macrophage counts in mild to moderate atopic asthma. The change in sputum macrophage count suggests potential areas for investigation of statins in other chronic lung diseases.

Bronchodilatory Effect of the PPAR-γ Agonist Rosiglitazone in Smokers With Asthma

Smokers with asthma show a reduced response to inhaled corticosteroids. We hypothesized that a peroxisome proliferator–activated receptor‐γ (PPAR‐γ) agonist would be superior for the clinical treatment of these asthma patients. Forty‐six smokers with asthma were randomized to inhaled beclometasone dipropionate (200 µg per day) or rosiglitazone (8 mg per day) for 4 weeks. Rosiglitazone produced improvements in lung function (forced expiratory volume in 1 s (FEV1) = 183 ml, P = 0.051; forced expiratory flow between 25 and 75% of the forced vital capacity (FEF25–75) = 0.24 l/s, P = 0.030) as compared with inhaled beclometasone dipropionate. Further trials using PPAR‐γ agonists in steroid‐resistant airway disease are indicated.

Role of symptoms and lung function in determining asthma control in smokers with asthma

Background:  Cigarette smoking in asthma increases the severity and accelerates the decline in lung function. The relative role of symptoms and lung function in determining asthma control in smokers with asthma is not known.

Effects of short-term treatment with atorvastatin in smokers with asthma - a randomized controlled trial

BackgroundThe immune modulating properties of statins may benefit smokers with asthma. We tested the hypothesis that short-term treatment with atorvastatin improves lung function or indices of asthma control in smokers with asthma.MethodsSeventy one smokers with mild to moderate asthma were recruited to a randomized double-blind parallel group trial comparing treatment with atorvastatin (40 mg per day) versus placebo for 4 weeks. After 4 weeks treatment inhaled beclometasone (400 μg per day) was added to both treatment arms for a further 4 weeks. The primary outcome was morning peak expiratory flow after 4 weeks treatment. Secondary outcome measures included indices of asthma control and airway inflammation.ResultsAt 4 weeks, there was no improvement in the atorvastatin group compared to the placebo group in morning peak expiratory flow [-10.67 L/min, 95% CI -38.70 to 17.37, p = 0.449], but there was an improvement with atorvastatin in asthma quality of life score [0.52, 95% CI 0.17 to 0.87 p = 0.005]. There was no significant improvement with atorvastatin and inhaled beclometasone compared to inhaled beclometasone alone in outcome measures at 8 weeks.ConclusionsShort-term treatment with atorvastatin does not alter lung function but may improve asthma quality of life in smokers with mild to moderate asthma.Trial RegistrationClinicaltrials.gov identifier:NCT00463827

Peripheral blood dendritic cell subtypes are significantly elevated in subjects with asthma

Background Dendritic cells (DCs) are crucial for the processing of antigens, T lymphocyte priming and the development of asthma and allergy. Smokers with asthma display altered therapeutic behaviour and a reduction in endobronchial DC CD83 expression compared with non‐smokers with asthma. No information is available on the impact of smoking on peripheral blood DC profiles.

Assessment of the Presence of Occult Myocardial Infarction in Chronic Obstructive Pulmonary Disease Using Contrast-Enhanced Cardiac Magnetic Resonance Imaging

Background: Chronic obstructive pulmonary disease (COPD) has been identified as a risk factor for ischaemic heart disease, independent of smoking history, and inflammation is thought to play a role. Objectives: We sought to ascertain whether occult myocardial infarction (MI) was present in the COPD population, and to assess its relationship with inflammation and natriuretic peptides. Method: We recruited 25 patients with moderate/severe COPD and 17 control smokers without lung disease. All participants had no known cardiac disease. Contrast-enhanced cardiac magnetic resonance imaging was performed and analysed for delayed contrast enhancement (DE), indicative of previous MI. All participants had venous blood samples taken for assessment of NT-proBNP and inflammatory markers. Results: DE was not found in any participant. Right ventricular ejection fraction was lower in COPD patients. Other cardiac measurements and NT-proBNP levels were similar in the 2 groups. C-reactive protein, IL-8, GM-CSF, IL-1β and TNF-α were all significantly higher in the COPD group. Conclusion: DE, indicating previous MI, was not found in patients with moderate/severe COPD. Occult MI does not appear to be common in this population, but a larger study would be needed to conclusively test this.