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.

Quadrupling the dose of inhaled corticosteroid to prevent asthma exacerbations: a randomized, double-blind, placebo-controlled, parallel-group clinical trial.

RATIONALE: Asthma exacerbations are unpredictable, disruptive, and frightening, and are therefore important to prevent. OBJECTIVES: We investigated whether a policy of quadrupling the dose of inhaled corticosteroid when asthma control starts to deteriorate reduces asthma exacerbations requiring treatment with oral corticosteroids. METHODS: A total of 403 people with asthma were given a self-management plan and randomized to take an active or placebo corticosteroid inhaler in addition to their usual asthma treatment when their PEF fell by 15% on 2 consecutive days or by 30% on 1 day. The study inhalers provided a quadrupling or no change in corticosteroid dose. MEASUREMENTS AND MAIN RESULTS: Eighteen of 197 (9%) and 29 of 203 (14%) participants had an exacerbation of asthma requiring treatment with oral corticosteroids in the active and placebo groups, respectively, giving a risk ratio of 0.64 (95% confidence interval, 0.37-1.11, P = 0.11). Of the 94 participants who started the study inhaler far fewer required treatment with oral corticosteroids in the active compared with the placebo group: 12 of 56 (21%) in the active group and 19 of 38 (50%) in the placebo group, giving a risk ratio of 0.43 (95% confidence interval, 0.24-0.78, P = 0.004). CONCLUSIONS: Although our primary outcome did not reach statistical significance, quadrupling the dose of inhaled corticosteroid when asthma control starts to deteriorate appears to reduce acute exacerbations of asthma and deserves further investigation. Clinical trial registered with www.controlled-trials.com (ISRCTN 46018181).

Effect of mouth taping at night on asthma control--a randomised single-blind crossover study.

BACKGROUND: Nose breathing ensures that inspired air is warm, filtered and moist and may therefore benefit patients with asthma. It features in some complementary approaches to treat asthma and is encouraged at night in the Buteyko technique by the use of mouth taping. In this pragmatic study we sought to determine whether taping the mouth at night has any effect on asthma control compared with usual breathing in patients with symptomatic asthma, since if it was effective it would be a simple intervention to implement. METHODS: This was a randomised, single-blind, crossover study of participants (n=51) with symptomatic asthma (mean FEV(1) 86% predicted). A 4-week period of usual breathing at night was followed by use of mouth taping with microporous tape, as in the Buteyko technique, or vice versa, with a 2-week run-in period and a minimum 2-week washout period of usual breathing between 'treatments'. Primary outcomes were morning peak expiratory flow and symptom scores (Asthma Control Diary). Outcomes were measured and analysed without knowledge of treatment allocation. RESULTS: Fifty participants completed the study and reported taping their mouth for a median 26 of 28 nights. Although 36 participants said mouth taping was very or fairly acceptable there were no differences between treatments for morning peak expiratory flow (mean difference -1l/min (95%CI, -9 to 7)) or symptoms scores (mean difference -0.12 (95%CI, -0.30 to 0.06)) nor for any secondary measures. CONCLUSIONS: Taping the mouth at night had no effect on asthma control in patients with symptomatic asthma.

Poor adherence with inhaled corticosteroids for asthma: can using a single inhaler containing budesonide and formoterol help?

BACKGROUND: Poor adherence with inhaled corticosteroids is an important problem in asthma management. Previous approaches to improving adherence have had limited success. AIM: To determine whether treatment with a single inhaler containing a long-acting beta(2)-agonist and a corticosteroid for maintenance treatment and symptom relief can overcome the problem of poor adherence with inhaled corticosteroids. DESIGN OF STUDY: Randomised, parallel group, open-label trial. SETTING: Forty-four general practices in Nottinghamshire. METHOD: Participants who used less than 70% of their prescribed dose of inhaled corticosteroid and had poorly controlled asthma were randomised to budesonide 200 microg one puff twice daily plus their own short-acting beta(2)-agonist as required (control group), or budesonide/formoterol 200/6 microg one puff once daily and as required (active group) for 6 months. The primary outcome was inhaled corticosteroid dose. RESULTS: Seventy-one participants (35 control, 36 active group) were randomised. Adherence with budesonide in the control group was approximately 60% of the prescribed dose. Participants in the active group used approximately 80% more budesonide than participants in the control group (448 versus 252 microg/day, mean difference 196 mug, 95% confidence interval 113 to 279; P<0.001) and were less likely to withdraw from the study (3 versus 13; P<0.01). No safety issues were identified. CONCLUSION: Using a single inhaler for both maintenance treatment and symptom relief approximately doubled the dose of inhaled corticosteroid taken, suggesting this could be a useful strategy to overcome the problems related to poor adherence with inhaled corticosteroids.

Effects of rac-albuterol on arterial blood gases in patients with stable hypercapnic chronic obstructive pulmonary disease.

AIMS: Many patients with chronic obstructive pulmonary disease (COPD) are treated with high dose beta(2)-adrenoceptor agonists, which can increase ventilation/perfusion mismatching, and tremor and cardiac output, thereby increasing oxygen uptake and carbon dioxide output (VCO(2)). Patients with severe COPD and hypercapnia may be unable to increase ventilation in response to increased VCO(2), in which case arterial carbon dioxide tension (P(a)CO(2)) may rise. Our aim was to determine whether high dose nebulized rac-albuterol could increase P(a)CO(2) in patients with COPD, limited bronchodilator reversibilty and hypercapnia. METHODS: We compared 10 mg and 400 microg rac-albuterol, given in two doses 1 h apart on nonconsecutive days, in a double-blind randomized crossover study in 14 patients with severe COPD. P(a)CO(2), arterial oxygen tension (P(a)O(2)) and heart rate were measured over 120 min and change from baseline was plotted against time to obtain an area under the curve. RESULTS: Mean P(a)CO(2) fell slightly over 120 min, with no difference between treatments (0.03 kPa h(-1) (95% confidence interval 0.02, 0.04)) and only three subjects had an increase in P(a)CO(2) after high dose rac-albuterol. High dose rac-albuterol caused a greater fall in P(a)O(2)[0.1 kPa h(-1) (95% confidence interval 0, 0.2)] and increase in heart rate than the low dose, although the differences were small. CONCLUSIONS: Under stable conditions most subjects with severe COPD and hypercapnia will have a fall in P(a)CO(2) and P(a)O(2) following 10 mg rac-albuterol, suggesting that they maintain capacity to respond to any increase in VCO(2) and prevent a rise in P(a)CO(2).

The impact of oral corticosteroid use on bone mineral density and vertebral fracture.

The use of oral corticosteroids is associated with an increased risk of fracture, but there is limited information on the relationship between corticosteroid dose, bone mineral density (BMD), and fracture. We examined this relationship in a community population (more than 50 years) taking oral corticosteroids for chronic lung disease. Details of corticosteroid use and lifestyle were obtained by questionnaire, general practice records, and patient interview. BMD was assessed at the lumbar spine and femur and vertebral fracture by morphometric X-ray absorptiometry. Of the 117 patients who participated (median age, 69), 48% were female. Fifty-eight percent had osteoporosis (a T score of less than -2.5), and 61% had a vertebral fracture. The presence of vertebral fracture was related to BMD at the femoral neck, with an odds ratio of 1.6 for a 1 SD reduction in BMD. The cumulative prednisolone dose ranged from 3.4 to 175 g and was strongly associated with vertebral fracture, with the odds ratio between the highest and lowest dose quartiles being 4.4 (95% confidence interval, 1.04, 18.8). The difference in femoral neck BMD between the same dose quartiles was only modest, however (0.5 SD; 95% confidence interval, 0.09, 0.94). In patients taking long-term oral corticosteroids for chronic lung disease, the relationship between vertebral fracture risk and BMD is similar to that seen in other populations. Cumulative prednisolone dose is strongly related to fracture risk, and this effect is independent of its more modest impact on BMD.