Preventing Severe Asthma Exacerbations in Children. A Randomized Trial of Mite-Impermeable Bedcovers.

RATIONALE: Allergen exposure in sensitized individuals with asthma interacts with viruses to increase the risk of asthma exacerbation. OBJECTIVES: To evaluate the use of house dust mite-impermeable bedding and its impact on severe asthma exacerbations in children. METHODS: We randomized mite-sensitized children with asthma (ages 3-17 yr) after an emergency hospital attendance with an asthma exacerbation to receive mite-impermeable (active group) or control (placebo group) bed encasings. MEASUREMENTS AND MAIN RESULTS: Over a 12-month intervention period, the occurrence of severe asthma exacerbations was investigated. Of 434 children with asthma who consented, 286 (mean age, 7.7 yr; male sex, 65.8%) were mite sensitized, and 284 were randomized (146 to the active group and 138 to the placebo group). At 12 months, significantly fewer children in the active group than in the placebo group had attended the hospital with an exacerbation (36 [29.3%] of 123 vs. 49 [41.5%] of 118; P = 0.047). In the multivariable analysis, the risk of emergency hospital attendance was 45% lower in the active group (hazard ratio, 0.55; 95% confidence interval [CI], 0.36-0.85; P = 0.006) than in the placebo group. The annual rate of emergency hospital attendance with exacerbations was 27% lower in the active group than in the placebo group, but this did not reach significance (estimated marginal mean [95% CI], active, 0.38 [0.26-0.56] vs. placebo, 0.52 [0.35-0.76]; P = 0.18). No difference between the groups in the risk of prednisolone use for exacerbation was found (hazard ratio, 0.82; 95% CI, 0.58-1.17; P = 0.28). CONCLUSIONS: Mite-impermeable encasings are effective in reducing the number of mite-sensitized children with asthma attending the hospital with asthma exacerbations but not the number requiring oral prednisolone. This simple measure may reduce the health care burden of asthma exacerbations in children. Clinical trial registered with www.isrctn.com (ISRCTN 69543196).

Predictors of objective cough frequency in chronic obstructive pulmonary disease.

RATIONALE: Cough is one of the principal symptoms of chronic obstructive pulmonary disease (COPD) but the potential drivers of cough are likely to be multifactorial and poorly understood. OBJECTIVES: To quantify cough frequency in an unselected group of subjects with COPD and investigate the relationships between cough, reported sputum production, smoking, pulmonary function, and cellular airway inflammation. METHODS: We studied 68 subjects with COPD (mean age, 65.6 ± 6.7 yr; 67.6% male; 23 smokers; 45 ex-smokers) and 24 healthy volunteers (mean age, 57.5 ± 8.9 yr; 37.5% male; 12 smokers; 12 nonsmokers). Subjects reported cough severity, cough-specific quality of life, and sputum expectoration and performed spirometry, sputum induction, cough reflex sensitivity to capsaicin, and 24-hour ambulatory cough monitoring. MEASUREMENTS AND MAIN RESULTS: COPD current smokers had the highest cough rates (median, 9 coughs/h [interquartile range, 4.3-15.6 coughs/h]), almost double that of COPD ex-smokers (4.9 [2.3-8.7] coughs/h; P = 0.018) and healthy smokers (5.3 [1.2-8.3] coughs/h; P = 0.03), whereas healthy volunteers coughed the least (0.7 [0.2-1.4] coughs/h). Cough frequency was not influenced by age or sex and only weakly correlated with cough reflex sensitivity to capsaicin (log C5 r = -0.36; P = 0.004). Reported sputum production, smoking history, and current cigarette consumption strongly predicted cough frequency, explaining 45.1% variance in a general linear model (P < 0.001). In subjects producing a sputum sample, cough frequency was related to current cigarette consumption and percentage of sputum neutrophils (P = 0.002). CONCLUSIONS: Ambulatory objective monitoring provides novel insights into the determinants of cough in COPD, suggesting sputum production, smoking, and airway inflammation may be more important than sensitivity of the cough reflex.

Objective measurement of cough in otherwise healthy volunteers with acute cough.

Cough is one of the commonest reasons for medical consultation and acute cough associated with upper respiratory tract infections (URTIs) is a global problem. In otherwise healthy volunteers complaining of cough associated with symptoms of URTI, we aimed to assess objective and subjective measures of cough and their repeatability and perform power calculations for the design of future studies to test therapies. We studied 54 otherwise healthy volunteers with acute cough (<3 weeks) (median age 22 yrs (interquartile range 21-26 yrs), 64% female, mean forced expiratory volume in 1 s 97.6±10.5% predicted). All subjects performed 24-h ambulatory cough monitoring and reported cough frequency and severity using visual analogue scales (VAS) on 2 consecutive days. Sample size calculations were performed for crossover and parallel group study designs. Objective cough frequency was high (session 1: geometric mean 12.1 coughs·h(-1) (95%CI 9.7-15.2)) and fell significantly (session 2: 9.0 coughs·h(-1) (95%CI 6.9-11.6); p<0.001). Repeatability was higher for objective cough frequency (intra-class correlation coefficient (ICC)=0.94, p<0.001) than reported cough frequency (daytime VAS ICC=0.784, p<0.001). Crossover/parallel studies require <15 and <41 subjects per arm to detect a 50% reduction in cough frequency with 90% power, respectively. Acute cough frequency is highly repeatable over any 48-h period, allowing small sample sizes to be used when investigating the effectiveness of novel anti-tussives.

A comparison of objective and subjective measures of cough in asthma.

BACKGROUND: Cough is widely recognized as a key symptom in the diagnosis and the monitoring of asthma, but little is known about how best to assess cough in asthma. OBJECTIVE: To determine how objective cough rates correlate with subjective measures of cough in asthma. METHODS: We studied 56 subjects, median age 42.0 years (range, 28.5-71), 34 (60.7%) female, with asthma. Subjects performed cough reflex sensitivity testing (concentration of citric acid causing 2 and 5 coughs [C2 and C5]), 24-hour fully ambulatory cough recordings, subjectively scored the severity of their cough (visual analog scales and 0-5 score) and completed a cough-related quality of life questionnaire (Leicester Cough Questionnaire). Ambulatory cough recordings were manually counted and reported in cough seconds per hour (cs/h). RESULTS: The median time spent coughing was 2.6 cs/h (range, 0.0-14.2), with subjects spending more time coughing by day (median, 3.9 cs/h [0.0-18.5]) than by night (median, 0.3 cs/h [0.0-8.7]; P < .001). A weak inverse relationship was seen between day cough rates and log(10)C2 (r = -0.39; P = .03) but not log(10)C5 (r = -0.08; P = .65). Objective time spent coughing was also weak-moderately associated with subjective cough scores and visual analog scales, and most strongly correlated with cough-related quality of life (r = -0.54; P < .001). CONCLUSION: Subjective measures of cough and cough reflex sensitivity are poor surrogates for objective cough frequency in asthma. When designing studies to assess interventions for cough in asthma, we advocate a combination of both objective measures of cough and cough-related quality of life.