1.
Physiotherapy, and speech and language therapy intervention for patients with refractory chronic cough: a multicentre randomised control trial.
Chamberlain Mitchell, SA, Garrod, R, Clark, L, Douiri, A, Parker, SM, Ellis, J, Fowler, SJ, Ludlow, S, Hull, JH, Chung, KF, et al
Thorax. 2017;(2):129-136
Abstract
BACKGROUND Physiotherapy, and speech and language therapy are emerging non-pharmacological treatments for refractory chronic cough. We aimed to investigate the efficacy of a physiotherapy, and speech and language therapy intervention (PSALTI) to improve health-related quality of life (HRQoL) and to reduce cough frequency in patients with refractory chronic cough. METHODS In this multicentre randomised controlled trial, patients with refractory chronic cough were randomised to four weekly 1:1 sessions of either PSALTI consisting of education, laryngeal hygiene and hydration, cough suppression techniques, breathing exercises and psychoeducational counselling or control intervention consisting of healthy lifestyle advice. We assessed the change in HRQoL at week 4 with the Leicester Cough Questionnaire (LCQ). Secondary efficacy outcomes included 24-hour objective cough frequency (Leicester Cough Monitor) and cough reflex sensitivity. The primary analysis used an analysis of covariance adjusted for baseline measurements with the intention-to-treat population. This study was registered at UK Clinical Research Network (UKCRN ID 10678). FINDINGS Between December 2011 and April 2014, we randomly assigned 75 participants who underwent baseline assessment (34 PSALTI and 41 controls). In the observed case analysis, HRQoL (LCQ) improved on average by 1.53 (95% CI 0.21 to 2.85) points more in PSALTI group than with control (p=0.024). Cough frequency decreased by 41% (95% CI 36% to 95%) in PSALTI group relative to control (p=0.030). The improvements within the PSALTI group were sustained up to 3 months. There was no significant difference between groups in the concentration of capsaicin causing five or more coughs. INTERPRETATION Greater improvements in HRQoL and cough frequency were observed with PSALTI intervention. Our findings support the use of PSALTI for patients with refractory chronic cough. TRIAL REGISTRATION NUMBER UKCRN ID 10678 and ISRCTN 73039760; Results.
2.
Montelukast for postinfectious cough in adults: a double-blind randomised placebo-controlled trial.
Wang, K, Birring, SS, Taylor, K, Fry, NK, Hay, AD, Moore, M, Jin, J, Perera, R, Farmer, A, Little, P, et al
The Lancet. Respiratory medicine. 2014;(1):35-43
Abstract
BACKGROUND Postinfectious cough is common in primary care, but has no proven effective treatments. Cysteinyl leukotrienes are involved in the pathogenesis of postinfectious cough and whooping cough (pertussis). We investigated the effectiveness of montelukast, a cysteinyl leukotriene receptor antagonist, in the treatment of postinfectious cough. METHODS In this randomised, placebo-controlled trial, non-smoking adults aged 16-49 years with postinfectious cough of 2-8 weeks' duration were recruited from 25 general practices in England. Patients were tested for pertussis (oral fluid anti-pertussis toxin IgG) and randomly assigned (1:1) to montelukast 10 mg daily or image-matched placebo for 2 weeks. Patients chose whether to continue study drug for another 2 weeks. The randomisation sequence was computer-generated and stratified by general practice. Patients, health-care professionals, and researchers were masked to treatment allocation. Effectiveness was assessed with the Leicester Cough Questionnaire to measure changes in cough-specific quality of life; the primary outcomes were changes in total score between baseline and two follow-up stages (2 weeks and 4 weeks). The primary analysis was by intention to treat with imputation by last observation carried forward. Recruitment closed on Sept 21, 2012, and follow-up has been completed. This trial is registered with EudraCT (2010-019647-19), UKCRN Portfolio (ID 8360), and ClinicalTrials.gov (NCT01279668). FINDINGS From April 13, 2011, to Sept 21, 2012, we randomly assigned 276 patients to montelukast (n=137) or placebo (n=139). 70 (25%) patients had laboratory-confirmed pertussis. Improvements in cough-specific quality of life occurred in both groups after 2 weeks (montelukast: mean 2·7, 95% CI 2·2-3·3; placebo: 3·6, 2·9-4·3), but the difference between groups did not meet the minimum clinically important difference of 1·3 (mean difference -0·9, -1·7 to -0·04, p=0·04). This difference was not statistically significant in any sensitivity analyses. After 2 weeks, 192 of 259 participants from whom data were available elected to continue study drug (99 [77%] of 129 participants on montelukast; 93 [72%] of 130 on placebo). After 4 weeks, there were no significant between-group differences in cough-specific quality of life improvement (montelukast: 5·2, 4·5-5·9; placebo: 5·9, 5·1-6·7; mean difference -0·5, -1·5 to 0·6, p=0·38) or adverse event rates (21 (15%) of 137 patients on montelukast reported one or more adverse events; 31 (22%) of 139 on placebo; p=0·14). The most common adverse events reported were increased mucus production (montelukast, n=6; placebo, n=2), gastrointestinal disturbance (montelukast, n=3; placebo, n=5), and headache (montelukast, n=2; placebo, n=6). One serious adverse event was reported (placebo, n=1), which was unrelated to study drug (shortness of breath and throat tightness after severe coughing bouts). INTERPRETATION Montelukast is not an effective treatment for postinfectious cough. However, the burden of postinfectious cough in primary care is high, making it an ideal setting for future antitussive treatment trials. FUNDING National Institute for Health Research School for Primary Care Research, UK.
3.
Multisite comparison of mucociliary and cough clearance measures using standardized methods.
Bennett, WD, Laube, BL, Corcoran, T, Zeman, K, Sharpless, G, Thomas, K, Wu, J, Mogayzel, PJ, Pilewski, J, Donaldson, S
Journal of aerosol medicine and pulmonary drug delivery. 2013;(3):157-64
Abstract
BACKGROUND A standardized protocol for measuring mucociliary (MCC) and cough clearance (CC) was developed and tested at the University of North Carolina at Chapel Hill, NC (UNC), Johns Hopkins University (JHU), and the University of Pittsburgh (Pitt). METHODS A total of 50 healthy nonsmoking adults with normal lung function were studied at the three sites: 30 [21 males/9 females (21M/9F)] at UNC, 10 (6M/4F) at JHU, and 10 (4M/6F) at Pitt. Subjects inhaled an aerosol of (99m)technetium sulfur colloid in 0.9% saline (mass median aerodynamic diameter=5.4 μm) under controlled breathing conditions (500 mL/sec, 30 breaths/min) by following a metronome and flow signal from a commercial dosimeter. Following inhalation, subjects sat in front of a gamma camera as sequential lung images were acquired for 60 min. Subjects then coughed 60 times, and images were acquired after each set of 20 coughs, i.e., at 70, 80, and 90 min. Subjects returned to the laboratory approximately 24 hr later for a final image of residual lung activity. Initial aerosol distribution was measured as a central/peripheral (C/P) ratio of activity. MCC/CC was expressed as the area under the retention versus time curve over 90 min (AUC90). RESULTS A multivariate analysis of clearance versus time with site and C/P as covariates showed no significant site-specific differences. Interestingly, MCC/CC was greater in females (n=19) versus males (n=31), with AUC90=0.84 ± 0.11 and 0.90±0.07, respectively (p=0.03), for the combined data set from all sites (not significant for any given site). There were no gender differences for either C/P ratio or 24-hr clearance. CONCLUSIONS This standardized protocol may prove beneficial in multicenter trials for testing new therapies that are designed to improve MCC/CC.
4.
[Treatment of acute bronchitis in children and adolescents. Non-interventional postmarketing surveillance study confirms the benefit and safety of a syrup made of extracts from thyme and ivy leaves].
Marzian, O
MMW Fortschritte der Medizin. 2007;(27-28 Suppl):69-74
Abstract
OBJECTIVE For the investigation of the benefits and tolerability of a syrup made of extracts from thyme and ivy (Bronchipret Saft) in children and adolescents (ages: 2-17 years) with acute bronchitis and productive cough, a non-interventional postmarketing surveillance study was carried out. METHODS Prerequisites for participation in the surveillance study were productive cough for a maximum of two days, at least ten coughing fits per day prior to the initiation of treatment (estimation of the parents or adolescent) and a Bronchitis Severity Score (BSS) of at least five points. The primary outcome measure was the change in the clinical symptoms based on the BSS. Treatment was carried out using age-appropriate dosages prescribed by the doctor on a case-by-case basis in accordance with the summary of product characteristics. Documentation of the course of treatment for the surveillance study was to be taken on treatment days 0, 4 and 10. RESULTS For the descriptive, statistical evaluation of the surveillance study, the data from 1234 children and adolescents (623 boys and 611 girls) in the age groups < 2 years (N = 12), 2-5 years (N = 372), 6-11 years (N = 438) and 12-17 years (N = 412) were available. The correspondence of the dosages to the age-specific recommendations of the valid summary of product characteristics varied from 81.7% to 93.9% in the different age groups. The average BSS value decreased from 8.8 points to 4.8 on treatment day 4 and to 1.3 points after about ten days of treatment. Compared to that of the initial examination, the number of documented coughing fits had decreased on the average by 18.7 (81.3%) on day 10. The responder rates of the various age groups were 92.0% to 96.5%. The tolerability was rated as very good to good by the physicians in 96.5% of the cases. Two female patients had temporary, not serious adverse drug reactions (stomache ache, mild nausea). CONCLUSION Acute bronchitis with productive cough in (young) children and adolescents can be treated safely and effectively with the thyme and ivy syrup. A ten-day treatment using age-appropriate dosages led to a clear improvement in the symptoms or cure with very good tolerability.