The short and long term effects of exercise training in non-cystic fibrosis bronchiectasis--a randomised controlled trial.
ABSTRACT: BACKGROUND:Exercise training is recommended for non-cystic fibrosis (CF) bronchiectasis, but the long-term effects are unclear. This randomised controlled trial aimed to determine the effects of exercise training and review of airway clearance therapy (ACT) on exercise capacity, health related quality of life (HRQOL) and the incidence of acute exacerbations in people with non-CF bronchiectasis. METHODS:Participants were randomly allocated to 8 weeks of supervised exercise training and review of ACT, or control. Primary outcomes of exercise capacity and HRQOL (Chronic respiratory disease questionnaire) and secondary outcomes of cough-related QOL (Leicester cough questionnaire) and psychological symptoms (Hospital anxiety and depression scale) were measured at baseline, following completion of the intervention period and at 6 and 12 months follow up. Secondary outcomes of the exacerbation rate and time to first exacerbation were analysed over 12 months. RESULTS:Eighty-five participants (mean FEV1 74% predicted; median Modified Medical Research Council Dyspnoea grade of 1 (IQR [1-3]) were included. Exercise training increased the incremental shuttle walk distance (mean difference to control 62 m, 95% CI 24 to 101 m) and the 6-minute walking distance (mean difference to control 41 m, 95% CI 19 to 63 m), but these improvements were not sustained at 6 or 12 months. Exercise training reduced dyspnoea (p?=?0.009) and fatigue (p?=?0.01) but did not impact on cough-related QOL or mood. Exercise training reduced the frequency of acute exacerbations (median 1[IQR 1-3]) compared to the control group (2[1-3]) over 12 months follow up (p?=?0.012), with a longer time to first exacerbation with exercise training of 8 months (95% CI 7 to 9 months) compared to the control group (6 months [95% CI 5 to 7 months], p?=?0.047). CONCLUSIONS:Exercise training in bronchiectasis is associated with short term improvement in exercise capacity, dyspnoea and fatigue and fewer exacerbations over 12 months. TRIAL REGISTRY:ClinicalTrials.gov (NCT00885521).
Project description:BACKGROUND:Recurrent bronchiectasis exacerbations are related to deterioration of lung function, progression of the disease, impairment of quality of life, and to an increased mortality. Improved detection of exacerbations has been accomplished in chronic obstructive pulmonary disease through the use of patient completed diaries. These tools may enhance exacerbation reporting and identification. The aim of this study was to develop a novel symptom diary for bronchiectasis symptom burden and detection of exacerbations, named the BEST diary. METHODS:Prospective observational study of patients with bronchiectasis conducted at Ninewells Hospital, Dundee. We included patients with confirmed bronchiectasis by computed tomography, who were symptomatic and had at least 1 documented exacerbation of bronchiectasis in the previous 12?months to participate. Symptoms were recorded daily in a diary incorporating cough, sputum volume, sputum colour, dyspnoea, fatigue and systemic disturbance scored from 0 to 26. RESULTS:Twenty-one patients were included in the study. We identified 29 reported (treated exacerbations) and 23 unreported (untreated) exacerbations over 6-month follow-up. The BEST diary score showed a good correlation with the established and validated questionnaires and measures of health status (COPD Assessment Test, r =?0.61, p =?0.0037, Leicester Cough Questionnaire, r =?-?0.52,p =?0.0015, St Georges Respiratory Questionnaire, r =?0.61,p <?0.0001 and 6?min walk test, r =?-?0.46,p =?0.037). The mean BEST score at baseline was 7.1 points (SD 2.2). The peak symptom score during exacerbation was a mean of 16.4 (3.1), and the change from baseline to exacerbation was a mean of 9.1 points (SD 2.5). Mean duration of exacerbations based on time for a return to baseline symptoms was 15.3?days (SD 5.7). A minimum clinically important difference of 4 points is proposed. CONCLUSIONS:The BEST symptom diary has shown concurrent validity with current health questionnaires and is responsive at onset and recovery from exacerbation. The BEST diary may be useful to detect and characterise exacerbations in bronchiectasis clinical trials.
Project description:BACKGROUND:Pulmonary rehabilitation improves exercise capacity and reduces risk of future exacerbation in COPD when performed after an exacerbation. There have been no previous studies of post-exacerbation rehabilitation in bronchiectasis. METHODS:Parallel group randomized controlled trial compared pulmonary rehabilitation (PR) to standard care (SC) in patients followed an antibiotic treated exacerbation of bronchiectasis. Patients were randomized following a 14?day course of antibiotics was completed. The primary outcome was 6-min walk distance (6?MW) at 8?weeks. Secondary outcomes were time to the next exacerbation, St.Georges Respiratory Questionnaire, COPD CAT score, Leicester cough questionnaire (LCQ) and FEV1 at 8 and 12?weeks post exacerbation. RESULTS:Forty eight patients were enrolled but only 27 had exacerbations within 12?months of enrolment. Nine patients received pulmonary rehabilitation and 18 received standard care. The 6?MW improved significantly from post-exacerbation to 8?weeks in both groups, with no significant difference between PR and SC- mean difference of 11?m (95% CI -34.3 to 56.3,p?=?0.6). Time to the next exacerbation was not significantly different hazard ratio 0.83 (0.31-2.19, p?=?0.7). No significant differences were seen between groups in terms of LCQ, CAT, FEV1 or SGRQ between groups. An analysis of probability based on the patients enrolled suggested >?1000 subjects are likely be required to have an >?80% probability of observing a statistically significant difference between PR and SC and any such differences would be likely to be too small to be clinically relevant. CONCLUSIONS:This pilot study identified no significant benefits associated with pulmonary rehabilitation after exacerbations of bronchiectasis. TRIAL REGISTRATION:NCT02179983, registered on Clinicaltrials.gov 29th June 2014.
Project description:Non-cystic fibrosis bronchiectasis is characterised by sputum production, exercise limitation and recurrent infections. Although pulmonary rehabilitation is advocated for this patient group, its effects are unclear. The aims of this study are to determine the short and long term effects of pulmonary rehabilitation on exercise capacity, cough, quality of life and the incidence of acute pulmonary exacerbations.This randomised controlled trial aims to recruit 64 patients with bronchiectasis from three tertiary institutions. Participants will be randomly allocated to the intervention group (supervised, twice weekly exercise training with regular review of airway clearance therapy) or a control group (twice weekly telephone support). Measurements will be taken at baseline, immediately following the intervention and at six and 12 months following the intervention period by a blinded assessor. Exercise capacity will be measured using the incremental shuttle walk test and the six-minute walk test. Quality of life and health status will be measured using the Chronic Respiratory Questionnaire, Leicester Cough Questionnaire, Assessment of Quality of Life Questionnaire and the Hospital Anxiety and Depression Scale. The rate of hospitalisation will be captured as well as the incidence of acute pulmonary exacerbations using a daily symptom diary.Results from this study will help to determine the efficacy of supervised twice-weekly pulmonary rehabilitation upon exercise capacity and quality of life in patients with bronchiectasis and will contribute to clinical practice guidelines for physiotherapists in the management of this population.This study protocol is registered with ClinicalTrials.gov (NCT00885521).
Project description:Non-cystic fibrosis bronchiectasis is characterized by the irreversible dilatation of the medium-sized bronchi as a result of airway injury from recurrent or chronic inflammation and lower respiratory tract infections. Bronchiectasis airways are commonly colonized with bacterial species. Infections of the airways play important role in bronchiectasis exacerbations. The non-specific prevention of recurrent airway infections by immunostimulating agents has gained growing interest. OM-85, consisting of extracts of eight kinds of bacteria important in respiratory infections, could support the respiratory tract resistance to the pathogens. OM-85 has been shown to be a benefit by decreasing the risk of acute exacerbation of chronic obstructive pulmonary disease (COPD) in several perspective clinical trials. Exacerbation of bronchiectasis substantially contributes to a more rapid decline in lung function, reduced quality of life, and healthcare costs. In this context, we plan to conduct a clinical trial to investigate the PReventive effect of OM-85 on Bronchiectasis Exacerbation in Chinese patients (iPROBE).This study is designed as a prospective, randomized, double blind, placebo-controlled multicenter trial. A total of 244 patients with bronchiectasis, who have had at least one exacerbation of bronchiectasis in the previous year, will be included. The subjects will randomly receive two courses of 7 mg of OM-85 or a matching placebo. The treatment dose of OM-85 will be one daily capsule taken orally for 10 days each month for 3 consecutive months at the beginning of the study, followed by 3 months of no drug. This schedule will repeat until the patient has been seen for one year.We will investigate whether long-term treatment with an oral immunostimulant (OM-85) could decrease exacerbations of bronchiectasis over a one-year period. We will also assess other relevant outcomes, including the rate of event-based exacerbation, lung function parameters, and total scores judged by the St George's respiratory questionnaire, Leicester cough questionnaire, and inflammatory index. We hope that this study will provide new information on the preventive effects of OM-85 on bronchiectasis exacerbations and will address a knowledge gap for this understudied disease.This study is registered at http://www.clinicaltrials.gov (identifier NCT01968421) on 19 October 2013.
Project description:Cough in bronchiectasis is associated with significant impairment in health status. This study aimed to quantify cough frequency objectively with a cough monitor and investigate its relationship with health status. A secondary aim was to identify clinical predictors of cough frequency.Fifty-four patients with bronchiectasis were compared with thirty-five healthy controls. Objective 24-h cough, health status (cough-specific: Leicester Cough Questionnaire LCQ and bronchiectasis specific: Bronchiectasis Health Questionnaire BHQ), cough severity and lung function were measured. The clinical predictors of cough frequency in bronchiectasis were determined in a multivariate analysis.Objective cough frequency was significantly raised in patients with bronchiectasis compared to healthy controls [geometric mean (standard deviation)] 184.5 (4.0) vs. 20.6 (3.2) coughs/24-h; mean fold-difference (95% confidence interval) 8.9 (5.2, 15.2); p < 0.001 and they had impaired health status. There was a significant correlation between objective cough frequency and subjective measures; LCQ r = -0.52 and BHQ r = -0.62, both p < 0.001. Sputum production, exacerbations (between past 2 weeks to 12 months) and age were significantly associated with objective cough frequency in multivariate analysis, explaining 52% of the variance (p < 0.001). There was no statistically significant association between cough frequency and lung function.Cough is a common and significant symptom in patients with bronchiectasis. Sputum production, exacerbations and age, but not lung function, were independent predictors of cough frequency. Ambulatory objective cough monitoring provides novel insights and should be further investigated as an outcome measure in bronchiectasis.
Project description:Aims: To determine how respiratory pediatricians across Australia and New Zealand prescribe azithromycin for children with chronic wet cough, including recurrent protracted bacterial bronchitis, chronic suppurative lung disease (CSLD) and bronchiectasis. Methods: A prospective web-based questionnaire was emailed to members of the Pediatric Special Interest Group of the Thoracic Society of Australia and New Zealand (TSANZ) between April and May 2018. It comprised eight demographic and 15 clinically focused questions. Results: Of the 73 respiratory pediatricians listed across Australia and New Zealand, 29 (40%) responded and all prescribed azithromycin for chronic wet cough. Twelve (41%) indicated that they would consider prescribing a short-course (2-4 weeks) of azithromycin for children with a chronic wet cough. Although most respondents reported prescribing long-term (>4-weeks) azithromycin for either CSLD (n = 23, 79%) or bronchiectasis (n = 24, 83%), only nine (31%) respondents would commence treatment if in the previous 12-months these children experienced three non-hospitalized exacerbations and just 12 (41%) would do so if there had been two hospitalisations for severe exacerbations during the same period in accordance with the TSANZ national guidelines. A lower threshold for prescribing azithromycin was described for Indigenous children or if co-morbidities were present. None prescribed azithromycin for >24-months. Macrolide-resistance was reported in Streptococcus pneumoniae and Staphylococcus aureus. Conclusion: Although Australian and New Zealand respiratory pediatricians in this survey prescribed azithromycin for chronic wet cough most often in children with either CSLD or bronchiectasis, many did so outside the current national guidelines. Reasons for this need exploring.
Project description:<h4>Background</h4>Bronchiectasis in children is an important, but under-researched, chronic pulmonary disorder that has negative impacts on health-related quality of life. Despite this, it does not receive the same attention as other chronic pulmonary conditions in children such as cystic fibrosis. We measured health resource use and health-related quality of life over a 12-month period in children with bronchiectasis.<h4>Methods</h4>We undertook a prospective cohort study of 85 children aged <?18-years with high-resolution chest computed-tomography confirmed bronchiectasis undergoing management in three pediatric respiratory medical clinics in Darwin and Brisbane, Australia and Auckland, New Zealand. Children with cystic fibrosis or receiving cancer treatment were excluded. Data collected included the frequency of healthcare attendances (general practice, specialists, hospital and/or emergency departments, and other), medication use, work and school/childcare absences for parents/carers and children respectively, and both parent/carer and child reported quality of life and cough severity.<h4>Results</h4>Overall, 951 child-months of observation were completed for 85 children (median age 8.7-years, interquartile range 5.4-11.3). The mean (standard deviation) number of exacerbations was 3.3 (2.2) per child-year. Thirty of 264 (11.4%) exacerbation episodes required hospitalization. Healthcare attendance and antibiotic use rates were high (30 and 50 per 100 child-months of observation respectively). A carer took leave from work for 53/236 (22.5%) routine clinic visits. Absences from school/childcare due to bronchiectasis were 24.9 children per 100 child-months. Quality of life scores for both the parent/carer and child were highly-correlated with one another, remained stable over time and were negatively associated with cough severity.<h4>Conclusions</h4>Health resource use in this cohort of children is high, reflecting their severe disease burden. Studies are now needed to quantify the direct and societal costs of disease and to evaluate interventions that may reduce disease burden, particularly hospitalizations.
Project description:Pulmonary rehabilitation (PR), delivered as a supervised multidisciplinary program including exercise training, is one of the cornerstones in the chronic obstructive pulmonary disease (COPD) management. We performed a systematic review and meta-analysis to assess the effect on mortality of a supervised early PR program, initiated during or within 4 weeks after hospitalization with an acute exacerbation of COPD compared with usual post-exacerbation care or no PR program. Secondary outcomes were days in hospital, COPD related readmissions, health-related quality of life (HRQoL), exercise capacity (walking distance), activities of daily living (ADL), fall risk and drop-out rate.We identified randomized trials through a systematic search using MEDLINE, EMBASE and Cocharne Library and other sources through October 2017. Risk of bias was assessed regarding randomization, allocation sequence concealment, blinding, incomplete outcome data, selective outcome reporting, and other biases using the Cochrane Risk of Bias tool.We included 13 randomized trials (801 participants). Our meta-analyses showed a clinically relevant reduction in mortality after early PR (4 trials, 319 patients; RR?=?0.58 (95% CI: [0.35 to 0.98])) and at the longest follow-up (3 trials, 127 patients; RR?=?0.55 (95% CI: [0.12 to 2.57])). Early PR reduced number of days in hospital by 4.27 days (1 trial, 180 patients; 95% CI: [-?6.85 to -?1.69]) and hospital readmissions (6 trials, 319 patients; RR?=?0.47 (95% CI: [0.29 to 0.75])). Moreover, early PR improved HRQoL and walking distance, and did not affect drop-out rate. Several of the trials had unclear risk of bias in regard to the randomization and blinding, for some outcome there was also a lack of power.Moderate quality of evidence showed reductions in mortality, number of days in hospital and number of readmissions after early PR in patients hospitalized with a COPD exacerbation. Long-term effects on mortality were not statistically significant, but improvements in HRQoL and exercise capacity appeared to be maintained for at least 12 months. Therefore, we recommend early supervised PR to patients with COPD-related exacerbations. PR should be initiated during hospital admission or within 4 weeks after hospital discharge.
Project description:Pseudomonas aeruginosa (P. aeruginosa) occupies an important niche in the pathogenic microbiome of bronchiectasis. The objective of this study is to evaluate the clinical characteristics and prognostic value of P. aeruginosa in Chinese adult patients with bronchiectasis.This retrospective and follow-up study enrolled 1188 patients diagnosed with bronchiectasis at Shanghai Pulmonary Hospital between January 2011 and December 2012. The patients' clinical data including anthropometry, clinical symptoms, serum biomarkers, radiographic manifestations and lung function indices were reviewed. The median follow-up duration (IQR) was 44 (40-54) months, during which 289 patients were lost to follow-up. Data from 899 patients were collected and analysed for the outcomes of mortality, annual exacerbation frequency and health-related quality of life.P. aeruginosa was isolated from 232 patients, alongside other pathogens such as Aspergillus (n=75) and Candida albicans (n=72). There were 74 deaths (12% of patients with P. aeruginosa, 7.3% of those without) over the course of the follow-up. The isolation of P. aeruginosa was a risk factor for all-cause mortality (HR, 3.07; 95%?CI 1.32 to 7.15) and was associated with high rates of exacerbations (ie, ?3 exacerbations per year of follow-up) (HR, 2.40; 95%?CI 1.20 to 4.79). Patients with P. aeruginosa also had worse scores on the Hospital Anxiety and Depression Scale (anxiety, p=0.005; depression, p<0.001), the Leicester Cough Questionnaire (p=0.033) and the modified Medical Research Council scale (p=0.001) compared with those without P. aeruginosa.Isolation of P. aeruginosa in patients with bronchiectasis is a significant prognostic indicator and should be a major factor in the clinical management of the disease.
Project description:<h4>Background</h4>Thoracic computed tomography (CT) scans are widely performed in clinical practice, often leading to detection of airway or parenchymal abnormalities in asymptomatic or minimally symptomatic individuals. However, clinical relevance of CT abnormalities is uncertain in the general population.<h4>Methods</h4>We evaluated data from 1361 participants aged ?40 years from a Canadian prospective cohort comprising 408 healthy never-smokers, 502 healthy ever-smokers, and 451 individuals with spirometric evidence of chronic obstructive pulmonary disease (COPD) who had thoracic CT scans. CT images of subjects were visually scored for respiratory bronchiolitis(RB), emphysema(E), bronchial-wall thickening(BWT), expiratory air-trapping(AT), and bronchiectasis(B). Multivariable logistic regression models were used to assess associations of CT features with respiratory symptoms, dyspnea, health status as determined by COPD assessment test, and risk of clinically significant exacerbations during 12 months follow-up.<h4>Results</h4>About 11% of life-time never-smokers demonstrated emphysema on CT scans. Prevalence increased to 30% among smokers with normal lung function and 36%, 50%, and 57% among individuals with mild, moderate or severe/very severe COPD, respectively. Presence of emphysema on CT was associated with chronic cough (OR,2.11; 95%CI,1.4-3.18); chronic phlegm production (OR,1.87; 95% CI,1.27-2.76); wheeze (OR,1.61; 95% CI,1.05-2.48); dyspnoea (OR,2.90; 95% CI,1.41-5.98); CAT score?10(OR,2.17; 95%CI,1.42-3.30) and risk of ?2 exacerbations over 12 months (OR,2.17; 95% CI, 1.42-3.0).<h4>Conclusions</h4>Burden of thoracic CT abnormalities is high among Canadians ?40 years of age, including never-smokers and smokers with normal lung function. Detection of emphysema on CT scans is associated with pulmonary symptoms and increased risk of exacerbations, independent of smoking or lung function.