There are no risk stratification tools for morbidity and mortality in bronchiectasis. Identifying patients at risk of exacerbations, hospital admissions, and mortality is vital for future research.
...This study describes the derivation and validation of the Bronchiectasis Severity Index (BSI).
Derivation of the BSI used data from a prospective cohort study (Edinburgh, UK, 2008-2012) enrolling 608 patients. Cox proportional hazard regression was used to identify independent predictors of mortality and hospitalization over 4-year follow-up. The score was validated in independent cohorts from Dundee, UK (n = 218); Leuven, Belgium (n = 253); Monza, Italy (n = 105); and Newcastle, UK (n = 126).
Independent predictors of future hospitalization were prior hospital admissions, Medical Research Council dyspnea score greater than or equal to 4, FEV1 < 30% predicted, Pseudomonas aeruginosa colonization, colonization with other pathogenic organisms, and three or more lobes involved on high-resolution computed tomography. Independent predictors of mortality were older age, low FEV1, lower body mass index, prior hospitalization, and three or more exacerbations in the year before the study. The derived BSI predicted mortality and hospitalization: area under the receiver operator characteristic curve (AUC) 0.80 (95% confidence interval, 0.74-0.86) for mortality and AUC 0.88 (95% confidence interval, 0.84-0.91) for hospitalization, respectively. There was a clear difference in exacerbation frequency and quality of life using the St. George's Respiratory Questionnaire between patients classified as low, intermediate, and high risk by the score (P < 0.0001 for all comparisons). In the validation cohorts, the AUC for mortality ranged from 0.81 to 0.84 and for hospitalization from 0.80 to 0.88.
The BSI is a useful clinical predictive tool that identifies patients at risk of future mortality, hospitalization, and exacerbations across healthcare systems.
Bronchiectasis in adults is a chronic disorder associated with poor quality of life and frequent exacerbations in many patients. There have been no previous international guidelines.The European ...Respiratory Society guidelines for the management of adult bronchiectasis describe the appropriate investigation and treatment strategies determined by a systematic review of the literature.A multidisciplinary group representing respiratory medicine, microbiology, physiotherapy, thoracic surgery, primary care, methodology and patients considered the most relevant clinical questions (for both clinicians and patients) related to management of bronchiectasis. Nine key clinical questions were generated and a systematic review was conducted to identify published systematic reviews, randomised clinical trials and observational studies that answered these questions. We used the GRADE approach to define the quality of the evidence and the level of recommendations. The resulting guideline addresses the investigation of underlying causes of bronchiectasis, treatment of exacerbations, pathogen eradication, long term antibiotic treatment, anti-inflammatories, mucoactive drugs, bronchodilators, surgical treatment and respiratory physiotherapy.These recommendations can be used to benchmark quality of care for people with bronchiectasis across Europe and to improve outcomes.
Testing for underlying etiology is a key part of bronchiectasis management, but it is unclear whether the same extent of testing is required across the spectrum of disease severity.
The aim of the ...present study was to identify the etiology of bronchiectasis across European cohorts and according to different levels of disease severity.
We conducted an analysis of seven databases of adult outpatients with bronchiectasis prospectively enrolled at the bronchiectasis clinics of university teaching hospitals in Monza, Italy; Dundee and Newcastle, United Kingdom; Leuven, Belgium; Barcelona, Spain; Athens, Greece; and Galway, Ireland. All the patients at every site underwent the same comprehensive diagnostic workup as suggested by the British Thoracic Society.
Among the 1,258 patients enrolled, an etiology of bronchiectasis was determined in 60%, including postinfective (20%), chronic obstructive pulmonary disease related (15%), connective tissue disease related (10%), immunodeficiency related (5.8%), and asthma related (3.3%). An etiology leading to a change in patient's management was identified in 13% of the cases. No significant differences in the etiology of bronchiectasis were present across different levels of disease severity, with the exception of a higher prevalence of chronic obstructive pulmonary disease-related bronchiectasis (P < 0.001) and a lower prevalence of idiopathic bronchiectasis (P = 0.029) in patients with severe disease.
Physicians should not be guided by disease severity in suspecting specific etiologies in patients with bronchiectasis, although idiopathic bronchiectasis appears to be less common in patients with the most severe disease.
Exacerbations are key events in the natural history of bronchiectasis, but clinical predictors and outcomes of patients with frequently exacerbating disease are not well described.
To establish if ...there is a "frequent exacerbator phenotype" in bronchiectasis and the impact of exacerbations on long-term clinical outcomes.
We studied patients with bronchiectasis enrolled from 10 clinical centers in Europe and Israel, with up to 5 years of follow-up. Patients were categorized by baseline exacerbation frequency (zero, one, two, or three or more per year). The repeatability of exacerbation status was assessed, as well as the independent impact of exacerbation history on hospitalizations, quality of life, and mortality.
A total of 2,572 patients were included. Frequent exacerbations were the strongest predictor of future exacerbation frequency, suggesting a consistent phenotype. The incident rate ratios for future exacerbations were 1.73 (95% confidence interval CI, 1.47-2.02; P < 0.0001) for one exacerbation per year, 3.14 (95% CI, 2.70-3.66; P < 0.0001) for two exacerbations, and 5.97 (95% CI, 5.27-6.78; P < 0.0001) for patients with three or more exacerbations per year at baseline. Additional independent predictors of future exacerbation frequency were Haemophilus influenzae and Pseudomonas aeruginosa infection, FEV
, radiological severity of disease, and coexisting chronic obstructive pulmonary disease. Patients with frequently exacerbating disease had worse quality of life and were more likely to be hospitalized during follow-up. Mortality over up to 5 years of follow-up increased with increasing exacerbation frequency.
The frequent exacerbator phenotype in bronchiectasis is consistent over time and shows high disease severity, poor quality of life, and increased mortality during follow-up.
Patients with bronchiectasis often have concurrent comorbidities, but the nature, prevalence, and impact of these comorbidities on disease severity and outcome are poorly understood. We aimed to ...investigate comorbidities in patients with bronchiectasis and establish their prognostic value on disease severity and mortality rate.
An international multicentre cohort analysis of outpatients with bronchiectasis from four European centres followed up for 5 years was done for score derivation. Eligible patients were those with bronchiectasis confirmed by high-resolution CT and a compatible clinical history. Comorbidity diagnoses were based on standardised definitions and were obtained from full review of paper and electronic medical records, prescriptions, and investigator definitions. Weibull parametric survival analysis was used to model the prediction of the 5 year mortality rate to construct the Bronchiectasis Aetiology Comorbidity Index (BACI). We tested the BACI as a predictor of outcomes and explored whether the BACI added further prognostic information when used alongside the Bronchiectasis Severity Index (BSI). The BACI was validated in two independent international cohorts from the UK and Serbia.
Between June 1, 2006, and Nov 22, 2013, 1340 patients with bronchiectasis were screened and 986 patients were analysed. Patients had a median of four comorbidities (IQR 2-6; range 0-20). 13 comorbidities independently predicting mortality rate were integrated into the BACI. The overall hazard ratio for death conferred by a one-point increase in the BACI was 1·18 (95% CI 1·14-1·23; p<0·0001). The BACI predicted 5 year mortality rate, hospital admissions, exacerbations, and health-related quality of life across all BSI risk strata (p<0·0001 for mortality and hospital admissions, p=0·03 for exacerbations, p=0·0008 for quality of life). When used in conjunction with the BSI, the combined model was superior to either model alone (p=0·01 for combined vs BACI; p=0·008 for combined vs BSI).
Multimorbidity is frequent in bronchiectasis and can negatively affect survival. The BACI complements the BSI in the assessment and prediction of mortality and disease outcomes in patients with bronchiectasis.
European Bronchiectasis Network (EMBARC).
Eradication and suppression of Pseudomonas aeruginosa is a key priority in national guidelines for bronchiectasis and is a major focus of drug development and clinical trials. An accurate estimation ...of the clinical impact of P. aeruginosa in bronchiectasis is therefore essential.
Data derived from 21 observational cohort studies comparing patients with P. aeruginosa colonization with those without it were pooled by random effects meta-analysis. Data were collected for key longitudinal clinical outcomes of mortality, hospital admissions, exacerbations, and lung function decline, along with cross-sectional outcomes such as quality of life.
In the aggregate, the included studies comprised 3,683 patients. P. aeruginosa was associated with a highly significant and consistent increase in all markers of disease severity, including mortality (odds ratio OR, 2.95; 95% confidence interval CI, 1.98-4.40; P < 0.0001), hospital admissions (OR, 6.57; 95% CI, 3.19-13.51; P < 0.0001), and exacerbations (mean difference, 0.97/yr; 95% CI, 0.64-1.30; P < 0.0001). The patients with P. aeruginosa also had worse quality of life on the basis of their St. George's Respiratory Questionnaire results (mean difference, 18.2 points; 95% CI, 14.7-21.8; P < 0.0001). Large differences in lung function and radiological severity were also observed. The definitions of colonization were inconsistent among the studies, but the findings were robust regardless of the definition used.
P. aeruginosa is associated with an approximately threefold increased risk of death and an increase in hospital admissions and exacerbations in adult bronchiectasis.
is responsible for chronic infection in many bronchiectasis patients but it is not known whether it is associated with worse clinical outcomes independent of the underlying severity of disease.This ...study analysed data from 2596 bronchiectasis patients included from 10 different bronchiectasis clinical centres across Europe and Israel, with a 5-year follow-up period. Prevalence of
chronic infection and its independent impact on exacerbations, hospitalisations, quality of life and mortality was assessed.The prevalence of
chronic infection was 15.0% (n=389).
was associated with a higher mortality in a univariate analysis (hazard ratio (HR) 2.02; 95% (confidence interval) CI 1.53-2.66; p<0.0001) but an independent impact on mortality was not found in a multivariate analysis (HR 0.98; 95% CI 0.70-1.36; p=0.89).
was independently associated with increased mortality only in patients with frequent exacerbations (two or more per year) (HR 2.03; 95% CI 1.36-3.03; p=0.001). An independent association with worse quality of life of 7.46 points (95% CI 2.93-12.00; p=0.001) was found in a multivariable linear regression.
was therefore found to be independently associated with exacerbation frequency, hospital admissions and worse quality of life. Mortality was increased in patients with
particularly in the presence of frequent exacerbations.
Bronchiectasis is a heterogeneous disease. This study aimed at identifying discrete groups of patients with different clinical and biological characteristics and long-term outcomes.This was a ...secondary analysis of five European databases of prospectively enrolled adult outpatients with bronchiectasis. Principal component and cluster analyses were performed using demographics, comorbidities, and clinical, radiological, functional and microbiological variables collected during the stable state. Exacerbations, hospitalisations and mortality during a 3-year follow-up were recorded. Clusters were externally validated in an independent cohort of patients with bronchiectasis, also investigating inflammatory markers in sputum.Among 1145 patients (median age 66 years; 40% male), four clusters were identified driven by the presence of chronic infection with Pseudomonas aeruginosaor other pathogens and daily sputum: "Pseudomonas" (16%), "Other chronic infection" (24%), "Daily sputum" (33%) and "Dry bronchiectasis" (27%). Patients in the four clusters showed significant differences in terms of quality of life, exacerbations, hospitalisations and mortality during follow-up. In the validation cohort, free neutrophil elastase activity, myeloperoxidase activity and interleukin-1β levels in sputum were significantly different among the clusters.Identification of four clinical phenotypes in bronchiectasis could favour focused treatments in future interventional studies designed to alter the natural history of the disease.
Background
Chronic obstructive pulmonary disease (COPD) is a chronic respiratory condition characterised by shortness of breath, cough and recurrent exacerbations. People with COPD often live with ...one or more co‐existing long‐term health conditions (comorbidities). People with more severe COPD often have a higher number of comorbidities, putting them at greater risk of morbidity and mortality.
Objectives
To assess the effectiveness of any single intervention for COPD adapted or tailored to their comorbidity(s) compared to any other intervention for people with COPD and one or more common comorbidities (quantitative data, RCTs) in terms of the following outcomes: Quality of life, exacerbations, functional status, all‐cause and respiratory‐related hospital admissions, mortality, pain, and depression and anxiety.
To assess the effectiveness of an adapted or tailored single COPD intervention (simple or complex) that is aimed at changing the management of people with COPD and one or more common comorbidities (quantitative data, RCTs) compared to usual care in terms of the following outcomes: Quality of life, exacerbations, functional status, all‐cause and respiratory‐related hospital admissions, mortality, pain, and depression and anxiety.
To identify emerging themes that describe the views and experiences of patients, carers and healthcare professionals when receiving or providing care to manage multimorbidities (qualitative data).
Search methods
We searched multiple databases including the Cochrane Airways Trials Register, CENTRAL, MEDLINE, Embase, and CINAHL, to identify relevant randomised and qualitative studies. We also searched trial registries and conducted citation searches. The latest search was conducted in January 2021.
Selection criteria
Eligible randomised controlled trials (RCTs) compared a) any single intervention for COPD adapted or tailored to their comorbidity(s) compared to any other intervention, or b) any adapted or tailored single COPD intervention (simple or complex) that is aimed at changing the management of people with COPD and one or more comorbidities, compared to usual care. We included qualitative studies or mixed‐methods studies to identify themes.
Data collection and analysis
We used standard Cochrane methods for analysis of the RCTs. We used Cochrane's risk of bias tool for the RCTs and the CASP checklist for the qualitative studies. We planned to use the Mixed Methods Appraisal tool (MMAT) to assess the risk of bias in mixed‐methods studies, but we found none. We used GRADE and CERQual to assess the quality of the quantitative and qualitative evidence respectively. The primary outcome measures for this review were quality of life and exacerbations.
Main results
Quantitative studies
We included seven studies (1197 participants) in the quantitative analyses, with interventions including telemonitoring, pulmonary rehabilitation, treatment optimisation, water‐based exercise training and case management. Interventions were either compared with usual care or with an active comparator (such as land‐based exercise training). Duration of trials ranged from 4 to 52 weeks. Mean age of participants ranged from 64 to 72 years and COPD severity ranged from mild to very severe. Trials included either people with COPD and a specific comorbidity (including cardiovascular disease, metabolic syndrome, lung cancer, head or neck cancer, and musculoskeletal conditions), or with one or more comorbidities of any type.
Overall, we judged the evidence presented to be of moderate to very low certainty (GRADE), mainly due to the methodological quality of included trials and imprecision of effect estimates.
Intervention versus usual care
Quality of life as measured by the St George's Respiratory Questionnaire (SGRQ) total score may improve with tailored pulmonary rehabilitation compared to usual care at 52 weeks (mean difference (MD) −10.85, 95% confidence interval (CI) −12.66 to −9.04; 1 study, 70 participants; low‐certainty evidence). Tailored pulmonary rehabilitation is likely to improve COPD assessment test (CAT) scores compared with usual care at 52 weeks (MD −8.02, 95% CI −9.44 to −6.60; 1 study, 70 participants, moderate‐certainty evidence) and with a multicomponent telehealth intervention at 52 weeks (MD −6.90, 95% CI −9.56 to −4.24; moderate‐certainty evidence). Evidence is uncertain about effects of pharmacotherapy optimisation or telemonitoring interventions on CAT improvement compared with usual care.
There may be little to no difference in the number of people experiencing exacerbations, or mean exacerbations with case management compared with usual care (OR 1.09, 95% CI 0.75 to 1.57; 1 study, 470 participants; very low‐certainty evidence).
For secondary outcomes, six‐minute walk distance (6MWD) may improve with pulmonary rehabilitation, water‐based exercise or multicomponent interventions at 38 to 52 weeks (low‐certainty evidence). A multicomponent intervention may result in fewer people being admitted to hospital at 17 weeks, although there may be little to no difference in a telemonitoring intervention. There may be little to no difference between intervention and usual care for mortality.
Intervention versus active comparator
We included one study comparing water‐based and land‐based exercise (30 participants). We found no evidence for quality of life or exacerbations.
There may be little to no difference between water‐ and land‐based exercise for 6MWD (MD 5 metres, 95% CI −22 to 32; 38 participants; very low‐certainty evidence).
Qualitative studies
One nested qualitative study (21 participants) explored perceptions and experiences of people with COPD and long‐term conditions, and of researchers and health professionals who were involved in an RCT of telemonitoring equipment.
Several themes were identified, including health status, beliefs and concerns, reliability of equipment, self‐efficacy, perceived ease of use, factors affecting usefulness and perceived usefulness, attitudes and intention, self‐management and changes in healthcare use. We judged the qualitative evidence presented as of very low certainty overall.
Authors' conclusions
Owing to a paucity of eligible trials, as well as diversity in the intervention type, comorbidities and the outcome measures reported, we were unable to provide a robust synthesis of data. Pulmonary rehabilitation or multicomponent interventions may improve quality of life and functional status (6MWD), but the evidence is too limited to draw a robust conclusion. The key take‐home message from this review is the lack of data from RCTs on treatments for people living with COPD and comorbidities.
Given the variation in number and type of comorbidity(s) an individual may have, and severity of COPD, larger studies reporting individual patient data are required to determine these effects.
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