Mechanisms of immune dysfunction and bacterial persistence in non-cystic fibrosis bronchiectasis

Chalmers, James D.; Hill, Adam T.

doi:10.1016/j.molimm.2012.09.011

Cited by 153 publications

(132 citation statements)

References 95 publications

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“…Bronchiectasis not due to cystic fibrosis ("non-CF bronchiectasis", henceforth referred to simply as bronchiectasis) is characterised radiologically by permanent dilation of the bronchi, and clinically by a syndrome of cough, sputum production and recurrent respiratory infections [1]. Having been previous regarded as a neglected "orphan" disease, recent years have seen renewed interest in the disease, resulting in more clinical research and the development of new treatments [2].…”

Section: Introductionmentioning

confidence: 99%

Management of bronchiectasis in adults

2015

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Formerly regarded as a rare disease, bronchiectasis is now increasingly recognised and a renewed interest in the condition is stimulating drug development and clinical research. Bronchiectasis represents the final common pathway of a number of infectious, genetic, autoimmune, developmental and allergic disorders and is highly heterogeneous in its aetiology, impact and prognosis.The goals of therapy should be: to improve airway mucus clearance through physiotherapy with or without adjunctive therapies; to suppress, eradicate and prevent airway bacterial colonisation; to reduce airway inflammation; and to improve physical functioning and quality of life.Fortunately, an increasing body of evidence supports interventions in bronchiectasis. The field has benefited greatly from the introduction of evidence-based guidelines in some European countries and randomised controlled trials have now demonstrated the benefit of long-term macrolide therapy, with accumulating evidence for inhaled therapies, physiotherapy and pulmonary rehabilitation.This review provides a critical update on the management of bronchiectasis focussing on emerging evidence and recent randomised controlled trials. @ERSpublications Bronchiectasis is a rapidly developing field: review of recent RCTs and progress towards developing new therapies

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Section: Introductionmentioning

confidence: 99%

Management of bronchiectasis in adults

2015

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“…Recurrent infection leads to tissue damage and inflammation that leads to excess mucus production and delayed mucociliary clearance, predisposing the patient to recurrent and chronic infections [2]. This in turn creates a cycle of further tissue damage and infection [3], leading to recurrent exacerbations, hospitalisations and loss of lung function.…”

Section: Introductionmentioning

confidence: 99%

Predicting mortality in bronchiectasis using bronchiectasis severity index and FACED scores: a 19-year cohort study

Ellis

Cowman

Fernandes³

et al. 2015

Eur Respir J

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The clinical course of bronchiectasis is unpredictable, posing a challenge both in clinical practice and in research. Two mortality prediction scores, the bronchiectasis severity index (BSI) and FACED scores, have recently been developed. The aim of this study was to assess the ability of these scores to predict long-term mortality and to compare the two scores.The study was a single-centre retrospective cohort analysis consisting of 91 subjects originally recruited in 1994. BSI and FACED scores were calculated at the time of enrolment and long-term mortality ascertained. Data was available for 74 patients with a median of 18.8 years of follow-up.Both scoring systems had similar predictive power for 5-year mortality (area under receiver operator characteristic curve (AUC) 0.79 for BSI and 0.8 for FACED). Both scores were able to predict 15-year mortality with the FACED score showing slightly superior predictive power (AUC 0.82 versus 0.69, p=0.0495).This study provides further validation of the FACED and BSI scores for the prediction of mortality in bronchiectasis and demonstrates their utility over a longer period than originally described. Whilst both scores had excellent predictive power, the FACED score was superior for 15-year mortality. @ERSpublications BSI and FACED bronchiectasis severity scores identify patients at high risk of death over a 19-year follow-up period

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“…Non-cystic fibrosis (CF) bronchiectasis (hereafter referred to as bronchiectasis) is a chronic respiratory disorder characterized by recurrent cough, sputum production, and respiratory infections (1). Pathologically, patients have abnormally dilated bronchi leading to impairment of host defense, chronic colonization with bacteria, and airways inflammation (2,3).…”

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The Bronchiectasis Severity Index. An International Derivation and Validation Study

Chalmers

Goeminne²,

Aliberti

et al. 2014

Am J Respir Crit Care Med

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Rationale: 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.Objectives: This study describes the derivation and validation of the Bronchiectasis Severity Index (BSI).Methods: Derivation of the BSI used data from a prospective cohort study (Edinburgh, UK, 2008 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).Measurements and Main Results: Independent predictors of future hospitalization were prior hospital admissions, Medical Research Council dyspnea score greater than or equal to 4, FEV 1 , 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 FEV 1 , 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. Conclusions:The BSI is a useful clinical predictive tool that identifies patients at risk of future mortality, hospitalization, and exacerbations across healthcare systems.

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Mechanisms of immune dysfunction and bacterial persistence in non-cystic fibrosis bronchiectasis

Cited by 153 publications

References 95 publications

Management of bronchiectasis in adults

Management of bronchiectasis in adults

Predicting mortality in bronchiectasis using bronchiectasis severity index and FACED scores: a 19-year cohort study

The Bronchiectasis Severity Index. An International Derivation and Validation Study

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