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Respiratory Care Feb 2020Although better insights into the natural course of cystic fibrosis (CF) have led to treatment approaches that have improved pulmonary health and increased the life... (Review)
Review
Although better insights into the natural course of cystic fibrosis (CF) have led to treatment approaches that have improved pulmonary health and increased the life expectancy of individuals with this disorder, lung disease remains the main cause of morbidity and mortality in patients with CF. Evidence suggests that airway epithelial defects in ions-water transport lead to dehydrated mucus, impaired mucus clearance, and mucus adhesion to airway surfaces. An increase in mucin secretion is also suggested by the formation of endobronchial mucus plaques and plugs, which become the main sites of air flow obstruction, infection, and inflammation conducing to early small airways disease followed by the development of bronchiectasis. The lung involvement is usually progressive with intermittent exacerbations. Aggressive management and advances in treatment delay, but, do not prevent progression of lung disease. Respiratory failure ensues and is the major cause of death. The lung parenchyma is virtually untouched for much of the course of the disease. This review focuses on the lung involvement in cystic fibrosis and summarizes new developments on the diagnostic approach of CF and pathogenesis of related lung disease. Current therapeutic modalities, novel therapies targeting the basic genetic defect, and lung transplantation are also reviewed.
Topics: Bronchiectasis; Cystic Fibrosis; Humans; Lung; Mucociliary Clearance; Mucus
PubMed: 31772069
DOI: 10.4187/respcare.06697 -
Respiratory Medicine Feb 2022Inhaled antibiotics have been incorporated into contemporary European and British guidelines for bronchiectasis, yet no inhaled antibiotics have been approved in the... (Review)
Review
BACKGROUND
Inhaled antibiotics have been incorporated into contemporary European and British guidelines for bronchiectasis, yet no inhaled antibiotics have been approved in the United States or Europe for the treatment of bronchiectasis not related to cystic fibrosis. Pseudomonas aeruginosa infection is common in patients with bronchiectasis, contributing to a cycle of progressive inflammation, exacerbations, and airway remodelling.
OBJECTIVE
The aim of the current study was to identify and evaluate published studies of inhaled tobramycin solution or powder in patients with bronchiectasis and P. aeruginosa infection not associated with cystic fibrosis.
METHODS
A literature review was conducted utilising the PubMed and Cochrane databases. Studies published in the English language that reported safety and/or efficacy outcomes of inhaled tobramycin either alone or in combination with other antibiotics were included.
RESULTS
Seven clinical trials published between 1999 and 2021 were identified that met inclusion criteria. Inhaled tobramycin therapy was effective in reducing P. aeruginosa microbial density in the sputum of patients with bronchiectasis. Several studies demonstrated favourable impacts on hospitalisations, number and severity of exacerbations, and symptoms. Other studies were underpowered for these clinical outcomes or were exploratory in nature. Although tobramycin was generally well tolerated, some evidence of treatment-associated wheezing was reported.
CONCLUSIONS
In patients with bronchiectasis and chronic P. aeruginosa infection, inhaled tobramycin was effective in reducing the density of bacteria in sputum, which may be associated with additional clinical benefits. Definitive phase 3 trials of inhaled tobramycin in patients with bronchiectasis are indicated to determine clinical efficacy and long-term safety.
Topics: Administration, Inhalation; Anti-Bacterial Agents; Bronchiectasis; Humans; Pseudomonas Infections; Pseudomonas aeruginosa; Tobramycin
PubMed: 34998112
DOI: 10.1016/j.rmed.2021.106728 -
European Respiratory Review : An... Dec 2019Bronchiectasis is a heterogeneous chronic disease. Heterogeneity characterises bronchiectasis not only in the stable state but also during exacerbations, despite... (Review)
Review
Bronchiectasis is a heterogeneous chronic disease. Heterogeneity characterises bronchiectasis not only in the stable state but also during exacerbations, despite evidence on clinical and biological aspects of bronchiectasis, exacerbations still remain poorly understood.Although the scientific community recognises that bacterial infection is a cornerstone in the development of bronchiectasis, there is a lack of data regarding other trigger factors for exacerbations. In addition, a huge amount of data suggest a primary role of neutrophils in the stable state and exacerbation of bronchiectasis, but the inflammatory reaction involves many other additional pathways. Cole's vicious cycle hypothesis illustrates how airway dysfunction, airway inflammation, infection and structural damage are linked. The introduction of the concept of a "vicious vortex" stresses the complexity of the relationships between the components of the cycle. In this model of disease, exacerbations work as a catalyst, accelerating the progression of disease. The roles of microbiology and inflammation need to be considered as closely linked and will need to be investigated in different ways to collect samples. Clinical and translational research is of paramount importance to achieve a better comprehension of the pathophysiology of bronchiectasis, microbiology and inflammation both in the stable state and during exacerbations.
Topics: Bronchiectasis; Disease Progression; Humans
PubMed: 31748420
DOI: 10.1183/16000617.0055-2019 -
Clinical Medicine (London, England) Nov 2021Bronchiectasis is a heterogeneous and increasingly prevalent chronic pulmonary disease that is associated with significant morbidity. In this review, we outline how... (Review)
Review
Bronchiectasis is a heterogeneous and increasingly prevalent chronic pulmonary disease that is associated with significant morbidity. In this review, we outline how patients with bronchiectasis may present clinically and describe an approach to its diagnosis, including how to identify an underlying aetiology. We discuss the important considerations when treating either acute exacerbations or stable disease and provide an overview of the role of long-term antimicrobials, airway clearance methods and other supportive management.
Topics: Anti-Bacterial Agents; Bronchiectasis; Humans
PubMed: 34862215
DOI: 10.7861/clinmed.2021-0651 -
Respiratory Medicine May 2020Bronchiectasis is a complex, chronic respiratory condition, characterized by frequent cough and exertional dyspnea due to a range of conditions that include inherited... (Review)
Review
Bronchiectasis is a complex, chronic respiratory condition, characterized by frequent cough and exertional dyspnea due to a range of conditions that include inherited mucociliary defects, inhalational airway injury, immunodeficiency states and prior respiratory infections. For years, bronchiectasis was classified as either being caused by cystic fibrosis or non-cystic fibrosis. Non-cystic fibrosis bronchiectasis, once considered an orphan disease, is more prevalent worldwide in part due to greater availability of chest computed tomographic imaging. Identification of the cause of non-cystic fibrosis bronchiectasis with the use of chest imaging, laboratory testing, and microbiologic assessment of airway secretions can lead to initiation of specific therapies aimed at slowing disease progression. Nonpharmacologic therapies such as airway clearance techniques and pulmonary rehabilitation improve patient symptoms. Inhaled corticosteroids should not be routinely prescribed unless concomitant asthma or COPD is present. Inhaled antibiotics prescribed to individuals with >3 exacerbations per year are well tolerated, reduce airway bacteria load and may reduce the frequency of exacerbations. Likewise, chronic macrolide therapy reduces the frequency of exacerbations. Medical therapies for cystic fibrosis bronchiectasis may not be effective in treatment of non-cystic fibrosis bronchiectasis.
Topics: Administration, Inhalation; Anti-Bacterial Agents; Bronchiectasis; Cystic Fibrosis; Disease Progression; Humans; Rare Diseases; Respiratory System; Respiratory Therapy; Respiratory Tract Infections; Tomography, X-Ray Computed
PubMed: 32250872
DOI: 10.1016/j.rmed.2020.105940 -
American Journal of Respiratory and... Apr 2023Emerging data support the existence of a microbial "gut-lung" axis that remains unexplored in bronchiectasis. Prospective and concurrent sampling of gut (stool) and...
Emerging data support the existence of a microbial "gut-lung" axis that remains unexplored in bronchiectasis. Prospective and concurrent sampling of gut (stool) and lung (sputum) was performed in a cohort of = 57 individuals with bronchiectasis and subjected to bacteriome (16S rRNA) and mycobiome (18S Internal Transcribed Spacer) sequencing (total, 228 microbiomes). Shotgun metagenomics was performed in a subset ( = 15; 30 microbiomes). Data from gut and lung compartments were integrated by weighted similarity network fusion, clustered, and subjected to co-occurrence analysis to evaluate gut-lung networks. Murine experiments were undertaken to validate specific driven gut-lung interactions. Microbial communities in stable bronchiectasis demonstrate a significant gut-lung interaction. Multibiome integration followed by unsupervised clustering reveals two patient clusters, differing by gut-lung interactions and with contrasting clinical phenotypes. A high gut-lung interaction cluster, characterized by lung , gut , and gut , is associated with increased exacerbations and greater radiological and overall bronchiectasis severity, whereas the low gut-lung interaction cluster demonstrates an overrepresentation of lung commensals, including , , and with gut . The lung gut relationship, observed in the high gut-lung interaction bronchiectasis cluster, was validated in a murine model of lung infection. This interaction was abrogated after antibiotic (imipenem) pretreatment in mice confirming the relevance and therapeutic potential of targeting the gut microbiome to influence the gut-lung axis. Metagenomics in a subset of individuals with bronchiectasis corroborated our findings from targeted analyses. A dysregulated gut-lung axis, driven by lung , associates with poorer clinical outcomes in bronchiectasis.
Topics: Animals; Mice; Prospective Studies; RNA, Ribosomal, 16S; Lung; Bronchiectasis; Microbiota
PubMed: 36288294
DOI: 10.1164/rccm.202205-0893OC -
Australian Journal of General Practice Dec 2022Bronchiectasis is a common chronic lung disease that is prevalent in the Australian community and is a significant disease burden in the Australian Aboriginal community....
BACKGROUND
Bronchiectasis is a common chronic lung disease that is prevalent in the Australian community and is a significant disease burden in the Australian Aboriginal community. It significantly affects quality of life and increases healthcare costs; however, it is poorly reported and documented.
OBJECTIVE
The aim of this article is to provide a comprehensive summary of the important features to recognise in bronchiectasis and an updated guide to the management of bronchiectasis.
DISCUSSION
Bronchiectasis is an obstructive lung disease that is often associated with various underlying conditions that can occur as a result of infectious insult or impaired host defence. The main features of bronchiectasis are dilated airways with increased sputum production, recurrent exacerbations and impaired quality of life. Management is aimed at investigating and managing secondary causes with a focus on sputum clearance, reduction in exacerbations and improvement of quality of life.
Topics: Humans; Quality of Life; Australia; Bronchiectasis; Cost of Illness
PubMed: 36451317
DOI: 10.31128/AJGP-08-22-6520 -
Pulmonology 2023Bronchiectasis is a highly complex entity that can be very challenging to investigate and manage. Patients are diverse in their aetiology, symptoms, risk of... (Meta-Analysis)
Meta-Analysis Review
Bronchiectasis is a highly complex entity that can be very challenging to investigate and manage. Patients are diverse in their aetiology, symptoms, risk of complications and outcomes. "Endotypes"- subtypes of disease with distinct biological mechanisms, has been proposed as a means of better managing bronchiectasis. This review discusses the emerging field of endotyping in bronchiectasis. We searched PubMed and Google Scholar for randomized controlled trials (RCT), observational studies, systematic reviews and meta-analysis published from inception until October 2022, using the terms: "bronchiectasis", "endotypes", "biomarkers", "microbiome" and "inflammation". Exclusion criteria included commentaries and non-English language articles as well as case reports. Duplicate articles between databases were initially identified and appropriately excluded. Studies identified suggest that it is possible to classify bronchiectasis patients into multiple endotypes deriving from their co-morbidities or underlying causes to complex infective or inflammatory endotypes. Specific biomarkers closely related to a particular endotype might be used to determine response to treatment and prognosis. The most clearly defined examples of endotypes in bronchiectasis are the underlying causes such as immunodeficiency or allergic bronchopulmonary aspergillosis where the underlying causes are clearly related to a specific treatment. The heterogeneity of bronchiectasis extends, however, far beyond aetiology and it is now possible to identify subtypes of disease based on inflammatory mechanisms such airway neutrophil extracellular traps and eosinophilia. In future biomarkers of host response and infection, including the microbiome may be useful to guide treatments and to increase the success of randomized trials. Advances in the understanding the inflammatory pathways, microbiome, and genetics in bronchiectasis are key to move towards a personalized medicine in bronchiectasis.
Topics: Humans; Precision Medicine; Bronchiectasis; Biomarkers; Inflammation; Comorbidity
PubMed: 37030997
DOI: 10.1016/j.pulmoe.2023.03.004 -
The European Respiratory Journal Aug 2021There is increasing awareness of bronchiectasis in children and adolescents, a chronic pulmonary disorder associated with poor quality of life for the child/adolescent...
There is increasing awareness of bronchiectasis in children and adolescents, a chronic pulmonary disorder associated with poor quality of life for the child/adolescent and their parents, recurrent exacerbations, and costs to the family and health systems. Optimal treatment improves clinical outcomes. Several national guidelines exist, but there are no international guidelines.The European Respiratory Society (ERS) Task Force for the management of paediatric bronchiectasis sought to identify evidence-based management (investigation and treatment) strategies. It used the ERS standardised methodology that included a systematic review of the literature and application of the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to define the quality of the evidence and level of recommendations.A multidisciplinary team of specialists in paediatric and adult respiratory medicine, infectious disease, physiotherapy, primary care, nursing, radiology, immunology, methodology, patient advocacy and parents of children/adolescents with bronchiectasis considered the most relevant clinical questions (for both clinicians and patients) related to managing paediatric bronchiectasis. 14 key clinical questions (seven PICO (Patient, Intervention, Comparison, Outcome) and seven narrative) were generated. The outcomes for each PICO were decided by voting by the panel and parent/patient advisory group.This guideline addresses the definition, diagnostic approach and antibiotic treatment of exacerbations, pathogen eradication, long-term antibiotic therapy, asthma-type therapies (inhaled corticosteroids and bronchodilators), mucoactive drugs, airway clearance, investigation of underlying causes of bronchiectasis, disease monitoring, factors to consider before surgical treatment, and the reversibility and prevention of bronchiectasis in children/adolescents. Benchmarking quality of care for children/adolescents with bronchiectasis to improve clinical outcomes and evidence gaps for future research could be based on these recommendations.
Topics: Adolescent; Adrenal Cortex Hormones; Adult; Asthma; Bronchiectasis; Bronchodilator Agents; Child; Humans; Quality of Life
PubMed: 33542057
DOI: 10.1183/13993003.02990-2020 -
European Respiratory Review : An... Mar 2023The strength of association between comorbidities and asthma has never been ranked in relation to the prevalence of the comorbidity in the nonasthma population. We... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The strength of association between comorbidities and asthma has never been ranked in relation to the prevalence of the comorbidity in the nonasthma population. We investigated the strength of association between comorbidities and asthma.
METHODS
A comprehensive literature search was performed for observational studies reporting data on comorbidities in asthma and nonasthma populations. A pairwise meta-analysis was performed and the strength of association calculated by anchoring odds ratios and 95% confidence intervals with the rate of comorbidities in nonasthma populations Cohen's method. Cohen's 0.2, 0.5 and 0.8 were cut-off values for small, medium and large effect sizes, respectively; very large effect size resulted for Cohen's >0.8. The review was registered in the PROSPERO database; identifier number CRD42022295657.
RESULTS
Data from 5 493 776 subjects were analysed. Allergic rhinitis (OR 4.24, 95% CI 3.82-4.71), allergic conjunctivitis (OR 2.63, 95% CI 2.22-3.11), bronchiectasis (OR 4.89, 95% CI 4.48-5.34), hypertensive cardiomyopathy (OR 4.24, 95% CI 2.06-8.90) and nasal congestion (OR 3.30, 95% CI 2.96-3.67) were strongly associated with asthma (Cohen's >0.5 and ≤0.8); COPD (OR 6.23, 95% CI 4.43-8.77) and other chronic respiratory diseases (OR 12.85, 95% CI 10.14-16.29) were very strongly associated with asthma (Cohen's >0.8). Stronger associations were detected between comorbidities and severe asthma. No bias resulted according to funnel plots and Egger's test.
CONCLUSION
This meta-analysis supports the relevance of individualised strategies for disease management that look beyond asthma. A multidimensional approach should be used to assess whether poor symptom control is related to uncontrolled asthma or to uncontrolled underlying comorbidities.
Topics: Humans; Asthma; Comorbidity; Bronchiectasis
PubMed: 36889783
DOI: 10.1183/16000617.0202-2022