We searched PubMed using the search terms ”bronchiectasis”, ”endotype”, ”genotype”, ”microbiome”, and ”heterogeneity”. We focused on papers and reviews published from Jan 1, 2010 to March 1, 2018 in English. We also searched author names of key people in the bronchiectasis field. From key papers, we reviewed reference lists to find additional pertinent papers and to redefine search terms. For the concept of endotyping, we searched this term in combination with other major pulmonary diseases
SeriesAdvances in bronchiectasis: endotyping, genetics, microbiome, and disease heterogeneity
Introduction
Bronchiectasis is defined as permanent enlargement of the airways,1 and is mostly the result of an intrinsic airway pathology resulting in dilation. Multiple causes of bronchiectasis and a broad array of clinical presentations exist.2 The extent of bronchiectasis can range from focal disease (limited to one segment or lobe) to diffuse disease (involving both lungs and all lobes). Bronchiectatic findings range from subtle dilation to cystic changes in the airways. Some patients will be asymptomatic and the bronchiectasis is discovered unexpectedly, whereas others will have daily symptoms of cough and sputum production with periodic exacerbations.3 The diagnosis of bronchiectasis is increasing worldwide. Previously classified as a rare or orphan disease, bronchiectasis has now been reported at rates of up to 566 per 100 000 population with an incidence that has increased by 40% in the past 10 years.4
Despite having its own diagnostic code, there are no medications or therapies approved by regulatory authorities in the USA or Europe for most cases of bronchiectasis. The exception is bronchiectasis due to cystic fibrosis, for which several approved medications exist, but none are approved as treatments for bronchiectasis of other causes.5 However, guidelines that recommend treatments for bronchiectasis are available,5 and reports have shown that some therapies are associated with clinical benefit,6, 7 suggesting that we need to improve our ability to identify those patients with bronchiectasis.8, 9 The pathway to more precise treatment will require a better understanding of patients beyond imaging studies. Here, we review recent studies, particularly focusing on the past 2 years, that have attempted to better describe patients according to a heterogeneous group of endotypes (defined by a distinct functional or pathobiological mechanism10) or clinical phenotypes (defined by relevant and common features of the disease11).
Section snippets
Pathophysiology of disease
The list of conditions known to cause or be associated with bronchiectasis is long, but most have common features that lead to the remodelling and dilation of the airways. A useful pathophysiological pathway has described the process as a cycle of events promoting impaired mucociliary clearance and retention of airway secretions. These events disrupt the host's defences and render the airways more susceptible to establishment of chronic infection. The persistence of bacterial pathogens incites
Endotypes and genotypes
Although most patients will be diagnosed with idio-pathic bronchiectasis, indicating that the cause could not be found following testing, reviewing conditions with well known, genetics-based pathways offers insights into understanding the underlying mechanisms of bronchiectasis pathogenesis. These insights can aid in the development of specific treatment regimens. However, the interactions between genetics, endotypes, environment, and therapeutic interventions can vary. In asthma, for example,
Disease heterogeneity beyond causes: clinical phenotypes
Assessing patients with bronchiectasis requires knowledge of the heterogeneity of clinical presentation and variable clinical course. Patients with apparently mild symptoms at presentation could still have adverse prognostic factors and have rapid progression of disease, whereas others with seemingly severe symptoms at the outset might be easily managed and have a good prognosis.53 A multidimensional approach to patient assessment should incorporate clinical history, physical examination,
Microbiology and the microbiome
Chronic bacterial infection is a characteristic in many patients with bronchiectasis. The term chronic infection is preferred to colonisation because colonisation implies a benign process whereas chronic infection is more reflective of the long-term interaction between microorganisms and the host leading to progressive tissue damage. Sputum culture remains an important part of management because the presence of some organisms has prognostic implications. This information can help guide
Conclusion
Ultimately, clinical variables can only provide modest predictive accuracy for bronchiectasis outcomes and provide little information about the underlying biology of the disease. Recent progress in understanding genotypes and endotypes, the process of defining groups of patients by pathobiology often with use of biomarkers, is at an early stage in bronchiectasis but offers promising approaches to develop therapeutic interventions for some patients with bronchiectasis. Hopefully, in the near
Search strategy and selection criteria
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