Bronchiectasis in the 21th century: Diagnosis and management

Abstract

The unmet need: Bronchiectasis had a declining incidence over the last century. However in the recent 15 years, the global resurgence of bronchiectasis in children and adults has been highlighted.1,2,3 Despite its increasing prevalence3 and its substantial impact on morbidity1 and mortality,4 bronchiectasis remains relatively underresearched. Critical knowledge gaps,1 especially in children, persist.2 The unmet needs of people with bronchiectasis are huge and there are few randomized controlled trials (RCTs).1,2,5 Indeed, the European Respiratory Society (ERS) deems bronchiectasis unrelated to cystic fibrosis (CF) as one of the most neglected lung diseases in clinical practice. While the burden of bronchiectasis is known to be high in some settings (eg the prevalence among Indigenous Australians and Alaskan Indian children is 1 in every 63-68 children), it is often unappreciated that it is also an important chronic disease in mainstream settings in affluent countries;6 for example 40% increase in bronchiectasis prevalence over the last 10-years in the United Kingdom (UK).3 In Australasia, bronchiectasis is more common and more severe in Indigenous than nonindigenous patients, where the mortality gap exceeds 20-years.4 The paradigm: A paradigm for bronchiectasis development and its progression is internationally accepted.1,2 This paradigm is based on decades-old and more recent studies using new technology. It is framed around the notion that primary prevention of bronchiectasis is possible and the knowledge that early detection of causal conditions (eg hypogammaglobulinemia) substantially reduces the risk of the future development of bronchiectasis through early initiation of treatment and optimal care. In children, mild (ie when detected early) bronchiectasis is potentially reversible.1,2 Many factors influence progression of the illness, most of which are modifiable and represent potential intervention points. These factors (secondary prevention) include better clinical management and guideline implementation. Thus, prompt diagnosis and optimal management of bronchiectasis is particularly important in childhood, thereby allowing opportunities for its reversal and/or halting disease progression.1,2 Diagnosis: Prompt and accurate detection of bronchiectasis is pivotal when starting treatment to reverse early disease. Diagnosis requires clinical suspicion and objective tests and thus appropriate case ascertainment is important. The clinical findings of children with bronchiectasis, summarized in a recent review,6 varies considerably among global cohorts and would be dependent on disease severity. Chronic cough, the most consistent symptom of bronchiectasis, may be reported only intermittently (35-100%)6 as cough may resolve after treatment.7 Also, cough may be wet rather than productive in children, as young children usually do not expectorate. Symptoms of dyspnea and hemoptysis are generally rare in pediatric cohorts in high-income countries where bronchiectasis is generally diagnosed earlier (and hence milder disease). Cohorts based in low-income countries generally reported a higher prevalence of wheeze (up to 66%), hemoptysis (up to 41%), digital clubbing (up to 41%) compared to high-income countries outside of Indigenous settings.6 Other pointers include failure to thrive and chest wall deformity (present in 45% and 95% of cohorts respectively),6 recurrent protracted bacterial bronchitis and failure of the wet/productive cough to respond to 4 weeks of antibiotics (ORadj 20.9, 95%CI, 5.4-81.8).7 Objective diagnosis of bronchiectasis is based upon the pathognomonic radiological finding of an increased broncho-arterial ratio (BAR) on chest CT scans.1,2 The widely used BAR diagnostic threshold of 1.0 was derived several decades ago from adult studies using now outdated CT protocols and applied to all ages, despite large differences in mean BAR between young children and the elderly.1,2 This approach limits the early detection of pediatric bronchiectasis and the window of opportunity for its reversal.2 While we have advocated using pediatric-specific criteria for bronchiectasis diagnosis since 20088 (instead of adult-derived BAR > 1.0), this is still not accepted universally and more studies in different cohorts are required. Nevertheless, there are however robust reasons why a pediatric derived cut-off are more appropriate than adult-derived.1 In recent years, other techniques include MRI with or without inhaled agents (eg hyperpolarized helium or xenon) that adds information about gas exchange.9 Although there are reports that MRI has a good correlation with CT scores, currently, MRI (compared to chest CT) takes longer, is more expensive, and still nonideal for assessing small airways morphology, required for diagnosing bronchiectasis. 9 Management: A myriad of heterogenous risk and/or etiological factors may lead to bronchiectasis in children.1,2 While these factors vary among settings, they share a common thread of chronic cough and recurrent acute exacerbations with persistent lower airway infection/inflammation. Interrupting these processes as early as possible is necessary to reverse and/or halt disease progression and further tissue damage. Effective clinical management reduces short and long term morbidity associated with bronchiectasis.1,10 There is increasing evidence that intensive treatment of children who either have bronchiectasis, or who are at risk of developing severe bronchiectasis, prevents poor lung function in adulthood. New approaches to managing people with other chronic airway diseases,3 include the concept of phenotypes and 'treatable traits',2 which we suggested for pediatric bronchiectasis recently. These treatable traits overlap with disease phenotypes, although this is yet to be consolidated in adults with bronchiectasis and not yet clearly established in children. Proposed pediatric bronchiectasis 'pediatric treatable traits' are nonexclusive traits and can be subgrouped into 'infection', 'inflammation', 'co-morbidities', 'underlying disease' and 'generic modifiable factors'. While they may be useful, clinical validation and more knowledge is needed to understand how these concepts would improve short-term clinical outcomes and long-term prognosis in children with bronchiectasis. Center management goals include; (a) optimizing postnatal lung growth, (b) preventing premature respiratory decline, (c) optimizing QoL, (d) minimizing exacerbations and, (e) preventing complications. Ideally a team approach with incorporation of allied health expertise (nursing, physiotherapy, nutritionist, social work) is used as this model improves outcomes of chronic diseases.2 While many options are available, there are few with high-level evidence data. Indeed, with few RCTs in children with bronchiectasis, treatment recommendations are based largely on expert opinion and extrapolation of studies conducted in CF patients and in adults with bronchiectasis.2,5 The possible dangers of some of these approaches were previously highlighted. Much more needs to be done to reduce the burden of bronchiectasis and improve the lives of children with bronchiectasis and their families, on all fronts from research, clinical care and resource allocation. The field is a long way off in all fronts but there is now more hope with recent RCTs that have focused on bronchiectasis unrelated to CF.L6287102772019-08-05 <br />