Bronchiectasis in children: diagnosis and treatment

doi:10.1016/S0140-6736(18)31554-X

The Lancet

Volume 392, Issue 10150, 8–14 September 2018, Pages 866-879

https://doi.org/10.1016/S0140-6736(18)31554-X Get rights and content

Summary

Bronchiectasis is conventionally defined as irreversible dilatation of the bronchial tree. Bronchiectasis unrelated to cystic fibrosis is an increasingly appreciated cause of chronic respiratory-related morbidity worldwide. Few randomised controlled trials provide high-level evidence for management strategies to treat the children affected by bronchiectasis. However, both decades-old and more recent studies using technological advances support the notion that prompt diagnosis and optimal management of paediatric bronchiectasis is particularly important in early childhood. Although considered to be of a non-reversible nature, mild bronchiectasis determined by radiography might be reversible at any age if treated early, and the lung function decline associated with disease progression could then be halted. Although some management strategies are extrapolated from cystic fibrosis or adult-based studies, or both, non-cystic fibrosis paediatric-specific data to help diagnose and manage these children still need to be generated. We present current knowledge and an updated definition of bronchiectasis, and review controversies relating to the management of children with bronchiectasis, including applying the concept of so-called treatable traits.

Introduction

Bronchiectasis unrelated to cystic fibrosis has gained prominence in the past decade with the increasing appreciation that it is more common than previously thought.1, 2, 3 Although the burden of bronchiectasis is particularly high among Indigenous populations (one in 63–68 children⁴) and low-income settings (wherein the epidemiology [the cause and burden of disease] is changing⁵), it is also present in major cities.² Few reliable prevalence estimates exist for bronchiectasis; extrapolation of published data suggests its prevalence ranges widely (0·2–735·0 cases per 100 000 children).²

Although the paediatric bronchiectasis knowledge base is increasing slowly, bronchiectasis remains neglected compared with other chronic respiratory diseases (eg, cystic fibrosis).⁶ We provide an update of data and controversies relating to the diagnosis and management of paediatric bronchiectasis unrelated to cystic fibrosis. This includes proposing an updated definition to raise awareness and encourage an evidence-based approach, with the hope of improving the lives of the many children at risk of, or affected by, this condition. High-quality evidence in this field is scarce, and unless otherwise specified, recommendations are based on expert opinion.

Section snippets

Clinical diagnosis

Awareness of the symptoms and signs of bronchiectasis is important for case ascertainment (table 1, figure 1). Presence of key symptoms should alert clinicians to assess the child for bronchiectasis. When bronchiectasis is identified, a minimum set of tests are warranted to establish whether an underlying cause is present and for clinical care. Chronic wet or productive cough, the dominant symptom of bronchiectasis,² can be intermittent after treatment.¹ Recurrent (>3 episodes per year)

Framework of pathogenesis of chronic suppurative lung disease and bronchiectasis

Except for congenital tracheobronchomegaly (Mounier-Kuhn syndrome), the presence of underlying conditions associated with future development of bronchiectasis (eg, hypogammaglobulinaemia) do not always result in bronchiectasis, provided treatment is initiated early. This theory is supported by several cohorts showing that with optimal treatment, and irrespective of the underlying cause, lung function improves initially and does not decline 3–5 years later.24, 25 Our proposed framework (figure 3

Biomarkers, phenotypes, endotypes, and traits

Airway neutrophilia is the dominant airway inflammatory profile in bronchiectasis, but several cohorts showed additional eosinophilic inflammation (up to 34% of the cohort).1, 22 Many possible biomarkers (eg, neutrophilic inflammation) exist,1, 44 but none are well accepted or used clinically. Among adults with bronchiectasis, latent cluster-analysis suggests phenotypes exist and endotypes have been proposed.³ However, these phenotypes and endotypes have not been validated and there are no

Management

With few RCTs assessing children with bronchiectasis, treatment recommendations are based largely on expert opinion and extrapolation of studies done in patients with cystic fibrosis and in adults with bronchiectasis.47, 48, 49 The possible dangers of some of these approaches were highlighted previously elsewhere.⁴⁸ Nevertheless, cystic fibrosis-based data show that good clinical care alone (attention to infection and nutrition) before availability of CFTR-targeted therapy substantially

Conclusion

A myriad of heterogeneous risk or causative factors, or both, can lead to bronchiectasis in children. These factors and the various clinical symptoms vary among settings and countries, but share the common thread of cycles of chronic cough, recurrent respiratory infections, and endobronchial suppuration with persistent infection and inflammation. Interrupting these processes as early as possible is necessary to reverse or halt disease progression, and prevent further tissue damage. This

Search strategy and selection criteria

We searched PubMed and Cochrane databases with no language or date restrictions but we prioritised publications since January, 2010. For the diagnosis component, we used the search terms: “bronchiectasis” or ”suppurative lung disease”, and “diagnosis” or “endotypes”, or “phenotypes”, or “biomarkers”, and “children”. For the management component, we used the search terms: “treatment” or “management”, or “trials” and “bronchiectasis” or ”suppurative lung disease”, and “children”. In the

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Improving the Diagnosis and Treatment of Paediatric Bronchiectasis Through Research and Translation
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Bronchiectasis, particularly in children, is an increasingly recognised yet neglected chronic lung disorder affecting individuals in both low-to-middle and high-income countries. It has a high disease burden and there is substantial inequity within and between settings. Furthermore, compared with other chronic lung diseases, considerably fewer resources are available for children with bronchiectasis. The need to prevent bronchiectasis and to reduce its burden also synchronously aligns with its high prevalence and economic costs to health services and society.
Like many chronic lung diseases, bronchiectasis often originates early in childhood, highlighting the importance of reducing the disease burden in children. Concerted efforts are therefore needed to improve disease detection, clinical management and equity of care. Modifiable factors in the causal pathways of bronchiectasis, such as preventing severe and recurrent lower respiratory infections should be addressed, whilst also acknowledging the role played by social determinants of health.
Here, we highlight the importance of early recognition/detection and optimal management of bronchiectasis in children, and outline our research, which is attempting to address important clinical knowledge gaps discussed in a recent workshop. The research is grouped under three themes focussing upon primary prevention, improving diagnosis and disease characterisation, and providing better management. Our hope is that others in multiple settings will undertake additional studies in this neglected field to further improve the lives of people with bronchiectasis. We also provide a resource list with links to help inform consumers and healthcare professionals about bronchiectasis and its recognition and management.
Pulmonary immune profiling reveals common inflammatory endotypes of childhood wheeze and suppurative lung disease
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Suppurative lung disease and wheezing are common respiratory diseases of childhood, however, due to poor understanding of underlying pathobiology, there are limited treatment options and disease recurrence is common. We aimed to profile the pulmonary and systemic immune response in children with wheeze and chronic suppurative lung disease for identification of endotypes that can inform improved clinical management. We used clinical microbiology data, highly multiplexed flow cytometry and immunoassays to compare pulmonary [bronchoalveolar lavage (BAL)] and systemic immunity in children with lung disease and controls. Unsupervised analytical approaches were applied to BAL immune data to explore biological endotypes. We identified two endotypes that were analogous in both frequency and immune signature across both respiratory diseases. The hyper-inflammatory endotype had a 12-fold increase in neutrophil infiltration and upregulation of 14 soluble signatures associated with type 2 inflammation and cell recruitment to tissue. The non-inflammatory endotype was not significantly different from controls. We showed these endotypes are measurable in a clinical setting and can be defined by measuring only three immune factors in BAL. We identified hyper-inflammatory and non-inflammatory endotypes common across pediatric wheeze and chronic suppurative lung disease that, if validated in future studies, have the potential to inform clinical management.
A core outcome set for bronchiectasis in children and adolescents for use in clinical research: an international consensus study
2024, The Lancet Respiratory Medicine
Improving the treatment of non-cystic fibrosis bronchiectasis in children and adolescents requires high-quality research with outcomes that meet study objectives and are meaningful for patients and their parents and caregivers. In the absence of systematic reviews or agreement on the health outcomes that should be measured in paediatric bronchiectasis, we established an international, multidisciplinary panel of experts to develop a core outcome set (COS) that incorporates patient and parent perspectives. We undertook a systematic review from which a list of 21 outcomes was constructed; these outcomes were used to inform the development of separate surveys for ranking by parents and patients and by health-care professionals. 562 participants (201 parents and patients from 17 countries, 361 health-care professionals from 58 countries) completed the surveys. Following two consensus meetings, agreement was reached on a ten-item COS with five outcomes that were deemed to be essential: quality of life, symptoms, exacerbation frequency, non-scheduled health-care visits, and hospitalisations. Use of this international consensus-based COS will ensure that studies have consistent, patient-focused outcomes, facilitating research worldwide and, in turn, the development of evidence-based guidelines for improved clinical care and outcomes. Further research is needed to develop validated, accessible measurement instruments for several of the outcomes in this COS.
The Economic Burden of Bronchiectasis: A Systematic Review
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Bronchiectasis, a previously neglected condition, now has renewed research interest. There are a few systematic reviews that have reported on the economic and societal burden of bronchiectasis in adults, but none have reported on children. We undertook this systematic review to estimate the economic burden of bronchiectasis in children and adults.
What is the health care resource utilization and economic burden of bronchiectasis in adults and children?
We performed a systematic review identifying publications from Embase, PubMed, Web of Science, Cochrane (trials, reviews, and editorials), and EconLit about the economic burden and health care utilization in adults and children with bronchiectasis between January 1, 2001, and October 10, 2022. We used a narrative synthesis approach and estimated aggregate costs for several countries.
We identified 53 publications reporting on the economic burden and/or health care utilization of people with bronchiectasis. Total annual health care costs per adult patient ranged from 2021 $3,579 to $82,545 USD and were predominantly driven by hospitalization costs. Annual indirect costs including lost income because of illness (reported in only five studies) ranged from $1,311 to $2,898 USD. Total health care costs in children with bronchiectasis were $23,687 USD annually in the one study that estimated them. Additionally, one publication found that children with bronchiectasis missed 12 school days per year. We estimated aggregate annual health care costs for nine countries, ranging from $101.6 million per year in Singapore to $14.68 billion per year in the United States. We also estimated the aggregate cost of bronchiectasis in Australian children to be $17.77 million per year.
This review highlights the substantial economic burden of bronchiectasis for patients and health systems. To our knowledge, it is the first systematic review to include the costs for children with bronchiectasis and their families. Future research to examine the economic impact of bronchiectasis in children and economically disadvantaged communities, and to further understand the indirect burden of bronchiectasis on individuals and the community, is needed.
Phenotypic Features of Pediatric Bronchiectasis Exacerbations Associated With Symptom Resolution After 14 Days of Oral Antibiotic Treatment
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Respiratory exacerbations in children and adolescents with bronchiectasis are treated with antibiotics. However, antibiotics can have variable interindividual effects when treating exacerbations.
Can phenotypic features associated with symptom resolution after a 14-day course of oral antibiotics for a nonsevere exacerbation of bronchiectasis be identified?
Combining data from two multicenter randomized controlled trials, we identified 217 children with bronchiectasis assigned to at least 14 days of oral antibiotics to treat nonsevere (nonhospitalized) exacerbations. Univariable and then multivariable logistic regression were used to identify factors associated with symptom resolution within 14 days of commencing antibiotics. Identified associations were re-evaluated by mediation analysis.
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SeriesBronchiectasis in children: diagnosis and treatment

Summary

Introduction

Section snippets

Clinical diagnosis

Framework of pathogenesis of chronic suppurative lung disease and bronchiectasis

Biomarkers, phenotypes, endotypes, and traits

Management

Conclusion

Search strategy and selection criteria

Chest

Chest

Chest

J Pediatr

J Allergy Clin Immunol Pract

Chest

Chest

J Pediatr

Chest

Chest

Semin Fetal Neonatal Med

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Bronchiectasis in children: diagnosis and treatment