Noncystic Fibrosis Bronchiectasis: Evaluation of an Extensive Diagnostic Protocol in Determining Pediatric Lung Disease Etiology

Abstract

Introduction: Pediatric noncystic fibrosis (CF) bronchiectasis has a variety of causes. An early and accurate diagnosis may prevent disease progression and complications. Current diagnostics and yield regarding etiology are evaluated in a pediatric cohort at a tertiary referral center.

Methods: Available data, including high-resolution computed tomography (HRCT) characteristics, microbiological testing, and immunological screening of all children diagnosed with non-CF bronchiectasis between 2003 and 2017, were evaluated.

Results: In 91% of patients [n = 69; median age 9 (3–18 years)] etiology was established in the diagnostic process. Postinfection (29%) and immunodeficiency (29%) were most common, followed by congenital anomalies (10%), aspiration (7%), asthma (6%), and primary ciliary dyskinesia (1%). HRCT predominantly showed bilateral involvement in immunodeficient patients (85%) and those with idiopathic bronchiectasis (83%). Congenital malformations (71%) were associated with unilateral disease. Completion of the diagnostic process often led to a change of treatment as started after initial diagnosis.

Conclusion: Using a comprehensive diagnostic protocol, the etiology of pediatric non-CF bronchiectasis was established in more than 90% of patients. HRCT provides additional diagnostic information as it points to either a more systemic or a more localized etiology. Adequate diagnostics and data analysis allow treatment to be specifically adapted to prevent disease progression.

Introduction

Bronchiectasis in children without cystic fibrosis (CF) arises from recurrent infections and long-term inflammation of the lower respiratory tract (LRT) due to a stagnant clearance of mucus.¹ Lung function gradually declines as a result of the developing fibrosis. Finally, bronchiectasis can only be treated by drastic measures like a lobectomy in localized bronchiectasis or a lung transplantation.² An early diagnosis is usually based on high-resolution computed tomography (HRCT), which shows a characteristic pattern of bronchial dilatation and thickening of the bronchial wall.³

The incidence of pediatric non-CF bronchiectasis is unknown, but in Europe estimates vary between 0.2 and 2.3/100,000.^4,5 This indicates uncertainty about the actual incidence, possibly as a result of underreporting true genetic differences in etiology or different exposure risks.

Since a delay in diagnosis potentially leads to a worse outcome, it is important to diagnose non-CF bronchiectasis at the earliest possible stage and immediately start treatment.^6,7 In addition to airway clearance techniques and exercise, pharmacotherapeutic interventions and vaccinations are the cornerstones of treatment. Antibiotics and muco-active agents, as well as bronchodilators and (inhaled) corticosteroids in the case of concurrent asthma, are used to treat pediatric non-CF bronchiectasis symptomatically.⁸ Often used in combinations these drugs may effectively prevent progression.^6,9,10

In developing countries and socially disadvantaged populations of high-income countries, recurrent suboptimally treated primary LRT infections are the main cause of pediatric non-CF bronchiectasis.^5,7,11–13 However, in high-income countries immunodeficiencies rather than primary LRT infections account for the majority of cases.^5,7 In the latter case genetic variations, accountable for diseases such as primary ciliary dyskinesia (PCD), also play an important role. Nevertheless, despite the extensive array of diagnostic tools presently available, the etiology of a large proportion of cases is still unknown.^5,7 Therefore, it may be worthwhile to intensify the search for a wider range of primary lung diseases and immunological disorders with unknown causes and focus on possible underlying genetic factors, especially when a rapidly growing number of diagnostic tools becomes accessible for patient care. It is also important that the etiology of these diseases is defined more accurately, because this is generally the first step toward a more effective treatment.^7,14

There are no recent data on children with non-CF bronchiectasis in high-income countries. As our understanding of the disease improves and diagnostics become more extensive and precise, an accurate evaluation of cases, including the assessment of the diagnostic strategies that have been applied, is appropriate. The present study aims to fully map and evaluate all diagnostic data of a pediatric non-CF bronchiectasis cohort in a tertiary referral center.

Materials and Methods

Study population

The study population consisted of patients with non-CF bronchiectasis of the Emma Children's hospital at the Amsterdam University Medical Center (AUMC) in Amsterdam, The Netherlands. The research protocol was exempted from review by the medical ethics committee. Patient data were extracted from the medical files. The search consisted first of a review of all pulmonary HRCTs made in children ≤18 years of age between 2003 and 2017.

Medical files and radiology reports were examined on a case-by-case basis, having excluded patients known to suffer from CF or screened by pulmonary HRCT because of oncological disease. Swallow tests were only performed on indication (gastrointestinal regurgitation, frequent complaints about heartburn, regular burping, difficulties swallowing, or anamnestically suspected tracheoesophageal fistulation) and have not been part of the routine measures in our diagnostic protocol.

To avoid registration bias, ICD-10 codes were not used. Patients were included on the basis of the radiology report containing the word or diagnosis “bronchiectasis” but children with CF diagnosed by abnormal sweat test or genetic mutations after subsequent screening were excluded. Bronchiectasis on HRCTs was defined by bronchial wall thickening, bronchial dilatation, bronchial diameter exceeding the adjacent pulmonary arterial diameter (signet ring sign), or lack of normal bronchial tapering. The presence of bronchioles within 1 cm of the pleural surface was also considered bronchiectasis.¹⁵

Study design

Medical files were retrospectively reviewed using a standardized case report form. The following data were collected: patient demographics, age at HRCT diagnosis, diagnostic test results, previous treatment(s), and suspected or confirmed etiology of the bronchiectasis. In the case of inconclusiveness with respect to etiology, a second opinion by a panel of a pediatric pulmonologist, radiologist, and immunologist was sought. All HRCTs were reviewed by a pediatric radiologist with more than 5 years of experience, using the Bronchiectasis Radiologically Indexed CT Score (BRICS) to assess the severity of the bronchiectasis on HRCT.¹⁶ BRICS is a simple CT scoring system, derived from the more complex Bhalla score¹⁷ and modified Reiff score.¹⁸ It is based on the extent of bronchial dilation compared to the adjacent arterial vessel [absent = 0; mild = 1 (lumen just>diameter of adjacent vessel); moderate = 2 (lumen 2–3 times>diameter of adjacent vessel); severe = 3 (lumen >3 times diameter of adjacent vessel)] and number of bronchopulmonary segments with emphysema (absent = 0; 1–5 = 1; > 5 = 2). The score ranges from 0 to 5, with a higher score indicating increased disease severity (1 = mild disease, 2–3 = moderate disease, >3 = severe disease).

Our diagnostic protocol aims to systematically determine the etiology of the bronchiectasis and to standardize treatment. It comprises: (1) bacterial culture of sputum or cough swab to assess pathogen sensitivity and select specific antibiotic treatment; (2) spirometry if possible due to age, physical condition, and/or cooperativeness, in which case the highest value of forced expiratory volume in 1 s (FEV1) and its corresponding forced vital capacity (FVC) is registered (expressed as % of predicted age-based normal values); (3) an immunology workup, including total serum immunoglobulins, IgG subclasses, specific antibody responses to tetanus toxoid and capsular polysaccharides of Streptococcus pneumoniae upon immunization, lymphocyte subsets (typing of T-, B-, and NK cells and their subpopulations), and lymphocyte proliferation tests.^19–25 Tests for antinuclear antibodies (ANA/ENA), antineutrophil cytoplasmic autoantibodies, and rheumatoid factor are performed if there is an indication to consider the presence of rheumatic or systemic autoimmune diseases; (4) bronchoscopy and bronchoalveolar lavage (i.e., to exclude an aspirated foreign body if bronchiectasis is limited to 1 lobe) to obtain representative sputum for bacterial culture (and cytological examination in certain cases) and perform a biopsy for evaluation of pathology or start culturing mucosal cells for PCD diagnostics (if a nasal ciliary biopsy was not performed before bronchoscopy).

Intracutaneous testing with purified protein derivative (Mantoux test) to exclude tuberculosis (TB) is registered as well. In addition to HRCT, the abovementioned diagnostic tools are used in a flexible manner, depending on the clinical presentation of the patient. This approach is essentially similar to the diagnostic pathway recently described by Chang et al.⁷ If no underlying etiology can be identified on the basis of protocol test results, non-CF bronchiectasis is diagnosed as idiopathic. Postinfective causes were determined using corresponding evidence provided by history, location of infection as confirmed by radiology findings, and microbiological data.

Statistical analyses

Statistical analyses were performed using IBM SPSS Statistics for Windows, version 24.0 (IBM Corp., Armonk, NY). Continuous variables are presented as mean ± standard deviation for normally distributed variables and as median (range) for non-normally distributed variables. t-Test and one-way analysis of variance test were used for normally distributed measures. P values of ≤0.05 were considered significant.

Results

In total, 69 predominantly Caucasian patients were included for examination of their medical file, radiology reports, and follow-up (Fig. 1). Any syndromic background previously identified was absent unless clearly specified. Apart from the lack of information about proven allergy or smoking habits at home, also the economic status of the parents could not be evaluated from the patient files but may be of less relevance because differences in living conditions are relatively small and health care is widely available to all income groups in The Netherlands at full insurance coverage. The HRCT diagnosis was made at a median age of 9 years (3–18 years). At the time of the study evaluation their median age was 18 years (6–30 years). Of these patients 38 (55%) were male. The diagnostics performed according to the local protocol are presented in Table 1.

FIG. 1.

Patient selection. All pulmonary HRCTs made in children ≤18 years of age between 2003 and 2017 were assessed. Patients suffering from CF or screened by pulmonary HRCT because of oncological disease and/or treatment were excluded. If no follow-up was available patients were excluded. CF, cystic fibrosis; HRCT, high-resolution computed tomography.

Table 1.

Diagnostics in Noncystic Fibrosis Bronchiectasis

Diagnostics	Non-CF bronchiectasis (N = 69), n (%)
Pulmonary workup
Lung function at diagnosis	57 (83)
Bronchoscopy with bronchoalveolar lavagea	42 (61)
Ciliary function test	32 (46)
Primary microbiology workup
Bacterial culture of sputum at diagnosisa	51 (74)
Mantoux test	18 (26)
Immunology workup
Immunoglobulins	58 (84)
Vaccine responses	36 (52)
Lymphocyte subset typing	45 (65)

^aIn 61/69 (88%) patients a bacterial culture was obtained at diagnosis either by expectoration or by bronchoalveolar lavage

CF, cystic fibrosis.

In total, 42 (61%) patients underwent bronchoscopy. Microbiological cultures of the material obtained by bronchoalveolar lavage were successfully performed in 38 of these patients. On 61 (88%) patients sputum was obtained for culture—either by expectoration or by bronchoalveolar lavage. The most frequently isolated microorganism was noncapsulated Haemophilus influenzae in 27 (44.2%) of 61 patients followed by S. pneumoniae in 5 (8.2%) patients (Table 2). Mantoux testing was positive in 2 out of 18 (26%) patients tested. Bacterial culture of sputum of these 2 patients showed growth of Mycobacterium tuberculosis.

Table 2.

Diagnostic Results

Diagnostic results
Microbiology at diagnosis (N = 61)	n (%)
Haemophilus influenzae	27 (44.2)
Streptococcus Pneumoniae	5 (8.2)
Pseudomonas aeruginosa	3 (4.9)
Moraxella catarrhalis	3 (4.9)
Mycobacterium tuberculosis	2 (3.3)
Staphylococcus aureus	1 (1.6)
Other	3 (4.9)
Lung function at diagnosis %	Mean ± SD	Range
FEV1	76 ± 21	36–116
FVC	77 ± 20	33–108
Result of immunology workup	n
Primary immunodeficiency	15
CID (combined humoral and cellular)	10
Other	4
Unclassified	1
Secondary immunodeficiency	5
HIV related	2
Post-transplantation (liver, kidney, HSCT)	3

CID, combined immunodeficiency; FEV1, forced expiratory volume in 1 s; FVC, forced vital capacity; HSCT, hematopoietic stem cell transplantation; SD, standard deviation.

Lung function tests were performed at diagnosis in 57 (83%) patients as far as allowed by age and physical ability. The mean percentage of predicted FVC at diagnosis was 77 ± 20, and the mean FEV1 was 76 ± 21. Screening tests for immunoglobulins were performed in 58 (84%) patients. More extensive immunological diagnostic testing, such as in vivo vaccine responses and lymphocyte subset typing, was performed in 36 (52%) and 45 (65%) of the patients, respectively.

Ciliary biopsy during bronchoscopy or by nasal brush was performed in 32 (46%) patients of which only a single patient was positive.

The etiology of bronchiectasis was established in 63 (91%) patients. No cause was found in the remaining 6 (9%) patients. The most common etiologies found were “post-infection” (n = 20, 29%) and “immunodeficiency” (n = 20, 29%), either primary or secondary (Table 2), followed by “congenital anomalies” (n = 7, 10%), “aspiration” (n = 5, 7%), “asthma” (n = 4, 6%), and “PCD” (n = 1, 1%). Remaining etiologies were “autoinflammatory/autoimmune,” “extrinsic allergic alveolitis,” and a single case with a “carcinoid tumor” (Fig. 2). In 3 patients, aspiration-related bronchiectasis was caused by a neurological disorder. Patients with multiple causes were not found. A complete overview of immunodeficiencies is presented in Supplementary Table S1.

FIG. 2.

Etiology of non-CF bronchiectasis. Immunodeficiency includes primary and secondary immunodeficiencies. Aspiration includes chronic aspiration and foreign body aspiration. Other includes auto-inflammatory/immune disease, extrinsic allergic alveolitis, and carcinoid.

The distribution of bronchiectasis in our cohort was subsequently assessed and scored (Table 3). In the patient groups with the most common etiologies, bilateral involvement was predominant in patients with an immunodeficiency (85%), whereas in postinfectious cases there was as much bilateral as unilateral bronchiectasis (50%). Unilateral disease was mainly seen in patients with congenital malformations (71.4%). Single-lobe involvement was mainly observed in cases with congenital malformation and postinfection, whereas diffuse and multilobar disease was more commonly present in patients with an immunodeficiency, asthma, and an autoinflammatory/autoimmune disease, as well as those with idiopathic bronchiectasis. The exact distribution, including involvement of the specific lobes, is presented in Table 4.

Table 3.

Distribution of Bronchiectasis According to Primary HRCT, Presented by Etiology

Etiology	Bilateral, n (%)	Unilateral, n (%)	Diffuse	Multilobar	Unilobar
Immunodeficiencya	17 (85)	3 (15)	7	11	2
Postinfection	10 (50)	10 (50)	3	9	8
Congenital malformationb	2 (28.6)	5 (71.4)	1	3	3
Asthma	3 (75)	1 (25)	3	0	1
Aspiration	2 (40)c	3 (60)	2	2	1
Idiopathic	5 (83.3)	1 (17.7)	2	4	0
Autoinflammatory/autoimmune	4 (100)	0 (0)	3	1	0
PCD	0 (0)	1 (100)	0	0	1
Carcinoid	0 (0)	1 (100)	0	0	1
Extrinsic allergic alveolitis	1 (100)	0 (0)	1	0	0
Total	44 (63.8)	25 (36.2)	22	30	17

^aImmunodeficiency includes PIDs and SIDs.

^bCongenital malformation consists of tracheomalacia and/or bronchomalacia.

^cFrequently recurrent aspiration based on neurologic complications or muscular weakness due to mitochondrial disease and metabolic disorder (guanidinoacetate methyltransferase deficiency).

Diffuse, if ≥4 lobes involved; multilobar, 2 or 3 lobes involved; unilobar, 1 lobe involved; HRCT, high-resolution computed tomography; PCD, primary ciliary dyskinesia; PIDs, primary immunodeficiencies; SIDs, secondary immunodeficiencies.

Table 4.

Distribution of Bronchiectasis According to Primary HRCT, Presented by Etiology

Etiology	Diffuse	LLL	LUL	RLL	RML	RUL	Lingula	Perihilar
Immunodeficiencya	7	10		10	1		3
Postinfection	3	7	1	8	6	1	3
Congenital malformationb	1	2		2	2		1
Asthma			1	1				3
Aspirationc	2	1	1		2	1
Idiopathic	4	2	1	3	1		1
Autoinflammatory/autoimmune	4					1
PCD					1
Carcinoid			1
Extrinsic allergic alveolitis	1
Total	22	22	5	23	13	3	8	3

^aImmunodeficiency includes PIDs and SIDs.

^bCongenital malformation consists of tracheomalacia and/or bronchomalacia.

^cFrequently recurrent aspiration due to mitochondrial disease and metabolic disorder (guanidinoacetate methyltransferase deficiency).

Diffuse, if ≥4 lobes involved; LLL, left lower lobe; LUL, left upper lobe; RLL, right lower lobe; RML, right middle lobe; RUL, right upper lobe.

The average BRICS of all patients was 3.54 (0–5). Of the total group, 61% of patients scored “severe” and 39% “moderate.” There were no patients with a mild severity score (BRICS = 1) (Fig. 3). Severe disease was mainly observed in patients with an immunodeficiency (90%) and idiopathic bronchiectasis (83%). In postinfectious cases and patients with a congenital malformation, there was as much moderate as severe disease. Moderate disease was present in patients with asthma (100%). There was no significant correlation between the BRICS and FEV1 of patients.

FIG. 3.

Bronchiectasis radiologically indexed CT score presented by etiology. Sixty-one percent of the patients scored “severe” and 39% “moderate.” There were no patients with a mild severity score. Severe disease was mainly observed in patients with an immunodeficiency (90%) and idiopathic bronchiectasis (83%). In postinfectious cases and patients with a congenital malformation there was as much moderate as severe disease. Moderate disease was present in patients with asthma (100%).

Nonetheless, apart from being distinct for their BRICS pattern, a difference between the 2 major categories was indicated by pulmonary function tests. The lowest FVC and FEV1 values were found in patients with an underlying immunodeficiency as final diagnosis with a mean FVC of 69 ± 18 and a mean FEV1 of 68 ± 22 (Table 2). This FEV1 value was significantly lower than in the group of patients with a postinfectious cause with a mean FEV1 of 87 ± 5 (P = 0.003).

With respect to outcome, in 15 (22%) patients, in whom bronchiectasis was diagnosed first and subsequent diagnostics led to an underlying cause of the non-CF bronchiectasis, knowledge of the etiology led to a change in management. For instance, patients with immunodeficiencies on prophylactic antibiotics started with immunoglobulin substitution (n = 3) or—if already receiving IgG infusions—were considered for hematopoietic stem cell transplantation (HSCT; n = 3). One patient with PCD was referred to a PCD tertiary referral center, and patients with chronic aspiration were given intensive antiacid treatment. In 2 cases a vascular sling causing tracheobronchomalacia was surgically removed. In addition, an aspirated foreign body and a carcinoid tumor were removed by rigid bronchoscopy.

Discussion

In the present study the medical files of 69 patients diagnosed with non-CF bronchiectasis were evaluated. In 91% of patients an etiology was identified. The number of patients where no underlying cause could be determined is much less than that observed in other studies in comparable populations reporting percentages of idiopathic non-CF bronchiectasis between 26% and 55%.^4,14,26,27 Most likely, this results from rigorously using the extensive set of diagnostic tools included in the protocol, which allows identification of previously unknown etiologies, including a variety of immunodeficiencies. This approach resembles that recently described by Chang et al.⁷ As a result of the growing availability of additional in-depth testing methods, including genome-wide genetics, it is well possible that in the near future the etiology of the remaining cases of idiopathic non-CF bronchiectasis will also be established.

The etiologies most commonly found were “immunodeficiency” (29%) and “post-infection” in which an immunodeficiency had been excluded (29%). As in other studies the group of immunodeficient diseases is very heterogeneous and varies from mild to extremely severe. The proportion of bronchiectasis caused by infection is decreasing as studies from the 1950s and 1960s showed percentages of 60%–70%.^28,29 This may be explained by the availability of newer antibiotics and the increasing knowledge and tools available for immunological diagnoses. However, the lower incidence of postinfection bronchiectasis may also be due to selection bias in certain studies by preferential inclusion of patients with TB or childhood infections.¹⁴ TB is not a common disease in the Netherlands (about 800 new cases in total in over 17 million residents in 2018³⁰).

In the greater Amsterdam area it is mostly observed in immigrant children. Only a small number of patients appeared to be from Asian or North African descent. The low prevalence of PCD in the present study compared to other studies can be explained by referral bias, as suspected PCD patients are directly referred to a tertiary referral center in the same region with specific PCD expertise. Moreover, as there is little consanguinity in the Netherlands, the number of PCD cases in our Dutch cohort of patients of non-CF bronchiectasis will be for that reason much lower than the relatively high numbers found in children in other studies.^12,14,27,31

In only 9% of patients the etiology of non-CF bronchiectasis was not clarified. This implies that the local protocol used to systematically determine the etiology of bronchiectasis is thorough, even considering that not all patients underwent the whole spectrum of diagnostic tools. Incomplete diagnostic workup partially results from the order in which tests were performed. For example, a patient diagnosed with an evident tracheomalacia or bronchomalacia upon bronchoscopy, explaining the presence of localized bronchiectasis, is unlikely to undergo extensive immunological testing. Moreover, 8 patients diagnosed with a specific immunodeficiency were not further examined by means of, for example, ciliary function tests or bronchoscopy unless pulmonary cultures were required.

Identifying the etiology is of great importance to improve prognosis since it often leads to a change in management resulting in a more appropriate treatment, which may prevent progression of airway damage. It was previously demonstrated by Li et al.¹⁴ that change in management following etiological workup occurred in 56% of patients. However, in this cohort this percentage was considerably lower (22%), possibly as a result of more adequate preventive measures resembling standardized care introduced after diagnostic workup. The current era of rapidly developing diagnostic tools should make it possible to search more intensively for now unknown causes of bronchiectasis and focus on underlying genetic factors.

According to a recent review which included 860 children from predominantly high-income countries, the pathogen most frequently isolated from sputum cultures was H. influenzae (40%), followed by S. pneumoniae (20%), Moraxella catarrhalis (8.5%), Pseudomonas aeruginosa (7.9%), and Staphylococcus aureus (7.6%).³² Similar distributions of bacterial strains were found in our study. The first 3 pathogens form the basis of empiric antimicrobial therapy for exacerbations as they are most commonly found in children with non-CF bronchiectasis.⁹ Since delayed treatment is associated with a further decline of lung function, it is important to start specific treatment as soon as possible.⁹ This also highlights the need to routinely perform a bacterial culture of sputum to verify the adequacy of antibiotic coverage.

Systemic etiologies, such as immunodeficiencies, appeared to have a more diffuse and multilobar distribution of bronchiectasis, whereas single-lobe involvement was mainly observed in localized causes such as “congenital malformations” and “post-infection.” Although there is no conclusive distribution pattern linked to one of the common etiologies,^14,18,33 our data suggest that in multilobar or more diffuse bronchiectasis a systemic disease is the underlying etiology. In contrast, in unilobar bronchiectasis, a more localized cause of non-CF bronchiectasis is implied. The idiopathic cases had a diffuse or multilobar involvement that points to a more systemic etiology. Thus, in addition to being a means to diagnose bronchiectasis, HRCT also provides a possible clue for additional diagnostic testing taking age, risk of microbial exposure, and also the familial and genetic background into account.

In line with the distribution of bronchiectasis, severe disease according to the severity score by BRICS was predominantly present in patients with an immunodeficiency. This category also had the highest percentage of bilateral involvement. As the consequence of being a tertiary referral center there were no patients with mild disease. The BRICS validation study was performed in adult patients and only those with postinfectious or idiopathic bronchiectasis. Patients with immunodeficiencies and other etiologies of bronchiectasis were excluded from this study.¹⁶

The limited differentiating capacity of BRICS is possibly also related to the fact that the morphology of bronchiectasis in children and adults differs,¹⁰ indicating that the use of this evaluation method has limited added value in children. In contrast to the original study,¹⁶ we found no significant correlation between the FEV1 and disease severity. This relationship was also not observed when the analysis was limited to patients with postinfection and idiopathic bronchiectasis as in the original BRICS validation study (data not shown). These mixed results may be due to the decrease of FEV1 with increasing duration of bronchiectasis and frequency of exacerbation. However, with respect to a correlation between HRCT data and FEV1, mixed results have been obtained before, both in children and adults with various non-CF etiologies.^27,34–38

The strength of our study is the consistent use of a comprehensive diagnostic program over a longer period of time (10 years). There are also some limitations. First, BRICS evaluation has not been validated for children with non-CF bronchiectasis. However, in the absence of a scoring system for children, BRICS was considered the most suitable alternative as it is a simplified easy-to-score system. Second, the present study only provides cross-sectional retrospective data. Therefore, it is not possible to comment on the effectiveness of interventions like pharmacotherapeutic treatment and progression, which is the subject of other studies.

Conclusion

In summary, using a comprehensive diagnostic protocol in more than 90% of the cases in a high-income country, non-CF bronchiectasis etiologies can be identified. This enables treatment to be adapted to the specific needs of the patients, which is likely to prevent progression of airway damage at young age.^6,9,10 Lung distribution of bronchiectasis as diagnosed by HRCT provides additional information as it points to either a more systemic or a more local etiology. To date there are no prospective studies on the course of non-CF bronchiectasis in children. Future research should focus on evaluating the effect of treatment on progression by collecting standardized follow-up data.

Author Disclosure Statement

No competing financial interests exist.

Funding Information

No funding was received for this article.

Supplementary Material

Supplementary Table S1