Bronchiectasis in children: Pathophysiology and causes

INTRODUCTION — Bronchiectasis in children is defined as the presence of abnormal bronchial dilatation on computed tomography (CT) scans, in combination with a clinical syndrome of recurrent or persistent wet/productive cough, airway infection, and/or inflammation infections [1,2]. It is the end result of a variety of pathophysiologic processes that involve chronic or recurrent infection and airway obstruction and/or impaired mucociliary clearance, resulting in a vicious cycle that causes progressive damage to the bronchial walls.

In resource-abundant/high-income settings, cystic fibrosis (CF) is the most common condition leading to bronchiectasis. The evaluation and management of CF-related bronchiectasis is discussed in detail in separate topic reviews. (See "Cystic fibrosis: Clinical manifestations of pulmonary disease" and "Cystic fibrosis: Overview of the treatment of lung disease" and "Cystic fibrosis: Management of advanced lung disease".)

The pathogenesis and causes of bronchiectasis in children are outlined below. The evaluation and treatment of bronchiectasis in children without CF are discussed separately. (See "Bronchiectasis in children: Clinical manifestations and evaluation" and "Bronchiectasis in children without cystic fibrosis: Management".)

EPIDEMIOLOGY — Bronchiectasis was once considered rare in children but is increasingly recognized over the last two decades, likely due to increasing awareness of the condition and availability of sensitive diagnostic methods [3]. In particular, multidetector high-resolution CT (HRCT) is now widely available and can detect milder disease compared with less sensitive forms of radiography (eg, HRCT alone or plain chest radiographs) [4,5]. In addition, case identification is enhanced by using pediatric criteria for radiographic diagnosis compared with adult criteria [3,6,7]. The importance of this chronic disease and its burden in both adults and children are now recognized [8].

The incidence of bronchiectasis in children is highly variable, ranging from 0.2 to 735 per 100,000 children annually, based on extrapolation of published data [9]. Bronchiectasis affects children from low-, middle-, and high-income countries [9]. For example, reported incidence of bronchiectasis in children aged 0 to 14 years old ranges from 0.2 per 100,000 child-years in England to 3.7 per 100,000 child-years in New Zealand [9-11]. In a study from the United States, bronchiectasis unrelated to cystic fibrosis (CF) was diagnosed in 4.2 per 100,000 young adults [12].

The prevalence of bronchiectasis is likely higher than that reported in populations with limited resources and high frequency of respiratory infections [9,13-15]. In children, the highest published prevalence of bronchiectasis is from several indigenous populations, including natives of Polynesia, Alaska, Australia, and New Zealand, where it is as high as 15 per 1000 children [13,16,17]. The incidence of severe bronchiectasis (based on hospitalization) among children in New Zealand was 11.8 per 100,000, with the highest rates among the Māori and Pacific people [18]. The relatively high rates of bronchiectasis in these populations have been attributed to environmental conditions that are associated with recurrent respiratory infections during childhood, such as air pollution (indoor and outdoor), overcrowding, poor hygiene, and limited access to health care. In some cases, a predisposition to bronchiectasis might be related to heritable defects in immunity or pulmonary clearance [16,19,20]. In other populations, a high prevalence of bronchiectasis is due to endemic diseases such as tuberculosis [14]. Tuberculosis remains prevalent in many low- and middle-income countries but is rare in high-income countries [9].

Mortality trends due to bronchiectasis have changed with time and depend upon the availability of optimal clinical care [21]. In New Zealand, a 2011 report described fatal outcomes in 6 percent of children with bronchiectasis managed in a tertiary center [22], while a 2020 report described no deaths in children under 15 years of age [18]. Similarly, in Australia and the United States, pediatric deaths related to bronchiectasis are now rare [23,24].

PATHOPHYSIOLOGY

●Pathogenesis – Bronchiectasis is the result of the interplay between various factors:

•Host factors – Patient's age, swallowing and pulmonary function, immune function, genetics and epigenetics

•Environmental factors – Exposure to inhaled or aspirated pathogens and environmental pollutants

•Local pulmonary factors – Airflow limitation or obstruction [25]

•Infection – With related inflammation, neutrophil infiltration, and tissue destruction

•Abnormal mucous composition and impaired clearance [26-28]

The relative contributions of these factors vary. Factors that promote infection, especially environmental exposures or airway obstruction, are central to many cases of bronchiectasis in children. In some cases, primary immunodeficiency or subtle immune dysregulation (eg, impaired immune response to nontypeable Haemophilus influenzae) play a role [29-31]. These processes tend to result in a vicious cycle, in which chronic or recurrent lower airway infection causes inflammation, leading to impaired mucociliary clearance, which, in turn, promotes bacterial colonization and infection, causing progressive damage to the lower airway structure and worsening bronchiectasis [32]. An important example in children is recurrent protracted bacterial bronchitis (PBB), in which chronic lower airway infection can progress to bronchiectasis, which is initially reversible but eventually becomes irreversible unless the cycle is interrupted by appropriate antibiotic treatment and airway clearance therapies (figure 1) [33,34]. (See "Causes of chronic cough in children", section on 'Chronic endobronchial suppurative disease'.)

Molecular mechanisms that contribute to airway damage in bronchiectasis are discussed in a separate topic review. (See "Clinical manifestations and diagnosis of bronchiectasis in adults", section on 'Pathophysiology'.)

●Histopathology – Key histopathologic features in bronchiectasis are dilation and inflammation of the bronchial wall, particularly in the peripheral airways. Early changes include bronchial wall edema and destruction of elastin, which eventually leads to destruction of nearby muscle and cartilage and progressive bronchial dilation [35]. Biopsies of bronchial mucosa show tissue neutrophilia with increased interleukin 8 expression, mononuclear cell infiltrate (composed mainly of CD4+ T cells and CD68+ macrophages), mucous gland hypertrophy, and increased airway smooth muscle mass [36,37].

●Gross appearance – The gross features of bronchiectasis in children are often classified according to the classic Reid classification used for adults [38], based on the appearance on imaging (figure 2):

•Cylindrical – Smooth tubular dilation of the bronchi

•Varicose (or fusiform) – Bronchi are dilated with multiple indentations (narrowed segments)

•Cystic (or saccular) – Dilated bronchi terminate in blind-ending sacs

High-resolution CT (HRCT) scoring systems utilize cylindrical and cystic changes as markers of disease severity [38]. In children in high-income countries where there is good access to imaging, cylindrical bronchiectasis is most common [39]. Several studies suggest that cylindrical bronchiectasis may be reversible if the underlying cause is successfully treated, while later stages of bronchiectasis may be irreversible but can still improve with optimal treatment [40,41]. (See "Bronchiectasis in children: Clinical manifestations and evaluation", section on 'Imaging'.)

CAUSES OF BRONCHIECTASIS IN CHILDREN

Overview — The main causes of bronchiectasis in children are listed in the table (table 1). These are similar to the causes of bronchiectasis in adults but with a higher proportion of congenital immune defects or structural anomalies. Identifying specific treatable causes of bronchiectasis can delay progression or even reverse bronchiectasis in some cases [7,42-44]. In a majority of adults with bronchiectasis, the disease process began during childhood but was not recognized until much later in life [45-47]. Adults with childhood onset of symptoms have more severe bronchiectasis and poorer outcomes compared with those with adult-onset symptoms.

In a literature review that included almost 1000 children with bronchiectasis, 63 percent had an identified predisposing condition (including 19 percent with protracted bacterial bronchiectasis or other infections) [48]. However, the prevalence and nature of underlying conditions vary depending on the population studied and intensity of evaluation [9,49,50]. Accordingly, infectious causes such as tuberculosis, pertussis, and measles [13,51] are likely to predominate where these conditions are still prevalent, whereas causes such as oropharyngeal aspiration (with underlying neuromuscular or swallowing disorders), allergic bronchopulmonary aspergillosis (ABPA), and immunodeficiency are more likely to be identified in resource-abundant settings where intensive diagnostic methods are available and utilized [42,44,52,53]. Registry data from Australia report that infective/idiopathic bronchiectasis is, by far, the most common cause of bronchiectasis (84 percent), followed by immunodeficiency (4 percent), recurrent small-volume aspiration (4 percent), and primary ciliary dyskinesia (PCD; 3 percent); foreign body aspiration accounted for only 1 percent of cases in this cohort [39].

Bronchiectasis is sometimes classified by its anatomic distribution (generalized versus focal/segmental). Generalized bronchiectasis is typically seen in cases with an underlying systemic disease or condition, whereas focal bronchiectasis is usually the end result of a localized disease process such as bronchial obstruction (table 2). This anatomic classification can help to target the evaluation and investigations but is not a reliable predictor of the underlying diagnosis. (See "Bronchiectasis in children: Clinical manifestations and evaluation".)

The discussion below outlines key causes of bronchiectasis in children, grouped by primary mechanism.

Postinfectious conditions — In socially disadvantaged populations or in resource-limited settings, chronic or untreated respiratory infections are a common cause of bronchiectasis in children [54,55]. By contrast, in resource-abundant settings, infection is not as common a cause of bronchiectasis unless there is an underlying anatomic or immunologic defect. The key causes are listed below.

Protracted bacterial bronchitis — Protracted bacterial bronchitis (PBB) is increasingly recognized as a contributor to chronic lung disease in young children worldwide, including certain indigenous populations in Australia, New Zealand, and Alaska [56]. It is characterized by chronic wet cough and bronchial infection with common respiratory pathogens. Identification and treatment of PBB is important because it may be a precursor to chronic suppurative lung disease, including bronchiectasis (figure 1). Two prospective longitudinal cohort studies described a link between PBB and bronchiectasis in young children, especially those with recurrent PBB (>3 episodes year) and H. influenzae infection in lower airway cultures [57,58]. (See "Causes of chronic cough in children", section on 'Protracted bacterial bronchitis'.)

Specific pathogens — Specific pathogens that have been associated with bronchiectasis during childhood include:

●Pertussis and measles – Childhood infections with pertussis and measles have been associated with the development of bronchiectasis [59,60]. These childhood infections are uncommon since the advent of routine vaccinations but occasionally occur in unvaccinated children. In a series of 23 children from Italy with bronchiectasis, six cases (26 percent) were triggered by measles or pertussis, all in unvaccinated children [61]. The initial infection occurred at a mean age of 3.6 years and was followed by recurrent pneumonias, ultimately leading to bronchiectasis. (See "Measles: Clinical manifestations, diagnosis, treatment, and prevention", section on 'Complications' and "Pertussis infection in infants and children: Clinical features and diagnosis".)

●Adenovirus – Adenovirus infection in early life has been associated with bronchiectasis. A retrospective study of 193 Canadian children admitted to a hospital with adenovirus infection identified eight cases of bronchiectasis in long-term follow-up [62]. Adenovirus in early infancy has been associated with the development of Swyer-James syndrome (described below). In the bronchoalveolar lavage of children with bronchiectasis and PBB, human adenovirus C was the most common strain identified [63].

●Mycoplasma – Mycoplasma pneumonia usually has a benign course. However, in a series of 38 children hospitalized with mycoplasma pneumonia, eight were found to have bronchiectasis when evaluated with high-resolution CT (HRCT) scan in long-term follow-up [64]. A separate case series described 17 children who developed bronchiolitis obliterans and central bronchiectasis (ie, bronchiectasis involving the large airways) diagnosed between two and eight months after mycoplasma pneumonia [65]. (See "Mycoplasma pneumoniae infection in children".)

●Mycobacteria – Tuberculosis remains an important cause of bronchiectasis in children from endemic countries and in children with human immunodeficiency virus (HIV) infection [13,66,67]. The mechanisms include hilar adenopathy (causing obstructive bronchiectasis) and parenchymal disease and fibrosis (causing traction bronchiectasis) [66,68]. (See "Tuberculosis disease in children: Epidemiology, clinical manifestations, and diagnosis" and "Pulmonary tuberculosis: Clinical manifestations and complications", section on 'Bronchiectasis'.)

Mycobacterium avium-intracellulare complex, an opportunistic infection usually associated with immunodeficiencies or cystic fibrosis (CF), results in lung pathology including adenopathy, cavitation, and bronchiectasis [69]. (See "Mycobacterium avium complex (MAC) infections in persons with HIV".)

Other — Other patterns of postinfectious bronchiectasis include:

●Bacterial pneumonia – Bacterial pneumonia occasionally leads to bronchiectasis, particularly if it is recurrent or associated with an underlying anatomic or immune defect. A case control study in First Nations children in Australia found a strong association between pneumonia requiring hospitalization and bronchiectasis (odds ratio [OR] 15.2, 95% CI 4.4-52.7) [70].

●Postinfectious bronchiolitis obliterans (PIBO) – Bronchiolitis obliterans describes a pattern of histologic abnormalities affecting the small airways, characterized by large-airway bronchiectasis and fibroproliferative thickening of the bronchiolar walls that narrows the bronchiolar lumen and may progress to the complete obliteration of bronchioles. In children, the most common cause is postinfection, which has been particularly described after adenovirus and, less commonly, with mycoplasma pneumonia [71-73]. (See "Classification of diffuse lung disease (interstitial lung disease) in infants and children", section on 'Bronchiolitis obliterans' and "Overview of bronchiolar disorders in adults", section on 'Definitions'.)

Bronchiolitis obliterans also can be a complication after transplantation. (See 'Systemic autoimmune or inflammatory disorders' below.)

●Swyer-James syndrome – Swyer-James syndrome, (also known as unilateral hyperlucent lung) is a subset of PIBO and characterized by decreased pulmonary vascularity and hyperinflation that may be confined to one lung or one lobe, with or without bronchiectasis. It was initially thought to be a congenital anomaly but is now recognized as a postinfectious form of bronchiolitis obliterans that can be caused by a variety of infections occurring during infancy or childhood, including adenovirus and measles. (See "Congenital lobar emphysema", section on 'Differential diagnosis'.)

Bronchial narrowing or obstruction

Congenital abnormalities — Causes of congenital airway or bronchial obstruction include:

●Congenital airway malacia (tracheomalacia and bronchomalacia) – Tracheomalacia and bronchomalacia can be caused by primary defects in the airway wall or may be secondary to external compression by another structure, such as a vascular ring/sling or pulmonary artery dilatation. If the obstruction is severe, it can lead to recurrent infections and bronchiectasis. A case-control study confirmed an association of tracheomalacia with bronchiectasis; the adjusted OR was 13.2 (95% CI 3.2-55) when tracheomalacia was defined by bronchoscopy and 24.4 (95% CI 3.4 to infinity) when European Respiratory Society criteria were used [74]. (See "Congenital anomalies of the intrathoracic airways and tracheoesophageal fistula", section on 'Bronchomalacia' and "Congenital anomalies of the intrathoracic airways and tracheoesophageal fistula", section on 'Tracheomalacia'.)

●Other congenital anomalies

•Tracheal or bronchial stenosis (see "Congenital anomalies of the intrathoracic airways and tracheoesophageal fistula")

•Bronchogenic cyst (see "Congenital anomalies of the intrathoracic airways and tracheoesophageal fistula", section on 'Bronchogenic cyst')

•Tracheal bronchus (ectopic bronchus) (see "Congenital anomalies of the intrathoracic airways and tracheoesophageal fistula", section on 'Tracheal bronchus')

•Bronchopulmonary sequestration (intralobar type) (see "Bronchopulmonary sequestration")

•Congenital pulmonary airway malformation, formerly known as congenital cystic adenomatoid malformation (see "Congenital pulmonary airway malformation")

•Congenital lobar emphysema (see "Congenital lobar emphysema")

Foreign body aspiration — The most common cause of focal bronchiectasis in previously healthy children is endobronchial obstruction due to foreign body aspiration [75]. Foreign body aspiration is commonly seen in infants and younger children and often involves food items that are not radiopaque, such as peanuts. It typically presents with sudden onset of choking or cough. If the aspiration event is not recognized, the child may present with chronic wet cough weeks or even months after the aspiration event, so the caregivers may not recall a history of choking. If the foreign body is not identified and removed, postobstructive pneumonia and bronchiectasis may develop, sometimes complicated by pneumothorax or hemoptysis [75-77]. (See "Airway foreign bodies in children".)

Endobronchial obstruction — A variety of other disorders tends to cause mucus plugging, including postoperative atelectasis and asthma. If the plugging is prolonged or recurrent, it can lead to bronchiectasis. Disorders mediated by mucoid impaction are:

●Middle lobe syndrome – Middle lobe syndrome is a pattern of chronic or recurrent atelectasis that usually affects the right, middle, or left lingular lobes of the lung. It is sometimes seen in children with asthma who recover from an acute exacerbation with improved respiratory symptoms, but the atelectatic lobe does not reexpand, because of mucous impaction and airway obstruction. This leads to repeated episodes of obstruction, infection, and inflammation that may eventually lead to bronchiectasis in that area [78-80]. (See "Radiologic patterns of lobar atelectasis", section on 'Right middle lobe' and "Atelectasis in children".)

●ABPA – This is a pulmonary hypersensitivity reaction to Aspergillus fumigatus that causes intense chronic airway inflammation. Repeated episodes of inflammation, mucoid impaction, and bronchial obstruction can lead to central bronchiectasis, fibrosis, and respiratory compromise. This disorder typically occurs in patients with asthma or CF [81]. (See "Clinical manifestations and diagnosis of allergic bronchopulmonary aspergillosis".)

●Bronchocentric granulomatosis – This is a destructive, granulomatous lesion of the bronchi and bronchioles that is generally believed to represent a nonspecific response to a variety of types of airway injury. Approximately one-half of all cases are associated with ABPA. (See "Bronchocentric granulomatosis".)

Very rarely, endobronchial tumors in children can lead to obstructive bronchiectasis.

External airway compression — Pulmonary granulomatous diseases, particularly tuberculosis or histoplasmosis, can cause bronchiectasis, in part due to extrinsic compression of a bronchus by enlarged lymph nodes, as well as other mechanisms. (See 'Postinfectious conditions' above.)

Severe scoliosis can rarely lead to bronchiectasis due to external compression of the airways [82]. Rare causes of external bronchial compression include lung masses or vascular compression. (See "Clinical manifestations and diagnosis of bronchiectasis in adults".)

Immunodeficiencies

Hereditary — Primary immunodeficiency disorders predispose the host to recurrent sinopulmonary infections and to the development of bronchiectasis. Early identification of these immunodeficiencies can prevent progression or even reverse the bronchiectasis [44]. The type of pulmonary infection varies depending on the nature of the immunodeficiency. (See "Approach to the child with recurrent infections".)

Conditions causing primary immunodeficiency are discussed elsewhere:

●Immunoglobulin (Ig) deficiencies

•X-linked agammaglobulinemia (MIM #300755) (see "Agammaglobulinemia")

•IgG subclass deficiencies (see "Primary humoral immunodeficiencies: An overview")

•Common variable immunodeficiency (see "Common variable immunodeficiency in children")

•Selective IgA deficiency (bronchiectasis is uncommon but reported [83,84]) (see "Selective IgA deficiency: Clinical manifestations, pathophysiology, and diagnosis", section on 'Sinopulmonary')

●Combined immunodeficiencies

•Severe combined immunodeficiency (MIM #300400 and others) (see "Severe combined immunodeficiency (SCID): An overview")

•Other combined immunodeficiencies (see "Combined immunodeficiencies: An overview")

•DiGeorge syndrome (MIM #188400) or velocardiofacial syndrome (MIM #192430) (see "DiGeorge (22q11.2 deletion) syndrome: Clinical features and diagnosis")

•Ataxia-telangiectasia (MIM #208900) (see "Ataxia-telangiectasia")

•Major histocompatibility complex deficiencies, which cause bare lymphocyte syndrome (MIM #604571) (see "CD3/T cell receptor complex disorders causing immunodeficiency", section on 'MHC (HLA) class I deficiency')

●Leukocyte dysfunction – Chronic granulomatous disease and other disorders causing leukocyte dysfunction (see "Primary disorders of phagocyte number and/or function: An overview")

●Complement deficiencies (see "Inherited disorders of the complement system")

Acquired — Acquired immunodeficiencies can lead to bronchiectasis through the same cycle of recurrent infection, inflammation, and progressive damage to the lower airway structure. Examples include HIV [85,86] and any pharmacologic immunosuppression, including after solid organ transplant [87].

Impaired mucociliary clearance — In the following disorders, impaired mucociliary clearance is a primary mechanism that predisposes to recurrent pulmonary infection and leads to bronchiectasis. Because these disorders usually affect the entire airway, the infection and bronchiectasis tend to be diffusely distributed.

●CF – CF is the most common genetic cause of bronchiectasis in children and adults in resource-abundant countries. Mutations in the CFTR gene (CF transmembrane conductance regulator) result in abnormal ion and water transport across the respiratory epithelial cell, resulting in thick, desiccated mucus and causing chronic airway obstruction, infection, and an excessive host inflammatory response. (See "Cystic fibrosis: Clinical manifestations of pulmonary disease" and "Cystic fibrosis: Overview of the treatment of lung disease" and "Cystic fibrosis: Management of advanced lung disease".)

Whether the carrier state for CF predisposes to developing bronchiectasis is uncertain, but some data have suggested that there may be an association. In a study of more than 100,000 Danish individuals, among which 3 percent were carriers for heterozygous for the CFTR F508del mutation, carriers had a hazard ratio of 1.88 (95% CI 1.03–3.45) for bronchiectasis [88]. Similarly, in a case-control study, carriers of a CFTR mutation had a fivefold increase in risk of developing bronchiectasis (OR 5.62, 95% CI 3.85-8.21) [89].

●PCD – PCD (MIM # 244400 and others) is a disorder of ciliary function due to ultrastructural defects or functional abnormality of motile cilia, leading to impaired mucociliary clearance in the airway. PCD can be associated with male infertility and organ laterality defects; the combination of PCD and situs inversus is known as Kartagener syndrome. Children typically present with recurrent sinusitis, complex otitis media, and recurrent pneumonia. Bronchiectasis ultimately develops in most of these patients. (See "Primary ciliary dyskinesia (immotile-cilia syndrome)".)

●Young syndrome – Young syndrome (MIM 279000) is characterized by obstructive azoospermia and sinopulmonary infections but no evidence of CF, ciliary dysfunction, or structural defect [90]. Mucociliary clearance is impaired, and bronchiectasis has been reported. This diagnosis is now extremely rare, perhaps because some cases attributed to Young syndrome in the past are now diagnosed as a variant of CF or PCD. (See "Clinical manifestations and diagnosis of bronchiectasis in adults", section on 'Young syndrome' and "Cystic fibrosis: Clinical manifestations and diagnosis", section on 'CFTR-related disorder'.)

In addition, airway inflammation (due to infection or other disorder) interferes with mucociliary function and contributes to the pathogenesis of bronchiectasis. (See 'Pathophysiology' above.)

Miscellaneous

Aspiration — Aspiration during swallowing (known as primary aspiration) is seen in congenital conditions like laryngeal cleft [91], tracheoesophageal fistula, neuromuscular conditions associated with dysphagia [92,93], and some syndromes with swallowing dysfunction [94].

Aspiration of refluxed gastric contents (known as secondary aspiration) can be seen in patients with gastroesophageal reflux disease (GERD). In a large study of neurologically normal children, those with GERD had a modestly increased risk for bronchiectasis (OR 2.3, 95% CI 1.7-3.2) [95]. (See "Aspiration due to swallowing dysfunction in children" and "Clinical manifestations and diagnosis of gastroesophageal reflux disease in children and adolescents", section on 'Recurrent pneumonia'.)

Ineffective cough/mucus clearance — Muscular dystrophies and other diseases with neuromuscular weakness are often associated with impaired mucus clearance due to ineffective cough, chest wall deformities, and swallowing dysfunction (causing aspiration), all of which can lead to recurrent pulmonary infection and bronchiectasis. (See "Duchenne and Becker muscular dystrophy: Clinical features and diagnosis" and "Myotonic dystrophy: Etiology, clinical features, and diagnosis".)

Systemic autoimmune or inflammatory disorders

●Autoimmune diseases – Bronchiectasis has been associated with multiple rheumatic diseases including rheumatoid arthritis, Sjögren's disease, systemic lupus erythematosus, and scleroderma. For example, bronchiectasis is seen on HRCT in 15 to 20 percent of adult patients with rheumatoid arthritis or systemic sclerosis [96,97]. Bronchiectasis is a rare manifestation of these disorders in children and adolescents. The bronchiectasis associated with these disorders may be caused by recurrent aspiration and/or traction in patients with interstitial lung disease. (See "Childhood-onset systemic lupus erythematosus (SLE): Clinical manifestations and diagnosis", section on 'Pulmonary' and "Pulmonary manifestations of systemic lupus erythematosus in adults" and "Clinical manifestations of Sjögren’s disease: Extraglandular disease".)

●Sarcoidosis – Sarcoidosis is a multisystem granulomatous disorder of unknown etiology that is typically first diagnosed during adolescence or young adulthood. The disease often causes granulomatous inflammation of the bronchial mucosa and peribronchial, perivascular, and subpleural areas of the lung, which can lead to traction bronchiectasis [98,99]. (See "Clinical manifestations and diagnosis of sarcoidosis".)

●Inflammatory bowel disease (IBD) – The extraintestinal manifestations of IBD occasionally include pulmonary disorders, including chronic bronchitis, bronchiectasis, interstitial lung disease including organizing pneumonia (formerly termed bronchiolitis obliterans organizing pneumonia), and subglottic stenosis. Among children with IBD, bronchiectasis is rare but has been reported [100-102]. (See "Pulmonary complications of inflammatory bowel disease" and "Clinical manifestations and complications of inflammatory bowel disease in children and adolescents", section on 'Extraintestinal manifestations'.)

●Other interstitial lung diseases – Traction bronchiectasis is caused by mechanical traction around the airway due to fibrosis or loss of parenchymal integrity, leading to dilatation of the airway. It can be a complication of several types of diffuse/interstitial lung diseases, although it is much rarer in children compared with adults. (See "Classification of diffuse lung disease (interstitial lung disease) in infants and children" and "Approach to the infant and child with diffuse lung disease (interstitial lung disease)".)

Bronchiolitis obliterans — Bronchiolitis obliterans is usually a postinfectious process (see 'Postinfectious conditions' above) but is also a relatively common complication of bone marrow transplantation or other solid organ transplants (including lung transplantation), related to chronic rejection. It has also been reported as a manifestation of interstitial lung diseases in children and as a consequence of Stevens-Johnson syndrome [103]. (See "Chronic lung allograft dysfunction: Bronchiolitis obliterans syndrome" and "Classification of diffuse lung disease (interstitial lung disease) in infants and children".)

Environmental exposures — Exposure to household air pollution contributes to chronic lung diseases including bronchiectasis. Pollutants include secondhand tobacco smoke, biomass fuels or coal (which include irritants and particulate matter), and nitrogen dioxide from unvented gas heating [104].

Inhaled toxins can lead to acute lung injury and bronchiectasis [105]. Examples include:

●Hydrocarbon inhalation and ingestion [106]

●Chronic inhalation of ammonia, talc, silicate, or coal dust [107-109]

●Chronic inhalation of mineral oils like paraffin (leading to lipoid pneumonia that progresses to bronchiectasis) [110]

●Exposure to arsenic in drinking water [111]

Genetic syndromes — Bronchiectasis has been associated with a variety of genetic disorders, likely representing different genetic mechanisms that predispose to lung injury [112,113]. Clinical syndromes in which bronchiectasis is a prominent feature include:

●Cartilage deficiency (Williams-Campbell syndrome; MIM 211450) – This is a rare congenital disorder characterized by deficient cartilage in the bronchial tree, causing generalized tracheomalacia [114,115]. Because the bronchial cartilage is absent or deficient, the segmental and subsegmental bronchi are dilated and collapse easily. Children typically present before three years of age with cough, wheezing, and recurrent febrile illness. Based on the few cases reported in the literature, the prognosis is variable.

●Congenital tracheobronchomegaly (Mounier-Kuhn syndrome) – This is a congenital disorder that is characterized by markedly dilated trachea and main bronchi, resulting in dynamic dilation and collapse during inspiration and exhalation [116]. Outpouching of redundant mucosal tissue results in pooling of secretions and recurrent atelectasis and pneumonia, leading to bronchiectasis [117]. The clinical manifestations range from minimal disease to respiratory failure and death. Diagnostic criteria for adults on imaging are transverse tracheal diameter >30 mm, right mainstem bronchus >24 mm, and left mainstem bronchus >23 mm [118]. On pathologic examination, there is atrophy or absence of elastic tissue as well as thinning of the muscular components of the airway. (See "Tracheomalacia in adults: Clinical features and diagnostic evaluation", section on 'Congenital (tracheomegaly)'.)

Other genetic disorders that are occasionally associated with bronchiectasis include (among many others):

●Marfan syndrome – Marfan syndrome is an inherited abnormality of connective tissue that is occasionally complicated by bronchiectasis [119]. It is postulated that bronchiectasis develops due to intrinsic bronchial wall defect from fibrillin-1 degeneration or due to the higher risk of recurrent lung infections if chest wall deformities are present [120]. (See "Genetics, clinical features, and diagnosis of Marfan syndrome and related disorders".)

●Yellow nail syndrome (MIM %153300). (See "Overview of nail disorders", section on 'Yellow nail syndrome'.)

●Autosomal dominant polycystic kidney disease (MIM #173900, MIM #613095) [121,122]. (See "Autosomal dominant polycystic kidney disease (ADPKD) in children".)

●Syndromes associated with immune deficiency (eg, ataxia-telangiectasia, DiGeorge syndrome). (See 'Hereditary' above.)

SUMMARY

●Epidemiology – Bronchiectasis was once considered rare in children but is increasingly recognized over the last two decades, likely primarily due to increasing awareness of the condition and availability of sensitive diagnostic methods such as multidetector high-resolution CT (HRCT). (See 'Epidemiology' above.)

●Pathogenesis – The pathogenesis of bronchiectasis usually involves a combination of chronic or recurrent infection, airway inflammation, and airway obstruction and/or impaired mucociliary clearance, interacting in a vicious cycle that causes progressive damage to the lower airway structure. (See 'Pathophysiology' above.)

●Causes – The relative prevalence of different causes of bronchiectasis in children varies substantially depending on the population studied. Important considerations include (table 1):

•Postinfectious – Including protracted bacterial bronchitis (PBB); specific infections including tuberculosis, pertussis, and measles; and postinfectious bronchiolitis obliterans (PIBO). (See 'Postinfectious conditions' above.)

•Bronchial narrowing or obstruction – Including pulmonary airway anomalies, foreign body aspiration, and mucoid impaction. (See 'Bronchial narrowing or obstruction' above.)

•Immunodeficiencies – Including primary immunodeficiencies (eg, common variable immunodeficiency) or acquired immunodeficiencies (HIV or pharmacologic immunosuppression). (See 'Immunodeficiencies' above.)

•Impaired mucociliary clearance – In cystic fibrosis (CF) and primary ciliary dyskinesia (PCD). (See 'Impaired mucociliary clearance' above.)

•Other – Other causes include chronic aspiration (eg, in neurologic disorders), ineffective cough (eg, in neuromuscular disorders), systemic autoimmune or inflammatory disorders (eg, systemic lupus erythematosus), post-transplant bronchiolitis obliterans, or environmental exposures (toxic inhalations). (See 'Miscellaneous' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Khoulood Fakhoury, MD, and Adaobi Kanu, MD, who contributed to earlier versions of this topic review.