Prevalence Across Time and Countries

In most affluent countries, the prevalence of childhood bronchiectasis has substantially declined since the 1940s. Field reported on 160 children with bronchiectasis over a 20-year period noting a decline in the incidence from 48 to 10 cases per 10,000 people from the 1940s to the 1960s. By 1994, an English study found that only 1% of 4000 children referred to a respiratory specialty service had bronchiectasis. The reduced incidence over time has been ascribed to reduced crowding, improved immunization programs, better hygiene and nutrition, and early access to medical care. However, bronchiectasis is now increasingly recognized worldwide as an important contributor to chronic respiratory morbidity in less affluent countries and both indigenous and nonindigenous populations in affluent countries. Indeed bronchiectasis is not rare in affluent countries, but is more common among certain groups for example, the Alaskan Yupik children in the United States, Aboriginals in Australia, and Maori and Pacific Islanders in New Zealand. Among these populations, the prevalence of childhood bronchiectasis is 147 to 200 per 10,000 children. A Canadian study conservatively estimated that the prevalence of bronchiectasis among Inuit children living in Nunavut was 20 per 10,000. The only available national incidence data on children is that from New Zealand with a rate of 3.7 per 100,000 under 15 year old children per year, which is almost twice that of CF. In the Northern Territory (Australia with a high proportion of Indigenous people) the incidence in the first year of life is 12 per 10,000.

In adults, the estimated prevalence rate has been increasing (annual change of 8.8% from 2000 to 2007) based on a 5% sample of outpatient Medicare claims in the United States. In the United Kingdom (UK), the prevalence of bronchiectasis in people aged 18 to 29 years increased from 29.3 (95% confidence interval [CI] 20.4 to 41.9) per 100,000 in 2004 to 43.4 (32.3 to 58.4) per 100,000 in 2013. These estimates far exceed the prevalence of CF. Given the need for a CT scan to diagnose bronchiectasis, prevalence or incidence data would be an underestimation. Furthermore, recognition of bronchiectasis is physician dependent and it is not surprising that many cases in children and adults are misdiagnosed as “difficult asthma” or chronic obstructive pulmonary disease (COPD). A proportion of adults with COPD (29% of 110) have underlying bronchiectasis. Importantly, the majority of bronchiectasis in adulthood has its roots in childhood. One study of adults with bronchiectasis found that 80% of patients had chronic respiratory symptoms from childhood.

Hospitalization rates for adults with non-CF bronchiectasis in the United States have also increased in the last two decades; from 1993 to 2006, the age-adjusted rate increased significantly with an average annual percent increase of 2.4% among men and 3.0% among women. German hospital statistics for 2005–2011 have also increased over that period with an annual age-adjusted rate for bronchiectasis of 9.4 hospitalizations per 100,000 population. Likewise, an Australian state (Queensland) documented an increase in hospitalization from 65 to 83 per 100,000 population between 2005 and 2009.

Data from less affluent countries suggest that bronchiectasis is still associated with poor outcomes, for example, 22% with respiratory failure in a 6.6-year Tunisian follow-up study. Mortality from pediatric bronchiectasis is rarely reported. Arguably, no child without a serious comorbidity should die from bronchiectasis. However, an England and Wales study reported 12 deaths in the 0 to 14 years age group between 2001 and 2007, and 6 (7%) of 91 children died while attending a single New Zealand center between 1991 and 2006. The premature mortality from bronchiectasis may carry over into young adulthood particularly in circumstances with nonoptimal management. This is depicted by a retrospective cohort study of 120 Central Australian Indigenous adults with bronchiectasis (50 diagnosed as children) hospitalized between 2000 and 2006 that reported 34% died during the period at a median age of 42.5 years. In the UK, a recent study described that the crude mortality for men aged 18 to 49 years with bronchiectasis was 13.1 (95% CI 3.4 to 22.8) per 1000 population and 6.4 (0.8 to 12.0) for women compared to the general population, which are rates of 1.3 (1.3 to 1.4) and 0.8 (0.7 to 0.8), respectively. These represent excess mortality rates of 8 to 10 times the general population.

Economic Cost

There is little data on the economic cost of bronchiectasis and none specific to children. In an United States-based case-control study involving 9146 children and adults (6.7% were aged <18 years), the direct medical cost increased by US$2319 per patient per year relative to the matched control from the preceding year. The cost specifically for children was not described. An earlier study found that in the United States, adults with bronchiectasis averaged 2.0 (95% CI 1.7 to 2.3) additional days in hospital and that the average total annual medical-care expenditures (in 2001) were US$5681 ($4862 to $6593) higher for bronchiectasis patients than age, gender matched controls with other chronic diseases such as diabetes, COPD, and congestive heart failure.

Other Burden of Disease

In recent years, four pediatric studies in three different continents evaluated the impact of bronchiectasis on the child’s and/or parents’ health-related quality of life (QoL). Using the Parent Cough-Specific Quality of Life (PC-QoL) and the Depression, Anxiety and Stress (DASS-21) questionnaires, a Malaysian study described that children with CF had better parental mental health compared to children with non-CF CSLD. Overall, 77% of parents had abnormal DASS-21 scores (54% stressed and 51% depressed). An Australian study examined PC-QoL and DASS-21 scores during the stable-state and exacerbations in 69 children (median age 7 years) and their parents. In the stable state, the median PC-QoL was 6.5 (interquartile range [IQR] 5.3 to 6.9) and DASS-21 was 6 (0 to 20). Both scores were significantly worse during exacerbations (PC-QoL = 4.6 [3.8 to 5.4], P ≤ .001 and DASS = 22 [9 to 42], P < .001). DASS score showed that 38% had elevated anxiety and that 54% had abnormal depression/stress scores during the exacerbation. In the stable state, poorer QoL was significantly recorded with younger children, but QoL did not relate to the radiological extent, lung function, or underlying etiology. In contrast, a Turkish study described that the severity and frequency of symptoms were inversely related to the pulmonary function and the QoL scores (nonpediatric scales were used) in 42 children aged 9 to 18 years. Another Turkish study involving 76 Caucasian children with bronchiectasis and 65 controls used self-reported questionnaires to evaluate the psychological status (using the Child Depression Inventory, State-Trait Anxiety Inventories for Children, and Pediatric Quality of Life Inventories). In this older cohort of children (mean age 11.7, SD 2.6 years), depression and trait anxiety scores were not elevated in those with bronchiectasis, but the child-rated physical health QoL scores were significantly lower in those with bronchiectasis compared to controls. The determinants of QoL were related to age, forced expiratory volume in one second (FEV ₁ )/forced vital capacity (FVC) % predicted, and dyspnea severity.

The differences between the Australian and Turkish studies likely relate to the different QoL scales used and severity of disease. It is likely that QoL scores correlate to disease severity only in more severe disease, similar to the relationship between spirometry and radiological extent of bronchiectasis; spirometry is often normal in mild or localized disease, and significant correlations between spirometry indices and radiology scores are seen only in more severe disease. Nevertheless, all studies showed the negative impact of bronchiectasis on the children and/or their parents QoL and mental health. Poor sleep quality has also been reported.

Etiologic Risk Factors

Bronchiectasis is the result of a variety of airway insults and predisposing conditions that ultimately injure the airways and lead to recurrent or persistent airway infection and destruction. Examples of these conditions are listed in Table 26.1 . Bronchiectasis develops in some individuals when structural airway abnormalities, such as bronchomalacia, endobronchial tuberculosis, central airway compression, or retained aspirated foreign bodies impair mucus and bacterial clearance. However, there is currently no evidence of airway malacia causing bronchiectasis in human studies. Persistent airway injury and narrowing associated with bronchiolitis obliterans (BO; due to viral injury or following lung transplantation) can lead to bronchiectasis. Recurrent airway injury, such as occurs with aspiration syndromes, can also result in bronchiectasis. Selected pediatric cohorts from various settings and countries that describe the frequencies of these associated conditions are summarized in Table 26.2 .

Impaired upper airway defenses may also predispose to bronchiectasis based on the common association between rhinosinusitis and bronchitis/bronchiectasis. Indeed, the sinuses and Eustachian tubes have been considered a “sanctuary site” for bacterial pathogens and cytokines that may predispose to recurrent lower airway infection. Finally, there are variations in host inflammatory responses, for example, cytokine and metalloproteinase levels, and counterbalancing antiinflammatory mechanisms, for example, antioxidants and antiproteases, which may explain why some children develop bronchiectasis, while others do not despite similar exposures and living conditions.

Previous Acute Lower Respiratory Infections

It is well documented that acute lower respiratory tract infections (ALRIs) in children can lead to subsequent respiratory morbidity and lung function abnormalities. Classic epidemiological studies have linked acute ALRIs from adenovirus and other infections with chronic bronchitis and productive cough later in childhood. Recent large epidemiological studies have also shown that those with ALRIs in early childhood are at risk of lower lung function in adulthood. Although low lung function at birth may be the underlying factor of the significant association found, single severe ALRIs and multiple ALRIs in early childhood can undoubtedly lead to CSLD and bronchiectasis. These single ALRIs associated with bronchiectasis have been described with tuberculosis, pertussis, adenovirus, measles, and severe viral pneumonia. Although these infections do not frequently cause bronchiectasis, they remain common ALRIs in less affluent countries and are still considered important antecedents to childhood bronchiectasis.

In cohort studies, the most common associated cause or ascribed etiology for the bronchiectasis is past pneumonic events with lobar or diffuse alveolar infiltrates (see Table 26.2 ). In the sole case-control study of childhood pneumonia and radiographically proven bronchiectasis, a strong association between hospitalized pneumonia and bronchiectasis was found. Children who had been previously hospitalized due to pneumonia were 15 times more likely to develop bronchiectasis. A dose effect was also shown; recurrent (>1) hospitalization for pneumonia and more severe pneumonia (episodes with longer hospital stay or oxygen requirement) increased the risk of bronchiectasis later in childhood. Bronchiectasis was 3 times more likely in children with four or five episodes of pneumonia and 21 times more likely if they had 6 or more pneumonias. The overall number of pneumonias rather than the site of pneumonia were associated with bronchiectasis. In an Alaskan cohort, there was no association between lobe affected by first ALRI and the eventually bronchiectatic lobe, but there was an association between lobe most severely affected by ALRI and the lobes later affected by bronchiectasis. Specific infectious etiologies were not described in these studies. A review on the long-term effects of pneumonia in young children described a mixture of obstructive and restrictive lung deficits when followed up long term. However, the majority of studies in the review were limited with case ascertainment and follow-up issues.

Some authors have suggested that bronchiolitis is an important precursor of bronchiectasis. An Alaskan 5-year case-control follow-up of children hospitalized in infancy specifically with severe RSV infections described that they were not more likely to have been diagnosed with bronchiectasis. In contrast, a study of Indigenous children hospitalized with bronchiolitis in Australia found that on CT scans performed at a median 13 months (range 3 to 23) posthospitalization, infants with persistent cough at 3 week (n = 31) after hospitalization were significantly more likely to have bronchiectasis compared to those without a cough (n = 126), OR 3.0, 95% CI 1 to 7, P = .03. We surmise that bronchiectasis is not a consequence of specific viruses that produce bronchiolitis.

Upper Airway Infection and Aspiration

Mechanisms by which upper respiratory infections predispose to lower airway inflammation and injury are reviewed elsewhere. Bacterial pathogens colonizing the nose and mouth are shed into saliva and contaminate the lower airways. Proinflammatory cytokines from the oropharynx may also be aspirated and augment neutrophilic responses in the lower airways. Hydrolytic enzymes in infected upper airway secretions impair protective secretory molecules such as mucins in the lower airways, and thereby predispose the lower airways to infection. In vitro studies have shown that some bacteria produce factors that cause ciliary slowing, dyskinesia, and stasis, setting the stage for chronic bacterial colonization of the lower airways. Whether the concentration or persistence of these pathogens in upper airways represents a significant risk factor for development or progression of bronchiectasis is unknown. In indigenous Australian children with bronchiectasis, a study relating nasopharyngeal to bronchoalveolar lavage (BAL) bacteria found a high density and diversity of respiratory bacteria along with strain concordance between upper and lower airways. The study suggests a possible pathogenic role of recurrent aspiration of nasopharyngeal secretions.

Bronchiectasis and other forms of suppurative lung disease have been described among individuals with neurologic and neuromuscular conditions that reduce the frequency and effectiveness of cough and also increase the risk of aspirating oropharyngeal contents. Brook reported on 10 children with such conditions who developed anaerobic pulmonary infections; six had poor oral hygiene.

Public Health Issues

In 1949, Field wrote “Irreversible bronchiectasis is not commonly seen in the better social and economic classes. Good nutrition and home conditions probably give the child a better chance of more complete recovery from lung damaging disease.” Poor public health conditions, including malnutrition, crowding, lack of running water, and environmental pollution, increase the risk of ALRIs and bronchitis. These issues are particularly important in developing countries. In affluent countries, those communities with higher prevalence of bronchiectasis are also those where poverty and low standards of housing are common. In a qualitative study, community members and health care providers believed that potential contributing factors to acute and chronic lung diseases were smoke, dust, feeding practices, socioeconomic conditions, and mold.

Macro and selected micro malnutrition increases infection risks, as it creates an immune deficiency state and leads to the malnutrition-infection-malnutrition cycle. However, data on malnutrition specifically preceding bronchiectasis are limited and inconsistent. In Central Australia, Indigenous children with bronchiectasis are 3 times more likely to have had malnutrition in early childhood prior to the diagnosis of bronchiectasis, but this is not seen in Alaska or New Zealand. Breast-feeding is a known protective factor against development of bronchiectasis. Bronchiectasis may itself predispose to malnutrition as a result of chronic pulmonary infection, diminished appetite, and reduced caloric intake. The caloric needs and daily oxygen consumption of children with non-CF-related bronchiectasis have not been reported. One series described that children with bronchiectasis and low (<80%) baseline FEV ₁ % predicted values, and those with immunodeficiency had significantly lower body mass index at diagnosis, and they significantly improved after appropriate therapy was instituted. Also, in a double-blind randomized controlled trial on the effect of long-term azithromycin, Indigenous children randomized to the azithromycin group (c.f. placebo) had a significant improvement in weight z-score, concurrent with a reduction in exacerbations (incidence rate ratio = 0.5, 95% CI 0.35 to 0.71). This suggests that effective management of children with bronchiectasis improves nutrition.

Another predisposing factor to bronchiectasis is the presence of inhaled irritants, including indoor and outdoor pollutants, particularly in the presence of impaired airway clearance. The effects of environmental tobacco smoke (ETS) on children’s respiratory system are well known from both in utero and ex utero exposure and include reduced airway caliber, increased lower respiratory tract infections, and middle ear disease. Reviews of ETS and its effects on the developing lung and accelerated lung decline are available elsewhere. Exposure to indoor biomass combustion increases coughing illness associated with ALRIs with an exposure-response effect. Exposures to other indoor pollutants (nitrogen dioxide, gas cooking) and traffic are also associated with increased cough in children in both cross-sectional and longitudinal studies. There is no direct evidence of pollutants causing bronchiectasis, and the pathogenic role is likely indirect through an increased frequency of ALRIs and increased airway mucus production. In Chile, increased arsenic exposure has been associated with a variety of chronic disorders including bronchiectasis.

Genetics

The interplay between genotype, epigenetics, and environment is increasingly recognized as the key in phenotypic expression of respiratory diseases. An increased frequency of cystic fibrosis transmembrane conductance regulator (CFTR) genotypes associated with CF, presenting as heterozygotes, has been described in several case series of adults with diffuse bronchiectasis. While heterozygotes for alpha-1 antitrypsin have also been described more frequently in those individuals with diffuse bronchiectasis, a causal relationship remains controversial. Older guidelines suggest optional screening for alpha-1 antitrypsin deficiency for patients with idiopathic diffuse bronchiectasis, but newer guidelines described a lack of evidence and do not suggest alpha-1 antitrypsin deficiency testing for people with bronchiectasis. A Turkish study (where consanguinity of parents is common) described transporter associated with antigen presentation (TAP) gene polymorphisms in their cohort of children with bronchiectasis. It is interesting to note the high rate of consanguinity in several series of children with bronchiectasis from different countries. As with other diseases, an increasing number of gene aberrations have been associated with syndromes where bronchiectasis may occur. Examples include primary ciliary dyskinesia, autosomal dominant polycystic kidney disease (PKD1 on chromosome 16p13.3 and PKD2 on chromosome 4p21), and prolidase deficiency (PEPD gene).

Aside from variations in specific gene frequencies, overexpression of innate pulmonary immune mechanisms, such as proinflammatory cytokine and adhesion molecule production, and receptor expression, may contribute to the development of bronchiectasis in certain children. An increased or exaggerated neutrophilic response in Australian Indigenous children as a group has been described. Similarly, metalloproteinases, for example, MMP-2 and 9, have been isolated from the sputum and BAL of bronchiectatic subjects, suggesting a role in airway destruction by gelatinases and collagenases. Whether proinflammatory cytokine and collagenase overexpression are associated with early onset disease or, particularly, progressive disease in childhood remains unknown.

Airway and Systemic Markers

The majority of studies on airway inflammation have been performed in adults where, unlike children, assessment by using sputum is easy. Airway secretions are usually excessive in those with more severe bronchiectasis. The sputa from Alaskan native children with stable idiopathic bronchiectasis are less viscous (by one-third), less elastic (by one-fifth), less adhesive (by half), and more transportable (by 50%) compared to sputum from children with CF.

Neutrophilia is the dominant type of airway inflammation, although eosinophilia has also been described in some populations and when treated, airway inflammation may be absent. Increased percentages of neutrophils, neutrophil elastase, myeloperoxidase, mellatoproteinases, tumor necrosis factor-α (TNF-α), interleukin (IL-8), and IL-6 have been described in lower airway secretions. These generally reflect neutrophilic inflammation and are not specific to bronchiectasis. The intensity of the airway and systemic inflammation is ameliorated by treatment. An adult cohort involving 385 patients described a direct relationship between airway bacterial load and markers of airway inflammation (myeloperoxidase, neutrophil elastase, TNF-α, IL-8, and IL-1β) with a dose response such that higher inflammation correlated with higher bacterial loads. High bacterial loads were associated with higher serum intercellular adhesion molecule-1 (ICAM-1), E-selectin, and vascular cell adhesion molecule-1 (VCAM-1), reflective of systemic inflammation. Using both short (14 days)- and long (12 months)-term antibiotic treatments, the study demonstrated a significant reduction in the airway bacterial load and inflammation (both airway and systemic) compared to those who did not receive antibiotic therapies. However, there is a poor correlation between systemic and bronchial inflammatory mediators, suggesting that the inflammatory process is mostly compartmentalized to the airways. There is paucity of data on BAL or sputum markers in children. A small study in children described increased median values of systemic markers (white cells, C-reactive protein [CRP], and fibrinogen) in children whose airways were colonized (n = 14) compared to those without identified bacteria in their sputum (white cell count: 8.2 [IQR 6.4 to 9.5] vs. 6.4 [5.8 to 7.7] × 10 ³ /mm ³ ; CRP: 0.91 [0.45 to 1.29] vs. 0.42 [0.30 to 0.77] mg/dL; fibrinogen: 433.5 [390.3 to 490.3] vs. 392.0 [327.0 to 416.0] mg/dL, P < .05 for all). While the authors concluded that systemic inflammation was absent in children with bronchiectasis compared to controls, it is highly likely that a type-1 error was present in the study. In an in-depth study, the blood of children with bronchiectasis had a significant increase in the percentage of CD8+ T cells and T and natural killer T-cells (NKT)-like subsets expressing perforin/granzyme, interferon gamma (IFNγ), and TNFα compared with controls. The proinflammatory cytotoxic T cells were more marked in Indigenous children compared to non-Indigenous children.

Exaggerated or persistent pulmonary inflammation present in bronchiectasis leads to increased lung destruction by many mechanisms. The balance between proteases and antiproteases is increasingly recognized as important to the protection of airways against hostile agents and destruction of lung tissue. Upregulation of circulating adhesion molecules (E-selectin, ICAM-1, and vascular adhesion molecule VCAM-1) have also been suggested as playing a role in the pathogenesis of bronchiectasis. Collagenase activity present in the BAL of adults with moderately severe bronchiectasis originates from neutrophils and bacteria. These collagenolytic proteases are likely contributors to tissue destruction. As described above, the airways of people with bronchiectasis contains collagenolytic proteinases of bacterial origin. and neutrophilic-associated cytokines that, unabated, lead to increased tissue damage (e.g., metalloproteinases [MMP-2,8, and 9]). MMP-9 (but not tissue inhibitors of metalloproteinase-1) measured in exhaled breath condensate of children with non-CF bronchiectasis (42.8 ± 18.1 ng/mL) were similar to those with CF (48.9 ± 26.8) and significantly higher than controls (30 ± 3.7). Endobronchial biopsies in adults with bronchiectasis demonstrated an overexpression of neutrophil matrix metalloproteinases (MMPs). Using sputum from adults with bronchiectasis, Shum et al. showed that serine proteases derived from neutrophils were responsible for degradation of proteoglycans in a matrix model and that the protease secretion was stimulated by TNF-α in the presence of factors found in the sputum sol.

There are additional pathogenic processes associated with bronchiectasis that contribute to the persistence of airway inflammation and obstruction. Increased airway permeability has also been described with bronchiectasis when purulent sputum and significant colonization of the respiratory tract by bacterial pathogens are present. Also, resolution of inflammation is normally associated with the orderly removal of apoptotic inflammatory cells, and impaired removal of apoptotic inflammatory cells has been described in children and adults with bronchiectasis. The pediatric study also examined specifically for phagocytic activity for nontypeable Haemophilus influenzae (NTHi), whereas the adult study investigated apoptosis in relation to inflammation. The adult study reported that impaired apoptosis occurred in a dose-response fashion with increasing neutrophil elastase, a marker of neutrophilic inflammation. In children with bronchiectasis, the macrophage phagocytic capacity of BAL cells to apoptotic cells (efferocytosis) and to NTHi was significantly lower than in controls (efferocytosis: 14.1%, IQR 10 to 16 vs. 18.1%, IQR 16 to 21 respectively, P < .001 and NTHi: 13.7%, IQR 11 to 16 vs. 19.0%, IQR 13 to 21 respectively, P = .004). Mannose receptor expression in BAL was also found to be significantly reduced in the bronchiectasis group compared to controls ( P = .019).

Other Immune Markers and Response

Innate defense mechanisms also play a role in the pathogenesis and upregulated response to infection in people with bronchiectasis. However, there is little data specific to children. In a study involving 26 children with human immunodeficiency virus (HIV)-related bronchiectasis, the soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), an innate immune marker, was upregulated and more highly expressed than in children with CF. sTREM-1 also correlated with IL-8 and neutrophil elastase derived from BAL.

The increased expression of innate immune receptors (e.g., receptors TLR2, TLR4, and CD14) and cytokine responses (e.g., IL-8 and IL-1β) seen in adults with bronchiectasis are also found in those with neutrophilic asthma and children with PBB, a likely forerunner of bronchiectasis. This raises the possibility that some people with neutrophilic asthma have unrecognized CSLD. Indeed, many of children with PBB were previously misdiagnosed with asthma and in some settings has been classified as “difficult or severe asthma.”

There is an emerging body of evidence that impaired cell-mediated immune responses and dysregulated airway inflammation are linked and could contribute to the pathobiology of CSLD. A study on systemic immunity found that children with CSLD or bronchiectasis produced significantly less IFN-γ in response to NTHi than healthy control children, whereas mitogen-induced IFN-γ production was similar in both groups. The production of systemic NTHi-specific IFN-γ was significantly negatively associated with the BAL IL-6 ( P = .001) and IL-1β ( P = .001). The presence of bacterial or viral infection and severity of bronchiectasis using modified CT Bhalla score did not influence systemic NTHi-specific IFN-γ response.

Presenting Clinical Features: Symptoms and Signs

The clinical case definition of bronchiectasis is imprecise, but the diagnosis should be considered when children have a chronic “wet” sounding or productive cough with or without exertional dyspnea, recurrent wheezing and chest infections, hemoptysis, growth failure, clubbing, or hyperinflation. The most common symptom is persistent or recurrent wet/productive cough with purulent or mucopurulent sputum. Sputum color reflects neutrophilic airway inflammation. The frequency of chest wall deformity (hyperinflation) and digital clubbing vary among case series (5% to 60%). Digital clubbing can disappear after medical or surgical treatment in association with the disappearance of purulent sputum. Although hemoptysis is much less common among children than in adults with bronchiectasis, a presenting finding of hemoptysis should raise the possibility of airway bleeding due to bronchiectasis. Chest auscultation may be entirely normal or reveal coarse inspiratory crackles over the affected regions. Reduced oxygen saturations and abnormal cardiac sounds associated with pulmonary hypertension are very late signs in bronchiectasis. Similar to any other serious chronic respiratory illness, children with bronchiectasis may have growth failure that is associated with delayed diagnosis of bronchiectasis.

The median age of diagnosis of bronchiectasis unrelated to CF in affluent countries is 4 to 5 years. A New Zealand cohort was older at 9 to 10 years old at diagnosis but also experienced more advanced disease. Idiopathic bronchiectasis is rare in infancy, but when present, it is likely to reflect congenital pulmonary malformations, such as cystic lung disease or tracheobronchomegaly, or alternatively, primary ciliary dyskinesia. Only 50% of those with ciliary dyskinesia have the Kartagener triad of situs inversus, bronchiectasis, and sinusitis.

Radiological risk factors for development of bronchiectasis are the presence of atelectasis and persistent lobar abnormalities. In Alaska, children were more likely to develop bronchiectasis if chest radiographs obtained in children less than 2 years of age showed lung parenchymal densities, persistent parenchymal densities greater than 6 months duration, or repeated parenchymal densities. Among Aboriginal Australian children hospitalized with lobar changes on admission chest radiographs, children with alveolar abnormalities were more likely to have bronchiectasis on follow-up. In a prospective radiographic study of alveolar changes (179 lobes in 112 hospitalized children), the two most common involved lobes were the right upper lobe and left lower lobes. Both lobes had similar rates of radiological clearance on follow-up (22% and 27% respectively).

Comorbid Conditions

Children with postinfectious bronchiolitis obliterans and CSLD share some common clinical features (airway obstruction, chronic cough, recurrent ALRIs) in addition to the same etiological insult. In an Australian study, 6 of 19 children with postinfectious BO developed bronchiectasis. A South American cohort follow-up study (mean period of 12 years, SD 3.5) described that mean FVC increased by 11%/year (95% CI 9.3 to 12.6), FEV ₁ by 9%/year (95% CI 7.7 to 10.2), and FEV ₁ /FVC ratio decreased by 1.9%/year (95% CI 1 to 2.8). Seventy-eight percent of the 46 children in that cohort had bronchiectasis.

Phenotypes of childhood wheeze have been recognized and airway hyperreactivity occurs in some individuals with bronchiectasis. The presence of features of asthma has been described as a bad prognostic factor in both children and adults with bronchiectasis. The frequency of airway hyperreactivity in children with bronchiectasis varies from 26% to 74%. As a corollary, clinicians must recognize that wheeze and cough may not be related to asthma but to increased airway secretions and airway collapse as features of bronchiectasis.

Gastroesophageal reflux disease (GERD) may coexist with any chronic respiratory illness and should be appropriately treated. However, data in adults indicate that GERD may resolve or significantly improve once the underlying respiratory disorder has been treated. There is, however, no evidence-based approach to the management of GERD associated with bronchiectasis. Caution is necessary with regard to overdiagnosis, and unnecessary treatment of GERD is given the increasing evidence of increased risk of respiratory infections in children and adults receiving proton pump inhibitors in community and hospital cohorts. Readers are referred to the pediatric guidelines on diagnosis and treatment of GERD.

Hypertrophic osteoarthropathy (clubbing, periostosis of the tubular bones, and arthritis-like signs and symptoms) may occur in children with bronchiectasis. Systemic amyloidosis has also been reported as a complication or comorbidity. Cardiac dysfunction, although rare, has also been reported and may not be accompanied by pulmonary hypertension. A study of 21 children with bronchiectasis showed that the ventricular systolic function was normal but some patients had changes in left ventricular diastolic function. The authors also found that isovolumetric relaxation time had a significant negative correlation with the clinical severity score. Other reported comorbid conditions associated with bronchiectasis are osteopenia, scoliosis, chronic suppurative ear disease, social problems, past urinary tract infections, and developmental delay.

In adults, vitamin D deficiency has been reported to be associated with increased severity of bronchiectasis and chronic bacterial colonization of the airways. However, as serum vitamin D is a negative acute phase reactant (i.e., values fall with increased inflammation), deciphering cause and effect is problematic.

Diagnostic Criteria

Chest HRCT is the gold standard for diagnosis, because plain chest radiographs are insensitive. It has been long recognized that chest x-rays can be normal in people with bronchiectasis. With modern CT scanners, the images are best acquired using an MDCT scan with HRCT reconstruction which provides the best sensitivity. The scan protocol must be child-appropriate to minimize radiation risk. Radiology centers inexperienced in dealing with children often utilize adult protocols that subject children to higher doses of radiation. Radiological features of bronchiectasis can also occur in association with pulmonary fibrosis, congenital lesions such as Mounier-Kuhn, and Williams-Campbell syndrome, and as a result of traction in nonsuppurative lung disease.

The characteristic radiographic finding on HRCT in bronchiectasis is the presence of a “signet ring” where a dilated bronchus is greater than the diameter of the accompanying blood vessel in cross section ( Fig. 26.5 ). However, the cutoff (>1 to 1.5) whereby the ratio is considered abnormal should be reduced to 0.8 in children when CSLD symptoms are present. While this is generally appreciated by pulmonologists, radiologists may still use the adult criteria. The presence of bronchial dilatation relative to the accompanying vessel does not always equate to the presence of bronchiectasis, as this finding can also be present in other conditions ( Box 26.2 ). Other c-HRCT signs of bronchiectasis include abnormalities in the surrounding lung may include parenchyma loss, emphysema, scars and nodular foci, a linear array or cluster of cysts, dilated bronchi in the periphery of the lung, and bronchial wall thickening ( Box 26.1 ). Image quality and hence detection of bronchiectasis is dependent on the radiological technique used (tube setting, radiation dose, collimation distance, and image intervals). False positive and false negative situations that may occur are listed in Box 26.2 . HRCT does not differentiate the etiologies of bronchiectasis.

High resolution CT finding in bronchiectasis. Image illustrates the “signet ring” appearance of a dilated airway adjacent to smaller associated pulmonary vessels. In adults, abnormal dilatation is considered present when the bronchoarterial ratio (inner diameter of bronchus: external diameter of adjacent artery) is greater than 1. In children, a cutoff of 0.8 is considered abnormal when clinical features of bronchiectasis are present.

Etiologic Evaluation

As most patients are usually diagnosed with bronchiectasis after many years of symptoms, it may be difficult to define the etiology. Differentiating idiopathic from postinfectious bronchiectasis is particularly problematic. A common feature of many patients is impaired local or systemic host defenses to infection. Often, no cause is found even with extensive investigation, and many retain the label of idiopathic or presumed postinfectious bronchiectasis (see Table 26.2 ). Difficulties with ascribing an etiology to CSLD/bronchiectasis arise due to unavailability of certain tests, for example, functional tests for ciliary motility and extended immune testing, lack of a standardized approach to diagnosis, the population studied, and the CT definitions used.

Identifying etiology and assessing disease severity can influence surveillance frequency, treatment intensity, and prognosis. Investigations for specific causes of CSLD/bronchiectasis are recommended, even though many patients will lack an identifiable etiology. Current best practices for investigating possible etiology are outlined in Table 26.3 . The diagnosis of ciliary dyskinesia is addressed in another chapter (see Chapter 71 ).

Bronchoscopic Findings

Bronchoscopy is indicated to identify obstructive bronchiectasis, which can be intraluminal (tumors and foreign body), in the wall (tracheobronchomalacia [TBM]), or extramural from external airway compression. Bronchiectasis is a complication of inhaled foreign bodies and occurs among 25% of patients whose diagnosis of aspiration was delayed by greater than 30 days. In a prospective study involving 56 children with bronchiectasis undergoing flexible bronchoscopy, there were 25 occasions in 23 children where bronchoscopic results altered empiric treatment. BAL microbiology results led to antibiotic changes in five (9%) children, and an unsuspected foreign body was found in one (2%).

Bronchoscopic findings of major airways related to bronchiectasis have been described as five types: type I: mucosal abnormality/inflammation only; type II: bronchomalacia ( Fig. 26.6A ); type III: obliterative-like ( Fig. 26.6B ); type IV: malacia/obliterative-like combination; and type V: no abnormality. The frequencies of these findings among 28 children with non-CF bronchiectasis were 58%, 17%, 17%, 4%, and 2% for types I through V respectively. In the 33 children with postinfectious bronchiectasis and CSLD, structural airway lesions were present in 40%. A retrospective study involving 93 Greek children (0.6 to 16.4 years) described that type III (OR 5.4, 95% CI 1.9 to 15.4) and type IV (OR 8.9, 95% CI 2.5 to 15.4) bronchoscopic lesions significantly correlated to worse radiological scores, reflecting severity, and correlated with the percentage of BAL neutrophils (r = 0.23, P = .036).

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