French physician Rene Laennec first described CSLD in the early nineteenth century (23), with the first surgery (24) and imaging (25) performed around 100 years later. In the 1930s, Roles described the poor prognosis of CSLD patients at the time and highlighted the importance of early diagnosis and the potential of lobectomy for enhanced survival (26). The benefit of surgery over medical management was unclear in several subsequent studies (27–30), though a surgical case series of CSLD conducted decades later was convincing, particularly for children (13). With the introduction of broad spectrum antibiotics in the 1950s, significant reductions in CSLD incidence were reported. In the United Kingdom (UK) between 1952 and 1960 (12), CSLD admissions fell fivefold from 23.8 to 4.9 per 1,000 total admissions. Similar findings were reported elsewhere in the UK (10) and in the United States of America (USA) (11). Childhood CSLD became confined to disadvantaged populations of high-income countries, earning it the label of an “orphan disease” (14). Alaskan native children <16 years of age appeared vulnerable with a conservatively estimated case prevalence of 41/100,000 population over the decade 1956–1966, largely in the Yukon–Kuskokwim (YK) Delta and with one-third of cases associated with tuberculosis infection (16). In the 1960s, the prevalence of CSLD among Scottish children (<10 years of age) was 10.6/100,000 (27), and in the early 1970s, a substantial burden of CSLD was reported among indigenous children living in Central Australia (31). In this study, 83 indigenous children with CSLD were identified (60% <2 years of age) from an estimated population of around 1,000, despite near complete eradication of tuberculosis, measles, and pertussis, previously considered to be key etiological pathogens (31). In one of the few African studies, 70/1,150 patients consecutively admitted to the University Hospital in Nigeria with respiratory or cardiovascular disease between 1975 and 1979 were diagnosed with CSLD, of which 10 (14%) were children (32).

In the following section, we review the population incidence of pediatric CSLD in the modern era (1980–2016), when immunization and antibiotic interventions control many of the major etiological pathogens of the past, including tuberculosis, pertussis, measles, and pneumococcus.

We performed a systematic literature review of the PubMed library followed by a bibliography search within all relevant articles. The PubMed search terms: (CSLD OR bronchiectasis) AND (pediatric OR child OR children OR infant) AND (epidemiology) yielded 351 articles, which was reduced to 243 when confined to non-cystic fibrosis-related bronchiectasis articles published since 1990 and performed after 1980, human research, and non-review articles written in English. From these, 13 relevant studies reported CSLD rates: either directly (incidence rate) or indirectly (included a bronchiectasis disease numerator, an estimate of the population denominator, and an observation period). In one New Zealand (NZ) study, age-specific data could not be accurately extracted or obtained from the authors and were, therefore, excluded (33). A government report capturing similar national NZ CSLD data was included in its place (34).

In our defined modern era (1980–2016), the burden of childhood CSLD remains difficult to characterize. In the 1980–1990s, wheezing and persistent cough were often considered clinical features of asthma and not related to CSLD. Thus, due to lack of robust evidence, misclassification was likely and management (e.g., antibiotics) possibly suboptimal. Peer reviewed published burden data were available from only nine countries, diagnostic criteria varied, population denominators were often approximate, and incidence/prevalence data were inconsistently reported. Further, hospital-based studies utilizing International Classification of Diseases coding to identify CSLD (ICD8 518, ICD9 J494, and ICD10 J47) were common. ICD coding does not provide radiological information (though several studies confirmed cHRCT diagnosis via medical records or subsequently performed cHRCT) nor distinguish between primary and repeat admissions (exacerbations), which must be ascertained by diagnosis in conjunction with date of presentation. While rare in most high-income countries, in some settings (e.g., Australian indigenous children) as many as 1 in 136 children have a new case of CSLD detected annually (8). Despite limitations in data accuracy, the trends toward higher rates of CSLD among socially disadvantaged populations were clear though perhaps partially attributed to enhanced surveillance. The collated global epidemiology data are summarized in Table 1.

In most affluent European populations, pediatric CSLD was relatively uncommon with average annual rates ranging from 0.2/100,000 in the UK (37) to 2.3/100,000 in Ireland (38), however, in the equally affluent, yet non-European United Arab Emirates (UAE; 13.3/100,000) (36) and largely non-European NZ (15.0/100,000) (34), CSLD was more common. The indigenous Arabic children in the UAE children were predominantly from a wealthy social demographic with almost universal immunization coverage, therefore, the surprisingly high rates may be related to an inherited predisposition or to moderate levels of educational attainment. In NZ, the high national rate is a reflection of the high proportion of less affluent Maori and Pacific Islander people (~40%) for which there is a well-established susceptibility to respiratory infection (19, 43, 44). In this particular report by Simpson (34), CSLD cases were not reported by ethnicity. As clarified in the next section, the annual rate was much lower (1.5/100,000) for NZ people of European heritage (18, 20).

The highest reported pediatric CSLD rates occur among socially disadvantaged indigenous populations of the Pacific Islands (19), NZ (18, 20), Australia (8, 39, 40), Alaska (16), and Canada (17). In the Pacific, Native Fijian children (5–14 years of age) had over 20-fold more CSLD hospital admissions (7.0 versus ~0.3/100,000) than their Indo-Fijian counterparts between 1985 and 1989 (19). Two NZ studies spanning 1998–2002, one examining national CSLD cases reported by pediatricians (20) and the other CSLD hospital admissions in Auckland (43), demonstrated the disproportionate average annual incidence among Maori (4.8–7.9/100,000) and Pacific Islander (17.8–18.3/100,000) compared to European children (1.5/100,000). This disparity is directly related to child poverty. In NZ, substantially more Maori and Pacific Islander families live in poor (28–34%), overcrowded (25–50%) households with high unemployment rates (15%) compared to European families (16, 5, and 5%, respectively) (34). Similarly, in Australia and Alaska, CSLD is largely confined to indigenous children.

In the early 2000s, the average annual incidence of cHRCT confirmed bronchiectasis among indigenous children living in Central Australia was high at 735/100,000 (8). Almost all children (95%) had pneumonia at an early age (median 6 months) and nearly two-thirds had concurrent chronic suppurative otitis media (8). Two further hospital-based studies have investigated CSLD among Australian indigenous children. The first study, a historical cohort examining the entire indigenous population of Australia’s Northern Territory (NT) (both Central and Northern Australia from 1999 to 2004) showed an average CSLD incidence of 118/100,000 child-years in the first 12 months of life (39). One in five of these infants were also hospitalized with an ALRI. The early burden of respiratory illness is of particular concern in this region. The second study, a retrospective chart review conducted during 2007–2011 at the Mount Isa Base Hospital in Queensland (Qld), demonstrated an average annual incidence of 410/100,000 in children <2 years of age (40).

Alaskan Natives are also historically at high risk of CSLD. In a conglomeration of CSLD data from the YK Delta region (collated from a state-wide registry, historical and current patients of YK Delta Regional Hospital, or Alaska Native Medical Center), the average annual incidence of CSLD among children born between 1980 and 1990 (the review defined modern era) was 140/100,000 (16); equivalent to the incidence reported among the same population born in the 1940s (16). For a similar population, the Inuit children of Nunavut, Canada, the average annual incidence (1998–2011) of pediatric cHRCT confirmed bronchiectasis ascertained via health record reviews was lower but also substantial at 15.5/100,000 (17).

Nationally in NZ (20), and among indigenous children of Australia (8), Alaska (16), and Canada (17), CSLD was diagnosed at around 5 years of age. In Auckland though, the age was slightly older at 8 years (18) and under 2 years of age for Australian indigenous infants (39, 40). Common to disadvantaged populations of high-income countries, was low socioeconomic status, inadequate and overcrowded housing, complex environmental and social issues, limited access to health care, frequent exposure to camp or cooking fires, high smoking rates, and almost a universal history of early infant pneumonia and/or recurrent ALRIs (8, 16–20, 39, 40). In affluent countries, CSLD is more frequently associated with non-infectious etiology (see “Etiology”).

Published pediatric CSLD data (etiological, management, diagnostic, etc.) are widespread. Countries including Turkey (45–48), Saudi Arabia (49), Taiwan (50), Malaysia (51), Tunisia (52), Italy (53, 54), and England (55) have published excellent research (etiological, management, diagnostic, etc.), however, population-incidence could not be accurately elucidated or was not the focus of these research articles. We did not identify any incidence data among low- to middle-income countries.

The 26 studies of pediatric CSLD encompassed 2,103 children from 15 countries around the world; 13 high-income (including studies within disadvantaged sub-populations) and 13 low- and middle-income countries (Table 2). The age of symptom onset varied significantly among the studies (range 0–16 years) but was consistently present many years prior to a diagnosis of CSLD [Table 2; mean/median differences ranging from 0.8 to 7 years (Table 2)]. Some of the earliest reported symptoms were among indigenous infants from Australia (0.3years) (8), and Alaska (0.2 years) (9), and New Zealand (0.5 years) emphasizing the early origins of CSLD in high-risk children. Interestingly, Malaysian (low and middle income) and Italian (high income) children had a similar age of symptom onset (0.5 years). Thus, early symptom identification is essential to preventing CSLD progressing and long-term decline in lung function (68–70).

As with studies reporting incidence (several of which overlap), the demographic, etiological, and clinical data varied in their nature relating to differences from study design, study era (e.g., clinical reporting) and the age at diagnosis of children involved (e.g., unable to perform lung function <4 years).

Chronic suppurative lung disease is the end result of chronic airway inflammation that is driven by persistent infection (2). As such, the natural history of CSLD depends largely on the susceptibility to both acute and chronic infection (71). Historically, congenital malformations, cystic fibrosis, immune deficiency, and aspiration are common antecedents (5), although a primary cause is not always identified. Further, measles, tuberculosis, and pertussis (27, 72), once the most common causes of CSLD may be less important today in the wake of advances (5) in vaccinations, antibiotics, and access to health care (67). Reviews of CSLD etiology from pediatric cohorts have been published in 2011 (67) and 2014 (6). Using a systematic search, we further updated the etiology literature, which remains similar as previous reviews and is briefly summarized below (Table 3) (17, 38, 48, 51, 58, 61, 63–66).

Less than half of the CSLD reported in high-income countries (4–35%) (38, 54, 55, 59–61, 73) and low- and middle-income countries (10–40%) (45–52, 62, 63) was identified as postinfectious; yet, a history of early infant pneumonia and/or recurrent ALRIs was almost universally common to indigenous children of Alaska (93%) (16), Australia (90%) (8), and Canada (94%) (17). A separate case-control study in Central Australia also found a strong relationship between severe recurrent pneumonia in early childhood and development of CSLD (74). In the South Korean study by Kim et al., 89% (17/19) children with infectious etiology had tuberculosis (63). Taken together, these findings reinforce the notion that the high burden of CSLD among indigenous children is related to substandard living conditions and is essentially preventable.

In affluent European populations where CSLD is less common, immune deficiency was identified in a larger proportion of cases (10–34%) (38, 54, 55, 59–61, 73) than among indigenous populations (0–12%) (8, 16–18, 20, 58) and in low- and middle-income countries (4–19%) (45–52, 62–66), where acute respiratory infections are endemic and CSLD is more common. Other main differences highlighted in Table 3 were the higher proportion of children with primary ciliary dyskinesia (PCD) in high- and low- and middle-income countries (1–24 and 3–26%, respectively) (38, 45–52, 54, 55, 59–63, 73) compared to indigenous children where PCD was not reported (8, 16–18, 20, 58). Despite improved diagnostics and case management globally, the proportion of CSLD cases with unknown etiology was relatively consistent (0–55%; Table 3) apart from in London (2%) (59) and among indigenous children (0%) where most cases were accounted for (8, 16). It is likely that previous infections play more of a role in the development of CSLD than is currently known. This is of particular concern in low- and middle-income countries where children with recurrent respiratory infections often have limited access to medical care. Even more concerning is that the actual burden of CSLD in these countries is largely unknown.