INTRODUCTION
Bronchiolitis, a common acute lower respiratory infections (ALRIs) among infants worldwide1 causes considerable morbidity and hospitalisations annually (e.g. >3 million hospitalisations)2. It is a heterogenous, multi-dimensional disorder from many perspectives, including clinical phenotypes (during acute disease3 and future outcomes4-7), likely pathophysiology8 and risk factors9-11.
The importance of improved phenotyping respiratory disorders (e.g. asthma12 and bronchiectasis13) are increasingly appreciated as such data will likely improve targeted interventions. Indeed, to characterise clinical phenotypes (both during the acute disease and future outcomes) of infants with bronchiolitis using a multi-dimensional approach, Dumas and colleagues undertook two important studies4. Using latent class analysis (LCA), Dumas and colleagues described 4 phenotypes in a large USA cohort, of which 2 were replicated (with the remaining 2 combined in a single phenotype) in a Finnish cohort3. Later, using LCA and they then described a profile (breathing problems/eczema in infancy and non-respiratory syncytial virus [RSV], mostly human rhinoviruses [hRV] infection) associated with increased risk of future asthma phenotype (doctor-diagnosed asthma Hazard Ratio=2.79; 95% confidence interval [CI] 1.78-4.39 by 3-years of age)4. These infants also had “higher eosinophil counts, higher cathelicidin levels, and increased proportions of Haemophilus-dominant or Moraxella-dominant microbiota profiles”4.
These longer-term outcomes of infants hospitalised with bronchiolitis are of considerable interest with associations with asthma14 and data linking viral agents (particularly RSV and hRV)15 and/or nasopharyngeal bacteria5 to future childhood asthma and allergy16. However, while asthma and allergy are relevant and important outcomes in mainstream settings, these are inconsistently reported among and across different populations and settings2,17. In settings where acute respiratory infections are prevalent and bronchiectasis is relatively common, such as among Indigenous children living in high-income countries10, bronchiolitis is more common and severe and their non-Indigenous counterparts11. In these settings, the long-term outcomes are also likely different. Indeed, Singleton and colleagues found that Alaskan Native children aged <2-years hospitalized for RSV infection had increased risk for chronic productive cough at 5 to 8 years of age and recurrent lower respiratory infections, but not asthma18. Further, we found that within 13-months post-hospitalisation for bronchiolitis, Aboriginal and/or Torres Strait Islander (from here referred as Indigenous) infants 19% (30/157) had bronchiectasis on chest high-resolution computed tomography (HRCT) scan7.
A better understanding of clinical phenotypes including outcomes in Indigenous settings are important, in the context of (a) Dumas and colleagues’3,4 likely paradigm-changing findings for future intervention studies; (b) the absence of further studies using LCA to define these bronchiolitis clinical phenotypes; and (c) the differential long-term outcomes in populations at high-risk of bronchiectasis. We used LCA to analyse data from Indigenous infants from Australia who participated in our previous prospective hospitalised bronchiolitis studies19-21. We aimed to identify distinct clinical profiles particularly those at-risk of future bronchiectasis.