More than just a wheeze: bronchiolitis and obstructive sleep apnea in children

Lower respiratory tract illnesses (LRTI) are highly prevalent in young children, and are a common cause of hospitalization, particularly in infants with a history of prematurity and other comorbidities [1–3]. There is increasing evidence that LRTI in the first 2 years of life related to rhinovirus or respiratory syncytial virus (RSV) are associated with asthma in childhood and later in life [4, 5]. As rhinovirus and RSV result in nasopharyngeal inflammation, and the nasopharynx is a key contributor to obstructive sleep apnea (OSA) in children, it is possible that LRTI in young children could be associated with an increased risk for OSA later in childhood. This association is particularly relevant for lower-income, minority children who are at increased risk for both LRTI and OSA [6, 7]. A previous study of 21 children who had RSV bronchiolitis in the first year of life found an increased obstructive apnea–hypopnea index compared to 63 control participants, but larger studies have not been conducted [8].

The study by Gutierrez et al. [9] in the current edition of SLEEP provides compelling evidence of an association between early-childhood LRTI and subsequent OSA, identifying a potential target to reduce the prevalence of OSA in children. The authors examined the association between a diagnosis of LRTI and associated hospitalization with a diagnosis of OSA using 3114 children from the Boston Birth Cohort, which prospectively collects clinical data in predominantly low-income infants. The analysis covaried for a number of maternal factors, including race, smoking, and asthma history, and child factors, including gestational age and breastfeeding status. In those with LRTI in the first 2 years of life, the investigators found an adjusted hazard ratio for incident OSA of 1.53 during the first 5 years of life, and a twofold increase in the odds of OSA among children hospitalized for bronchiolitis during the first 2 years of life. Interestingly, LRTI between 2 and 5 years of age was not associated with OSA diagnosis by age five.

One potential explanation for this association involves the nasal immune response resulting in inflammation and remodeling. In infants infected with RSV, an increase in type-2 and type-17 cytokines has been associated with subsequent recurrent wheezing [10], and interleukin-6 has been associated with both RSV and OSA [11, 12]. Inflammation associated with viral causes of bronchiolitis may result in airway hyperresponsiveness and remodeling in the nasopharynx and other sites of OSA in children, including the tonsils and adenoids [13, 14].

The association between bronchiolitis and OSA in young children may be bidirectional. In children under 2 years old hospitalized with bronchiolitis, OSA was recently shown to be associated with greater need for invasive mechanical ventilation, and this relationship was stronger in children with Down syndrome [15]. In addition, a diagnosis of OSA has been strongly correlated with community-acquired pneumonia in young children [16].

Early-life factors associated with OSA later in childhood are important to identify to assist in screening and prevention. In addition to exposure to LRTI, the current study found an association between prematurity and childhood OSA, which supports the findings of other cohorts [17, 18]. Interestingly, there was no association found between breastfeeding status and development of OSA by 5 years. In a prospective study of 196 habitually snoring children, a history of breastfeeding was associated with protection against OSA later in childhood [19]. Breastfeeding has also been associated with lower risk of recurrent wheezing in the first 2 years of life and LRTI-associated healthcare utilization [20, 21], and this relationship is important to explore further to improve evidence-based guidance for prevention and evaluation of childhood OSA.

The study had several important limitations. As a secondary analysis of an existing dataset, the diagnosis of OSA was made by chart review rather than polysomnography, and the duration of time between LRTI and OSA symptoms and diagnosis could not be established. The analysis was limited to the first 5 years of life, so association between LRTI and OSA later in childhood could not be explored. While LRTI between 2 and 5 years of age was not associated with OSA by age five in this cohort, it is possible that there could be a relationship later in childhood. Large longitudinal pediatric cohorts are needed to better understand LRTI and other risk factors throughout a broader age range. As a single-site study, environmental associations beyond the Boston metro area could not be evaluated, and there could be inherent bias in the evaluation and diagnosis of OSA at that site that limit generalizability. In addition, the role of socioeconomic and environmental factors in the relationship between LRTI and OSA was not explored. Collecting data such as socioeconomic status, population density, and pollution in prospective cohorts and the use of tools such as geocoding can be used to better understand the role of these factors in OSA [22, 23] and reduce sleep health disparities in children.

In summary, the current study identifies LRTI early in life as a potential risk factor for childhood OSA. Future studies should evaluate the anatomic, neuromotor, genetic, and immunologic mechanisms that modulate OSA after LRTI early in childhood, identify which children are at greatest risk, and evaluate the impact of public health measures to reduce the burden of LRTI, particularly in the children most vulnerable to severe infection, which may in turn have the greatest benefit in OSA prevention.

Funding

None declared.

Disclosure Statement

None declared.

References