Hospital admissions for respiratory infections due to RSV remain a significant health problem among young children and this is despite provision of immunoprophylaxis to children with medical factors placing them most at risk of this outcome. In an effort to find new strategies to reduce the burden of severe RSV we aimed to identify additional environmental factors that might be associated with RSV hospitalization. In this study we found that colder air temperatures during the most prevalent exposure period for RSV infection are associated with increased likelihood of RSV hospitalization.
This finding is in alignment with other studies of RSV infection in temperate climates that have noted a relationship with colder air temperature. For example, one study from the UK found that an increase in mean daily temperatures in central England observed over 2 decades (1981 – 2004) (i.e. global warming), was associated with a gradual shortening of the RSV season over time.27 Our identification of a relationship between temperature and severe RSV infections may reflect RSV - host virulence factors or human behavioural factors influencing transmission.
There is some evidence for increased stability of RSV in liquid droplets at lower temperatures which might lead to prolonged survival of RSV on environmental surfaces and increased infection risk during colder periods.28,29 Nasal and airway epithelium may be more susceptible to RSV infection and less able to clear infections when exposed to cold. For example, disruption and damage to the respiratory mucosal barrier caused by dry and cold air conditions can increase risk of penetration and infection by RSV.30 Furthermore, inhalation of cold air slows the mucociliary escalator (a non-specific respiratory immune defence) and causes increased susceptibility to infection as well as impaired ability to effectively clear infections which may lead to increased severity and hospitalization.23,28,29,31
However, another explanation for our finding of increased odds of RSV infection with cold temperatures could be due to the tendency of people to spend more time indoors during cold weather periods. In the setting of a household with one infected member, this would increase the duration of exposure of the others to the virus and facilitate RSV infection transmission amongst family members including vulnerable young children. Increased duration of exposure due to indoor cohorting may also increase the inoculum size and viral load. This, in combination with an impaired naso-epithelial barrier and reduced mucociliary clearance if there were any recent cold air contact in the exposed children, would likely increase the severity of illness and risk of subsequent hospitalization.32,33 In our sensitivity analysis we did confirm that a higher number of siblings was independently associated with an increased likelihood of having an RSV admission, and previous studies have shown that infants are most likely to contract RSV from household members.34 A similar mechanism has been hypothesized for the observation of increased RSV infection during periods of increased heat and humidity in tropical countries when people may spend more time indoors. Studies of indoor air quality conducted in Canada’s far northern regions where average household size is typically more than 6 persons further support this mechanism and have shown an association between reduced indoor ventilation and increased rates of respiratory infections, including RSV, among young Inuit children.35
The link between cold air temperatures and RSV hospitalization in our study was independent of multiple confounding factors that we included in our adjusted model, including geographic variables and socioeconomic status. Indeed we did observe an association between lower neighbourhood income quintile and increased odds of RSV admission as previously noted in the literature.36,37 The relationship between respiratory illnesses, and overall greater acute health services use with lower socioeconomic status has been well documented in many Canadian studies. In our primary model, we noted a weak association between ground level ozone and increased likelihood of RSV hospitalization. Associations between increased ambient air pollution levels (e.g. PM 2.5, Ozone) and respiratory tract infections, including bronchiolitis in children have been reported previously in the literature.38-40 One proposed mechanism for this relationship is that particulate matter and other air pollutants cause airway inflammation and impair mucociliary clearance, thereby reducing lung defenses against infection.41 Nonetheless, we did not see the association between RSV hospitalization and air pollution in our sensitivity analysis or find any association with overall AQHI. These potential associations may be underestimated in our study as we were only able to capture annualized ozone levels and AQHI and it is possible these may not be accurate indicators of the air quality during the time of RSV infection.
Though not the main focus of our study, we did note a relationship between RSV admission and geographical location. Living in the southern ecozones (warmer climates, more urbanization) was associated with an increased odds of RSV admission that was not related to rural versus urban residence. It is possible that environmental parameters beyond temperature or air quality, such as humidity or barometric pressure, as identified in other studies, as well as other unmeasured ecological factors may influence the risk of RSV infection and illness severity among Ontario children.
It has been previously shown that the majority of RSV hospitalizations among children in Ontario occur in those who would not have received immunoprophylaxis.10 Our work suggests an opportunity to identify risk factors beyond comorbid health conditions that could be targeted to refine our current criteria for providing this preventative therapy. For example, a cost-benefit analysis could be performed to determine the effect of extending criteria for immunoprophylaxis to additional vulnerable populations just during the coldest winter months, rather than for the entire RSV season, or considering socioeconomic factors or number of siblings in the home when determining who qualifies for RSV immunization. In our study we excluded children of <36 weeks gestational age as they might have qualified for immunoprophylaxis, but many children between gestational ages 32-35 weeks in fact do not receive this intervention as they do not meet all qualifying criteria. For this population in particular, the consideration of additional risk factors in determining who meets criteria for public provision of immunoprophylaxis could have significant health impact and further reduce RSV hospitalizations which have remained constant in the last decade.
The use of health administrative data in this study allowed us to explore the association between climate factors and RSV hospitalization across the entire population of the vast geographic expanse of Ontario. Though this methodology provided significant power, there are some limitations, including lack of information on potential contributory factors such as environmental tobacco smoke or indoor air quality. In an effort to eliminate the confounding influence of immunoprophylaxis on the odds of RSV admission, we excluded all children who would have possibly met the most common criteria for immunoprophylaxis for RSV such as prematurity, or the presence of chronic lung disease, congenital heart disease or trisomy 21. As such, our study results are not generalizable to all children. It is also possible that some children in our cohort of RSV cases may have received immunoprophylaxis (due to individual risk factors identified on a case-by case basis), though we would expect this to be a very small proportion and unlikely to alter the main study findings. Finally, other spatio-temporally clustered factors beyond the geographic and climate variables explored in this study may account for some of the associations seen, but given our data limitations, these were not examined here.