Extreme temperature and storm exacerbations of pediatric asthma: evidence and prevention strategies

Asthma is the most common chronic disease in children and a main cause of hospitalizations, with substantial costs to patients, families, and society. Existing disparities in asthma will likely be impacted by the increasing adverse consequences of climate change and the disproportionate impact on low-income and minority communities. Increased extreme temperatures, weather events, air pollution, and allergens linked to climate change exacerbate pediatric asthma. There is a need for greater understanding of the climate change-related risk factors specifically impacting pediatric asthma exacerbations, increased attention to health disparities, and development of strategies for prevention and management. This perspective piece describes selected research on temperature and storm-related asthma exacerbations in children and includes a discussion on possible mechanisms for weather phenomena and climate change associations, research gaps, and possible solutions related to secondary prevention (figure 1).


Introduction
Asthma is the most common chronic disease in children and a main cause of hospitalizations, with substantial costs to patients, families, and society. Existing disparities in asthma will likely be impacted by the increasing adverse consequences of climate change and the disproportionate impact on low-income and minority communities. Increased extreme temperatures, weather events, air pollution, and allergens linked to climate change exacerbate pediatric asthma. There is a need for greater understanding of the climate change-related risk factors specifically impacting pediatric asthma exacerbations, increased attention to health disparities, and development of strategies for prevention and management. This perspective piece describes selected research on temperature and storm-related asthma exacerbations in children and includes a discussion on possible mechanisms for weather phenomena and climate change associations, research gaps, and possible solutions related to secondary prevention (figure 1).

Temperature and storm events have been shown to increase asthma-related health care utilization in children
Both low and high extreme temperatures have been associated with increased asthma attacks in children. A study of 32 220 pediatric asthma hospital visits from 2013-2016 in Hefei, China demonstrated an association between cold spells and childhood asthma admissions occurring within five days (lag day 1-lag day 5) of exposure, with the largest effect occurring at lag day 3 (relative risk [ [2]. A change in daily maximum temperature from 27 • C to 32 • C (25th to 75th percentile) was associated with increased pediatric asthma ED visits, with the strongest single day association observed on lag day 2 (RR = 1.06 [1.03, 1.09]), in a study of 51 360 visits in Atlanta, United States from 1993-2012 [3].
Cold and hot temperatures precipitate asthma attacks through varying mechanisms, characterized by bronchoconstriction and airway inflammation. Cold air may increase airway reactivity and drying or thickening of the nasal mucosa [4]. Heat exposure also increases inflammatory responses, leading to bronchoconstriction via stimulation of vagal bronchopulmonary C-fiber sensory nerves and the cholinergic reflex pathway [4]. Both low and high extreme temperatures may enhance susceptibility to viruses, allergens, and pollution [4]. For example, cold and dry weather can facilitate the survival of influenza and respiratory syncytial viruses, reducing the humidity of airway mucosa and damaging epithelial cilia [4]. This physiologic effect subsequently increases vulnerability to other triggers, leading to asthma attacks [4]. Climate change causes increased frequency and intensity of extreme high temperature events, negatively impacting children's respiratory health [4].
Fewer studies have examined the effects of daily temperature changes on pediatric asthma exacerbations. Existing research suggests that large diurnal temperature range (DTR), the maximum change in temperature in a 24 hour period, may trigger pediatric asthma attacks. Xu et al found a statistically significant association between DTR and pediatric asthma, with the greatest effect for lag 0-9 d, during which a 31% [95% CI: 11%, 58%] increase of EDAs occurred per 5 • C increment of DTR [2]. A study in Korea from 2007-2013 demonstrated that among children aged 0-9 years, a larger daily temperature difference was associated with both increased hospitalizations (incidence rate ratio [IRR] = 4.159 [3.449, 5.018]) and emergency department use (IRR = 3.405 [3.294, 3.518]) for asthma [5]. Despite an established epidemiologic association of large DTR with asthma exacerbations, the wide range of exposure to exacerbation time frames and lack of inclusion of variables (e.g. pollen) and confounders indicates a need for further research.
Increased storm frequency is another trigger for acute asthma attacks. The physiologic mechanisms underlying storm-related asthma exacerbations likely resemble those leading to DTR-associated asthma attacks and they often occur simultaneously, although these two events can occur independently. Thunderstorm outflows may concentrate aeroallergens such as pollen, and thunderstorm-associated humidity and rainfall may contribute to osmotic shock, which is a change to the solute concentration around a cell, causing the rupture of pollen grains and release of their allergenic contents [6]. Individuals with asthma may be particularly sensitive to these increased concentrations of aeroallergens [6]. A study in Ottawa, Canada from 1992-2000 of 18 970 pediatric asthma-related emergency department visits found that summertime thunderstorm activity was associated with increased risk of an emergency room visit (odds ratio OR = 1.35 [1.02, 1.77]) compared to summer periods with no activity [7]. In 2016, one of the largest epidemic thunderstorm events took place in Melbourne, Australia, involving a 10 • C drop in temperature, a rise in humidity above 70%, increased concentrations of particulate matter, and extreme grass pollen concentrations [8]. This event resulted in an estimated 476 (992%) excess asthma-related hospital admissions, with those aged less than 20 years comprising 30% of these admissions [8]. Similarly, a study of the impact of Hurricane Katrina found that out of 102 children with asthma, 78.4% reported requiring more asthma medication and 39.5% reported worsened symptoms following the hurricane [9]. The association between storms and asthma exacerbations in children is relevant for guiding potential intervention strategies.
It is known that both temperature and storm events are linked to asthma exacerbations, but there is a gap in the research studying how these two risk factors interact, as well as how other associated variables impact this relationship. For example, there is a need for further exploration of the impact of large DTR, especially during storms, on pediatric asthma, especially as climate change increases storm frequency and likely increases the number of days with large DTR [6,8,10]. Additionally, lag time between DTR and its relationship to severity of asthma exacerbations is still poorly understood. In the context of temperature change and storm events, few prior asthma studies have accounted for the synergistic effects of pollution, viral exposures, and allergens [10]. These confounding variables must be accounted for in future research in this field.

Race and social determinants of health
The prevalence of asthma and rates of asthma exacerbations are higher in children of Indigenous and minority populations. Climate change and its subsequent socioeconomic impacts will likely worsen these disparities. Existing evidence from the United States includes a 5.3% higher prevalence of heat-related mortality in African Americans, a 3.64-fold higher risk of emergency department visits in minority children compared to White children, and a 3.34-fold higher risk of asthma-related mortality in African Americans compared to White individuals [11][12][13].
As with many other health outcomes, racial and ethnic disparities in asthma are compounded by social determinants of health. Historic and current environmental injustices have resulted in greater exposure to air pollution among racial and ethnic minorities, contributing to higher rates of asthma and allergic disease. Structural and systemic inequities have led to poor infrastructure (e.g. sewage systems), low tree coverage, and lower prevalence of air conditioning (50.6% vs 70.1%) in minority neighborhoods compared to White neighborhoods in the United States [14]. These structural factors make minority populations particularly vulnerable to temperature and storm exacerbations of asthma.
It is vital to address these racial disparities when designing future research and prevention strategies. A longitudinal analysis of 544 children in the Chicago Initiative to Raise Asthma Health Equity found that health literacy and education were important mediators of racial and ethnic disparities in asthma [15]. Another study of 4321 children in the D.C. Pediatric Asthma Registry found that decreased educational attainment and violent crime were the social determinants of health most significantly associated with risk of asthma emergency department visits and hospitalizations [16]. These findings must be considered when implementing community education and warning systems.

Secondary prevention and management of climate change-related childhood asthma exacerbations
There are two main methods of addressing climate change-related asthma morbidity: climate change mitigation and secondary asthma prevention and treatment. This article will focus on proposing solutions for secondary prevention of pediatric asthma exacerbations. However, we underscore that climate change mitigation is the ultimate solution as it targets the root cause of this issue and must be prioritized by policymakers. For example, an assessment of the U.S. Regional Greenhouse Gas Initiative found that 537 child asthma cases were avoided over 5 years (2009-2014) as a result of their program that reduced annual CO 2 emissions within the Northeast United States by 50% from 2005 to 2017 [17]. A systematic review concluded that reducing air pollution from fossil fuel combustion would save $23 573 per case of childhood asthma not persisting into adulthood [18]. Together, these two studies highlight the vast medical and economic benefit of systemic climate change mitigation policies and actions on childhood asthma.
Beyond climate change mitigation, we propose four main strategies to prevent asthma exacerbations: climate adaptation, enhancing community education, improving healthcare provider education, and creating predictive models and early warning systems (table 1).
We suggest that climate adaptation efforts focus on enhancing comfort and air quality indoors, which may entail improving heating, ventilation, and air conditioning, specifically in low-income and minority neighborhoods. A randomized controlled trial of 409 children with asthma in households from five communities in New Zealand found that installing more effective heating led to 1.  [19]. Another randomized controlled trial of 177 children in the United Kingdom found that improvement of household ventilation and heating shifted 17% of children from severe to moderate asthma and found that this was a cost-effective use of public resources [20]. More limited evidence exists on the impact of improvement of home environments after large storms, including hurricanes, due to increased mold and dampness, so we recommend further study.
Enhancing community education is a key aspect of reducing asthma exacerbations, as it is a large mediator of racial and ethnic disparities. A 2002 randomized controlled trial of 134 inner-city children demonstrated that an asthma self-management and education computer program led to a significant reduction (OR = 0.52, p = 0.03) of asthma-related limitations in activity [21]. However, community education programs must be accompanied by community engagement efforts to best understand community needs. Everhart et al describes how community engagement can better prioritize the interventions that reduce asthma disparities in the Richmond, United States area [22]. Additionally, a key Reduced asthma-related limitations in activity [21] Medication prophylaxis [23] Risk prediction [24] Evidence/Reasoning 2 Decreased asthma severity [20] Reduced disparities [22] Recognition of climate triggers Improved community education & awareness Evidence/Reasoning 3 Cost-effective [20] Promotes low-risk behaviors Improved patient counseling Increased trigger avoidance aspect currently missing in many community education efforts is storm preparation information. Future education should include data on the harmful effects of thunderstorms and hurricanes on pediatric asthma, and mention how individuals can take precautions to avoid or manage these effects. Along with community education, healthcare provider education is also vital. Organizations such as the Global Consortium on Climate and Health Education and Medical Society Consortium on Climate and Health can help connect providers with resources to further their climate health knowledge. By improving healthcare provider education, providers will be better able to recognize climate triggers of asthma exacerbation in their patients and assist patients in finding solutions to avoid and prevent triggers. Healthcare providers may also reduce asthma exacerbations through medication prophylaxis. A study of a thunderstorm in 1997 in Australia found that asthmatic patients who did not experience a severe attack were more likely to be using inhaled corticosteroids than those who did require hospital admission for asthma [23]. Further studies are needed to confirm this finding, but it suggests that inhaled corticosteroids could potentially be used to prevent storm exacerbations of asthma.
Lastly, creating predictive models and early warning systems is an important community level intervention. Models predicting dates of high heat or temperature fluctuation as well as dates of expected heavy storms and hurricanes should be combined with community advisories. For example, a pilot forecasting system developed in Victoria, Australia combined forecasts of gusty winds in severe thunderstorms with forecasts of high ambient grass pollen concentrations to predict epidemic thunderstorm asthma risk [24]. This system involved coordination with health and emergency management sectors, as well as public awareness and education programs [24]. Future warning systems should specifically prioritize people with asthma in low-income and minority neighborhoods.

Conclusion
Further research should elucidate the relative effectiveness of different prevention strategies for pediatric asthma exacerbations. Understanding asthma phenotypes and genomics that predict vulnerability to temperature and thunderstorm exacerbations may also help prevention efforts. In the face of worsening climate change, better characterization of triggers precipitating pediatric asthma exacerbations and implementation of prevention and management strategies is critical, especially in vulnerable populations.

Data availability statement
No new data were created or analysed in this study.