Reduction in forced vital capacity in asthmatic children on days with bushfire smoke exposure in the Australian 2019/2020 bushfire.

While bushfires have long been a part of Australia's ecosystem, the 2019–20 bushfires were an unprecedented event leading to 5.5 million hectares of land being affected in New South Wales (NSW) alone.1 This is approximately the same as the area burnt in the combined bushfire seasons of 1993–94 and 2018–19.2 Air pollution has been recognized as a risk factor for asthma development.3 An increase in emergency department visits and hospital admissions has been described in asthmatic children exposed to bushfire smoke.4 Bushfire smoke contains a complex range of gases and particles, including a particulate matter measuring less than 2.5 microns (PM2.5) composition, carbon monoxide, ozone, methane, and nitrogen oxides which is different from the one emitted by fossil fuel combustion.5 The NSW Air Quality Monitoring Network reported that 74% of the spring and summer days in 2019–20 met poor air quality standards according to the Air Quality Index.6 This study therefore aimed to determine the effects of bushfire smoke exposure during the 2019–20 bushfire season on lung function in asthmatic children. Our study used routinely collected data from children with asthma who attended the John Hunter Children's Hospital outpatient childhood asthma clinic between January 2019 and April 2020. Data were collected from electronic medical records and clinical lung function databases from children aged 4 to 16 years of age, with a confirmed diagnosis of asthma seen by a Pediatric respiratory specialist. Only children with a valid spirometry meeting ATS/ERS standards during their clinical visit were included.7 Before the appointment, parents and patients were instructed not to take the following medications for the times indicated, unless they are breathless and need to use them: short-acting inhalers (Ventolin, Atrovent, Flixotide, Bricanyl, Asmol, Airomir, Epaq) for 8 h; and long-acting inhalers (Symbicort, Seretide, Serevent, Spiriva, Oxis, Foradile) for 12 h. Data included demographic characteristics, lung function (spirometry and fraction of exhaled nitric oxide at a flow rate of 50 ml/s [FeNO50] if available), and symptom control in the past 4 weeks. Global Lung Initiative (GLI) reference equations were used to calculate spirometry measurements (FEV1, FVC, and FEV1/FVC ratio percent of predicted value [% predicted]). Bronchodilator reversibility was calculated after administration of inhaled rapid-onset beta2 agonist bronchodilator (SABA).8 For first nation Australian children, the GLI ‘Other/Mixed equation reference’ was used for the data collection. PM2.5 exposure during the period was assessed for participants located within the Sydney Greater Metropolitan Region (GMR) study region in NSW, an area of approximately 1860 square kilometers. Daily 24-h mean PM2.5 data from fixed-site government air quality monitoring stations within the study regions were measured9 and interpolated using an inverse distance weighting procedure to estimate daily PM2.5 exposure concentration for participant's residential location.10 Bushfire days were defined when three prerequisites were met: (1) the entire study region's 24-h average of PM2.5 concentration exceeded the 95th percentile (based on the period 01/01/2010 to 31/12/2018 for the Sydney GMR), (2) visual confirmation of fire for that day or up to 3 days before or after via satellite imagery, and (3) interpolated PM2.5 reading for each participant's residential address also exceed the 95th percentile for the region, to control for spatial variability in the region.10 This approach has been successfully used to identify bushfire-smoke-affected study days in several previous epidemiological studies.10, 11 Categorical measures were described using counts and percentages, while continuous measures were characterized using means with standard deviation (SD). Statistical significances were calculated using two-tailed Mann–Whitney U test or Student's t test as appropriate and chi-square test if categorical. As this was a longitudinal study with different time points, we used mixed effect regression models with a random intercept to estimate the total effect of bushfire-related smoke exposure on lung function of children. Outputs of fixed and random effects were calculated for the presence of bushfire smoke on the day of the test and for PM2.5 levels on the day of the lung function testing. Models were adjusted to account for differences found between the groups in the univariate analysis and to account for factors that usually can influence lung function, including sex, age, weight, height, being a first nation Australian, tobacco smoke exposure at home, and season. A specific sample size was not targeted; instead, a convenience sample was used. Statistical analysis was performed using STATA version 15 (Texas, USA). A p-value of <.05 was considered statistically significant. This study was approved by the Hunter New England Human Research Ethics Committee (2020/ETH00361). As we collected data from medical records and clinical databases, a waiver of consent was granted. One hundred twenty-nine children visited the asthma clinic and performed lung function tests. Of those, 49 children attended one visit, 78 children attended two visits, one child attended three visits, and one child attended four visits, leaving us with a sample of 212 occasions. PM2.5 levels and bushfire information were available for all visits. We compared data collected on a non-bushfire day (n = 176) to those on a bushfire day (n = 36). Groups were similar within themselves. Of note, first nation Australian children were more likely to be tested on a bushfire day (19.4% vs 5.8%, p = .01) and were found to reside in rural areas more commonly in this study; however, first nation Australian children did not differ on lung function values compared to non-first nation Australian children (p = .642). No differences were found in the Asthma Control Test (ACT) score for children tested on a bushfire day and children tested on a non-bushfire day. As expected PM2.5 mean levels at visit day were significantly higher on a bushfire day (35.7 μg/m3 [SD = 16.8, Min = 15.0, Max = 71.6] vs 8.3 μg/m3 [SD = 3.2, min = 3.3, max = 20.8], p < .001). Using mixed model a significant mean decrease of 5% in FVC% predicted was found in asthmatic children when they visited the clinic on a bushfire day (Table 1). Notably, the FVC decline was ameliorated 10 min after administration of bronchodilators (−3.00, 95% CI −6.83 to 0.82, p = .12). No significant decrease was found in FEV1 and FEV1/FVC ratio % predicted. When taking data from same children tested both on a bushfire and non-bushfire (n = 59), the effects of a bushfire day were comparable, even though the significance levels were not reached (−4.36, 95% CI −9.24 to 0.55, p = .08). When analyzing mean PM2.5 concentrations on the day of the clinic visit as a continuous independent variable, we found a significant decrease in FVC and FEV% predicted for each μg per cubic meter increase in PM2.5 (Table 1). Our results show for the first time that wildfire exposure around the time of lung function testing is associated with a mean decrease of 5% in FVC % predicted in asthmatic children. This effect size is considered to be of clinical importance.5, 12, 13 For instance, specific cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulators have demonstrated a therapeutical effect improvement of around 5% in FEV1 and FVC and their use in CF patients is nowadays accepted standard of care.14 We observed that the FVC decline may be, at least in part, reversible after bronchodilator inhalation. The improvement in FVC—which is static volumes of the lung—after SABA administration might be due to the reduction in the child's hyperinflation, improving inspiratory capacity. In adults with Chronic Obstructive Pulmonary Disease (COPD), administration of bronchodilator results in less air trapping as it allows better lung emptying, reducing the work of breathing.15 It has been suggested that in adults with severe airway obstruction changes in FVC should be evaluated as a clinically important relief of hyperinflation.16 In children, this needs further investigation to verify the clinical importance of a reduction in FVC. Our modeling suggests that exposure to the highest mean PM2.5 concentration of 71.6 μg/m3 on bushfire days in this study may result in a decrease of 14% in FVC % predicted and 10% in FEV1 % predicted compared to the lower level of 8.3 μg/m3 on non-bushfire days. Smoke exposure to the Australian 2019/2020 bushfire has been linked with adverse effects among both people with and without respiratory conditions in a cross-sectional study using a symptom online survey.17 To our knowledge, our study is the first to demonstrate the effects of the Australian 2019/2020 using an objective measurement—spirometry—in asthmatic children, as most studies focus on emergency department visits and hospital admissions.4, 18 A recent study in a North American pediatric asthma population only found an association between wildfire smoke exposure and FEV1 in children older than 12 years of age.19 A reduction in peak expiratory flow rate was associated with PM2.5 wildfire exposure in Brazilian children—however, a greater effect was found in children without asthma than on asthmatic children.20 While our study result is in line with previous reports, we cannot exclude that the true effect on FEV1 is so small that it remained undetected as a result of analyzing only a small sample with potentially large variability. In either case, our results suggest that bushfire smoke exposure may predominately result in a restrictive lung function limitation21 while PM2.5 exposure is associated with a mixed, restrictive and obstructive, deficit in asthmatic children. Lung volume studies would be required to confirm this hypothesis. A previous study has shown greater effects of ambient ozone exposure on FVC in a non-selected child cohort from Southern Germany22 corroborating the hypothesis that a large number of pollutants found in wildfire smoke, including PM and ozone, contribute to the induction of clinically significant FVC deficits. The investigation of potential long-term effects on FVC growth as a result of repeated exposure to bushfire requires further studies. Differences between PM2.5 and PM10 effects have been demonstrated. Even though PM2.5 is a large fraction of PM10, PM2.5 seems to be of greater health concern due to its longer residence time in the atmosphere, and its accumulation due to persistent atmospheric stability which in turn reduces its removal. This may be relevant if we compare our results that investigated PM2.5 levels and find a reduction in lung function of asthmatic children with the study by Jalaludin and associates, which did not find an association between levels of PM10 during the 1994 Australian bushfire and lung function in children with wheeze.23 We therefore speculate that finer particulate matter may affect asthmatic children more significantly due to its composition and accumulation in the air. As compared to the study by Jalaludin et al, we also used a satellite confirmation of bushfire, which could be an improved modeling of lung health effects beyond the consideration of particle size. The strengths of this study include its retrospective longitudinal design, using data from children whose asthma diagnosis is established, whose treatment is supervised by a specialist, and who were measured with identical equipment by clinical staff at a respiratory clinic. Importantly, the lung function effects occurred despite the children receiving specialist asthma treatment. In addition, our data do not suggest a selection bias where children would have attended multiple appointments due to a bushfire episodes as repeated clinical visits were not associated with bushfire days (75% vs 77.3%, p = .83) and visits were scheduled as routine follow-ups and not arranged for acute symptoms that arose from bushfire exposure. We used complex and previously employed methodology to classify bushfire day. Limitations of this study include a small and selected sample which might reflect more severe asthma phenotypes, and thus, our results may not be representative for a non-selected pediatric asthma population. Mechanistically, the toxic effects of bushfire smoke have been linked to oxidative stress24 and inflammatory responses25 highlighting potential preventive and therapeutic strategies to reduce lung function deficits and resultant disease burden caused by wildfire smoke exposure, in particular in susceptible populations such as asthmatics. Open access publishing facilitated by The University of Newcastle, as part of the Wiley - The University of Newcastle agreement via the Council of Australian University Librarians.