Wheezing Episodes in Children Before and After the Onset of the COVID-19 Pandemic in Brussels

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The aim of this study was to describe the epidemiology of childhood wheezing episodes before and after the start of the COVID-19 pandemic in relation to their potentially associated environmental triggers. Methods: Files of all children treated with salbutamol for a wheezing episode in September and October 2019, 2020 and 2021 were retrospectively reviewed. Infection epidemiology, daily concentrations of air pollutants (NO 2 , O 3, PM 10 and PM 2.5 ) and fungal spores were collected over the same time period. Results: In 2021, 298 episodes of wheezing were observed compared to 111 in 2020 and 86 in 2019 (p<0.001). Compared to 2019, children with wheezing in 2021 were significantly older (p<0.001), less likely to have a history of recurrent wheezing (p<0.001) and required less hospitalization (p=0.034). Adenovirus and SARS-CoV-2 were more prevalent in 2021 as compared to 2019 (p<0.001). The concentration of PM 10 , PM 2.5 and O 3 was higher in 2021, as compared to both 2019 and 2020 (p<0.001) while the concentration of NO 2 and airborne spores was lower in 2021 compared to 2019 (p<0.0001). Conclusion: A threefold increase in wheezing episodes was observed in the autumn post-COVID (2021) compared to pre-COVID (2019) together with a significant increase in some viruses and most air pollutants. We hypothesize that this abnormal surge may be related to the release of restrictions with rapid spread of viruses in children who were exposed to high levels of air pollution. air pollution pediatric epidemiology fungal spores SARS-CoV-2 Figures Figure 1 Figure 2 Figure 3 Figure 4 What is known - what is new What is known? The epidemiology of respiratory illnesses changed during and after the COVID-19 pandemic. Environmental factors such as viral infections, air pollution and allergens play a role in the prevalence of wheezing episodes. What is new? Wheezing episodes in Brussels children increased threefold in the autumn post-COVID (2021) compared to the autumn pre-COVID (2019) especially in children without history of recurrent wheezing. A surge in viral infections, an increase in air pollution and an “asthma triggering” effect of current or prior SARS-CoV-2 infection probably contributed to this “back-from-lockdown” asthma. Introduction Preventive measures taken during the coronavirus disease 2019 (COVID-19) pandemic led to a reduction of the number of pediatric hospitalizations for respiratory diseases [ 1 ], decreased respiratory morbidity in infants [ 2 ] and improved asthma control [ 3 ] in 2020. A decrease in the transmission of common respiratory viruses, such as rhinovirus and respiratory syncytial virus (RSV), a decrease in exposure to outdoor allergens and a reduction in air pollution may all have played a role in reducing respiratory morbidity [ 4 ]. Re-exposure to viruses, allergens, and pollutants in a pediatric population that was relatively unaffected in 2020 could lead to a respiratory illness surge as was indeed reported in several studies [ 5 , 6 ]. Moreover, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at a young age could be associated with subsequent episodes of wheezing [ 7 ] as it is observed with RSV and rhinovirus [ 8 ]. Longitudinal studies have described a strong association between outdoor air pollution and incident asthma, asthma exacerbations, hospitalization for asthma, and lower lung function [ 9 , 10 ]. Similar findings were described for exposure to allergens such as grass pollen and outdoor fungal spores [ 11 , 12 ]. The aim of this study was to determine if the number of episodes of wheezing that required salbutamol prescription at the Centre Hospitalier Universitaire (CHU) Saint-Pierre was different in the years before and after the start of the COVID-19 pandemic. We limited the study to September and October, because this is a period after the reopening of schools that is usually associated with a peak in asthma exacerbations, the so-called “Back to School asthma” [ 13 , 14 ]. Moreover, this period avoids the peak in RSV bronchiolitis admissions in Belgium usually occurring at the end of December [ 15 ]. Different environmental characteristics that could influence the epidemiology of wheezing episodes were investigated. Materials and Methods Study Population and Study Design This retrospective single-center study was conducted at the CHU Saint-Pierre in Brussels. The study population included children up to 16 years of age attending the outpatient or emergency wards for a wheezing episode requiring salbutamol treatment. Data were collected through pharmacy records on the use of salbutamol. A wheezing episode was defined as a doctor’s diagnosis of bronchiolitis, viral induced wheezing or asthma. Children treated with salbutamol for a different reason were excluded, as was consultation for a wheezing episode in the same child within the week. Asthma was defined as any doctor’s diagnosis of asthma in the patient’s hospital file. Known asthma and recurrent wheezing were defined as having asthma diagnosed or at least 1 episode of wheezing before the study episode, respectively. The study-period included the months September and October of the years 2019, 2020 and 2021. In order to validate the study period chosen, we analyzed the number of salbutamol prescriptions and RSV hospital admissions from September 2019 to February 2022. After selection of the study population, electronic files of the patients were reviewed for clinical and virological data. Viral testing was performed on nasopharyngeal aspiration or swab specimens in children according to the decision made by the attending physician. Nasopharyngeal testing is routinely done for all hospitalized patients and on indication in the outpatient setting. An antigen test was performed for 2-3 seasonal viruses together with a viral culture. In September 2020, adenovirus and parainfluenza virus were included in the routine panel, while for September-October 2019 and 2021 and October 2020, parainfluenza virus, adenovirus and RSV were tested. SARS-CoV-2 was tested separately by polymerase chain reaction (PCR). To assess a possible overall change in activity in our department, the total number of visits to our pediatric emergency and outpatient department during the study period were compared over the three study years. Infection epidemiology during the study period Data on infection epidemiology were provided by Sciensano, the Belgian institute for health, in accordance with standard academic and scientific practices. Data on RSV, adenovirus, parainfluenza virus and Mycoplasma Pneumoniae were collected from sentinel laboratories and recorded as the weekly number of positive tests in children up to 16 years of age. The number of weekly SARS-CoV-2 cases was obtained from Sciensano’s COVID-19 open data portal [16]. Because of age groups defined by Sciensano, only children up to the age of 9 were included. For rhinovirus, which is not included in the Sciensano surveillance, we extracted viral cultures done in children up to 16 years on respiratory specimens in CHU St Pierre, and compared the proportion of positive cultures over the different study periods. Air Pollution Exposure Data Data were collected via the Brussels Environment Air Quality Laboratory after agreement with the Belgian Interregional Environment Agency. A monitoring station gives air quality data that is representative of a certain area around the station. Different methods are used for the measurement of the different pollutants: O 3 (ozone) is measured by ultraviolet photometry, nitrogen dioxide (NO 2 ) by chemiluminescence and particulate matter 10 microns (PM 10 ) and particulate matter 2.5 microns (PM 2.5 ) by automatic weighing by oscillating microbalance. The measured hourly concentrations of NO 2 , PM 10 , PM 2.5 and O 3 from September 1 st to October 31 st in the year 2019, 2020 and 2021 were recorded for all stations within a 5 kilometer radius around the hospital. The overall mean (± standard deviation (SD)) daily concentration was calculated over the two study months of the years 2019, 2020 and 2021. These data were compared between the different years and to the World Health Organization (WHO) air quality guideline (AQG) [17]. Additionally, to be able to interpret these data in a broader context, the monthly means of all four pollutants were recorded from January 2019 to December 2021. Aeroallergen Exposure Data The main allergenic pollen season in Belgium ends in the beginning of September [18], and the exposure of patients to airborne pollen was thus considered negligible during the study period. Exposure of patients to airborne fungal spores was analyzed from data provided by the Belgian aerobiological surveillance network of Sciensano. The mean daily spore concentrations in the outdoor air (spore/m³) were measured in Brussels, deemed representative for at least 30 km around [19], during the study period by the Hirst method [20]. Although the indoor environment of the patients was not specifically monitored in this study, it has been assumed that the indoor fungal composition is strongly governed by the outdoor seasonality [21]. The spore integral (spore*days/m³) of the allergenic fungal taxa Basidiospora , Alternaria and Cladosporium was calculated by summing the mean daily concentrations from September 1 st to October 31 st for each of the three study years. Spore integral mean values over the study period in 2021 and 2020 were compared to 2019. Statistical Data Analysis Statistical analysis was performed using Stata/IC15.0 and Jamovi 2.2.5. Continuous variables are expressed as mean ± SD or median + interquartile range (IQR) and compared using t-tests or Mann Whitney tests according to distribution. Categorical variables are expressed in numbers and percentage and compared with Chi 2 tests. Outpatient attendance rate ratios, exact 95% confidence intervals (95% CI) and mid p-values were computed. Comparisons of numbers per year were done by Poisson-tests, and Incidence Rate Ratio (IRR) comparing 2020 and 2021 to 2019 are presented. All tests were two-tailed and the significance level was set at alpha = 0.05. Ethical Approval The study was approved by the Local Hospital Ethics Committee of CHU Saint-Pierre (file number CE/22-01-08). Results Epidemiology of Wheezing Episodes In total, 509 prescriptions of salbutamol have been recorded for 479 children over the 3 study periods. Fourteen children did not meet the inclusion criteria and were excluded. Among the 495 childhood wheezing episodes (observed in 465 children) 86 occurred in 2019, 111 in 2020 and 298 in 2021. The number of wheezing episodes in 2021 was significantly higher than in 2019 (p<0.001) (figure 1). Our longitudinal data confirmed a peak in salbutamol prescriptions in September and October 2019, 2020 and 2021 during a period of low RSV hospitalizations (supplemental figure 1). The total number of visits to our pediatric emergency and outpatient department during the study period was 10 263 in 2019, 6989 in 2020 and 10 296 in 2021. The attendance rate of 2020 was lower than in 2019 (IRR 0.68 (95%CI: 0.66-0.70, p<0.0001)), while in 2021, the attendance rate was similar to 2019 (IRR =1.00 (95%CI: 0.98-1.03)). Study Population Demographic, clinical and treatment characteristics of the study population are presented in table 1. Table 1 - Demographic, clinical and treatment characteristics of the study population 2019 n=86 2020 n=111 2021 n=298 P value 2020 vs 2019 P value 2021 vs 2019 Age (years) (mean ± SD) 3.62 ± 2.78 4.13 ± 2.80 4.55 ± 2.98 0.207 0.011 Gender: Male (n (%)) 54 (63) 75 (68) 167 (56) 0.484 0.265 Hospitalization (n (%)) 28 (33) 28 (25) 64 (22) 0.258 0.034 Origin (n (%)) 0.009 0.388 Caucasian 14 (16) 15 (14) 34 (11) Nord Africa 27 (31) 35 (32) 100 (34) Sub-Saharan Africa 9 (11) 30 (27) 38 (13) Other 14 (16) 7 (6) 29 (10) Unknown 22 (26) 24 (22) 97 (33) Known asthma (n (%)) 23 (27) 27 (24) 59 (20) 0.699 0.166 Recurrent wheezing (n (%)) 55 (64) 69 (62) 128 (43) 0.780 <0.001 Mean duration of symptoms before presentation (days) (mean ± SD) 2.60 ± 2.90 2.18 ± 2.82 2.86 ± 4.71 0.315 0.642 Diagnoses (n (%)) Asthma 15 (17) 29 (26) 87 (29) 0.336 0.070 Bronchiolitis 16 (19) 20 (18) 39 (13) Viral induced wheezing 55 (64) 62 (56) 172 (58) Treatment Salbutamol dose a 0.43 0.46 0.42 0.560 0.325 Methylprednisolone (n (%)) 20 (23) 27 (24) 56 (19) 0.861 0.360 Ipratropium (n (%)) 3 (4) 2 (2) 2 (1) 0.455 0.042 Magnesium sulphate (n (%)) 0 0 3 (1) / 0.350 Oxygen therapy (n (%)) 23 (27) 21 (19) 52 (18) 0.191 0.055 a) Salbutamol dose is expressed in number of puffs per kilo over the 1 st hour SD: standard deviation Children attending the clinic with wheezing were significantly older in 2021 compared to 2019 (p=0.011) whilst no difference was noted between 2019 and 2020 (p=0.207). Overall, the most common diagnosis was viral induced wheezing, followed by asthma and bronchiolitis. Children with known asthma represented about 20-25% of the population in all three study periods. However, in 2021, the number of patients without antecedent of wheezing was significantly higher (p<0.001). Due to inclusion criteria, all children received salbutamol therapy with a mean of 0.4 puff per kilogram (corresponding to 4 puffs per 10 kilograms) over the first hour. Around 25% of children were treated with a systemic corticosteroid while ipratropium and magnesium sulfate were seldomly used. There were no significant changes in treatment practices over the three study years. The proportion of children with wheezing who were hospitalized was lower in 2021 than in 2019 (21% versus 32%, p=0.034). Characteristics of hospitalized children were presented in table 2. Table 2 - Characteristics of hospitalized patients 2019 2020 2021 P value 2020 vs 2019 P value 2021 vs 2019 n = 28 n = 28 n = 64 0.258 0.034 Duration of hospitalization (days) (mean ± SD) 4.86 ± 4.40 3.26 ± 1.10 3.77 ± 1.55 0.073 0.089 Transfer to ICU (n (%)) 0 1 (3) 4 (6) Respiratory support (n (%)) 21 (75) 21 (72) 51 (80) 0.191 0.055 Low flow oxygen 13 (62) 14 (67) 41 (80) High flow oxygen 7 (33) 5 (24) 9 (18) CPAP 1 (5) 2 (10) 1 (2) SD: standard deviation, ICU: intensive care unit, CPAP: continuous positive airway pressure Infection Data Not all children benefited from viral testing. In 2019, 25 out of 86 children (29%) were tested. In 2020, 42 out of 111 children (38%) were tested for SARS-CoV-2 and 11 (10%) for other viruses and in 2021, 77 out of 298 children (26%) benefited from SARS-CoV-2 PCR tests and 40 (13%) were tested for other viruses. The details of viral testing are depicted in table 3. Table 3 – Viral testing (number of positive results/total tested) 2019 2020 2021 Respiratory syncytial virus 4/25 0/11 5/40 Influenza 0/25 0/11 0/40 Parainfluenza 5/25 0/11 3/40 Metapneumovirus 0/25 0/11 1/40 Adenovirus 1/25 0/11 0/40 SARS CoV-2 / 0/42 4/77 Rhinovirus 3/25 3/11 3/40 Other 0/25 2/11 1/40 Data on viral epidemiology from the surveillance network are presented in figures 2 and 3. September and October 2020 were characterized by the absence of RSV and parainfluenza but ongoing circulation of adenovirus (number of infections comparable to 2019 (p= 0.291)). In 2021 there were fewer RSV (p<0.001) but more adenovirus infections (p<0.001) than in 2019 whilst the number of parainfluenza infections did not differ between the two years (p= 0.344). The number of SARS-Co-V-2 infections was 3 to 9 times higher in 2021 than in 2020, depending on the week of the year (p<0.001). Mycoplasma Pneumoniae infections were less frequent in 2020 (p=0.003) and 2021 (p=0.005) than in 2019. The number of viral cultures in our hospital was 271 in 2019, 131 in 2020 and 133 in 2021 with a proportion of positive cultures for rhinovirus of 14%, 11% and 9% respectively (p= 0.338). Air Pollution There were five monitoring stations within a 5 km radius of the hospital and in total, 392 of 465 children (82%) lived in a municipality located within this area. In September and October 2020, the concentration of NO 2 was significantly lower (p<0.001) and the concentration of O 3 and PM 2.5 were higher than in 2019 (p<0.001). In 2021, the concentration of NO 2 remained lower than pre-COVID levels (p=0.001) but all other pollutants continued to rise significantly (p<0.001) moving further away from the WHO AQG level (table 4). Table 4 - Averages of pollutant concentrations in the months September-October over the three study years compared to the WHO AQG level 2019 2020 2021 WHO AQG level P value 2020 vs 2019 P value 2021 vs 2020 P value 2021 vs 2019 NO 2 (µg/m3) 26.3 ± 11.8 25.8 ± 15.7 25.6 ± 12.8 10 <0.001 0.427 0.001 O 3 (µg/m3) 36.0 ± 17.5 39.6 ± 20.9 42.1 ± 22.8 60 <0.001 <0.001 <0.001 PM 10 (µg/m3) 12.8 ± 6.10 14.4 ± 10.5 15.6 ± 8.46 15 0.972 <0.001 <0.001 PM 2.5 (µg/m3) 6.40 ± 3.93 7.93 ± 6.62 10.0 ± 6.71 5 <0.001 <0.001 <0.001 Values are mean ± SD: standard deviation NO 2 : nitrogen dioxide, O 3 : ozone, PM 10 : particulate matter 10 microns, PM 2.5 : particulate matter 2.5 microns, WHO AQG: World Health Organization Air Quality Guidelines The monthly mean concentration of air pollutants throughout the three study years are depicted in supplemental figure 2. Only O 3 showed a clear seasonality with a peak in spring-summer (April-July). From 2019 to 2021, the year-round concentration in NO 2 decreased significantly (p=0.038) whilst no change was notable for PM 10 , PM 2.5 and O 3 (supplemental table 1). Aeroallergens Compared to 2019, the daily concentrations of Alternaria and Cladosporium spores were higher in 2020 (IRR 1.08 (p<0.0001) and IRR 1.07 (p<0.0001) respectively) and lower in 2021 (IRR 0.66 (p<0.0001) and IRR 0.84 (p<0.0001) respectively). For the Basidiospora , the daily concentration was lower in both 2020 (IRR 0.84 (p<0.0001)) and in 2021 (IRR 0.52 (p<0.0001)) compared to 2019 (figure 4). Discussion We compared the number of wheezing episodes in September and October of the years 2019, 2020 and 2021. During autumn 2020, when many COVID-19 restrictions in Brussels were still in place [22,23], no decrease in the number of wheezing episodes (as compared to 2019) was observed despite a reduction in overall outpatient attendance. This finding contrasts with other studies that all documented a decrease in wheezing episodes with the onset of the COVID-19 pandemic and its lockdown measures in 2020 [24–27]. However, most of the studies report on the annual incidence [25,26] or incidence during strict lockdown periods [24,27] which makes comparison difficult. In autumn 2021, characterized by a release of most of the restrictions, we observed a threefold increase of the number of wheezing episodes compared to the same time period in 2019 without a significant increase in overall outpatient visits. These findings coincide with the results of a large multicenter study in the Netherlands [28] reporting a 49% increase in admissions due to asthma or wheezing in September 2021 as compared to September 2017-2019. Similarly, Be’er et al. [6] described a peak of respiratory emergency visits for asthma, named “back-from-lockdown” asthma in June 2020 in Israel, 2 weeks after local lockdown was lifted. Children presenting with wheezing in 2021 were older, had less antecedents of recurrent wheezing and required less hospitalization. It is likely that children who had less natural exposure to viruses during the different lockdown periods, presented a first episode of wheeze at a later age. This older group of children, added onto the usual asthma burden in September-October, might have contributed to the asthma peak. Moreover, the overall reduced immunological memory might have led to more rapid spread of viruses. Given the risk of aerosolization and the burden caused by testing for SARS-CoV-2, the frequency of nasopharyngeal testing in our outpatient department declined after the onset of the COVID-19 pandemic (30% and 10% in 2019 and 2020-2021). As such, little conclusions can be drawn from the viral testing results in the population studied. In line with other studies [29–34], data from the Belgian surveillance platform demonstrate that September and October 2020 were characterized by the absence of common seasonal respiratory viruses such as RSV and parainfluenza with continued circulation of adenovirus. A recrudescence of seasonal respiratory viruses has been described from early spring 2021 onwards [29–33] and in one study [33] an extraordinary increase in the number of viral respiratory infections in autumn 2021 was noted. In our study, autumn 2021 was characterized by an increase in adenovirus infections (as compared to 2019) and an important rise in SARS-CoV-2 infections compared to 2020. Indeed, SARS-CoV-2 seroprevalence in Belgian pupils rose steeply from 24% in June 2021 to 60% in December 2021 with more than half of these pupils infected during the fourth pandemic wave which was dominated by the delta variant [35]. SARS-CoV-2 has so far not been described as an important childhood wheeze trigger except in the report of Ruano et al. [36] describing an increased use of reliever therapy in a group of asthmatic children with probable COVID-19. In our study, only 4 out of 77 SARS-CoV-2 swabs were PCR positive in 2021, as such, it is difficult to argue that SARS-CoV-2 infections caused the observed peak in wheezing episodes. In addition to direct SARS-CoV-2 induced wheezing, it is possible that SARS-CoV-2 infection leads to increased susceptibility for wheezing episodes as was shown in a study by Chou et al. [7]. However, there was no SARS-CoV-2 serology performed in our study, making a possible relationship with wheezing illness merely explorative. Multiple studies describe an ongoing incidence of rhinovirus during the pandemic [34,37–39] with increased incidence after release of restrictions [37] and a clear correlation with pediatric wheezing admissions [34]. However, in our hospital the proportion of viral cultures positive for rhinovirus did not increase over the three study periods. We investigated other environmental factors, such as allergens and pollution, that could have led to an increase in wheezing episodes. From 2019 to 2021, the year-round concentration in air pollutants didn’t change except for a significant decrease in NO 2 , a pollutant strongly related to traffic, a finding that was observed before in a study in Grenoble [40]. However, we found a significantly higher concentration of PM 10 , PM 2.5 and O 3 in our study period (September and October) in 2021 as opposed to 2019. The highest increase was seen for PM 2.5 , a pollutant strongly associated with airway inflammation and childhood asthma [40,41] . In addition to the risk of asthma exacerbation, exposure to air pollution has also been linked to increased susceptibility to viral respiratory infections, including SARS-CoV-2 [42]. It is as such difficult to estimate the relative importance of different environmental factors in this study and we hypothesize that different factors contributed and interacted. Some limitations of this study are to be mentioned. Firstly, the data were collected from a single hospital in the center of Brussels and more studies will be needed to confirm these findings on a regional/rural or national scale. Unfortunately, very few children had viral testing done and data about viral epidemiology in Belgium did not include rhinovirus. Finally, only the months of September and October were analyzed. A longitudinal analysis of the whole three years would have described the epidemiology in more detail with possibly other insights. Despite these limitations, our study is adding onto the growing data about the epidemiology of respiratory diseases in the post-COVID-19 era, which brought to light the vast interrelation between climate change, pollution and viral respiratory infections as risk factors for wheezing disorders. We are encouraged to continue monitoring the burden of childhood wheezing illnesses in the inner city of Brussels along with surveillance of Brussels air quality and epidemiological trends. Abbreviations Declarations Acknowledgements We thank Sandrine Bladt, Thierry De Vos, Dr Nathalie Bossuyt and Dr Juliette Destrée for their help with the air pollution, virological and RSV hospitalization data respectively. The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. There are no competing interests to declare, nor financial or non-financial interests. References Wilder JL, Parsons CR, Growdon AS, Toomey SL, Mansbach JM. 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Pediatr Pulmonol. 58(4):1229-1236. doi:10.1002/ppul.26327 Van Brusselen D, De Troeyer K, ter Haar E, et al. (2021) Bronchiolitis in COVID-19 times: a nearly absent disease? Eur J Pediatr. 180(6):1969-1973. doi:10.1007/s00431-021-03968-6 Di Mattia G, Nenna R, Mancino E, et al. (2021) During the COVID‐19 pandemic where has respiratory syncytial virus gone? Pediatr Pulmonol. 56(10):3106-3109. doi:10.1002/ppul.25582 Fourgeaud J, Toubiana J, Chappuy H, et al. (2021) Impact of public health measures on the post-COVID-19 respiratory syncytial virus epidemics in France. Eur J Clin Microbiol Infect Dis. 40(11):2389-2395. doi:10.1007/s10096-021-04323-1 Hernández-Rivas L, Pedraz T, Calvo C, San Juan I, Mellado M a J, Robustillo A. (2023) Respiratory syncytial virus outbreak during the COVID-19 pandemic. How has it changed? Enferm Infecc Microbiol Clin. 41(6):352-355. doi:10.1016/j.eimc.2021.12.003 Maison N, Peck A, Illi S, et al. (2022) The rising of old foes: impact of lockdown periods on “non-SARS-CoV-2” viral respiratory and gastrointestinal infections. Infection. 50(2):519-524. doi:10.1007/s15010-022-01756-4 Teo KW, Patel D, Sisodia S, Roland D, Gaillard EA, Tang JW. (2022) Rhinovirus persistence during the COVID‐19 pandemic—Impact on pediatric acute wheezing presentations. J Med Virol. 94(11):5547-5552. doi:10.1002/jmv.27986 Merckx J, Callies M, Kabouche I, Desombere I, Duysburgh E, Roelants M. (2023) SARS-CoV-2 seroprevalence and determinants for salivary seropositivity among pupils and school staff: a prospective cohort study. Epidemiol Infect. 151:e75. doi:10.1017/S0950268823000584 Ruano FJ, Somoza Álvarez ML, Haroun-Díaz E, et al. (2020) Impact of the COVID-19 pandemic in children with allergic asthma. J Allergy Clin Immunol Pract. 8(9):3172-3174.e1. doi:10.1016/j.jaip.2020.07.019 Huang QS, Wood T, Jelley L, et al. (2021) Impact of the COVID-19 nonpharmaceutical interventions on influenza and other respiratory viral infections in New Zealand. Nat Commun. 12(1):1001. doi:10.1038/s41467-021-21157-9 Sullivan SG, Carlson S, Cheng AC, et al. (2020) Where has all the influenza gone? The impact of COVID-19 on the circulation of influenza and other respiratory viruses, Australia, March to September 2020. Eurosurveillance. 25(47):2001847. doi:10.2807/1560-7917.ES.2020.25.47.2001847 Tang JW, Bialasiewicz S, Dwyer DE, et al. (2021) Where have all the viruses gone? Disappearance of seasonal respiratory viruses during the COVID‐19 pandemic. J Med Virol. 93(7):4099-4101. doi:10.1002/jmv.26964 Aix ML, Petit P, Bicout DJ. (2022) Air pollution and health impacts during the COVID-19 lockdowns in Grenoble, France. Environ Pollut Barking Essex 1987. 303:119134. doi:10.1016/j.envpol.2022.119134 Agache I, Sampath V, Aguilera J, et al. (2022) Climate change and global health: A call to more research and more action. Allergy. 77(5):1389-1407. doi:10.1111/all.15229 Burbank AJ. (2023) Risk Factors for Respiratory Viral Infections: A Spotlight on Climate Change and Air Pollution. J Asthma Allergy. 16:183-194. doi:10.2147/JAA.S364845 Additional Declarations No competing interests reported. Supplementary Files Supplementarymaterial.docx Supplfigure1.jpg Supplfigure2.jpg Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3886091","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":269348423,"identity":"2879c7c2-4eed-413c-b796-b1f33b16fc3c","order_by":0,"name":"Clémentine Delporte","email":"","orcid":"","institution":"Centre Hospitalier Universitaire de Saint-Pierre","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Clémentine","middleName":"","lastName":"Delporte","suffix":""},{"id":269348425,"identity":"14706d9e-3c44-40ad-a304-b8acfd10710d","order_by":1,"name":"Lore Van Bruwaene","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABCElEQVRIiWNgGAWjYBACPhjDAMbgBxEJBbi1sGFokWwAaTHAphiXFoMDKFwsWth7Hz5gbLPLM5c+Yybxo+KOnPH51YkfHhgwyPOLHcCuhee4sQFjW3KxZV+OmWTPmWfGZjfebpYAOsxw5uwE7Fok0tgkGM4wJ244w2N2g7ftcOK2G2c3gLQkGNzGqYX9B8OZerCWm3//Ha7fPOPs5h8EtABDoOIwWMtt3obDCQb8vdvw28JzjFkioeJ44s4etvLfMscOG864wbvNIsFAAqdf+NnbGD98MKhO3M7DvNnwTc1hef7+s5tv/qiwkeeXxq4FDFClJMBcCdzKsVh8gBTVo2AUjIJRMAIAANCCW/imH6yLAAAAAElFTkSuQmCC","orcid":"","institution":"Centre Hospitalier Universitaire de Saint-Pierre","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Lore","middleName":"Van","lastName":"Bruwaene","suffix":""},{"id":269348426,"identity":"2cef6fc4-e9b5-4322-840c-988d0157f9d7","order_by":2,"name":"Nicolas Bruffaerts","email":"","orcid":"","institution":"Sciensano (Belgium)","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Nicolas","middleName":"","lastName":"Bruffaerts","suffix":""},{"id":269348427,"identity":"78d7570d-73de-48c0-959c-fb079bdb1983","order_by":3,"name":"Elisabeth Rebuffat","email":"","orcid":"","institution":"Centre Hospitalier Universitaire de Saint-Pierre","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Elisabeth","middleName":"","lastName":"Rebuffat","suffix":""},{"id":269348429,"identity":"9450adac-fa97-405a-b3c6-7a510d156f15","order_by":4,"name":"Tessa Goetghebuer","email":"","orcid":"","institution":"Centre Hospitalier Universitaire de Saint-Pierre","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Tessa","middleName":"","lastName":"Goetghebuer","suffix":""}],"badges":[],"createdAt":"2024-01-21 22:29:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3886091/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3886091/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":50383575,"identity":"7c0b48d6-18a6-4141-aaeb-e17758c194a9","added_by":"auto","created_at":"2024-01-30 17:26:12","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":31835,"visible":true,"origin":"","legend":"\u003cp\u003eNumber of wheezing episodes per week for the years 2019, 2020 and 2021\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3886091/v1/d9583d06bc750e1fc59b8516.jpg"},{"id":50385666,"identity":"5b5f61ed-f2e0-4dff-ae3a-6fecca2ac308","added_by":"auto","created_at":"2024-01-30 17:34:12","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":69643,"visible":true,"origin":"","legend":"\u003cp\u003eWeekly positive tests of different organisms from sentinel laboratories in the study period (children 0-16 years).\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3886091/v1/8fbf67c4cfebde1ccd1509a6.jpg"},{"id":50383576,"identity":"f0b8fe0a-fcb3-4bec-ad13-d1e14635368a","added_by":"auto","created_at":"2024-01-30 17:26:12","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":22549,"visible":true,"origin":"","legend":"\u003cp\u003eWeekly SARS-CoV-2 cases from the open data interactive platform (children 0-9 years). SARS-CoV-2, Severe Acute Respiratory Syndrome Coronavirus-2\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3886091/v1/34ee57377c6daf8604a6b676.jpg"},{"id":50383578,"identity":"aa2fb709-2fc7-4fcc-9fee-efe0d0da512a","added_by":"auto","created_at":"2024-01-30 17:26:13","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":87030,"visible":true,"origin":"","legend":"\u003cp\u003eDaily concentrations and integrals of airborne spores in Brussels during the study period\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3886091/v1/bd1b453f75ba15211738431f.jpg"},{"id":51289895,"identity":"9a7e8f5a-84d3-4d8c-a696-9701d3e97f17","added_by":"auto","created_at":"2024-02-18 19:37:25","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":507678,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3886091/v1/a56debb1-514b-47f0-9524-1f1ab3f2dc1c.pdf"},{"id":50383580,"identity":"3b714ffd-1f88-4727-8d01-8c7c28923680","added_by":"auto","created_at":"2024-01-30 17:26:13","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":287019,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarymaterial.docx","url":"https://assets-eu.researchsquare.com/files/rs-3886091/v1/37d42155fb7c84a7ebd61daf.docx"},{"id":50385667,"identity":"1bb79b28-56a2-4575-9633-942a52fce1a3","added_by":"auto","created_at":"2024-01-30 17:34:13","extension":"jpg","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":150528,"visible":true,"origin":"","legend":"","description":"","filename":"Supplfigure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3886091/v1/2a608643ede7f2e837f717d5.jpg"},{"id":50383579,"identity":"c21aee36-7505-451f-9271-19da66777b80","added_by":"auto","created_at":"2024-01-30 17:26:13","extension":"jpg","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":120539,"visible":true,"origin":"","legend":"","description":"","filename":"Supplfigure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3886091/v1/a65449877d9c0b99832bcd89.jpg"}],"financialInterests":"No competing interests reported.","formattedTitle":"Wheezing Episodes in Children Before and After the Onset of the COVID-19 Pandemic in Brussels","fulltext":[{"header":"What is known - what is new ","content":"\u003cp\u003eWhat is known?\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003eThe epidemiology of respiratory illnesses changed during and after the COVID-19 pandemic.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eEnvironmental factors such as viral infections, air pollution and allergens play a role in the prevalence of wheezing episodes.\u0026nbsp;\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eWhat is new?\u0026nbsp;\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003eWheezing episodes in Brussels children increased threefold in the autumn post-COVID (2021) compared to the autumn pre-COVID (2019) especially in children without history of recurrent wheezing.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eA surge in viral infections, an increase in air pollution and an \u0026ldquo;asthma triggering\u0026rdquo; effect of current or prior SARS-CoV-2 infection probably contributed \u0026nbsp;to this \u0026ldquo;back-from-lockdown\u0026rdquo; asthma.\u0026nbsp;\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Introduction","content":"\u003cp\u003ePreventive measures taken during the coronavirus disease 2019 (COVID-19) pandemic led to a reduction of the number of pediatric hospitalizations for respiratory diseases [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], decreased respiratory morbidity in infants [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] and improved asthma control [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] in 2020. A decrease in the transmission of common respiratory viruses, such as rhinovirus and respiratory syncytial virus (RSV), a decrease in exposure to outdoor allergens and a reduction in air pollution may all have played a role in reducing respiratory morbidity [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRe-exposure to viruses, allergens, and pollutants in a pediatric population that was relatively unaffected in 2020 could lead to a respiratory illness surge as was indeed reported in several studies [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Moreover, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at a young age could be associated with subsequent episodes of wheezing [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] as it is observed with RSV and rhinovirus [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eLongitudinal studies have described a strong association between outdoor air pollution and incident asthma, asthma exacerbations, hospitalization for asthma, and lower lung function [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Similar findings were described for exposure to allergens such as grass pollen and outdoor fungal spores [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe aim of this study was to determine if the number of episodes of wheezing that required salbutamol prescription at the Centre Hospitalier Universitaire (CHU) Saint-Pierre was different in the years before and after the start of the COVID-19 pandemic. We limited the study to September and October, because this is a period after the reopening of schools that is usually associated with a peak in asthma exacerbations, the so-called \u0026ldquo;Back to School asthma\u0026rdquo; [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Moreover, this period avoids the peak in RSV bronchiolitis admissions in Belgium usually occurring at the end of December [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Different environmental characteristics that could influence the epidemiology of wheezing episodes were investigated.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eStudy Population and Study Design\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective single-center study was conducted at the CHU Saint-Pierre in \u0026nbsp;Brussels. The study population included children up to 16 years of age attending the outpatient or emergency wards for a wheezing episode requiring salbutamol treatment. Data were collected through pharmacy records on the use of salbutamol. A wheezing episode was defined as a doctor\u0026rsquo;s diagnosis of bronchiolitis, viral induced wheezing or asthma. Children treated with salbutamol for a different reason were excluded, as was consultation for a wheezing episode in the same child within the week. Asthma was defined as any doctor\u0026rsquo;s diagnosis of asthma in the patient\u0026rsquo;s hospital file. Known asthma and recurrent wheezing were defined as having asthma diagnosed or at least 1 episode of wheezing before the study episode, respectively. \u0026nbsp;The study-period included the months September and October of the years 2019, 2020 and 2021. \u0026nbsp;In order to validate the study period chosen, we analyzed the number of salbutamol prescriptions and RSV hospital admissions from September 2019 to February 2022.\u003c/p\u003e\n\u003cp\u003eAfter selection of the study population, electronic files of the patients were reviewed for clinical and virological data.\u003c/p\u003e\n\u003cp\u003eViral testing was performed on nasopharyngeal aspiration or swab specimens in children according to the decision made by the attending physician. Nasopharyngeal testing is routinely done for all hospitalized patients and on indication in the outpatient setting. An antigen test was performed for 2-3 seasonal viruses together with a viral culture. In September 2020, adenovirus and parainfluenza virus were included in the routine panel, while for September-October 2019 and 2021 and October 2020, parainfluenza virus, adenovirus and RSV were tested. SARS-CoV-2 was tested separately by polymerase chain reaction (PCR).\u003c/p\u003e\n\u003cp\u003eTo assess a possible overall change in activity in our department, the total number of visits to our pediatric emergency and outpatient department during the study period were compared over the three study years.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eInfection epidemiology during the study period\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData on infection epidemiology were provided by Sciensano, the Belgian institute for health, in accordance with standard academic and scientific practices. Data on RSV, adenovirus, parainfluenza virus and Mycoplasma Pneumoniae were collected from sentinel laboratories and recorded as the weekly number of positive tests in children up to 16 years of age. The number of weekly SARS-CoV-2 cases was obtained from Sciensano\u0026rsquo;s COVID-19 open data portal [16]. Because of age groups defined by Sciensano, only children up to the age of 9 were included.\u003c/p\u003e\n\u003cp\u003eFor rhinovirus, which is not included \u0026nbsp;in the Sciensano surveillance, we extracted viral cultures done in children up to 16 years on respiratory specimens in CHU St Pierre, and compared the proportion of positive cultures over the different study periods.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAir Pollution Exposure Data\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData were collected via the Brussels Environment Air Quality Laboratory after agreement with the Belgian Interregional Environment Agency.\u003c/p\u003e\n\u003cp\u003eA monitoring station gives air quality data that is representative of a certain area around the station. Different methods are used for the measurement of the different pollutants: O\u003csub\u003e3\u003c/sub\u003e (ozone) is measured by ultraviolet photometry, nitrogen dioxide (NO\u003csub\u003e2\u003c/sub\u003e) by chemiluminescence and particulate matter 10 microns (PM\u003csub\u003e10\u003c/sub\u003e) and particulate matter 2.5 microns (PM\u003csub\u003e2.5\u003c/sub\u003e) by automatic weighing by oscillating microbalance.\u003c/p\u003e\n\u003cp\u003eThe measured hourly concentrations of NO\u003csub\u003e2\u003c/sub\u003e, PM\u003csub\u003e10\u003c/sub\u003e, PM\u003csub\u003e2.5\u003c/sub\u003e and O\u003csub\u003e3\u003c/sub\u003e from September 1\u003csup\u003est\u003c/sup\u003e to October 31\u003csup\u003est\u003c/sup\u003e in the year 2019, 2020 and 2021 were recorded for all stations within a 5 kilometer radius around the hospital. The overall mean (\u0026plusmn; standard deviation (SD)) daily concentration was calculated over the two study months of the years 2019, 2020 and 2021. These data were compared between the different years and to the World Health Organization (WHO) air quality guideline (AQG) [17]. Additionally, to be able to interpret these data in a broader context, the monthly means of all four pollutants were recorded from January 2019 to December 2021.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAeroallergen Exposure Data\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe main allergenic pollen season in Belgium ends in the beginning of September [18], and the exposure of patients to airborne pollen was thus considered negligible during the study period.\u003c/p\u003e\n\u003cp\u003eExposure of patients to airborne fungal spores was analyzed from data provided by the Belgian aerobiological surveillance network of Sciensano. The mean daily spore concentrations in the outdoor air (spore/m\u0026sup3;) were measured in Brussels, deemed representative for at least 30 km around [19], during the study period by the Hirst method [20]. Although the indoor environment of the patients was not specifically monitored in this study, it has been assumed that the indoor fungal composition is strongly governed by the outdoor seasonality [21].\u003c/p\u003e\n\u003cp\u003eThe spore integral (spore*days/m\u0026sup3;) of the allergenic fungal taxa \u003cem\u003eBasidiospora\u003c/em\u003e, \u003cem\u003eAlternaria\u003c/em\u003e and \u003cem\u003eCladosporium\u003c/em\u003e was calculated by summing the mean daily concentrations from September 1\u003csup\u003est\u003c/sup\u003e to October 31\u003csup\u003est\u003c/sup\u003e for each of the three study years. Spore integral mean values over the study period in 2021 and 2020 were compared to 2019.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eStatistical Data Analysis\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStatistical analysis was performed using Stata/IC15.0 and Jamovi 2.2.5. Continuous variables are expressed as mean \u0026plusmn; SD or median + interquartile range (IQR) and compared using t-tests or Mann Whitney tests according to distribution. Categorical variables are expressed in numbers and percentage and compared with Chi\u003csup\u003e2\u003c/sup\u003e tests. Outpatient attendance rate ratios, exact 95% confidence intervals (95% CI) and mid p-values were computed. Comparisons of numbers per year were done by Poisson-tests, and Incidence Rate Ratio (IRR) comparing 2020 and 2021 to 2019 are presented. All tests were two-tailed and the significance level was set at alpha = 0.05.\u003cbr\u003e \u003cstrong\u003e\u003cem\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eEthical Approval\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Local Hospital Ethics Committee of CHU Saint-Pierre (file number CE/22-01-08).\u0026nbsp;\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eEpidemiology of Wheezing Episodes\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn total, 509 prescriptions of salbutamol have been recorded for 479 children over the 3 study periods. Fourteen children did not meet the inclusion criteria and were excluded. Among \u0026nbsp;the 495 childhood wheezing episodes (observed in 465 children) 86 occurred in 2019, 111 in 2020 and 298 in 2021. The number of wheezing episodes in 2021 was significantly higher than in 2019 (p\u0026lt;0.001) (figure 1).\u003c/p\u003e\n\u003cp\u003eOur longitudinal data confirmed a peak in salbutamol prescriptions in September and October 2019, 2020 and 2021 during a period of low RSV hospitalizations (supplemental figure 1).\u003c/p\u003e\n\u003cp\u003eThe total number of visits to our pediatric emergency and outpatient department during the study period was 10 263 in 2019, 6989 in 2020 and 10 296 in 2021. The attendance rate of 2020 was lower than in 2019 (IRR \u0026nbsp;0.68 (95%CI: 0.66-0.70, p\u0026lt;0.0001)), while in 2021, the attendance rate was similar to 2019 (IRR =1.00 (95%CI: 0.98-1.03)).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eStudy Population\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDemographic, clinical and treatment characteristics of the study population are presented in table 1.\u003c/p\u003e\n\u003cp\u003eTable 1 - Demographic, clinical and treatment characteristics of the study population\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"103%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e2019\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003en=86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e2020\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003en=111\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e2021\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003en=298\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value 2020 vs 2019\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value 2021 vs 2019\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003eAge (years) (mean \u0026plusmn; SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e3.62 \u0026plusmn; 2.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e4.13 \u0026plusmn; 2.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e4.55 \u0026plusmn; 2.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" valign=\"top\"\u003e\n \u003cp\u003e0.207\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.011\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003eGender: Male (n (%))\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e54 (63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e75 (68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e167 (56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" valign=\"top\"\u003e\n \u003cp\u003e0.484\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e0.265\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003eHospitalization (n (%))\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e28 (33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e28 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e64 (22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" valign=\"top\"\u003e\n \u003cp\u003e0.258\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.034\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003eOrigin (n (%))\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" rowspan=\"6\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.009\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" rowspan=\"6\"\u003e\n \u003cp\u003e0.388\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"42.30769230769231%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Caucasian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e14 (16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e15 (14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e34 (11)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"42.30769230769231%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Nord Africa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e27 (31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e35 (32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e100 (34)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"42.30769230769231%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Sub-Saharan Africa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e9 (11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e30 (27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e38 (13)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"42.30769230769231%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Other\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e14 (16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e7 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e29 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"42.30769230769231%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Unknown\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e22 (26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e24 (22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e97 (33)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003eKnown asthma (n (%))\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e23 (27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e27 (24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e59 (20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" valign=\"top\"\u003e\n \u003cp\u003e0.699\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e0.166\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003eRecurrent wheezing (n (%))\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e55 (64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e69 (62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e128 (43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" valign=\"top\"\u003e\n \u003cp\u003e0.780\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003eMean duration of symptoms before presentation (days) (mean \u0026plusmn; SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e2.60 \u0026plusmn; 2.90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e2.18 \u0026plusmn; 2.82\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e2.86 \u0026plusmn; 4.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" valign=\"top\"\u003e\n \u003cp\u003e0.315\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e0.642\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003eDiagnoses (n (%))\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Asthma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e15 (17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e29 (26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e87 (29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" rowspan=\"3\"\u003e\n \u003cp\u003e0.336\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" rowspan=\"3\"\u003e\n \u003cp\u003e0.070\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"42.30769230769231%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Bronchiolitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e16 (19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e20 (18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e39 (13)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"42.30769230769231%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Viral induced wheezing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e55 (64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e62 (56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.23076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e172 (58)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003eTreatment\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Salbutamol dose \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e0.43\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e0.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e0.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" valign=\"top\"\u003e\n \u003cp\u003e0.560\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e0.325\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Methylprednisolone (n (%))\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e20 (23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e27 (24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e56 (19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" valign=\"top\"\u003e\n \u003cp\u003e0.861\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e0.360\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Ipratropium (n (%))\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e3 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e2 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e2 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" valign=\"top\"\u003e\n \u003cp\u003e0.455\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.042\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Magnesium sulphate (n (%))\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e0 \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e3 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" valign=\"top\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e0.350\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Oxygen therapy (n (%))\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e23 (27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e21 (19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.151515151515152%\" valign=\"top\"\u003e\n \u003cp\u003e52 (18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.1010101010101%\" valign=\"top\"\u003e\n \u003cp\u003e0.191\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.11111111111111%\" valign=\"top\"\u003e\n \u003cp\u003e0.055\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"6\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003ea) Salbutamol dose is expressed in number of puffs per kilo over the 1\u003csup\u003est\u003c/sup\u003e hour\u003cbr\u003e\u0026nbsp;SD: standard deviation\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eChildren attending the clinic with wheezing were significantly older in 2021 compared to 2019 (p=0.011) whilst no difference was noted between 2019 and 2020 (p=0.207).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOverall, the most common diagnosis was viral induced wheezing, followed by asthma and bronchiolitis. Children with known asthma represented about 20-25% of the population in all three study periods. However, in 2021, the number of \u0026nbsp;patients without antecedent of wheezing was significantly higher \u0026nbsp;(p\u0026lt;0.001). Due to inclusion criteria, all children received salbutamol therapy with a mean of 0.4 puff per kilogram (corresponding to 4 puffs per 10 kilograms) over the first hour. Around 25% of children were treated with a systemic corticosteroid while ipratropium and magnesium sulfate were seldomly used. There were no significant changes in treatment practices over the three study years.\u003c/p\u003e\n\u003cp\u003eThe proportion of children with wheezing who were hospitalized was lower in 2021 than in 2019 (21% versus 32%, p=0.034). Characteristics of hospitalized children were presented in table 2.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 2 -\u0026nbsp;Characteristics of hospitalized patients\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"104%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.416666666666664%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e2019\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e2020\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e2021\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value 2020 vs 2019\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value 2021 vs 2019\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.416666666666664%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"top\"\u003e\n \u003cp\u003en = 28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"top\"\u003e\n \u003cp\u003en = 28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"top\"\u003e\n \u003cp\u003en = 64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"top\"\u003e\n \u003cp\u003e0.258\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.034\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.416666666666664%\" valign=\"top\"\u003e\n \u003cp\u003eDuration of hospitalization (days) (mean \u0026plusmn; SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"top\"\u003e\n \u003cp\u003e4.86 \u0026plusmn; 4.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"top\"\u003e\n \u003cp\u003e3.26 \u0026plusmn; 1.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"top\"\u003e\n \u003cp\u003e3.77 \u0026plusmn; 1.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"top\"\u003e\n \u003cp\u003e0.073\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"top\"\u003e\n \u003cp\u003e0.089\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.416666666666664%\" valign=\"top\"\u003e\n \u003cp\u003eTransfer to ICU (n (%))\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"top\"\u003e\n \u003cp\u003e1 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"top\"\u003e\n \u003cp\u003e4 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.416666666666664%\" valign=\"top\"\u003e\n \u003cp\u003eRespiratory support (n (%))\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"top\"\u003e\n \u003cp\u003e21 (75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"top\"\u003e\n \u003cp\u003e21 (72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"top\"\u003e\n \u003cp\u003e51 (80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"top\"\u003e\n \u003cp\u003e0.191\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"top\"\u003e\n \u003cp\u003e0.055\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.416666666666664%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Low flow oxygen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"top\"\u003e\n \u003cp\u003e13 (62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"top\"\u003e\n \u003cp\u003e14 (67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"top\"\u003e\n \u003cp\u003e41 (80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" rowspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" rowspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"44.73684210526316%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; High flow oxygen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.42105263157895%\" valign=\"top\"\u003e\n \u003cp\u003e7 (33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.42105263157895%\" valign=\"top\"\u003e\n \u003cp\u003e5 (24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.42105263157895%\" valign=\"top\"\u003e\n \u003cp\u003e9 (18)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"44.73684210526316%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; CPAP\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.42105263157895%\" valign=\"top\"\u003e\n \u003cp\u003e1 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.42105263157895%\" valign=\"top\"\u003e\n \u003cp\u003e2 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.42105263157895%\" valign=\"top\"\u003e\n \u003cp\u003e1 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"6\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eSD: standard deviation, ICU: intensive care unit, CPAP: continuous positive airway pressure\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eInfection Data\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot all children benefited from viral testing. In 2019, 25 out of 86 children (29%) were tested. In 2020, 42 out of 111 children (38%) were tested for SARS-CoV-2 and 11 (10%) for other viruses and in 2021, 77 out of 298 children (26%) benefited from SARS-CoV-2 PCR tests and 40 (13%) were tested for other viruses. The details of viral testing are depicted in table 3.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 3 \u0026ndash; Viral testing (number of positive results/total tested)\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"87%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.795918367346935%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e2019\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e2020\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e2021\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.795918367346935%\" valign=\"top\"\u003e\n \u003cp\u003eRespiratory syncytial virus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\" valign=\"top\"\u003e\n \u003cp\u003e4/25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\" valign=\"top\"\u003e\n \u003cp\u003e0/11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\" valign=\"top\"\u003e\n \u003cp\u003e5/40\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.795918367346935%\" valign=\"top\"\u003e\n \u003cp\u003eInfluenza\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\" valign=\"top\"\u003e\n \u003cp\u003e0/25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\" valign=\"top\"\u003e\n \u003cp\u003e0/11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\" valign=\"top\"\u003e\n \u003cp\u003e0/40\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.795918367346935%\" valign=\"top\"\u003e\n \u003cp\u003eParainfluenza\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\" valign=\"top\"\u003e\n \u003cp\u003e5/25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\" valign=\"top\"\u003e\n \u003cp\u003e0/11\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\" valign=\"top\"\u003e\n \u003cp\u003e3/40\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.795918367346935%\" valign=\"top\"\u003e\n \u003cp\u003eMetapneumovirus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\" valign=\"top\"\u003e\n \u003cp\u003e0/25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\" valign=\"top\"\u003e\n \u003cp\u003e0/11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\" valign=\"top\"\u003e\n \u003cp\u003e1/40\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.795918367346935%\" valign=\"top\"\u003e\n \u003cp\u003eAdenovirus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\" valign=\"top\"\u003e\n \u003cp\u003e1/25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\" valign=\"top\"\u003e\n \u003cp\u003e0/11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\" valign=\"top\"\u003e\n \u003cp\u003e0/40\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.795918367346935%\" valign=\"top\"\u003e\n \u003cp\u003eSARS CoV-2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\" valign=\"top\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\" valign=\"top\"\u003e\n \u003cp\u003e0/42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\" valign=\"top\"\u003e\n \u003cp\u003e4/77\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.795918367346935%\" valign=\"top\"\u003e\n \u003cp\u003eRhinovirus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\" valign=\"top\"\u003e\n \u003cp\u003e3/25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\" valign=\"top\"\u003e\n \u003cp\u003e3/11\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\" valign=\"top\"\u003e\n \u003cp\u003e3/40\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.795918367346935%\" valign=\"top\"\u003e\n \u003cp\u003eOther\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.428571428571427%\" valign=\"top\"\u003e\n \u003cp\u003e0/25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\" valign=\"top\"\u003e\n \u003cp\u003e2/11\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.387755102040817%\" valign=\"top\"\u003e\n \u003cp\u003e1/40\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eData on viral epidemiology from the surveillance network are presented in figures 2 and 3.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSeptember and October 2020 were characterized by the absence of RSV and parainfluenza but ongoing circulation of adenovirus (number of infections comparable to 2019 (p= 0.291)). In 2021 there were fewer RSV (p\u0026lt;0.001) but more adenovirus infections (p\u0026lt;0.001) than in 2019 whilst the number of parainfluenza infections did not differ between the two years (p= 0.344). \u0026nbsp;The number of SARS-Co-V-2 infections was 3 to 9 times higher in 2021 than in 2020, depending on the week of the year (p\u0026lt;0.001). Mycoplasma Pneumoniae infections were less frequent in 2020 (p=0.003) and 2021 (p=0.005) than in 2019.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe number of viral cultures in our hospital was 271 in 2019, 131 in 2020 and 133 in 2021 with a proportion of positive cultures for rhinovirus of 14%, 11% and 9% respectively (p= 0.338).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAir Pollution\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere were five monitoring stations within a 5 km radius of the hospital and in total, 392 of 465 children (82%) lived in a municipality located within this area.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn September and October 2020, the concentration of NO\u003csub\u003e2\u003c/sub\u003e was significantly lower (p\u0026lt;0.001) and the concentration of O\u003csub\u003e3\u003c/sub\u003e and PM\u003csub\u003e2.5\u0026nbsp;\u003c/sub\u003ewere higher than in 2019 (p\u0026lt;0.001). In 2021, the concentration of NO\u003csub\u003e2\u003c/sub\u003e remained lower than pre-COVID levels (p=0.001) but all other pollutants continued to rise significantly (p\u0026lt;0.001) moving further away from the WHO AQG level (table 4).\u003c/p\u003e\n\u003cp\u003eTable 4 - Averages of pollutant concentrations in the months September-October over the three study years compared to the WHO AQG level\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"614\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.214983713355048%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.472312703583063%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e2019\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.309446254071661%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e2020\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.472312703583063%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e2021\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.283387622149837%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eWHO AQG level\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.749185667752442%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value 2020 vs 2019\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.749185667752442%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value 2021 vs 2020\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.749185667752442%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value 2021 vs 2019\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.214983713355048%\" valign=\"top\"\u003e\n \u003cp\u003eNO\u003csub\u003e2\u003c/sub\u003e (\u0026micro;g/m3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.472312703583063%\" valign=\"top\"\u003e\n \u003cp\u003e26.3 \u0026plusmn; 11.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.309446254071661%\" valign=\"top\"\u003e\n \u003cp\u003e25.8 \u0026plusmn; 15.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.472312703583063%\" valign=\"top\"\u003e\n \u003cp\u003e25.6 \u0026plusmn; 12.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.283387622149837%\" valign=\"top\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.749185667752442%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.749185667752442%\" valign=\"top\"\u003e\n \u003cp\u003e0.427\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.749185667752442%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.214983713355048%\" valign=\"top\"\u003e\n \u003cp\u003eO\u003csub\u003e3\u003c/sub\u003e (\u0026micro;g/m3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.472312703583063%\" valign=\"top\"\u003e\n \u003cp\u003e36.0 \u0026plusmn; 17.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.309446254071661%\" valign=\"top\"\u003e\n \u003cp\u003e39.6 \u0026plusmn; 20.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.472312703583063%\" valign=\"top\"\u003e\n \u003cp\u003e42.1 \u0026plusmn; 22.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.283387622149837%\" valign=\"top\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.749185667752442%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.749185667752442%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.749185667752442%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.214983713355048%\" valign=\"top\"\u003e\n \u003cp\u003ePM\u003csub\u003e10\u003c/sub\u003e (\u0026micro;g/m3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.472312703583063%\" valign=\"top\"\u003e\n \u003cp\u003e12.8 \u0026plusmn; 6.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.309446254071661%\" valign=\"top\"\u003e\n \u003cp\u003e14.4 \u0026plusmn; 10.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.472312703583063%\" valign=\"top\"\u003e\n \u003cp\u003e15.6 \u0026plusmn; 8.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.283387622149837%\" valign=\"top\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.749185667752442%\" valign=\"top\"\u003e\n \u003cp\u003e0.972\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.749185667752442%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.749185667752442%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.214983713355048%\" valign=\"top\"\u003e\n \u003cp\u003ePM\u003csub\u003e2.5\u003c/sub\u003e (\u0026micro;g/m3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.472312703583063%\" valign=\"top\"\u003e\n \u003cp\u003e6.40 \u0026plusmn; 3.93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.309446254071661%\" valign=\"top\"\u003e\n \u003cp\u003e7.93 \u0026plusmn; 6.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.472312703583063%\" valign=\"top\"\u003e\n \u003cp\u003e10.0 \u0026plusmn; 6.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.283387622149837%\" valign=\"top\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.749185667752442%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.749185667752442%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.749185667752442%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"8\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eValues are mean \u0026plusmn; SD: standard deviation\u003cbr\u003e NO\u003csub\u003e2\u003c/sub\u003e:\u0026nbsp;\u003c/em\u003e\u003cem\u003enitrogen dioxide, O\u003csub\u003e3\u003c/sub\u003e: ozone, PM\u003csub\u003e10\u003c/sub\u003e: particulate matter 10 microns, PM\u003csub\u003e2.5\u003c/sub\u003e: particulate matter 2.5 microns, WHO AQG:\u0026nbsp;\u003c/em\u003e\u003cem\u003eWorld Health Organization Air Quality Guidelines\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eThe monthly mean concentration of air pollutants throughout the three study years are depicted in supplemental figure 2.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOnly O\u003csub\u003e3\u003c/sub\u003e showed a clear seasonality with a peak in spring-summer (April-July). From 2019 to 2021, the year-round concentration in NO\u003csub\u003e2\u003c/sub\u003e decreased significantly (p=0.038) whilst no change was notable for PM\u003csub\u003e10\u003c/sub\u003e, PM\u003csub\u003e2.5\u003c/sub\u003e and O\u003csub\u003e3\u003c/sub\u003e (supplemental table 1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAeroallergens\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCompared to 2019, the daily concentrations of \u003cem\u003eAlternaria\u003c/em\u003e and \u003cem\u003eCladosporium\u003c/em\u003e spores were higher in 2020 (IRR 1.08 (p\u0026lt;0.0001) and \u0026nbsp;IRR 1.07 (p\u0026lt;0.0001) respectively) and lower in 2021 (IRR 0.66 (p\u0026lt;0.0001) and \u0026nbsp;IRR 0.84 (p\u0026lt;0.0001) respectively). For the \u003cem\u003eBasidiospora\u003c/em\u003e, the daily concentration was \u0026nbsp;lower in both 2020 (IRR 0.84 (p\u0026lt;0.0001)) and in 2021 (IRR 0.52 (p\u0026lt;0.0001)) compared to 2019 (figure 4).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe compared the number of wheezing episodes in September and October of the years 2019, 2020 and 2021.\u003c/p\u003e\n\u003cp\u003eDuring autumn 2020, when many COVID-19 restrictions in Brussels were still in place [22,23], no decrease in the number of wheezing episodes (as compared to 2019) was observed despite a reduction in overall outpatient attendance. This finding contrasts with other studies that all documented a decrease in wheezing episodes with the onset of the COVID-19 pandemic and its lockdown measures in 2020 [24\u0026ndash;27]. However, most of the studies report on the annual incidence [25,26] or incidence during strict lockdown periods [24,27] which makes comparison difficult.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn autumn 2021, characterized by a release of most of the restrictions, we observed a threefold increase of the number of wheezing episodes compared to the same time period in 2019 without a significant increase in overall outpatient visits. These findings coincide with the results of a large multicenter study in the Netherlands [28] reporting a 49% increase in admissions due to asthma or wheezing in September 2021 as compared to September 2017-2019. Similarly, Be\u0026rsquo;er et al. [6] described a peak of respiratory emergency visits for asthma, named \u0026ldquo;back-from-lockdown\u0026rdquo; asthma in June 2020 in Israel, 2 weeks after local lockdown was lifted.\u003c/p\u003e\n\u003cp\u003eChildren presenting with wheezing in 2021 were older, had less antecedents of recurrent wheezing and required less hospitalization. It is likely that children who had less natural exposure to viruses during the different lockdown periods, presented a first episode of wheeze at a later age. This older group of children, added onto the usual asthma burden in September-October, might have contributed to the asthma peak. Moreover, the overall reduced immunological memory might have led to more rapid spread of viruses.\u003c/p\u003e\n\u003cp\u003eGiven the risk of aerosolization and the burden caused by testing for SARS-CoV-2, the frequency of nasopharyngeal testing in our outpatient department declined after the onset of the COVID-19 pandemic (30% and 10% in 2019 and 2020-2021). As such, little conclusions can be drawn from the viral testing results in the population studied.\u003c/p\u003e\n\u003cp\u003eIn line with other studies [29\u0026ndash;34], data from the Belgian surveillance platform demonstrate that September and October 2020 were characterized by the absence of common seasonal respiratory viruses such as RSV and parainfluenza with continued circulation of adenovirus. A recrudescence of seasonal respiratory viruses has been described from early spring 2021 onwards [29\u0026ndash;33] and in one study [33] an extraordinary increase in the number of viral respiratory infections in autumn 2021 was noted. In our study, autumn 2021 was characterized by an increase in adenovirus infections (as compared to 2019) and an important rise in SARS-CoV-2 infections compared to 2020. Indeed, SARS-CoV-2 seroprevalence in Belgian pupils rose steeply from 24% in June 2021 to 60% in December 2021 with more than half of these pupils infected during the fourth pandemic wave which was dominated by the delta variant [35]. SARS-CoV-2 has so far not been described as an important childhood wheeze trigger except in the report of Ruano et al. [36] describing an increased use of reliever therapy in a group of asthmatic children with probable COVID-19. In our study, only 4 out of 77 SARS-CoV-2 swabs were PCR positive in 2021, as such, it is difficult to argue that SARS-CoV-2 infections caused the observed peak in wheezing episodes.\u003c/p\u003e\n\u003cp\u003eIn addition to direct SARS-CoV-2 induced wheezing, it is possible that SARS-CoV-2 infection leads to increased susceptibility for wheezing episodes as was shown in a study by Chou et al. [7]. However, there was no SARS-CoV-2 serology performed in our study, making a possible relationship with wheezing illness merely explorative.\u003c/p\u003e\n\u003cp\u003eMultiple studies describe an ongoing incidence of rhinovirus during the pandemic [34,37\u0026ndash;39] with increased incidence after release of restrictions [37] and a clear correlation with pediatric wheezing admissions [34]. However, in our hospital the proportion of \u0026nbsp;viral cultures positive for rhinovirus did not increase over the three study periods.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;We investigated other environmental factors, such as allergens and pollution, that could have led to an increase in wheezing episodes. From 2019 to 2021, the year-round concentration in air pollutants didn\u0026rsquo;t change except for a significant decrease in NO\u003csub\u003e2\u003c/sub\u003e, a pollutant strongly related to traffic, a finding that was observed before in a study in Grenoble [40]. However, we found a significantly higher concentration of \u0026nbsp;PM\u003csub\u003e10\u003c/sub\u003e, PM\u003csub\u003e2.5\u003c/sub\u003e and O\u003csub\u003e3\u0026nbsp;\u003c/sub\u003ein our study period (September and October) in 2021 as opposed to 2019. The highest increase was seen \u0026nbsp;for PM\u003csub\u003e2.5\u003c/sub\u003e, a pollutant strongly associated with airway inflammation and childhood asthma [40,41]\u003cem\u003e.\u003c/em\u003e In addition to the risk of \u0026nbsp;asthma exacerbation, exposure to air pollution has also been linked to increased susceptibility to viral respiratory infections, including SARS-CoV-2 [42]. It is as such difficult to estimate the relative importance of different environmental factors in this study and we hypothesize that different factors contributed and interacted.\u003c/p\u003e\n\u003cp\u003eSome limitations of this study are to be mentioned. Firstly, the data were collected from a single hospital in the center of Brussels and more studies will be needed to confirm these findings on a regional/rural or national scale. Unfortunately, very few children had viral testing done and data about viral epidemiology in Belgium did not include rhinovirus. \u0026nbsp;Finally, only the months of September and October were analyzed. A longitudinal analysis of the whole three years would have described the epidemiology in more detail with possibly other insights.\u003c/p\u003e\n\u003cp\u003eDespite these limitations, our study is adding onto the growing data about the epidemiology of respiratory diseases in the post-COVID-19 era, which brought to light the vast interrelation between climate change, pollution and viral respiratory infections as risk factors for wheezing disorders. We are encouraged to continue monitoring the burden of childhood wheezing illnesses in the inner city of Brussels along with surveillance of Brussels air quality and epidemiological trends.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cimg 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\"\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank Sandrine Bladt, Thierry De Vos, Dr Nathalie Bossuyt and Dr Juliette Destr\u0026eacute;e for their help with the air pollution, virological and RSV hospitalization data respectively.\u003c/p\u003e\n\u003cp\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript. There are no competing interests to declare, nor financial or non-financial interests.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWilder JL, Parsons CR, Growdon AS, Toomey SL, Mansbach JM. (2020) Pediatric Hospitalizations During the COVID-19 Pandemic. Pediatrics. 146(6):e2020005983. doi:10.1542/peds.2020-005983\u003c/li\u003e\n\u003cli\u003eRosenfeld N, Mandelberg A, Dalal I, et al. (2022) The impact of the COVID-19 pandemic on respiratory morbidity during infancy: A birth-cohort study. Pediatr Pulmonol. 57(4):848-856. doi:10.1002/ppul.25822\u003c/li\u003e\n\u003cli\u003ePapadopoulos NG, Custovic A, Deschildre A, et al. (2020) Impact of COVID-19 on Pediatric Asthma: Practice Adjustments and Disease Burden. J Allergy Clin Immunol Pract. 8(8):2592-2599.e3. doi:10.1016/j.jaip.2020.06.001\u003c/li\u003e\n\u003cli\u003eGupta A, Bush A, Nagakumar P. 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(2023) Risk Factors for Respiratory Viral Infections: A Spotlight on Climate Change and Air Pollution. J Asthma Allergy. 16:183-194. doi:10.2147/JAA.S364845\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"air pollution, pediatric, epidemiology, fungal spores, SARS-CoV-2","lastPublishedDoi":"10.21203/rs.3.rs-3886091/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3886091/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose: \u003c/strong\u003eStudies have demonstrated important changes in the seasonality of pediatric respiratory illnesses since the onset of the COVID-19 pandemic. The aim of this study was to describe the epidemiology of childhood wheezing episodes before and after the start of the COVID-19 pandemic in relation to their potentially associated environmental triggers.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eFiles of all children treated with salbutamol for a wheezing episode in September and October 2019, 2020 and 2021 were retrospectively reviewed. Infection epidemiology, daily concentrations of air pollutants (NO\u003csub\u003e2\u003c/sub\u003e, O\u003csub\u003e3, \u003c/sub\u003ePM\u003csub\u003e10\u003c/sub\u003e and PM\u003csub\u003e2.5\u003c/sub\u003e) and fungal spores were collected over the same time period.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eIn 2021,\u003cstrong\u003e \u003c/strong\u003e298 episodes of wheezing were observed compared to 111 in 2020 and 86 in 2019 (p\u0026lt;0.001). Compared to 2019, children with wheezing in 2021 were significantly older (p\u0026lt;0.001), less likely to have a history of recurrent wheezing (p\u0026lt;0.001) and required less hospitalization (p=0.034). Adenovirus and SARS-CoV-2 were more prevalent in 2021 as compared to 2019 (p\u0026lt;0.001). The concentration of PM\u003csub\u003e10\u003c/sub\u003e, PM\u003csub\u003e2.5\u003c/sub\u003e and O\u003csub\u003e3\u003c/sub\u003e was higher in 2021, as compared to both 2019 and 2020 (p\u0026lt;0.001) while the concentration of NO\u003csub\u003e2\u003c/sub\u003e and airborne spores was lower in 2021 compared to 2019 (p\u0026lt;0.0001).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eA threefold increase in wheezing episodes was observed in the autumn post-COVID (2021) compared to pre-COVID (2019) together with a significant increase in some viruses and most air pollutants. We hypothesize that this abnormal surge may be related to the release of restrictions with rapid spread of viruses in children who were exposed to high levels of air pollution.\u003c/p\u003e","manuscriptTitle":"Wheezing Episodes in Children Before and After the Onset of the COVID-19 Pandemic in Brussels","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-30 17:26:08","doi":"10.21203/rs.3.rs-3886091/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c4df751b-d156-4a11-83da-fe6aba49254c","owner":[],"postedDate":"January 30th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-02-18T19:29:18+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-30 17:26:08","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3886091","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3886091","identity":"rs-3886091","version":["v1"]},"buildId":"WrCJVZZCHTDjtuVLN7oU0","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}