atmosphere Article Ambient PM2.5 and Daily Hospital Admissions for Acute Respiratory Infections: Effect Modification by Weight Status of Child Hironori Nishikawa 1,* , Chris Fook Sheng Ng 1 , Lina Madaniyazi 1,2, Xerxes Tesoro Seposo 1 , Bhim Gopal Dhoubhadel 1,3 , Dhiraj Pokhrel 4, Amod K. Pokhrel 4, Sharat Chandra Verma 4, Dhruba Shrestha 5, Ganendra Bhakta Raya 5 and Masahiro Hashizume 1,6 1 Department of Global Health, School of Tropical Medicine and Global Health, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan; [email protected] (C.F.S.N.); [email protected] (L.M.); [email protected] (X.T.S.); [email protected] (B.G.D.); [email protected] (M.H.) 2 Department of Pediatric Infectious Disease, Institute of Tropical Medicine, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan 3 Department of Respiratory Infections, Institute of Tropical Medicine, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan 4 LEADERS Nepal, P.O. Box 8846, 3rd Floor Radhakuti Arcade, Putalisadak, Kathmandu 44600, Nepal; [email protected] (D.P.); [email protected] (A.K.P.); [email protected] (S.C.V.) 5 Siddhi Memorial Hospital, Siddhi Memorial Foundation, P.O. Box 40, Bhimsensthan-7, Bhaktapur 44800, Nepal; [email protected] (D.S.); [email protected] (G.B.R.) 6 Department of Global Health Policy, School of International Health, Graduate School of Medicine, Citation: Nishikawa, H.; Ng, C.F.S.; The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan Madaniyazi, L.; Seposo, X.T.; * Correspondence: [email protected] Dhoubhadel, B.G.; Pokhrel, D.; Pokhrel, A.K.; Verma, S.C.; Shrestha, Abstract: The high level of ambient particulate matter in many developing countries constitutes a D.; Raya, G.B.; et al. Ambient PM2.5 major health burden, but evidence on its impact on children’s health is still limited in these regions. and Daily Hospital Admissions for We conducted a time-stratified case-crossover analysis to quantify the short-term association between Acute Respiratory Infections: Effect Modification by Weight Status of fine particulate matter (PM2.5) and hospital admissions due to acute respiratory infections (ARI) Child. Atmosphere 2021, 12, 1009. among children in Bhaktapur district, Nepal, and to investigate the potential modification of the https://doi.org/10.3390/ effect by nutritional characteristic. We analyzed 258 children admitted to the pediatric hospital for atmos12081009 ARI between February 2014 to February 2015. We observed evidence of increased risk on the same (lag 0) and preceding day (lag 1). The cumulative estimate of their average (lag 01) suggested each Academic Editor: Hwan-Cheol Kim 3 10 µg/m increase in PM2.5 was associated with a relative risk (RR) of 1.16 (95% confidence interval [CI]: 1.02–1.31). The strongest evidence from a stratified analysis of three categories of weights was Received: 3 July 2021 observed in the overweight group (RR: 1.77; 95% CI: 1.17–2.69) at lag 01, while the estimates for the Accepted: 2 August 2021 normal weight and underweight groups were closer to the non-stratified estimates for all-ARI cases. Published: 5 August 2021 The findings suggests that pediatric ARI is an important morbidity associated with inhalable PM2.5 and that more research is needed to elucidate and validate the observed dissimilarity by weight. Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in Keywords: fine particulate matter; inhalation exposure; acute respiratory infection; body weight; published maps and institutional affil- nutritional status iations. 1. Introduction Copyright: © 2021 by the authors. In Kathmandu Valley, the capital of Nepal, the air pollution level has been estimated Licensee MDPI, Basel, Switzerland. to be five times higher than the WHO Air Quality Guidelines [1], constituting a significant This article is an open access article public health issue due to rapid urbanization. The lack of good air quality data, notably the distributed under the terms and conditions of the Creative Commons highly inhalable particulate matter of less than 2.5 micrometer in diameter (PM2.5), and the Attribution (CC BY) license (https:// subpar quality of medical record keeping have resulted in a scarcity of studies important to creativecommons.org/licenses/by/ inform policies [2]. Although the association between air pollutants and human health has 4.0/). been well-documented [3–5], most of the studies were conducted in high-income countries Atmosphere 2021, 12, 1009. https://doi.org/10.3390/atmos12081009 https://www.mdpi.com/journal/atmosphere Atmosphere 2021, 12, x FOR PEER REVIEW 2 of 10 important to inform policies [2]. Although the association between air pollutants and hu- Atmosphere 2021, 12, 1009 man health has been well-documented [3–5], most of the studies were conducted in 2high- of 10 income countries where results may not be directly applicable to understand the health burden of high air pollution level in cities such as Kathmandu Valley. More importantly, whereknowledge results gaps may remain not be given directly the applicable different toem understandission sources the healththat can burden lead to of different high air pollutiontoxicities levelin different in cities locations such as and Kathmandu the different Valley. population More importantly, characteristics knowledge in the lower gaps remainmiddle-income given the countries different (LMICs emission especially sources that poor can countries lead to differentwith limited toxicities economic in different ability locationsto mitigate and exposure the different [6]. population characteristics in the lower middle-income countries (LMICsPoor especially air quality poor affects countries growing with children limited economic differently ability [7]. In to this mitigate age subgroup, exposure [6sus-]. ceptibilityPoor airto qualityair pollution affects can growing be influenced children by differently the health [ 7status]. In thisof a agechild subgroup, [1]. In Nepal, sus- ceptibilityacute respiratory to air pollution infection can(ARI) be was influenced responsi byble the for health about status15% of of deaths a child among [1]. In children Nepal, acuteaged under respiratory five in infection 2013 [8]. (ARI)However, was susceptibility responsible for of aboutthis subgroup 15% of deathsto PM2.5 among is not well- chil- drenunderstood aged under despite five previous in 2013 reports [8]. However, linking susceptibilityPM2.5 and ARI of [9,10]. this subgroup A second to important PM2.5 is notrisk well-understoodfactor affecting children despite previousin the region reports is malnutrition, linking PM2.5 whichand ARIis a [significant9,10]. A second health importantburden with risk a substantial factor affecting impact children on the in Disabi the regionlity Adjusted is malnutrition, Life Year which (DALY) is a in significant the coun- healthtry [11]. burden Thirty-six with percent a substantial of children impact under on the age Disability five are Adjustedstunted (short Life Year for their (DALY) age), in 10% the countryare wasted [11]. (thin Thirty-six for their percent height), of children 27% are under underweight age five are(thin stunted for their (short age), for and their 1% age), are 10%overweight are wasted (heavy (thin for for their their height) height), in 27%Nepal are [12]. underweight Likewise, (thinthe influence for their of age), the andnutritional 1% are overweightstatus on the (heavy health for effects their of height) PM2.5 inis Nepallittle studied [12]. Likewise, and not thewell-understood. influence of the nutritional statusAgainst on the healththis backdrop, effects of we PM conducted2.5 is little studieda study and(1) to not quantify well-understood. the short-term associa- tion betweenAgainst this ambient backdrop, PM2.5 we and conducted daily ARI a hospital study (1) admissions to quantify among the short-term children, association and (2) to betweeninvestigate ambient the potential PM2.5 andmodification daily ARI ofhospital health effects admissions by weight among status. children, and (2) to investigate the potential modification of health effects by weight status. 2. Materials and Methods 2. Materials and Methods 2.1. Study Site 2.1. Study Site The study location is in Bhaktapur district, one of the three districts that makes up The study location is in Bhaktapur district, one of the three districts that makes up KathmanduKathmandu Valley (Figure 11).). This area is is a a mixture mixture of of urban urban and and rural rural areas. areas. Outdoor Outdoor air airpollution pollution comes comes from from multiple multiple sources, sources, such such as as the the burning burning of of biomass biomass fuel fuel in homes,homes, moderatemoderate traffictraffic onon thethe nearestnearest roads,roads, andand brickbrick kilnskilns onon thethe outskirtsoutskirtsof ofthe thecity city[ 13[13].]. 35° N 30° N Kathmandu 25° N Bhaktapur 20° N Latitude 15° N Lalitpur 10° N 5° N 70° E 75° E 80° E 85° E 90° E 95° E Longitude FigureFigure 1.1. MapMap ofof KathmanduKathmandu ValleyValley showingshowing BhaktapurBhaktapur andand thethe locationslocations ofof thethe hospital,hospital, thethe PMPM monitormonitor (on(on thethe rooftoprooftop ofof thethe hospital),hospital), andand thethe NOAANOAA stationstation (at(at TribhuvanTribhuvan International International Airport). Airport). Atmosphere 2021, 12, 1009 3 of 10 2.2. Study Design Data on health outcomes and exposure were available from 13 February 2014 to 12 February 2015. PM2.5 data after our study period cannot be investigated since they contain lots of missing periods due to the April 2015 Nepal earthquake. We employed a time-stratified case-crossover (TSCCO) study design to estimate the short-term associations between daily PM2.5 and ARI admissions [14–16]. The method is commonly used in epidemiological studies of air pollution and health [17–19]. Briefly, with this method, each patient serves as his/her own control, and the exposure level on the day of hospitalization (or a few days before) is compared to the exposure level on the same days of the week within the same month of hospitalization.