Research Modification by Influenza on Health Effects of Air Pollution in Hong Kong Chit Ming Wong,1 Lin Yang,1 Thuan Quoc Thach,1 Patsy Yuen Kwan Chau,1 King Pan Chan,1 G. Neil Thomas,1 Tai Hing Lam,1 Tze Wai Wong,2 Anthony J. Hedley,1 and J.S. Malik Peiris3 1Department of Community Medicine and School of Public Health, University of Hong Kong, Hong Kong Special Administration Region, People’s Republic of China; 2Department of Family and Community Medicine, Chinese University of Hong Kong, Hong Kong Special Administration Region, People’s Republic of China; 3Department of Microbiology, University of Hong Kong, Hong Kong Special Administration Region, People’s Republic of China o Bjectivs pollutants. Background : Both influenza viruses and air pollutants have been well documented as major hazards to human health, but few epidemiologic studies have assessed effect modification of influ- enza on health effects of ambient air pollutants. : We aimed to assess modifying effects of influenza on health effects of ambient air Methods : We applied Poisson regression to daily numbers of hospitalizations and mortality to develop core models after adjustment for potential time-varying confounding variables. We assessed modification of influenza by adding variables for concentrations of single ambient air pollutants and proportions of influenza-positive specimens (influenza intensity) and their cross-product terms. r sulte : We found significant effect modification of influenza (p < 0.05) for effects of ozone. When influenza intensity is assumed to increase from 0% to 10%, the excess risks per 10-µg/m3 increase in concentration of O3 increased 0.24% and 0.40% for hospitalization of respiratory disease in the all- ages group and ≥ 65 year age group, respectively; 0.46% for hospitalization of acute respiratory dis- ease in the all-ages group; and 0.40% for hospitalization of chronic obstructive pulmonary disease in the ≥ 65 group. The estimated increases in the excess risks for mortality of respiratory disease and chronic obstructive pulmonary disease in the all-ages group were 0.59% and 1.05%, respectively. We found no significant modification of influenza on effects of other pollutants in most disease outcomes under study. c noisulcno : Influenza activity could be an effect modifier for the health effects of air pollutants par- ticularly for O3 and should be considered in the studies for short-term effects of air pollutants on health. k ey words : air pollution, cardiorespiratory disease, effect modification, hospitalization, influenza, mortality. Environ Health Perspect 117:248–253 (2009). doi:10.1289/ehp.11605 available via http://dx.doi.org/ [Online 3 October 2008] The deleterious effects of air pollution on human health have been well studied. Numerous studies have demonstrated that air pollution is associated with respiratory and cardiovascular diseases (CVDs) (Health Effects Institute 2004; Samet et al. 2000; Spix et al. 1998). Similarly, influenza also contributes a heavy burden of morbidity and mortality from respiratory diseases (RDs) and CVDs (Chow et al. 2006; Thompson et al. 2003, 2004; Wong et al. 2004, 2006). The effects of air pol‑ lutants and influenza viruses on disease patho‑ genesis could potentially interact synergistically because both of them affect the respiratory system, from the nasal cavity and nasophar‑ ynx to the main airways and alveoli, and also through systemic effects on the cardiovascular system. The transmission of influenza viruses is believed to rely on short‑distance disper ‑ sion of droplets. However, there is speculation that ambient air pollutants, especially particu‑ late matter ≤ 10 µm in aerodynamic diameter (PM10), may facilitate the spread of influenza viruses by providing condensation nuclei for the virus droplets. This is believed to be critical to longr‑ange transmission of influenza viruses (Hammond et al. 1989). Laboratory studies have provided some evidence to support interaction between influenza and air pollution on their adverse 248 effects on human health. As early as the 1970s, a series of experiments in mice infected by influenza viruses showed an increased inci‑ dence of pneumonia after exposure to sulfur dioxide (Fairchild et al. 1972). A more recent study showed that exposure to diesel exhaust, an important source of PM10, could gener‑ ate oxidative stress in human nasal and bron‑ chial epithelial cells and could also enhance the attachment of influenza virus to these cells (Jaspers et al. 2005). However, the relevance of these experimental studies is uncertain in that the concentrations of pollutants in animal and human laboratory studies were 10–1,000 times higher than the average ambient levels observed in even relatively highly polluted locations such as Hong Kong. Population‑based studies are needed to assess the effects of human exposure in the community. Despite numerous attempts to study the biologic mechanisms behind the interaction between air pollutants and influenza viruses, to date only the confounding effect of influ‑ enza has been considered in the short‑ term effects of air pollution on human health in several multicity projects (Katsouyanni et al. 2001; Touloumi et al. 2005). In our study we evaluated such an interaction from an epi‑ demiologic perspective. This study is part of the Public Health and Air Pollution in Asia (PAPA) project (Health Effects Institute 2006), which involves four Asian cities and aims to provide insight on the short‑ term effects of air pollution on mortality and hos‑ pitalization. In particular, we examined four major ambient air pollutants in Hong Kong: SO2, nitrogen dioxide, ozone, and PM10. Specifically, we assessed effect modifica‑ tion of influenza on air‑pollution–associated hospitalization for RD and its subcategories acute respiratory disease (ARD) and chronic obstructive pulmonary disease (COPD) and on CVD, as well as on airp‑ollution– associated mortality of RD, COPD, and CVD. Materials and Methods Sources of data. We retrieved daily counts of hospitalization from the 14 general hospi‑ tals of the Hospital Authority of Hong Kong for the period 1996–2002. We based these counts on discharge diagnoses of admission records coded according to the International Classification of Diseases, 9th Revision (ICD9‑) (World Health Organization 1977) and 10th Revision (ICD‑10) ( World Health Organization 1994). The selected disease categories included CVD (ICD‑9 codes 390–459; ICD‑10 codes I00–I99) and RD (ICD‑9 codes 460–519; ICD‑10 codes J00– J98), and subcategories of COPD (ICD‑9 codes 490–496; ICD1‑0 codes J40–J47) and ARD (ICD‑9 codes 460–466, 480–487; ICD‑ 10 codes J00‑ J05). We divided these data into three age groups [all ages com‑ bined, ≥ 65 years of age, and 0–14 years of age (for ARD)] and three sex groups (males and females and combined). We obtained Address correspondence to A.J. Hedley, Department of Community Medicine and School of Public Health, University of Hong Kong, 5th Floor, William MW Mong Block, Faculty of Medicine Building, 21 Sassoon Rd., Hong Kong SAR, China. Telephone: 852‑ 2819‑ 9282. Fax: 852‑ 2855‑ 9528. E‑mail: hrmrajh@hkucc.hku.hk Supplemental Material is available online at http:// www.ehponline.org/members/2008/11605/suppl.pdf We thank the Hong Kong Environmental Protection Department, Census, and Statistics Department and Hospital Authority of Hong Kong for providing the data. This study is part of the Public Health and Air Pollution in Asia project, funded by the Health Effects Institute in the United States (agreement 4713‑RFIQ03‑3/04‑9‑2). The authors declare they have no competing financial interests. Received 3 April 2008; accepted 3 October 2008. ovlume 117 | number 2 | February 2009 • Environmental Health Perspectives