A Case-Crossover Analysis of the Association between Exposure to Total PM2.5 and Its Chemical Components and Emergency Ambulance Dispatches in Tokyo.

A limited number of studies have investigated the association between short-term exposure to PM2.5 components and morbidity. The present case-crossover study explored the association between exposure to total PM2.5 and its components and emergency ambulance dispatches, which is one of the indicators of morbidity, in the 23 Tokyo wards. Between 2016 and 2018 (mean mass concentrations of total PM2.5 13.5 µg/m3), we obtained data, from the Tokyo Fire Department, on the daily cases of ambulance dispatches. Fine particles were collected at a fixed monitoring site and were analyzed to estimate the daily mean concentrations of carbons and ions. We analyzed 1038301 cases of health-based all-cause ambulance dispatches by using a conditional logistic regression model. The average concentrations of total PM2.5 over one and the previous day were positively associated with the number of ambulance dispatches. In terms of PM2.5 components, the percentage increase per interquartile range (IQR) increase was 0.8% for elemental carbon (IQR = 0.8 µg/m3; 95% CI = 0.3-1.3%), 0.9% for sulfate (2.1 µg/m3; 0.5-1.4%), and 1.1% for ammonium (1.3 µg/m3; 0.4-1.8%) in the PM2.5-adjusted models. This is the first study to find an association between some specific components in PM2.5 and ambulance dispatches.

Hourly association between ambient PM2.5 and emergency ambulance dispatches in 11 cities in Japan.

Numerous epidemiological studies have demonstrated that short-term exposure to ambient PM2.5 increases mortality and morbidity. Investigating the association using hourly ambient PM2.5 exposure may provide important insights, as current evidence is limited mostly to daily lag term. This study aimed to investigate the hourly association between ambient PM2.5 concentrations and all-cause emergency ambulance dispatches (EAD) in 11 cities in Japan. We used a time-stratified case-crossover design and examined the hourly lags of ambient PM2.5 up to 24 h (unconditional distributed lags and moving average lags) using a conditional Poisson regression model. A significant increase in all-cause EAD was observed at lag 0 h [relative risk (RR): 1.0037 (95% CI: 1.0000, 1.0074)] and all moving average lags. The highest RR was observed within the first 6 h (at lag 0-5 h) [RR: 1.0091 (95% CI: 1.0068, 1.0114)], with a slight ascending pattern. This was followed by a descending pattern at lags 0-11, 0-17, and 0-23 h, but significant positive RR was observed even at lag 0-23 h, when the lowest RR was observed [RR: 1.0072 (95% CI: 1.0044, 1.0100)]. Though similar pattern was observed among the elderly, a different pattern was observed among the children (gradually ascending pattern). We conclude that all-cause EAD could be triggered by ambient PM2.5 exposure with very short lags.

Relative and Absolute Sensitivity Analysis on Ozone Production in Tsukuba, a City in Japan.

The change in the ozone production rate on reducing its precursors, namely, ozone production sensitivity, is important information for developing a strategy to reduce ozone. We expanded a conventional sensitivity analysis theory by including peroxy radical loss by uptake onto particle surfaces in the aim of examining their potential impact. We also propose a new concept of absolute sensitivity that enables us to evaluate the quantitative effectiveness of precursor reduction toward mitigating ozone production over a given period and area. This study applies the theory to observations in Tsukuba, a city in Japan. The relative sensitivity analysis shows that ozone production was more sensitive to volatile organic compounds (VOCs) in the morning and evening, and it became more sensitive to NOx in the afternoon. NO depletion was a main trigger in this sensitivity regime transition. The absolute sensitivity analysis indicates that the VOC-sensitive period in the morning determines the total ozone production sensitivity in a day. While particles did not have significant impact on regime classification in Tsukuba, they have a potential to decrease the mitigating effect of VOC reduction on ozone production and to moderate the enhancement effect of NOx reduction depending upon uptake coefficients. A further study will benefit from a combination with an observation-constrained box model simulation or chemical transport modeling system, which may provide sensitivity analysis over a large spatial and temporal range.

Japanese Nationwide Study on the Association Between Short-term Exposure to Particulate Matter and Mortality.

BACKGROUND: From around 2012, the use of automated equipment for fine particulate matter (PM2.5) measurement with equivalence to a reference method has become popular nationwide in Japan. This enabled us to perform a national health effect assessment employing PM2.5 concentrations based on the standardized measurement method. We evaluated the association between non-accidental mortality and short-term exposure to PM2.5 and coarse particulate matter (PM), with the latter estimated as the difference between suspended particulate matter and PM2.5, for the fiscal years 2012-2014. METHODS: This was a time-stratified case-crossover study in 100 highly-populated Japanese cities. Mortality data was obtained from the Ministry of Health, Labour and Welfare. City-specific estimates of PM-mortality association were calculated by applying a conditional logistic regression analysis, and combined with a random-effects meta-analysis. RESULTS: The respective averages of daily mean concentration were 14.6 µg/m3 for PM2.5 and 6.4 µg/m3 for coarse PM. A 10 µg/m3 increase in PM2.5 concentrations for the average of the day of death and the previous day was associated with an increase of 1.3% (95% confidence interval (CI), 0.9-1.6%) in total non-accidental mortality. For cause-specific mortality, PM2.5 was positively associated with cardiovascular and respiratory mortality. After adjustment for PM2.5, we observed a 1.4% (95% CI, 0.2-2.6%) increase in total mortality with a 10 µg/m3 increase in coarse PM. CONCLUSION: The study revealed that short-term exposure to PM2.5 had adverse effects on total non-accidental, cardiovascular, and respiratory mortality in Japan. Coarse PM exposure also increased the risk of total mortality.

Aerosol Health Effects from Molecular to Global Scales.

Poor air quality is globally the largest environmental health risk. Epidemiological studies have uncovered clear relationships of gaseous pollutants and particulate matter (PM) with adverse health outcomes, including mortality by cardiovascular and respiratory diseases. Studies of health impacts by aerosols are highly multidisciplinary with a broad range of scales in space and time. We assess recent advances and future challenges regarding aerosol effects on health from molecular to global scales through epidemiological studies, field measurements, health-related properties of PM, and multiphase interactions of oxidants and PM upon respiratory deposition. Global modeling combined with epidemiological exposure-response functions indicates that ambient air pollution causes more than four million premature deaths per year. Epidemiological studies usually refer to PM mass concentrations, but some health effects may relate to specific constituents such as bioaerosols, polycyclic aromatic compounds, and transition metals. Various analytical techniques and cellular and molecular assays are applied to assess the redox activity of PM and the formation of reactive oxygen species. Multiphase chemical interactions of lung antioxidants with atmospheric pollutants are crucial to the mechanistic and molecular understanding of oxidative stress upon respiratory deposition. The role of distinct PM components in health impacts and mortality needs to be clarified by integrated research on various spatiotemporal scales for better evaluation and mitigation of aerosol effects on public health in the Anthropocene.

Ulcers on the epiglottis caused by a nasogastric tube in three adults with severe motor and intellectual disabilities.

Nasogastric tube feeding is a common method of parenteral nutrition. We observed ulcers on the epiglottis caused by a nasogastric tube in three adults with severe motor and intellectual disabilities (SMID) during examination with a laryngeal fiberscope while swallowing. These ulcers were healed by changing the method of inserting the nasogastric tube. The patients were three men aged 25, 39, and 55 years. The muscle tone of the whole body was increased in all of the patients. Two patients had severe scoliosis, and the other patient had lordosis in the thoracic vertebrae and had received laryngo-tracheal diversion. All of the patients received intermittent or continuous respiratory care. The pharynx of the patients with severe scoliosis became thinner and the feeding tubes ran obliquely. The feeding tube in the patient who received laryngo-tracheal diversion entered the cut and closed trachea through the glottis. Ulcers were observed on the laryngeal side of the epiglottis in all of the patients. The ulcers were healed by preventing feeding tubes from running obliquely or by using the naso-gastric tube made of different materials in the patients with severe scoliosis. In the patient who received laryngo-tracheal diversion, we succeeded in avoiding the glottis by keeping his face forward while inserting the feeding tube. Then feeding tubes were changed with guidewires, and the ulcers were healed. When using nasogastric tube feeding for persons with SMID with a large increase in muscle tone and/or with severe scoliosis, adopting a method of inserting feeding tubes that avoids damaging the epiglottis with a laryngeal fiberscope is required.

Incidence of childhood primary immune thrombocytopenic purpura.

There is a discrepancy in the reported incidence of childhood immune thrombocytopenic purpura (ITP) between Europe (2.9-5.3 per 100 000 persons) and Japan (1.91). Ise district is a suitable area in which to conduct epidemiological study because there is little fluctuation in the sociodemographic factors. We performed a retrospective population-based study to clarify the incidence of primary childhood ITP. We calculated person-years for children aged <15 years based on the Ise district demographics between 2002 and 2012. The calculated person-years were 298 533. The number of hospitalized patients in Ise district was 25 (M/F, 14/11) during the study period. The calculated incidence was therefore 8.4 per 100 000 person-years. It is possible that the difference in incidence between the present calculation and that of the European studies is due to variation in accuracy and/or registration criteria between the studies.

Combination of prednisolone and cyclosporine A as third-line therapy for refractory Kawasaki disease.

BACKGROUND: The selection of drugs as third-line therapy for patients with Kawasaki disease (KD) who are resistant to second-line therapy remains controversial. METHODS: We reviewed the medical records of 354 patients (216 males/137 females) with KD who were treated in our department from July 2003 to January 2016. The age range was 1 month to 10 years, and the median age was 2 years and 1 month. A combination of 2 g/kg intravenous immunoglobulin (IVIG) plus 30 mg/kg of aspirin was used as first-line therapy. Patients who were refractory to the first-line therapy were administered 2 mg/kg of prednisolone (PSL) in combination with IVIG. Five patients who were refractory to the second-line therapy were treated with cyclosporine A (CsA) combined with PSL as the third-line therapy. RESULTS: All five patients immediately responded to the third-line therapy. One of the five patients showed a transient dilatation of the coronary artery that regressed to its normal size by the 60th day of illness. CONCLUSIONS: We suggest that the combination of CsA and steroids might be a promising therapeutic strategy for refractory KD.

Role of oxides of nitrogen in the ozone-cardiorespiratory visit association.

Ozone (O3)-induced health effects vary in terms of severity, from deterioration of lung function and hospitalization to death. Several studies have reported a linear increase in health risks after O3 exposure. However, current evidence suggests a non-linear U- and J-shaped concentration-response (C-R) function. The potential increasing risks with decreasing O3 concentrations may seem counterintuitive from the traditional standpoint that decreasing exposure should lead to decreasing health risks. Tus, the question of whether the increasing risks with decreasing concentrations are truly O3-induced or might be from other C-R mechanisms. If these potential risks were not accounted for, this may have contributed to the risks observed at the low ozone concentration range. In this study, we examined the short-term effects of photochemical oxidant (Ox, parts per billiion) on outpatient cardiorespiratory visits in 21 Japanese cities after adjusting for other air pollutant-specific C-R functions. Daily cardiorespiratory visits from January 1, 2014 to December 31, 2016 were obtained from the Japanese Medical Data Center Co. Ltd. Similar period of meteorological and air pollution variables were obtained from relevant data sources. We utilized a time-stratified case crossover design coupled with the generalized additive mixed model (TSCC-GAMM) to estimate the association between Ox and cardiorespiratory outpatient visits, after adjusting for several covariates. A total of 2,588,930 visits were recorded across the study period, with a mean of 111.87 and a standard deviation of 138.75. The results revealed that crude Ox-cardiorespiratory visits exhibited a U-shaped pattern. However, adjustment of the oxides of nitrogen, particularly nitrogen monoxide (NO), attenuated the lower risk curve and subsequently altered the shape of the C-R function, with a substantial reduction observed during winter. NO- and nitrogen dioxide (NO2)-adjusted Ox-cardiorespiratory associations increased nearly linearly, without an apparent threshold. Current evidence suggests the importance of adjusting the oxides of nitrogen in estimating the Ox C-R risk functions.

Acute motor-sensory axonal Guillain-Barré syndrome with unilateral facial nerve paralysis after rotavirus gastroenteritis in a 2-year-old boy.

Guillain-Barré syndrome (GBS) is well known as presenting with acute immune-mediated polyneuropathies, with strong associations with antecedent infections. Several variant forms of GBS have been described, including acute inflammatory demyelinating polyneuropathy, acute motor axonal neuropathy, acute motor-sensory axonal neuropathy, and sensory GBS. We present a rare case of 2-year-old boy with acute motor and sensory polyneuropathy and left-sided facial nerve paralysis after rotavirus infection. He received immunoglobulin i.v. with subsequent satisfactory recovery.

Exposure to chemical components of fine particulate matter and ozone, and placenta-mediated pregnancy complications in Tokyo: a register-based study.

BACKGROUND: Maternal exposure to fine particulate matter (PM2.5) was associated with pregnancy complications. However, we still lack comprehensive evidence regarding which specific chemical components of PM2.5 are more harmful for maternal and foetal health. OBJECTIVE: We focused on exposure over the first trimester (0-13 weeks of gestation), which includes the early placentation period, and investigated whether PM2.5 and its components were associated with placenta-mediated pregnancy complications (combined outcome of small for gestational age, preeclampsia, placental abruption, and stillbirth). METHODS: From 2013 to 2015, we obtained information, from the Japan Perinatal Registry Network database, on 83,454 women who delivered singleton infants within 23 Tokyo wards (≈627 km2). Using daily filter sampling of PM2.5 at one monitoring location, we analysed carbon and ion components, and assigned the first trimester average of the respective pollutant concentrations to each woman. RESULTS: The ORs of placenta-mediated pregnancy complications were 1.14 (95% CI = 1.08-1.22) per 0.51 µg/m3 (interquartile range) increase of organic carbon and 1.11 (1.03-1.18) per 0.06 µg/m3 increase of sodium. Organic carbon was also associated with four individual complications. There was no association between ozone and outcome. SIGNIFICANCE: There were specific components of PM2.5 that have adverse effects on maternal and foetal health.

Maternal exposure to fine particulate matter over the first trimester and umbilical cord insertion abnormalities.

BACKGROUND: Our hypothesis was that exposure to fine particulate matter (PM2.5) is related to abnormal cord insertion, which is categorized as a form of placental implantation abnormality. We investigated the association between exposure to total PM2.5 and its chemical components over the first trimester and abnormal cord insertion, which contributes to the occurrence of adverse birth outcomes. METHODS: From the Japan Perinatal Registry Network database, we used data on 83 708 women who delivered singleton births at 39 cooperating hospitals in 23 Tokyo wards (2013-2015). We collected PM2.5 on a filter and measured daily concentrations of carbon and ion components. Then, we calculated the average concentrations over the first trimester (0-13 weeks of gestation) for each woman. A multilevel logistic-regression model with the hospital as a random effect was used to estimate the odds ratios (ORs) of abnormal cord insertion. RESULTS: Among the 83 708 women (mean age at delivery = 33.7 years), the frequency of abnormal cord insertion was 4.5%, the median concentration [interquartile range (IQR)] of total PM2.5 was 16.1 (3.61) µg/m3 and the OR per IQR for total PM2.5 was 1.14 (95% confidence interval = 1.06-1.23). In the total PM2.5-adjusted models, total carbon, organic carbon, nitrate, ammonium and chloride were positively associated with abnormal insertion. Organic carbon was consistently, and nitrate tended to be, associated with specific types of abnormal insertion (marginal or velamentous cord insertion). CONCLUSIONS: Exposure to total PM2.5 and some of its components over the first trimester increased the likelihood of abnormal cord insertion.

Maternal Exposure to Fine Particulate Matter and Its Chemical Components Increasing the Occurrence of Gestational Diabetes Mellitus in Pregnant Japanese Women.

Introduction: PM2.5 exposure is a suspected risk factor for diabetes. It is hypothesized that maternal PM2.5 exposure contributes to the development of gestational diabetes mellitus (GDM). The association between PM2.5 exposure and GDM is controversial and limited evidence is available for the exposure to PM2.5 chemical components. We investigated the association between maternal exposure to total PM2.5 mass and its components, particularly over the first trimester (early placentation period), and GDM. Methods: Data were obtained from the Japan Perinatal Registry Network database, which includes all live births and stillbirths after 22 weeks of gestation at 39 cooperating hospitals in 23 Tokyo wards (2013-2015). At one fixed monitoring site, we performed daily filter sampling of fine particles and measured daily concentrations of carbon and ion components. The average concentrations of total PM2.5 and its components over the 3 months before pregnancy and the first (0-13 gestational weeks) and second (14-27 gestational weeks) trimesters were calculated and assigned to each woman. We estimated the odds ratios (ORs) of GDM in a multilevel logistic regression model. Results: Among 82,773 women (mean age at delivery = 33.7 years) who delivered singleton births, 3,953 (4.8%) had GDM. In the multiexposure period model, an association between total PM2.5 exposure and GDM was observed for exposure over the first trimester (OR per interquartile range (IQR = 3.63 µg/m3) increase = 1.09; 95% confidence interval (CI) = 1.02-1.16), but not for the 3 months before pregnancy or the second trimester. For PM2.5 components, only organic carbon exposure over the first trimester was positively associated with GDM (OR per IQR (0.51 µg/m3) increase = 1.10; 1.00-1.21). Conclusions: This is the first evidence that exposure to total PM2.5 and one of its components, organic carbon, over the first trimester increases GDM occurrence in Japan.

Evaluation of Japanese practice guidelines for newly diagnosed childhood idiopathic thrombocytopenic purpura.

BACKGROUND: Practice guidelines for childhood idiopathic thrombocytopenic purpura (ITP) were proposed in 1998 and 2004 in Japan. It is important to evaluate the feasibility and validity of the guidelines because the guidelines are based not on evidence but on opinion. METHODS: Records of 30 consecutive hospitalized patients aged 0-15 years (median, 3 years; 17 boys, 13 girls) were retrospectively reviewed. The feasibility and validity of the 2004 guidelines were evaluated by calculating an implementation rate, a response rate to first treatments, and a final clinical outcome. RESULTS: Deviation from the guidelines was found in two patients. Management of the other 28 patients followed the guidelines. The implementation rate was 93.3%. Twenty-one of the 28 eligible patients (75%) responded to the first treatment, whereas seven patients (25%) required additional treatment. In 23 patients (76.7%) platelet counts returned to normal within 6 months. Seven patients (23.3%) developed chronic conditions. All patients had no complications and achieved a platelet count >150 000/µL within 6 years. CONCLUSION: The 2004 Japanese guidelines are feasible and valid for the management of newly diagnosed childhood ITP patients.

Effects of exposure to chemical components of fine particulate matter on mortality in Tokyo: A case-crossover study.

Fine particulate matter (PM2.5) is composed of a variety of chemical components, and the dependency of the health effects of total PM2.5 on specific components is still under discussion. We hypothesised that specific PM2.5 components are responsible for the health effects, and investigated the association between PM2.5 components and mortality in 23 Tokyo wards. We obtained mortality data from the Ministry of Health, Labour and Welfare for the period from April 2013 to March 2017. At a monitoring site within the study area, we collected daily samples of PM2.5 on a filter, and determined the daily mean concentrations of total carbon (organic carbon and elemental carbon) and ions such as nitrate and sulphate. A case-crossover design was employed, and a conditional logistic regression model was used to estimate the strength of the association. Over the study period, we identified 280,460 total non-accidental deaths, and the average daily mean concentration of total PM2.5 was 16.0 (standard deviation = 8.9) µg/m3. We observed a positive association of total PM2.5 with total, cardiovascular, and respiratory mortality. After adjustment for total PM2.5 and its components associated with mortality in the single-component models, the percentage increase per interquartile range (2.3 µg/m3) increase in the average total carbon concentration of the case- and previous-day was 2.1% (95% confidence interval = 1.0 to 3.1%) for total mortality. Carbon elements were associated with respiratory but not cardiovascular mortality. Our results suggest that specific components of PM2.5 account for its adverse health effects.

Trimester-Specific Association of Maternal Exposure to Fine Particulate Matter and its Components With Birth and Placental Weight in Japan.

OBJECTIVE: We investigated which trimester of exposure to PM2.5 and its components was associated with birth and placental weight, and the fetoplacental weight ratio. METHODS: The study included 63,990 women who delivered singleton term births within 23 Tokyo wards between 2013 and 2015. Each day, we collected fine particles on a filter, and analyzed their chemical constituents, including carbons and ions. Trimester-specific exposure to each pollutant was estimated based on the average daily concentrations. RESULTS: Over the third trimester, sulfate exposure tended to be inversely associated with birth weight, and decreased placental weight (difference for highest vs lowest quintile groups = -6.7 g, 95% confidence interval = -12.5 to -0.9). For fetoplacental weight ratio, there was no relationship. CONCLUSIONS: Sulfate exposure over the third trimester may reduce birth weight, particularly placental weight.

Source contributions to multiple toxic potentials of atmospheric organic aerosols.

Fine particulate matter (PM2.5) in the atmosphere is of high priority for air quality management efforts to address adverse health effects in human. We believe that emission control policies, which are traditionally guided by source contributions to PM mass, should also consider source contributions to PM health effects or toxicity. In this study, we estimated source contributions to the toxic potentials of organic aerosols (OA) as measured by a series of chemical and in-vitro biological assays and chemical mass balance model. We selected secondary organic aerosols (SOA), vehicles, biomass open burning, and cooking as possible important OA sources. Fine particulate matter samples from these sources and parallel atmospheric samples from diverse locations and seasons in East Asia were collected for the study. The source and atmospheric samples were analyzed for chemical compositions and toxic potentials, i.e. oxidative potential, inflammatory potential, aryl hydrocarbon receptor (AhR) agonist activity, and DNA-damage, were measured. The toxic potentials per organic carbon (OC) differed greatly among source and ambient particulate samples. The source contributions to oxidative and inflammatory potentials were dominated by naphthalene-derived SOA (NapSOA), followed by open burning and vehicle exhaust. The AhR activity was dominated by open burning, followed by vehicle exhaust and NapSOA. The DNA damage was dominated by vehicle exhaust, followed by open burning. Cooking and biogenic SOA had smaller contributions to all the toxic potentials. Regarding atmospheric OA, urban and roadside samples showed stronger toxic potentials per OC. The toxic potentials of remote samples in summer were consistently very weak, suggesting that atmospheric aging over a long time decreased the toxicity. The toxic potentials of the samples from the forest and the experimentally generated biogenic SOA were low, suggesting that toxicity of biogenic primary and secondary particles is relatively low.

Vaccine-associated paralytic poliomyelitis in an infant with perianal abscesses.

We describe a case of vaccine-associated paralytic poliomyelitis (VAPP) in a 7-month-old infant with perianal abscesses. The infant had suffered from perianal abscesses from 3 weeks after birth. The abscesses repeatedly developed and spontaneously drained through the orifice. Twenty-seven days before admission, a live attenuated oral poliovirus vaccine (OPV) was given to the infant for the first time for routine immunization. His body temperature rose to 38°C 19 days after receiving the OPV and fell 4 days later. Flaccid paralysis of the right leg appeared 26 days after receipt of the OPV. A Sabin type 3 poliovirus was isolated from a stool obtained at admission. The DNA sequences of the VP1 region of the isolated virus were more than 99% identical with those of the vaccine strain. Mild muscle atrophy with moderate motor impairment in the right leg persisted at 18 months of age. One VAPP case provoked by a perianal abscess has been reported from the United Kingdom. Database search revealed that one of nine VAPP cases reported during 2003-2008 in Japan had a perianal abscess. Taken together, these reports and our case imply that we should give OPV with caution to infants with a perianal abscess.

Short-term effects of air pollution on daily single- and co-morbidity cardiorespiratory outpatient visits.

Several studies have noted that the existence of comorbidities lead to an increase in the risk of premature mortality and morbidity. Most of the studies examining the effects of air pollution on comorbidity visits were from Northern American countries, with scarce literature from Asia. This study contributes to existing, yet limited understanding of air pollution-comorbidity by examining the effects of daily air pollutants on outpatient single morbidity and comorbid cardiorespiratory visits in Japan. A total of 1,452,505 outpatient cardiorespiratory visits were recorded among the 21 Japanese cities from 2013 to 2016. Daily outpatient cardiorespiratory visit data were obtained from a health insurance claims database managed by the Japan Medical Data Center Co., Ltd. (JMDC). A time-stratified case crossover analysis coupled with Generalized Additive Mixed Model was used to analyze the association of daily air pollutants (particulate matter 2.5 µm or less in diameter, ozone and nitrogen dioxide) on daily single (respiratory and cardiovascular) and comorbidity health outcomes. We further examined single and cumulative effects for 0-3 and 0-14 lag periods. Ozone, NO2, and PM2.5 were positively associated with cardiorespiratory visits in either shorter or longer lags, with more apparent comorbidity associations with NO2 exposure. A 10-unit increase in NO2, after adjusting for ozone, was associated with a 2.24% (95% CI: 1.34-3.15) and 6.49% (95% CI: 5.00-8.01) increase in comorbidity visit at Lag 0 (of Lag 0-3) and cumulative lag 0-3, respectively. Our results contribute to existing evidence suggesting that short-term and extended exposure to air pollution elicit health risks on cardiovascular, respiratory and comorbid clinic visits. Exposure to NO2, in particular, was associated with increase in the risk of single and comorbidity cardiorespiratory visits. Results can be potentially utilized for both individual health (e.g. risk population health management) and health facility management (e.g. health visit influx determination).