COVID-19 Infection and Medicines in Pregnancy in Canada

Background: Although over 100 million pregnant women worldwide are at risk of infection with SARS-CoV-2, little data exists on the impact of COVID-19 and related treatments on maternal/neonatal health. Objective(s): (1) To quantify the prevalence of medication use in pregnancy to treat COVID-19, and (2) To quantify and compare the risk of adverse pregnancy/neonatal outcomes in those with and without COVID-19. Method(s): In the Canadian Mother-Child population-based cohort (CAMCCO), two sub-cohorts were identified using prospective data collection of medical services, prescription drugs, hospitalization archives data, and COVID-19 surveillance testing program (02/28/2020- 2021). The first cohort included all pregnant women during the study period regardless of pregnancy status (delivery, induced/planned or spontaneous abortion);this cohort was further stratified on COVID-19 status. The second cohort included all nonpregnant women (aged 15-45) with a positive COVID-19 test. COVID-19 in pregnant or nonpregnant women was assessed using COVID-19 test results or ICD-10CM code U07.1 from hospital data. COVID-19 severity was categorized based on hospital admission. Women were considered exposed to COVID-19 medications if they filled at least one prescription for a medicine included in the WHO list in the 30 days pre- or 30 days post-COVID-19 positive test/diagnosis. Considering potential confounders, association between COVID-19 during pregnancy, treated vs not, and perinatal outcomes were quantified using log-binomial regression models. Result(s): 150,345 pregnant women (3,464 (2.3%) had COVID-19), and 112,073 nonpregnant women with COVID-19 diagnoses were included. Pregnant women with COVID-19 were more likely to have severe infections compared to nonpregnant women with COVID-19 (11.4% vs 1.6%, p<0.001). The most frequent medications used in pregnancy to treat COVID-19 were antibacterials (13.96%), psychoanaleptics (7.35%), and medicines for obstructive airway disease (3.20%). In pregnancy COVID-19 was associated with spontaneous abortions (adjRR 1.76, 95%CI 1.37, 2.25), gestational diabetes (adjRR 1.52, 95%CI 1.18, 1.97), prematurity (adjRR 1.30, 95%CI 1.01, 1.67), NICU admissions (adjRR 1.32, 95%CI 1.10, 1.59);COVID-19 severity was increasing these risks but exposures to COVID-19 medications reduced all risks. Conclusion(s): COVID-19 severity was higher in pregnancy. Antibacterials, psychoanaleptics, and medicines for obstructive airway disease were the most used overall. COVID-19 was associated with adverse outcomes for mothers and newborns.

Prevalence of asthmatic patients and clinical trend among hospitalized for Sars-Cov2 infection during the first pandemic wave in North-West Italy

Background: In first pandemic wave, SARS-CoV2 infection was hypothesized to be more frequent and severe in asthmatic patients with reduced anti-viral immune response and typical disease flares during viral respiratory infections. Despite this, the studies performed to date have not confirmed these data. The purpose of our research is to evaluate the prevalence and clinical trend in patients with bronchial asthma among hospitalized for COVID-19 in North-West Italy. Method(s): In our multicentre retrospective study, we enrolled all patients hospitalized for COVID-19 from February to July 2020 at four leading hospitals: City of Health and Science of Turin (Molinette-unit), Umberto I Hospital (Turin), Umberto Parini Hospital (Aosta) and Santa Croce and Carle Hospital (Cuneo). We inclueded all patients with SARS-CoV- 2 positive nasopharyngeal swab and/or serology and/or clinical features highly suggestive of SARS-CoV- 2 infection and a hospital stay for COVID-19 of more than 48 hours. We excluded patients with exacerbation of disease not related to SARS-CoV- 2 and fewer than 48 hours of hospital stay;for each patient were collected demographic and clinical data before and during admission. Result(s): We evalueted 1016 patients: 110 (10.8%) had obstructive airway disease [71 COPD (6.9%) and 39 bronchial asthma (6.9%)]. The majority of patients with asthma took an inhaled corticosteroids (ICS) with or without Short or Long Acting Beta-Agonists (SABA, LABA) at home (56.4%);only two cases had severe asthma, both in therapy with biologics. A comparison of clinical trend and outcomes in patients with asthma, COPD and no history of obstructive lung disease is in Table 1. Conclusion(s): The prevalence of asthma among hospitalized for COVID-19 was lower than the prevalence data reported in the general population (3.8 vs 6.6% reported by ISTAT), in Piedmont and Val d'Aosta1 (3.8 vs 5.7%) and in recent meta-analysis2 (3.8 vs 8.08%). There were no significant differences between asthmatics and non-asthmatics in gender, age, smoking habits, associated comorbidities, length of hospital stay, development of disease complications, invasive and/or non-invasive ventilation, treatment with hydroxychloroquine, antivirals or biologics or mortality.

Comparison of clinician diagnosis of COVID-19 against real-time polymerase chain reaction in a general adult population

Background: Whilst the gold standard real-time polymerase chain reaction (RT-PCR) is costly and can take time to obtain results, there is a dearth of data comparing clinician diagnosis based on recommended ICD codes and RTPCR. Aim(s): In this study, we compared clinician diagnosis of COVID-19 with RT-PCR in a general adult population and evaluated any differences in accuracy by age, gender, pre-COVID-19 BMI, and obstructive airway diseases. Material(s) and Method(s): Data from a cohort of 42,621 adult-representative samples in Sweden, included 5705 clinician-diagnosed and 3936 RT-PCR-diagnosed COVID-19 patients. Using RT-PCR as the reference standard, estimates of the accuracy of clinician's diagnosis were determined. Result(s): The sensitivity and specificity of clinician diagnosis in identifying COVID-19 was 78% (95%CI 77-80%) and 93% (95%CI 93-93%), respectively. The positive predictive value was 54% (95%CI 53-55%), negative predictive value was 98% (95%CI 98-98%) and the Youden's Index was 71% (95%CI 70-72%). These accuracy measures were similar between men and women, across age groups, BMI categories, and between patients with and without asthma. However, while the specificity, negative predictive value, and Youden's index were similar between patients with and without COPD, the sensitivity was slightly higher in patients with COPD (84%, 95%CI 74-90%) than those without (78%, 95%CI 77-79%) COPD. Conclusion(s): The accuracy of clinician's diagnosis for COVID-19 is adequate, regardless of gender, age, pre-COVID19 BMI, asthma, and COPD, thus can be used for screening purposes to supplement RT-PCR.

IMPACT OF COVID-19 INFECTION ON PATIENTS WITH OSA: A LONGITUDINAL STUDY

SESSION TITLE: Sleep Disordered Breathing and Narcolepsy Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/18/2022 01:30 pm - 02:30 pm PURPOSE: To study the impact of COVID 19 infection in patients already diagnosed with Obstructive Sleep Apnea (OSA). To study the change of OSA status after COVID 19 infection. METHODS: This is a 11 months observational descriptive longitudinal study. 31 patients diagnosed with OSA in January to April 2021, out of this, 19 patients suffered from COVID 19 infection over next six months and 12 patients were studied finally as 3 patients died and 4 patients lost to follow up. This patients were studied after three months of discharge from COVID ward. Patients were assessed with detailed examination and comorbidity profile, along with COVID 19 infection medical record (hospitalisation days, severity of COVID 19 infection, requirement of mode of oxygen therapy and mechanical ventilation), repeat Epworth Sleepiness Score, present complaints and repeat Polysomnography parameters (apnea hypopnea index, maximum desaturation during sleep). Both values of pre and post covid were compared. RESULTS: 12 subjects had mean age of 52.92(SD: 6.88) and majority were male 8 (66.7%) and mean BMI was 27.72(SD:3.60).All 12 patients had hypertension, 10 had diabetes and 6 had Obstructive Airway Disease. All diagnosed OSA patients were on CPAP therapy. Most of the OSA patients (66.7%) suffered from Severe COVID 19 infection and of them majority were male (62.5%). Severity of COVID correlated significantly with BMI and AHI (r=0.774;p 0.003 and r=0.907;p<0.001 respectively) and associated with mean hospital stay of 27.33 (SD:10.7). Mean AHI and ESS scores increased in post covid period (mean AHI of 22.58;SD:11.12 to AHI of 24.58;SD:12.01 and mean ESS of 15.08;SD:3.67 to ESS of 18.67;SD: 3.52). Both AHI and ESS values changed in post COVID period significantly (r=0.907 and r= 0.893) and maximum desaturation during sleep dropped significantly from mean 83.33 (SD:4.83) to 79.50 (SD:4.81) (r=-0.727;p=0.007). Out of 12 patients 10 (83.33%) patients required HFNO and 6 (50%) patients received NIV. 2 patients required mechanical ventilatory support & both of them were severe OSA category patients. CONCLUSIONS: This study reveals that most of OSA patients suffered from severe COVID. Increased BMI correlated significantly with severity of COVID 19 infection. OSA patients, particularly severe OSA patients required more ventilatory support. In Post COVID period, OSA parameters were deranged and worsened as more sleepiness and fatigue were found in majority of the patients. This findings may give us a clue regarding the persistent Post COVID symptoms seen in OSA patients. CLINICAL IMPLICATIONS: OSA being in the background or forefront of several pathophysiological pathways, patients tend to severe COVID 19 infection as well as seek more healthcare support. OSA itself worsens after COVID as we found in this study. So, this patients may experience wide spectrum of persistant post COVID symptoms. Though significant amount of knowledge and evidence are lacking in this issue till date. DISCLOSURES: No relevant relationships by Samarjit Das

CHLORINE GAS EXPOSURE AND OBSTRUCTIVE AIRWAY DISEASE: A CASE REPORT AND CASE-BASED DISCUSSION

SESSION TITLE: Occupational and Environmental Lung Disease Cases SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: Chlorine gas is a pulmonary irritant with pungent odor that damages the respiratory tract. Chlorine gas exposure occurs in industrial or household exposures,Chlorine gas has two forms either a liquid or gas, toxicity of chlorine gas depends on the dose and duration of exposure. Chlorine gas used in manufacturing products like paper, insecticides, Chlorine is used to treat bottled and swiming pool water. CASE PRESENTATION: A 37 Y.O Male, no PMH presents with progressive dyspnea for three days worse with activity,decreases with rest, denied cough fever or chest pain he is vaccinated for COVID,no smoking history. The patient worked at a chlorine gas factory in the Dominican Republic for 15 years. Exam: Vitals: BP 124/72 mmHg. HR 100 BPM. RR 21 BPM. SpO2 84%. General: acute distress. Heart: normal S1, S2. RRR. Lung: wheeze bilaterally. Abdomen: Soft. Musculoskeletal: no pitting edema. he was placed on 6 LPM NC saturation improved to 90%. CBC and Chemistry were unremarkable, he was started on steroid, breathing treatment with antibiotics. ABG showed hypoxemia. he was placed on Venturi mask and his saturation improved to 95%.CTA was negative for PE. EKG, troponin were unremarkable. A proBNP normal. The antibiotics were discontinued because of a negative workup. A TTE study was normal. HRCT scan of the chest, showed atelectasis and infiltrates of lower lobes. No interstitial fibrosis.A PFT showed obstructive airway disease. He was discharged on oral and inhaled steroids.Hi new onset obstructive airway could be due to chlorine gas exposure. DISCUSSION: Chlorine gas causes cellular injury through oxidative damage but further damage results from activation and recruitment of inflammatory cells with subsequent release of oxidants and proteolytic enzymes. Humans can detect chlorine gas odor at a concentration between 0.1-0.3 ppm. At 1-3 ppm,it causes irritation of oral,eye mucosal membranes. At 30-40 ppm causes cough, chest pain, and SOB. At 40-60 ppm, toxic pneumonitis and pulmonary edema and can be fatal at 430 ppm concentration or higher within thirty minutes. Chronic exposure to chlorine gas lead to chest pain, cough, sore throat, hemoptysis, recurrent asthma. Physical exam findings include tachypnea cyanosis, wheezing, intercostal retractions, decreased breath sounds. Pulmonary function tests may reveal obstructive lung function disease. Chronic exposure to a low level was found to be associated with an increased risk of asthma in swimmers. CONCLUSIONS: Chlorine exposure results in direct chemical toxicity to the airways with acute airways obstruction or airways hyperreactivity, presentation varies from acute overwhelming intoxication with acute lung injury and or death, occupational exposure increase the likelihood of chronic bronchitis or isolated wheezing attacks. Treatment for chlorine exposure is largely supportive. Reference #1: 1- Center of disease control and prevention website/emergency preparedness and response/ https://emergency.cdc.gov/agent/chlorine/basics/facts.asp Reference #2: 2- C- Morim A, Guldner GT. Chlorine Gas Toxicity. [Updated 2021 Jul 25]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing;2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537213/. Reference #3: A- Gummin DD, Mowry JB, Beuhler MC, et al. 2020 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 38th Annual Report. Clin Toxicol (Phila). 2021;59(12):1282-1501. doi:10.1080/15563650.2021.1989785 DISCLOSURES: No relevant relationships by Abdallah Khashan No relevant relationships by Samer Talib no disclosure on file for Matthew Yotsuya;

EARLY VS LATE MORTALITY IN PATIENTS HOSPITALIZED WITH COVID-19 AT A COUNTY HOSPITAL

SESSION TITLE: Studies on COVID-19 Infections Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/18/2022 01:30 pm - 02:30 pm PURPOSE: To evaluate factors associated with early versus late mortality in hospitalized patient with COVID-19. METHODS: This observational study analyzed data of patients who died from COVID-19 at Ben Taub Hospital, a tertiary care County teaching hospital, between from March 2020 to February 2022. Demographic, comorbidities, laboratory values as well as COVID-19 treatments were examined. Patients were divided into two groups: those who had early mortality and those with late mortality (death ≤7 days or >7 days of admission, respectively). RESULTS: 212 patients with COVID-19 died during that period. Of these, 46 patients had early mortality and 166 patients had late mortality. 19/46 (41.3%) of the patients in early mortality group died within 72 hours of presentation. There were no differences between the two groups with regards to age, gender, ethnicity, or body mass index. Both groups were similar with regards to history of tobacco use, hypertension, diabetes mellitus, coronary artery disease, congestive heart failure, cerebrovascular accident, atrial fibrillation, obstructive airway disease, cancer, liver cirrhosis and human immunodeficiency virus infection. There were no differences with regards to COVID vaccination status between the two groups. Peak D dimer, peak C-reactive protein, peak ferritin, peak lactate dehydrogenase and lymphocyte nadir during the hospital course were also similar between the two groups. Patients in the early mortality group had shorter time from symptom onset to admission {3.91 days (SD 5.63) in early vs 6.85 days (SD 8.01) in late}. There were no differences between the two groups regarding use of mechanical ventilation. Patients with late mortality were more likely to have received systemic steroids (90.9% vs 60.9%), anticoagulation (94.6% vs 65.2%), remdesivir (75.3% vs 32.6%), inhaled epoprostenol (50.6% vs 19.6%) compared to early mortality, respectively. In addition to severity of symptoms and clinical condition at the outset of the disease, early death may have been related to not receiving some of these medications.1 CONCLUSIONS: Early mortality in patients with COVID-19 is associated with shorter time to symptoms onset and the lower likelihood to have received systemic steroids, systemic anticoagulation, remdesivir and inhaled epoprostenol. CLINICAL IMPLICATIONS: Early recognition and intervention may prevent early mortality in COVID-19 patients. Reference: Sun, Q., Qiu, H., Huang, M. et al. Lower mortality of COVID-19 by early recognition and intervention: experience from Jiangsu Province. Ann. Intensive Care 10, 33 (2020). https://doi.org/10.1186/s13613-020-00650-2 DISCLOSURES: No relevant relationships by Muhammad Adrish Advisory Committee Member relationship with AstraZeneca, Genentech, GSK, Mylan, Sanofi Please note: 2020-2021 by Nicola Hanania, value=Consulting fee Consultant relationship with AstraZeneca, Genentech, GSK, Mylan, Sanofi Please note: 2020-2021 by Nicola Hanania, value=Consulting fee Advisory Committee Member relationship with Regeneron, Amgen, and Teva Please note: 2020-2021 by Nicola Hanania, value=Consulting fee Consultant relationship with Regeneron, Amgen, and Teva Please note: 2020-2021 by Nicola Hanania, value=Consulting fee Removed 08/02/2022 by Nicola Hanania Research support relationship with Boehringer Ingelheim, GSK, Novartis Please note: 2020-2021 by Nicola Hanania, value=Grant/Research Support Research support relationship with Sanofi Genzyme and Genentech Please note: 2020-2021 by Nicola Hanania, value=Grant/Research Support No relevant relationships by Stephanie Stalcup

Effect of maintenance macrolide antibiotics withdrawal in obstructive airway diseases

Introduction/Aim: While effective and recommended, concerns remain over the widespread, long-term use of macrolide antibiotics in obstructive airway diseases (OADs), particularly relating to antimicrobial resistance. The main objective of this study is to evaluate the effect of deescalation of maintenance macrolide antibiotics during the Australian summer season on exacerbations of OADs. Methods: A double-blind, placebo-controlled, non-inferiority, randomized-controlled trial designed using telehealth. All assessments are conducted over the phone, and the allocated study medication is mailed to participants. We plan to recruit 160 adult participants who are on maintenance macrolide therapy for at least 6 months for the management of asthma, COPD or bronchiectasis. Participants will be randomized to two arms at the start of summer, arm-1 participants will switch from their current macrolide to azithromycin 500 mg for 9 months while arm-2 participants will switch to an identical placebo for the same duration. Telephone follow-up interviews will be conducted at 3-, 6- and 9-months with two additional safety check-in calls during the initial 3 months. The primary outcome is exacerbation. Results: The recruitment and follow-ups are ongoing, without interruption by the COVID-19 lockdowns. We have recruited 39 patients (mean age ± SD 70.0 ± 9.32;54% male) in 2020, and 28 (72%) successfully completed the 9-month treatment with allocated study medication. Of the remaining, 10 were discontinued due to worsening symptoms/exacerbations, and one due to a serious adverse event (SAE). The retention rate at 9-month is currently at 97%. A total of seven unrelated SAEs have been reported so far (all resolved). Conclusion: This novel study will allow us to determine the effect of treatment breaks during periods of lower exacerbation risk. The telehealth-based study design is COVID-19 appropriate and provided greater flexibility for participants to attend interviews, improving the recruitment and retention rate.

Role of Modified RALES and Brixia Scores in Predicting the COVID-19 Positivity among the Suspected Patients: A Cross-sectional Observational Study

Introduction: Computed Tomography (CT) chest plays an important role in triaging and managing patients of suspected COVID-19, especially in those where Coronavirus Disease 2019 (COVID-19) report is pending but CT chest has constraints of availability and cost. Chest X-ray (CXR) is a readily available investigation and is cheaper than a CT chest. Hence, any scoring on CXR which proves to be helpful in triaging and managing suspected COVID-19 patients will alleviate the dependency on CT chest. Modified Radiographic Assessment of Lung Edema Score (mRALES) and Brixia scores have been used to assess severity of disease and prognosis in COVID-19 confirmed cases. However, these two scores have never been used as a method to predict the confirmed COVID-19 pateints among the the suspected COVID-19 cases. Aim: To evaluate the role of mRALES and Brixia score along with clinical and laboratory parameters in predicting confirmed positive cases among suspected COVID-19 patients. Materials and Methods: This retrospective cross-sectional, observational study was conducted in Department of Medicine at Atal Bihari Vajpayee Institute of Medical Sciences (ABVIMS) and Dr. Ram Manohar Lohia Hospital, New Delhi, India, from 1st to 15th December 2020. Case records of patients admitted with severe acute respiratory illness (suspected COVID-19) were accessed and used to fill up a proforma where clinical and laboratory parameters were recorded. Chest radiographs (posteroanterior and anteroposterior) of the patients were evaluated to calculate mRALES and Brixia scores. Sensitivity, specificity, positive preditive value and negative predictive value were calculated. The p-value <0.05 was considered as statistically significant. Results: Out of the 113 patients, 62 were males and 51 females. The COVID-19 positivity rate was 15.04% (n=17). Mean age of patients was 52.64±15.63 years. Overall, the mean mRALES and Brixia scores were not statistically different between suspected (mRALES=3.94±2.51, Brixia=7.29±4.642), and confirmed COVID-19 (mRALES=4.25±2.56, Brixia=7.73±4.84) patients. However, in the subgroup of patients with history of obstructive airway disease, Brixia score was significantly higher among COVID-19 positive patients (7.09±4.70) as compared to COVID-19 suspected patients (0.53±4.31). Presence of low TLC {<9550/mm3 with sensitivity of 70.62%, specificity of 67.3%, Positive Predictive Value (PPV) of 26.7% and Negative Predictive Value (NPV) of 92.4%} and low ANC {< 7580/mm3 with sensitivity of 64.7%, specificity of 63.2%, PPV of 22.9% and NPV of 90.5%} significantly predicted the COVID-19 positivity among the suspected COVID-19 patients. Conclusion: mRALES and Brixia scores on CXR are not significantly different between suspected and confirmed COVID-19 patients and hence, cannot be used to judge who among suspected COVID-19 patients will turn out to be COVID-19 positive later. However, a TLC of less than 9550/ mm3 and an ANC of less than 7580/mm3 can predict COVID-19 positivity among suspected patients.

Optimizing Peripandemic Care for Veteran Major Non-Traumatic Lower Extremity Amputees: A Proposal Informed by a National Retrospective Descriptive Analysis of COVID-19 Risk Factor Prevalence

In response to the Coronavirus 2019 (COVID-19) pandemic, vascular surgeons in the Veteran Affairs Health Care System have been undertaking only essential cases, such as advanced critical limb ischemia. Surgical risk assessment in these patients is often complex, considers all factors known to impact short- and long-term outcomes, and the additional risk thatCOVID-19 infection could convey in this patient population is unknown. The European Centre for Disease Prevention and Control (ECDC) published risk factors (ECDC-RF) implicated in increased COVID-19 hospitalization and case-fatality which have been further evidenced by initial reports from the United States Centers for Disease Control and Prevention. CDC reports additionally indicate that African American (AA) patients have incurred disparate infection outcomes in the United States. We set forth to survey the Veterans Affairs Surgical Quality Improvement Program (VASQIP) database over a nearly 20 year span to inform ongoing risk assessment with an estimation of the prevalence of ECDC-RF in our veteran critical limb ischemia population and investigate whether an increased COVID-19 comorbidity burden exists for AA veterans presenting for major non-traumatic amputation.

Long term exposure to air pollution and COVID-19 incidence in the city of Varese, Northern Italy: A complete-year, individual-level analysis

Introduction Studies on air pollution and COVID-19 are limited to the first pandemic wave (April/June 2020) and by their ecological design. Objectives To investigate the association between airborne pollutants and SARS-CoV-2 incidence up to March 2021 in the Varese city (Lombardy region), with individual-level data on exposures, disease and confounders. Methods Varese citizens aged 18+ years as of Dec31st,2019 were linked by residential address to 2018 average annual exposure to outdoor concentrations of PM2.5, PM10, NO2, NO and O3 modelled using FARM chemical-transport model (linkage coverage: 97.4%). Citizens were linked to Regional datasets for COVID-19 case ascertainment (positive nasophar-yngeal swab specimens) and to define age, sex, residential care home living, population density and comorbidities. We estimated rate ratios and additional number of COVID-19 cases for 1 mg/m3 increase in air pollutants, from single-and bi-pol-lutant Poisson regression models. Results Among the 62.848 residents, we observed 4408 COVID-19 cases. Yearly average PM2.5 exposure was 12.5 mg/m3. Cumulative incidence curves suggest an increased risk for PM2.5>13.5 mg/m3 in correspondence of downtrend periods in the pandemic curve. Age, residential care home living, history of stroke, medications for diabetes, hypertension and obstructive airway disease were independently associated with COVID-19 rate. In single-pollutant multivariate model, 1 mg/m3 increase in PM2.5 was associated with 5.1% increase in COVID-19 rate (95%CI: 2.7%-7.5%), corresponding to 294 additional cases per 100.000 person-years. These figures were confirmed in bi-pollutant models and after excluding subjects in residential care homes. Similar findings were observed for PM10, NO2 and NO. O3 was associated with a 2% decrease in disease rate, the association being reversed in bi-pollutant models. Conclusions In our study, long term exposure to low-levels of air pollutants, especially PM2.5, positively affected COVID-19 incidence. Causality warrants confirmation in future studies;meanwhile, governmental efforts to further reduce air pollution should continue.