BACKGROUND:The US Air Quality Index (AQI) is the most widely reported tool for public communication of air pollution health risks in the United States, yet its effectiveness in protecting individuals with respiratory conditions remain poorly understood. GOALS:The American Thoracic Society (ATS) convened an ad hoc multidisciplinary committee, including participation from relevant officials, to assess the current evidence and define research priorities related to the AQI and respiratory health. METHODS:The committee conducted a systematic search of the peer-reviewed literature and held a meeting to discuss key topics. Subsequent engagement refined the findings and established consensus on priority research questions. RESULTS:The systematic search indicated significant gaps in the literature, including limited evaluation of AQI effectiveness in changing behavior, few studies assessing health outcomes associated with AQI use, and minimal research on how people with respiratory disease interpret and respond to AQI messaging. Priority research areas span key domains: AQI structure, sub-daily exposure estimation, communication strategies, clinical and community implementation, and evaluation of health and exposure reductions. Specific research recommendations include evaluating AQI structures that better reflect cumulative and multi-pollutant exposures, developing methods to assess how patients with respiratory conditions interpret and act on AQI messaging, and measuring whether AQI-informed behaviors result in meaningful reductions in exposure and improvements in health outcomes. CONCLUSIONS:This research statement outlines a framework for strengthening the scientific foundation of the AQI and improving its effectiveness as a respiratory health protection tool.

Significance: Sensory and subjective effects contribute to consumer response toward electronic nicotine delivery systems (ENDS). Evaluating the relative contributions of nicotine concentration, form (salt vs freebase), and carrier concentration (PG/VG ratio) is important to understanding why formulations may be more attractive. Methods: Participants were 78 adults (age ≥21) with no sensory deficits who used ENDS daily, randomized to one of two sub-studies. In Study A, 38 participants sampled tobacco-flavored e-liquids varying in PG/VG ratio (30/70, 60/40, 100/0) and nicotine concentration (0, 18, 36 mg/mL freebase). In Study B, 40 participants sampled e-liquids varying in nicotine form (salt, freebase) and concentration (0, 18, 36 mg/mL). Questionnaires assessed sensory and subjective effects. Generalized estimating equation (GEE) models examined the effects of experimental factors on these ratings. Results: Nicotine concentration was strongly related to a wide array of sensory and subjective effects measures, generally following a dose-response pattern. PG/VG showed relationships with a subset of hedonic effects independent of nicotine. There were no significant differences observed for sensory or subjective measures between salt versus freebase nicotine. Conclusions: Nicotine concentration showed consistent associations with sensory response to e-liquids when delivered in the same device. Sensory and behavioral responses to different e-liquid compositions may help contextualize ENDS usage patterns, risk perceptions, and behaviors.

We previously identified a blood-based 4-gene signature that accurately discriminates bacterial from nonbacterial acute respiratory infection (ARI) in 504 hospitalized adults (area under the receiver operating characteristic curve [AUC] = 0.90). Here, we evaluate how well this global signature performs within subgroups of patients based on underlying lung disease or presence of pneumonia, comparing it to newly developed subgroup-specific signatures assessing whether performance is improved by tailoring unique gene signatures to homogeneous subgroups. Our global gene signature strongly discriminated bacterial from nonbacterial ARI within every clinical subgroup, including pneumonia (AUC = 0.77-0.94), and outperformed every subgroup-specific signature (AUC = 0.57-0.90), suggesting broad applicability in adults with ARI.

The rate of respiratory viral infection (RVI) associated with acute air pollution exposure is well established, but whether bacterial and viral infections respond similarly to traffic related air pollution (TRAP) exposure is less well understood. Using a novel seasonal time-stratified case-crossover design and conditional logistic regression, we separately estimated the rate of hospitalization for 465 patients with RVI, respiratory bacterial infection (RBI), or combined respiratory viral and bacterial infection (RVBI) associated with increased ambient particulate matter ≤2.5 µm (PM2.5), black carbon (BC), nitrogen dioxide (NO2) and carbon monoxide (CO) concentrations in the previous 1, 2, and 3 weeks (lag days 0-6, 7-13, 14-20). In a novel approach, a four-physician panel adjudicated each case of infection to accurately classify the type of infection present and only patients with the highest diagnostic certainty were enrolled in this study. Associations were strongest between TRAP and RVI at the 0-6 lag period, with fewer, less precise associations at later lag times for RVBI and RBI. Each 2.6 µg/m3 increase in PM2.5 on lag days 0-6 was associated with a 22.1% increased rate of RVI hospitalization (95% CI: 1.6%, 46.7%). Each 0.1 µg/m3 increase in BC was associated with a 30.0% increase (95% CI: 5.0%, 61.1%) in the rate of hospitalization for RVI. Rates of hospitalization for RVI associated with increased PM2.5 were generally largest for lag days 0-6 and 7-13. The RVI/BC rate ratio was larger for females than males for days 0-13, but not for PM2.5 and NO2. Short term increases in PM2.5, BC, NO2, and CO concentrations (markers of traffic pollution) were associated with an increased rate of RVI hospitalization, while sex-specific associations were observed between BC and RVI for females. Further study of the mechanism underlying the effect of TRAP on RVI is needed.

BACKGROUND:Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) cause acute respiratory infections (ARI) in persons of all ages. The viruses are structurally similar although HMPV lacks 2 nonstructural proteins of RSV known to suppress interferon signaling. METHODS:We analyzed data from 2 studies that prospectively enrolled hospitalized adults with ARI and compared clinical characteristics and outcomes of HMPV and RSV infection. Gene expression was compared between subjects with HMPV and RSV using DESeq2 to analyze read counts from samples of globin-reduced RNA from whole blood, sequenced using Illumina NovaSeq. RESULTS:Of 1914 illnesses evaluated, 127 (6.6%) had RSV and 90 (4.7%) had HMPV identified as a sole viral pathogen. Demographics and preexisting conditions were similar although HMPV patients had significantly less active tobacco use and numerically less underlying heart and lung disease. Sore throat, temperature >38°C, and clinically adjudicated pneumonia were significantly more frequent with HMPV compared to RSV. Restricting analysis to those subjects adjudicated as viral alone without bacterial coinfection, we identified 197 differentially expressed genes between RSV- and HMPV-infected subjects. Genes with higher expression in HMPV-infected individuals were associated with antigen binding, immunoglobulin production, and adaptive immunity. Genes increased in RSV-infected individuals were associated with NK T cells. CONCLUSIONS:Although RSV and HMPV are closely related viruses, we found differences in the clinical features of adults with HMPV patients presenting with more flu-like symptoms and viral pneumonia. Peripheral blood gene expression of hospitalized HMPV-infected patients also differed compared to those hospitalized and infected with RSV.

Rational: Human metapneumovirus (HMPV) and Respiratory syncytial virus (RSV) both can cause respiratory illness in people of all ages. The clinical syndromes associated with these two viruses are similar and range from mild upper respiratory infection to severe lower respiratory tract infections (LRTI) that require hospitalization. Here, we sought to identify peripheral blood gene expression patterns associated with HMPV- or RSV-associated LRTI in hospitalized adults. Methods: 1112 adults hospitalized with LRTI were enrolled with consent under IRB approval. All subjects underwent comprehensive microbiologic testing. Globin reduced RNA isolated from whole blood was used to generate libraries for RNASeq using the Illumina NovaSeq. We compared expression patterns for subjects with HMPV infection (n=43), RSV infection (n=54) and non-infected controls (n=62) using the Wald test in DESeq2.Results: A total of 7,352 genes passed quality control filtering criteria and were used for differential expression analysis. We identified a set of genes (n=93) showing significant differences in expression (FDR<0.05) in patients with HMPV versus RSV. Excluding subjects with bacterial co-infection increased the number of genes identified (n=197). Genes identified which were increased in HMPV (n=120 at log2 FC>0.5 of 141 at FDR<0.05) were associated with antigen binding, immunoglobulin production and adaptive immunity. The genes identified which were decreased in HMPV (n=16 of 56) were associated with CD8 T and NK T cells. Interestingly, fewer genes were significantly different when comparing non-infected controls to HMPV (n=0 or 2) or RSV (n=13 or 99).Summary: We can detect peripheral blood gene expression patterns for adult LRTI subjects with HMPV, which are distinct from those with RSV. The results from the study provide novel insight, which may help to guide future prophylactic and interventional strategies, and/or measure the efficacy of existing strategies.

We examined the association between air pollution and neutralizing antibody responses to COVID-19 vaccination in participants enrolled in a phase 3 clinical trial. Seventy-four adults were vaccinated with two doses of the AstraZeneca ChAdOx1 vectored vaccine (AZD1222) (5 x 1010 viral particles) at baseline and day 29, between Aug 28, 2020, to Jan 15, 2021, in Monroe County, NY. SARS-CoV-2 pseudovirus neutralizing ID50 titers (NAb) and total spike protein IgG were assessed at baseline and 15, 29, 43, 57 and 90 days after vaccination. In this pilot study, each participant's dates of neutralization titers were matched to Monroe County ambient concentrations of fine particles (PM2.5; ≤ 2.5 µm), black carbon (BC; marker of traffic), among other particulate and gaseous pollutants. Using linear mixed models, we estimated the association between each interquartile range (IQR) difference in air pollutant concentrations in the 14 days prior to blood collection and antibody responses at each post vaccination timepoint. Though not statistically significant, we observed a 23% reduction in NAb titer (95% CI: -67%, 79%) measured on day 43 (i.e., 14 days after second vaccination) associated with each 0.32 µg/m3 increase in BC concentrations in the prior 14 days. We also observed a 42% increase in spike protein IgG (95% CI: -16%, 141%) measured on day 15 (i.e., 14 days after primary vaccination) associated with each 0.26 µg/m3 increase in BC concentrations in the 14 days prior. A similar pattern for total spike protein IgG was observed at day 29 (42%; 95% CI: -22%, 157%) and 90 (43%; 95% CI: -11%, 127%). Future research will need to explore the possible association between air pollution exposure and antibody response to SARS-CoV-2 vaccination given the potential for compromised vaccine efficacy.

Abstract Background RSV and HMPV cause acute respiratory infections (ARI) in children and adults. Two RSV vaccines for older adults are now licensed, and HMPV vaccines are in development. Limited data exist comparing clinical disease and impact of HMPV to RSV in older adults.Table 1.Demographic and Baseline Characteristics Methods We analyzed data from two studies of prospectively enrolled hospitalized adults with ARI from 2008-2012 and 2018-2023 and compared demographics, clinical characteristics and outcomes of HMPV and RSV. Similar inclusion/exclusion criteria and RT-PCR diagnosis were used for both studies, with addition of serology only in the first. All cases were adjudicated for bacterial coinfection and radiographic pneumonia by 1 pulmonary and 3 ID physicians. Comparisons used t-test or χ2.Table 2.Signs and Symptoms at Admission, Clinical Characteristics, and Outcomes Results Of 2,012 patients enrolled, 127 (6.3%) and 90 (4.5%) had RSV or HMPV, respectively: 5 patients with RSV/HMPV co-infection were excluded from analysis. Mean age (67 years), sex, race and ethnicity were similar (Table 1). HMPV patients were less likely to reside in congregate settings (7.8 v 14.9%, p=0.14) or have COPD (31.5 v 40.9%, p=0.16), CHF (17.8 v 26.0%, p=0.15), or active tobacco use (17.8 v 30.7%, p=0.03). Clinical presentation also differed with HMPV more associated with sore throat (50.0 v 33.9%, p=0.02), feverishness (64.4 v 48.0%, p=0.02), temperature >38oC (33.3 v 21.3%, p=0.05), and constitutional symptoms (75.6 v 66.1%, p=0.14). (Table 2) HMPV patients required less ICU care (5.6 v 12.6%, p=0.08) and mechanical ventilation (1.1 v 5.5%, p=0.09). Bacterial coinfection occurred equally, but HMPV patients judged as viral infection alone were more often adjudicated as pneumonia (35.6 v 22.8%, p=0.006). (Fig. 1).Figure 1.Adjudicated Radiographic Pneumonia with Microbiologic Diagnosis Conclusion Although RSV and HMPV are closely related viruses, we found differences in the clinical features of adults hospitalized with ARI. While HMPV accounted for about 3/4 the number of cases compared to RSV, HPMV patients were generally healthier and community-dwelling with fewer high-risk cardiopulmonary conditions. Notably, HMPV patients presented with more flu-like symptoms and were judged more often to have viral pneumonia. These results support development of an adult HMPV vaccine. Ongoing gene expression analyses may elucidate mechanisms underlying these differences. Disclosures Ann R. Falsey, MD, ADMA: Board Member|BioFire Diagnostics: Grant/Research Support|CyanVac: Grant/Research Support|GSK: Advisor/Consultant|GSK: Travel support|Janssen: Grant/Research Support|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant|Sanofi Pasteur: Travel support|VaxCo: Grant/Research Support Angela R. Branche, MD, Cyanvac: Grant/Research Support|GSK: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Grant/Research Support|Moderna: Honoraria|Novavax: Advisor/Consultant|Pfizer: Grant/Research Support|Sanofi: Honoraria|VaxCo: Grant/Research Support Edward E. Walsh, MD, Enanta: Advisor/Consultant|Enanta: Honoraria|GSK: Advisor/Consultant|Janssen: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support

Adverse environmental exposures worsened by our changing climate threaten respiratory health and exacerbate existing social inequities that further undermine environmental justice (EJ). EJ is the capacity of all people, regardless of sociodemographic characteristics, to minimize harmful exposures and live a healthy life. EJ is achieved through the development, implementation, and enforcement of environmental laws, regulations, and policies. In 2023, an American Thoracic Society workshop convened a group of 39 clinicians, researchers, community advocates, research program administrators, and health policy experts to characterize the respiratory health threats and EJ concerns arising from climate change. The workshop explored four main climate areas through a socioecological and EJ perspective: 1) respiratory health risks, 2) respiratory health impacts in low- and middle-income countries, 3) climate mitigation and adaptation strategies, and 4) priority research infrastructure needs. The workshop committee concluded that climate change can directly and indirectly impair respiratory health and that persistently excluded or marginalized communities (including those in low- and middle-income countries) are disproportionately impacted. These disproportionately impacted communities also lack hazard monitoring and resources to evaluate and advocate for mitigation of adverse environmental exposures. Future respiratory health research must inform mitigation strategies to reduce climate-related emissions from industry to net zero. Researchers, communities, and policymakers require training and support to meaningfully engage with systems-thinking research as well as policy solutions focused on mitigating and adapting to climate change. Finally, the workshop committee recommends a rapid transition away from fossil fuel dependence to a world that provides an equitable allocation of clean transportation options and renewable sources of energy production.

Electronic nicotine delivery systems are marketed as safer than cigarettes, but their flavoring agents may be toxic. We evaluated reproductive effects of menthol- and strawberry-flavored e-liquids in Caenorhabditis elegans using wild-type and chemosensory-defective mutants ( ocr-2 ; osm-9 ; ocr-1 ; trpa-1 ). L4-stage worms were exposed to flavored e-liquids on peptone-free media with Escherichia coli or natural microbiota ( Lelliottia amnigena , Stenotrophomonas indicatrix , Comamonas piscis ). Flavored exposure reduced brood size; menthol delayed egg-laying. Microbiota mitigated effects in most strains except ocr-2 ; osm-9 ; ocr-1 with strawberry. Findings show flavored e-liquids harm reproduction, and microbiota may protect against flavor-induced toxicity.

Rationale: Unnecessary antibiotic use is a major driver of increasing antimicrobial resistance, one of the most urgent threats to global public health. Although polymerase chain reaction (PCR) testing allows rapid diagnosis of respiratory viruses, impact on management of hospitalized patients has been minimal. There is a clear need for sensitive and specific diagnostic tests for determining the presence or absence of bacterial etiology in acute respiratory infections (ARI). Methods: 1,111 adults hospitalized with ARI were enrolled and underwent comprehensive microbiologic testing. Illnesses were adjudicated by a committee of clinicians, and those with a definitive microbiologic etiology underwent RNA sequencing. RNA isolated from globin reduced whole blood from adults with viral infection (V; n=280), bacterial infection (B; n=129), or mixed viral and bacterial co-infection (VB; n=95) was used to generate libraries to perform RNASeq using the Illumina NovaSeq. Reads were aligned using STAR, with counts summarized through HT-Seq and normalized as counts per million. Genes were filtered to remove those undetected or displaying >15% variability attributable to sequencing batch. Univariate differential expression between viral alone (V) and any bacterial infection (B and BV) was assessed using deSeq2. A leave-one-batch-out nested cross-validation (CV) procedure was used to tune a hard-thresholded, mostly relaxed, LASSO-constrained logistic regression model to select a parsimonious set of genes capable of discriminating bacterial (B and VB) from non-bacterial (V) infection. Results: A total of 7,352 genes passed quality control filtering criteria and were used for signature discovery. At FDR < 0.05, we identified >4,000 genes as significantly differentially expressed between bacterial (B+BV; n=224) and non-bacterial (V; n=280) infection. Our procedure selected four genes (IFIT1, ITGA7, IFI27, FAM20A) highly capable of discriminating bacterial from non-bacterial infection (CV-AUC = 0.90). The 4-gene signature also demonstrated excellent ability to discriminate bacterial from non-bacterial infections in two independent cohorts (AUC = 0.90 for GSE211567; AUC = 0.94 for phs001248.v1.p1). Thresholding the 4-gene risk score to yield 90% sensitivity to detect bacterial infection, and thus >90% negative predictive value, resulted in an estimated 67.5% specificity. Summary: Using a novel approach, we developed and validated a 4-gene signature that defines the absence of bacterial involvement in ARI. This signature may serve as an effective diagnostic to support a physician's decision to withhold or discontinue antibiotics in ARI.

Rationale: In 2017, introduction of Tier 3 light duty vehicles with reduced emissions began in NY State, with declining PM2.5 concentrations statewide. We hypothesized that Tier 3 vehicle controls would result in a reduction in the rates of hospitalization and emergency department (ED) visits for respiratory syncytial virus (RSV) associated with increased PM2.5. Methods: From the Statewide Planning and Research Cooperative System (SPARCS), we retained adult and pediatric patients hospitalized or having an ED visit for respiratory syncytial virus (RSV) living within 15 miles of the Buffalo, Rochester, Albany, Bronx, Manhattan, or Queens air quality monitoring sites. Using a case-crossover design and conditional logistic regression, we estimated the excess rates (ER) of RSV hospitalizations and ED visits associated with increased ambient PM2.5 concentrations in the previous 0-6 days in relation to age and sex. We then evaluated whether these relative rates differed in the period prior to the Tier 3 introduction (2014-2016) or after (2017-2019). Results: We observed a non-statistically significant increase in the rate of hospitalizations for RSV demonstrated in males within all age subgroups in 2017-2019 compared to 2014-2016. Specifically, adult males had 21.8% increased rate of RSV hospitalizations (95% CI: -9.5, 63.7) during 2017-2019 compared to a 13% decreased rate of hospitalizations (95% CI = -31.6,10.8) in 2014-2016 associated with a 4.6 ug/m3 increase in PM2.5 in the 0-6 day lag period. A similar non-statistical increase in ED visits for RSV was observed in 2017-2019 period compared to 2014-2016. In female patients, there generally appeared to be a decreased rate of hospitalizations and ED visits associated with IQR increases in PM2.5 at all lag periods and there were no consistent differences between periods. Conclusions: Despite the early implementation period of Tier 3 vehicles with lower pollutant emissions in 2017-2019, we did not observe a reduction in excess rates of hospitalizations and ED visits for RSV in males and females. Unexpectedly, the rate of healthcare encounters for males appeared to increase in the early implementation period compared with the period prior to implementation. A potential susceptibility of males to the change in the toxicity per unit mass of the PM mixture after the Tier 3 standards may explain the different pattern of hospitalizations and ED visits when comparing the sex-specific results.

We examined associations between seven source-specific PM 2.5 concentrations and rates of asthma and COPD hospitalizations and emergency department (ED) visits in New York State and compared the changes in excess rates (ERs) between pre- (2014-2016) and post-implementation (2017-2019) of the Tier 3 automobile emission controls on new vehicles policy. A modified time-stratified case-crossover design and conditional logistic regression were employed to estimate the ERs of asthma and COPD hospitalizations and ED visits associated with interquartile range (IQR) increases in source-specific PM 2.5 concentrations. The 7 PM 2.5 sources were spark- ignition emissions (GAS), diesel (DIE), biomass burning (BB), road dust (RD), secondary nitrate (SN), secondary sulfate (SS), and pyrolyzed organic rich (OP). Residual PM 2.5 (PM2.5 - specific source [e.g., GAS]), daily temperature, relative humidity, weekday, and holidays were included in the model. IQR increases in GAS, SS, RD, BB, and SN were associated with increased ERs of asthma ED visits (highest ERs: 0.5 %-3.1 %), while a negative association was observed with DIE and OP. The rate of asthma hospitalizations was associated with increased RD concentrations (ERs: 1.3 %-1.7 %). Both COPD ED visit and hospitalization rates were associated with increased OP (ERs: 2.1 %-3.4 %), and increased SS was positively associated with COPD ED visits (ER = 3.8 %). In summary, after Tier 3 implementation (2017-2019), we found lower ERs for COPD admissions associated with BB, RD, SN, and SS compared to 2014-2016. However, rates of asthma ED visits associated with source-specific PM 2.5 concentrations were generally higher for all sources, except DIE, post- versus pre- implementation, requiring further research for validation.

Unnecessary antibiotic use is a major driver of antimicrobial resistance, an urgent public health threat. Acute respiratory infection (ARI) is a leading cause of inappropriate antibiotic use, creating an unmet need for improved diagnostics to identify bacterial etiology in ARI. In this work we show a 4-gene signature defining the absence of bacterial ARI which may be useful for managing antibiotics in ARI. Hospitalized adults with ARI underwent comprehensive microbiologic testing and those with definitive viral (n = 280), bacterial (n = 129), or mixed viral-bacterial infection (n = 95) had whole blood RNA sequencing. A hard-thresholded, mostly relaxed, LASSO-constrained logistic regression model is used to select a parsimonious gene set (ITGB4, ITGA7, IFI27, FAM20A) highly capable of discriminating any bacterial from nonbacterial infection (cross-validated AUC = 0.90). The 4-gene signature is validated in five independent adult RNAseq cohorts (AUC = 0.89-0.98), two adult microarray cohorts (AUC = 0.73-0.90), and one pediatric pneumonia RNAseq cohort (AUC 0.74). Thresholding the 4-gene risk score to yield 90% sensitivity to detect bacterial infection results in 71% specificity and 91% negative predictive value.

The introduction of Tier 3 light-duty vehicles with reduced emissions began in New York State (NYS) in 2017, with required compliance by 2025. We hypothesized that improved air quality during the early implementation of Tier 3 (2017-2019) would result in reduced rates of hospitalizations and emergency department (ED) visits for respiratory infection associated with increased PM2.5 compared to 2014-2016 (pre-Tier 3). Using data on adult patients hospitalized or having an ED visit for influenza, upper respiratory infection, culture-negative pneumonia, or respiratory bacterial infection, living within 15 miles of six air quality monitoring sites in NY, and a case-crossover design and conditional logistic regression, we estimated the rates of respiratory infection hospitalizations and ED visits associated with increased ambient PM2.5 concentrations in the previous 0-6 days and each week thereafter up to 1 month. Interquartile range (IQR) increases in PM2.5 in the previous 6 days were associated with 4.6% (95% CI: -0.5, 10.1) and 11.9% (95% CI = 6.1, 18.0) increased rates of influenza hospitalizations in 2014-2016 and 2017-2019, respectively. This pattern of larger relative rates in 2017-2019 observed at all lag times was only present in males hospitalized for influenza but not other infections or in females. The rates of respiratory infection visits associated with increased PM2.5 were generally not reduced in this early Tier 3 implementation period compared to 2014-2016. Limited fleet penetration of Tier 3 vehicles and differences in particle deposition, infection type, and sex by period may all have contributed to this lack of improvement.

[This corrects the article DOI: 10.1016/j.jctube.2024.100460.].

Evidence from in vitro and animal models has identified the pulmonary toxicity of flavors in electronic cigarettes (ECIGs); however, less is known from epidemiological studies about the effects of flavors in the respiratory health. This study examined the longitudinal association between exposure to ECIGs flavors and nocturnal dry cough among ECIGs users. A secondary analysis of data from the Population Assessment of Tobacco and Health Study (2014-2019) was conducted. The study population included adults who provided information (n = 18,925) for a total of 38,638 observations. Weighted-incidence estimates and weighted- generalized estimating equation models were performed to assess unadjusted and adjusted associations. The weighted incidence proportion (WIP) of nocturnal dry cough was significantly higher among current (WIP:16.6%; 95%CI 10.5, 21.2) and former fruit flavored ECIGs users (WIP:16.6%; 95%CI 11.3, 21.9) as compared to non-ECIGs users (WIP:11.1%; 95%CI 10.6, 11.6). Current ECIGs users of fruit flavors showed 40% higher risk of reporting cough than non-ECIGs users (aRR:1.40, 95%CI 1.01, 1.94). Former ECIGs users of multiple flavors and other flavors had 300% and 66% higher risk to develop cough, respectively (aRR:3.33, 95%CI 1.51, 7.34 and aRR:1.66, 95%CI 1.0.9, 2.51), relative to non-ECIGs users. We observed a significantly higher risk of developing nocturnal dry cough in the past 12 months in current and former ECIGs users of fruit flavors and in former ECIGs users of multiple flavors. To the extent that cough may serve as an early indicator of respiratory inflammation and potential disease risk, the association between ECIGs use and cough raises potential concerns.