CSP7 Protects Alveolar Epithelial Cells by Targeting p53-Fibrinolytic Pathways During Lung Injuries.

Impaired alveolar epithelial regeneration in patients with idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) is attributed to telomere dysfunction in type II alveolar epithelial cells (A2Cs). Genetic susceptibility, aging, and toxicant exposures, including tobacco smoke (TS), contribute to telomere dysfunction in A2Cs. Here we investigated whether improvement of telomere function plays a role in CSP7-mediated protection of A2Cs against ongoing senescence and apoptosis during bleomycin (BLM)-induced pulmonary fibrosis (PF) as well as alveolar injury caused by chronic TS exposure. We found a significant telomere shortening in A2Cs isolated from IPF and COPD lungs in line with other studies. These cells showed increased p53 in addition to its post-translational modification with induction of activated caspase-3 and ß-galactosidase, suggesting a p53-mediated loss of A2C renewal. Further, we found increased expression of SIAH-1, a p53-inducible E3 ubiquitin ligase known to down-regulate telomere repeats binding factor 2 (TRF2). Consistent with the loss of TRF2 and upregulation of TRF1, telomerase reverse transcriptase (TERT) was downregulated in A2Cs. A2Cs from fibrotic lungs of mice either repeatedly instilled with BLM or isolated from chronic TS exposure-induced lung injury model showed reduced telomere length along with induction of p53, PAI-1, SIAH1 and TRF1 as well as loss of TRF2 and TERT, which were reversed in wild-type mice after treatment with CSP7. Interestingly, PAI-1-/- mice, or those lacking microRNA-34a expression in A2Cs, resisted telomere dysfunction, while uPA-/- mice failed to respond to CSP7 treatment, suggesting p53-microRNA-34a feed-forward induction and p53-uPA pathway contributes to telomere dysfunction.

Impairment of Gal-9 and Tim-3 crosstalk between Tregs and Th17 cells drives tobacco smoke-induced airway inflammation.

Overexpression of T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) on T cells has been observed in smokers. However, whether and how galectin-9 (Gal-9)/TIM-3 signal between T-regulatory cells (Tregs) and type 17 helper (Th17) cells contributes to tobacco smoke-induced airway inflammation remains unclear. Here, we aimed to explore the role of the Gal-9/TIM-3 signal between Tregs and Th17 cells during chronic tobacco smoke exposure. Tregs phenotype and the expression of TIM-3 on CD4+ T cells were detected in a mouse model of experimental emphysema. The role of TIM-3 in CD4+ T cells was explored in a HAVCR2-/- mouse model and in mice that received recombinant anti-TIM3. The crosstalk between Gal-9 and Tim-3 was evaluated by coculture Tregs with effector CD4+ T cells. We also invested the expression of Gal-9 in Tregs in patients with COPD. Our study revealed that chronic tobacco smoke exposure significantly reduces the frequency of Tregs in the lungs of mice and remarkably shapes the heterogeneity of Tregs by downregulating the expression of Gal-9. We observed a pro-inflammatory but restrained phenotypic transition of CD4+ T cells after tobacco smoke exposure, which was maintained by TIM-3. The restrained phenotype of CD4+ T cells was perturbed when TIM-3 was deleted or neutralised. Tregs from the lungs of mice with emphysema displayed a blunt ability to inhibit the differentiation and proliferation of Th17 cells. The inhibitory function of Tregs was partially restored by using recombinant Gal-9. The interaction between Gal-9 and TIM-3 inhibits the differentiation of Th17 cells and promotes apoptosis of CD4+ T cells, possibly by interfering with the expression of retinoic acid receptor-related orphan receptor gamma t. The expression of Gal-9 in Tregs was reduced in patients with COPD, which was associated with Th17 response and lung function. These findings present a new paradigm that impairment of Gal-9/Tim-3 crosstalk between Tregs and Th17 cells during chronic tobacco smoke exposure promotes tobacco smoke-induced airway/lung inflammation.

Airway inflammation in a novel mouse model of asthma-COPD overlap induced by co-exposure to papain and tobacco smoke.

Asthma and chronic obstructive pulmonary disease (COPD) are respiratory diseases associated with airway inflammation, which is the main pathogenesis. Although their causes and characteristics differ, in some cases, asthma and COPD may coexist in the same patient in a condition called asthma-COPD overlap (ACO). The prognosis of ACO is more unfavourable than those of asthma or COPD alone, without any treatment strategies demonstrating efficacy. Owing to its intricate spectrum of features, the detailed pathogenesis of how ACO exacerbates respiratory features remains unclear. In this study, we exposed papain-induced asthma model mice to tobacco smoke to establish an ACO mouse model, in which features of airway inflammation observed in both asthma and COPD were incorporated. This model exhibited distinctive mixed and corticosteroid-resistant airway inflammation and emphysematous changes that are characteristic of ACO. The novel mouse model established here is expected to significantly contribute to elucidating the mechanisms of the broad pathologies of ACO and identifying potential therapeutic targets.

The impact of exposure to tobacco smoke and e-cigarettes on asthma-related outcomes: Systematic review informing the EAACI guidelines on environmental science for allergic diseases and asthma.

To inform the clinical practice guidelines' recommendations developed by the European Academy of Allergy and Clinical Immunology systematic reviews (SR) assessed using GRADE on the impact of environmental tobacco smoke (ETS) and active smoking on the risk of new-onset asthma/recurrent wheezing (RW)/low lung function (LF), and on asthma-related outcomes. Only longitudinal studies were included, almost all on combustion cigarettes, only one assessing e-cigarettes and LF. According to the first SR (67 studies), prenatal ETS increases the risk of RW (moderate certainty evidence) and may increase the risk of new-onset asthma and of low LF (low certainty evidence). Postnatal ETS increases the risk of new-onset asthma and of RW (moderate certainty evidence) and may impact LF (low certainty evidence). Combined in utero and postnatal ETS may increase the risk of new-onset asthma (low certainty evidence) and increases the risk of RW (moderate certainty evidence). According to the second SR (24 studies), ETS increases the risk of severe asthma exacerbations and impairs asthma control and LF (moderate certainty evidence). According to the third SR (25 studies), active smoking increases the risk of severe asthma exacerbations and of suboptimal asthma control (moderate certainty evidence) and may impact asthma-related quality-of-life and LF (low certainty evidence).

Environmental tobacco smoke increased risk of gestational diabetes mellitus: A birth cohort study in Sichuan, China.

INTRODUCTION: Studies on the relationship between environmental tobacco smoke (ETS) and gestational diabetes mellitus (GDM) are limited. In this study, we aimed to clarify the association between ETS at different trimesters of pregnancy and the risk of GDM among non-smoking pregnant women. METHODS: A total of 16,893 non-smoking mothers from the Southwest Birth Cohort, China, were included in the final analyses. Exposure and outcome measures included self-reported ETS status at different trimesters of pregnancy and GDM diagnosis. Multivariable logistic regression models were constructed to estimate the association between ETS and GDM. RESULTS: The prevalence of ETS exposure was 25.7%. Compared with no ETS, ever ETS had an increased risk of GDM, with an adjusted odds ratio (95% confidence intervals) of 1.21 (1.09, 1.33). The association remained consistent at different trimesters of pregnancy ETS exposure. In the last trimester and with continuous ETS exposure, the risk of GDM increased significantly with the increase in the duration of the exposure. The risk of GDM associated with ever ETS during pregnancy significantly increased in mothers over 30 years old and pre-pregnancy overweight (P for interaction <0.05). CONCLUSIONS: ETS exposure at different trimesters of pregnancy was associated with an increased risk of GDM among non-smoking pregnant women. These findings emphasise the importance of preventing ETS exposure during pregnancy.

Tobacco smoke condensate-induced senescence in endothelial cells was ameliorated by colchicine treatment via suppression of NF-κB and MAPKs P38 and ERK pathways activation.

Smoking is the major cause of cardiovascular diseases and cancer. It induces oxidative stress, leading to DNA damage and cellular senescence. Senescent cells increase the expression and release of pro-inflammatory molecules and matrix metalloproteinase, which are known to play a vital role in the initiation and progression of cardiovascular diseases and metastasis in cancer. The current study investigated the smoking induced cellular senescence and employed colchicine that blocked senescence in endothelial cells exposed to tobacco smoke condensate. Colchicine prevented oxidative stress and DNA damage in tobacco smoke-condensate-treated endothelial cells. Colchicin reduced ß-gal activity, improved Lamin B1, and attenuated cell growth arrest markers P21 and P53. Colchicine also ameliorated the expression of SASP factors and inhibited the activation of NF-kB and MAPKs P38 and ERK. In summary, colchicine inhibited tobacco smoke condensate-induced senescence in endothelial cells by blocking the activation of NF-kB and MAPKs P38 and ERK.

Exocyclic DNA adducts and oxidative stress parameters: useful tools for biomonitoring exposure to aldehydes in smokers.

CONTEXT: Exocyclic DNA adducts have been shown to be potential biomarkers of cancer risk related to oxidative stress and exposure to aldehydes in smokers. In fact, aldehydes potentially arise from tobacco combustion directly and endogenously through lipid peroxidation. OBJECTIVE: This study aims to investigate the relationship between a profile of nine aldehydes-induced DNA adducts and antioxidant activities, in order to evaluate new biomarkers of systemic exposure to aldehydes. METHODS: Using our previously published UPLC-MS/MS method, adducts levels were quantified in the blood DNA of 34 active smokers. The levels of antioxidant vitamins (A, C and E), coenzyme Q10, ß-carotene, superoxide dismutase (SOD) and autoantibodies against oxidized low-density lipoprotein were measured. RESULTS: Adducts induced by tobacco smoking-related aldehydes were quantified at levels reflecting an oxidative production from lipid peroxidation. A significant correlation between SOD and crotonaldehyde-induced adducts (p = 0.0251) was also observed. ß-Carotene was negatively correlated with the adducts of formaldehyde (p = 0.0351) and acetaldehyde (p = 0.0413). Vitamin C tended to inversely correlate with acetaldehyde-induced adducts (p = 0.0584). CONCLUSION: These results are promising, and the study is now being conducted on a larger cohort with the aim of evaluating the impact of smoking cessation programs on the evolution of adducts profile and antioxidants activities.

Role of parental smoking and environmental tobacco smoke exposure in childhood cancer: A study using hair cotinine analysis and questionnaires.

OBJECTIVES: In the etiology of childhood cancers, many genetic and environmental factors play a role. One of these factors could be cigarette smoking, and the main source of tobacco smoke exposure of children is parental smoking. However, establishing a causal relationship between parental smoking and childhood cancers has proven challenging due to difficulties in accurately detecting tobacco smoke exposure METHODS: To address this issue, we used hair cotinine analysis and a questionnaire to get information about tobacco smoke exposures of pediatric cancer patients and healthy children. A total of 104 pediatric cancer patients and 99 healthy children participated in our study. Parental smoking behaviors (pre-conceptional, during pregnancy, and current smoking) and environmental tobacco smoke (ETS) exposures of children are compared. RESULTS: We have found no differences between two groups by means of maternal smoking behaviors. However, the rates of paternal pre-conceptional smoking and smoking during pregnancy were significantly low in cancer patients (p < .05). These data suggest that social desirability bias among fathers of cancer patients may have contributed to this discrepancy. According to questionnaire, cancer patients had significantly lower ETS exposures than healthy children (p < .05). However, ETS exposure assessment through cotinine analysis demonstrated that cancer patients had higher exposure to ETS compared to healthy children (p < .001). CONCLUSION: Our findings provide evidence supporting the potential role of smoking as a risk factor for childhood cancers. This study also revealed that questionnaires could cause biases. We suggest that cotinine analysis along with validated questionnaires can be used to prevent biases in studies of tobacco smoke in the etiology of childhood cancers.

Parental smoking and respiratory outcomes in young childhood cancer survivors.

BACKGROUND: Passive exposure to cigarette smoke has negative effects on respiratory health. Childhood cancer survivors (CCS) are at increased risk for respiratory disease due to treatment regimens that may harm the respiratory system. The objective of this study was to assess the prevalence of parental smoking among CCS and investigate its association with respiratory outcomes. PROCEDURE: As part of the Swiss Childhood Cancer Survivor Study, between 2007 and 2022, we sent questionnaires to parents of children aged ≤16 years who had survived ≥5 years after a cancer diagnosis. Parents reported on their children's respiratory outcomes including recurrent upper respiratory tract infections (otitis media and sinusitis), asthma, and lower respiratory symptoms (chronic cough persisting >3 months, current and exercise wheeze), and on parental smoking. We used multivariable logistic regression to investigate associations between parental smoking and respiratory outcomes. RESULTS: Our study included 1037 CCS (response rate 66%). Median age at study was 12 years (interquartile range 10-14 years). Eighteen percent of mothers and 23% of fathers reported current smoking. CCS exposed to smoking mothers were more likely to have recurrent upper respiratory tract infections (OR 2.1; 95%CI 1.1-3.7) and lower respiratory symptoms (OR 2.0; 95%CI 1.1-3.7). We found no association with paternal smoking. CONCLUSIONS: A substantial proportion of CCS in Switzerland have parents who smoke. Exposure to maternal smoking was associated with higher prevalence of upper and lower respiratory problems. Healthcare providers can support families by addressing caregiver smoking behaviors and providing referrals to smoking cessation programs.

PD-L2 mediates tobacco smoking-induced recruitment of regulatory T cells via the RGMB/NFκB/CCL20 cascade.

Programmed cell death ligand 2 (PD-L2), a ligand for the receptor programmed cell death 1 (PD-1), has an identity of 34% with its twin ligand PD-L1 and exhibits higher binding affinity with PD-1 than PD-L1. However, the role of PD-L2 in non-small cell lung cancer (NSCLC) progression, especially tobacco-induced cancer progression, has not been fully understood. Here, we found that PD-L2 promoted tumor growth in murine models with recruitment of regulatory T cells (Tregs). In patients with NSCLC, PD-L2 expression level in tumor samples was higher than in counterpart normal controls and was positively associated with patients' response to anti-PD-1 treatment. Mechanismly, PD-L2 bound its receptor Repulsive guidance molecule B (RGMB) on cancer cells and activated extracellular signal-regulated kinase (Erk) and nuclear factor κB (NFκB), leading to increased production of chemokine CCL20, which recruited Tregs and contributed to NSCLC progression. Consistently, knockdown of RGMB or NFκB p65 inhibited PD-L2-induced CCL20 production, and silencing of PD-L2 repressed Treg recruitment by NSCLC cells. Furthermore, cigarette smoke and carcinogen benzo(a)pyrene (BaP) upregulated PD-L2 in lung epithelial cells via aryl hydrocarbon receptor (AhR)-mediated transcription activation, whose deficiency markedly suppressed BaP-induced PD-L2 upregulation. These results suggest that PD-L2 mediates tobacco-induced recruitment of Tregs via the RGMB/NFκB/CCL20 cascade, and targeting this pathway might have therapeutic potentials in NSCLC.

Secondhand tobacco exposure assessed using urinary cotinine among 10-year-old children in Japan: An 11-year repeated cross-sectional study.

INTRODUCTION: The emergence of heated tobacco products (HTPs) has made it important to monitor HTP-generated aerosols in addition to combustible cigarette (CC) smoke as a source of secondhand tobacco (SHT) exposure. We investigated the trend of SHT exposure in school-aged children and assessed whether SHT exposure depended on household tobacco use status. METHODS: This repeated cross-sectional study from 2011 to 2021 (15,927 participants) was based on data from an annual survey of fourth-grade students (aged 10 years) in Kumagaya City, Japan. In addition to a questionnaire which includes questions about household tobacco use status, we measured urinary cotinine levels of each participant by their first morning urine sample to objectively assess SHT exposure. We defined the participants with urinary cotinine levels ≥5.0 ng/ml as being exposed to SHT. RESULTS: The prevalence of SHT exposure decreased over the 11-year period from 18.6% in 2011 to 5.3% in 2021. It was significantly higher in households with tobacco users than without tobacco users (t-test P<0.001). Prevalence of SHT exposure was 1.4% among the 68.1% of households not using tobacco, 22.9% among the 16.5% using only CC, 3.1% among the 12.3% using only HTP and 27.6% among the 3.9% of households using CC and HTP. CONCLUSIONS: While the prevalence of SHT exposure showed a decreasing trend from 2011 to 2021, the prevalence of SHT exposure was higher in children with household members using tobacco products, regardless of the type of tobacco product, than in those without tobacco users. IMPLICATIONS: This study observed that the prevalence of SHT exposure was higher among children in households with tobacco users than among those without tobacco users, regardless of the type of tobacco product. Our findings highlight the importance of advocating that HTPs do not reduce the likelihood of SHT exposure to bystanders.

Fractional exhaled nitric oxide (FeNO) among school children in Java and Sumatra, Indonesia: associations with respiratory symptoms, house dust mite sensitization and the home environment.

OBJECTIVE: To study associations between fractional exhaled nitric oxide (FeNO) and asthma, airway symptoms, sensitization to common allergens, outdoor pollution and home environment among 380 students in eight junior high schools in two areas in Indonesia. METHODS: Data on health and home were collected by a face-to face interview before measuring FeNO and performing skin prick test against common allergens. Exploratory linear mixed and logistic regression models were employed. RESULTS: Geometric mean of FeNO was 17.8 ppb (GSD 2.09) and 139 students (36.6%) had elevated FeNO (>20 ppb). In total, 107 students (28.2%) were sensitized to house dust mite (HDM) (Der p1 or Der f1), 4 (1.1%) to cat and 3 (0.8%) to mold (Cladosporium or Alternaria). Moreover, 20 students (5.3%) had diagnosed asthma, 38 (10.0%) had current wheeze, and 107 (28.2%) had current rhinitis. HDM sensitization, diagnosed asthma, current wheeze, and current rhinitis were associated with FeNO. In total, 281 students (73.9%) had mold or dampness, 232 (61.1%) had environmental tobacco smoke (ETS) and 43 (11.3%) had other odor at home. Indoor mold or dampness and other odor at home were associated with FeNO. ETS was negatively associated with FeNO. CONCLUSION: HDM sensitization and elevated FeNO can be common among children in this part of Indonesia. The high prevalence of elevated FeNO indicate that undiagnosed childhood asthma is common. Dampness, mold and odor at home can be associated with increased FeNO while ETS can be associated with decreased FeNO.

Early life exposure to secondhand tobacco smoke and eating behaviors at age 12 years.

BACKGROUND: Prenatal or early childhood secondhand tobacco smoke (SHS) exposure increases obesity risk. However, the potential mechanisms underlying this association are unclear, but obesogenic eating behaviors are one pathway that components of SHS could perturb. Our aim was to assess associations of prenatal and early childhood SHS exposure with adolescent eating behaviors. METHODS: Data came from a prospective pregnancy and birth cohort (N = 207, Cincinnati, OH). With multiple informant models, we estimated associations of prenatal (mean of 16 and 26 weeks of gestation maternal serum cotinine concentrations) and early childhood cotinine (average concentration across ages 12, 24, 36, and 48 months) with eating behaviors at age 12 years (Child Eating Behaviors Questionnaire). We tested whether associations differed by exposure periods and adolescent's sex. Models adjusted for maternal and child covariates. RESULTS: We found no statistically significant associations between cotinine measures and adolescent's eating behaviors. Yet, in females, prenatal cotinine was associated with greater food responsiveness (ß: 0.23; 95% CI: 0.08, 0.38) and lower satiety responsiveness (ß: -0.14; 95% CI: -0.26, -0.02); in males, prenatal and postnatal cotinine was related to lower food responsiveness (prenatal: ß: -0.25; 95% CI: -0.04, -0.06; postnatal: ß: -0.36; 95% CI: -0.06, -0.11). No significant effect modification by sex or exposure window was found for other eating behaviors. CONCLUSION: Prenatal and early childhood SHS exposures were not related to adolescent's eating behavior in this cohort; however, biological sex may modify these associations.

Role of active and environmental tobacco smoke on susceptibility to osteoporosis in women undergoing dual-X-ray absorptiometry.

PURPOSE: Current smoking is a risk factor for osteoporosis (Op), but few data are available regarding the passive smoke impact on Op susceptibility. This cross-sectional study aimed to evaluate the association between the smoking habits and Op in community-dwelling women undergoing dual-energy X-ray absorptiometry (DXA). METHODS: On 01/06/2018, general practitioners from "COMEGEN" Medical Cooperative, Naples, Italy, selected the medical records from the last 10 years of women who had a measurement of bone mineral density performed and simultaneously completed a questionnaire about their smoking behaviour and their cohabiters'. The binary logistic regression analysis was used to estimate the role of passive smoke on the risk of Op, adjusting for age and body mass index (BMI). RESULTS: Among 10,616 subjects, 3942 were currently smokers [CS; mean age 69.4 ± 10.4 years; BMI 27.0 ± 4.9 kg/m2], 873 were passive smokers (PS; mean age 67.8 ± 11.6 years; BMI 27.0 ± 4.9 kg/m2) and 5781 were never smokers (NS; mean age 67.8 ± 11.6 years; body mass index (BMI) 27.0 ± 4.9 kg/m2). Of all, 8562 women (mean age 70.3 ± 10.2 yrs; BMI 27.0 ± 4.9 kg/m2) received the Op diagnosis. PS showed an increased Op risk compared to NS [odds ratio (OR) 1.38 (1.14-1.67)] and comparable to CS [OR 1.02 (0.84-1.24)]. CONCLUSION: The study results demonstrate an association between passive smoke and Op in community-dwelling women already presenting with susceptibility to Op according to Italian essential assistance levels, suggesting that passive and active smoke are equivalent Op risk factors in women.

Sex differences in the tumor promoting effects of tobacco smoke in a cRaf transgenic lung cancer disease model.

Tobacco smoke (TS) is the leading cause for lung cancer (LC), and female smokers are at a greater risk for LC. Yet, the underlying causes are unknown. We performed whole genome scans in TS exposed wild type and histologically characterized tumor lesions of cRaf transgenic mice. We constructed miRNA-gene and transcription factor-miRNA/gene regulatory networks and determined sex-specific gene regulations by evaluating hormone receptor activities. We validated the findings from TS exposed cRaf mice in a large cohort of smoking and never-smoking LC patients. When compared to males, TS prompted a sevenfold increase in tumor multiplicity in cRaf females. Genome-wide scans of tumor lesions identified 161 and 53 genes and miRNAs, which code for EGFR/MAPK signaling, cell proliferation, oncomirs and oncogenes, and 50% of DEGs code for immune response and tumor evasion. Outstandingly, in transgenic males, TS elicited upregulation of 20 tumor suppressors, some of which are the targets of the androgen and estrogen receptor. Conversely, in females, 18 tumor suppressors were downregulated, and five were specifically repressed by the estrogen receptor. We found TS to perturb the circadian clock in a sex-specific manner and identified a female-specific regulatory loop that consisted of the estrogen receptor, miR-22-3p and circadian genes to support LC growth. Finally, we confirmed sex-dependent tumor promoting effects of TS in a large cohort of LC patients. Our study highlights the sex-dependent genomic responses to TS and the interplay of circadian clock genes and hormone receptors in the regulation of oncogenes and oncomirs in LC growth.

Association between serum cotinine levels and urinary incontinence in adults in the United States: a population-based cross-sectional analysis.

Environmental tobacco smoke (ETS) exposure has been shown to be associated with a variety of diseases, but evidence regarding the association between it and urinary incontinence (UI) is limited. Cotinine, a metabolite of nicotine in the human body, can more accurately quantify the level of human exposure to tobacco smoke. The study utilized data from seven survey cycles (2007-March 2020 Pre-pandemic) of the National Health and Nutrition Examination Survey (NHANES) program. Weighted multivariable logistic regression analysis, subgroup analysis, interaction tests, smooth curve fitting, and threshold effect models were used to analyze the relationship between serum cotinine and UI. Additionally, a 1:1 nearest neighbor propensity score matching (PSM) method was employed to minimize the impact of confounding factors. Before and after PSM, serum cotinine levels were higher in individuals with UI than those without (P < 0.05). Both before and after PSM, UI was positively correlated with serum cotinine levels, with a significantly increased risk of urinary incontinence when serum cotinine levels were in the Q3 range (before PSM: OR = 1.89, 95% CI = 1.59-2.24; after PSM: OR = 1.60, 95% CI = 1.28-2.00). Smooth curve fitting before and after PSM showed an approximate J-shaped non-linear dose-response relationship between log-transformed serum cotinine levels and UI. This study indicates that among American adults, there is a positive relationship between serum cotinine levels and UI, which is also significant in self-reported non-smoking populations. Therefore, reducing exposure to environmental tobacco smoke (e.g., avoiding second-hand smoke) in work and daily life may help alleviate the occurrence of UI, and serum cotinine levels have the potential to be a tool for predicting the degree of risk of developing UI.

Effect of twice daily inhaled albuterol on cardiopulmonary exercise outcomes, dynamic hyperinflation, and symptoms in secondhand tobacco-exposed persons with preserved spirometry and air trapping: a randomized controlled trial.

BACKGROUND: In tobacco-exposed persons with preserved spirometry (active smoking or secondhand smoke [SHS] exposure), air trapping can identify a subset with worse symptoms and exercise capacity. The physiologic nature of air trapping in the absence of spirometric airflow obstruction remains unclear. The aim of this study was to examine the underlying pathophysiology of air trapping in the context of preserved spirometry and to determine the utility of bronchodilators in SHS tobacco-exposed persons with preserved spirometry and air trapping. METHODS: We performed a double-blinded placebo-controlled crossover randomized clinical trial in nonsmoking individuals at risk for COPD due to exposure to occupational SHS who had preserved spirometry and air trapping defined as either a residual volume-to-total lung capacity ratio (RV/TLC) > 0.35 or presence of expiratory flow limitation (EFL, overlap of tidal breathing on maximum expiratory flow-volume loop) on spirometry at rest or during cardiopulmonary exercise testing (CPET). Those with asthma or obesity were excluded. Participants underwent CPET at baseline and after 4-week trials of twice daily inhalation of 180 mcg of albuterol or placebo separated by a 2-week washout period. The primary outcome was peak oxygen consumption (VO2) on CPET. Data was analyzed by both intention-to-treat and per-protocol based on adherence to treatment prescribed. RESULTS: Overall, 42 participants completed the entire study (66 ± 8 years old, 91% female; forced expiratory volume in 1 s [FEV1] = 103 ± 16% predicted; FEV1 to forced vital capacity [FVC] ratio = 0.75 ± 0.05; RV/TLC = 0.39 ± 0.07; 85.7% with EFL). Adherence was high with 87% and 93% of prescribed doses taken in the treatment and placebo arms of the study, respectively (P = 0.349 for comparison between the two arms). There was no significant improvement in the primary or secondary outcomes by intention-to-treat or per-protocol analysis. In per-protocol subgroup analysis of those with RV/TLC > 0.35 and ≥ 90% adherence (n = 27), albuterol caused an improvement in peak VO2 (parameter estimate [95% confidence interval] = 0.108 [0.014, 0.202]; P = 0.037), tidal volume, minute ventilation, dynamic hyperinflation, and oxygen-pulse (all P < 0.05), but no change in symptoms or physical activity. CONCLUSIONS: Albuterol may improve exercise capacity in the subgroup of SHS tobacco-exposed persons with preserved spirometry and substantial air trapping. These findings suggest that air trapping in pre-COPD may be related to small airway disease that is not considered significant by spirometric indices of airflow obstruction.

Effect of dietary antioxidant quality score on tobacco smoke exposure and asthma in children and adolescents: a cross-sectional study from the NHANES database.

BACKGROUND: Asthma is a common non-communicable disease in children, and airway inflammation is the main pathological change of asthma. Tobacco smoke exposure (TSE) can cause systematic inflammation and oxidative stress, which may further aggravate the progression of asthma. Dietary antioxidants can relieve the inflammation and oxidative stress in human body. This study aims to assess the effect of overall antioxidant capacity of dietary intake, evaluating by dietary antioxidant quality score (DAQS), in the association between TSE and childhood asthma. METHODS: Data of this cross-sectional study were extracted from the National Health and Nutrition Examination Surveys (NHANES) 2007-2018. DAQS was calculated based on the daily dietary intake of selenium, zinc, magnesium, vitamin A, C and E. TSE was measured by serum cotinine concentration. The weighted univariate and multivariate logistic regression models were employed to evaluate the role of DAQS in the association between TSE and asthma among children and adolescents. Subgroup analysis was conducted to further evaluate the association based on gender. RESULTS: Totally 11,026 children and adolescents were included, of whom 1,244 (11.28%) had asthma. After adjusted all covariates, TSE was associated with the high odds of childhood asthma (OR = 1.26, 95%CI = 1.05-1.52). Among children exposed to tobacco smoke, those with higher DAQS level (OR = 1.15, 95%CI: 0.88-1.50) had a reduced risk of asthma compared with those children with lower DAQS level (OR = 1.43, 1.08-1.89), especially among girls (OR = 1.42, 95%CI: 0.93-2.17). CONCLUSION: High DAQS may have a moderating effect on asthma in children; that is, the higher DAQS, the lower the odds of asthma in children who exposed to tobacco smoke. Our study provides a reference for developing more targeted strategies for prevention and treatment of asthma in children.

Tobacco advertising and oral health among never smokers: the mediating role of secondhand smoke exposure.

OBJECTIVE: To determine whether the association between tobacco advertising (TA) exposure and poor self-rated oral health (SROH) is mediated through secondhand smoke (SHS) exposure in Brazilian adults who have never smoked. METHODS: Secondary cross-sectional analysis of The Brazilian National Health Survey 2019 data. The daily, weekly, or monthly exposure to SHS at home or at work was set as the mediator. Mediation analysis within a counterfactual approach used adjusted binary logistic regressions for both poor SROH and SHS exposure, to estimate the natural direct effect (NDE), natural indirect effect (NIE) through SHS exposure, and marginal total effect (MTE) of TA exposure on poor SROH. To assess the robustness of the results, we calculated the E-value for the MTE. RESULTS: The sample comprised 53,295 never smoker adults. The MTE of TA exposure on poor SROH was 1.09 (1.03, 1.16), with the indirect effect through SHS exposure responsible for only 16.6% of the total (NIE: 1.01 [1.01, 1.02] and NDE: 1.08 [1.02, 1.14]). An effect of 1.42 would be required for an unmeasured confounder to explain away the association between TA and SROH. CONCLUSION: More individuals exposed to TA have poor SROH than those unexposed, with secondhand smoke exposure explaining only a small portion of this effect. Upstream tobacco policies should consider oral health outcomes.

Maternal vitamin D status modifies the effects of early life tobacco exposure on child lung function.

BACKGROUND: Prior studies suggest that vitamin D may modify the effects of environmental exposures; however, none have investigated gestational vitamin D and cumulative tobacco smoke exposure (TSE) throughout pregnancy and early life. OBJECTIVES: This study investigated the effects of early life TSE on child lung function and the modulatory effects of gestational vitamin D on this association. METHODS: The VDAART (Vitamin D Antenatal Asthma Reduction Trial) recruited nonsmoking pregnant women and followed the mother-child pairs to age 6 years. TSE was assessed with questionnaires and plasma cotinine measurements in the mothers (10-18 and 32-38 gestational weeks) and children (1, 3, and 6 years). Cumulative TSE was calculated from the repeated cotinine measurements. 25-hydroxyvitamin D (25[OH]D) levels were measured at 10-18 and 32-38 gestational weeks. Lung function was assessed at 6 years with spirometry and impulse oscillometry. RESULTS: Of the 476 mother-child pairs, 205 (43%) had increased cotinine levels at ≥1 time point. Cumulative TSE was associated with decreased FEV1 (ß = -0.043 L, P = .018) and increased respiratory resistance at 5 Hz (R5; ß = 0.060 kPa/L/s, P = .002). This association persisted in subjects with insufficient (<30 ng/mL) 25(OH)D levels throughout pregnancy (ß = 0.077 kPa/L/s, P = .016 for R5) but not among those with sufficient levels throughout pregnancy. CONCLUSIONS: Cumulative TSE from pregnancy to childhood is associated with dose- and duration-dependent decreases in child lung function at 6 years even in the absence of reported maternal smoking. Gestational vitamin D may modulate this effect and have therapeutic potential for minimizing the adverse effect of TSE on lung throughout early life. RANDOMIZED TRIAL: Maternal Vitamin D Supplementation to Prevent Childhood Asthma (VDAART); clinicaltrials.gov identifier: NCT00920621.