Characterization of the lung microbiome and inflammatory cytokine levels in women exposed to environmental risk factors: A pilot study.

INTRODUCTION: Lung microbiome dysbiosis affects the immune system balance and promotes lung inflammation. We aimed to characterize and compare the lung bacteriome composition and the cytokine profile in women with normal lung function exposed to risk factors for chronic lung diseases (tobacco smoking and biomass-burning smoke exposure). METHODS: We included women with biomass-burning smoke exposure (BE, n = 11) and current smokers women (TS, n = 10). The bacteriome composition was performed in induced sputum, sequencing the 16 rRNA gene. Cytokine levels were measured using enzyme-linked immunosorbent assay multiplex assay in the supernatant of induced sputum. For quantitative variables, we used medians and minimum and maxim values. For the amplicon sequence variants (ASV) differential abundance testing between groups. RESULTS: At the taxa level, the phylum Proteobacteria was found in a higher proportion in the TS group concerning BE (p = .045); however, after the false discovery rate adjustment, this difference was not retained (p = .288). We found a higher concentration of IL-1ß in the TS group than in the BE group (248.6 vs. 177.9 pg/mL, p = .010). Women with high biomass-burning smoke exposure in an hour per day had a positive correlation with the abundance of Bacteroidota (ρ = 0.71, p = .014) and Fusobacteriota (ρ = 0.73, p = .011). FEV1/FVC had a positive correlation with an abundance of Bacteroidota, Proteobacteria, and Fusobacteria (ρ = 0.74, p = .009, ρ = 0.85, p = .001, and ρ = 0.83, p = .001, respectively). In tobacco smoking, women had a positive correlation (ρ = 0.77, p = .009) between cigarettes per day and Firmicutes' abundance. CONCLUSION: Compared to biomass-burning smoke-exposed women, current smokers have poor lung function and high levels of IL-1ß in sputum. Women with biomass-burning smoke exposure present an increased abundance of Bacteroidota and Fusobacteriota.

Prevalence, attitude, knowledge, and risk perception towards COVID-19 in COPD patients associated to biomass exposure.

Chronic obstructive pulmonary disease (COPD) patients due to biomass exposure (BE-COPD) could be more affected than COPD due to tobacco smoke (TE-COPD) by the coronavirus disease 2019 (COVID-19) pandemic. The aim of this work was to determine the prevalence of COVID-19 in BE-COPD and TE-COPD and if housing conditions, poor attitude, knowledge, and risk perception towards COVID-19, particularly in BE-COPD women, could represent a risk factor for contagion.An 11% prevalence of COVID-19 was found with no significant difference between COPD groups. The BE-COPD group showed poorer socioeconomic status. No significant differences were found to be associated with SARS-CoV-2 infection regarding housing conditions, poor knowledge, attitude, and risk perception towards COVID-19. Living in urban areas and perceiving risk in COVID-19 were significantly associated with increased adherence to sanitary measures and concern of contagion. Around 40% of all patients showed poor risk perception and adherence to sanitary measures towards COVID-19.

Air quality in Mexico City during the COVID-19 lockdown possibly decreased COPD exacerbations.

The reduction of air pollution during the #COVID19 lockdown in Mexico City possibly reduced the exacerbation rate in #COPD patients due to biomass and tobacco despite that the self-isolation was not as strict as expected. https://bit.ly/3Iyv98t.

Clinical and microbiological characteristics and inflammatory profile during an exacerbation of COPD due to biomass exposure. A comparison with COPD due to tobacco exposure.

BACKGROUND: Patients with biomass exposure-related COPD (BE-COPD) is a prevalent disease in developing countries and requires a detailed study of its clinical and inflammatory characteristics, specifying interventions that may differ from tobacco exposure-related COPD (TE-COPD). The objective was to describe clinical characteristics, biomarkers of inflammation, T-helper cells, and microbiological agents during a COPD exacerbation in BE-COPD in comparison with TE-COPD. METHODS: A prospective observational study in patients with moderate or severe exacerbation was recruited either in the emergency room or the COPD clinic. At enrollment, nasopharyngeal swabs and sputum were collected to identify viral and bacterial pathogens. Blood samples were also collected to measure inflammatory biomarkers and T-helper cells levels. Days of hospitalization and mechanical ventilation requirement was evaluated. RESULTS: Clinical characteristics, vaccination history, hospitalization, history of exacerbations, and microbiological pattern between BE-COPD and TE-COPD were similar. The Th2 profile was higher in BE-COPD than in TE-COPD (2.10 [range 1.30-3.30] vs. 1.40 [range 1.20-1.80], p = 0.001). The Th2/Th1 ratio was higher in BE-COPD than TE-COPD (1.22 [range 0.58-2.57 ] vs. 0.71 [range 0.40-1.15], p = 0.004). The need of mechanical ventilation (MV) was higher in TE-COPD than BE-COPD (13% vs. 31.1%, p = 0.01). Nonvaccination history and high CRP levels were significantly associated with hospitalization [OR 1.48 (CI 95% 1.30-4.61, p = 0.005) and OR 1.17 (CI 95% 1.10-1.24, p = 0.001), respectively]. CONCLUSIONS: Clinical characteristics, inflammatory markers, and microbiological isolates were similar in both groups but BE-COPD show a tendency to present higher inflammatory Th2 cells and low requirement MV compared with TE-COPD.

Protective Role of Genetic Variants in HSP90 Genes-Complex in COPD Secondary to Biomass-Burning Smoke Exposure and Non-Severe COPD Forms in Tobacco Smoking Subjects.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is an inflammatory disease characterized by airflow obstruction, commonly present in smokers and subjects exposed to noxious particles product of biomass-burning smoke (BBS). Several association studies have identified single-nucleotide polymorphisms (SNP) in coding genes related to the heat shock proteins family-genes that codify the heat shock proteins (Hsp). Hsp accomplishes critical roles in regulating immune response, antigen-processing, eliminating protein aggregates and co-activating receptors. The presence of SNPs in these genes can lead to alterations in immune responses. We aimed to evaluate the association of SNPs in the HSP90 gene complex and COPD. METHODS: We enrolled 1549 participants, divided into two comparison groups; 919 tobacco-smoking subjects (cases COPD-TS n = 294 and, controls SWOC n = 625) and 630 chronic exposed to BBS (cases COPD-BBS n = 186 and controls BBES n = 444). We genotyped 2 SNPs: the rs13296 in HSP90AB1 and rs2070908 in HSP90B1. RESULTS: Through the dominant model (GC + CC), the rs2070908 is associated with decreased risk (p < 0.01, OR = 0.6) to suffer COPD among chronic exposed BBS subjects. We found an association between rs13296 GG genotype and lower risk (p = 0.01, OR = 0.22) to suffer severe COPD-TS forms in the severity analysis. CONCLUSIONS: single-nucleotide variants in the HSP90AB1 and HSP90B1 genes are associated with decreased COPD risk in subjects exposed to BBS and the most severe forms of COPD in tobacco-smoking subjects.

Hypomethylation of AHRR (cg05575921) Is Related to Smoking Status in the Mexican Mestizo Population.

Tobacco smoking results in a multifactorial disease involving environmental and genetic factors; epigenome-wide association studies (EWAS) show changes in DNA methylation levels due to cigarette consumption, partially reversible upon tobacco smoking cessation. Therefore, methylation levels could predict smoking status. This study aimed to evaluate the DNA methylation level of cg05575921 (AHRR) and cg23771366 (PRSS23) and their correlation with lung function variables, cigarette consumption, and nicotine addiction in the Mexican smoking population. We included 114 non-smokers (NS) and 102 current tobacco smokers (TS); we then further subclassified them as heavy smokers (HS) (n = 53) and light smokers (LS) (n = 49). We used restriction enzymes (MspI/HpaII) and qPCR to determine the DNA methylation level. We observed significant hypomethylation of cg05575921 in smokers compared to NS (p = 0.003); further analysis found a difference between HS and NS (p = 0.02). We did not observe differences between other groups or a positive correlation between methylation levels and age, BMI, cigarette consumption, nicotine addiction, or lung function. In conclusion, the cg05575921 site of AHRR is significantly hypomethylated in Mexican smokers, especially in HS (≥20 cigarettes per day).

The "Slow Horse Racing Effect" on Lung Function in Adult Life in Chronic Obstructive Pulmonary Disease Associated to Biomass Exposure.

Although different trajectories in lung function decline have been identified in patients with COPD associated to tobacco exposure (TE-COPD), genetic, environmental, and infectious factors affecting lung function throughout life have not been fully elucidated in patients with COPD associated to biomass (BE-COPD). In this review, we present current epidemiological findings and notable advances in the natural history of lung decline in BE-COPD, as well as conditions modeling the FEV1 trajectory, such as health insults, during the first years of childhood. Evidence shows that women exposed to biomass smoke reach adult life with a lower FEV1 than expected. However, in contrast to the "horse racing effect" predicting an excessive lung-function decline in forthcoming years, as observed in smokers, this decline is slower in non-smokers, and no rapid decliners are observed. Accordingly, BE-COPD might be considered another phenotype of COPD based on assessments of lung function decline. Likewise, other functional and clinical aspects described in this review suggest that this condition might be similar to TE-COPD. More research is needed to fully characterize this subgroup of variants of COPD.

Lung Damage Caused by Heated Tobacco Products and Electronic Nicotine Delivery Systems: A Systematic Review.

The tobacco industry promotes electronic nicotine delivery systems (ENDS) and heated tobacco products (HTP) as a safer alternative to conventional cigarettes with misleading marketing sustained by studies with conflict of interest. As a result, these devices sell without regulations and warnings about their adverse effects on health, with a growing user base targeting young people. This systematic review aimed to describe the adverse effects on the respiratory system in consumers of these devices. We conducted a systematic review and bibliometric analysis of 79 studies without conflict of interest evaluating ENDS and HTP effects in the respiratory system in experimental models, retrieved from the PubMed database. We found that the damage produced by using these devices is involved in pathways related to pulmonary diseases, involving mechanisms previously reported in conventional cigarettes as well as new mechanisms particular to these devices, which challenges that the tobacco industry's claims. The present study provides significant evidence to suggest that these devices are an emerging public health problem and that they should be regulated or avoided.

Bronchodilators for hyperinflation in COPD associated with biomass smoke: clinical trial.

Introduction: The efficacy of long-acting bronchodilators for COPD associated with biomass (BE-COPD) has not been properly evaluated. Objective: To determine the acute effect of indacaterol (IND) 150 µg q.d and tiotropium (TIO) 18 µg q.d. on lung hyperinflation, walking distance (WD) and dyspnea during the six-minute walking test (6MWT) in moderate BE-COPD at 30, 60 and 240 mins post-drug administration. Design: Randomized, controlled, open-level, crossover noninferiority clinical trial. Forty-two women with BE-COPD were randomly assigned to a bronchodilator sequence: IND-TIO or vice versa. Results: There were statistically significant changes over time in inspiratory capacity (IC) (p<0.0001), FEV1 (p<0.0001) and FVC (p<0.0001) when IND was used. When TIO was administered, an increase over all time periods was observed only for FEV1 (p<0.0001) and FVC (p<0.0001), whereas for IC an increase was observed only at 30 mins and 24 hrs after TIO administration. We did not find clinically significant increases in WD and dyspnea after the administration of both bronchodilators. Conclusion: Both IND and TIO showed significant and fast onset improvement in hyperinflation. Therefore, either of them may be recommended as a first line of treatment for COPD associated with BE-COPD.

Data on genotype frequency for SNPs associated to age of smoking onset and successful smoking cessation treatment.

This article contains data on the allele and genotype frequency for single nucleotide polymorphisms (SNPs) in candidate genes CHRNA5 (rs16969968, rs17408276, rs680244) CHRNA3 (rs6495307, rs12914385) NRXN1 (rs10865246, rs1882296, rs985919) and HTR2A (rs6311, rs6313) previously evaluated as genetic risk variants for cigarette smoking at an early age and relapse to smoking cessation treatment Pérez-Rubio et al., 2018. These SNPs were selected due to previous associations in other populations, including Mexican Mestizos. Smokers were classified according to the age at onset, cigarettes per day, nicotine dependence, COPD status and therapy received.

Genetic variants as risk factors for cigarette smoking at an early age and relapse to smoking cessation treatment: A pilot study.

OBJECTIVES: Tobacco smoking is a complex and multifactorial disease involving both environmental and genetic factors. In the Mexican mestizo population, single-nucleotide polymorphisms (SNPs) associated with cigarette smoking and a greater degree of nicotine addiction have been identified; however, no possible roles have been explored in regard to the age of onset of smoking or in the success of quitting. METHODS: In this study, 151 Mexican mestizo, who smoke cigarettes, were included. They were grouped according to the age at which they started smoking: those who started smoking before 18 years of age (early smokers, ES) and those who started smoking ≥18 years of age (late smokers, LS). In addition, relapse in smoking was evaluated at the first month after the end of treatment. Genetic association was evaluated characterizing 10 SNPs in 4 genes (CHRNA5, CHRNA3, NRXN1, and HTR2A). RESULTS: According to the dominant model of genetic inheritance, rs6313 (CT+TT) of the HTR2A gene was associated (p = 0.0201) with cigarette consumption at early ages (OR = 2.68, CI = 1.18-6.07). When the risk of relapse was analyzed one month after the end of treatment, regardless of the age of onset, the T allele (rs6313) of HTR2A appeared to be a risk factor for relapse (OR = 2.92, 95% CI = 1.06-8.11); the T allele was found more frequently in those who relapsed (50.0%) compared with people who maintained abstinence (25.4%) (p = 0.0332). CONCLUSIONS: Our findings suggest that in Mexican mestizos who smoke cigarettes, the presence of the T allele in rs6313 of the HTR2A gene increases the risk for the early onset of cigarette smoking as well as the risk for relapsing one month after completing smoking cessation treatment.

SMALLa AIRWAY DISEASE IN COPD ASSOCIATED TO BIOMASS EXPOSURE.

Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous entity that may result from different causative agents and risk factors and may follow diverse clinical courses, including COPD secondary to biomass smoke exposure. At present, this phenotype is becoming more important for two reasons: first, because at least almost half of the world's population is exposed to biomass smoke, and second, because the possibility of it being diagnosed is increasing. Biomass smoke exposure COPD affects primarily women and is related with insults to the airways occurred during early life. Although constituents of biomass smoke and tobacco smoke are similar, the physiopathological changes they induce differ depending not only on the chemical composition (related with the type of fuel used) but also on the particle size and the inhalation pattern. Evidence has shown that biomass smoke exposure affects the airway, predominantly the small airways causing anthracofibrosis and peribronchiolar fibrosis changes that will clinically translate into chronic bronchitis symptoms, with a high impact on the quality of life. In this review, we focus especially on the main epidemiological and clinical differences between COPD secondary to biomass exposure and COPD caused by tobacco exposure.

Small airway disease in COPD associated to biomass exposure

Abstract Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous entity that may result from different causative agents and risk factors and may follow diverse clinical courses, including COPD secondary to biomass smoke exposure. At present, this phenotype is becoming more important for two reasons: first, because at least almost half of the world’s population is exposed to biomass smoke, and second, because the possibility of it being diagnosed is increasing. Biomass smoke exposure COPD affects primarily women and is related with insults to the airways occurred during early life. Although constituents of biomass smoke and tobacco smoke are similar, the physiopathological changes they induce differ depending not only on the chemical composition (related with the type of fuel used) but also on the particle size and the inhalation pattern. Evidence has shown that biomass smoke exposure affects the airway, predominantly the small airways causing anthracofibrosis and peribronchiolar fibrosis changes that will clinically translate into chronic bronchitis symptoms, with a high impact on the quality of life. In this review, we focus especially on the main epidemiological and clinical differences between COPD secondary to biomass exposure and COPD caused by tobacco exposure.

Prevalence of COPD and respiratory symptoms associated with biomass smoke exposure in a suburban area.

Introduction: Biomass smoke exposure (BSE) is a recognized cause of COPD particularly in rural areas. However, little research has been focused on BSE in suburban areas. Objective: The aim of this study was to determine the prevalence of COPD, respiratory symptoms (RS) and BSE in women living in a suburban area of Mexico City exposed to BSE. Methods: A cross-sectional epidemiological survey of a female population aged >35 years was performed using a multistage cluster sampling strategy. The participants completed questionnaires on RS and COPD risk factors. The COPD prevalence was based on the postbronchodilator forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC) ratio. Of the 1,333 women who completed the respiratory questionnaires, spirometry data were obtained from 1,190, and 969 of these were scored as A-C. Results: The prevalence of BSE was 47%, and the estimated prevalence of COPD was 2.5% for the total population (n=969) and 3.1% for those with BSE only. The spirometry and oximetry values were significantly lower in women with greater exposure levels. The prevalence of RS (cough, phlegm, wheezing and dyspnea) was significantly higher in the women with BSE compared to those without exposure. We concluded that the association of COPD with biomass exposure is not only a rural phenomenon but also may be observed in the suburban areas of the big cities.

Data on polymorphisms in CYP2A6 associated to risk and predispose to smoking related variables.

This article contains data on the single nucleotide polymorphisms (SNPs) rs1137115, rs1801272 and rs28399433 rs4105144 in CYP2A6 associated to smoking related variables in Mexican Mestizo smokers (Pérez-Rubio et al., 2017) [1]. These SNPs were selected due to previous associations with other populations. Mexican Mestizo smokers were classified according their smoking pattern. A genetic association test was performed.

Polymorphisms in HTR2A and DRD4 Predispose to Smoking and Smoking Quantity.

BACKGROUND: Genes encoding the receptors involved in the dopaminergic and serotonergic pathways are potential candidates in the mechanisms of nicotine addiction. AIMS: To identify genetic variants in the promoter regions and exons of the DRD4 and HTR2A genes associated with tobacco smoking and the degree of nicotine addiction in Mexican mestizos. METHODS: The study included 438 non-smokers (NS) and 1,157 current smokers, ranked based on their consumption of cigarettes per day (cpd): 574 heavy smokers (HS, >20 cpd) and 583 light smokers (LS, 1-10 cpd). Genotyping was performed for 4 and 8 single nucleotide polymorphisms (SNPs) in the DRD4 and HTR2A genes, respectively. RESULTS: The C allele of rs1800955 in DRD4 was found to be associated with cigarette smoking in the HS vs. NS and LS vs. NS comparisons (p = 2.34E-03 and p = 1.13E-03, respectively); the association was maintained in the homozygous CC genotype (p = 5.00E-04 and p = 2.00E-04, respectively). The T allele of rs6313 in HTR2A was significantly associated with cigarette smoking and a greater degree of nicotine addiction (p = 4.77E-03, OR = 1.55); the association was maintained in the homozygous genotype (TT) (p = 4.90E-03, OR = 1.96). The A allele of rs6313 was associated with cigarette smoking in the HS vs. NS comparison (p = 1.53E-02, OR = 1.36); the risk was nearly doubled in the homozygous AA genotype (p = 1.30E-03, OR = 1.83) compared with the heterozygous GA genotype (OR = 1.38). CONCLUSIONS: Among Mexican mestizos, the C allele of rs1800955 in the DRD4 gene and the A allele of rs6311 in the HTR2A gene are associated with cigarette smoking, whereas the T allele of rs6313 in HTR2A is associated with cigarette smoking and the degree of nicotine addiction.

Use of varenicline for more than 12 months for smoking cessation in heavy chronic obstructive pulmonary disease smokers unmotivated to quit: a pilot study.

INTRODUCTION: Use of varenicline for as long as necessary to achieve abstinence has not been studied. The aim of this study was to test whether smokers with mild-to-moderate chronic obstructive pulmonary disease (COPD) are able to quit if they use varenicline for a sufficient length of time. METHODS: A total of 30 heavy smokers with COPD took varenicline for sufficiently long enough for smoking cessation. Smokers were allowed to smoke without a fixed quit date. The main endpoints were the time of voluntary abstinence (VA) and the continuous abstinence rate (CAR) at 12 and 18 months. RESULTS: Of 28 subjects, eight subjects continued to smoke and 20 subjects stopped smoking, demonstrating a CAR up to 18 months (71%). Median time of treatment was 6 (range 3-24) and 2 (range 1-8) months for abstainers and non-abstainers, respectively, and the median time of VA for abstainers was 4 (range 1-21) months. CONCLUSIONS: Use of varenicline for more than the traditional 12 recommended weeks may be a good strategy to increase the cessation rate in heavy smokers with mild COPD.

SNPs in NRXN1 and CHRNA5 are associated to smoking and regulation of GABAergic and glutamatergic pathways.

AIM: To identify genetic variants associated with greater tobacco consumption in a Mexican population. PATIENTS & METHODS: Daily smokers were classified as light smokers (LS; n = 742), heavy smokers (HS; n = 601) and nonsmokers (NS; n = 606). In the first stage, a genotyping microarray that included 347 SNPs in CHRNA2-CHRNA7/CHRNA10, CHRNB2-CHRNB4 and NRXN1 genes and 37 ancestry-informative markers was used to analyze 707 samples (187 HS, 328 LS and 192 NS). In the second stage, 14 SNPs from stage 1 were validated in the remaining samples (HS, LS and NS; n = 414 in each group) using real-time PCR. To predict the role of the associated SNPs, an in silico analysis was performed. RESULTS: Two SNPs in NRXN1 and two in CHRNA5 were associated with cigarette consumption, while rs10865246/C (NRXN1) was associated with high nicotine addiction. The in silico analysis revealed that rs1882296/T had a high level of homology with Hsa-miR-6740-5p, which encodes a putative miRNA that targets glutamate receptor subunits (GRIA2, GRID2) and GABA receptor subunits (GABRG1, GABRA4, GABRB2), while rs1882296/C had a high level of homology with Hsa-miR-6866-5p, which encodes a different miRNA that targets GRID2 and GABRB2. CONCLUSION: In a Mexican Mestizo population, greater consumption of cigarettes was influenced by polymorphisms in the NRXN1 and CHRNA5 genes. We proposed new hypotheses regarding the putative roles of miRNAs that influence the GABAergic and glutamatergic pathways in smoking addiction.

Genetic Variants in IL6R and ADAM19 are Associated with COPD Severity in a Mexican Mestizo Population.

Chronic obstructive pulmonary disease (COPD) is a complex and multifactorial disease with a strong genetic component. Our objective is to identify the genetic variants associated with COPD risk and its severity in Mexican Mestizo population. We evaluated 1285 single-nucleotide polymorphisms (SNPs) of candidate genes in 299 smokers with COPD (COPD-S) and 531 smokers without COPD (SWOC) using an Illumina GoldenGate genotyping microarray. In addition, 251 ancestry informative markers were included. Allele A of rs2545771 in CYP2F2P is associated with a lower risk of COPD (p = 4.02E-10, odds ratio [OR] = 0.104, confidence interval [CI] 95% 0.05-0.18). When the COPD group was stratified by severity according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD; levels III + IV vs. I + II), 3 SNPs (rs4329505 and rs4845626 in interleukin 6 receptor [IL6R] and rs1422794 in a disintegrin and metalloproteinase domain 19 [ADAM19]) were associated with a lower risk of suffering the most severe stages of the disease. rs2819096 in the surfactant protein D (SFTPD) gene was associated with a higher risk of COPD GOLD III + IV (p = 7.79E-03, OR = 1.80, CI 95% 1.16-2.79). Finally, the haplotype in IL6R was associated with a lower risk of suffering from more severe COPD, whereas the haplotype in ADAM19 was associated with a higher risk (p = 7.40E-03, OR = 2.83, CI 95% 1.20-6.86) of suffering from the severe stages of the disease. Our data suggest that there are alleles and haplotypes in the IL6R, ADAM19, and SFTPD genes associated with different severity stages of COPD; in CYP2F2P, rs25455771 is associated with a lower risk of COPD.