scholarly journals Identifying miRNA-mRNA Networks Associated With COPD Phenotypes

2021 ◽  
Vol 12 ◽  
Author(s):  
Yonghua Zhuang ◽  
Brian D Hobbs ◽  
Craig P Hersh ◽  
Katerina Kechris
Keyword(s):  
Lung Function ◽  
Mrna Expression ◽  
Statistical Power ◽  
Biomarker Discovery ◽  
Smoking Status ◽  
Airflow Limitation ◽  
Covariate Adjustment ◽  
Chronic Obstructive ◽  
Sequencing Data ◽  
Network Identification

Chronic obstructive pulmonary disease (COPD) is characterized by expiratory airflow limitation and symptoms such as shortness of breath. Although many studies have demonstrated dysregulated microRNA (miRNA) and gene (mRNA) expression in the pathogenesis of COPD, how miRNAs and mRNAs systematically interact and contribute to COPD development is still not clear. To gain a deeper understanding of the gene regulatory network underlying COPD pathogenesis, we used Sparse Multiple Canonical Correlation Network (SmCCNet) to integrate whole blood miRNA and RNA-sequencing data from 404 participants in the COPDGene study to identify novel miRNA–mRNA networks associated with COPD-related phenotypes including lung function and emphysema. We hypothesized that phenotype-directed interpretable miRNA–mRNA networks from SmCCNet would assist in the discovery of novel biomarkers that traditional single biomarker discovery methods (such as differential expression) might fail to discover. Additionally, we investigated whether adjusting -omics and clinical phenotypes data for covariates prior to integration would increase the statistical power for network identification. Our study demonstrated that partial covariate adjustment for age, sex, race, and CT scanner model (in the quantitative emphysema networks) improved network identification when compared with no covariate adjustment. However, further adjustment for current smoking status and relative white blood cell (WBC) proportions sometimes weakened the power for identifying lung function and emphysema networks, a phenomenon which may be due to the correlation of smoking status and WBC counts with the COPD-related phenotypes. With partial covariate adjustment, we found six miRNA–mRNA networks associated with COPD-related phenotypes. One network consists of 2 miRNAs and 28 mRNAs which had a 0.33 correlation (p = 5.40E-12) to forced expiratory volume in 1 s (FEV1) percent predicted. We also found a network of 5 miRNAs and 81 mRNAs that had a 0.45 correlation (p = 8.80E-22) to percent emphysema. The miRNA–mRNA networks associated with COPD traits provide a systems view of COPD pathogenesis and complements biomarker identification with individual miRNA or mRNA expression data.

scholarly journals Longitudinal decline in lung function: a community-based cohort study in Korea

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ah Young Leem ◽  
Boram Park ◽  
Young Sam Kim ◽  
Joon Chang ◽  
Sungho Won ◽  
...  
Keyword(s):  
Smoking Cessation ◽  
Lung Function ◽  
Mixed Model ◽  
Smoking Status ◽  
Airflow Limitation ◽  
Chronic Obstructive ◽  
Lung Function Decline ◽  
Rate Of Decline ◽  
Never Smokers ◽  
Over Time

Abstract Progressive decline in lung function is the hallmark of chronic obstructive pulmonary disease (COPD). We aimed to assess the rate of decline in forced expiratory volume in 1 second (FEV1) in patients from a community cohort database in Korea. 5,865 subjects aged 40–69 years from the Ansung-Ansan cohort database I–III (2001–2006) were included in this study. We assessed the annual rate of decline in FEV1 over time in relation to smoking status, patient sex, and presence or absence of pre-bronchodilator airflow limitation using a generalized additive mixed model. The mean follow-up duration was 3.8 years. The annual mean decline in FEV1 in the entire cohort was significantly more rapid for men than women (31.3 mL vs 27.0 mL, P = 0.003). Among men without pre-bronchodilator airflow limitation, annual mean declines in FEV1 were 31.5, 35.5, and 40.1 mL for never smokers, former smokers (P = 0.09 vs. never smokers), and current smokers (P < 0.001 vs. never smokers), respectively; and 23.4, 19.7, and 33.9 mL, respectively, for men with pre-bronchodilator airflow limitation. Thus, among Korean males, smoking accelerates lung function decline over time whereas smoking cessation slows the rate of FEV1 decline regardless of pre-bronchodilator airflow limitation. This underscores the importance of smoking cessation in Koreans.

scholarly journals Smoking Interaction with a Polygenic Risk Score for Reduced Lung Function

2021 ◽  
Author(s):  
Woori Kim ◽  
Matthew Moll ◽  
Dandi Qiao ◽  
Brian D. Hobbs ◽  
Nick Shrine ◽  
...  
Keyword(s):  
Lung Function ◽  
Genetic Risk ◽  
Smoking Status ◽  
Airflow Limitation ◽  
European Ancestry ◽  
Chronic Obstructive ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Product Term ◽  
Smoking Exposure

Importance: Risk to airflow limitation and Chronic Obstructive Pulmonary Disease (COPD) is influenced by combinations of cigarette smoking and genetic susceptibility, yet it remains unclear whether gene-by-smoking interactions contribute to quantitative measures of lung function. Objective: Determine whether smoking modifies the effect of a polygenic risk score's (PRS's) association with reduced lung function. Design: United Kingdom (UK) Biobank prospective cohort study. Setting: Population cohort. Participants: UK citizens of European ancestry aged 40-69 years, with genetic and spirometry data passing quality control metrics. Exposures: PRS, self-reported pack-years of smoking, ever- versus never-smoking status, and current- versus former-/never-smoking status. Main Outcomes and Measures: Forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC). We tested for interactions with models including the main effects of PRS, different smoking variables, and their cross-product term(s). We also compared the effects of pack-years of smoking on FEV1/FVC for those in the highest versus lowest decile of predicted genetic risk for low lung function. Results: We included 319,730 individuals (24,915 with moderate-to-severe COPD). The PRS and pack-years were significantly associated with lower FEV1/FVC, as was the interaction term (β [interaction] = -0.0028 [95% CI: -0.0029, -0.0026]; all p < 0.0001). A stepwise increment in estimated effect sizes for these interaction terms was observed per 10 pack-years of smoking exposure (all p < 0.0001). There was evidence of significant interaction between PRS with ever/never smoking status (β [interaction] = -0.0064 [95% CI: -0.0068, -0.0060]) and current/not-current smoking (β [interaction] = -0.0091 [95% CI: -0.0097, -0.0084]). For any given level of pack-years of smoking exposure, FEV1/FVC was significantly lower for individuals in the tenth compared to the first decile of genetic risk (p < 0.0001). For every 20 pack-years of smoking, those in the top compared to the bottom decile of genetic risk showed nearly a twofold reduction in FEV1/FVC. Conclusions and Relevance: COPD is characterized by diminished lung function, and our analyses suggest there is substantial interaction between genome-wide PRS and smoking exposures. While smoking has negative effects on lung function across all genetic risk categories, effects of smoking are highest in those with higher predicted genetic risk.

scholarly journals How different are COPD-specific patient reported outcomes, health status, dyspnoea and respiratory symptoms? An observational study in a working population

BMJ Open ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. e025132 ◽  
Author(s):  
Koichi Nishimura ◽  
Toru Oga ◽  
Kazuhito Nakayasu ◽  
Miyoko Ogasawara ◽  
Yoshinori Hasegawa ◽  
...  
Keyword(s):  
Health Status ◽  
Respiratory Symptoms ◽  
Smoking Status ◽  
Fixed Ratio ◽  
Airflow Limitation ◽  
Chronic Obstructive ◽  
Working Population ◽  
Specific Patient ◽  
Patient Reported ◽  
D 12

ObjectivesWe hypothesised that chronic obstructive pulmonary disease (COPD)-specific health status measured by the COPD assessment test (CAT), respiratory symptoms by the evaluating respiratory symptoms in COPD (E-RS) and dyspnoea by Dyspnoea-12 (D-12) are independently based on specific conceptual frameworks and are not interchangeable. We aimed to discover whether health status, dyspnoea or respiratory symptoms could be related to smoking status and airflow limitation in a working population.DesignThis is an observational, cross-sectional study.Participants1566 healthy industrial workers were analysed.ResultsRelationships between D-12, CAT and E-RS total were statistically significant but weak (Spearman’s correlation coefficient=0.274 to 0.446). In 646 healthy non-smoking subjects, as the reference scores for healthy non-smoking subjects, that is, upper threshold, the bootstrap 95th percentile values were 1.00 for D-12, 9.88 for CAT and 4.44 for E-RS. Of the 1566 workers, 85 (5.4%) were diagnosed with COPD using the fixed ratio of the forced expiratory volume in one second/forced vital capacity <0.7, and 34 (2.2%) using the lower limit of normal. The CAT and E-RS total were significantly worse in non-COPD smokers and subjects with COPD than non-COPD never smokers, although the D-12 was not as sensitive. There were no significant differences between non-COPD smokers and subjects with COPD on any of the measures.ConclusionsAssessment of health status and respiratory symptoms would be preferable to dyspnoea in view of smoking status and airflow limitation in a working population. However, these patient-reported measures were inadequate in differentiating between smokers and subjects with COPD identified by spirometry.

scholarly journals Associations between antioxidants and all-cause mortality among US adults with obstructive lung function

2014 ◽  
Vol 112 (10) ◽  
pp. 1662-1673 ◽  
Author(s):  
Earl S. Ford ◽  
Chaoyang Li ◽  
Timothy J. Cunningham ◽  
Janet B. Croft
Keyword(s):  
Lung Function ◽  
Vitamin C ◽  
Smoking Status ◽  
Chronic Obstructive ◽  
Continuous Variables ◽  
Total Carotenoids ◽  
Obstructive Pulmonary Disease ◽  
Health And Nutrition ◽  
All Cause Mortality ◽  
Β Carotene

Chronic obstructive pulmonary disease is characterised by oxidative stress, but little is known about the associations between antioxidant status and all-cause mortality in adults with this disease. The objective of the present study was to examine the prospective associations between concentrations of α- and β-carotene, β-cryptoxanthin, lutein/zeaxanthin, lycopene, Se, vitamin C and α-tocopherol and all-cause mortality among US adults with obstructive lung function. Data collected from 1492 adults aged 20–79 years with obstructive lung function in the National Health and Nutrition Examination Survey III (1988–94) were used. Through 2006, 629 deaths were identified during a median follow-up period of 14 years. After adjustment for demographic variables, the concentrations of the following antioxidants modelled as continuous variables were found to be inversely associated with all-cause mortality among adults with obstructive lung function: α-carotene (P= 0·037); β-carotene (P= 0·022); cryptoxanthin (P= 0·022); lutein/zeaxanthin (P= 0·004); total carotenoids (P= 0·001); vitamin C (P< 0·001). In maximally adjusted models, only the concentrations of lycopene (P= 0·013) and vitamin C (P= 0·046) were found to be significantly and inversely associated with all-cause mortality. No effect modification by sex was detected, but the association between lutein/zeaxanthin concentrations and all-cause mortality varied by smoking status (Pinteraction= 0·048). The concentrations of lycopene and vitamin C were inversely associated with all-cause mortality in this cohort of adults with obstructive lung function.

scholarly journals Impact of smoking status on the efficacy of inhaled corticosteroids in chronic obstructive pulmonary disease: a systematic review

BMJ Open ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. e037509
Author(s):  
Kimberley Sonnex ◽  
Hanna Alleemudder ◽  
Roger Knaggs
Keyword(s):  
Systematic Review ◽  
Chronic Obstructive Pulmonary Disease ◽  
Lung Function ◽  
Pulmonary Disease ◽  
Inhaled Corticosteroids ◽  
Smoking Status ◽  
Steroid Resistance ◽  
Cochrane Library ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease

ObjectivesInhaled corticosteroids (ICS) reduce exacerbation rates and the decline in lung function in people with chronic obstructive pulmonary disease (COPD). There is evidence that smoking causes ‘steroid resistance’ and thus reduces the effect of ICS. This systematic review aimed to investigate the effect of smoking on efficacy of ICS in COPD in terms of lung function and exacerbation rates.DesignSystematic review.Data sourcesAn electronic database search of PubMed, Ovid MEDLINE, Ovid Embase and Cochrane Library (January 2000 to January 2020).Eligibility criteriaFully published randomised controlled trials (RCTs), in the English language, evaluating the use of ICS in COPD adults that stratified the participants by smoking status. Trials that included participants with asthma, lung cancer and pneumonia were excluded. The primary outcome measures were changes in lung function and yearly exacerbation rates.Data extraction and synthesisTwo independent reviewers extracted data and assessed risk of bias using the Cochrane Collaboration’s tool.ResultsSeven studies were identified. Four trials (17 892 participants) recorded change in forced expiratory volume in one second (FEV1) from baseline to up to 30 months after starting treatment. Heavier smokers (>36 pack years) using ICS had a greater decline in FEV1that ranged from −22 mL to −75 mL in comparison to lighter smokers. Smokers using ICS had mixed results in FEV1change: −8 mL to +77 mL in comparison to ex-smokers. Four trials (21 270 participants) recorded difference in COPD exacerbation rates at 52 weeks. The rate ratios favoured more exacerbations in ICS users who were current or heavier smokers than those who were ex-smokers or lighter smokers (0.81 to 0.99 vs 0.92 to 1.29).ConclusionsIn COPD, heavier or current smokers do not gain the same benefit from ICS use on lung function and exacerbation rates as lighter or ex-smokers do, however effects may not be clinically important.PROSPERO registration numberCRD42019121833

scholarly journals A krónikus obstruktív tüdőbetegség metabolikus következményei

2021 ◽  
Vol 162 (5) ◽  
pp. 185-191
Author(s):  
Mónika Fekete ◽  
Vince Fazekas-Pongor ◽  
Gergő Szőllősi ◽  
János Tamás Varga
Keyword(s):  
Quality Of Life ◽  
Metabolic Syndrome ◽  
Lung Function ◽  
Smoking Status ◽  
International Diabetes Federation ◽  
Walking Distance ◽  
Chronic Obstructive ◽  
Copd Patients ◽  
Co Morbidity

Összefoglaló. Bevezetés: Krónikus obstruktív tüdőbetegségben (COPD) az obesitas mellett a csökkent fizikai aktivitás nagymértékben fokozza a metabolikus szindróma kialakulásának valószínűségét. Célkitűzés: Kutatásunk célja volt felmérni a metabolikus szindróma prevalenciáját COPD-ben, valamint azt, hogy milyen mértékben függ össze az életkorral, a nemmel, a társbetegségekkel, a tüdőfunkció károsodásának mértékével, a tápláltsági állapottal, a fizikai terhelhetőséggel és az életminőséggel. Módszer: Keresztmetszeti vizsgálatot végeztünk az Országos Korányi Pulmonológiai Intézet Légzésrehabilitációs Osztályán fekvő betegek körében 2019. július 1. és december 31. között. A véletlenszerűen kiválasztott 300, 40 év feletti betegnek ismertük az antropometriai, légzésfunkciós vizsgálati eredményét és laboratóriumi paramétereit. Adatokat gyűjtöttünk a dohányzási szokásokról, az előző évi exacerbatiók számáról és a kortikoszteroidok használatáról is. Az életminőség mérésére a betegségspecifikus Szent György-féle Légzési Kérdőív magyar nyelvre validált változatát használtuk. A metabolikus szindrómát a Nemzetközi Diabetes Szövetség kritériumai alapján határoztuk meg. Eredmények: A metabolikus szindróma a betegek 72%-ánál fordult elő, férfi: 65,9% nő: 77,2% (p = 0,031). A metabolikus szindrómás betegek esetében rövidebb 6 perces sétatávolságot mértünk ([m] 250 [150–330] vs. 295 [162–360]; p = 0,384), és szignifikánsan több volt az előző évi exacerbatiók száma (3 [0–6] vs. 1 [1–2]; p<0,001) a nem metabolikus szindrómás betegekhez képest. A BMI-re történő stratifikáció után a metabolikus szindróma jelenléte nagyobb volt BMI≥25 kg/m2 esetén. A hasi elhízás, a magas vérnyomás, a hyperlipidaemia és a hyperglykaemia szignifikánsan gyakoribb volt BMI≥25 kg/m2 esetén (p<0,001). Következtetés: Eredményeink azt sugallják, hogy a metabolikus szindrómás betegekben megnő az együttes morbiditási index, különösen azok körében, akik túlsúlyosak vagy elhízottak. Ezért a COPD-s betegekben nagyon fontos időben felismerni és megfelelően kezelni a metabolikus szindrómát. Orv Hetil. 2021; 162(5): 185–191. Summary. Introduction: Both obesity and the lack of physical activity among chronic obstructive pulmonary disease (COPD) patients increase the risk of developing metabolic syndrome. Objective: The goal of our study was to assess the prevalence of metabolic syndrome among COPD patients and to examine its correlation with age, gender, comorbidities, lung function values, nutritional status, exercise capacity, and quality of life. Method: A cross-sectional study was performed at the Department of Pulmonary Rehabilitation of the Hungarian National Korányi Institute for Pulmonology between July 1st and December 31st, 2019. A total of 300 patients aged over 40 were selected at random. Anthropometric data were collected along with lung function values, laboratory parameters, smoking status, the number of exacerbations in the previous year, and the use of corticosteroids. Quality of life was measured by the validated Hungarian, COPD-specific Saint George Respiratory Questionnaire. Metabolic syndrome was defined according to the International Diabetes Federation criteria. Results: Metabolic syndrome affected 72% of COPD patients (male: 65.9%, female 77.2%; p = 0.031). In patients with metabolic syndrome, shorter 6-minute walking distance was measured ([m] 250 [150–330] vs. 295 [162–360]; p = 0.384) and the number of exacerbations in the previous year was significantly higher (3 [0–6] vs. 1 [1–2]; p<0.001) compared to patients with no metabolic syndrome. After stratification for BMI, metabolic syndrome was more frequent in the case of BMI≥25 kg/m2. Central adiposity, hypertension, hyperlipidemia, and hyperglycemia were also significantly more frequent among patients with BMI≥25 kg/m2 (p<0.001). Conclusion: Our results suggest that the co-morbidity index increases in patients with metabolic syndrome, especially in overweight or obese patients. Therefore, early detection and appropriate treatment of metabolic syndrome in patients with COPD is very important. Orv Hetil. 2021; 162(5): 185–191.

LUNG FUNCTION IN SUBJECTS WITH OCCUPATIONAL CHRONIC OBSTRUCTIVE PULMONARY DISEASE EXPOSED TO INDUSTRIAL AEROSOLS CONTAINING NANOPARTICLES

2021 ◽  
Author(s):  
L.A. Shpagina ◽  
◽  
E.B. Logashenko ◽  
E.V. Anikina ◽  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Lung Function ◽  
Silica Nanoparticles ◽  
Pulmonary Disease ◽  
Mass Concentration ◽  
Airflow Limitation ◽  
Chronic Obstructive ◽  
Lung Volumes ◽  
Obstructive Pulmonary Disease ◽  
Occupational Copd

Abstract: Despite decrease in industrial aerosol impact on workers’ health there are disproportionately high prevalence of occupational lung diseases. So, it is of interest to investigate the role of nanoparticles. Objective was to establish lung function features in subjects with occupational chronic obstructive pulmonary disease (COPD) exposed to aerosols containing nanoparticles. Methods. It was a cross-sectional observational study. Subjects with occupational COPD (GOLD 2011-2021 criteria) exposed to aerosols containing metal (n=26) or silica nanoparticles (n=24) enrolled. Comparison group – tobacco smokers with COPD (n=50). Nanoparticles at workplaces air were measured by inductively coupled plasma atomic emission spectrometry and by scanning electron microscopy. Groups were matched by gender, age, COPD duration. Results. Occupational COPD in conditions of metal nanoparticles exposure was characterized by severe airflow limitation – forced expiratory volume in one second (FEV1) was 38%(35%;42%), by prominent increase in lung volumes – functional residual capacity (FRC) was 192% (184%;203%) and by highest decrease in diffusing lung capacity for carbon monoxide (DLco/Va), 34% (31%;38%). In occupational COPD subjects exposed to silica nanoparticles mild airflow limitation, mild increase in lung volumes and substantial decrease in DLco/Va, were seen. In logistic regression model metal nanoparticles mass concentration was associated with DLco/Va, FRC, FEV1, Raw and silica nanoparticles mass concentration – with DLco and FEV1. Conclusion. Nanoparticles in industrial aerosols are associated with occupational COPD phenotype.

Association of Plasma Heat Shock Protein 70 with Disease Severity, Smoking and Lung Function of Patients with Chronic Obstructive Pulmonary Disease

2020 ◽  
Author(s):  
Iva Hlapčić ◽  
Andrea Hulina-Tomašković ◽  
Marija Grdić Rajković ◽  
Sanja Popović-Grle ◽  
Andrea Vukić Dugac ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Heat Shock ◽  
Lung Function ◽  
Heat Shock Protein ◽  
Disease Severity ◽  
Heat Shock Protein 70 ◽  
Smoking Status ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients

Abstract Background: Extracellular heat shock protein 70 (eHsp70) acts like a damage-associated molecular pattern (DAMP) and it might modulate immune responses in patients with chronic obstructive pulmonary disease (COPD). The aim of the study was to explore plasma eHsp70 concentration in patients with stable COPD, its association with disease severity and smoking status as well as its diagnostic performance in COPD assessment.Methods: Blood samples were collected from 137 COPD patients and 95 healthy individuals. COPD patients were subdivided into GOLD 2-4 stages based on airflow obstruction severity and GOLD A-D groups regarding symptoms and exacerbations. Concentration of eHsp70 was assessed in EDTA plasma by the commercially available ELISA kit. Statistic analysis was performed by MedCalc statistical software.Results: eHsp70 concentration was increased in COPD patients when compared to controls and was increasing with the severity of airflow limitation as well as symptoms burden and exacerbation history. There were no differences in eHsp70 concentrations among COPD patients based on smoking status, yet eHsp70 was increased in healthy smokers compared to healthy non-smokers. Interestingly, healthy smokers had similar eHsp70 level as COPD patients in GOLD 2 stage and those in GOLD A group. In addition, eHsp70 showed significant negative correlation with lung function parameters FEV1 and FEV1/FVC and positive correlation with COPD multicomponent indices BODCAT, BODEx, CODEx and DOSE. Finally, eHsp70 showed great predictive value (OR=7.63) and correctly classified 76% of cases.Conclusions: Plasma eHsp70 is associated with COPD prediction and disease severity and might have a potential of becoming an additional biomarker in COPD assessment.

scholarly journals Association of NLRP1 Coding Polymorphism with Lung Function and Serum IL-1β Concentration in Patients Diagnosed with Chronic Obstructive Pulmonary Disease (COPD)

Genes ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 783 ◽  
Author(s):  
Ozretić ◽  
da Silva Filho ◽  
Catalano ◽  
Sokolović ◽  
Vukić-Dugac ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Lung Function ◽  
Pulmonary Disease ◽  
Minor Allele ◽  
Fine Tuning ◽  
Airflow Limitation ◽  
Smoking History ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
The Impact

Chronic obstructive pulmonary disease (COPD) is a chronic disease characterized by a progressive decline in lung function due to airflow limitation, mainly related to IL-1β-induced inflammation. We have hypothesized that single nucleotide polymorphisms (SNPs) in NLRP genes, coding for key regulators of IL-1β, are associated with pathogenesis and clinical phenotypes of COPD. We recruited 704 COPD individuals and 1238 healthy controls for this study. Twenty non-synonymous SNPs in 10 different NLRP genes were genotyped. Genetic associations were estimated using logistic regression, adjusting for age, gender, and smoking history. The impact of genotypes on patients’ overall survival was analyzed with the Kaplan–Meier method with the log-rank test. Serum IL-1β concentration was determined by high sensitivity assay and expression analysis was done by RT-PCR. Decreased lung function, measured by a forced expiratory volume in 1 s (FEV1% predicted), was significantly associated with the minor allele genotypes (AT + TT) of NLRP1 rs12150220 (p = 0.0002). The same rs12150220 genotypes exhibited a higher level of serum IL-1β compared to the AA genotype (p = 0.027) in COPD patients. NLRP8 rs306481 minor allele genotypes (AG + AA) were more common in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) definition of group A (p = 0.0083). Polymorphisms in NLRP1 (rs12150220; OR = 0.55, p = 0.03) and NLRP4 (rs12462372; OR = 0.36, p = 0.03) were only nominally associated with COPD risk. In conclusion, coding polymorphisms in NLRP1 rs12150220 show an association with COPD disease severity, indicating that the fine-tuning of the NLRP1 inflammasome could be important in maintaining lung tissue integrity and treating the chronic inflammation of airways.

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