Lung Function Decline In Smokers Research Articles

Tobacco smoking is associated with combined pulmonary fibrosis and emphysema and worse outcomes in interstitial lung disease.

Tobacco smoking is an established cause of pulmonary disease whose contribution to interstitial lung disease (ILD) is incompletely characterized. We hypothesized that compared with nonsmokers, subjects who smoked tobacco would differ in their clinical phenotype and have greater mortality. We performed a retrospective cohort study of tobacco smoking in ILD. We evaluated demographic and clinical characteristics, time to clinically meaningful lung function decline (LFD), and mortality in patients stratified by tobacco smoking status (ever vs. never) within a tertiary center ILD registry (2006-2021) and replicated mortality outcomes across four nontertiary medical centers. Data were analyzed by two-sided t tests, Poisson generalized linear models, and Cox proportional hazard models adjusted for age, sex, forced vital capacity (FVC), diffusion capacity of the lung for carbon monoxide (DLCO), ILD subtype, antifibrotic therapy, and hospital center. Of 1,163 study participants, 651 were tobacco smokers. Smokers were more likely to be older, male, have idiopathic pulmonary fibrosis (IPF), coronary artery disease, CT honeycombing and emphysema, higher FVC, and lower DLCO than nonsmokers (P < 0.01). Time to LFD in smokers was shorter (19.7 ± 20 mo vs. 24.8 ± 29 mo; P = 0.038) and survival time was decreased [10.75 (10.08-11.50) yr vs. 20 (18.67-21.25) yr; adjusted mortality HR = 1.50, 95%CI 1.17-1.92; P < 0.0001] compared with nonsmokers. Smokers had 12% greater odds of death for every additional 10 pack yr of smoking (P < 0.0001). Mortality outcomes remained consistent in the nontertiary cohort (HR = 1.51, 95%CI = 1.03-2.23; P = 0.036). Tobacco smokers with ILD have a distinct clinical phenotype strongly associated with the syndrome of combined PF and emphysema, shorter time to LFD, and decreased survival. Smoking prevention may improve ILD outcomes.NEW & NOTEWORTHY Smoking in ILD is associated with combined pulmonary fibrosis and emphysema and worse clinical outcomes.

Chronic viral hepatitis accelerates lung function decline in smokers.

Although hepatitis B virus (HBV) and hepatitis C virus (HCV) are hepatotrophic viruses, they may affect pulmonary diseases. The purpose of this study was to assess whether chronic viral hepatitis (CVH) infection was associated with a rapid decline in lung function. Repeated measurements of lung function were obtained from a well-curated health check-up database. A case was defined as an individual positive for HBsAg or anti-HCV antibody. A control was randomly selected (from the same dataset) after 1:1 matching in terms of age, sex, height, the body mass index, and smoking status. Separate analyses of non-smokers and smokers were performed. A total of 701 cases were enrolled (586 with HBV and 115 with HCV). In cross-sectional analysis, both forced expiratory volume in 1s (FEV1) and forced vital capacity (FVC) decreased significantly only in smokers (smoking cases vs. smoking controls) (adjusted p = 6.6 × 10-5 and adjusted p = 2.2 × 10-3, respectively). In longitudinal analysis, smoking cases showed significantly greater FEV1 and FVC decline rates than did smoking controls (adjusted p = 8.5 × 10-3 and adjusted p = 1.2 × 10-5, respectively). Such associations were particularly high in smoking cases at intermediate-to-high risk of hepatic fibrosis, as evaluated by the non-invasive Fibrosis-4 index. In summary, CVH was associated with both decreased lung function and accelerated lung function decline in smokers. A non-invasive measurement of hepatic fibrosis may be useful in predicting rapid lung function decline in smokers with CVH.

Recent advances in airway imaging using micro-computed tomography and computed tomography for chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a complex lung disease characterized by a combination of airway disease and emphysema. Emphysema is classified as centrilobular emphysema (CLE), paraseptal emphysema (PSE), or panlobular emphysema (PLE), and airway disease extends from the respiratory, terminal, and preterminal bronchioles to the central segmental airways. Although clinical computed tomography (CT) cannot be used to visualize the small airways, micro-CT has shown that terminal bronchiole disease is more severe in CLE than in PSE and PLE, and micro-CT findings suggest that the loss and luminal narrowing of terminal bronchioles is an early pathological change in CLE. Furthermore, the introduction of ultra-high-resolution CT has enabled direct evaluation of the proximal small (1 to 2-mm diameter) airways, and new CT analytical methods have enabled estimation of small airway disease and prediction of future COPD onset and lung function decline in smokers with and without COPD. This review discusses the literature on micro-CT and the technical advancements in clinical CT analysis for COPD. Hopefully, novel micro-CT findings will improve our understanding of the distinct pathogeneses of the emphysema subtypes to enable exploration of new therapeutic targets, and sophisticated CT imaging methods will be integrated into clinical practice to achieve more personalized management.

CC16 levels correlate with cigarette smoke exposure in bronchial epithelial cells and with lung function decline in smokers

BackgroundClub cell protein-16 (CC16) expression has been associated with smoking-related lung function decline. The study hypothesis was that CC16 expression in both serum and bronchial epithelium is associated with lung function decline in smokers, and exposure to cigarette smoke will lead to reduction in CC16 expression in bronchial epithelial cells.MethodsIn a cohort of community-based male Chinese subjects recruited for lung function test in 2000, we reassessed their lung function ten years later and measured serum levels of CC16. CC16 expression was further assayed in bronchial epithelium from endobronchial biopsies taken from an independent cohort of subjects undergoing autofluorescence bronchoscopy, and tested for correlation between CC16 immunostaining intensity and lung function. In an in-vitro model, bronchial epithelial cells were exposed to cigarette smoke extract (CSE), and the expression levels of CC16 were measured in bronchial epithelial cells before and after exposure to CSE.ResultsThere was a significant association between FEV1 decline and serum CC16 levels in smokers. Expression of CC16 in bronchial epithelium showed significant correlation with FEV1/FVC. Bronchial epithelial cells showed significant decrease in CC16 expression after exposure to CSE, followed by a subsequent rise in CC16 expression upon removal of CSE.ConclusionsResults of these clinical and laboratory investigations suggested that low serum CC16 was associated with smoking-related decline in lung function, demonstrated the first time in a Chinese cohort. The data also lend support to the putative role of CC16 in protection against smoking-related bronchial epithelial damage.( word count: 243)US clinical trial registryNCT01185652, first posted 20 August, 2010.

Plasma pro-surfactant protein B and lung function decline in smokers.

Plasma pro-surfactant protein B (pro-SFTPB) levels have recently been shown to predict the development of lung cancer in current and ex-smokers, but the ability of pro-SFTPB to predict measures of chronic obstructive pulmonary disease (COPD) severity is unknown. We evaluated the performance characteristics of pro-SFTPB as a biomarker of lung function decline in a population of current and ex-smokers. Plasma pro-SFTPB levels were measured in 2503 current and ex-smokers enrolled in the Pan-Canadian Early Detection of Lung Cancer Study. Linear regression was performed to determine the relationship of pro-SFTPB levels to changes in forced expiratory volume in 1 s (FEV1) over a 2-year period as well as to baseline FEV1 and the burden of emphysema observed in computed tomography (CT) scans. Plasma pro-SFTPB levels were inversely related to both FEV1 % predicted (p=0.024) and FEV1/forced vital capacity (FVC) (p<0.001), and were positively related to the burden of emphysema on CT scans (p<0.001). Higher plasma pro-SFTPB levels were also associated with a more rapid decline in FEV1 at 1 year (p=0.024) and over 2 years of follow-up (p=0.004). Higher plasma pro-SFTPB levels are associated with increased severity of airflow limitation and accelerated decline in lung function. Pro-SFTPB is a promising biomarker for COPD severity and progression.

Rapid Lung Function Decline in Smokers Is a Risk Factor for COPD and Is Attenuated by Angiotensin-Converting Enzyme Inhibitor Use

Cigarette smoking is the most important risk factor for COPD in the United States. Host factors that influence the rapid rate of FEV1 decline in smokers and how decline rate influences risk for developing COPD are unknown. The aim of this study was to characterize the rate of FEV1 decline in ever smokers, compare the risk of incident COPD between those with rapid decline and others, and determine the effect of selected drugs on rapid decline. A total of 1,170 eligible ever smokers from the longitudinal Lovelace Smokers Cohort with repeat spirometry tests over a minimum follow-up period of 3 years (mean follow-up, 5.9 years) were examined, including 809 ever smokers without a spirometric abnormality at baseline. Longitudinal absolute decline in postbronchodilator FEV1 from the slope of the spirometric values over all examinations was annualized and classified as rapid (≥30 mL/y), normal (0-29.9 mL/y), or no (>0 mL/y) decline. Logistic regression and Kaplan-Meier survival curves were used for the analysis. Approximately 32% of ever smokers exhibited rapid decline. Among ever smokers without a baseline spirometric abnormality, rapid decline was associated with an increased risk for incident COPD (OR, 1.88; P=.003). The use of angiotensin-converting enzyme (ACE) inhibitors at baseline examination was protective against rapid decline, particularly among those with comorbid cardiovascular disease, hypertension, or diabetes (ORs 0.48, 0.48, and 0.12, respectively; P≤.02 for all analyses). Ever smokers with a rapid decline in FEV1 are at higher risk for COPD. Use of ACE inhibitors by smokers may protect against this rapid decline and the progression to COPD.

Predicting an accelerated lung function decline in smokers: is there a proper threshold?

From the authors: We thank F.A.A. Mohamed Hoesein and P. Zanen for their interest in our work [1]. In our study, we performed secondary analyses on data from the Lung Health Study (LHS) [2]. We subdivided the LHS study population into four categories based on the presence or absence of airflow obstruction as defined the fixed forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <0.70 cut-off point and by the lower fifth percentile using the LMS (lambda, mu, sigma) method definitions. The LMS method accounts for sex- and age-specific predicted values (mu), and adjusts for nonuniform dispersion (sigma) and skewness of the lung function values distribution (lambda). The original LHS study population consisted of 5887 smokers aged 35–60 years. We excluded 1842 subjects because 1276 subjects were in different categories based on the fixed and LMS definitions for airflow obstruction during their baseline and first annual visits, and 566 subjects …

Accelerated Lung Function Decline in Smokers

Accelerated Lung Function Decline in Smokers

Vitamin D deficiency, smoking, and lung function in the Normative Aging Study.

Vitamin D has immunomodulatory and antiinflammatory effects that may be modified by cigarette smoke and may affect lung function. To examine the effect of vitamin D deficiency and smoking on lung function and lung function decline. A total of 626 men from the Normative Aging Study had 25-hydroxyvitamin D levels measured at three different times between 1984 and 2003 with concurrent spirometry. Vitamin D deficiency was defined as serum level ≤ 20 ng/ml. Statistical analysis was performed using multivariable linear regression and mixed effects models. In the overall cohort, there was no significant effect of vitamin D deficiency on lung function or on lung function decline. In both cross-sectional and longitudinal multivariable models, there was effect modification by vitamin D status on the association between smoking and lung function. Cross-sectional analysis revealed lower lung function in current smokers with vitamin D deficiency (FEV(1), FVC, and FEV(1)/FVC; P ≤ 0.0002), and longitudinal analysis showed more rapid rates of decline in FEV(1) (P = 0.023) per pack-year of smoking in subjects with vitamin D deficiency as compared with subjects who were vitamin D sufficient. Vitamin D deficiency was associated with lower lung function and more rapid lung function decline in smokers over 20 years in this longitudinal cohort of elderly men. This suggests that vitamin D sufficiency may have a protective effect against the damaging effects of smoking on lung function. Future studies should seek to confirm this finding in the context of smoking and other exposures that affect lung function.

Heme oxygenase 1 variations and lung function decline in smokers: proof of replication

We provide supportive evidence for a role of the promoter polymorphism (GT-repeat) in heme oxygenase 1 (HO-1) in relation to lung function loss over time. This observation has been made...

Statin May Slow Lung Function Decline in Smokers

Statin May Slow Lung Function Decline in Smokers

Transforming growth factor-β1 polymorphisms, airway responsiveness and lung function decline in smokers

Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation in the airways, parenchyma and vessels, which can cause a structural remodeling with increased fibrosis that narrows and fixes the airway lumen. Transforming growth factor-beta1 (TGF-beta1), a multifunctional growth factor, was reported to be increased in the airways of COPD patients. In this study, we hypothesized that polymorphisms in the TGF-beta1 gene would be associated with an accelerated rate of decline of forced expiratory volume in 1s (FEV(1)). Three polymorphisms, -509 (C-->T), +869 (T-->C) and +915 (G-->C), located in TGF-beta1 gene were genotyped. We determined the prevalence of these polymorphisms in 590 continuing smokers who had the fastest (n=283) and slowest (n=307) rate of decline of lung function from the NHLBI Lung Health Study. There was no association between these TGF-beta1 polymorphisms and the rate of decline of FEV(1), but in a post-hoc analysis the genotype distribution at +869 was significantly different between high and low responders to methacholine (P=0.04). These data suggest that the T-C polymorphism at position +869 in the TGF-beta1 gene contributes to airway hyperresponsiveness, but not to rapid decline of lung function.

The European Respiratory Society study on chronic obstructive pulmonary disease (EUROSCOP): recruitment methods and strategies

The European Respiratory Society's study on chronic obstructive pulmonary disease (EUROSCOP) is a multicentre study performed initially in 12 countries to assess the effect of 3 years' treatment with inhaled corticosteroids on lung function decline in smokers with chronic obstructive pulmonary disease (COPD). It aimed at recruiting 50 subjects in 50 European centres. This study discusses the most successful, countrywise, recruitment strategies, an important issue since many multicentre European studies may follow in the future. The total number of recruited subjects was 2147 in 39 participating centres. In total, at least 25 000 screening spirometries were performed, and about 80 000 hospital records were checked. The most effective way of recruiting subjects was to screen subjects by spirometry after mass media campaigns (eight out of nine countries). Others used workplace screenings and different types of population survey, and only a few centres successfully recruited participants by hospital records. Inclusion criteria were slightly changed upon low initial accrual rate. Initial surveys in one country, where 2405 subjects were screened by spirometry, gave an important indication for the change of the inclusion criteria. Extension of the upper age limit from 60 to 65 yr considerably improved recruitment, as did a change of the upper limit of FEV 1 from below 80% predicted normal to below 100% predicted normal, while maintaining the FEV 1 VC ratio below 70%. A tremendous effort is needed to recruit individuals with preclinical COPD, but this is certainly feasible with adequate strategies adjusted to each country.