Rapid Decline In FEV1 Research Articles

Lung function decline in people with serious mental illness: A call to action

This prospective observational study aimed to evaluate the rate of change in forced expiratory volume in the first second (FEV1) and to explore the factors associated with changes in FEV1 in people with serious mental illness (SMI). Sixty subjects diagnosed with schizophrenia or bipolar disorder who were smokers and without history of respiratory illness agreed to participate. The mean (range) follow-up period was 3.54 (3.00–4.98) years. The mean (standard deviation) annual rate of change in FEV1 decreased by 39.1 (105.2) mL/year. Thirty-one (51.7 %) patients experienced a decrease in the FEV1 ≥40 mL/year (i.e. a rapid decline). The factors associated with the absolute change in FEV1 were the baseline International Physical Activity Questionnaire activity score in metabolic equivalents of tasks (β 0.145, 95 % confidence interval [CI] 0.043 to 0.246; p = 0.005), baseline FEV1 (β -0.025, 95 % CI -0.076 to 0.027; p = 0.352), and the interaction term of both variables (β -3.172e-05, 95 % CI -6.025e-05 to -0.319e-05; p = 0.029). The factors associated with rapid FEV1 decline were income (odds ratio [OR] 0.999, 95 % CI 0.995 to 1.003; p = 0.572), the rate of change in abdominal circumference (OR 0.000, 95 % CI 0.000 to 0.890; p = 0.081), and the interaction term of both variables (OR 1.038, 95 % CI 1.010 to 1.082; p = 0.026). In conclusion, a substantial proportion of people with SMI experienced a rapid decrease in FEV1. If our results are confirmed in larger samples, the routine evaluation of lung function in people with SMI would be an opportunity to identify individuals at greater risk of morbidity and mortality.

Biomarkers of Inflammation and Longitudinal Evaluation of Lung Function, Physical Activity, and Grip Strength: A Secondary Analysis in the CASCADE Study.

Physical activity, lung function, and grip strength are associated with exacerbations, hospitalizations, and mortality in people with chronic obstructive pulmonary disease (COPD). We tested whether baseline inflammatory biomarkers were associated with longitudinal outcomes of these physiologic measurements. The COPD Activity: Serotonin Transporter, Cytokines, and Depression (CASCADE) study was a prospective observational study of individuals with COPD. A total of 14 inflammatory biomarkers were measured at baseline. Participants were followed for 2 years. We analyzed associations between baseline biomarkers and forced expiratory volume in 1 second (FEV1), physical activity, and grip strength. We used a hierarchical hypothesis testing procedure to reduce type I error. We used Pearson correlations to test associations between baseline biomarkers and longitudinal changes in the outcomes of interest. We used Fisher's linear discriminant analysis to test if linear combinations of baseline biomarkers predict rapid FEV1 decline. Finally, we used linear mixed modeling to test associations between baseline biomarkers and outcomes of interest at baseline, year 1, and year 2; models were adjusted for age, smoking status, baseline biomarkers, and FEV1. A total of 302 participants (age 67.5 ± 8.5 years, 19.5% female, 28.5% currently smoking) were included. Baseline biomarkers were not associated with longitudinal changes in grip strength, physical activity, or rapid FEV1 decline. Higher interleukin-6 and C-reactive protein were associated with lower physical activity at baseline and these relationships persisted at year 1 and year 2. Baseline inflammatory biomarkers did not predict changes in lung function or physical activity, but higher inflammatory biomarkers were associated with persistently low levels of physical activity.

A blood and bronchoalveolar lavage protein signature of rapid FEV1 decline in smoking-associated COPD

Accelerated progression of chronic obstructive pulmonary disease (COPD) is associated with increased risks of hospitalization and death. Prognostic insights into mechanisms and markers of progression could facilitate development of disease-modifying therapies. Although individual biomarkers exhibit some predictive value, performance is modest and their univariate nature limits network-level insights. To overcome these limitations and gain insights into early pathways associated with rapid progression, we measured 1305 peripheral blood and 48 bronchoalveolar lavage proteins in individuals with COPD [n = 45, mean initial forced expiratory volume in one second (FEV1) 75.6 ± 17.4% predicted]. We applied a data-driven analysis pipeline, which enabled identification of protein signatures that predicted individuals at-risk for accelerated lung function decline (FEV1 decline ≥ 70 mL/year) ~ 6 years later, with high accuracy. Progression signatures suggested that early dysregulation in elements of the complement cascade is associated with accelerated decline. Our results propose potential biomarkers and early aberrant signaling mechanisms driving rapid progression in COPD.

Association of Pseudomonas aeruginosa infection stage with lung function trajectory in children with cystic fibrosis

BackgroundPseudomonas aeruginosa (Pa) infection in cystic fibrosis (CF) is characterized in stages: never (prior to first positive culture) to incident (first positive culture) to chronic. The association of Pa infection stage with lung function trajectory is poorly understood and the impact of age on this association has not been examined. We hypothesized that FEV1 decline would be slowest prior to Pa infection, intermediate after incident infection and greatest after chronic Pa infection. MethodsParticipants in a large US prospective cohort study diagnosed with CF prior to age 3 contributed data through the U.S. CF Patient Registry. Cubic spline linear mixed effects models were used to evaluate the longitudinal association of Pa stage (never, incident, chronic using 4 different definitions) with FEV1 adjusted for relevant covariates. Models contained interaction terms between age and Pa stage. Results1,264 subjects born 1992–2006 provided a median 9.5 (IQR 0.25 to 15.75) years of follow up through 2017. 89% developed incident Pa; 39–58% developed chronic Pa depending on the definition. Compared to never Pa, incident Pa infection was associated with greater annual FEV1 decline and chronic Pa infection with the greatest FEV1 decline. The most rapid FEV1 decline and strongest association with Pa infection stage was seen in early adolescence (ages 12–15). ConclusionsAnnual FEV1 decline worsens significantly with each Pa infection stage in children with CF. Our findings suggest that measures to prevent chronic infection, particularly during the high-risk period of early adolescence, could mitigate FEV1 decline and improve survival.

Association between preserved ratio impaired spirometry and sleep apnea in a Chinese community

Objective This study investigated the association between obstructive sleep apnea (OSA) and preserved ratio impaired spirometry (PRISm) in a community population. Methods Baseline data from a prospective cohort study, the Predictive Value of Combining Inflammatory Biomarkers and Rapid Decline of FEV1 for COPD (PIFCOPD), were used for cross-sectional analysis. Participants aged 40–75 years were recruited from the community and their demographic information and medical history were collected. The STOP-Bang questionnaire (SBQ) was used to assess the risk of OSA. Pulmonary function tests were performed using a portable spirometer (COPD-6) and forced expiratory volume in 1 s (FEV1) and 6 s (FEV6) were measured. Routine blood, biochemical, high-sensitivity C-reactive protein (hs-CRP), and interleukin-6 tests were also performed. The pH of the exhaled breath condensate was determined. Results A total of 1183 participants were enrolled, of which 221 with PRISm and 962 with normal lung function. The neck circumference, waist-to-hip ratio, hs-CRP concentration, proportion of males, cigarette exposure, number of current smoker, high risk of OSA, and prevalence of nasal and ocular allergy symptoms were significantly higher in the PRISm group than in the non-PRISm group (p < .05). Logistic regression showed that the risk of OSA (odds ratio, 1.883; 95% confidence interval, 1.245–2.848), waist-to-hip ratio, current smoking, and prevalence of nasal allergy symptoms were independently associated with PRISm after correcting for age and sex. Conclusion These findings showed that OSA prevalence is independently associated with PRISm prevalence. Further studies should confirm the relationship between systemic inflammation in OSA, localized inflammation of the airways, and impaired lung function.

Risk of Rapid Lung Function Decline in Young Adults With Chronic Obstructive Pulmonary Disease: A Community-Based Prospective Cohort Study.

It is unclear whether young adults with chronic obstructive pulmonary disease (COPD) are at an increased risk of rapid lung function decline. A total of 2,934 Korean adults aged 40-49 years who had consecutive lung function measurements were included. COPD was defined as pre-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity < lower limit of normal. The risk of rapid decline in FEV1, defined as ≥ 60 mL/year, was assessed using multivariable logistic regression analysis. In the multivariable model, a significantly higher risk of rapid decline in FEV1 was observed for the COPD group compared with the non-COPD group (adjusted odds ratio, 1.89; 95% confidence interval, 1.18-2.95), which was especially significant in subjects with FEV1 less than the median value (< 110%pred) (Pinteraction = 0.017) and inactive physical activity (Pinteraction = 0.039). In conclusion, the risk of rapid FEV1 decline was higher in young adults with COPD than in those without COPD, especially in those with FEV1 less than the median value and inactive physical activity.

Clinical characteristics of patients requiring lung transplantation referral in national cystic fibrosis registry data.

We aimed to determine the number of cystic fibrosis (CF) patients recorded in the Cystic Fibrosis Registry of Türkiye (CFRT) who were in need of lung transplantation (LT) referral and examine clinical differences between patients who were LT candidates due to rapid forced expiratory volume in one second (FEV₁) decline and LT candidates without rapid FEV₁ decline in the last year to identify a preventable cause in patients with such rapid FEV₁ decline. All CF patients recorded in the CFRT in 2018 were evaluated in terms of LT. Patients were divided into those with FEV₁ below 50% and in need of LT due to a decrease of 20% or more in the previous year (Group 1) and those who did not have FEV₁ decline of more than 20% in the previous year but had other indications for LT (Group 2). Demographic and clinical features were compared between the two groups. Of 1488 patients registered in CFRT, 58 had a need for LT. Twenty patients were included in Group 1 and others in Group 2. Our findings did not reveal any significant variations in treatment, chronic infection status, or complications between the two groups. The average weight z-score was significantly higher in Group 1. Positive correlations were detected between weight z-score and FEV₁ in 2017 in Group 1 and between FEV₁ values in 2017 and 2018 in Group 2. There appears to be a relationship between the nutritional status and weight z-scores of CF patients and pulmonary function, which may indirectly affect the need for lung transplantation referral.

Association of serum CC16 levels with eosinophilic inflammation and respiratory dysfunction in severe asthma

BackgroundThere are knowledge gaps in the potential role of Club cell 16-kDa secretory protein (CC16) in severe asthma phenotypes and type 2 inflammation, as well as the longitudinal effect of CC16 on pulmonary function tests and exacerbation risk in epidemiological studies. Objective and methodsTo assess whether serum CC16 is associated with eosinophilic inflammation in patients with severe asthma. We also examined the effect of this protein on the annual decline in forced expiratory volume in the first second (FEV1) and the risk of exacerbation using a longitudinal approach. We recruited 127 patients with severe asthma from 30 hospitals/pulmonary clinics in Hokkaido, Japan. The least square means and standard error were calculated for T-helper 2 (Th2) biomarkers and pulmonary function test across CC16 tertiles at baseline. We did the same for asthma exacerbation and annual decline in FEV1 with 3 and 5 years’ follow-up, respectively. ResultsWe found that serum CC16 was inversely associated with sputum eosinophils and blood periostin in a dose-response manner. Baseline CC16 and FEV1/forced vital capacity ratio were positively associated in adjusted models (p for trend = 0.008). Patients with the lowest tertile of serum CC16 levels at baseline had a −14.3 mL decline in FEV1 than those with the highest tertile over 5 years of follow-up (p for trend = 0.031, fully adjusted model). We did not find any association of CC16 with exacerbation risk. ConclusionPatients with severe asthma with lower circulatory CC16 had enhanced eosinophilic inflammation with rapid FEV1 decline over time.

Risk Factors of Rapid FEV1 Decline in a Real-World Chronic Obstructive Pulmonary Disease Cohort

Background: Rapid forced expiratory volume in 1 s (FEV₁) decliners have been considered a unique subgroup of patients with chronic obstructive pulmonary disease (COPD). Rapid FEV₁ decline manifests early and is associated with poor prognosis. This necessitates the pre-emptive identification of risk factors for rapid FEV₁ decline. Objectives: We aimed to determine the risk factors and clinical outcomes in patients with COPD. Methods: This longitudinal, observational study was based on the Korea COPD Subgroup Study cohort (NCT02800499) from January 2012 to December 2019 across 54 medical centers in South Korea. Eligible patients were followed up for 3 years with serial spirometric tests. We calculated the annualized percentage change in FEV₁ from baseline. Rapid decliners were defined as the quartile of patients with the highest annualized percentage FEV₁ decline. Results: Of the 518 patients, 130 were rapid decliners who lost 6.2%/year and 100 mL/year of FEV₁. The multivariable logistic regression identified male sex, current smoking, blood eosinophil count <150/µL, and high forced vital capacity as the independent risk factors for rapid FEV₁ decline. Among rapid decliners, the lung function deteriorated more rapidly in current smokers and patients with severe dyspnea, while triple combination therapy attenuated lung function decline in comparison with mono-bronchodilator therapy. Rapid decliners had a higher rate of severe exacerbation than nonrapid decliners (0.2/year vs. 0.1/year, p value = 0.032). Conclusions: We identified the independent risk factors for rapid FEV₁ decline. This information may assist physicians in the early detection and pertinent management of rapid decline among patients with COPD.

CASE STUDY OF CONCURRENT ALPHA-1 ANTITRYPSIN DEFICIENCY AND ASTHMA.

<h3>Introduction</h3> Asthma and alpha-1 antitrypsin deficiency (AATD) differ in pathogenesis but can present with similar clinical symptoms, such as dyspnea, wheezing and cough. The similarity of symptoms can often lead to delayed or missed diagnosis of AATD in patients with concurrent asthma. Our abstract focuses on the importance of assessing for AATD in those with fixed obstructive lung disease. <h3>Case Description</h3> Patient A is a 65-year-old male with a history of longstanding asthma, who exhibited rapid progressive decline in FEV1 on serial pulmonary function tests (PFTs). Subsequent workup revealed MZ genotype of alpha-1 antitrypsin deficiency. His symptoms were thought to be primarily asthma-related, given air trapping and bronchodilator reversibility on PFTs. Patient B is a 58-year-old male with known alpha-1 antitrypsin deficiency (ZZ genotype), although he was only mildly symptomatic. Increasing episodes of wheezing and decreasing FEV1 prompted FeNO testing, which supported superimposed asthma. <h3>Discussion</h3> Concurrent asthma and AATD can worsen pulmonary inflammation. Alpha-1 antitrypsin can have immunomodulatory effects on inflammatory cells and inactivate elastase, thus preserving lung function. Shared symptoms and vague screening guidelines for coincident asthma and AATD can often delay diagnosis in patients with both diseases, potentially worsening patient outcomes. In our patients, further testing was only prompted due to progressive clinical decline, which ideally could have been preempted. We hope that these cases will bring increased awareness to diagnostic and therapeutic challenges in patients with AATD and asthma.

The effect of TGF-β1 polymorphisms on pulmonary disease progression in patients with cystic fibrosis

BackgroundTransforming Growth Factor-β1 (TGF-β1) is a genetic modifier in patients with cystic fibrosis (CF). Several single nucleotide polymorphisms (SNPs) of TGF-β1 are associated with neutrophilic inflammation, lung fibrosis and loss of pulmonary function.AimThe aim of this study was to assess the relationship between genetic TGF-β1 polymorphisms and pulmonary disease progression in CF patients. Furthermore, the effect of TGF-β1 polymorphisms on inflammatory cytokines in sputum was investigated.Methods56 CF-patients and 62 controls were genotyped for three relevant SNPs in their TGF-β1 sequence using the SNaPshot® technique. Individual “slopes” in forced expiratory volume in 1 s (FEV1) for all patients were calculated by using documented lung function values of the previous five years. The status of Pseudomonas aeruginosa (Pa) infection was determined. Sputum concentrations of the protease elastase, the serine protease inhibitor elafin and the cytokines IL-1β, IL-8, IL-6, TNF-α were measured after a standardized sputum induction and processing.ResultsThe homozygous TT genotype at codon 10 was associated with a lower rate of chronic Pa infection (p < 0.05). The heterozygous GC genotype at codon 25 was associated with lower lung function decline (p < 0.05). Patients with homozygous TT genotype at the promotor SNP showed higher levels of TNF-α (p < 0,05). Higher levels of TGF-β1 in plasma were associated with a more rapid FEV1 decline over five years (p < 0.05).ConclusionsOur results suggest that polymorphisms in the TGF-β1 gene have an effect on lung function decline, Pa infection as well as levels of inflammatory cytokines. Genotyping these polymorphisms could potentially be used to identify CF patients with higher risk of disease progression. TGF-β1 inhibition could potentially be developed as a new therapeutic option to modulate CF lung disease.

Rapid FEV1 Decline and Lung Cancer Incidence in South Korea

Impaired lung function is associated with a higher risk of developing lung cancer. However, lung function is a dynamic variable and must be evaluated longitudinally. This study reports on the relationship between accelerated lung function decline and development of lung cancer. Is accelerated lung function decline associated with the development of lung cancer? A longitudinal, observational study was performed by using epidemiologic data from two population-based studies comprising subjects assessed biannually from 2001 to 2019 in South Korea. Eligible subjects were between 40 and 69 years of age and were followed up by using spirometry. Spirometry measurements were made at each follow-up. Patients with a decline in FEV1 > 60mL per year were defined as rapid FEV1 decliners. The relationship between lung cancer and rapid FEV1 decline was evaluated by using adjusted Cox regression models with covariates, including age, sex, smoking history, FEV1/FVC, and WBC count. Among the 8,549 eligible subjects, 1,287 (15.1%) had rapid FEV1 decline, and 48 (0.6%) had newly developed lung cancer. The risk of lung cancer development was increased in the subjects aged≥ 45 years and those with≥ 30 pack-years of smoking, low baseline FEV1/FVC, low forced expiratory flow between 25%and 75%of vital capacity, rapid FEV1 decline, and increased WBC count. Rapid FEV1 decline was an independent risk factor for lung cancer development (adjusted hazard ratio, 2.34; 95%CI, 1.28-4.28; P= .006). Time-dependent net reclassification improvement showed a benefit of FEV1 decline rate in determining subjects at risk of lung cancer when added to conventional practice (categorical, 0.32 [95%CI, 0.00-0.64]; continuous, 0.83 [95%CI, 0.14-1.25]). The FEV1 decline rate may be a potential biomarker for lung cancer development. Further study is needed to identify whether patients with rapid FEV1 decline warrant lung cancer assessment or screening.

Wood smoke exposure affects lung aging, quality of life, and all-cause mortality in New Mexican smokers

BackgroundThe role of wood smoke (WS) exposure in the etiology of chronic obstructive pulmonary disease (COPD), lung cancer (LC), and mortality remains elusive in adults from countries with low ambient levels of combustion-emitted particulate matter. This study aims to delineate the impact of WS exposure on lung health and mortality in adults age 40 and older who ever smoked.MethodsWe assessed health impact of self-reported “ever WS exposure for over a year” in the Lovelace Smokers Cohort using both objective measures (i.e., lung function decline, LC incidence, and deaths) and two health related quality-of-life questionnaires (i.e., lung disease-specific St. George's Respiratory Questionnaire [SGRQ] and the generic 36-item short-form health survey).ResultsCompared to subjects without WS exposure, subjects with WS exposure had a more rapid decline of FEV1 (− 4.3 ml/s, P = 0.025) and FEV1/FVC ratio (− 0.093%, P = 0.015), but not of FVC (− 2.4 ml, P = 0.30). Age modified the impacts of WS exposure on lung function decline. WS exposure impaired all health domains with the increase in SGRQ scores exceeding the minimal clinically important difference. WS exposure increased hazard for incidence of LC and death of all-cause, cardiopulmonary diseases, and cancers by > 50% and shortened the lifespan by 3.5 year. We found no evidence for differential misclassification or confounding from socioeconomic status for the health effects of WS exposure.ConclusionsWe identified epidemiological evidence supporting WS exposure as an independent etiological factor for the development of COPD through accelerating lung function decline in an obstructive pattern. Time-to-event analyses of LC incidence and cancer-specific mortality provide human evidence supporting the carcinogenicity of WS exposure.

Relationships between lung function decline and skeletal muscle and fat mass changes: a longitudinal study in healthy individuals.

BackgroundThe associations between long‐term changes in body mass composition and decline in lung function in healthy adults are unknown.MethodsUsing a well‐defined health check‐up database, we first assessed individual longitudinal changes in muscle mass (MM) and fat mass (FM) measured via bioelectrical impedance analyses. Then we classified the enrolled individuals into five body composition groups according to their MM index (MMI) [MM (kg)/height (m)2] or FM index (FMI) [FM (kg)/height (m)2] change rate quartiles. Linear mixed models adjusted for age, smoking status, height, and body mass index were used to analyse the rate of forced expiratory volume in 1 s (FEV1) decline and body composition groups.ResultsA total of 15 476 middle‐aged individuals (6088 women [mean age ± standard deviation: 50.74 ± 7.44] and 9388 men [mean age ± standard deviation: 49.36 ± 6.99]) were enrolled. The mean number of measurements was 6.96 (interquartile range [IQR]: 5–9) over an average follow‐up period of 8.95 years (IQR: 6.73–11.10). Decrease in MMI was significantly associated with accelerated FEV1 decline in men only (P = 1.7 × 10−9), while increase in FMI was significantly associated with accelerated FEV1 decline in both women and men (P = 7.9 × 10−10 and P < 2.0 × 10−16 respectively). Linear mixed model analyses indicated that annual increase of 0.1 kg/m2 in MMI was related to accelerated FEV1 decline by 30.79 mL/year (95% confidence interval [CI]: 26.10 to 35.48 mL/year) in men. Annual increase of 0.1 kg/m2 in FMI was related to accelerated FEV1 decline by 59.65 mL/year in men (95% CI: 56.84 to 62.28 mL/year) and by 22.84 mL/year in women (95% CI: 18.95 to 26.74 mL/year). In body composition analysis, we found increase in MMI was significantly associated with attenuated FEV1 decline in men only (P = 1.7 × 10−9), while increase in FMI was significantly associated with accelerated FEV1 decline in both women and men (P = 7.9 × 10−10 and P < 2.0 × 10−16 respectively). Individuals characterized with gain MM combined with loss of FM were associated with the most favourable outcome (i.e. the smallest rate of decline in FEV1) in both women and men. In men, loss of FM over time is more closely related with attenuated FEV1 decline than change in MM (gain or loss).ConclusionsChange in body composition over time can be used to identify healthy middle‐aged individuals at high risk for rapid FEV1 decline.

Blood leukocyte count as a systemic inflammatory biomarker associated with a more rapid spirometric decline in a large cohort of iron and steel industry workers

ObjectiveIron and steel industry workers are exposed to high levels of inhalable dust particles that contain various elements, including metals, and cause occupational lung diseases. We aim to assess the relationship between occupational dust exposure, systemic inflammation, and spirometric decline in a cohort of Chinese iron and steel workers.MethodsWe studied 7513 workers who participated in a Health Surveillance program at Wugang Institute for Occupational Health between 2008 and 2017. Time-weighted exposure intensity (TWEI) of dust was quantified based on self-reported dust exposure history, the experience of occupational hygienists, and historical data of dust exposure for workers with certain job titles. A linear mixed-effects model was used for association analyses.ResultsThe average annual change of lung function was − 50.78 ml/year in forced expiratory volume in 1 s (FEV1) and − 34.36 ml/year in forced vital capacity (FVC) in males, and − 39.06 ml/year in FEV1 and − 26.66 ml/year in FVC in females. Higher TWEI prior to baseline was associated with lower longitudinal measurements of FEV1 and FVC but not with their decline rates. Higher WBC and its differential at baseline were associated with lower longitudinal measurements and a more rapid decline of FEV1 and FVC in a dose-dependent monotonically increasing manner. Moreover, the increase of WBC and its differential post-baseline was also associated with a more rapid decline of FEV1 and FVC.ConclusionsOur findings support the important role of systemic inflammation in affecting the temporal change of lung function in iron and steel industry workers.

Bronchial gene expression signature associated with rate of subsequent FEV1 decline in individuals with and at risk of COPD

BackgroundCOPD is characterised by progressive lung function decline. Leveraging prior work demonstrating bronchial airway COPD-associated gene expression alterations, we sought to determine if there are alterations associated with differences in...

Mild catalytic defects of tert rs61748181 polymorphism affect the clinical presentation of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a disorder of accelerated lung aging. Multiple pieces of evidence support that the aging biomarker short telomeres, which can be caused by mutations in telomerase reverse transcriptase (TERT), contribute to COPD pathogenesis. We hypothesized that short telomere risk-associated single nucleotide polymorphisms (SNPs) in TERT, while not able to drive COPD development, nonetheless modify the disease presentation. We set out to test the SNP carrying status in a longitudinal study of smokers with COPD and found that rapid decline of FEV1 in lung function was associated with the minor allele of rs61748181 (adjusted odds ratio 2.49, p = 0.038). Biochemical evaluation of ex vivo engineered human cell models revealed that primary cells expressing the minor allele of rs61748181 had suboptimal telomere length maintenance due to reduced telomerase catalytic activity, despite having comparable cell growth kinetics as WT-TERT expressing cells. This ex vivo observation translated clinically in that shorter telomeres were found in minor allele carriers in a sub-population of COPD patients with non-declining lung function, over the 5-year period of the longitudinal study. Collectively, our data suggest that functional TERT SNPs with mild catalytic defects are nonetheless implicated in the clinical presentation of COPD.

Gender modifies the effect of body mass index on lung function decline in mild-to-moderate COPD patients: a pooled analysis

BackgroundLow body weight is associated with poor prognosis in patients with chronic obstructive pulmonary disease (COPD). However, it is not known whether gender modifies this relationship.MethodsWe pooled data of 8686 COPD patients from 7 studies with a median length of 36-months of follow up. Using a longitudinal natural cubic spline regression model, we examined the dose–response relationship between body mass index (BMI) and the rate of decline in forced expiratory volume in one second (FEV1) in patients with GOLD 1 and 2 disease, stratified by gender and adjusted for age, smoking status, and cohort effects.ResultsThere was an inverse linear relationship between BMI and the rate of FEV1 decline in GOLD Grades 1 and 2, which was modified by gender (p < 0.001). In male patients, an increase of BMI by 1 kg/m2 reduced FEV1 decline by 1.05 mL/year (95% CI 0.96, 1.14). However, in female patients, BMI status did not have a clinically meaningful impact on FEV1 decline: an increase of baseline BMI by 1 kg/m2 reduced FEV1 decline by 0.16 ml/year (95% CI 0.11, 0.21). These gender-modified relationships were similar between GOLD 1 and 2 patients, and between current and former smokers.ConclusionIn mild to moderate COPD, higher BMI was associated with a less rapid decline of FEV1 in male patients whereas this association was minimal in females patients. This gender-specific BMI effect was independent of COPD severity and smoking status.

Pulmonary Arterial Pruning and Longitudinal Change in Percent Emphysema and Lung Function: The Genetic Epidemiology of COPD Study

Pulmonary endothelial damage has been shown to precede the development of emphysema in animals, and vascular changes in humans have been observed in COPD and emphysema. Is intraparenchymal vascular pruning associated with longitudinal progression of emphysema on CT imaging or decline in lung function over 5 years? The Genetic Epidemiology of COPD Study enrolled ever smokers with and without COPD from 2008 through 2011. The percentage of emphysema-like lung, or "percent emphysema," was assessed at baseline and after 5 years on noncontrast CT imaging as the percentage of lung voxels< -950 Hounsfield units. An automated CT imaging-based tool assessed and classified intrapulmonary arteries and veins. Spirometry measures are postbronchodilator. Pulmonary arterial pruning was defined as a lower ratio of small artery volume (< 5mm2 cross-sectional area) to total lung artery volume. Mixed linear models included demographics, anthropomorphics, smoking, and COPD, with emphysema models also adjusting for CT imaging scanner and lung function models adjusting for clinical center and baseline percent emphysema. At baseline, the 4,227 participants were 60 ± 9 years of age, 50%were women, 28%were Black, 47%were current smokers, and 41%had COPD. Median percent emphysema was 2.1 (interquartile range, 0.6-6.3) and progressed 0.24 percentage points/y (95%CI, 0.22-0.26 percentage points/y) over 5.6 years. Mean FEV1 to FVC ratio was 68.5±14.2%and declined 0.26%/y (95%CI, -0.30 to -0.23%/y). Greater pulmonary arterial pruning was associated with more rapid progression of percent emphysema (0.11 percentage points/y per 1-SD increase in arterial pruning; 95%CI, 0.09-0.16 percentage points/y), including after adjusting for baseline percent emphysema and FEV1. Arterial pruning also was associated with a faster decline in FEV1 to FVC ratio (-0.04%/y per 1-SD increase in arterial pruning; 95%CI, -0.008 to -0.001%/y). Pulmonary arterial pruning was associated with faster progression of percent emphysema and more rapid decline in FEV1 to FVC ratio over 5 years in ever smokers, suggesting that pulmonary vascular differences may be relevant in disease progression. ClinicalTrials.gov; No.: NCT00608764; URL: www.clinicaltrials.gov.

From GOLD 0 to Pre-COPD.

Currently the diagnosis of chronic obstructive pulmonary disease (COPD) requires the demonstration of airflow limitation, defined as a post-bronchodilator FEV1/FVC <0.7, a measurement that remains methodologically robust and widely available. FEV1 is one of the most powerful predictors of clinically relevant outcomes including symptoms, exacerbations and mortality. However, reliable data suggest that respiratory symptoms, in particular chronic bronchitis, airway abnormality and emphysema detected using modern imaging techniques such as computed tomography (CT), and certain physiologic measures including rapid decline in FEV1 and DLCO are present among individuals who do not meet spirometric criteria for COPD. These abnormalities may help to identify individuals at increased risk for developing airflow limitation in the future. Here, we review the evidence that support the use of the term "pre-COPD" in individuals with symptoms (e.g., "Non-Obstructive Chronic Bronchitis" (NOCB)), physiologic (e.g., low DLCO) and/or imaging abnormalities (e.g. CT emphysema) but spirometry in the normal range, who are at risk of developing COPD defined by a reduced FEV1/FVC ratio. We acknowledge, however, that further research on early disease in young individuals will be critical to develop a clinically operable definition of "pre-COPD" that demonstrates good sensitivity and specificity. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).