Longitudinal Changes In Lung Function Research Articles

Longitudinal changes in lung function following post-9/11 military deployment in symptomatic veterans

RationaleExposure to burn pit smoke, desert and combat dust, and diesel exhaust during military deployment to Southwest Asia and Afghanistan (SWA) can cause deployment-related respiratory diseases (DRRDs) and may confer risk for worsening lung function after return. MethodsStudy subjects were SWA-deployed veterans who underwent occupational lung disease evaluation (n = 219). We assessed differences in lung function by deployment exposures and DRRD diagnoses. We used linear mixed models to assess changes in lung function over time. ResultsMost symptomatic veterans reported high intensity deployment exposure to diesel exhaust and burn pit particulates but had normal post-deployment spirometry. The most common DRRDs were deployment-related distal lung disease involving small airways (DDLD, 41%), deployment-related asthma (DRA, 13%), or both DRA/DDLD (24%). Those with both DDLD/DRA had the lowest estimated mean spirometry measurements five years following first deployment. Among those with DDLD alone, spirometry measurements declined annually, adjusting for age, sex, height, weight, family history of lung disease, and smoking. In this group, the forced expiratory volume in the first second/forced vital capacity (FEV1/FVC) ratio declined 0.2% per year. Those with more intense inhalational exposure had more abnormal lung function. We found significantly lower estimated FVC and total lung capacity five years following deployment among active duty participants (n = 173) compared to those in the reserves (n = 26). ConclusionsMore intense inhalational exposures were linked with lower post-deployment lung function. Those with distal lung disease (DDLD) experienced significant longitudinal decline in FEV1/FVC ratio, but other DRRD diagnosis groups did not.

The Upper Limit of Normal Rate of Lung Function Decline in Healthy Adults in the Framingham Heart Study

BackgroundLung function declines over the course of adulthood; however, a consensus on the normal range of decline in an individual’s lung function is lacking. Research QuestionWhat is the normal range and the upper limit of normal (ULN) decline in lung function of adults without prior tobacco use, occupational dust exposure, or a known diagnosis or symptoms of cardiopulmonary disease? Study Design and MethodsA retrospective analysis of healthy, never-smokers (n=1,305) from the Framingham Heart Study with repeated lung function meeting standards for acceptability and reproducibility was conducted. Longitudinal change was derived using a linear mixed-effects model and estimated to a 6-year interval. The ULN decline was defined as the 95th percentile. ResultsThe mean follow-up between spirometry examinations was 5.5 years, while the mean follow-up between diffusing capacity for carbon monoxide (DLCO) studies was 5.9 years. Decline in forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and DLCO accelerated with age, while decline in FEV1/FVC decelerated with age. Decline varied with sex, age, and height. Over a 6-year period, the ULN decline in FEV1 ranged from 383 mL to 667 mL, and the ULN decline in DLCO ranged from 3.6 ml/min/mmHg to 9.5 ml/min/mmHg. Overall, men had faster absolute rates of decline than women, while relative (%) rates of decline were similar between sexes. InterpretationLung function decline is non-linear and accelerates with age. In this cohort, the ULN decline over 6-years often exceeded current guidelines for interpreting significant longitudinal change in lung function.

Association of patient-reported outcome measures with lung function and mortality in fibrotic interstitial lung disease: a prospective cohort study.

Patient-reported outcome measures (PROMs) may provide clinicians and researchers with direct insights into disease impact and patient well-being. We assessed whether selected PROMs and their domains are associated with baseline and longitudinal changes in lung function and can predict mortality in patients with fibrotic interstitial lung disease (f-ILD). A single-centre prospective study of adult patients with f-ILD enrolled over 3 years was conducted assessing baseline and short-term changes in PROMs. Three questionnaires, the modified Medical Research Council dyspnoea scale (mMRC), Chronic Respiratory Questionnaire (CRQ) and Self-Management Ability Scale (SMAS-30) were administered at planned intervals and assessed for their association with baseline clinical findings, change in lung function (% predicted forced vital capacity (FVC%) and diffusion capacity of the lung for carbon monoxide (DLCO%)) and all-cause mortality. 199 patients were enrolled with a mean PROM follow-up of 9.6 months. When stratified by FVC% quartiles at presentation, lower mMRC (less dyspnoea), higher CRQ Physical and Emotional domain (better health-related quality of life) and higher total SMAS-30 scores (better self-management ability) were associated with higher FVC%. Short-term changes in all three PROMs appeared to be associated with changes in FVC% and DLCO%. Adjusted and unadjusted baseline and serial PROM changes were also predictive of mortality. Baseline and serial assessments of PROMs were associated with changes in lung function and predicted death in patients with f-ILD. PROMs may strengthen comprehensive assessments of disease impact in clinical practice as well as support patient-centred outcomes in research.

Acute Exacerbation and Longitudinal Lung Function Change of Preserved Ratio Impaired Spirometry.

Preserved ratio impaired spirometry (PRISm) is a heterogeneous disease entity. Limited data are available regarding its prevalence, clinical course, or prognosis. We aimed to evaluate the longitudinal clinical course of patients with PRISm compared with chronic obstructive pulmonary disease (COPD). A retrospective study enrolled PRISm and COPD patients who underwent chest computed tomography and longitudinal pulmonary function tests between January 2013 and December 2020. We compared the incidence of acute exacerbations and lung function changes between PRISm and COPD patients. Of the 623 patients, 40 and 583 had PRISm and COPD, respectively. Compared to COPD patients, PRISm patients were younger, more likely to be female and have a history of tuberculosis, and less likely to be smokers. They also had less severe comorbidities, lower forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO). The clinical course was not significantly different between the PRISm and COPD patients in terms of the risk of moderate-to-severe acute exacerbations or proportion of frequent exacerbators. During follow-up, PRISm patients had a significantly slower annual decline of forced expiratory volume in 1 second, FVC, and DLCO than COPD patients. PRISm patients had no significant difference in the risk of acute exacerbations, but a significantly slower decline of lung function during longitudinal follow-up, compared with COPD patients.

Antibody predictors of mortality and lung function trends in myositis spectrum interstitial lung disease.

The impact of autoantibody profiles on prognosis of idiopathic inflammatory myositis associated interstitial lung disease (IIM-ILD) and myositis spectrum ILD with Myositis Specific Antibodies (MSA) remains unclear. This retrospective cohort study examines whether serological profiles are associated with mortality and longitudinal lung function change. Baseline clinical/demographic characteristics and follow-up lung function of consecutive adult patients with IIM-ILD or Interstitial Pneumonia with Autoimmune Features (IPAF) positive for MSAs were extracted from three hospitals. Univariate and multi-variate Cox-Proportional Hazards analyses were used to compare mortality between autoantibodies. Regression models were used to analyse lung function trends. Of 430 included patients, 81% met IIM criteria, 19% were IPAF-MSA. On univariate analysis, risk factors associated with mortality included higher age, Charlson Co-morbidity Index and CRP; and lower BMI, baseline TLCO% and FEV1%. Compared to anti-MDA5-negativity, anti-MDA5-positivity (MDA5+) was associated with high mortality in the first 3 months (HR 65.2. 95%CI 14.1, 302.0), while no significant difference was seen thereafter (HR 0.55, 95%CI 0.14, 2.28). On multi-variate analysis, combined anti-synthetase antibodies carried a reduced risk of mortality (HR 0.63), although individually, mortality was reduced in anti-Jo1 + (HR 0.61, 95%CI 0.4-0.87) and increased in anti-PL7+ patients (HR 2.07, 95%CI 1.44-2.99). Anti-MDA5+ was associated with slow improvement in %FVC over the first 3 years, while anti-PL7+ was linked with a slow decline from 12 months onwards. Among autoantibody profiles in myositis spectrum disorders, anti-MDA5+ and anti-PL7+ confer higher mortality risks. Survivors of an early peak of mortality in anti-MDA5+ disease appear to have a favourable prognosis.

Long-term clinical outcomes of aspirin-exacerbated respiratory disease: Real-world data from an adult asthma cohort.

Aspirin-exacerbated respiratory disease (AERD) is a phenotype of severe asthma, but its disease course has not been well documented compared with that of aspirin-tolerant asthma (ATA). This study aimed to investigate the long-term clinical outcomes between AERD and ATA. AERD patients were identified by the diagnostic code and positive bronchoprovocation test in a real-world database. Longitudinal changes in lung function, blood eosinophil/neutrophil counts, and annual numbers of severe asthma exacerbations (AEx) were compared between the AERD and the ATA groups. Within a year after baseline, two or more severe AEx events indicated severe AERD, whereas less than two AEx events indicated nonsevere AERD. Among asthmatics, 353 had AERD in which 166 and 187 patients had severe and nonsevere AERD, respectively, and 717 had ATA. AERD patients had significantly lower FEV1%, higher blood neutrophil counts, and higher sputum eosinophils (%) (all p < .05) as well as higher levels of urinary LTE4 and serum periostin, and lower levels of serum myeloperoxidase and surfactant protein D (all p < .01) than those with ATA. In a 10-year follow-up, the severe AERD group maintained lower FEV1% with more severe AEs than the nonsevere AERD group. We demonstrated that AERD patients presented poorer long-term clinical outcomes than ATA patients in real-world data analyses.

Cigarette Smoking and Asthma

Cigarette smoking is a well-know health hazard, probably not least for patients suffering from asthma. This review gives a short overview concerning the effects of passive and active smoking on the inception and outcome with regard to longitudinal changes in lung function and mortality for patients with asthma. Substantial evidence suggests that smoking affects asthma adversely. Exposure to environmental tobacco smoke in children, especially maternal smoking, may be a significant risk factor for asthma. Environmental tobacco exposure in patients with established asthma is not only associated with more severe symptoms, but also with lower quality of life, reduced lung function, and increased health care utilisation for asthma, including hospital admissions. Active smoking appears not to be a significant risk factor for asthma, but it is associated with worse outcome with regard to both longitudinal changes in lung function and asthma-related mortality. Based on the current knowledge, it therefore seems of utmost importance to encourage patients with asthma not to smoke. In line with this, patients with asthma should be given full support in their right to a smoke-free environment.

Corticosteroid-induced remission and mycophenolate maintenance therapy in granulomatous lymphocytic interstitial lung disease: long-term, longitudinal change in lung function in a single-centre cohort

AimThe aim of the study was to evaluate the response in lung function to different treatment regimens for common variable immunodeficiency patients with granulomatous lymphocytic interstitial lung disease (GLILD).MethodA longitudinal retrospective cohort study was carried out. Patients were divided into three groups. To assess the response to different treatments, we compared baseline lung function with post-treatment tests.Results14 patients with GLILD were included, seven of whom were treated with acute corticosteroids for a mean duration of 132±65 days. Spirometry results were unchanged, but there was a significant improvement in diffusing capacity of the lung for carbon monoxide (DLCO)% and transfer coefficient of the lung for carbon monoxide (KCO)% (median change in DLCO%=7%, p=0.04, and KCO%=13%, p=0.02). Relapse occurred in three out of seven patients. Five patients were treated with long-term mycophenolate mofetil (MMF) with/without corticosteroids for a mean duration of 1277±917 days. No changes were found in spirometry; however, there was a significant increase in DLCO% and KCO% (median change in each of DLCO% and KCO%=10%, p=0.04). Four patients on steroids with MMF successfully weaned the prednisone dose over 12 months. Four patients never received immunosuppression therapy. A significant decline was found in their lung function assessed over 7.5 years. The median reduction in the forced vital capacity (FVC)%, forced expiratory volume in 1 s (FEV1)% and DLCO% was 15%, 7% and 15%, equivalent to 2%, 1% and 2% per year, respectively.ConclusionCorticosteroids improve gas transfer in GLILD, but patients often relapse. The use of MMF was associated with long-term effectiveness in GLILD and permits weaning of corticosteroids. A delay in initiating and continuing maintenance treatment could lead to disease progression.

A longitudinal analysis of early lung function trajectory in survivors of childhood Hodgkin lymphoma.

Childhood Hodgkin lymphoma survivors suffer from long-term effects decades after treatment completion with a prevalence of pulmonary dysfunction of up to 65.2%. This study explored the early trajectory of pulmonary function in pediatric cancer patients with Hodgkin lymphoma who received pulmonary toxic therapy. In this single-center, 20-year retrospective cohort study, we included patients who were <18 years old at diagnosis of Hodgkin lymphoma between January 1994 and December 2014, and received bleomycin or thoracic radiation. We measured pulmonary function and reported on percent predicted values for forced expiratory volume in 1 s, total lung capacity, and diffusing capacity of the lungs. We used linear mixed models to identify the association of clinical factors with longitudinal changes in lung function at time points before and after treatment completion. Of 80 children who met inclusion criteria, all were treated with bleomycin, and 83.8% received thoracic radiation. More than half (51.2%) of patients had any abnormalities in lung function measures during the study observation period which averaged 24.2months (±31.1SD). Females, younger age at diagnosis and treatment with radiation were associated with lower lung function measurements at various time points. While the majority of children experienced a recovery of their lung function within 1-2 years after treatment completion, some children with these risk factors did not. Pulmonary function abnormalities begin early in children treated for Hodgkin lymphoma. While the majority of children demonstrate a slow and continuous improvement in lung function back to baseline over time, we recommend routine asymptomatic screening of pulmonary function in certain childhood cancer survivors, particularly females, those diagnosed young and patients who received radiation therapy.

Clinical Deterioration and Lung Function Change in Patients With Concomitant Asthma and Bronchiectasis

Only limited data are available regarding the effects of bronchiectasis on the clinical course of asthma. This study evaluated longitudinal clinical outcomes according to bronchiectasis status in patients with asthma. This retrospective study included patients with asthma who underwent chest computed tomography and pulmonary function tests between January 2013 and December 2019. The annual incidence of episodes of moderate-to-severe acute clinical deterioration (exacerbations) and longitudinal changes in lung function were evaluated. Of 667 patients with asthma, 251 had bronchiectasis. Patients with bronchiectasis had significantly more history of tuberculosis and nontuberculous mycobacterial lung disease, and lower forced expiratory volume in 1 second and forced vital capacity, compared with patients without bronchiectasis, although there was no difference in smoking intensity and inhaled corticosteroid treatment. Bronchiectasis was significantly associated with higher annual rates of severe and moderate-to-severe acute exacerbations; it was also associated with greater risk of acute exacerbation during follow-up. The severity and progression of bronchiectasis were independent risk factors for acute exacerbation. There were no significant differences in annual decline of lung function according to bronchiectasis status or bronchiectasis progression. In patients with asthma, the presence and progression of bronchiectasis were significantly associated with increased risk of moderate-to-severe acute exacerbation, but they were not associated with longitudinal changes in lung function.

Longitudinal changes in lung function in very prematurely born young people receiving high-frequency oscillation or conventional ventilation from birth.

ObjectiveTo examine changes in lung function over time in extremely prematurely born adolescents.Working HypothesisChanges in lung function during adolescence would vary by ventilation mode immediately after birth.Study DesignLongitudinal follow‐up study.Patient Subject SelectionParticipants from the United Kingdom Oscillation Study who were randomized at birth to high‐frequency oscillation (HFO) or conventional ventilation (CV) were assessed at 11–14 years (n = 319) and at 16–19 years (n = 159).MethodologyForced expiratory flow (FEF), forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and lung volumes including functional residual capacity (FRC) were reported as z‐scores. The diffusion capacity of the lungs for carbon monoxide (DLCO) was measured. Lung function trajectories were compared by mode of ventilation using mixed models. Changes in z‐scores were scaled to 5‐year average follow‐up.ResultsThere were significant changes in the mean FEF75, FEF50, FEF25, FEV1, FVC, and DLCO z‐scores within the CV and HFO cohorts, but no significant differences in the changes between the two groups. The mean FRC z‐score increased in both groups, with an average change of greater than one z‐score. The mean FEV1/FVC z‐score increased significantly in the CV group, but not in the HFO group (difference in slopes: p = 0.02). Across the population, deterioration in lung function was associated with male sex, white ethnicity, lower gestational age at birth, postnatal corticosteroids, oxygen dependency at 36 weeks postmenstrual age, and lower birth weight, but not ventilation mode.ConclusionsThere was little evidence that the mode of ventilation affected changes in lung function over time.

Obesity-Related Indices Are Associated with Longitudinal Changes in Lung Function: A Large Taiwanese Population Follow-Up Study.

The global pandemic of obesity and the increasing incidence of chronic respiratory diseases are growing health concerns. The association between obesity and pulmonary function is uncertain. Therefore, this study aimed to explore associations between changes in lung function and obesity-related indices in a large longitudinal study. A total of 9059 participants with no personal histories of asthma, smoking, bronchitis, or emphysema were enrolled from the Taiwan Biobank and followed for 4 years. Lung function was assessed using spirometry measurements including forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC). Changes in FEV1/FVC (∆FEV1/FVC) between baseline and follow-up were calculated. The following obesity-related indices were studied: lipid accumulation product (LAP), body roundness index (BRI), conicity index (CI), body adiposity index (BAI), abdominal volume index (AVI), body mass index (BMI), waist–hip ratio (WHR), and waist-to-height ratio (WHtR). In multivariable analysis, the subjects with high BMI (p < 0.001), WHR (p < 0.001), WHtR (p < 0.001), LAP (p = 0.002), BRI (p < 0.001), CI (p = 0.005), BAI (p < 0.001), and AVI (p < 0.001) were significantly associated with a high baseline FEV1/FVC. After 4 years of follow-up, the subjects with high BMI (p < 0.001), WHR (p < 0.001), WHtR (p < 0.001), LAP (p = 0.001), BRI (p < 0.001), CI (p = 0.002), BAI (p < 0.001), and AVI (p < 0.001) were significantly associated with a low △FEV1/FVC. High obesity-related index values were associated with better baseline lung function and a rapid decrease in lung function at follow-up.

Longitudinal assessment of lung clearance index to monitor disease progression in children and adults with cystic fibrosis

BackgroundLung clearance index (LCI) is a valuable research tool in cystic fibrosis (CF) but clinical application has been limited by technical challenges and uncertainty about how to interpret longitudinal change....

Longitudinal change in lung function and subsequent risks of cardiovascular events: evidence from four prospective cohort studies

BackgroundLung function is constantly changing over the life course. Although the relation of cross-sectional lung function measure and adverse outcomes has been reported, data on longitudinal change and subsequent cardiovascular (CV) events risks are scarce. Therefore, this study is to determine the association of longitudinal change in lung function and subsequent cardiovascular risks.MethodsThis study analyzed the data from four prospective cohorts. Subjects with at least two lung function tests were included. We calculated the rate of forced respiratory volume in 1 s (FEV1) and forced vital capacity (FVC) decline for each subject and categorized them into quartiles. The primary outcome was CV events, defined as a composite of coronary heart disease (CHD), chronic heart failure (CHF), stroke, and any CV death. Cox proportional hazards regression and restricted cubic spline models were applied.ResultsThe final sample comprised 12,899 participants (mean age 48.58 years; 43.61% male). Following an average of 14.79 (10.69) years, 3950 CV events occurred. Compared with the highest FEV1 quartile (Q4), the multivariable HRs for the lowest (Q1), 2nd (Q2), and 3rd quartiles (Q3) were 1.33 (95%CI 1.19, 1.49), 1.30 (1.16, 1.46), and 1.07 (0.95, 1.21), respectively. Likewise, compared with the reference quartile (Q4), the group that experienced a faster decline in FVC had higher HRs for CV events (1.06 [95%CI 0.94–1.20] for Q3, 1.15 [1.02–1.30] for Q2, and 1.28 [1.14–1.44] for Q1). The association remained robust across a series of sensitivity analyses and nearly all subgroups but was more evident in subjects < 60 years.ConclusionsWe observed a monotonic increase in risks of CV events with a faster decline in FEV1 and FVC. These findings emphasize the value of periodic evaluation of lung function and open new opportunities for disease prevention.

Idiopathic Pulmonary Fibrosis Registry China study (PORTRAY): protocol for a prospective, multicentre registry study

IntroductionIdiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease characterised by a fibrotic histological pattern found in usual interstitial pneumonia. Its causes, pathogenesis, clinical phenotype and molecular mechanisms...

Arsenic exposure and its joint effects with cigarette smoking and physical exercise on lung function impairment: Evidence from an occupational cohort study

BackgroundArsenic (As) is an established toxic metal, but its effect on longitudinal lung function change among occupational workers is less conclusive. Methods1243 participants were recruited in a coke-oven plant and followed up from 2010 to 2014. Each individual provided 20 mL morning urine sample at baseline, which was then used for urinary levels of As (U–As) and polycyclic aromatic hydrocarbon (PAH) metabolites detecting. Lung function levels at both baseline and the end of follow-up were determined. Multiple linear regression models were used to analyze the associations between U–As with annual lung function changes, and to evaluate the joint effects of U–As with cigarette smoking and regular physical exercise. ResultsAmong all participants, each 2-fold increase in U–As was associated with −12.09 (95%CI: −19.37, −4.81) mL, −0.32% (95%CI: −0.54%, −0.10%), −15.04 (95%CI: −24.62, −5.46) mL, and −0.36% (95%CI: −0.64%, −0.08%) annual changes in reduced forced expiratory volume in 1 second (FEV1), percent predicted FEV1 (ppFEV1), forced vital capacity (FVC), and percent predicted FVC (ppFVC), respectively. These effects were more pronounced among coke-oven workers with smoking (especially heavy smoking with pack-years≥15) and without regular physical exercise. Compared to low-As-exposed (≤4.70 μg/mmol creatinine) non-smokers with regular physical exercise, the high-As-exposed (>4.70 μg/mmol creatinine) smokers without regular physical exercise had the worst annual declines in FEV1 [β (95%CI) = −69.01 (−106.67, −31.34) mL], ppFEV1 [β (95%CI) = −1.94% (−3.02%, −0.87%)], FVC [β (95%CI) = −78.66 (95%CI: −129.46, −27.86) mL], and ppFVC [β (95%CI) = −1.80% (−3.23%, −0.37%)]. ConclusionsThe findings in our prospective cohort study suggested the positively linear dose-response relationship of U–As with annual lung function decline. The adverse effects of As could be enhanced by cigarette smoking and attenuated by regular physical exercise. Specific emphasizes on tobacco control and physical exercise were suggested to prevent As exposure induced pulmonary impairment.

Clinical characterization of patients with interstitial lung disease: Report from a single Canadian Center

RATIONALE: Interstitial lung diseases (ILD) are a heterogeneous group of disorders characterized by inflammation and/or fibrosis of the lung. There have been few prior descriptions of the clinical characteristics of Canadian patients with ILD. OBJECTIVES This study aimed to characterize patients with ILD seen at a single subspecialty center in Canada. METHODS This is a single center prospective registry of adults with ILD in Canada. Descriptive statistics were used to characterize the cohort. Linear mixed models were used to describe longitudinal changes in lung function, and Kaplan-Meier curves used to compare survival between diagnostic groups. MEASUREMENTS AND MAIN RESULTS: Baseline patient demographics, lung function studies and diagnosis as determined by a multidisciplinary team discussion were recorded. Follow-up lung function studies were collected as part of routine clinical care for patients followed in the registry. A total of 159 patients were enrolled between 2007 and 2013. The most common diagnosis was idiopathic pulmonary fibrosis (IPF) (42%), while 25% of patients had unclassifiable ILD and 22% had ILD due to connective tissue disease. Sixty-five (41%) of patients died during the mean follow-up period of 4.7 years, with IPF patients having the highest mortality. CONCLUSIONS Patients with a wide variety of ILDs were followed at this single center subspecialty clinic, with IPF being the most frequent diagnosis. A total of 25% of patients had ILD, which was unclassifiable; most of these patients were clinically managed as IPF. Clinical outcomes of IPF patients followed in this clinic appear similar to other reported cohorts of IPF patients.

Impact of gastroesophageal reflux on longitudinal lung function and quantitative computed tomography in the COPDGene cohort

RationaleGastroesophageal reflux disease (GERD) is a common comorbidity in chronic obstructive pulmonary disease (COPD) and has been associated with increased risk of acute exacerbations, hospitalization, emergency room visits, costs, and quality-of-life impairment. However, it remains unclear whether GERD contributes to the progression of COPD as measured by lung function or computed tomography.ObjectiveTo determine the impact of GERD on longitudinal changes in lung function and radiographic lung disease in the COPDGene cohort.MethodsWe evaluated 5728 participants in the COPDGene cohort who completed Phase I (baseline) and Phase II (5-year follow-up) visits. GERD status was based on participant-reported physician diagnoses. We evaluated associations between GERD and annualized changes in lung function [forced expired volume in 1 s (FEV1) and forced vital capacity (FVC)] and quantitative computed tomography (QCT) metrics of airway disease and emphysema using multivariable regression models. These associations were further evaluated in the setting of GERD treatment with proton-pump inhibitors (PPI) and/or histamine-receptor 2 blockers (H2 blockers).ResultsGERD was reported by 2101 (36.7%) participants at either Phase I and/or Phase II. GERD was not associated with significant differences in slopes of FEV1 (difference of − 2.53 mL/year; 95% confidence interval (CI), − 5.43 to 0.37) or FVC (difference of − 3.05 mL/year; 95% CI, − 7.29 to 1.19), but the odds of rapid FEV1 decline of ≥40 mL/year was higher in those with GERD (adjusted odds ratio (OR) 1.20; 95%CI, 1.07 to 1.35). Participants with GERD had increased progression of QCT-measured air trapping (0.159%/year; 95% CI, 0.054 to 0.264), but not other QCT metrics such as airway wall area/thickness or emphysema. Among those with GERD, use of PPI and/or H2 blockers was associated with faster decline in FEV1 (difference of − 6.61 mL/year; 95% CI, − 11.9 to − 1.36) and FVC (difference of − 9.26 mL/year; 95% CI, − 17.2 to − 1.28).ConclusionsGERD was associated with faster COPD disease progression as measured by rapid FEV1 decline and QCT-measured air trapping, but not by slopes of lung function. The magnitude of the differences was clinically small, but given the high prevalence of GERD, further investigation is warranted to understand the potential disease-modifying role of GERD in COPD pathogenesis and progression.Clinical trials registrationNCT00608764.

Association of Neutrophil to Lymphocyte Ratio With Pulmonary Function in a 30-Year Longitudinal Study of US Veterans

Chronic obstructive pulmonary disease (COPD) is a critical public health burden. The neutrophil to lymphocyte ratio (NLR), an inflammation biomarker, has been associated with COPD morbidity and mortality; however, its associations with lung function decline and COPD development are poorly understood. To explore the associations of NLR with lung function decline and COPD risks. This longitudinal cohort study included white male veterans in the US with more than 30 years of follow-up to investigate the associations of NLR with lung function, COPD, and hypomethylation of cg05575921, the top DNA methylation marker of lung function changes in response to tobacco smoking. This study included 7466 visits from 1549 participants, each examined up to 13 times between 1982 and 2018. A subgroup of 1411 participants without COPD at baseline were selected to analyze the association of NLR with incident COPD. Data were analyzed from September 2019 to January 2020. The primary exposure was NLR, which was estimated using automated whole blood cell counts based on a blood sample collected at each visit. The methylation level of cg05575921 was measured in blood DNA from a subgroup of 1228 visits. The outcomes of interest were lung function, measured as forced respiratory volume in the first second (FEV1) in liters, forced vital capacity (FVC) in liters, percentage of FVC exhaled in the first second (FEV1/FVC), and maximal midexpiratory flow rate (MMEF) in liters per minute and COPD status, defined as meeting the Global Initiative for Chronic Obstructive Lung Diseases stage II (or higher) criteria. Both outcomes were measured as each visit. Among 1549 included men (mean [SD] age, 68.3 [9.3] years) with 7466 visits from 1982 to 2018, a 1-unit increase in NLR was associated with statistically significant mean (SE) decreases of 0.021 (0.004) L in FEV1, 0.016 (0.005) L in FVC, 0.290% (0.005) L in FVC, 0.290% (0.065%) in FEV1/FVC, and 3.65 (0.916) L/min MMEF. Changes in NLR up to approximately 10 years were associated with corresponding longitudinal changes in lung function. Furthermore, this increase in NLR was associated with 9% higher odds of COPD (odds ratio, 1.09 [95% CI, 1.03-1.15]) for all visits and 27% higher risk of incident COPD (odds ratio, 1.07 [95% CI, 1.07-1.51]) for participants without COPD at baseline. Additionally, a 1-unit increase in NLR was associated with a mean (SE) decrease of 0.0048 (0.0021 in cg05575921 hypomethylation, which may mediate the adverse association of NLR-related inflammation on lung function. These findings suggest that NLR may be a clinically relevant biomarker associated with high risk of lung function impairment and COPD alone or in combination with DNA methylation profiles.

Association of adult lung function with accelerated biological aging

Lung function, strongly associated with morbidity and mortality, decreases with age. This study examines whether poor adult lung function is associated with age accelerations (AAs). DNA methylation (DNAm) based AAs, lifespan predictors (GrimAge and plasminogen activator inhibitor 1-PAI1) and their related age-adjusted measures were estimated from peripheral blood at two time points (8-to-11 years apart) in adults from two cohorts: SAPALDIA (n=987) and ECRHS (n=509). Within each cohort and stratified by gender (except for estimators from GrimAge and PAI1), AAs were used as predictors in multivariate linear regression with cross-sectional lung function parameters, and in covariate-adjusted mixed linear regression with longitudinal change in lung function and meta-analysed.AAs were found cross-sectionally associated with lower mean FEV1 (Forced Expiratory Volume in one second) (AA-residuals:P-value=4x10-4; Intrinsic Epigenetic AA:P-value=2x10-4) in females at the follow-up time point only, and the same trend was observed for FVC (Forced Vital Capacity). Both lifespan and plasma level predictors were observed strongly associated with lung function decline and the decline was stronger in the follow-up time points (strongest association between FEV1 and DNAmAge GrimAge:P-value=1.25x10-17).This study suggests that DNAm based lifespan and plasma level predictors can be utilised as important factors to assess lung health in adults.