Rate Of FEV1 Decline Research Articles

Inhaled Corticosteroid Withdrawal and Change in Lung Function in Primary Care Patients with Chronic Obstructive Pulmonary Disease in England.

Rationale: In chronic obstructive pulmonary disease (COPD), inhaled corticosteroids (ICS) are associated with pneumonia, highlighting the importance of investigating subgroups of patients who may benefit from prolonged ICS use. Despite this, the WISDOM (Withdrawal of Inhaled Steroids during Optimized Bronchodilator Management) trial found a greater decline in forced expiratory volume in 1 second (FEV1) in patients with COPD who withdrew from ICS compared with patients who remained on triple therapy. Objectives: We investigated the association between ICS withdrawal and the rate of FEV1 decline in patients with COPD using routinely collected electronic healthcare records. Methods: Using CPRD (Clinical Practice Research Datalink) Aurum and Hospital episode statistics, we included patients with COPD who had been on triple therapy for at least 4 months. Patients were categorized into those who withdrew from ICS and those who remained on triple therapy during follow-up. Three cohorts were created: 1) patients meeting the WISDOM trial eligibility criteria; 2) patients with COPD not restricted by the WISDOM trial eligibility criteria; and 3) patients who would have been excluded from the WISDOM trial on the basis of their comorbidities. Mixed linear regression was used to model the association between ICS withdrawal and the rate of FEV1 decline (ml/year) adjusted for baseline characteristics. Results: A total of 6,008 patients with COPD met the WISDOM eligibility criteria, of which 9.0% withdrew from ICS. Mean rates of FEV1 declined -7.8 ml/year (95% confidence interval [CI], -19.7 to 4.1) for withdrawers and -15.2 ml/year (95% CI, -18.7 to -11.8) for those who remained on triple therapy (difference, P = 0.264). A total of 60,645 patients with COPD were not restricted by the WISDOM eligibility criteria. The mean rate of FEV1 decline was -32.6 ml/year (95% CI, -33.6 to -31.5) for withdrawers and -36.4 ml/year (95% CI, -39.4 to -33.4) for those who remained on triple therapy. A total of 32,882 patients with COPD were included in the last population representing those who would have been excluded from the WISDOM trial because of their comorbidities. The mean rate of FEV1 decline was -29.4 ml/year (95% CI, -30 to -28.1) in withdrawers and -31.3 ml/year (95% CI, -35 to -27.5) in those who remained on triple therapy. Conclusions: The rate of FEV1 decline was similar between patients on triple therapy and patients who withdrew from ICS regardless of the specific COPD population studied. In routine clinical practice, few patients with COPD meet WISDOM eligibility criteria, and few patients are withdrawn from ICS.

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.

Longitudinal changes in forced expiratory volume in 1\xa0s in patients with eosinophilic chronic obstructive pulmonary disease

BackgroundData on changes in lung function in eosinophilic chronic obstructive pulmonary disease (COPD) are limited. We investigated the longitudinal changes in forced expiratory volume in 1 s (FEV1) and effects of inhaled corticosteroid (ICS) in Korean COPD patients.MethodsStable COPD patients in the Korean COPD subgroup study (KOCOSS) cohort, aged 40 years or older, were included and classified as eosinophilic and non-eosinophilic COPD based on blood counts of eosinophils (greater or lesser than 300 cells/μL). FEV1 changes were analyzed over a 3-year follow-up period.ResultsOf 627 patients who underwent spirometry at least twice during the follow up, 150 and 477 patients were classified as eosinophilic and non-eosinophilic, respectively. ICS-containing inhalers were prescribed to 40% of the patients in each group. Exacerbations were more frequent in the eosinophilic group (adjusted odds ratio: 1.49; 95% confidence interval: 1.10–2.03). An accelerated FEV1 decline was observed in the non-eosinophilic group (adjusted annual rate of FEV1 change: − 12.2 mL/y and − 19.4 mL/y for eosinophilic and non-eosinophilic groups, respectively). In eosinophilic COPD, the adjusted rate of annual FEV1 decline was not significant regardless of ICS therapy, but the decline rate was greater in ICS users (− 19.2 mL/y and − 4.5 mL/y, with and without ICS therapy, respectively).ConclusionsThe annual rate of decline in FEV1 was favorable in eosinophilic COPD compared to non-eosinophilic COPD, and ICS therapy had no beneficial effects on changes in FEV1.

Comparison of clinical characteristics between chronic bronchitis and non-chronic bronchitis in patients with chronic obstructive pulmonary disease

BackgroundChronic bronchitis (CB) is associated with poor outcomes in patients with chronic obstructive pulmonary disease. The aim of this study was to identify the characteristics that distinguish chronic bronchitis (CB) from non-CB. In addition, the features of mild CB versus severe CB were compared and a cut-off level was defined according to CAT1 and CAT2 scores.MethodsThis study was based on the Korea COPD Subgroup Study (KOCOSS) database, constructed in a multicenter COPD cohort study that recruited patients from 54 centers. CB was defined as CAT1 and CAT2 scores ≥ 3; severe CB was defined as CAT1 and CAT2 scores ≥ 4, while mild CB was defined as either a CAT1 or a CAT2 score < 4. Baseline characteristics, 1-year exacerbation rate, and 3-year FEV1 decline were compared in non-CB versus CB patients and in patients with mild CB versus severe CB.ResultsAmong the 2162 patients enrolled in this study, 497 (23%) had CB. These patients were more likely than non-CB patients to be current smokers; they also had higher symptom and depression/anxiety scores. Lung function tests showed lower FEV1, FEV1/FVC, and DLco values in CB patients. Among CB patients, 67.6% had mild disease. Symptom and depression/anxiety scores were worse in patients with severe CB than in patients with mild CB. There were no significant differences in the lung function tests of the two groups. Analysis of 1-year exacerbation rates in CB patients and non-CB patients revealed that patients with CB more frequently had moderate-to-severe exacerbations (OR = 1.46, p < 0.01). More severe exacerbation was also present in patients with severe CB than in patients with mild CB (OR = 2.52, p = 0.01). The difference in annual FEV1 decline rate did not significantly differ either between CB patients and non-CB patients or between patients with severe CB and patients with mild CB.ConclusionsCB patients had worse symptoms and lung function than non-CB patients; CB patients also had more frequent moderate-to-severe exacerbation. Patients with severe CB had higher symptom scores and more frequent severe exacerbation than did patients with mild CB.

Porphyromonas pasteri and Prevotella nanceiensis in the sputum microbiota are associated with increased decline in lung function in individuals with cystic fibrosis.

Although anaerobic bacteria exist in abundance in cystic fibrosis (CF) airways, their role in disease progression is poorly understood. We hypothesized that the presence and relative abundance of the most prevalent, live, anaerobic bacteria in sputum of adults with CF were associated with adverse clinical outcomes. This is the first study to prospectively investigate viable anaerobic bacteria present in the sputum microbiota and their relationship with long-term outcomes in adults with CF. We performed 16S rRNA analysis using a viability quantitative PCR technique on sputum samples obtained from a prospective cohort of 70 adults with CF and collected clinical data over an 8 year follow-up period. We examined the associations of the ten most abundant obligate anaerobic bacteria present in the sputum with annual rate of FEV1 change. The presence of Porphyromonas pasteri and Prevotella nanceiensis were associated with a greater annual rate of FEV1 change; −52.3 ml yr−1 (95 % CI-87.7;−16.9), –67.9 ml yr−1 (95 % CI-115.6;−20.1), respectively. Similarly, the relative abundance of these live organisms were associated with a greater annual rate of FEV1 decline of −3.7 ml yr−1 (95 % CI: −6.1 to −1.3, P=0.003) and −5.3 ml yr−1 (95 % CI: −8.7 to −1.9, P=0.002) for each log2 increment of abundance, respectively. The presence and relative abundance of certain anaerobes in the sputum of adults with CF are associated with a greater rate of long-term lung function decline. The pathogenicity of anaerobic bacteria in the CF airways should be confirmed with further longitudinal prospective studies with a larger cohort of participants.

Changing lung function and associated health-related quality-of-life: A five-year cohort study of Malawian adults.

BackgroundIn Sub-Saharan Africa cross-sectional studies report a high prevalence of abnormal lung function indicative of chronic respiratory disease. The natural history and health impact of this abnormal lung function in low-and middle-income countries is largely unknown.MethodsA cohort of 1481 adults representative of rural Chikwawa in Malawi were recruited in 2014 and followed-up in 2019. Respiratory symptoms and health-related quality of life (HRQoL) were quantified. Lung function was measured by spirometry.Findings1232 (83%) adults participated; spirometry was available for 1082 (73%). Mean (SD) age 49.5 (17.0) years, 278(23%) had ever smoked, and 724 (59%) were women. Forced expiratory volume in one second (FEV1) declined by 53.4 ml/year (95% CI: 49.0, 57.8) and forced vital capacity (FVC) by 45.2 ml/year (95% CI: 39.2, 50.5) . Chronic airflow obstruction increased from 9.5% (7.6, 11.6%) in 2014 to 17.5% (15.3, 19.9%) in 2019. There was no change in diagnosed asthma or in spirometry consistent with asthma or restriction. Rate of FEV1 decline was not associated with diagnosed Chronic obstructive pulmonary disease (COPD), asthma, or spirometry consistent with asthma, COPD, or restriction. HRQoL was adversely associated with respiratory symptoms (dyspnoea, wheeze, cough), previous tuberculosis, declining FEV1 and spirometry consistent with asthma or restriction. These differences exceeded the minimally important difference.InterpretationIn this cohort, the increasing prevalence of COPD is associated with the high rate of FEV1 decline and lung function deficits present before recruitment. Respiratory symptoms and sub-optimal lung function are independently associated with reduced HRQoL.

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.

Challenges and Pitfalls of Using Repeat Spirometry Recordings in Routine Primary Care Data to Measure FEV1 Decline in a COPD Population.

BackgroundElectronic healthcare records (EHR) are increasingly used in epidemiological studies but are often viewed as lacking quality compared to randomised control trials and prospective cohorts. Studies of patients with chronic obstructive pulmonary disease (COPD) often use the rate of forced expiratory volume in 1 second (FEV1) decline as an outcome; however, its definition and robustness in EHR have not been investigated. We aimed to investigate how the rate of FEV1 decline differs by the criteria used in an EHR database.MethodsClinical Practice Research Datalink and Hospital Episode Statistics were used. Patient populations were defined using 8 sets of criteria around repeated FEV1 measurements. At a minimum, patients had a diagnosis of COPD, were ≥35 years old, were current or ex-smokers, and had data recorded from 2004. FEV1 measurements recorded during follow-up were identified. Thereafter, eight populations were defined based on criteria around: i) the exclusion of patients or individual measurements with potential measurement error; ii) minimum number of FEV1 measurements; iii) minimum time interval between measurements; iv) specific timing of measurements; v) minimum follow-up time; and vi) the use of linked data. For each population, the rate of FEV1 decline was estimated using mixed linear regression.ResultsFor 7/8 patient populations, rates of FEV1 decline (age and sex adjusted) were similar and ranged from −18.7mL/year (95% CI −19.2 to −18.2) to −16.5mL/year (95% CI −17.3 to −15.7). Rates of FEV1 decline in populations that excluded patients with potential measurement error ranged from −79.4mL/year (95% CI −80.7 to −78.2) to −46.8mL/year (95% CI −47.6 to −46.0).ConclusionFEV1 decline remained similar in a COPD population regardless of number of FEV1 measurements, time intervals between measurements, follow-up period, exclusion of specific FEV1 measurements, and linkage to HES. However, exclusion of individuals with questionable data led to selection bias and faster rates of decline.

The Effects of Inhaled Airway Directed Pharmacotherapy on Decline in Lung Function Parameters Among Indigenous Australian Adults With and Without Underlying Airway Disease.

BackgroundThe trajectory of lung function decline among Indigenous patients with or without underlying chronic airway disease (COPD and concomitant bronchiectasis) and with use of inhaled pharmacotherapy, including inhaled corticosteroids (ICS), has not been reported in the past.MethodsAdult Indigenous Australian patients identified to have undergone at least two or more lung function tests (LFTs) between 2012 and 2020 were assessed for changes in the lung function parameters (LFPs) between the first and last recorded LFTs.ResultsOf the total 1350 patients identified to have undergone LFTs, 965 were assessed to fulfil session quality, 115 (n=58 females) were eligible to be included with two or more LFTs. Among the 115 patients, 49% showed radiological evidence of airway diseases, and 77% were on airway directed inhaled pharmacotherapy. Median time between LFTs was 1.5 years (IQR 0.86,5.85), with no significant differences in LFPs noted between first and last LFT. Overall rate of change (mL/year) showed considerable variation for FVC (median −37.55 mL/year [IQR −159.88,92.67]) and FEV1 (−18.74 mL/year [−102.49,71.44]) with minimal change in FEV1/FVC (0.00 ratio/year [−0.03,0.01]). When stratified by inhaled pharmacotherapy group, however, patients using ICS showed significantly greater rate of FEV1 decline (−48.64 mL/year [−110.18,62.5]) compared to those using pharmacotherapy with no ICS (15.46 mL/year [−73.5,74.62]) and those using no pharmacotherapy (−5.76 mL/year [−63.19,67.34]) (p=0.022). Additionally, a greater proportion of these patients reached the threshold for excessive FEV1 decline (64%) compared to those using pharmacotherapy without ICS (44%) and those using no pharmacotherapy (52%).ConclusionDecline in LFPs occurs commonly among adult Indigenous population, especially, excessive so among those using inhaled pharmacotherapy containing ICS.

Longitudinal effects of ivacaftor and medicine possession ratio in people with the Gly551Asp mutation: a 5-year study

IntroductionIvacaftor was the first therapy licensed to address the underlying defect in cystic fibrosis (CF). The improvements in lung function, nutritional status and pulmonary exacerbations in patients carrying a Gly551Asp...

Serum Th‐2 cytokines and FEV1 decline in WTC‐exposed firefighters: A 19‐year longitudinal study

BackgroundAccelerated‐FEV1‐decline, defined as rate of decline in FEV1 > 64 ml/year, is a risk factor for asthma and chronic obstructive pulmonary disease in World Trade Center (WTC)‐exposed firefighters. Accelerated‐FEV1‐decline in this cohort is associated with elevated blood eosinophil concentrations, a mediator of Th‐2 response. We hypothesized that an association exists between Th‐2 biomarkers and FEV1 decline rate in those with accelerated‐FEV1‐decline.MethodsSerum was drawn from Fire Department of the City of New York (FDNY) firefighters 1–6 months (early) (N = 816) and 12–13 years (late) (N = 983) after 9/11/2001. Th‐2 biomarkers IL‐4, IL‐13, and IL‐5 were assayed by multiplex Luminex. Individual FEV1 decline rates were calculated using spirometric measurements taken: (1) between 9/11/2001 and 9/10/2020 for the early biomarker group and (2) between late measurement date and 9/10/2020 for the late biomarker group. Associations of early and late Th‐2 biomarkers with subsequent FEV1 decline rates were analyzed using multivariable linear regression controlling for demographics, smoking status, and other potential confounders.ResultsIn WTC‐exposed firefighters with accelerated‐FEV1‐decline, IL‐4, IL‐13, and IL‐5 measured 1–6 months post‐9/11/2001 were associated with greater FEV1 decline ml/year between 9/11/2001 and 9/10/2020 (−2.9 ± 1.4 ml/year per IL‐4 doubling; −8.4 ± 1.2 ml/year per IL‐13 doubling; −7.9 ± 1.3 ml/year per IL‐5 doubling). Among late measured Th‐2 biomarkers, only IL‐4 was associated with subsequent FEV1 decline rate (−4.0 ± 1.6 ml/year per IL‐4 doubling).ConclusionsIn WTC‐exposed firefighters with accelerated‐FEV1‐decline, elevated serum IL‐4 measured both 1–6 months and 12–13 years after 9/11 is associated with greater FEV1 decline/year. Drugs targeting the IL‐4 pathway may improve lung function in this high‐risk subgroup.

Firefighters and COVID-19: An Occupational Health Perspective.

Firefighters and COVID-19: An Occupational Health Perspective.

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...

Extracorporeal photopheresis to attenuate decline in lung function due to refractory obstructive allograft dysfunction.

BackgroundThis study was designed to prospectively evaluate the efficacy of extracorporeal photopheresis (ECP) to attenuate the rate of decline of FEV1 in lung transplant recipients with refractory bronchiolitis obliterans. Due to an observed higher than expected early mortality, a preliminary analysis was performed.Study Design and MethodsSubjects from 10 lung transplant centres were assigned to ECP treatment or to observation based on spirometric criteria, with potential crossover for those under observation. The primary endpoint of this study was to assess response to ECP (i.e., greater than a 50% decrease in the rate of FEV1 decline) before and 6 months after initiation of ECP. Mortality was also evaluated 6 and 12 months after enrolment as a secondary endpoint.ResultsOf 44 enrolled subjects, 31 were assigned to ECP treatment while 13 were initially assigned to observation on a non‐random basis using specific spirometric inclusion criteria (seven of the observation patients subsequently crossed over to receive ECP). Of evaluable patients, 95% of patients initially assigned to treatment responded to ECP with rates of FEV1 decline that were reduced by 93% in evaluable ECP‐treated patients. Mortality rates (percentages) at 6 and 12 months after enrolment was 32% and 41%, respectively. The most common (92%) primary cause of death was respiratory or graft failure. Significantly (p = 0.002) higher rates of FEV1 decline were observed in the non‐survivors (−212 ± 177 ml/month) when compared to the survivors (−95 ± 117 ml/month) 12 months after enrolment. In addition, 18 patients with bronchiolitis obliterans syndrome (BOS) diagnosis within 6 months of enrolment had lost 38% of their baseline lung function at BOS diagnosis and 50% of their lung function at enrolment.ConclusionsThese analyses suggest that earlier detection and treatment of BOS should be considered to appreciate improved outcomes with ECP.

Real-world use of ivacaftor in Canada: A retrospective analysis using the Canadian Cystic Fibrosis Registry

Background: Ivacaftor is a CFTR potentiator with demonstrated efficacy in clinical trials and has been rapidly adopted within the CF community. Given the uptake of ivacaftor in eligible people, identifying a comparator group not on modulators to measure effectiveness is difficult. We evaluated health outcomes in individuals with G551D and non-G551D genotypes on ivacaftor using real-world longitudinal data. Methods: This population-based observational study compared clinical trajectories pre-post ivacaftor using the Canadian CF Registry from 2006 to 01–01 through 2018–12–31. Piece-wise linear mixed-effects models were used to compare lung function, nutritional status, pulmonary exacerbations, and Pseudomonas colonization pre- and post-ivacaftor. Multivariable models were used to adjust for confounding factors. Results: Forced expiratory volume in 1 second (FEV1) increased significantly by 5.7 percent predicted (95% confidence interval (CI) 3.9, 7.5; p<0.001) after initiation of ivacaftor. FEV1 decline rate was attenuated to -0.30% (95% CI -0.9, 0.29; p = 0.32) predicted/year post-ivacaftor, compared with -0.75% (95% CI -1.12, -0.37; p<0.001) predicted/year pre-ivacaftor, although this difference did not reach statistical significance. BMI percentiles also increased post-ivacaftor (6.57 percentiles, 95% CI 3.91, 9.24; p<0.001). Pulmonary exacerbations showed a nonsignificant reduction of 18% (RR 0.82, 95% CI 0.61, 1.11; p = 0.19) and the odds of a positive sputum culture for Pseudomonas aeruginosa decreased in the post-ivacaftor period (odds ratio 0.44, 95% CI 0.30, 0.63; p<0.001). Conclusions: This real-world, observational study demonstrated improvement in health outcomes in a broad population of people with CF. Additional studies are needed to evaluate the impact of ivacaftor on quality of life and survival.

Outcomes Following ATG Therapy for Chronic Lung Allograft Dysfunction.

Background.Chronic lung allograft dysfunction (CLAD) is the major factor limiting survival post lung transplantation (LTx) with limited effective therapeutic options. We report our 12-y experience of antithymocyte globulin (ATG) as second-line CLAD therapy.Methods.Clinical and lung function data were collected on LTx patients receiving ATG. Rate of FEV1 decline (mL/d) was calculated before and after ATG. Partial response to ATG was defined by rate of FEV1 decline improving 20%. Complete response was defined by an absolute improvement or stability in baseline FEV1.Results.Seventy-six patients received ATG for CLAD. Of these, 5 patients who had a clinical diagnosis of antibody-mediated rejection and were treated with plasmapheresis before or after ATG were excluded from analysis. Sixteen (23%) were complete responders, 29 (40%) were partial responders, and 26 (37%) did not respond. Those with CLAD stage 2 or 3 and younger age were more likely to respond. Partial responders had a 65% lower risk of death or retransplant (HR, 0.35; P = 0.003), whereas complete responders reduced their risk by 70% (HR, 0.30; P = 0.006).Conclusions.ATG appears to stabilize or attenuate lung function decline in CLAD, which may lead to improved retransplant-free survival. Although certain predictors of response have been identified in this large single-center review, these findings need to be confirmed by a multicenter randomized-controlled trial to determine predictors of response to ATG for CLAD.

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.

Pre-COVID-19 lung function and other risk factors for severe COVID-19 in first responders.

Risk factors for #COVID19 infection and severe disease (hospitalisation or death) in NYC first responders: greater pre-pandemic rate of FEV1 decline is associated with severe COVID-19, as is emergency medical service work versus firefighting https://bit.ly/3nZPuZY

Accelerated FEV1 decline and risk of cardiovascular disease and mortality in a primary care population of COPD patients.

Accelerated lung function decline has been associated with increased risk of cardiovascular disease (CVD) in a general population, but little is known about this association in chronic obstructive pulmonary disease (COPD). We investigated the association between accelerated lung function decline and CVD outcomes and mortality in a primary care COPD population.COPD patients without a history of CVD were identified in the Clinical Practice Research Datalink (CPRD)-GOLD primary care dataset (n=36 382). Accelerated decline in forced expiratory volume in 1 s (FEV1) was defined using the fastest quartile of the COPD population's decline. A Cox regression was used to assess the association between baseline accelerated FEV1 decline and a composite CVD outcome over follow-up (myocardial infarction, ischaemic stroke, heart failure, atrial fibrillation, coronary artery disease and CVD mortality). The model was adjusted for age, sex, smoking status, body mass index, history of asthma, hypertension, diabetes, statin use, Modified Medical Research Council (mMRC) dyspnoea score, exacerbation frequency and baseline FEV1 % predicted.6110 COPD patients (16.8%) had a CVD event during follow-up; median length of follow-up was 3.6 years (interquartile range (IQR) 1.7–6.1 years). Median rate of FEV1 decline was –19.4 mL·year−1 (IQR –40.5–1.9); 9095 patients (25%) had accelerated FEV1 decline (> –40.5 mL·year−1), 27 287 (75%) did not (≤ –40.5 mL·year−1). Risk of CVD and mortality was similar between patients with and without accelerated FEV1 decline (HRadj 0.98, 95% CI 0.90–1.06). Corresponding risk estimates were 0.99 (95% CI 0.83–1.20) for heart failure, 0.89 (95% CI 0.70–1.12) for myocardial infarction, 1.01 (95% CI 0.82–1.23) for stroke, 0.97 (95% CI 0.81–1.15) for atrial fibrillation, 1.02 (95% CI 0.87–1.19) for coronary artery disease and 0.94 (95% CI 0.71–1.25) for CVD mortality. Rather, risk of CVD was associated with a mMRC score ≤2 and two or more exacerbations in the year prior.CVD outcomes and mortality were associated with exacerbation frequency and severity and increased mMRC dyspnoea score but not with accelerated FEV1 decline.

Pregnancy in lymphangioleiomyomatosis: clinical and lung function outcomes in two national cohorts

Pregnancy in women with lymphangioleiomyomatosis (LAM) has been associated with increased complications and worsening lung function although objective data to advise patients are not available. We assessed lung function and...