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Annual rates of change in pre- vs. post-bronchodilator FEV1 and FVC over 4 years in moderate to very severe COPD.

ABSTRACT: While the slope of decline in FEV1 has traditionally been calculated from the post- rather than the pre-bronchodilator measurement in COPD interventional trials, it is not clear whether and to what extent these two slopes differ in symptomatic patients with COPD. Therefore, we used data from the 4-year UPLIFT trial of tiotropium 18 mcg QD vs. placebo to compare annual rates of change in pre- vs. post-bronchodilator FEV1 in 5041 patients with moderate to very severe COPD (mean FEV1 48% pred) in whom the post-bronchodilator FEV1 was measured after 4 inhalations of two different classes of short-acting inhaled bronchodilators at baseline and 1 month and every 6 months post-randomization over 4 years. Linear mixed effects models were used to estimate annual rates of decline in FEV1 and FVC pre- and post-bronchodilator in each treatment group separately, after adjusting for height, gender, smoking status, baseline % predicted FEV1 or FVC, and baseline acute % improvement in lung function. The slopes of the post-bronchodilator FEV1 and FVC were significantly steeper than the pre-bronchodilator slopes regardless of treatment arm (p < 0.001), while the estimated variances of the slopes were similar. Post-bronchodilator increases in FEV1 and FVC diminished progressively and significantly (p < 0.0001) over the 4-year trial, suggesting a possible explanation for the significant differences between the pre- and post-bronchodilator slopes. While the reasons for these differences are not completely clear, they are important to consider when assessing treatment effects on rates of decline in FEV1 and FVC.

SUBMITTER: Tashkin DP

PROVIDER: S-EPMC4284059 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Annual rates of change in pre- vs. post-bronchodilator FEV1 and FVC over 4 years in moderate to very severe COPD.

Tashkin Donald P DP Li Ning N Halpin David D Kleerup Eric E Decramer Marc M Celli Bartolome B Elashoff Robert R

Respiratory medicine 20130822 12

While the slope of decline in FEV1 has traditionally been calculated from the post- rather than the pre-bronchodilator measurement in COPD interventional trials, it is not clear whether and to what extent these two slopes differ in symptomatic patients with COPD. Therefore, we used data from the 4-year UPLIFT trial of tiotropium 18 mcg QD vs. placebo to compare annual rates of change in pre- vs. post-bronchodilator FEV1 in 5041 patients with moderate to very severe COPD (mean FEV1 48% pred) in w ...[more]

PMID: 23972968

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Project description:ImportanceAccording to numerous current guidelines, the diagnosis of chronic obstructive pulmonary disease (COPD) requires a ratio of the forced expiratory volume in the first second to the forced vital capacity (FEV1:FVC) of less than 0.70, yet this fixed threshold is based on expert opinion and remains controversial.ObjectiveTo determine the discriminative accuracy of various FEV1:FVC fixed thresholds for predicting COPD-related hospitalization and mortality.Design, setting, and participantsThe National Heart, Lung, and Blood Institute (NHLBI) Pooled Cohorts Study harmonized and pooled data from 4 US general population-based cohorts (Atherosclerosis Risk in Communities Study; Cardiovascular Health Study; Health, Aging, and Body Composition Study; and Multi-Ethnic Study of Atherosclerosis). Participants aged 45 to 102 years were enrolled from 1987 to 2000 and received follow-up longitudinally through 2016.ExposuresPresence of airflow obstruction, which was defined by a baseline FEV1:FVC less than a range of fixed thresholds (0.75 to 0.65) or less than the lower limit of normal as defined by Global Lung Initiative reference equations (LLN).Main outcomes and measuresThe primary outcome was a composite of COPD hospitalization and COPD-related mortality, defined by adjudication or administrative criteria. The optimal fixed FEV1:FVC threshold was defined by the best discrimination for these COPD-related events as indexed using the Harrell C statistic from unadjusted Cox proportional hazards models. Differences in C statistics were compared with respect to less than 0.70 and less than LLN thresholds using a nonparametric approach.ResultsAmong 24 207 adults in the pooled cohort (mean [SD] age at enrollment, 63 [10.5] years; 12 990 [54%] women; 16 794 [69%] non-Hispanic white; 15 181 [63%] ever smokers), complete follow-up was available for 11 077 (77%) at 15 years. During a median follow-up of 15 years, 3925 participants experienced COPD-related events over 340 757 person-years of follow-up (incidence density rate, 11.5 per 1000 person-years), including 3563 COPD-related hospitalizations and 447 COPD-related deaths. With respect to discrimination of COPD-related events, the optimal fixed threshold (0.71; C statistic for optimal fixed threshold, 0.696) was not significantly different from the 0.70 threshold (difference, 0.001 [95% CI, -0.002 to 0.004]) but was more accurate than the LLN threshold (difference, 0.034 [95% CI, 0.028 to 0.041]). The 0.70 threshold provided optimal discrimination in the subgroup analysis of ever smokers and in adjusted models.Conclusions and relevanceDefining airflow obstruction as FEV1:FVC less than 0.70 provided discrimination of COPD-related hospitalization and mortality that was not significantly different or was more accurate than other fixed thresholds and the LLN. These results support the use of FEV1:FVC less than 0.70 to identify individuals at risk of clinically significant COPD.

Project description:BackgroundThe impact of interventions on the progressive course of COPD is currently assessed by the slope of the annual decline in FEV? determined from serial measurements of the post-, in preference to the pre-, bronchodilator FEV?. We therefore compared the yearly slope and the variability of the slope of the pre- versus the post-bronchodilator FEV? in men and women with mild to moderate COPD who participated in the 5-year Lung Health Study (LHS).MethodsData were analyzed from 4484 of the 5887 LHS participants who had measurements of pre- and post-bronchodilator FEV? at baseline (screening visit 2) and all five annual visits. The annual rate of decline in FEV? (±SE) measured pre- and post-bronchodilator from the first to the fifth annual visit was estimated separately using a random coefficient model adjusted for relevant covariates. Analyses were performed separately within each of the three randomized intervention groups. In addition, individual rates of decline in pre- and post-bronchodilator FEV? were also determined for each participant. Furthermore, sample sizes were estimated for determining the significance of differences in slopes of decline between different interventions using pre- versus post-bronchodilator measurements.ResultsWithin each intervention group, mean adjusted and unadjusted slope estimates were slightly higher for the pre- than the post-bronchodilator FEV? (range of differences 2.6-5.2 ml/yr) and the standard errors around these estimates were only minimally higher for the pre- versus the post-bronchodilator FEV? (range 0.05-0.11 ml/yr). Conversely, the standard deviations of the mean FEV? determined at each annual visit were consistently slightly higher (range of differences 0.011 to 0.035 L) for the post- compared to the pre-bronchodilator FEV?. Within each group, the proportion of individual participants with a statistically significant slope was similar (varying by only 1.4 to 2.7%) comparing the estimates from the pre- versus the post-bronchodilator FEV?. However, sample size estimates were slightly higher when the pre- compared to the post-bronchodilator value was used to determine the significance of specified differences in slopes between interventions.ConclusionSerial measurements of the pre-bronchodilator FEV? are generally sufficient for comparing the impact of different interventions on the annual rate of change in FEV?.

Project description:Few studies have investigated the significance of decreased FEV(1) in non-COPD, nonasthmatic healthy subjects. We hypothesized that a lower FEV(1) in these subjects is a potential marker of an increased susceptibility to obstructive lung disease such as asthma and COPD. This was a cross-sectional analysis of 1505 Japanese adults. We divided the population of healthy adults with no respiratory diseases whose FEV(1)/FVC ratio was ? 70% (n = 1369) into 2 groups according to their prebronchodilator FEV(1) (% predicted) measurements: < 80% (n = 217) and ? 80% (n = 1152). We compared clinical data - including gender, age, smoking habits, total IgE levels, and annual decline of FEV(1) - between these 2 groups. In addition, as our group recently found that TSLP variants are associated with asthma and reduced lung function, we assessed whether TSLP single nucleotide polymorphisms (SNPs) were associated with baseline lung function in non-COPD, nonasthmatic healthy subjects (n = 1368). Although about half of the subjects with lower FEV(1) had never smoked, smoking was the main risk factor for the decreased FEV(1) in non-COPD, nonasthmatic subjects. However, the subjects with lower FEV(1) had a significantly higher annual decline in FEV(1) independent of smoking status. Airflow obstruction was associated with increased levels of total serum IgE (P = 0.029) and with 2 functional TSLP SNPs (corrected P = 0.027-0.058 for FEV(1)% predicted, corrected P = 0.015-0.033 for FEV(1)/FVC). This study highlights the importance of early recognition of a decreased FEV(1) in healthy subjects without evident pulmonary diseases because it predicts a rapid decline in FEV(1) irrespective of smoking status. Our series of studies identified TSLP variants as a potential susceptibility locus to asthma and to lower lung function in non-COPD, nonasthmatic healthy subjects, which may support the contention that genetic determinants of lung function influence susceptibility to asthma.

Project description:ObjectiveGrowing evidence suggests that endothelial injury is involved in the pathophysiology of chronic obstructive pulmonary disease (COPD). Circulating endothelial microparticles (EMPs) increase in patients with COPD because of the presence of endothelial injury. We examined the relationship between EMP number and changes in forced expiratory volume in 1 s (FEV1) in patients with COPD.DesignProspective study.SettingOne hospital in Japan.ParticipantsA total 48 outpatients with stable COPD coming to the hospital from September 2010 to September 2011.Primary and secondary outcomes measuredBlood samples were collected and vascular endothelial (VE)-cadherin EMPs (CD144+ EMPs), E-selectin EMPs (CD62E+ EMPs) and platelet endothelial cell adhesion molecule EMPs (CD31+/CD41- EMPs) were measured using fluorescence-activated cell sorting. Annual FEV1 changes were evaluated using FEV1 data acquired a year before and a year after sample collection.ResultsThe number of E-selectin and VE-cadherin EMPs showed significant negative correlations with annual FEV1 changes (rs=-0.65, p<0.001, rs=-0.43, p=0.003, respectively). Leucocyte counts tended to be correlated with annual FEV1 changes, but this correlation was not significant (rs=-0.28, p=0.057). There were significant differences in annual FEV1 changes between with and without history of frequent exacerbation (p=0.006), and among Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages (p=0.009). Multiple linear regression analysis revealed E-selectin EMP to be the only significant parameter associated with annual FEV1 changes, independent of VE-cadherin EMP, GOLD stages, leucocyte counts, and history of frequent exacerbation. Receiver operating characteristic curves showed the optimum E-selectin EMP cut-off level for prediction of rapid FEV1 decline (>66 mL/year) to be 153.0/µL (areas under curve 0.78 (95% CI 0.60 to 0.89); sensitivity, 67%; specificity, 81%).ConclusionsThe high E-selectin EMP levels in stable patients with COPD are predictive of rapid FEV1 decline.Trial registration numberUMIN000005168.

Project description:BACKGROUND:Adipose tissue produces leptin, which is pro-inflammatory, and adiponectin, which has anti-inflammatory properties. Participants with chronic spinal cord injury (SCI) have increased body fat and are at increased risk for respiratory illness. OBJECTIVE:To assess the associations between leptin and adiponectin with pulmonary function in a chronic SCI cohort. DESIGN:Cross-sectional study. SETTING:Veterans Affairs Medical Center. PARTICIPANTS:A total of 285 participants (237 men and 48 women) with chronic SCI with mean (standard deviation) injury duration 17.8 (13.2) years from the VA Boston and the community participating in an epidemiologic study assessing factors associated with respiratory health. METHODS:Participants (24.6% cervical American Spinal Injury Association Impairment Scale (AIS) level A, B, and C; 33.6% other AIS A, B, and C; 41.8% AIS D) provided a blood sample, completed a respiratory health questionnaire, and underwent spirometry. Linear regression methods were used to assess cross-sectional associations between plasma leptin and adiponectin with spirometric measures of pulmonary function adjusted for age, race, gender, and height. Level and severity of SCI, mobility mode, body mass index, smoking, chronic obstructive pulmonary disease, asthma, chest injury history, laboratory batch, and other potential confounders were also considered. MAIN OUTCOME MEASUREMENTS:forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC. RESULTS:There was a statistically significant inverse relationship between plasma leptin assessed in quartiles or as a continuous covariate with FEV1 and FVC. In fully adjusted models, each interquartile range (16,214 pg/mL) increase in leptin was associated with a significant decrease in FEV1 (-93.1 mL; 95% confidence interval = -166.2, -20.0) and decrease in FVC (-130.7 mL; 95% confidence interval = -219.4, -42.0). There were no significant associations between leptin and FEV1/FVC or between plasma adiponectin with FEV1, FVC, or FEV1/FVC. CONCLUSION:Plasma leptin in individuals with chronic SCI is inversely associated with FEV1 and FVC, independently of SCI level and severity and other covariates. This finding suggests that plasma leptin may contribute to reduced pulmonary function in chronic SCI. LEVEL OF EVIDENCE:II.

Dataset Information

Annual rates of change in pre- vs. post-bronchodilator FEV1 and FVC over 4 years in moderate to very severe COPD.

Publications

Annual rates of change in pre- vs. post-bronchodilator FEV1 and FVC over 4 years in moderate to very severe COPD.

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