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Adverse health consequences in COPD patients with rapid decline in FEV1--evidence from the UPLIFT trial.

ABSTRACT: The rate of decline in forced expiratory volume in 1 second (FEV1) is representative of the natural history of COPD. Sparse information exists regarding the associations between the magnitude of annualised loss of FEV1 with other endpoints.Retrospective analysis of UPLIFT® trial (four-year, randomized, double-blind, placebo-controlled trial of tiotropium 18 ?g daily in chronic obstructive pulmonary disease [COPD], n = 5993). Decline of FEV1 was analysed with random co-efficient regression. Patients were categorised according to quartiles based on the rate of decline (RoD) in post-bronchodilator FEV1. The St George's Respiratory Questionnaire (SGRQ) total score, exacerbations and mortality were assessed within each quartile.Mean (standard error [SE]) post-bronchodilator FEV1 increased in the first quartile (Q1) by 37 (1) mL/year. The other quartiles showed annualised declines in FEV1 (mL/year) as follows: Q2 = 24 (1), Q3 = 59 (1) and Q4 = 125 (2). Age, gender, respiratory medication use at baseline and SGRQ did not distinguish groups. The patient subgroup with the largest RoD had less severe lung disease at baseline and contained a higher proportion of current smokers. The percentage of patients with ? 1 exacerbation showed a minimal difference from the lowest to the largest RoD, but exacerbation rates increased with increasing RoD. The highest proportion of patients with ? 1 hospitalised exacerbation was in Q4 (Q1 = 19.5% [tiotropium], 26% [control]; Q4 = 33.8% [tiotropium] and 33.1% [control]). Time to first exacerbation and hospitalised exacerbation was shorter with increasing RoD. Rate of decline in SGRQ increased in direct proportion to each quartile. The group with the largest RoD had the highest mortality.Patients can be grouped into different RoD quartiles with the observation of different clinical outcomes indicating that specific (or more aggressive) approaches to management may be needed.ClinicalTrials.gov number, NCT00144339.

SUBMITTER: Kesten S

PROVIDER: S-EPMC3190346 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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Adverse health consequences in COPD patients with rapid decline in FEV1--evidence from the UPLIFT trial.

Kesten Steven S Celli Bartolome B Decramer Marc M Liu Dacheng D Tashkin Donald D

Respiratory research 20110928

<h4>Background</h4>The rate of decline in forced expiratory volume in 1 second (FEV1) is representative of the natural history of COPD. Sparse information exists regarding the associations between the magnitude of annualised loss of FEV1 with other endpoints.<h4>Methods</h4>Retrospective analysis of UPLIFT® trial (four-year, randomized, double-blind, placebo-controlled trial of tiotropium 18 μg daily in chronic obstructive pulmonary disease [COPD], n = 5993). Decline of FEV1 was analysed with ra ...[more]

PMID: 21955733

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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:BackgroundThe rate of forced expiratory volume in 1 second (FEV1) decline ("beta") is a marker of chronic obstructive pulmonary disease risk. The reduction in beta after quitting smoking is an upper limit for the reduction achievable from switching to novel nicotine delivery products. We review available evidence to estimate this reduction and quantify the relationship of smoking to beta.MethodsStudies were identified, in healthy individuals or patients with respiratory disease, that provided data on beta over at least 2 years of follow-up, separately for those who gave up smoking and other smoking groups. Publications to June 2010 were considered. Independent beta estimates were derived for four main smoking groups: never smokers, ex-smokers (before baseline), quitters (during follow-up) and continuing smokers. Unweighted and inverse variance-weighted regression analyses compared betas in the smoking groups, and in continuing smokers by amount smoked, and estimated whether beta or beta differences between smoking groups varied by age, sex and other factors.ResultsForty-seven studies had relevant data, 28 for both sexes and 19 for males. Sixteen studies started before 1970. Mean follow-up was 11 years. On the basis of weighted analysis of 303 betas for the four smoking groups, never smokers had a beta 10.8 mL/yr (95% confidence interval (CI), 8.9 to 12.8) less than continuing smokers. Betas for ex-smokers were 12.4 mL/yr (95% CI, 10.1 to 14.7) less than for continuing smokers, and for quitters, 8.5 mL/yr (95% CI, 5.6 to 11.4) less. These betas were similar to that for never smokers. In continuing smokers, beta increased 0.33 mL/yr per cigarette/day. Beta differences between continuing smokers and those who gave up were greater in patients with respiratory disease or with reduced baseline lung function, but were not clearly related to age or sex.ConclusionThe available data have numerous limitations, but clearly show that continuing smokers have a beta that is dose-related and over 10 mL/yr greater than in never smokers, ex-smokers or quitters. The greater decline in those with respiratory disease or reduced lung function is consistent with some smokers having a more rapid rate of FEV1 decline. These results help in designing studies comparing continuing smokers of conventional cigarettes and switchers to novel products.

Project description:BackgroundReduced FEV1 is known to predict increased lung cancer risk, but previous reviews are limited. To quantify this relationship more precisely, and study heterogeneity, we derived estimates of β for the relationship RR(diff) = exp(βdiff), where diff is the reduction in FEV1 expressed as a percentage of predicted (FEV1%P) and RR(diff) the associated relative risk. We used results reported directly as β, and as grouped levels of RR in terms of FEV1%P and of associated measures (e.g. FEV1/FVC).MethodsPapers describing cohort studies involving at least three years follow-up which recorded FEV1 at baseline and presented results relating lung cancer to FEV1 or associated measures were sought from Medline and other sources. Data were recorded on study design and quality and, for each data block identified, on details of the results, including population characteristics, adjustment factors, lung function measure, and analysis type. Regression estimates were converted to β estimates where appropriate. For results reported by grouped levels, we used the NHANES III dataset to estimate mean FEV1%P values for each level, regardless of the measure used, then derived β using regression analysis which accounted for non-independence of the RR estimates. Goodness-of-fit was tested by comparing observed and predicted lung cancer cases for each level. Inverse-variance weighted meta-analysis allowed derivation of overall β estimates and testing for heterogeneity by factors including sex, age, location, timing, duration, study quality, smoking adjustment, measure of FEV1 reported, and inverse-variance weight of β.ResultsThirty-three publications satisfying the inclusion/exclusion criteria were identified, seven being rejected as not allowing estimation of β. The remaining 26 described 22 distinct studies, from which 32 independent β estimates were derived. Goodness-of-fit was satisfactory, and exp(β), the RR increase per one unit FEV1%P decrease, was estimated as 1.019 (95%CI 1.016-1.021). The estimates were quite consistent (I2 =29.6%). Mean age was the only independent source of heterogeneity, exp(β) being higher for age <50 years (1.024, 1.020-1.028).ConclusionsAlthough the source papers present results in various ways, complicating meta-analysis, they are very consistent. A decrease in FEV1%P of 10% is associated with a 20% (95%CI 17%-23%) increase in lung cancer risk.

Project description:BACKGROUND:Forced expiratory volume in one second (FEV1) characterizes the pathophysiology of COPD and different trajectories of FEV1 decline have been observed in patients with COPD (e.g. gradual or episodic). There is limited information about the development of patient-reported health-related quality of life (HRQL) over the full range of the natural history of COPD. We examined the longitudinal association between change in FEV1 and change in disease-specific and generic HRQL. METHODS:We analysed data of 1734 patients with COPD participating in the COSYCONET cohort with up to 3 years of follow-up. Patients completed the Saint George's Respiratory Questionnaire (SGRQ) and the EQ-5D Visual Analog Scale (EQ VAS). Change score models were used to investigate the relationship between HRQL and FEV1 and to calculate mean changes in HRQL per FEV1 change categories [decrease (? -?100?ml), no change, increase (? 100?ml)] after 3 years. Applying hierarchical linear models (HLM), we estimated the cross-sectional between-subject difference and the longitudinal within-subject change of HRQL as related to a FEV1 difference or change. RESULTS:We observed a statistically significant deterioration in SGRQ (total score?+?1.3?units) after 3 years, which was completely driven by the activity component (+?4?units). No significant change was found for the generic EQ VAS. Over the same period, 58% of patients experienced a decrease in FEV1, 28% were recorded as no change in FEV1, and 13% experienced an increase. The relationship between HRQL and FEV1 was found to be approximately linear with decrease in FEV1 being statistically significantly associated with a deterioration in SGRQ (+?3.20?units). Increase in FEV1 was associated with improvements in SGRQ (-?3.81?units). The associations between change in FEV1 and the EQ VAS were similar. Results of the HLMs were consistent and highly statistically significant, indicating cross-sectional and longitudinal associations. The largest estimates were found for the association between FEV1 and the SGRQ activity domain. CONCLUSIONS:Difference and change in FEV1 over time correlate with difference and change in disease-specific and generic HRQL. We conclude, that deterioration of HRQL should induce timely re-examination of physical status and lung function and possibly reassessment of therapeutic regimes. TRIAL REGISTRATION:NCT01245933. Date of registration: 18 November 2010.

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.

Dataset Information

Adverse health consequences in COPD patients with rapid decline in FEV1--evidence from the UPLIFT trial.

Publications

Adverse health consequences in COPD patients with rapid decline in FEV1--evidence from the UPLIFT trial.

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