FEV1 is a better predictor of mortality than FVC: the PLATINO cohort study.
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ABSTRACT: Objective
To determine whether the presence of chronic obstructive lung disease (COPD) and reduction of lung function parameters were predictors of mortality in a cohort.Materials/patients and methods
Population based cohorts were followed in Montevideo, Santiago and Sao Paulo during 5, 6 and 9 years, respectively. Outcomes included all-cause, cardiovascular, respiratory and cancer mortality; exposures were COPD, forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). Cox regression was used for analyses. Sensitivity, specificity, positive and negative predictive values, receiver operator characteristics curves and Youden's index were calculated.Results
Main causes of death were cardiovascular, respiratory and cancer. Baseline COPD was associated with overall mortality (HR?=?1.43 for FEV1/FVC
SUBMITTER: Menezes AM
PROVIDER: S-EPMC4186841 | biostudies-literature | 2014
REPOSITORIES: biostudies-literature
Publications
FEV1 is a better predictor of mortality than FVC: the PLATINO cohort study.
Menezes Ana Maria B AM Pérez-Padilla Rogelio R Wehrmeister Fernando César FC Lopez-Varela Maria Victorina MV Muiño Adriana A Valdivia Gonzalo G Lisboa Carmen C Jardim José Roberto B JR de Oca Maria Montes MM Talamo Carlos C Bielemann Renata R Gazzotti Mariana M Laurenti Ruy R Celli Bartolomé B Victora Cesar G CG
PloS one 20141006 10
<h4>Objective</h4>To determine whether the presence of chronic obstructive lung disease (COPD) and reduction of lung function parameters were predictors of mortality in a cohort.<h4>Materials/patients and methods</h4>Population based cohorts were followed in Montevideo, Santiago and Sao Paulo during 5, 6 and 9 years, respectively. Outcomes included all-cause, cardiovascular, respiratory and cancer mortality; exposures were COPD, forced expiratory volume in one second (FEV1) and forced vital capa ...[more]
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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.
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Project description:BACKGROUND:Systemic inflammation has been associated with reduced pulmonary function in individuals with and without chronic medical conditions. Individuals with chronic spinal cord injury (SCI) have clinical characteristics that promote systemic inflammation and also have reduced pulmonary function. We sought to assess the associations between biomarkers of systemic inflammation with pulmonary function in a chronic SCI cohort, adjusting for other potential confounding factors. METHODS:Participants (n = 311) provided a blood sample, completed a respiratory health questionnaire, and underwent spirometry. Linear regression methods were used to assess cross-sectional associations between plasma C-reactive protein (CRP) and interleukin-6 (IL-6) with forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC. RESULTS:There were statistically significant inverse relationships between plasma CRP and IL-6 assessed in quartiles or continuously with FEV1 and FVC. In fully adjusted models, each interquartile range (5.91 mg/L) increase in CRP was associated with a significant decrease in FEV1 (-55.85 ml; 95% CI: -89.21, -22.49) and decrease in FVC (-65.50 ml; 95% CI: -106.61, -24.60). There were similar significant findings for IL-6. There were no statistically significant associations observed with FEV1/FVC. CONCLUSION:Plasma CRP and IL-6 in individuals with chronic SCI are inversely associated with FEV1 and FVC, independent of SCI level and severity of injury, BMI, and other covariates. This finding suggests that systemic inflammation associated with chronic SCI may contribute to reduced pulmonary function.
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Project description:QUESTION: A 6-second spirometry test is easier than full exhalations. We compared the reliability of the ratio of the Forced expiratory volume in 1 second/Forced expiratory volume in 6 seconds (FEV1/FEV6) to the ratio of the FEV1/Forced vital capacity (FEV1/FVC) for the detection of airway obstruction. METHODS: The PLATINO population-based survey in individuals aged 40 years and over designed to estimate the prevalence of post-Bronchodilator airway obstruction repeated for the same study participants after 5-9 years in three Latin-American cities. RESULTS: Using the FEV1/FVC<Lower limit of normal (LLN) index, COPD prevalence apparently changed from 9.8 to 13.2% in Montevideo, from 9.7 to 6.0% in São Paulo and from 8.5 to 6.6% in Santiago, despite only slight declines in smoking prevalence (from 30.8% to 24.3%). These changes were associated with differences in Forced expiratory time (FET) between the two surveys. In contrast, by using the FEV1/FEV6 to define airway obstruction, the changes in prevalence were smaller: 9.7 to 10.6% in Montevideo, 8.6 to 9.0% in São Paulo, and 7.5 to 7.9% in Santiago. Changes in the prevalence of COPD with criteria based on FEV1/FVC correlated strongly with changes in the FET of the tests (R(2) 0.92) unlike the prevalence based on a low FEV1/FEV6 (R(2)?=0.40). CONCLUSION: The FEV1/FEV6 is a more reliable index than FEV1/FVC because FVC varies with the duration of the forced exhalation. Reporting FET and FEV1/FEV6<LLN helps to understand differences in prevalence of COPD obtained from FEV1/FVC-derived indices.
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Project description:African Americans are admixed with genetic contributions from European and African ancestral populations. Admixture mapping leverages this information to map genes influencing differential disease risk across populations. We performed admixture and association mapping in 3,300 African American current or former smokers from the COPDGene Study. We analyzed estimated local ancestry and SNP genotype information to identify regions associated with FEV1 /FVC, the ratio of forced expiratory volume in one second to forced vital capacity, measured by spirometry performed after bronchodilator administration. Global African ancestry inversely associated with FEV1 /FVC (P = 0.035). Genome-wide admixture analysis, controlling for age, gender, body mass index, current smoking status, pack-years smoked, and four principal components summarizing the genetic background of African Americans in the COPDGene Study, identified a region on chromosome 12q14.1 associated with FEV1 /FVC (P = 2.1 × 10(-6) ) when regressed on local ancestry. Allelic association in this region of chromosome 12 identified an intronic variant in FAM19A2 (rs348644) as associated with FEV1 /FVC (P = 1.76 × 10(-6) ). By combining admixture and association mapping, a marker on chromosome 12q14.1 was identified as being associated with reduced FEV1 /FVC ratio among African Americans in the COPDGene Study.
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Project description:Although respiratory dysfunction is common in chronic spinal cord injury (SCI), determinants of longitudinal change in FEV(1) and FVC have not been assessed.Determine factors that influence longitudinal lung function decline in SCI.A total of 174 male participants (mean age of 49 and 17 yr after injury) completed a respiratory questionnaire and underwent spirometry over an average follow-up of 7.5 years (range, 4-14 yr).In multivariate models, longitudinal decline in FEV(1) was significantly related to continued smoking, persistent wheeze, an increase in body mass index, and respiratory muscle strength. Aging was associated with an accelerated decline in FEV(1) (for ages <40, 40-60, >60 yr: -27, -37, and -71 ml/yr, respectively). Similar effects were observed for FVC.Longitudinal change in FEV(1) and FVC was not directly related to level and severity of SCI, but was attributable to potentially modifiable factors in addition to age. These results suggest that weight control, smoking cessation, trials directed at the recognition and treatment of wheeze, and efforts to improve respiratory muscle strength may slow lung function decline after SCI.
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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.
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Project description:The way in which spirometry is interpreted can lead to misdiagnosis of chronic obstructive pulmonary disease (COPD) resulting in inappropriate treatment. We compared the clinical relevance of 2 criteria for defining a low ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC): the fixed ratio and the lower limit of normal.We analyzed data from the cross-sectional phase of the population-based Canadian Cohort of Obstructive Lung Disease (CanCOLD) study. We determined associations of the spirometric criteria for airflow limitation with patient-reported adverse outcomes, including respiratory symptoms, disability, health status, exacerbations, and cardiovascular disease. Sensitivity analyses were used to explore the impact of age and severity of airflow limitation on these associations.We analyzed data from 4,882 patients aged 40 years and older. The prevalence of airflow limitation was 17% by fixed ratio and 11% by lower limit of normal. Patients classified as having airflow limitation by fixed ratio only had generally small, nonsignificant increases in the odds of adverse outcomes. Patients having airflow limitation based on both fixed ratio and lower limit of normal had larger, significant increases in odds. But strongest associations were seen for patients who had airflow limitation by both fixed ratio and lower limit of normal and also had a low FEV1, defined as one less than 80% of the predicted value.Our results suggest that use of the fixed ratio alone may lead to misdiagnosis of COPD. A diagnosis established by both a low FEV1/FVC (according to fixed ratio and/or lower limit of normal) and a low FEV1 is strongly associated with clinical outcomes. Guidelines should be reconsidered to require both spirometry abnormalities so as to reduce overdiagnosis of COPD.
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Project description:INTRODUCTION:Murine studies have shown that apolipoprotein E modulates pulmonary function during development, aging, and allergen-induced airway disease. It is not known whether the polymorphic human APOE gene influences pulmonary function. OBJECTIVES:We assessed whether an association exists between the polymorphic human APOE ?2, ?3, and ?4 alleles and pulmonary function among participants in the Long Life Family Study. METHODS:Data from 4,468 Caucasian subjects who had genotyping performed for the APOE ?2, ?3, and ?4 alleles were analyzed, with and without stratification by sex. Statistical models were fitted considering the effects of the ?2 allele, defined as ?2/2 or ?2/3 genotypes, and the ?4 allele, defined as ?3/4 or ?4/4 genotypes, which were compared to the ?3/3 genotype. RESULTS:The mean FEV1/FVC ratio (the forced expiratory volume in one second divided by the forced vital capacity) was lower among women with the ?4 allele as compared to women with the ?3/3 genotype or the ?2 allele. Carriage of the APOE ?4 allele was associated with FEV1/FVC, which implied lower values. Further analysis showed that the association primarily reflected women without lung disease who were older than 70 years. The association was not mediated by lipid levels, smoking status, body mass index, or cardiovascular disease. CONCLUSIONS:This study for the first time identifies that the APOE gene is associated with modified lung physiology in women. This suggests that a link may exist between the APOE ?4 allele, female sex, and a reduction in the FEV1/FVC ratio in older individuals.
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Project description:Despite the ongoing intense debate on the definition of airflow limitation by spirometry in the elderly population, there have only been few studies comparing the fixed ratio and the Z-score of forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) in terms of long-term mortalities. In this study, we aimed to identify the proper method for accurately defining the airflow limitation in terms of long-term mortality prediction in the elderly population.Data were collected from the Third National Health and Nutrition Examination Survey in the US. Non-Hispanic Caucasians aged 65-80 years were included. The receiver operating characteristic (ROC) curves of both methods were plotted and compared for 10-year all-cause, respiratory, and COPD mortalities.Of 1,331 subjects, the mean age was 71.7 years and 805 (60.5%) were males. For the 10-year all-cause mortality, the area under the curve (AUC) of the fixed ratio was significantly greater than that of the Z-score of FEV1/FVC, but both showed poor prediction performance (0.633 vs 0.616, p<0.001). For the 10-year respiratory and COPD mortalities, both the fixed ratio and the Z-score of FEV1/FVC showed comparable prediction performance with greater AUCs (0.784 vs 0.778, p=0.160, and 0.896 vs 0.896, p=0.971, respectively). Interestingly, the conventional cutoff of 0.7 in the fixed ratio was consistently higher than the optimal for the 10-year all-cause, respiratory, and COPD mortalities (0.70 vs 0.69, 0.62, and 0.61, respectively), whereas that of -1.64 in the Z-score of FEV1/FVC was consistently lower than the optimal cutoff (-1.64 vs -1.31, -1.47, and -1.41, respectively).In the elderly population, both the fixed ratio and the Z-score of FEV1/FVC showed comparable prediction performance for the 10-year respiratory and COPD mortalities. However, the conventional cutoff of neither 0.70 in the fixed ratio nor -1.64 in the Z-score of FEV1/FVC was optimal for predicting the long-term mortalities.
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Project description: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.
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