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Diagnostic accuracy of FEV1/forced vital capacity ratio z scores in asthmatic patients.

ABSTRACT: The FEV1/forced vital capacity (FVC) ratio is used as a criterion for airflow obstruction; however, the test characteristics of spirometry in the diagnosis of asthma are not well established. The accuracy of a test depends on the pretest probability of disease.We wanted to estimate the FEV1/FVC ratio z score threshold with optimal accuracy for the diagnosis of asthma for different pretest probabilities.Asthmatic patients enrolled in 4 trials from the Asthma Clinical Research Centers were included in this analysis. Measured and predicted FEV1/FVC ratios were obtained, with calculation of z scores for each participant. Across a range of asthma prevalences and z score thresholds, the overall diagnostic accuracy was calculated.One thousand six hundred eight participants were included (mean age, 39 years; 71% female; 61% white). The mean FEV1 percent predicted value was 83% (SD, 15%). In a symptomatic population with 50% pretest probability of asthma, optimal accuracy (68%) is achieved with a z score threshold of -1.0 (16th percentile), corresponding to a 6 percentage point reduction from the predicted ratio. However, in a screening population with a 5% pretest probability of asthma, the optimum z score is -2.0 (second percentile), corresponding to a 12 percentage point reduction from the predicted ratio. These findings were not altered by markers of disease control.Reduction of the FEV1/FVC ratio can support the diagnosis of asthma; however, the ratio is neither sensitive nor specific enough for diagnostic accuracy. When interpreting spirometric results, consideration of the pretest probability is an important consideration in the diagnosis of asthma based on airflow limitation.

SUBMITTER: Lambert A

PROVIDER: S-EPMC4562860 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Diagnostic accuracy of FEV1/forced vital capacity ratio z scores in asthmatic patients.

Lambert Allison A Drummond M Bradley MB Wei Christine C Irvin Charles C Kaminsky David D McCormack Meredith M Wise Robert R

The Journal of allergy and clinical immunology 20150409 3

<h4>Background</h4>The FEV1/forced vital capacity (FVC) ratio is used as a criterion for airflow obstruction; however, the test characteristics of spirometry in the diagnosis of asthma are not well established. The accuracy of a test depends on the pretest probability of disease.<h4>Objective</h4>We wanted to estimate the FEV1/FVC ratio z score threshold with optimal accuracy for the diagnosis of asthma for different pretest probabilities.<h4>Methods</h4>Asthmatic patients enrolled in 4 trials f ...[more]

PMID: 25863976

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Project description:BackgroundThe assumption that the assessment of forced expiratory flow between 25% and 75% of vital capacity (FEF(25-75)) does not provide additional information in asthmatic children with normal FEV(1) percent predicted has not been adequately tested.ObjectiveWe sought to determine whether the measurement of FEF(25-75) percent predicted offers advantages over FEV(1) percent predicted and FEV(1)/forced vital capacity (FVC) percent predicted for the evaluation of childhood asthma.MethodsThis is a secondary analysis of data from the Pediatric Asthma Controller Trial and the Characterizing the Response to a Leukotriene Receptor Antagonist and Inhaled Corticosteroid trials. Pearson correlation coefficients, Pearson partial correlation coefficients, canonical correlations, and receiver operating characteristic (ROC) curves were constructed.ResultsAmong 437 children with normal FEV(1) percent predicted, FEF(25-75) percent predicted, and FEV(1)/FVC percent predicted were (1) positively correlated with log(2) methacholine PC(20), (2) positively correlated with morning and evening peak expiratory flow percent predicted, and (3) negatively correlated with log(10) fraction of exhaled nitric oxide and bronchodilator responsiveness. Pearson partial correlations and canonical correlations indicated that FEF(25-75) percent predicted was better correlated with bronchodilator responsiveness and log(2) methacholine PC(20) than were FEV(1) percent predicted or FEV(1)/FVC percent predicted. In the ROC curve analysis, FEF(25-75) at 65% of predicted value had a 90% sensitivity and a 67% specificity for detecting a 20% increase in FEV(1) after albuterol inhalation.ConclusionFEF(25-75) percent predicted was well correlated with bronchodilator responsiveness in asthmatic children with normal FEV(1). FEF(25-75) percent predicted should be evaluated in clinical studies of asthma in children and might be of use in predicting the presence of clinically relevant reversible airflow obstruction.

Project description:Purpose: Poor forced vital capacity (FVC) effort has been considered to be the main reason for FVC reduction by the ATS/ERS guideline; however, this has rarely been mentioned in previous studies. The present study aims to determine whether reduced FVC in asthmatic children is correlated to poor FVC effort. Methods: A total of 209 asthmatic children within 5-13 years old were included and divided into reduced FVC ("restricted," n = 66) and typical obstruction group ("obstructed," n = 143). Forced expiratory flows before and after bronchodilation were recorded in asthmatic children. The differences in clinical characteristics, spirometric results, FVC effort, and bronchodilator response were compared between two groups. Exhalation time (ET) was divided into effective ET (ETe) and plateau ET (ETp) by the start point of exhalation plateau on the time-volume curve. FVC effort was assessed by ET, ETp, and back extrapolated volume (EV)/FVC (%). Results: Asthmatic children in the restricted group had significantly higher slow vital capacity (SVC)/FVC (%), higher EV/FVC (%), shorter ET, shorter ETe, and longer ETp, when compared with those with obstructed. In the obstructed group, ET (r = 0.201, P = 0.016) and ETe (r = 0.496, P < 0.001) positively correlated with FVC, and ETp (r = -0.224, P = 0.007) negatively correlated with FVC. In the restricted group, FVC positively correlated with ETe (r = 0.350, P = 0.004) but not ET and ETp. FVC z-score significantly correlated with total IgE (n = 51, r = -0.349, P = 0.012) and with FEF25-75% z-score (n = 66, r = 0.531, P < 0.001) in the restricted group. The further logistic regression revealed that the risk of restricted increased by 1.12 (95% CI, 1.04-1.22, P = 0.005) with every 1% increase in %ΔFVC. In subjects with restricted and bronchodilation tests, %ΔFVC was significantly associated with FeNO (n = 29, r = 0.386, P = 0.039), FEF25-75% z-score (n = 29, r = -0.472, P = 0.010), and SVC/FVC (%) (n = 19, r = 0.477, P = 0.039) but not with EV/FVC (%), ET, ETe, or ETp (P > 0.05). Conclusion: These findings suggested that "poor FVC effort" does not account for the FVC reduction in asthmatic children. Short ET and high SVC/FVC (%) are characteristics of reduced FVC.

Project description:BACKGROUND:Forced Vital Capacity (FVC) is an important predictor of all-cause mortality in the absence of chronic respiratory conditions. Epidemiological evidence highlights the role of early life factors on adult FVC, pointing to environmental exposures and genes affecting lung development as risk factors for low FVC later in life. Although highly heritable, a small number of genes have been found associated with FVC, and we aimed at identifying further genetic variants by focusing on lung development genes. METHODS:Per-allele effects of 24,728 SNPs in 403 genes involved in lung development were tested in 7,749 adults from three studies (NFBC1966, ECRHS, EGEA). The most significant SNP for the top 25 genes was followed-up in 46,103 adults (CHARGE and SpiroMeta consortia) and 5,062 children (ALSPAC). Associations were considered replicated if the replication p-value survived Bonferroni correction (p<0.002; 0.05/25), with a nominal p-value considered as suggestive evidence. For SNPs with evidence of replication, effects on the expression levels of nearby genes in lung tissue were tested in 1,111 lung samples (Lung eQTL consortium), with further functional investigation performed using public epigenomic profiling data (ENCODE). RESULTS:NCOR2-rs12708369 showed strong replication in children (p = 0.0002), with replication unavailable in adults due to low imputation quality. This intronic variant is in a strong transcriptional enhancer element in lung fibroblasts, but its eQTL effects could not be tested due to low imputation quality in the eQTL dataset. SERPINE2-rs6754561 replicated at nominal level in both adults (p = 0.036) and children (p = 0.045), while WNT16-rs2707469 replicated at nominal level only in adults (p = 0.026). The eQTL analyses showed association of WNT16-rs2707469 with expression levels of the nearby gene CPED1. We found no statistically significant eQTL effects for SERPINE2-rs6754561. CONCLUSIONS:We have identified a new gene, NCOR2, in the retinoic acid signalling pathway pointing to a role of vitamin A metabolism in the regulation of FVC. Our findings also support SERPINE2, a COPD gene with weak previous evidence of association with FVC, and suggest WNT16 as a further promising candidate.

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Diagnostic accuracy of FEV1/forced vital capacity ratio z scores in asthmatic patients.

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Diagnostic accuracy of FEV1/forced vital capacity ratio z scores in asthmatic patients.

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