Bronchodilator Response in FVC Is Larger and More Relevant Than in FEV1 in Severe Airflow Obstruction.

BACKGROUND: Recommendations on interpreting tests of bronchodilator responsiveness (BDR) are conflicting. We investigated the dependence of BDR criteria on sex, age, height, ethnicity, and severity of respiratory impairment. METHODS: BDR test data were available from clinical patients in the Netherlands, New Zealand, and the United States (n = 15,278; female subjects, 51.7%) and from surveys in Canada, Norway, and five Latin-American countries (n = 16,250; female subjects, 54.7%). BDR calculated according to FEV1, FVC, and FEV1/FVC was expressed as absolute change, a percentage of the baseline level (% baseline), a percentage of the predicted value (% predicted), and z score. RESULTS: Change (Δ) in FEV1 and FVC, in milliliters, was unrelated to the baseline value but was biased toward age, height, sex, and level of airways obstruction; ΔFEV1 was significantly lower in African Americans. In 1,106 subjects with low FEV1 (200-1,621 mL) the FEV1 increased by 12% to 44.7% relative to baseline but < 200 mL. Expressing BDR as a percentage of the predicted value or as a z score attenuated the bias and made the 200-mL criterion redundant, but reduced positive responses by half. ΔFEV1 % baseline increased with the level of airflow obstruction but decreased with severe obstruction when expressed as z scores or % predicted; ΔFVC, however expressed, increased with the level of airflow obstruction. CONCLUSIONS: Expressing FEV1 responsiveness as % baseline spuriously suggests that responsiveness increases with the severity of respiratory impairment. Expressing change in FEV1 or FVC as % predicted or as z scores eliminates this artifact and renders the required 200-mL minimum increase redundant. In severe airways obstruction ΔFVC should be critically evaluated as an index of clinically important relief of hyperinflation, with implications for bronchodilator drug trials.

Evaluation of the Global Lung Initiative 2012 Reference Values for Spirometry in African Children.

RATIONALE: Despite the high burden of respiratory disease, no spirometry reference values for African children are available. OBJECTIVES: Investigate whether the Global Lung Initiative (GLI-2012) reference values for spirometry are appropriate for children in sub-Saharan Africa and assess the impact of malnutrition on lung function. METHODS: Anthropometry and spirometry were obtained in children aged 6 to 12 years from urban and semiurban schools in three African countries. Spirometry z-scores were derived using the GLI-2012 prediction equations for African Americans. Thinness (body mass index z-score < -2) was a surrogate for malnutrition. Spirometry outcomes were compared with those of African American children from the third National Health and Nutrition Survey. MEASUREMENTS AND MAIN RESULTS: Spirometry data were analyzed from 1,082 schoolchildren (51% boys) aged 6.0 to 12.8 years in Angola (n = 306), Democratic Republic of the Congo (n = 377), and Madagascar (n = 399). GLI-2012 provided a good fit with mean (SD) z-scores of -0.11 (0.83) for FEV1, -0.08 (0.86) for FVC, and -0.07 (0.83) for FEV1/FVC. Because of low scatter, the fifth centile corresponded to -1.3 z-scores in boys and -1.5 z-scores in girls. Malnourished African children had a normal FEV1/FVC ratio but significant reductions of ∼0.5 z-scores (∼5%) in FEV1 and FVC compared with African American peers from the third National Health and Nutrition Survey. Children in Angola had the lowest, and those in Madagascar had the highest, zFEV1 and zFVC. CONCLUSIONS: The results of this study support the use of GLI-2012 reference values for schoolchildren in sub-Saharan Africa. Malnutrition affects body growth, leading to a proportionately smaller FEV1 and FVC without respiratory impairment, as shown by the normal FEV1/FVC ratio.

Global Lung Function Initiative 2012 reference equations for spirometry in the Norwegian population.

We studied the fit of the Global Lung Function Initiative (GLI) all-age reference values to Norwegians, compared them with currently used references (European Community for Steel and Coal (ECSC) and Zapletal) and estimated the prevalence of obstructive lung disease.Spirometry data collected in 30 239 subjects (51.7% females) aged 12-90 years in three population-based studies were converted to z-scores.We studied healthy non-smokers comprising 2438 adults (57.4% females) aged 20-90 years and 8725 (47.7% female) adolescents aged 12-19 years. The GLI-2012 prediction equations fitted the Norwegian data satisfactorily. Median±sd z-scores were respectively 0.02±1.03, 0.01±1.04 and -0.04±0.91 for forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC in males, and -0.01±1.02, 0.07±0.97 and -0.21±0.82 in females. The ECSC and Zapletal references significantly underestimated FEV1 and FVC. Stricter criteria of obstruction (FEV1/FVC GLI-2012 LLN. Corresponding comparison regarding myocardial infarction showed a four-fold higher risk for women.The GLI-2012 reference values fit the Norwegian data satisfactorily and are recommended for use in Norway. Correspondingly, the FEV1/FVC GLI-2012 LLN identifies higher risk of obstructive characteristics than FEV1/FVC <0.7.

Use the Lower Limit of Normal, Not 80% Predicted, in Judging Eligibility for Lung Resection.

BACKGROUND: Impaired lung function (LF) is a well-known risk factor for perioperative complications in patients qualified for lung resection surgery. The recent European guidelines recommend using values below 80% predicted as indicating abnormal LF rather than the lower limit of normal (LLN). OBJECTIVES: To assess how the choice of a cut-off point (80% predicted vs. LLN at -1.645 SD) affects the incidence of functional disorders and postoperative complications in lung cancer patients referred for lung resection. METHODS: Preoperative spirometry and the transfer factor for carbon monoxide (TL,CO) were retrospectively analysed in 851 consecutive lung cancer patients after resectional surgery. RESULTS: Airway obstruction was diagnosed in 369 (43.4%), and a restrictive pattern in 41 patients (4.8%). The forced expiratory volume in 1 s (FEV1) or TL,CO was below the LLN in 503 patients (59.1%), whereas the FEV1 or TL,CO was <80% predicted in 620 patients (72.9%; χ2 test: p < 0.0001). In all, 117 out of 851 patients had LF indices <80% predicted but not below the LLN. Odds ratios (ORs) for perioperative complications were higher in patients with impaired LF indices defined as below the LLN (1.59, p = 0.0005) with the exception of large resections (>5 segments). In patients with test results above the LLN and <80% predicted, the OR for perioperative complications was not different (1.14, p = 0.5) from that in patients with normal LF. CONCLUSIONS: LF impairments are common in candidates for lung resection. Using the LLN instead of 80% predicted diminishes the prevalence of respiratory impairment by 14% and allows for safe resectional surgery without additional function testing.

Physical Activity in Early Adolescence and Pulmonary Function Gain From 15 to 18 Years of Age in a Birth Cohort in Brazil.

BACKGROUND: The aim of this study was to evaluate the association between physical activity from 11 to 15 years of age and pulmonary function (PF) gain from 15 to 18 years of age among adolescents in a birth cohort in Brazil. METHODS: Longitudinal analysis of the individuals participating in the 1993 Pelotas Birth Cohort Study. Physical activity was assessed by self-report at ages 11 and 15, spirometry was performed at ages 15 and 18 (n = 3571). Outcome variables assessed were gains in forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and peak expiratory flow (PEF). Crude and adjusted linear regressions, stratified by sex, and mediation analyses were performed. RESULTS: Boys who were active (leisure-time and total physical activity) at ages 11 and 15 had higher gains in FEV1, FVC, and PEF than those who were inactive. Vigorous-intensity physical activity in boys was also associated with FEV1 and FVC gains. Mediation analyses showed that height at age 18 accounted for 5% to 75% of the association between physical activity and PF gains. No significant associations were found among girls. CONCLUSIONS: Physical activity in early adolescence is associated with gains in PF by the end of adolescence in boys.

Challenges in Collating Spirometry Reference Data for South-Asian Children: An Observational Study.

METHODS: Spirometry datasets from South-Asian children were collated from four centres in India and five within the UK. Records with transcription errors, missing values for height or spirometry, and implausible values were excluded(n = 110). RESULTS: Following exclusions, cross-sectional data were available from 8,124 children (56.3% male; 5-17 years). When compared with GLI-predicted values from White Europeans, forced expired volume in 1s (FEV1) and forced vital capacity (FVC) in South-Asian children were on average 15% lower, ranging from 4-19% between centres. By contrast, proportional reductions in FEV1 and FVC within all but two datasets meant that the FEV1/FVC ratio remained independent of ethnicity. The 'GLI-Other' equation fitted data from North India reasonably well while 'GLI-Black' equations provided a better approximation for South-Asian data than the 'GLI-White' equation. However, marked discrepancies in the mean lung function z-scores between centres especially when examined according to socio-economic conditions precluded derivation of a single South-Asian GLI-adjustment. CONCLUSION: Until improved and more robust prediction equations can be derived, we recommend the use of 'GLI-Black' equations for interpreting most South-Asian data, although 'GLI-Other' may be more appropriate for North Indian data. Prospective data collection using standardised protocols to explore potential sources of variation due to socio-economic circumstances, secular changes in growth/predictors of lung function and ethnicities within the South-Asian classification are urgently required.

Use of forced vital capacity and forced expiratory volume in 1 second quality criteria for determining a valid test.

The 2005 American Thoracic Society (ATS)/European Respiratory Society (ERS) spirometry guidelines define valid tests as having three acceptable blows and a repeatable forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). The aim of this study was to determine how reviewer and computer-determined ATS/ERS quality could affect population reference values for FVC and FEV1. Spirometry results from 7777 normal subjects aged 8-80 years (NHANES (National Health and Nutrition Examination Survey) III) were assigned quality grades A to F for FVC and FEV1 by a computer and one reviewer (reviewer 1). Results from a subgroup of 1466 Caucasian adults (aged 19-80 years ) were reviewed by two additional reviewers. Mean deviations from NHANES III predicted for FVC and FEV1 were examined by quality grade (A to F). Reviewer 1 rejected (D and F grade) 5.2% of the 7777 test sessions and the computer rejected ∼16%, primarily due to end-of-test (EOT) failures. Within the subgroup, the computer rejected 11.5% of the results and the three reviewers rejected 3.7-5.9%. Average FEV1 and FVC were minimally influenced by grades A to C allocated by reviewer 1. Quality assessment of individual blows including EOT assessments should primarily be used as an aid to good quality during testing rather than for subsequently disregarding data. Reconsideration of EOT criteria and its application, and improved grading standards and training in over-reading are required. Present EOT criteria results in the exclusion of too many subjects while having minimal impact on predicted values.

Secular changes in relative leg length confound height-based spirometric reference values.

BACKGROUND: Most but not all data from different ethnic groups fit the Global Lung Function Initiative (GLI) spirometric reference model. This study investigates to what extent discrepancies are caused by secular changes in body proportions. METHODS: FEV1 and FVC from 20,336 healthy Japanese subjects (13,492 women) aged 17 to 95 years were compared with GLI-2012 reference values for Europeans. Data on the sitting height/standing height ratio (Cormic index) in 17-year-old students, collected from 1949 to 2012 in successive birth cohorts, were used to assess secular changes in body frame. The cohort-specific Cormic index was used to assess how variation in body frame affected pulmonary function. RESULTS: FEV1 and FVC were lower than GLI-2012 reference values, with values progressively falling until age 35 to 40 years and then rising to European levels in the elderly. The Cormic index rose until 1942, then fell, with a nadir in the 1970s, before rising again until 1995. Nearly one-half of the spirometric variability from predicted values could be explained by differences in the Cormic index between birth cohorts. CONCLUSIONS: In low-income countries, improving health conditions are likely to drive increases in height and changes in relative leg length similar to those observed in Japan and, thus, to a change in body frame. This implies that height-based prediction equations for such populations will need to be periodically updated.

Reference values for spirometry, including vital capacity, in Japanese adults calculated with the LMS method and compared with previous values.

BACKGROUND: Reference values for lung function tests should be periodically updated because of birth cohort effects and improved technology. This study updates the spirometric reference values, including vital capacity (VC), for Japanese adults and compares the new reference values with previous Japanese reference values. METHODS: Spirometric data from healthy non-smokers (20,341 individuals aged 17-95 years, 67% females) were collected from 12 centers across Japan, and reference equations were derived using the LMS method. This method incorporates modeling skewness (lambda: L), mean (mu: M), and coefficient of variation (sigma: S), which are functions of sex, age, and height. In addition, the age-specific lower limits of normal (LLN) were calculated. RESULTS: Spirometric reference values for the 17-95-year age range and the age-dependent LLN for Japanese adults were derived. The new reference values for FEV(1) in males are smaller, while those for VC and FVC in middle age and elderly males and those for FEV(1), VC, and FVC in females are larger than the previous values. The LLN of the FEV(1)/FVC for females is larger than previous values. The FVC is significantly smaller than the VC in the elderly. CONCLUSIONS: The new reference values faithfully reflect spirometric indices and provide an age-specific LLN for the 17-95-year age range, enabling improved diagnostic accuracy. Compared with previous prediction equations, they more accurately reflect the transition in pulmonary function during young adulthood. In elderly subjects, the FVC reference values are not interchangeable with the VC values.

All-age relationship between arm span and height in different ethnic groups.

The objective of the present study was to establish multiethnic, all-age prediction equations for estimating stature from arm span in males and females. The arm span/height ratio (ASHR) from 13 947 subjects (40.9% females), aged 5-99 years, from nine centres (in China, Europe, Ghana, India and Iran) was used to predict ASHR as a function of age using the lambda, mu and sigma method. Z-scores for forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC in 1503 patients were calculated using measured height and height calculated from arm span and age. ASHR varied nonlinearly with age, was higher in males than in females and differed significantly between the nine sites. The data clustered into four groups: Asia, Europe, Ghana and Iran. Average predicted FEV1, FVC and FEV1/FVC using measured or predicted height did not differ, with standard deviations of 4.6% for FEV1, 5.0% for FVC and 0.3% for FEV1/FVC. The percentages of disparate findings for a low FEV1, FVC and FEV1/FVC in patients, calculated using measured or predicted height, were 4.2%, 3.2% and 0.4%, respectively; for a restrictive pattern, there were 1.0% disparate findings. Group- and sex-specific equations for estimating height from arm span and age to derive predicted values for spirometry are clinically useful.