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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 FEV 1 , FVC, and FEV 1 /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 FEV 1 and FVC, in milliliters, was unrelated to the baseline value but was biased toward age, height, sex, and level of airways obstruction; ΔFEV 1 was significantly lower in African Americans. In 1,106 subjects with low FEV 1 (200-1,621 mL) the FEV 1 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. ΔFEV 1 % 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 FEV 1 responsiveness as % baseline spuriously suggests that responsiveness increases with the severity of respiratory impairment. Expressing change in FEV 1 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., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

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 FEV 1 , -0.08 (0.86) for FVC, and -0.07 (0.83) for FEV 1 /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 FEV 1 /FVC ratio but significant reductions of ∼0.5 z-scores (∼5%) in FEV 1 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, zFEV 1 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 FEV 1 and FVC without respiratory impairment, as shown by the normal FEV 1 /FVC ratio.

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 (FEV 1 ), forced vital capacity (FVC) and FEV 1 /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 FEV 1 and FVC. Stricter criteria of obstruction (FEV 1 /FVC 1 /FVC <0.7 and >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 FEV 1 /FVC GLI-2012 LLN identifies higher risk of obstructive characteristics than FEV 1 /FVC <0.7., (Copyright ©ERS 2016.)

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 (FEV 1 ), 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 FEV 1 , FVC, and PEF than those who were inactive. Vigorous-intensity physical activity in boys was also associated with FEV 1 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.

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., (© 2016 S. Karger AG, Basel.)

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., (Copyright ©ERS 2015.)

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.

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., (©ERS 2014.)

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., (Copyright © 2014 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

The aim of this study was to determine the added value of measuring the forced expiratory flow at 25-75% of forced vital capacity (FVC) (FEF25-75%) and flow when 75% of FVC has been exhaled (FEF75%) over and above the measurement of the forced expiratory volume in 1 s (FEV1), FVC and FEV1/FVC ratio. We used spirometric measurements of FEV1, FVC and FEF25-75% from 11 654 white males and 11 113 white females, aged 3-94 years, routinely tested in the pulmonary function laboratories of four tertiary hospitals. FEF75% was available in 8254 males and 7407 females. Predicted values and lower limits of normal, defined as the fifth percentile, were calculated for FEV1, FVC, FEV1/FVC ratio, FEF25-75% and FEF75% using prediction equations from the Global Lung Function Initiative. There was very little discordance in classifying test results. FEF25-75% and FEF75% were below the normal range in only 2.75% and 1.29% of cases, respectively, whereas FEV1, FVC and FEV1/FVC ratio were within normal limits. Airways obstruction went undetected by FEF25-75% in 2.9% of cases and by FEF75% in 12.3% of cases. Maximum mid-expiratory flow and flow towards the end of the forced expiratory manoeuvre do not contribute usefully to clinical decision making over and above information from FEV1, FVC and FEV1/FVC ratio.

Objective: To determine the interpretative consequences of adopting the Global Lungs 2012 (GLI-2012) spirometric prediction equations in a pediatric hospital population., Material: Spirometric records from 2,192 white boys and 1,842 white girls, and 412 and 334 African-American boys and girls, respectively, aged 6.0-18.0 years, treated mainly for asthma, cystic fibrosis, cough, and dyspnoea., Methods: Predicted values and lower limits of normal were calculated for FEV1, FVC, and FEV1/FVC, using prediction equations from GLI-2012, Hankinson, Knudson, Polgar, Wang, and Zapletal. Obstruction was defined as FEV1/FVC < LLN, a restrictive pattern as FEV1/FVC > LLN and FVC < LLN., Results: There was good agreement for predicted values for FEV1, FVC, and FEV1/FVC from GLI-2012, Hankinson and Wang equations within ethnic groups. A near normal FEV1 but above normal FVC contributed to a low FEV1/FVC, particularly in African-Americans. Polgar, Knudson, and Zapletal predicteds produced disparate results. A restrictive pattern occurred in 2.2-11.2% of cases, with no statistical difference between GLI-2012 and Hankinson., Conclusions: Transition from Hankinson and Wang equations to GLI-2012 leads to grossly similar prevalence rates of abnormally low values for FEV1, FVC, and FEV1/FVC, unlike equations from Knudson, Polgar, and Zapletal., (© 2013 Wiley Periodicals, Inc.)

The objective of this study was to redesign the current grading of obstructive lung disease so that it is clinically relevant and free of biases related to age, height, sex and ethnic group. Spirometric records from 17 880 subjects (50.4% female) from hospitals in Australia and Poland, and 21 191 records (53.0% female) from two epidemiological studies (age range 18-95 years) were analysed. We adopted the American Thoracic Society(ATS)/European Respiratory Society (ERS) criteria for airways obstruction based on an forced expiratory volume in 1 s (FEV1)/(forced) vital capacity ((F)VC) ratio below the fifth percentile and graded the severity of pulmonary function impairment using z-scores for FEV1, which signify how many standard deviations a result is from the mean predicted value. Using the lower limit of normal for FEV1/(F)VC and z-scores for FEV1 of -2, -2.5, -3 and -4 to delineate severity grades of airflow limitation leads to close agreement with ATS/ERS severity classifications and removes age, sex and height related bias. The new classification system is simple, easily memorised and clinically valid. It retains previously established associations with clinical outcomes and avoids biases due to the use of per cent predicted FEV1. Combined with the Global Lung Function prediction equations it provides a worldwide diagnostic standard, free of bias due to age, height, sex and ethnic group.

Objective: Spirometric Z scores by lambda-mu-sigma (LMS) rigorously account for age-related changes in lung function. Recently, the Global Lung Function Initiative (GLI) expanded LMS spirometric Z scores to multiple ethnicities. Hence, in aging populations, the GLI provides an opportunity to rigorously evaluate ethnic differences in respiratory impairment, including airflow limitation and restrictive pattern., Methods: Using data from the Third National Health and Nutrition Examination Survey, including participants aged 40-80, we evaluated ethnic differences in GLI-defined respiratory impairment, including prevalence and associations with mortality and respiratory symptoms., Results: Among 3506 white Americans, 1860 African Americans and 1749 Mexican Americans, the prevalence of airflow limitation was 15.1% (13.9% to 16.4%), 12.4% (10.7% to 14.0%) and 8.2% (6.7% to 9.8%), and restrictive pattern was 5.6% (4.6% to 6.5%), 8.0% (6.9% to 9.0%) and 5.7% (4.5% to 6.9%), respectively. Airflow limitation was associated with mortality in white Americans, African Americans and Mexican Americans-adjusted HR (aHR) 1.66 (1.23 to 2.25), 1.60 (1.09 to 2.36) and 1.80 (1.17 to 2.76), respectively, but associated with respiratory symptoms only in white Americans-adjusted OR (aOR) 2.15 (1.70 to 2.73). Restrictive pattern was associated with mortality but only in white Americans and African Americans-aHR 2.56 (1.84 to 3.55) and 3.23 (2.06 to 5.05), and associated with respiratory symptoms but only in white Americans and Mexican Americans-aOR 2.16 (1.51 to 3.07) and 2.12 (1.45 to 3.08), respectively., Conclusions: In an aging population, we found ethnic differences in GLI-defined respiratory impairment. In particular, African Americans had high rates of respiratory impairment that were associated with mortality but not respiratory symptoms.

The aim of this study was to determine the diagnostic and interpretative consequences of adopting the Global Lungs Initiative (GLI) 2012 spirometric prediction equations. We assessed spirometric records from 17 572 subjects (49.5% females), aged 18-85 years, from hospitals in Australia and Poland. We calculated predicted forced expiratory volume in 1 s (FEV1), forced expiratory volume (FVC), FEV1/FVC and lower limits of normal (LLN) using European Community for Steel and Coal (ECSC), National Health and Nutrition Examination Survey (NHANES) III and GLI 2012 equations. Obstruction was defined as FEV1/FVCLLN and FVC20% underdiagnosis of airway obstruction up to the age of 55 years and to 16-23% overdiagnosis in older subjects. GLI 2012 equations increase the prevalence of a "restrictive spirometric pattern" compared to ECSC but decrease it compared to NHANES.

Background: Among older persons, within the clinical context of respiratory symptoms and mobility, evidence suggests that improvements are warranted regarding the current approach for identifying respiratory impairment (ie, a reduction in pulmonary function)., Methods: Among 3583 white participants aged 65 to 80 years (Cardiovascular Health Study), we calculated the prevalence of respiratory impairment using the current spirometric standard from the Global Initiative for Obstructive Lung Disease (GOLD) and an alternative spirometric approach termed "lambda-mu-sigma" (LMS). Results for GOLD- and LMS-defined respiratory impairment were evaluated for their (cross-sectional) association with respiratory symptoms and gait speed, and for the 5-year cumulative incidence probability of mobility disability., Results: The prevalence of respiratory impairment was 49.7% (1780/3583) when using the GOLD and 23.2% (831/3583) when using LMS. Differences in prevalence were most evident among participants who had no respiratory symptoms, with respiratory impairment classified more often by the GOLD (38.1% [326/855]) than LMS (12.3% [105/855]), as well as among participants who had normal gait speed, with respiratory impairment classified more often by the GOLD (46.4% [1003/2164]) than LMS (19.3% [417/2164]). Conversely, the 5-year cumulative incidence probability of mobility disability for respiratory impairment was higher for LMS than GOLD (0.313 and 0.249 for never-smokers, and 0.352 and 0.289 for ever-smokers, respectively), but was similar for normal spirometry by LMS or GOLD (0.193 and 0.185 for never-smokers, and 0.219 and 0.216 for ever-smokers, respectively)., Conclusions: Among older persons, the LMS approach (vs the GOLD approach) classifies respiratory impairment less frequently in those who are asymptomatic and is more strongly associated with mobility disability., (Published by Elsevier Inc.)

The aim of the Task Force was to derive continuous prediction equations and their lower limits of normal for spirometric indices, which are applicable globally. Over 160,000 data points from 72 centres in 33 countries were shared with the European Respiratory Society Global Lung Function Initiative. Eliminating data that could not be used (mostly missing ethnic group, some outliers) left 97,759 records of healthy nonsmokers (55.3% females) aged 2.5-95 yrs. Lung function data were collated and prediction equations derived using the LMS method, which allows simultaneous modelling of the mean (mu), the coefficient of variation (sigma) and skewness (lambda) of a distribution family. After discarding 23,572 records, mostly because they could not be combined with other ethnic or geographic groups, reference equations were derived for healthy individuals aged 3-95 yrs for Caucasians (n=57,395), African-Americans (n=3,545), and North (n=4,992) and South East Asians (n=8,255). Forced expiratory value in 1 s (FEV(1)) and forced vital capacity (FVC) between ethnic groups differed proportionally from that in Caucasians, such that FEV(1)/FVC remained virtually independent of ethnic group. For individuals not represented by these four groups, or of mixed ethnic origins, a composite equation taken as the average of the above equations is provided to facilitate interpretation until a more appropriate solution is developed. Spirometric prediction equations for the 3-95-age range are now available that include appropriate age-dependent lower limits of normal. They can be applied globally to different ethnic groups. Additional data from the Indian subcontinent and Arabic, Polynesian and Latin American countries, as well as Africa will further improve these equations in the future.

Prediction bias in spirometry reference equations can arise from combining equations for different age groups, rounding age or height to integers or using self-reported height. To assess the bias arising from these sources, the fit of 13 prediction equations was tested against the Global Lungs Initiative (GLI) dataset using spirometric data from 55,136 healthy Caucasians (54% female). The effects on predicted values of using whole-year age versus decimal age, and of a 1% bias in height, were quantified. In children, the prediction bias relative to GLI ranged from -22% to +17%. Switching equations at 18 yrs of age led to biases of between -846 (-14%) and +1,309 (+38%) mL. Using age in whole years rather than decimal age introduced biases from -8% to +7%, whereas a 1% overestimation of height introduced bias that ranged from +1% to +40%. Bias was greatest in children and adolescents, and in short elderly subjects. Using a single spirometry equation applicable across all ages and populations reduces prediction bias. Measuring and recording age and height accurately are also essential if bias is to be minimised.

The aim of our study was to determine the contribution of secular trends and sample size to lung function reference equations, and establish the number of local subjects required to validate published reference values. 30 spirometry datasets collected between 1978 and 2009 provided data on healthy, white subjects: 19,291 males and 23,741 females aged 2.5-95 yrs. The best fit for forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC) and FEV(1)/FVC as functions of age, height and sex were derived from the entire dataset using GAMLSS. Mean z-scores were calculated for individual datasets to determine inter-centre differences. This was repeated by subdividing one large dataset (3,683 males and 4,759 females) into 36 smaller subsets (comprising 18-227 individuals) to preclude differences due to population/technique. No secular trends were observed and differences between datasets comprising >1,000 subjects were small (maximum difference in FEV(1) and FVC from overall mean: 0.30- -0.22 z-scores). Subdividing one large dataset into smaller subsets reproduced the above sample size-related differences and revealed that at least 150 males and 150 females would be necessary to validate reference values to avoid spurious differences due to sampling error. Use of local controls to validate reference equations will rarely be practical due to the numbers required. Reference equations derived from large or collated datasets are recommended.

Background: Differences in COPD classification have been shown in population data sets when using fifth percentiles as the lower limit of normal (LLN) vs the current GOLD (Global Initiative for Chronic Obstructive Lung Disease) guidelines of FEV(1)/FVC < 0.70 for detecting airway obstruction and an FEV(1) of 80% predicted for detecting and classifying the severity of COPD (GOLD/PP). Many lung function laboratories use 80% predicted to determine whether results are abnormal. Misclassification of the full range of lung diseases in large patient groups when using GOLD/PP criteria instead of the LLN has not been explored previously., Methods: We determined the discrepancy rates in pulmonary function test interpretation between the GOLD/PP and LLN methods on prebronchodilator lung function results from a large number of adult patients from the United Kingdom, New Zealand, and the United States., Results: In 11,413 patients, the GOLD/PP method misclassified 24%. Ten percent of patients who had normal lung function were falsely classified with a disease category, and 7% of patients were falsely attributed with emphysema. The GOLD/PP method gave false-positive classifications for airflow obstruction and restrictive defects to significantly more men (P < .01) and older patients (P < .0001) and also missed airflow obstruction and restrictive defects in younger patients (P < .0001)., Conclusions: Using lung function tests on their own with 80% predicted and fixed cut points to determine whether a test is abnormal could misdiagnose > 20% of patients referred for pulmonary function tests. The GOLD/PP method introduces clinically important biases in assessing disease status that could affect allocation to treatment groups. This misclassification is avoided by using the LLN based on the fifth-percentile values.

In children, the ratio of forced expiratory volume in 1 s (FEV₁) to forced vital capacity (FVC) is reportedly constant or falls linearly with age, whereas the ratio of residual volume (RV) to total lung capacity (TLC) remains constant. This seems counter-intuitive given the changes in airway properties, body proportions, thoracic shape and respiratory muscle function that occur during growth. The age dependence of lung volumes, FEV₁/FVC and RV/TLC were studied in children worldwide. Spirometric data were available for 22,412 healthy youths (51.4% male) aged 4-20 yrs from 15 centres, and RV and TLC data for 2,253 youths (56.7% male) from four centres; three sets included sitting height (SH). Data were fitted as a function of age, height and SH. In childhood, FVC outgrows TLC and FEV₁, leading to falls in FEV₁/FVC and RV/TLC; these trends are reversed in adolescence. Taking into account SH materially reduces differences in pulmonary function within and between ethnic groups. The highest FEV₁/FVC ratios occur in those shortest for their age. When interpreting lung function test results, the changing pattern in FEV₁/FVC and RV/TLC should be considered. Prediction equations for children and adolescents should take into account sex, height, age, ethnic group, and, ideally, also SH.

Sarcoidosis is a systemic granulomatous disease with predominant manifestation in the lungs, often presenting as interstitial lung disease. Pulmonary function abnormalities in sarcoidosis include restriction of lung volumes, reduction in diffusing capacity of the lung for carbon monoxide (D(L,CO)), reduced static lung compliance (C(L,s)) and airway obstruction. The aim of the present study was to assess various lung function indices, including C(L,s) and D(L,CO), as markers of functional abnormality in sarcoidosis patients. Results from 830 consecutive patients referred for lung function tests with a diagnosis of sarcoidosis (223 in stage I, 486 in stage II and 121 in stage III) were retreospectively analysed. The mean ± sd age of the patients was 40 ± 11 yrs; 18% were active smokers and 24% were former smokers. Normal total lung capacity was found in 772 (93%) patients. Of these cases, 24.5% had a low C(L,s) and 21.5% had a low D(L,CO). At least one abnormality was observed in 39.3% of these patients, whereas, in restrictive patients, this figure was 88%. Airway obstruction was present in 11.7% of cases. Lung volumes usually remain within the normal range and measurement of either C(L,s) or D(L,CO) often reveal impaired lung function in sarcoidosis patients, even when their lung volumes are still in the normal range; these two measurements provide complementary information.

Objective: This study investigated whether there is a difference in pulmonary function between healthy adult US-born Asian Indians and immigrant Asian Indians attributable to country of birth, environmental, and socioeconomic factors., Design: FEV(1), FVC, and forced mid-expiratory flow between 25% and 75% of vital capacity (FEF(25-75)) were measured in India-born and US-born subjects residing in the Chicago metropolitan area. Hollingshead Index of Social Position was used to evaluate socioeconomic factors., Results: There were 262 India-born (61.8% male), and 200 US-born (50% male) subjects who were healthy lifelong nonsmokers; their age range was 16 to 36 years. US-born Asian Indian men and women were taller and had higher pulmonary function values for height and age compared with immigrant Asian Indian men and women. The differences were most pronounced in women: about 7% for FVC, 9% for FEV(1), and 17% for FEF(25-75). Immigrant and US-born subjects did not differ in socioeconomic position., Conclusion: We conclude that US-born Asian Indian men and women have higher pulmonary function values for age and height compared with immigrant Asian Indian men and women. This probably reflects the effect of differing environmental conditions, which cause year-of-birth trends in lung volumes.

Congenital diaphragmatic hernia (CDH) is associated with pulmonary hypoplasia and pulmonary hypertension. The objective of this study was to assess pulmonary function and exercise capacity and its early determinants in children and adolescents born with high-risk CDH (CDH-associated respiratory distress within the first 24 h) and to explore the relationship of these findings with CDH severity. Of 159 patients born with high-risk CDH, 84 survived. Of the 69 eligible patients, 53 children (mean+/-SD age 11.9+/-3.5 yrs) underwent spirometry, lung volume measurements and maximal cardiopulmonary exercise testing (CPET). Results of the pulmonary function tests were compared with those from a healthy control group matched for sex, age and height. CDH survivors had a significantly lower forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC), FEV(1)/FVC, maximum mid-expiratory flow and peak expiratory flow when compared with healthy controls. The residual volume/total lung capacity ratio was significantly higher. Linear regression analysis showed that gastro-oesophageal reflux disease was an independent determinant of reduced FEV(1) and FVC. CPET results were normal in those tested. High-risk CDH survivors have mild to moderate pulmonary function abnormalities when compared with a healthy matched control group, which may be related to gastro-oesophageal reflux disease in early life. Exercise capacity and gas exchange parameters were normal in those tested, indicating that the majority of patients do not have physical impairment.

Aim: To assess the impact of two modes of spirometry expert support on Family physicians' (FPs') diagnoses and planned management in patients with apparent respiratory disease., Method: A cluster-randomised trial was performed with family practices as the unit of randomisation. FPs from 44 family practices recorded their diagnosis and planned management before and after spirometry for 868 patients. Intervention consisted of spirometry interpretation support by either a chest physician or expert software. Both interventions were compared with usual care (i.e. no additional interpretation support). Change in FPs' diagnoses after spirometry served as the primary outcome. Secondary outcomes were referral rate, additional diagnostic tests, and disease management changes. Effects were expressed as percentages and Odds Ratios (OR) with 95% confidence intervals., Results: Diagnoses changed after intervention in all groups: 47.8% (95% CI 41.8 to 53.9) for chest physician support; 45.0% (95% CI 39.5 to 50.6) for software support; and 53.3% (95% CI 47.2 to 59.4) for usual care. Differences in the proportions of changed diagnosis were not statistically significant: chest physician support versus usual care OR 0.79 (95%CI 0.49 to 1.30); software support versus usual care OR 0.72 (95% CI 0.45 - 1.15). There were no differences in secondary outcomes., Conclusion: Neither chest physician spirometry support nor expert software spirometry support had a significant impact on FPs' diagnosis of respiratory conditions or management decisions., Trial Number: http://www.clinicaltrials.gov/ct/show/NCT00131157?order=1.

Primary care spirometry services can be provided by trained primary care staff, peripatetic specialist services, or through referral to hospital-based or laboratory spirometry. The first of these options is the focus of this Standards Document. It aims to provide detailed information for clinicians, managers and healthcare commissioners on the key areas of quality required for diagnostic spirometry in primary care--including training requirements and quality assurance. These proposals and recommendations are designed to raise the standard of spirometry and respiratory diagnosis in primary care and to provide the impetus for debate, improvement and maintenance of quality for diagnostic (rather than screening) spirometry performed in primary care. This document should therefore challenge current performance and should constitute an aspirational guide for delivery of this service.