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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 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.

No reference equation applies universally: default equations should not be used without considering potential biases http://ow.ly/29XB304sRrm

African-Americans have smaller lung function compared with European-Americans. The aim of this study was to disentangle the contribution of genetics from other variables on lung function. A cohort was followed from birth to 30 years of age in Brazil. Several variables were collected: genomic analysis based on DNA; forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) obtained by spirometry; height measured by anthropometrists; and thorax circumference evaluated by photonic scanner. Crude and adjusted linear regression models were calculated according to African ancestry. The sample comprised 2869 participants out of 3701 members of the cohort. Males with higher African ancestry by DNA analysis had a smaller FEV1 (−0.13 L, 95% CI −0.23– −0.03 L) and FVC (−0.21 L, 95% CI −0.32– −0.09 L) compared with those with less African ancestry, having accounted for height, sitting to standing height ratio and other confounders. Similar effects were seen in females. After adjustment, ancestry remained significantly associated with lung function, but the large effect of adjustment for confounding among males (but not females) does not allow us to exclude the possibility that residual confounding may still account for these findings., Smaller lung function is related to African ancestry but adjustments for confounders reduced the effect sizes http://ow.ly/Iq0Ve

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 FEV 1 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 FEV 1 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 proposal of a normal-spirometry, high- T LCO phenotype that predisposes to airway obstruction has several flaws http://ow.ly/XRmz2

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.

Lung function results can help with establishing a diagnosis, with assessment of treatment effects and with making a prognosis. However, arbitrary differences in the way lung function is expressed and interpreted may result in mismanagement of patients as well as hindering our understanding of the global burden of lung disease. In this article, we summarise the Global Lung Function Initiative spirometry reference equations and dispel some common myths related to the use and interpretation of spirometry results.

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 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 a restrictive pattern as FEV1/FVCLLN and FVCLLN. Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 2 and higher was defined as FEV1/FVC0.70 and FEV180% pred. GLI 2012 equations produce similar predicted values for FEV1 and FVC compared with NHANES, but produce larger values than ECSC. Differences in the LLN lead to an important increase in the prevalence rate of a low FVC compared to ECSC, and a significant decrease compared to NHANES prediction equations. Adopting GLI 2012 equations has small effects on the prevalence rate of airway obstruction. GOLD stages 2-4 lead to20% 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.

Despite the high burden of respiratory disease, no spirometry reference values for African children are available.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.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.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 FEVThe 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

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.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 FEVChange (Δ) in FEVExpressing FEV

In their article on the diagnosis of chronic obstructive pulmonary disease (COPD) in primary care, Conway and colleagues state that the diagnosis can be confirmed by a low FEV1/FVC (forced expiratory volume in one second/forced vital capacity) ratio,1 with a ratio

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 2 test: p < 0.0001). In all, 117 out of 851 patients had LF indices 5 segments). In patients with test results above the LLN and 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.

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.

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)/FVC0.70 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.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.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).Using lung function tests on their own with 80% predicted and fixed cut points to determine whether a test is abnormal could misdiagnose20% 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.

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.

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.

Contains fulltext : 81520.pdf (Publisher’s version ) (Closed access) 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.

Contains fulltext : 69320.pdf (Publisher’s version ) (Closed access) RATIONALE: Single and serial spirometric data are commonly compared with predicted values to assess pulmonary function and normal lung growth. OBJECTIVES: Do reference equations adequately describe pulmonary function in a population and in growing individuals? METHODS: We applied five sets of reference equations with appropriate age ranges to cross-sectional data of FEV(1), FVC, and FEV(1)/FVC from the United States, Estonia, and The Netherlands (1,487 boys and 1,340 girls, 6 to 18 years of age), and to serial measurements in Dutch (430 girls and 769 boys, 6 to 19 years of age) and in German and Austrian children (1,305 girls and 1,303 boys, 6 to 13 years of age). MEASUREMENTS AND MAIN RESULTS: Compared with reference equations from Polgar and Zapletal, cross-sectional FEV(1) and FVC declined between the ages of 6 and 12 and then increased, leading to a spurious change of up to 25% predicted; this pattern was most pronounced in boys. In cross-sectional data this trend was much weaker when using reference equations from Hankinson, Quanjer, and Stanojevic, and these equations provided a good fit from the age of 12 upward. In longitudinal data (i.e., within individuals), the trend was more pronounced for FEV(1) in boys than in girls. No set of equations provided a satisfactory fit in the lower limits of normal, but Hankinson and Stanojevic equations performed best. CONCLUSIONS: Spirometric reference equations that use only height for predicting pulmonary function are unsuitable for describing the progression of pulmonary function. Those that incorporate height and age demonstrate some discrepancy with longitudinal data. Failure to take these spurious trends into account leads to significant errors in estimating the natural course of respiratory disease, in allocating patients to treatment groups, or in assessing long-term effects of drug intervention in school children and adolescents.

Schermer T, Quanjer Ph. Opsporen van COPD in de huisartsenpraktijk: wie is er eigenlijk ziek? Huisarts Wet 2007;50(8):85-9.De huidige COPD-richtlijnen, waaronder de NHG-Standaard COPD en de Global Initiative on Obstructive Lung Disease (GOLD), adviseren om luchtwegobstructie vast te stellen aan de hand van een ‘vaste’ afkapwaarde van 0,70 voor het quotient van de eensecondewaarde en de geforceerde vitale longcapaciteit (FEV1/FVC). Steeds meer onderzoek laat echter zien dat deze benadering een aanzienlijk percentage foutpositieve uitslagen tot gevolg heeft, vooral in de categorie lichte tot matig ernstige obstructie. Daarnaast adviseren de richtlijnen om het FEV1, uitgedrukt als percentage van de voorspelde waarde, te gebruiken als maat voor de ernst van de obstructie. Ook deze werkwijze leidt tot vertekening: kleine mensen en ouderen, en vooral ouderen die klein zijn, lijken een abnormaal laag FEV1 te hebben terwijl zij feitelijk geen respiratoire afwijking hebben. Er is dus behoefte aan betere regels om de aanwezigheid en de ernst van luchtwegobstructie vast te stellen. Dit geldt in het bijzonder voor de huisarts, die vooral te maken heeft met de vroege stadia van COPD. Een eerste stap naar een betere classificatie van luchtwegobstructies zou zijn om, in plaats van een vaste waarde, de ‘ondergrens van normaal’ (LLN) voor het quotient FEV1/FVC als criterium te gebruiken.

INTRODUCTION: Underdiagnosis of COPD appears to be common, although the degree of underdiagnosis is rarely measured. To document the extent of underdiagnosis in a high risk group of ambulatory patients, we performed spirometry in smokers aged 40 years and over drawn from general practices in two countries. METHODS: Subjects were recruited from primary care practices in Aberdeen, Scotland, and Denver, Colorado, via random mailing. Current and former smokers aged 40 or older with no prior diagnosis of chronic obstructive respiratory disease (and no respiratory medications within the past year) were enrolled. Participants underwent pre- and post-bronchodilator spirometry. A study diagnosis of COPD was defined as post-bronchodilator FEV(1)/FVC < 0.70. RESULTS: Spirometric examination was complete in 818 patients, of whom 155 (18.9%) had a study diagnosis of COPD. Using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) severity criteria, the COPD was mild in 57.4%, moderate in 36.8%, and severe in 5.8%. No patients had very severe disease according to GOLD criteria. DISCUSSION: Screening of smokers over 40 in general practice may yield 10 — 20% undiagnosed COPD cases, with a substantial proportion of these having moderate to severe disease. Earlier diagnosis through targeted case-finding will allow early, aggressive smoking cessation efforts and may lead to a reduction in the burden of COPD symptoms and a reduced impact of the disease on health-related quality of life in these patients.

Background: In 2012 the Global Lung Function Initiative (GLI) published international reference values for the age range 3 to 95 years. We aimed to study the validity of GLI equations in Norwegians, and to compare them with currently used national (Gulsvik, Langhammer) and international (ECSC, Zapletal) equations in Norway. Methods: Spirometry data were included from random samples in three general population based studies; the Tromso 6 Study, the Hordaland County Cohort Study, and the Nord-Trondelag Health Study. Spirometry was performed at least once by 14,625 adults aged 20-90 years and 15,458 persons aged 12-19 years. The reference sample included never-smoking persons without self-reported respiratory symptoms or disease. The percent predicted values and z-scores for each subject were calculated by use of the GLI software and equations already in use in Norway, and the goodness of fit evaluated. Results: In total 1508 female and 1106 male adults and 4729 female and 4946 male adolescents met the inclusion criteria. The GLI-2012 prediction equation fitted the Norwegian data quite well. Average (SD) Z-scores (observed minus predicted /standard deviation) were 0.04 (1.03), 0.06 (1.04) and -0.06 (0.88) for FEV1, FVC and FEV1/FVC in men, respectively, and -0.01 (1.01), 0.11 (0.98) and -0.28 (0.79) in women, respectively. Hence the agreement between spirometric indices in a Norwegian population and predicted values by GLI-2012 was good; the ECSC and Zapletal9s prediction equations significantly underestimated FEV1 and FVC among adults and adolescents. Conclusions: The GLI-2012 reference values seem to fit Norwegian spirometry data quite well but may somewhat underestimate the prevalence of a low FVC in adults.

The study by Taylor-Robinson et al . [1] is unique because of the large number of subjects with cystic fibrosis, the careful follow-up and detailed statistical analysis upon which the authors base their conclusions. This remarkable study was performed in a population with reduced life expectancy. Evaluating the impact of socioeconomic status (SES) on lung function over many decades is particularly daunting in subjects with respiratory disease. Ever since the pioneering work of Villerme [2, 3], the founding father of social epidemiology, numerous studies have documented an association of SES with growth as well as with mortality in adulthood. It is also generally accepted that adverse conditions during childhood lead to stunted growth. For example, in a study of Indian children [4], stature was 4% smaller in the group with the lowest, compared with the highest, SES, and associated with up to 16.7% differences in forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC); adjusting for age and differences in height did not explain these differences. It is therefore attractive to conclude that the lower (“worse”, “poorer” or “compromised”) FEV1 and FVC represent damage associated with poor SES. Whereas this may well be the case, association is no proof of causality. The conclusion hinges entirely on the notion that stature is a good proxy for the dimensions of the chest cavity. However, poor SES or nutritional and health problems (lumped together as SES for short) during early childhood are associated with smaller leg length relative to the height of the upper body segment [5], which biases prediction equations of lung function based on height. There is no evidence that growth stunting due to poor SES is limited to height, so it is logical to assume that chest dimensions will also be affected. If poor SES leads to a 1%, 2% or 3% lower width, depth and height of the thoracic cage, this leads to a 3%, 6% and 9% lower volume of the chest cavity, respectively. Taking into account measurement error and individual variability, it will be difficult to assess such small differences, but they cannot be discarded and might (in part) explain the observed difference in growth of FEV1. Measurements of chest circumference in a large number of subjects might throw some light on the role of differences in body frame. It is bold to disregard the potential role of poor socioeconomic status in lung function over decades of adult life

In this issue of Respiratory Care, Vaz Fragoso et al[1][1] and Aggarwal et al[2][2] make important contributions to the ongoing discussion on how to properly diagnose COPD. Let us put the problem in perspective. In the past there was a growing concern that many cases of COPD went undetected and

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.

Pump systems are currently used to test the performance of both spirometers and peak expiratory flow (PEF) meters, but for certain flow profiles the input signal (i.e., requested profile) and the output profile can differ. We developed a mathematical model of wave action within a pump and compared the recorded flow profiles with both the input profiles and the output predicted by the model. Three American Thoracic Society (ATS) flow profiles and four artificial flow-versus-time profiles were delivered by a pump, first to a pneumotachograph (PT) on its own, then to the PT with a 32-cm upstream extension tube (which would favor wave action), and lastly with the PT in series with and immediately downstream to a mini-Wright peak flow meter. With the PT on its own, recorded flow for the seven profiles was 2.4 +/- 1.9% (mean +/- SD) higher than the pump's input flow, and similarly was 2.3 +/- 2.3% higher than the pump's output flow as predicted by the model. With the extension tube in place, the recorded flow was 6.6 +/- 6.4% higher than the input flow (range: 0.1 to 18.4%), but was only 1.2 +/- 2.5% higher than the output flow predicted by the model (range: -0.8 to 5.2%). With the mini-Wright meter in series, the flow recorded by the PT was on average 6.1 +/- 9.1% below the input flow (range: -23.8 to 2. 5%), but was only 0.6 +/- 3.3% above the pump's output flow predicted by the model (range: -5.5 to 3.9%). The mini-Wright meter's reading (corrected for its nonlinearity) was on average 1.3 +/- 3.6% below the model's predicted output flow (range: -9.0 to 1. 5%). The mini-Wright meter would be deemed outside ATS limits for accuracy for three of the seven profiles when compared with the pump's input PEF, but this would be true for only one profile when compared with the pump's output PEF as predicted by the model. Our study shows that the output flow from pump systems can differ from the input waveform depending on the operating configuration. This effect can be predicted with reasonable accuracy using a model based on nonsteady flow analysis that takes account of pressure wave reflections within pump systems.

Use of fixed ratio FEV1/FVC and % pred FEV1 cut-off points causes misclassification due to age bias http://ow.ly/Cr9xx

In this issue Braun et al . [1] make a plea for an international workshop to review aspects of race and ethnicity in relation to lung function. This is a timely initiative, as many people struggle in epidemiological and genetic studies, and in clinical practice, with the interpretation of test results in an increasingly multi-ethnic society [2]. Our notions of race derive from Blumenbach, who defined “Four varieties of mankind, one species” (adding a fifth variety in 1781) [3]. Definitions of “race” and “ethnic” are confusing and often used interchangeably. This ambiguity is reflected in the frequent use of race/ethnicity, a transitional concept adopted for use while phasing out “race” from the USA census [4]. At this stage the USA census recognises two ethnicities: “Hispanic or Latino”, and “not Hispanic or Latino”, and five races; Hispanic/Latino individuals have a mixed European, African and native American ancestry [5]. American citizens were allowed to self-identify with more than one race in 2000: 2.4% self-identified as multiracial. In sharp contrast, France passed a law in 1978 barring the government from collecting all racial and ethnic data (the Act prohibits collecting “any information that shows, directly or indirectly, racial or ethnic origins, political, philosophical or religious opinions, trade union membership, moral principles, or information that relates to health or sexual life” without either the written consent of the individual or an advance recommendation of the National Commission for Information Technology and Civil Liberties, which must first be approved by the Conseil d’Etat) [6]. The collection of data on race and ethnicity by governments serves administrative and statistical purposes; the classifications should not be interpreted as being scientific or anthropological in nature. However, this caveat is not heeded, and the classifications are …

To determine the interpretative consequences of adopting the Global Lungs 2012 (GLI-2012) spirometric prediction equations in a pediatric hospital population.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.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.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.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.

We investigated the relationship between tests of biochemical lung maturity [lecithin/ sphingomyelin ratio (L/S ratio)], static compliance of the respiratory system (Crs), and estimates of pulmonary gas transfer [venous admixture and arterial/alveolar (a/A) ratio] in a group of intubated preterm infants with and without respiratory distress syndrome (RDS). Thirty infants were studied once (n = 26) or twice (n = 4). The L/S ratio was obtained by means of high-performance thin-layer chromatography and determination of the phosphorus content. Crs was obtained by the multiple occlusion technique. Transcutaneous blood gases and the percentage of oxygen in the inspired gas were recorded and estimates of pulmonary gas transfer were calculated using algorithms. L/S ratio and Crs correlated well (r = 0.73), indicating a higher compliance in biochemically more mature lungs. Both the a/A ratio and venous admixture correlated significantly with the L/S ratio and Crs (P < 0.001). Crs L/S ratio, and a/A ratio decreased with increasing severity of radiological RDS, and the percentage venous admixture increased (P < 0.001). Sequential measurements in four infants during the acute phase and after RDS resolved indicated that clinical improvement coincided with improvements in biochemical lung maturity, Crs, and estimates of pulmonary gas transfer. Pediatr Pulmonol. 1995; 20:152–159. © 1995 Wiley-Liss, Inc.

Several studies have suggested that the TLC after childhood asthma is increased compared wtih that in healthy subjects. The aim of this study was to assess whether TLC is increased after childhood asthma and whether this is associated with an increased growth of the lung during adolescence. During a mean period of 29 months we studied 53 patients and 106 healthy control subjects who were matched for sex, age, and standing height. The patients had had asthma for a mean period of 10 yr. We found that in asthmatics TLC was increased in both sexes by about 7% predicted compared with that in the matched control subjects. The growth of TLC in ml/yr during adolescence was less in patients; this can be accounted for by a delay in pubertal development. When corrected for the delay in growth of stature, growth of TLC in ml/cm in asthmatics was similar to that found in control subjects. These findings support the hypothesis of a developmental change of enhanced lung growth during childhood asthma; they do not support a mechanism with progressive loss of elastic recoil of the lung.

Background. Growth in stature in asthmatic adolescents may be delayed compared to normals as a result of treatment with inhaled corticosteroids (CS) or because of a delay in puberty. However, growth rates in asthmatic children have never been studied when treatment with CS was randomized and when growth was compared with that of matched healthy control subjects. Objective. To assess the long-term effect of CS treatment on growth rates in asthmatic adolescents. Methods. Participants were 40 asthmatic teenagers (mean age 12.8 years) who received randomized treatment with 0.2 mg of albuterol (salbutamol) with either placebo three times a day (BA + PL) or 0.2 mg of budesonide three times a day (BA + CS) for a median period of 22 months in a double-blind controlled study. Growth rates were compared with those of 80 control subjects who were matched for sex, age, height, and duration of follow-up. Results. Growth rates in male patients, but not in female patients, were significantly less than in control subjects (P < .05), a finding consistent with a delay of puberty due to asthma. The mean difference (95% confidence interval) in growth rates between patients treated with BA + PL and their controls was -0.70 (–1.62, 0.22) cm/y; that between patients treated with BA + CS and their controls was -0.44 (–1.25, 0.37) cm/y. The observed mean (SEM) case-control difference between treatment groups was + 0.27 (0.58) cm/y in favor of BA + CS. Conclusion. Growth retardation observed in adolescents with asthma may be due to a delay in puberty but not to the prescription of 0.6 mg of budesonide daily.

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.

Dear colleagues, members of GOLD committee, This letter arises from discussions and correspondence between colleagues involved in respiratory research or the diagnosis and treatment of lung diseases, as well as from a review of the literature on chronic obstructive pulmonary disease (COPD). As discussed below, it is written in the hope that we can persuade members of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) committee to vote to change the method by which mild airway obstruction is defined by the GOLD guidelines. We very much welcome the continued efforts of the GOLD group to stimulate interest and awareness of the high prevalence of COPD, its morbidity, effects on quality of life and on mortality. There is no doubt that COPD is a major public health problem of which the public, health workers and health authorities were insufficiently aware. It is therefore an important achievement that the World Health Organization (WHO), the European Respiratory Society (ERS), the American Thoracic Society (ATS), the Asian Pacific Society of Respirology (APSR), the Asociacion Latinoamericana de Torax (ALAT), and the World Organization of Family Doctors (WONCA) and many distinguished individuals have joined forces to increase awareness about the burden of disease, by publishing reports and guidelines for diagnostic procedures and interventions which have been adopted by numerous international and national organisations. However, there is one area which has given rise to continuous published criticism: the criterion for confirming airway obstruction. It is well known that the forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio declines with increasing age and height, even in healthy lifelong nonsmokers, in whom the lower limit of normal drops below a ratio of 0.7 from about 45 yrs of age [1–6]. It has been shown 4–27 that using the fixed ratio causes up …

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.

In 28 healthy newborn infants (median age 3.5 days), we compared the weighted spirometer (WS) with the multiple occlusion (MO) method for measuring respiratory system compliance (Crs). The MO method was unsuccessful in 8 infants. On average the two methods gave comparable results for compliance (Crs,ws = 40.4 ± 13.8 and Crs,MO = 45.2 ± 10.4 mL·kPa−1) in the remaining 20 infants; however, within-individual differences were often considerable, so that the methods did not give interchangeable results. Individual pressure-volume curves almost always intercepted the volume axis below the functional residual capacity with the MO technique, compatible with dynamic elevation of end-expiratory lung volume (EEL) due to inspiratory muscle activity during expiration. A (small) negative volume intercept occurred in less than 50% of curves with the WS method; in these cases it probably reflects alinearity of the compliance curve, an alteration in laryngeal braking or in respiratory muscle control of EEL, or all of these. Both methods provide valuable means for the non-invasive determination of respiratory system compliance in newborn infants, the differences in Crs being small and of minimal physiological significance; however, for individual follow-up they should not be used interchangeably. Pediatr Pulmonol 1990; 8:273-279.

reasonable to conclude that if PSR inhibition occurred at a higher PaCO2 during PLV than GV then pulmonary stretch must have been higher during PLV than GV. That is, PSR activity was inhibited during PLV at a higher pressure than during GV since PaCO2 was high during PLV. In addition, since the model studied by Sindelar and coworkers was a small lung lavage–injured cat (2.3 1.0 kg), it is unlikely that the impact of perfluorocarbons on dependent lung would be the same as in an adult human. The difference in the height of the lungs (about 3 to 4 cm vs. 15 to 20 cm) would result in marked differences in the effect of the perfluorocarbon on dependent alveoli. Considering the quantity of perfluorocarbon instilled in adult patients (30 ml/kg or about 2,250 ml, 75 kg adult) versus the studied cats (30 ml/kg or about 69 ml, 2.3 kg) and a perfluorocarbon density of 1.9, it is difficult to conceive that the most gravity-dependent alveolar pressure during both inspiration and expiration would be similar during GV and PLV at the same airway gas pressure. It is important to remember that, during PLV, gas ventilation is provided on top of the perfluorocarbon-filled lungs. It is true that with gas ventilation the perfluorocarbon spreads over a larger lung area. However, there is still a column of fluid on top of dependent alveoli that is pressurized by the gas ventilation. Overall, what is clearly needed is additional research into the use of perfluorocarbon-assisted ventilation and the mechanisms associated with both its beneficial and detrimental effects.