FEV1Q: a race-neutral approach to assessing lung function.

BACKGROUND: Forced expiratory volume in 1 s quotient (FEV1Q) is a simple approach to spirometry interpretation that compares measured lung function to a lower boundary. This study evaluated how well FEV1Q predicts survival compared with current interpretation methods and whether race impacts FEV1Q. METHODS: White and Black adults with complete spirometry and mortality data from the National Health and Nutrition Examination Survey (NHANES) III and the United Network for Organ Sharing (UNOS) database for lung transplant referrals were included. FEV1Q was calculated as FEV1 divided by 0.4 L for females or 0.5 L for males. Cumulative distributions of FEV1 were compared across races. Cox proportional hazards models tested mortality risk from FEV1Q adjusting for age, sex, height, smoking, income and among UNOS individuals, referral diagnosis. Harrell's C-statistics were compared between absolute FEV1, FEV1Q, FEV1/height2, FEV1 z-scores and FEV1 % predicted. Analyses were stratified by race. RESULTS: Among 7182 individuals from NHANES III and 7149 from UNOS, 1907 (27%) and 991 (14%), respectively, were Black. The lower boundary FEV1 values did not differ between Black and White individuals in either population (FEV1 first percentile difference ≤0.01 L; p>0.05). Decreasing FEV1Q was associated with increasing hazard ratio (HR) for mortality (NHANES III HR 1.33 (95% CI 1.28-1.39) and UNOS HR 1.18 (95% CI 1.12-1.23)). The associations were not confounded nor modified by race. Discriminative power was highest for FEV1Q compared with alternative FEV1 approaches in both Black and White individuals. CONCLUSIONS: FEV1Q is an intuitive and simple race-neutral approach to interpreting FEV1 that predicts survival better than current alternative methods.

ERS/ATS technical standard on interpretive strategies for routine lung function tests.

BACKGROUND: Appropriate interpretation of pulmonary function tests (PFTs) involves the classification of observed values as within/outside the normal range based on a reference population of healthy individuals, integrating knowledge of physiological determinants of test results into functional classifications and integrating patterns with other clinical data to estimate prognosis. In 2005, the American Thoracic Society (ATS) and European Respiratory Society (ERS) jointly adopted technical standards for the interpretation of PFTs. We aimed to update the 2005 recommendations and incorporate evidence from recent literature to establish new standards for PFT interpretation. METHODS: This technical standards document was developed by an international joint Task Force, appointed by the ERS/ATS with multidisciplinary expertise in conducting and interpreting PFTs and developing international standards. A comprehensive literature review was conducted and published evidence was reviewed. RESULTS: Recommendations for the choice of reference equations and limits of normal of the healthy population to identify individuals with unusually low or high results are discussed. Interpretation strategies for bronchodilator responsiveness testing, limits of natural changes over time and severity are also updated. Interpretation of measurements made by spirometry, lung volumes and gas transfer are described as they relate to underlying pathophysiology with updated classification protocols of common impairments. CONCLUSIONS: Interpretation of PFTs must be complemented with clinical expertise and consideration of the inherent biological variability of the test and the uncertainty of the test result to ensure appropriate interpretation of an individual's lung function measurements.

Standardization of Spirometry 2019 Update. An Official American Thoracic Society and European Respiratory Society Technical Statement.

Background: Spirometry is the most common pulmonary function test. It is widely used in the assessment of lung function to provide objective information used in the diagnosis of lung diseases and monitoring lung health. In 2005, the American Thoracic Society and the European Respiratory Society jointly adopted technical standards for conducting spirometry. Improvements in instrumentation and computational capabilities, together with new research studies and enhanced quality assurance approaches, have led to the need to update the 2005 technical standards for spirometry to take full advantage of current technical capabilities.Methods: This spirometry technical standards document was developed by an international joint task force, appointed by the American Thoracic Society and the European Respiratory Society, with expertise in conducting and analyzing pulmonary function tests, laboratory quality assurance, and developing international standards. A comprehensive review of published evidence was performed. A patient survey was developed to capture patients' experiences.Results: Revisions to the 2005 technical standards for spirometry were made, including the addition of factors that were not previously considered. Evidence to support the revisions was cited when applicable. The experience and expertise of task force members were used to develop recommended best practices.Conclusions: Standards and consensus recommendations are presented for manufacturers, clinicians, operators, and researchers with the aims of increasing the accuracy, precision, and quality of spirometric measurements and improving the patient experience. A comprehensive guide to aid in the implementation of these standards was developed as an online supplement.

The effect of organic dust exposure on long-term change in lung function: a systematic review and meta-analysis.

Lung function is a predictor of morbidity and mortality, and the chronic nature of lung function decline allows for preventive initiatives. Proinflammatory constituents of organic dust are considered a possible cause of compromised respiratory health. The aim of this systematic review was to reveal the impact of organic dust exposure on long-term change in lung function. The literature search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. Predefined criteria concerned study design: longitudinal, ≥1 year follow-up, ≥50 exposed; exposure measures: organic dust, measured or estimated, in different occupational settings; and outcome measures: change in lung function measured by spirometry. Based on these criteria, 1580 potentially relevant publications were narrowed down to 20 included publications. Quality was evaluated and discussed based on six objectively defined criteria. Overall, 14 studies found some type of association between exposure to organic dust and long-term change in lung function. However, the results were inconsistent and no specific work exposure showed more clear associations to change in lung function. Meta-analysis revealed an overall small significant excess loss in forced expiratory volume in the 1st s for exposed compared with controls of 4.92 mL/year (95% CI 0.14 to 9.69). No significant association was seen overall for forced vital capacity. 12 studies revealed a significant exposure-response relation between organic dust and change in lung function. The results were inconsistent across varying study design and different exposure measures and outcomes. We therefore conclude that there is limited evidence of a causal association between general exposure to organic dust and long-term excess decline in lung function.

The effect of occupational farming on lung function development in young adults: a 15-year follow-up study.

OBJECTIVES: Longitudinal studies on the effect of farming on lung function in young participants are few. Our objective was to explore if exposure to farming impaired lung function in young adults. METHODS: We studied 1964 farming students and 407 controls in 1992/2004, and carried out follow-up in 2007/2008. Spirometry, skin prick test and bronchial hyper-responsiveness (BHR) were assessed, height and weight measured, and questionnaires covering health and occupation were collected. Cumulative dust and endotoxin exposures were estimated from modelled personal dust measurements. Lung function effect was expressed as change in z-score during follow-up using the Global Lung Initiative 2012 project prediction equations. Longitudinal data were available for 1134 young participants ≤25 years at baseline. RESULTS: We found no differences in lung function Δz-scores between farmers and controls, however, adjusted multivariable linear regression showed a negative effect among current farmers on ΔzFEV1 (forced expiratory volume in 1 s; -0.12, p=0.006) and ΔzFEV1/FVC (forced vital capacity; -0.15, p=0.009) compared to ex-farmers. An interaction was found between sex and farming, showing that current farming suppresses ΔzFEV1 and ΔzFVC more among females. Smoking in farmers had a deleterious effect on ΔzFEV1, which was not seen in controls, though no significant interaction was found. Farm upbringing protected against impairment of lung function, and BHR at baseline had a deleterious effect on ΔzFEV1 only in those not raised on a farm. CONCLUSIONS: We conclude that being a current farmer is associated with a negative effect on lung function, when compared to ex-farmers, with females being more susceptible. Being raised on a farm protects against the adverse effect of BHR on change in lung function.

Best lung function equations for the very elderly selected by survival analysis.

We evaluated which equations best predicted the lung function of a cohort of nonagenarians based on which best accounted for subsequent survival. In 1998, we measured lung function, grip strength and dementia score (Mini Mental State Examination (MMSE)) in a population-based sample of 2262 Danes born in 1905. Mortality was registered to 2011 when only five (0.2%) subjects were alive. In half the cohort, we recorded forced expiratory volume in 1 s (FEV1). Complete data were available in 592 subjects with results expressed as standardised residuals (SR) using various prediction equations. Cox proportional hazard regression found lower FEV1SR was a predictor of mortality having controlled for MMSE, grip strength and sex. The US National Health and Nutrition Examination Survey (NHANES) III (1999) equations gave a better spread of median survival by FEV1SR quartile: 3.94, 3.65, 3.51 and 2.61 years with a hazard ratio for death of 1, 1.16, 1.32 and 1.60 respectively, compared with equations derived with the inclusion of elderly subjects. We conclude that extrapolating from NHANES III equations to predict lung function in nonagenarians gave better survival predictions from spirometry than when employing equations derived using very elderly subjects with possible selection bias. These findings can help inform how future lung function equations for the elderly are derived.

TargetCOPD: a pragmatic randomised controlled trial of targeted case finding for COPD versus routine practice in primary care: protocol.

BACKGROUND: Many people with clinically significant chronic obstructive pulmonary disease (COPD) remain undiagnosed worldwide. There are a number of small studies which have examined possible methods of case finding through primary care, but no large RCTs that have adequately assessed the most cost-effective approach. METHODS/DESIGN: In this study, using a cluster randomised controlled trial (RCT) in 56 general practices in the West Midlands, we plan to investigate the effectiveness and cost-effectiveness of a Targeted approach to case finding for COPD compared with routine practice. Using an individual patient RCT nested in the Targeted arm, we plan also to compare the effectiveness and cost-effectiveness of Active case finding using a postal questionnaire (with supplementary opportunistic questionnaires), and Opportunistic-only case finding during routine surgery consultations.All ever-smoking patients aged 40-79 years, without a current diagnosis of COPD and registered with participating practices will be eligible. Patients in the Targeted arm who report positive respiratory symptoms (chronic cough or phlegm, wheeze or dyspnoea) using a brief questionnaire will be invited for further spirometric assessment to ascertain whether they have COPD or not. Post-bronchodilator spirometry will be conducted to ATS standards using an Easy One spirometer by trained research assistants.The primary outcomes will be new cases of COPD and cost per new case identified, comparing targeted case finding with routine care, and two types of targeted case finding (active versus opportunistic). A multilevel logistic regression model will be used to model the probability of detecting a new case of COPD for each treatment arm, with clustering of patients (by practice and household) accounted for using a multi-level structure.A trial-based analysis will be undertaken using costs and outcomes collected during the trial. Secondary outcomes include the feasibility, efficiency, long-term cost-effectiveness, patient and primary care staff views of each approach. DISCUSSION: This will be the largest RCT of its kind, and should inform how best to identify undiagnosed patients with COPD in the UK and other similar healthcare systems. Sensitivity analyses will help local policy-makers decide which sub-groups of the population to target first. TRIAL REGISTRATION: Current controlled trials ISRCTN14930255.

How to account for Inuit ancestry in lung function prediction.

Rigorous lung function prediction equations for the Inuit are lacking. We used spirometry from 351 Inuit and 29 people of other ancestry obtained during an occupational survey in Greenland to determine how to obtain valid lung function predictions for the Inuit using Global Lung Function Initiative (GLI) equations for Europeans. Standing height for the Inuit was used in the predictions as well as their height modified in line with the known differences in standing to sitting height ratio (SHR) for the Inuit. With recorded height in predicting lung function, mean±SD Inuit z-scores for FVC and FEV1 were significantly higher than predicted (0.81±1.20 and 0.53±1.36, respectively, p<0.0001) which was not true for the non-Inuit participants (-0.01±1.04 and 0.15±1.17, respectively). When using height modified for SHR the mean±SD Inuit z-scores for FVC and FEV1 were no longer significantly different from predicted (0.10±1.10 and -0.12±1.24, respectively). The mean±SD Inuit FEV1/FVC z-scores were not significantly different from the non-Inuit, being respectively -0.45±0.98 and -0.01±1.04. Modified height changed the mean±SD Inuit FEV1/FVC z-scores to -0.39±0.99. Representative lung function predictions from GLI equations can be made for Inuit by using standing height modified for the known differences in SHR between Inuit and those of European ancestry.

Sex, susceptibility to smoking and chronic obstructive pulmonary disease: the effect of different diagnostic criteria. Analysis of the Health Survey for England.

BACKGROUND: Some previous studies suggest there are sex differences in susceptibility to, and prevalence of, chronic obstructive pulmonary disease (COPD) but findings are inconsistent. In this study, whether different diagnostic criteria for COPD may contribute to these conflicting findings was examined. METHODS: Cross sectional analysis of data from the 1995, 1996 and 2001 Health Survey for England was undertaken, including participants of white ethnicity, aged 40+ years with a valid smoking history and lung function data. COPD was defined using Global Initiative for Chronic Obstructive Lung Disease (GOLD), National Institute for Health and Clinical Excellence (NICE) and lower limit of normal (LLN) spirometric criteria, in the absence of a diagnosis of asthma. RESULTS: COPD was present in 3035 (16.1%), 1304 (7.0%) and 1684 (9.0%) people, according to the GOLD, NICE and LLN criteria, respectively. With both the GOLD and NICE definitions, men had significant independent increased risks of COPD compared with women (OR 1.46 (95% CI 1.34 to 1.59) and 1.30 (1.15 to 1.48), respectively). With the LLN definition, this effect was removed (OR 0.96 (0.87 to 1.07). With the use of both the GOLD and NICE criteria, women had significantly greater susceptibility to COPD (25-30% higher risk) for the same level of pack years of exposure. This was not observed with the LLN criteria. CONCLUSIONS: The study indicates that sex differences in risk of COPD reported in previous studies are influenced by the definition used for COPD. When using a statistically driven definition (LLN), no independent sex difference was found and there was no evidence of an increased susceptibility to COPD among female compared with male smokers.

Validation of lung function prediction equations from patient survival data.

Diagnosing and managing pulmonary disease usually requires judging lung function against predicted values. We explored patient survival data to help identify the best equations for our population. The earliest spirometry, lung volumes and gas transfer data for all Caucasian patients were extracted from our database. Survival status was available for 8,139 patients. Lung function as standardised residuals (SR) from various prediction equations was used in Cox regression to predict the hazard ratio (HR) for death. The best lung function predictor of all-cause mortality was diffusing capacity of the lung for carbon monoxide (D(L,CO)), followed by forced vital capacity (FVC). These were best with the equations of Miller, derived from a US population, with Chi-squared values of 1,468 and 1,043 for D(L,CO) and FVC, respectively, having taken age, sex, smoking status and body mass index into account. The HR (95% CI) for SR < -3 were 8.5 (6.0-12.1) and 2.9 (2.3-3.5), respectively. Spirometric equation prediction models varied less than those for D(L,CO), with the Miller equations being slightly better than Lambda-Mu-Sigma (LMS) equations. Some D(L,CO) equations introduced sex bias (male sex HR of 3.0 versus 1.5 for other equations). We conclude that LMS or Miller spirometry equations and Miller's D(L,CO) equations were best for our patient population. Using patient survival data is a new approach to help select which lung function prediction equations to use.