Bruce H. Culver

Multi-ethnic reference values for spirometry for the 3-95-yr age range: The global lung function 2012 equations

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 (FEV1) and forced vital capacity (FVC) between ethnic groups differed proportionally from that in Caucasians, such that FEV1/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.

An official European Respiratory Society/American Thoracic Society technical standard: field walking tests in chronic respiratory disease

Field walking tests are commonly employed to evaluate exercise capacity, assess prognosis and evaluate treatment response in chronic respiratory diseases. In recent years, there has been a wealth of new literature pertinent to the conduct of the 6-min walk test (6MWT), and a growing evidence base describing the incremental and endurance shuttle walk tests (ISWT and ESWT, respectively). The aim of this document is to describe the standard operating procedures for the 6MWT, ISWT and ESWT, which can be consistently employed by clinicians and researchers. The Technical Standard was developed by a multidisciplinary and international group of clinicians and researchers with expertise in the application of field walking tests. The procedures are underpinned by a concurrent systematic review of literature relevant to measurement properties and test conduct in adults with chronic respiratory disease. Current data confirm that the 6MWT, ISWT and ESWT are valid, reliable and responsive to change with some interventions. However, results are sensitive to small changes in methodology. It is important that two tests are conducted for the 6MWT and ISWT. This Technical Standard for field walking tests reflects current evidence regarding procedures that should be used to achieve robust results. Technical Standard document: standard operating procedures for the 6MWT, ISWT and ESWT in chronic respiratory disease http://ow.ly/Bq2B9

An official systematic review of the European Respiratory Society/American Thoracic Society: measurement properties of field walking tests in chronic respiratory disease

This systematic review examined the measurement properties of the 6-min walk test (6MWT), incremental shuttle walk test (ISWT) and endurance shuttle walk test (ESWT) in adults with chronic respiratory disease. Studies that report the evaluation or use of the 6MWT, ISWT or ESWT were included. We searched electronic databases for studies published between January 2000 and September 2013. The 6-min walking distance (6MWD) is a reliable measure (intra-class correlation coefficients ranged from 0.82 to 0.99 in seven studies). There is a learning effect, with greater distance walked on the second test (pooled mean improvement of 26 m in 13 studies). Reliability was similar for ISWT and ESWT, with a learning effect also evident for ISWT (pooled mean improvement of 20 m in six studies). The 6MWD correlates more strongly with peak work capacity (r=0.59–0.93) and physical activity (r=0.40–0.85) than with respiratory function (r=0.10–0.59). Methodological factors affecting 6MWD include track length, encouragement, supplemental oxygen and walking aids. Supplemental oxygen also affects ISWT and ESWT performance. Responsiveness was moderate to high for all tests, with greater responsiveness to interventions that included exercise training. The findings of this review demonstrate that the 6MWT, ISWT and ESWT are robust tests of functional exercise capacity in adults with chronic respiratory disease. Systematic review: support for use of the 6MWT, ISWT and ESWT in adults with chronic respiratory disease http://ow.ly/Bq2Mz

ERS technical standard on bronchial challenge testing: General considerations and performance of methacholine challenge tests

This international task force report updates general considerations for bronchial challenge testing and the performance of the methacholine challenge test. There are notable changes from prior recommendations in order to accommodate newer delivery devices. Rather than basing the test result upon a methacholine concentration (provocative concentration (PC20) causing a 20% fall in forced expiratory volume in 1 s (FEV1)), the new recommendations base the result upon the delivered dose of methacholine causing a 20% fall in FEV1 (provocative dose (PD20)). This end-point allows comparable results from different devices or protocols, thus any suitable nebuliser or dosimeter may be used, so long as the delivery characteristics are known. Inhalation may be by tidal breathing using a breath-actuated or continuous nebuliser for 1 min (or more), or by a dosimeter with a suitable breath count. Tests requiring maximal inhalations to total lung capacity are not recommended because the bronchoprotective effect of a deep breath reduces the sensitivity of the test. The new ERS recommendation for methacholine challenge tests will be the provocative dose rather than concentration http://ow.ly/FBe5309yXn2

How should the lower limit of the normal range be defined

Lung function parameters vary considerably with age and body size, so that, unlike many laboratory tests, the normal range of expected values must be individualized. For spirometry, only low values are considered to be abnormal, so the lower limit of normal (LLN) is taken to be equal to the 5th percentile of a healthy, non-smoking population. Simple and commonly used “rules of thumb,” such as an FEV1/FVC < 0.70 to indicate air-flow obstruction, or assuming values < 80% of predicted to be abnormal, are inaccurate and will cause misclassification, specifically under-diagnosis of abnormalities in younger, taller individuals and over-diagnosis in those older or shorter. A much more accurate LLN for the FEV1/FVC ratio, which recognizes the change with age of this measurement, can be easily determined by subtracting 10 (10% or 0.10) from the age specific FEV1/FVC predicted for any individual. The analysis and mathematical descriptions of reference data have become increasingly sophisticated in recent years, but the interpretation of values near the LLN continues to carry uncertainty, due to an overlap in values between low normal values and those reflecting early disease. Among patients referred to a pulmonary function laboratory, the pre-test probability of disease may be relatively high, so that even individuals with values above the LLN may be more likely than not to have respiratory disease. A future goal for the pulmonary community would be the development of risk stratified outcome data that would allow an estimation of the probability of disease with progressive decrements in lung function. While interpreting spirometry results near the LLN will continue to be problematic, a more important task for the pulmonary community is to focus on finding the pool of individuals with clear-cut, but undiagnosed, COPD. And for this, good quality spirometry remains the best tool and must be widely available.

Recommendations for a Standardized Pulmonary Function Report. An Official American Thoracic Society Technical Statement

Background: The American Thoracic Society committee on Proficiency Standards for Pulmonary Function Laboratories has recognized the need for a standardized reporting format for pulmonary function tests. Although prior documents have offered guidance on the reporting of test data, there is considerable variability in how these results are presented to end users, leading to potential confusion and miscommunication. Methods: A project task force, consisting of the committee as a whole, was approved to develop a new Technical Standard on reporting pulmonary function test results. Three working groups addressed the presentation format, the reference data supporting interpretation of results, and a system for grading quality of test efforts. Each group reviewed relevant literature and wrote drafts that were merged into the final document. Results: This document presents a reporting format in test‐specific units for spirometry, lung volumes, and diffusing capacity that can be assembled into a report appropriate for a laboratorys practice. Recommended reference sources are updated with data for spirometry and diffusing capacity published since prior documents. A grading system is presented to encourage uniformity in the important function of test quality assessment. Conclusions: The committee believes that wide adoption of these formats and their underlying principles by equipment manufacturers and pulmonary function laboratories can improve the interpretation, communication, and understanding of test results.

Clinical aspects of pulmonary embolism

Pulmonary embolism is a common disease in the United States, affecting as many as 500,000 persons annually. Unfortunately, this disorder is commonly undiagnosed, resulting in significant excess morbidity and mortality. The clinical symptoms and signs caused by pulmonary embolism are nonspecific and may be confused with a variety of other cardiopulmonary disorders having similar presentations. However, accurate diagnostic tests are available for diagnosing pulmonary embolism, even in the face of coexistent cardiopulmonary disorders. This article describes the clinical characteristics of pulmonary venous thromboembolism, reviewing its typical symptoms and signs, its routine laboratory tests, and chest radiographic abnormalities.

Defining airflow obstruction

Using a very large number of predominantly Chinese nonsmoking females aged 30–79 years, Smith et al. [1] studied the relationship between airflow obstruction, household air pollution, household income, educational level and prior tuberculosis. They defined airflow obstruction as a ratio of forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) of <0.7 or <5th percentile, and graded the severity of respiratory impairment using FEV1 80% of predicted as a cut-off point, according to Global Lung Function Initiative 2012 prediction equations [2]. There are two fundamental problems with these criteria that affect the interpretation of their findings. Use of fixed ratio FEV1/FVC and % pred FEV1 cut-off points causes misclassification due to age bias http://ow.ly/Cr9xx

COPD (confusion over proper diagnosis) in the zone of maximum uncertainty

In an excellent statement on chronic obstructive lung disease (COPD) that focuses on questions that are relevant for the patients well-being and quality of life [1, 2], one issue should have received more critical attention. For research into COPD, it is vital that the diagnosis of airway obstruction, which traditionally hinges on a forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio below a threshold, can be accurately established. Celli et al. [1, 2] state that this threshold is uncertain, leaving the recommendations open ended to some extent. They refer to the discussion whether in ascertaining a diagnosis of COPD the threshold for the FEV1/FVC ratio should be the lower limit of normal (LLN), defined in respiratory medicine as the 5th centile in a representative sample of healthy nonsmokers, or the post-bronchodilator FEV1/FVC of 0.7 first proposed in 2001 by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) group [3]. The latter threshold has not been clinically validated; it was intended to simplify recognition and increase awareness of COPD, particularly in less developed countries where the LLN might not be presented with the test results. The use of the fixed ratio has been extensively criticised. Cross-sectional data show that it leads to underestimating the prevalence of airflow limitation in younger people and to large overestimates in those older than 45 years. In 80-year-old healthy subjects, this leads to a 75–80% false positive rate [4]. The Burden of Obstructive Lung Disease (BOLD) group also routinely uses the LLN cut-off for reporting the prevalence of abnormal ventilatory function [5]. Follow-up studies have shed light on the question of whether observations in the zone between the fixed ratio and LLN represent respiratory disease. In asymptomatic subjects and very elderly subjects, an FEV1/FVC above the LLN but below 0.7 was not associated with premature death [6–10], an abnormal decline in FEV1 [11–13], respiratory care use [11], hospitalisation [10] or quality of life [11]. Conversely, an FEV1/FVC ratio below the LLN is associated with increased risk of hospitalisation [10] and mortality [8–10, 12, 13]. Three reports [9, 16, 17] suggested that use of the LLN cut-off would miss individuals at risk, but these findings have been contested [18–21]. A A fixed cut-off in FEV1/FVC ratio is not an appropriate measure for diagnosing COPD http://ow.ly/RZyLe

Bronchial-atrial fistula after lung transplant resulting in fatal air embolism.

We describe a rare case of fatal air embolism in a patient in whom a left atrial-bronchial fistula developed 1 month after single lung transplant. The cause was a combination of mediastinal infection and bronchial necrosis.