Brian L. Graham

A Theoretical Analysis of the Single Breath Diffusing Capacity for Carbon Monoxide

We used a computerized lung model to examine methods of measuring the single breath diffusing capacity for carbon monoxide (DLCOSB). Although the single breath maneuver consists of inhalation, breath holding, and exhalation, current methods of measuring DLCOSB use one equation that is accurate only for breath holding, and they attempt to correct for the effects of inhalation and exhalation using a rigidly standardized procedure. Using a uniform lung model, we verified that variations in performing the standarized maneuver and variations in alveolar gas sampling, which frequently occur in practice, cause wide variability in the measured DLCOSB. We developed a new method of calculating DLCOSB based on three equations to describe diffusion in the lung during inhalation, breath holding, and exhalation. In computer simulations of the single breath maneuver, this method yielded accurate measurements of DLCOSB despite variations in flow rates, breath hold times, or the size and timing of the collected sample of exhaled alveolar gas. Furthermore, using a lung model in which the diffusing capacity was nonuniformly distributed, we found that this method gave an accurate estimate of the overall diffusing capacity of the lung from the collection of the entire exhaled alveolar gas sample, while previously accepted methods overestimated DLCOSB. We predict that a more precise calculation of the overall diffusing capacity using the entire alveolar gas sample can minimize errors in the test introduced by variations in the maneuver or variations in the distribution of diffusion.

2017 ERS/ATS standards for single-breath carbon monoxide uptake in the lung

This document provides an update to the European Respiratory Society (ERS)/American Thoracic Society (ATS) technical standards for single-breath carbon monoxide uptake in the lung that was last updated in 2005. Although both DLCO (diffusing capacity) and TLCO (transfer factor) are valid terms to describe the uptake of carbon monoxide in the lung, the term DLCO is used in this document. A joint taskforce appointed by the ERS and ATS reviewed the recent literature on the measurement of DLCO and surveyed the current technical capabilities of instrumentation being manufactured around the world. The recommendations in this document represent the consensus of the taskforce members in regard to the evidence available for various aspects of DLCO measurement. Furthermore, it reflects the expert opinion of the taskforce members on areas in which peer-reviewed evidence was either not available or was incomplete. The major changes in these technical standards relate to DLCO measurement with systems using rapidly responding gas analysers for carbon monoxide and the tracer gas, which are now the most common type of DLCO instrumentation being manufactured. Technical improvements and the increased capability afforded by these new systems permit enhanced measurement of DLCO and the opportunity to include other optional measures of lung function. Updated technical standards for measuring DLCO (TLCO) including the use of rapid gas analyser systems http://ow.ly/QUhv304PMsy

Spirometry in Primary Care

Canadian Thoracic Society (CTS) clinical guidelines for asthma and chronic obstructive pulmonary disease (COPD) specify that spirometry should be used to diagnose these diseases. Given the burden of asthma and COPD, most people with these diseases will be diagnosed in the primary care setting. The present CTS position statement was developed to provide guidance on key factors affecting the quality of spirometry testing in the primary care setting. The present statement may also be used to inform and guide the accreditation process for spirometry in each province. Although many of the principles discussed are equally applicable to pulmonary function laboratories and interpretation of tests by respirologists, they are held to a higher standard and are outside the scope of the present statement.

Effect of a deep breath on gas mixing and diffusion in the lung.

We examined the effect of a previous deep breath on both inert gas mixing and the single breath diffusing capacity (DLCOSB) during submaximal single breath maneuvers in normal subjects. Single breath washouts were performed either immediately after a deep breath or after breathing tidally for 10 min. Maneuvers consisted of inhaling test gas from functional residual capacity to 50% inspiratory capacity and, after either 0 or 6 s of breath holding, exhaling slowly back to residual volume. We measured the Fowler dead space, the Phase III slope of the alveolar plateau of the He washout (delta He/L), the amplitude of the cardiogenic oscillations (Oc), closing capacity, mixing efficiency (Emix) and DLCOSB using the three equation method. For maneuvers immediately after a deep breath we found that delta He/L was steeper and the Oc were larger for washouts with 6 s but not 0 s of breath holding, while Emix was significantly lower and DLCOSB significantly higher for both the 0 s and the 6 s breath holding maneuvers. We conclude that a deep breath increases DLCOSB but simultaneously also increases convective-dependent inhomogeneity in the lung.

Effect of high negative inspiratory pressure on single breath CO diffusing capacity

We measured the single breath diffusing capacity for carbon monoxide (DLcoSB) using a three-equation method to describe CO uptake in 10 normal seated subjects who either voluntarily inhaled slowly (0.5 L/sec) to total lung capacity (TLC), or inhaled slowly to TLC with maximal effort through a high inspiratory resistance which created high negative inspiratory pressure. Subjects then immediately exhaled slowly at a voluntarily controlled exhaled flow. Single breath maneuvers were performed in duplicate both with and without high negative inspiratory pressure while subjects were seated upright at rest and during steady-state bicycle exercise. We found that high negative inspiratory pressure increased DLcoSB by 10.5 +/- 4.9% (mean +/- 1 SD) at rest (P less than 0.001). In 7 subjects low level exercise alone increased DLcoSB by a similar amount (12.1 +/- 7.3%; P = 0.005). In six of the subjects there was a significant correlation between the increase in DLcoSB during high negative inspiratory pressure at rest and the increase in DLcoSB during steady-state exercise (r = 0.89; P less than 0.01). During steady-state exercise, high negative inspiratory pressure further increased DLcoSB 6.4 +/- 6.3% compared to exercise alone (P = 0.05). We conclude that the increase in DLcoSB with high negative inspiratory pressure at rest is a simple reproducible method of assessing recruitment of the pulmonary capillary bed in man.

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.

Official ERS technical standards: Global Lung Function Initiative reference values for the carbon monoxide transfer factor for Caucasians

There are numerous reference equations available for the single-breath transfer factor of the lung for carbon monoxide (T LCO); however, it is not always clear which reference set should be used in clinical practice. The aim of the study was to develop the Global Lung Function Initiative (GLI) all-age reference values for T LCO. Data from 19 centres in 14 countries were collected to define T LCO reference values. Similar to the GLI spirometry project, reference values were derived using the LMS (lambda, mu, sigma) method and the GAMLSS (generalised additive models for location, scale and shape) programme in R. 12 660 T LCO measurements from asymptomatic, lifetime nonsmokers were submitted; 85% of the submitted data were from Caucasians. All data were uncorrected for haemoglobin concentration. Following adjustments for elevation above sea level, gas concentration and assumptions used for calculating the anatomic dead space volume, there was a high degree of overlap between the datasets. Reference values for Caucasians aged 5–85 years were derived for T LCO, transfer coefficient of the lung for carbon monoxide and alveolar volume. This is the largest collection of normative T LCO data, and the first global reference values available for T LCO. This is the largest collection of normative TLCO data and represents a step towards standardised interpretation http://ow.ly/4PcZ30dB1tn

Sleep Laboratory Test Referrals in Canada: Sleep Apnea Rapid Response Survey

BACKGROUND An estimated 5.4 million Canadian adults have been diagnosed with sleep apnea or are at high risk of experiencing obstructive sleep apnea (OSA). There are no recent Canadian data regarding access to and predictors of referral for diagnostic testing in these populations. METHODS The Sleep Apnea Rapid Response survey sampled 8647 Canadian adults and captured information about risk, testing, diagnosis and treatment of sleep apnea. Predictors of sleep laboratory test referrals were assessed using log-linked binomial regression modelling. Information regarding sleep testing facilities was updated at the provincial and regional levels. RESULTS Approximately 76.8% (95% CI 70.1% to 83.6%) of adult Canadians with sleep apnea and 5.1% (95% CI 3.4% to 6.7%) of those at high risk for OSA reported being referred to a sleep laboratory. Significant predictors of sleep laboratory referral in the general population were male sex, middle age, overweight or obese, a chronic condition, having a regular medical doctor and reporting symptoms of sleep apnea. Region of residence was also a predictor of reported sleep laboratory referral, with individuals from Ontario being more likely to report being referred to a sleep laboratory versus individuals from other regions. CONCLUSION Individuals reporting risk factors and symptoms associated with OSA were more likely to report a sleep laboratory testing referral compared with those without risk factors or symptoms. However, Canadas diagnostic sleep laboratory testing capacity varies across regions and is believed to be inadequate given the number of individuals at high risk for OSA who did not report testing referral.

Implementing the Three-Equation Method of Measuring Single Breath Carbon Monoxide Diffusing Capacity

Conventional methods of measuring the single breath diffusing capacity of the lung for carbon monoxide (DLcoSB) are based on the Krogh equation, which is valid only during breath holding. Rigid standardization is used to approximate a pure breath hold manoeuvre, but variations in performing the manoeuvre cause errors in the measurement of DLcoSB. The authors previously described a method of measuring DLcoSB using separate equations describing carbon monoxide uptake during each phase of the manoeuvre: inhalation, breath holding and exhalation. The method is manoeuvre-independent, uses all of the exhaled alveolar gas to improve estimates of mean DLcoSB and lung volume, and is more accurate and precise than conventional methods. A slow, submaximal, more physiological single breath manoeuvre can be used to measure DLcoSB in patients who cannot achieve the flow rates and breath hold times necessary for the standardized manoeuvre. The method was initially implemented using prototype equipment but commercial systems are now available that are capable of implementing this method. The authors describe how to implement the method and discuss considerations to be made in its use.

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