Maureen P. Swanney

Using the lower limit of normal for the FEV1/FVC ratio reduces the misclassification of airway obstruction.

Aim: The prevalence of airway obstruction varies widely with the definition used. Objectives: To study differences in the prevalence of airway obstruction when applying four international guidelines to three population samples using four regression equations. Methods: We collected predicted values for forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) and its lower limit of normal (LLN) from the literature. FEV1/FVC from 40 646 adults (including 13 136 asymptomatic never smokers) aged 17–90+years were available from American, English and Dutch population based surveys. The prevalence of airway obstruction was determined by the LLN for FEV1/FVC, and by using the Global Initiative for Chronic Obstructive Lung Disease (GOLD), American Thoracic Society/European Respiratory Society (ATS/ERS) or British Thoracic Society (BTS) guidelines, initially in the healthy subgroup and then in the entire population. Results: The LLN for FEV1/FVC varied between prediction equations (57 available for men and 55 for women), and demonstrated marked negative age dependency. Median age at which the LLN fell below 0.70 in healthy subjects was 42 and 48 years in men and women, respectively. When applying the reference equations (Health Survey for England 1995–1996, National Health and Nutrition Examination Survey (NHANES) III, European Community for Coal and Steel (ECCS)/ERS and a Dutch population study) to the selected population samples, the prevalence of airway obstruction in healthy never smokers aged over 60 years varied for each guideline: 17–45% of men and 7–26% of women for GOLD; 0–18% of men and 0–16% of women for ATS/ERS; and 0–9% of men and 0–11% of women for BTS. GOLD guidelines caused false positive rates of up to 60% when applied to entire populations. Conclusions: Airway obstruction should be defined by FEV1/FVC and FEV1 being below the LLN using appropriate reference equations.

Interpreting lung function data using 80% predicted and fixed thresholds misclassifies more than 20% of patients.

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

Recommendations for epidemiological studies on COPD

The prevalence of chronic obstructive pulmonary disease (COPD) has been extensively studied, especially in Western Europe and North America. Few of these data are directly comparable because of differences between the surveys regarding composition of study populations, diagnostic criteria of the disease and definitions of the risk factors. Few community studies have examined phenotypes of COPD and included other ways of characterising the disease beyond that of spirometry. The objective of the present Task Force report is to present recommendations for the performance of general population studies in COPD in order to facilitate comparable and valid estimates on COPD prevalence by various risk factors. Diagnostic criteria in epidemiological settings, and standardised methods to examine the disease and its potential risk factors are discussed. The paper also offers practical advice for planning and performing an epidemiological study on COPD. The main message of the paper is that thorough planning is worth half the study. It is crucial to stick to standardised methods and good quality control during sampling. We recommend collecting biological markers, depending on the specific objectives of the study. Finally, studies of COPD in the population at large should assess various phenotypes of the disease.

The global lung initiative 2012 reference values reflect contemporary Australasian spirometry

We aimed to ascertain the fit of the European Respiratory Society Global Lung Initiative 2012 reference ranges to contemporary Australasian spirometric data. Z‐scores for spirometry from Caucasian subjects aged 4–80 years were calculated. The mean (SD) Z‐scores were 0.23 (1.00) for forced expirtory volume in 1 s (FEV1), 0.23 (1.00) for forced vital capacity (FVC), −0.03 (0.87) for FEV1/FVC and 0.07 (0.95) for forced expiratory flows between 25% and 75% of FVC. These results support the use of the Global Lung Initiative 2012 reference ranges to interpret spirometry in Caucasian Australasians.

Measurement of breath acetone concentrations by selected ion flow tube mass spectrometry in type 2 diabetes.

Selected ion flow tube-mass spectrometry (SIFT-MS) can measure volatile compounds in breath on-line in real time and has the potential to provide accurate breath tests for a number of inflammatory, infectious and metabolic diseases, including diabetes. Breath concentrations of acetone in type 2 diabetic subjects undertaking a long-term dietary modification programme were studied. Acetone concentrations in the breath of 38 subjects with type 2 diabetes were determined by SIFT-MS. Anthropomorphic measurements, dietary intake and medication use were recorded. Blood was analysed for beta hydroxybutyrate (a ketone body), HbA1c (glycated haemoglobin) and glucose using point-of-care capillary (fingerprick) testing. All subjects were able to undertake breath manoeuvres suitable for analysis. Breath acetone varied between 160 and 862 ppb (median 337 ppb) and was significantly higher in men (median 480 ppb versus 296 ppb, p = 0.01). In this cross-sectional study, no association was observed between breath acetone and either dietary macronutrients or point-of-care capillary blood tests. Breath analysis by SIFT-MS offers a rapid, reproducible and easily performed measurement of acetone concentration in ambulatory patients with type 2 diabetes. The high inter-individual variability in breath acetone concentration may limit its usefulness in cross-sectional studies. Breath acetone may nevertheless be useful for monitoring metabolic changes in longitudinal metabolic studies, in a variety of clinical and research settings.

Accurate, reproducible measurement of acetone concentration in breath using selected ion flow tube-mass spectrometry

Using selected ion flow tube-mass spectrometry (SIFT-MS) for on-line analysis, we aimed to define the optimal single-exhalation breathing manoeuvre from which a measure of expired acetone concentration could be obtained. Using known acetone concentrations in vitro, we determined the instruments accuracy, inter-measurement variability and dynamic response time. Further, we determined the effects of expiratory flow and volume on acetone concentration in the breath of 12 volunteers and calculated intra-individual coefficients of variation (CVs). At acetone concentrations of 600-3000 ppb on 30 days over 2 months there was an instrument measurement bias of 8% that did not change over time, inter-day and intra-day CVs were 5.6% and 0.0%, respectively, and the 10-90% response time was 500 ± 50 ms (mean ± SE). Acetone concentrations at exhalation flows of 193 ± 18 (mean ± SD) and 313 ± 32 ml s(-1) were 619 ± 1.83 (geometric mean ± logSD) and 618 ± 1.82 ppb in the fraction 70-85% by volume of exhaled vital capacity (V(70-85%)) and 636 ± 1.82 (geometric mean ± logSD) and 631 ± 1.83 ppb in V(85-100%). A difference was observed between acetone concentrations in the V(70-85%) and V(85-100%) fractions (p < 0.01), but flow had no effect. Median intra-individual CVs were 1.6-2.6%. On-line SIFT-MS measurement of acetone concentration in a single exhalation requires control of exhaled volume but not flow, and yields low intra-individual CVs and is potentially useful in approximating blood glucose and monitoring metabolic stress.

The all‐age spirometry reference ranges reflect contemporary Australasian spirometry

Background and objective:  Advances in statistical modelling have allowed the creation of smoothly changing spirometry reference ranges that apply across a wide age range and better define the lower limit of normal. The objective of this study was to assess the agreement of the Stanojevic 2009 all‐age reference ranges to contemporary lung function data to verify the appropriateness of this reference for clinical use in Australia and New Zealand.

Quantification of hydrogen cyanide (HCN) in breath using selected ion flow tube mass spectrometry—HCN is not a biomarker of Pseudomonas in chronic suppurative lung disease

Hydrogen cyanide (HCN) in exhaled breath has been proposed as a biomarker for airway inflammation, and also a marker of the presence in the airways of specific organisms, especially Pseudomonas aeruginosa. However the production of HCN by salivary peroxidase in the oral cavity increases orally exhaled concentrations, and may not reflect the condition of the lower airways. Using SIFT-MS we aimed to determine an appropriate single-exhalation breathing maneuver which avoids the interference of HCN produced in the oral cavity. We have established that the SIFT-MS Voice200™ is suitable for the online measurement of HCN in exhaled breath. In healthy volunteers a significantly higher end exhaled HCN concentration was measured in oral exhalations compared to nasal exhalations (mean ± SD) 4.5 ± 0.6 ppb versus 2.4 ± 0.3 ppb, p < 0.01. For the accurate and reproducible quantification of end exhaled HCN in breath a nasal inhalation to full vital capacity and nasal exhalation at controlled flow is recommended. This technique was subsequently used to measure exhaled HCN in a group of patients with chronic suppurative lung disease (CSLD) and known microbiological colonization status to determine utility of HCN measurement to detect P. aeruginosa. Median nasal end exhaled HCN concentrations were higher in patients with CSLD (3.7 ppb) than normal subjects (2.0 ppb). However no differences between exhaled HCN concentrations of subjects colonized with P. aeruginosa and other organisms were identified, indicating that breath HCN is not a suitable biomarker of P. aeruginosa colonization.

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

Adopting universal lung function reference equations

Since the dawn of spirometry and testing lung function [1, 2], clinicians have been aware that the values obtained from testing an individuals lung function can reflect the effects of lung diseases, and that this can be helpful with regard to all aspects of disease prevention and management. It was also recognised that the values obtained were also a reflection of the subjects sex, age and height; so to maximise the clinically relevant signal from the tests these aspects first needed to be taken into account. Studies were then undertaken to record lung function in subjects free from disease and free from the effects of tobacco smoke in order to have reference ranges of lung function. Clinicians have had to decide which of the many available prediction equations to use for their patients, realising that the different equations might lead to different judgements about the results obtained, because predicted values might vary by as much as 1 L for forced expiratory volume in 1 s (FEV1) [3]. Guidance in this choice has been based on the reference population being appropriate for the patients and the equipment used for recording the lung function being equivalent. Other considerations include the age span of the reference population and the statistical approach used to derive the various predicted equations. Many European centres used the equations derived for the European Community for Steel and Coal (ECSC) [4]. However, it was still …