Quality control of DL,CO instruments in global clinical trials.

High inter- and intra-laboratory variability exists for the single-breath diffusing capacity of the lung for carbon monoxide (D(L,CO)) test. To detect small changes in diffusing capacity in multicentre clinical trials, accurate measurements are essential. The present study assessed whether regular D(L,CO) simulator testing maintained or improved instrument accuracy and reduced variability in multicentre trials. The 125 pulmonary function testing laboratories that participated in clinical trials for AIR(R) Inhaled Insulin validated and monitored the accuracy of their D(L,CO) measuring devices using a D(L,CO) simulator, which creates known target values for any device. Devices measuring a simulated D(L,CO) different from target by >3 mL.min-1.mmHg(-1) failed testing and were serviced. Device accuracy was assessed over time and with respect to differences in several variables. Initially, 31 (25%) laboratories had a D(L,CO) device that failed simulator testing. After fixing or replacing devices, 124 (99%) laboratories had passing devices. The percentage of failed tests significantly decreased over time. Differences in geographical region, device type, breath-hold time, temperature and pressure were not associated with meaningful differences in D(L,CO) device accuracy. Regular diffusing capacity of the lung for carbon monoxide simulator testing allows pulmonary function testing laboratories to maintain the accuracy of their diffusing capacity measurements, leading to reduced variability across laboratories in multicentre clinical trials.

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 (FEV(1)/FVC) and its lower limit of normal (LLN) from the literature. FEV(1)/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 FEV(1)/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 FEV(1)/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 FEV(1)/FVC and FEV(1) being below the LLN using appropriate reference equations.

Consideraciones generales acerca de las pruebas de función pulmonar / Tittle

No disponible

Estandarización de la espirometría / Tittle

No disponible

Inflammatory markers are associated with ventilatory limitation and muscle dysfunction in obstructive lung disease in well functioning elderly subjects.

BACKGROUND: Inflammatory markers are increased in chronic obstructive pulmonary disease (COPD) and are hypothesised to play an important part in muscle dysfunction and exercise intolerance. METHODS: The Health Aging and Body Composition (Health ABC) study is a prospective observational cohort of well functioning individuals aged 70-79 years. A cross sectional analysis of the baseline data was conducted to examine the association between inflammatory markers and ventilatory limitation, muscle strength, and exercise capacity. These associations were compared in participants with and without obstructive lung disease (OLD). RESULTS: Of the 3075 participants enrolled in the Health ABC cohort, OLD was identified by spirometric testing in 268 participants and 2005 participants had normal spirometric results. Of the participants with OLD, 35%, 38%, and 27% participants had mild, moderate, and severe OLD, respectively. Participants with OLD had lower quadriceps strength (102.5 Nm v 108.9 Nm, p = 0.02), lower maximum inspiratory pressure (64.7 cm H(2)O v 74.2 cm H(2)O, p<0.0001), higher systemic interleukin (IL)-6 levels (2.6 pg/ml v 2.2 pg/ml, p<0.0001), and higher C-reactive protein (CRP) levels (3.5 mg/l v 2.5 mg/l, p<0.0001) than those with normal spirometry. In participants with OLD and those with normal spirometry, forced expiratory volume in 1 second (FEV(1)) was associated with IL-6 (adjusted regression coefficients (beta) = -5.3 (95% CI -9.1 to-1.5) and -3.1 (95% CI -4.3 to -1.9), respectively). IL-6 and TNF were also associated with quadriceps strength among participants with OLD and those with normal spirometry (beta = -6.4 (95% CI -12.8 to -0.03) and -3.4 (95% CI -5.4 to -1.3), respectively, for IL-6 and beta = -10.1 (95% CI -18.7 to -1.5) and -3.8 (95% CI -7 to -0.6), respectively, for TNF). IL-6, quadriceps strength, and maximum inspiratory pressures were independent predictors of reduced exercise capacity in both groups. CONCLUSIONS: In well functioning elderly subjects with or without OLD, IL-6 is associated with reduced FEV(1), quadriceps strength, and exercise capacity.

Spirometric reference values in a large Middle Eastern population.

Ethnic differences in pulmonary function have been frequently reported. The purposes of this study were to derive equations for the prediction of normative spirometry values for a large population of Persians in Isfahan and compare them to reference values from a White Euro-USA population. Spirometry measurements were obtained from 4,341 randomly selected healthy nonsmoker subjects in Isfahan, Iran, utilising American Thoracic Society guidelines and a vigorous quality assurance program. Measured data from 3,213 subjects were analysed using multiple regression techniques to derive prediction equations for spirometric variables; the remaining 1,128 subjects were used as a control group to test the validity of the derived equations. In addition, predicted values were compared with values derived from recently published equations for the USA. Derived prediction equations showed good performance for most spirometric parameters. Compared with USA Whites, adult Persians have minimally lower forced vital capacities, while the values for children are close to USA Whites. In comparison with reference equations based on European or USA populations, local reference values are more biologically and technically suitable for the interpretation of spirometric data from Iranian populations.

Airway inflammation in COPD: physiological outcome measures and induced sputum.

Chronic obstructive pulmonary disease (COPD) is a result of airway inflammation, and the best predictor of COPD is the early detection of airflow limitation by spirometry. The Global Initiative for Obstructive Lung Disease Workshop Report defines airflow limitation using simple spirometric indices. Available guidelines categorise the severity of COPD using forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), with symptoms playing a minor role in the assessment. Current standards define COPD by progressive loss of FEV1, and thus longitudinal decline in FEV1 will be the primary outcome variable for intervention studies aimed at preventing or reducing the loss of pulmonary function. There is evidence, however, that the variable FEV1/FVC and FEV1 are often not measured properly in all settings. This article will discuss the roles of physiological measurements in diagnosing COPD and physiological outcome measures for COPD. It does not formally compare physiological measures with other outcome measures, such as symptoms or quality of life. Additionally, improved treatment of established disease requires a better understanding of the inflammatory process and its clinical effects and treatment. The inflammatory process, and how drugs affect it, can be studied noninvasively or relatively noninvasively by using refined methods of examining spontaneous or induced sputum. Enhanced understanding of the use of induced sputum will assist in predicting patients' responses to short- and long-term inhaled corticosteroid treatment, and the methods of sputum examination need to be simplified so that they can be applied more easily to clinical practice.

Airflow limitation is underrecognized in well-functioning older people.

OBJECTIVES: Dyspnea is a common symptom in older people. A reduced forced expiratory volume in 1 second (FEV1) is associated with a higher mortality rate from cardiovascular and respiratory disease, and increased admissions to hospitals. Underrecognized or undertreated airflow limitation may exacerbate the problem. The purpose of this study was to assess the prevalence and treatment of airflow limitation in a cohort of well-functioning older people. DESIGN: Cross-sectional study. SETTING: Baseline of a clinical-epidemiological study of incident functional limitation. PARTICIPANTS: Participants attended the baseline examination of the Health, Aging, and Body Composition study, a prospective cohort study of 3,075 well-functioning subjects age 70 to 79. MEASUREMENTS: Demographic and clinical data were collected by interview. Spirometry was performed unless contraindicated and repeated until three acceptable sets of flow-volume loops were obtained. Patients on bronchodilator medications had spirometry performed posttherapy. Blinded readers assessed the flow-volume loops, and inadequate tests were omitted from analysis. Airflow limitation was defined as a reduced forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) as determined by age-, sex-, and race-normalized values. Severity of airflow limitation was defined by American Thoracic Society criteria. RESULTS: Two thousand four hundred eighty-five subjects (80.8%) had assessable spirometry and data on treatment and diagnosis (1,265 men, 1,220 women). The mean age was 73.6 years. Two hundred sixty-two subjects (10.5%) had airflow limitation; 43 (16.4%) of these never smoked. Only 37.4% of participants with airflow limitation and 55.6% of participants with severe airflow limitation reported a diagnosis of lung disease. Only 20.5% of subjects with at least moderate airflow limitation had used a bronchodilator in the previous 2 weeks. CONCLUSION: Despite their good functional status, airflow limitation was present, and underrecognized, in a considerable proportion of our older population. The low bronchodilator use suggests a significant reservoir of untreated disease. Physicians caring for older people need to be more vigilant for both the presence, and the need for treatment, of airflow limitation.

A simple diagnostic index for asthma.

BACKGROUND: Asthma is becoming increasingly prevalent and a number of research groups are investigating its genetic and environmental basis. OBJECTIVE: To produce a brief screening tool suitable for determining phenotype in asthma research. METHODS: The scores from eight questions on symptoms and history were obtained from 678 adults and 244 children from high asthma-incidence caucasian families. An independent physician diagnosis was also obtained with the use of a modified NHLBI-CSGA questionnaire and pulmonary function test. Stepwise logistic regression was applied to determine which of the eight questions had greatest predictive value for asthma, and the quality of the resultant models was evaluated using an independent set of 643 adults and 239 children. RESULTS: For adults, the most parsimonious model used responses from three of the eight questions. It had sensitivity and specificity of 0.94 and 0.96, respectively. For children, responses to two questions gave a model with sensitivity and specificity of 0.97. For both age groups, negative predictive values were above 0.87. Positive predictive values were 0.58 and 0.78 for adults and children respectively. The latter emphasize the need for conformation, by physician, of "affected" calls made by this initial screen. CONCLUSION: The brief questionnaires described are potentially useful in a research setting, as a preliminary screening mechanism of low cost. Their use will reduce the numbers of subjects that must undergo detailed phenotyping.

Single-breath carbon monoxide diffusing capacity.

Measurement of DL(CO) remains a clinically useful way to assess transfer of gases across the lung. It is important, however, to be vigilant in controlling the sources of variation and to be aware of those that remain when interpreting the measured values.