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.

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.

FEV(6) is an acceptable surrogate for FVC in the spirometric diagnosis of airway obstruction and restriction.

We analyzed the FEV(1)/FEV(6) and FEV(1)/FVC results of 502 consecutive patients in the spirometric diagnosis of airway obstruction. We also examined the agreement between FEV(6) and FVC in the spirometric diagnosis of restriction. Technically acceptable test results were obtained from 337 subjects (67%). The sensitivity of FEV(1)/FEV(6) for diagnosing airway obstruction as defined by FEV(1)/ FVC was 95.0%; the specificity was 97.4%. When interpretations differed, the measured values were all close to the lower limits of the reference ranges. When analysis included +/- 100-ml variability in FEV(1) and FEV(6), the sensitivity increased to 99.5% and the specificity to 100%. The reproducibility of FEV(6) was superior to that of FVC. These results suggest that FEV(6) is an accurate, reliable alternative to FVC for diagnosing airway obstruction and that FEV(6) is reasonably comparable to FVC for the spirometric diagnosis of restriction. FEV(6) is more reproducible and less physically demanding for patients.

Evidence for major genes influencing pulmonary function in the NHLBI family heart study.

Segregation analysis was performed on the pulmonary measures forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and the ratio of FEV1/FVC in 455 randomly ascertained families from the NHLBI Family Heart Study (FHS). Gender specific standardized residuals were used as the phenotypic variable in both familial correlation and segregation analyses. These residuals represented adjustments for the effects of age, age(2), age(3), Body Mass Index (BMI, kg/m(2)), height, the ratio of waist to hip measurements (WHR), the presence of coronary heart disease, smoking history, and pack years for current smokers. Sibling correlations were not different from parent-offspring correlations for all three traits, and heritability estimates for FEV1, FVC, and the FEV1/FVC ratio were 0. 515, 0.540, and 0.449, respectively. Segregation analysis of FEV1, a trait that measures airflow, indicated that a dominant major gene best fits the data, although a residual familial correlation supports the presence of an additional polygenic or common environmental component. For FVC, a trait that measures lung volume, alternative models could not be statistically differentiated, but the transmission probabilities do not support a Mendelian major gene. The best model for FEV1/FVC ratio is a non-Mendelian codominant model, perhaps due to the mixing of the individual underlying distributions influencing airflow and lung volume. These results support the hypothesis that complex relationships exist for lung function traits and that multiple genes and environmental factors influence lung function.

Controversies in the use of spirometry for early recognition and diagnosis of chronic obstructive pulmonary disease in cigarette smokers.

Office spirometry used to detect COPD in smokers ages 44 and above with respiratory symptoms probably meets the criteria for a population-based screening test and for clinical case finding: If not detected early, COPD causes substantial morbidity or mortality, and smoking cessation is more effective when COPD is recognized before exertional dyspnea develops. Office spirometry is a feasible testing strategy and may be used to encourage smoking cessation efforts that change behavior in at least some patients. Office spirometry is relatively simple and affordable, is safe, and includes an action plan with minimal adverse effects. On the other hand, the false-positive and false-negative rates of office spirometry in the primary care setting may be higher than diagnostic spirometry performed during epidemiologic studies or in diagnostic pulmonary function laboratories, and the incremental benefit of office spirometry on smoking cessation rates is poorly established (when added to referral to an AHCPR-based smoking cessation program).

Influence of leisure time physical activity and television watching on atherosclerosis risk factors in the NHLBI Family Heart Study.

Physical activity favorably influences atherosclerosis risk factors but only a few studies in adults considered the time watching television (TV) as a measure of physical inactivity. We therefore determined in a population-based sample of 1778 subjects from the NHLBI Family Heart Study (FHS) whether leisure time physical activity and TV watching have independent or interactive associations with cardiovascular disease risk factors and carotid artery intima-media wall thickness (IMT). Subjects were free from diabetes mellitus and clinically-ascertained coronary artery disease and did not take lipid-lowering or antihypertensive drugs. Only 0.7 and 1.3% of the variance in leisure time physical activity in women and men, respectively, was explained by the amount of TV watching. Leisure time physical activity had a clearly favorable, and TV watching an unfavorable association with anthropometric measurements (BMI (body mass index), waist girth, waist-hip ratio, subscapular and triceps skinfold thickness). The odds ratio (95% CI) of being overweight was 0.41 (0.28-0.62) in women and 0.69 (0.46-1.04) in men in the highest quartile of leisure time physical activity compared to the lowest quartile. The odds ratio increased for increasing quartiles of TV watching to 2.12 (1.45-3.10) in women and 1.61 (1.07-2.43) in men. Watching TV only 1 h per day in women with a BMI of 30 kg/m2 and doing about 75 min of moderate exercise per week was associated with a BMI 1.8 kg/m2 lower than in women watching TV 3 h per day and doing the same amount of exercise. Those with twice the amount of moderate exercise and watching TV 1 h per day had a BMI 0.45 kg/m2 lower. Furthermore, leisure time physical activity was negatively associated with concentrations of triglycerides and positively with HDL cholesterol in both genders. TV watching was significantly positively associated with triglycerides and slightly negatively with HDL cholesterol in men. The observed associations of leisure time physical activity and TV watching with atherosclerosis risk factors were independent from each other. Finally, we analyzed the relation between leisure time physical activity, TV watching and the degree of IMT of the carotid arteries. Neither of these two measures was significantly associated with IMT. In summary, TV watching, in addition to leisure time physical activity, shows an independent association with obesity-related anthropometric measurements, HDL and triglycerides. Decreasing the amount of TV watching might be effective as a first step in reducing atherosclerosis risk factors, especially overweight.

Arterial blood gas reference values for sea level and an altitude of 1,400 meters.

Blood gas measurements were collected on healthy lifetime nonsmokers at sea level (n = 96) and at an altitude of 1,400 meters (n = 243) to establish reference equations. At each study site, arterial blood samples were analyzed in duplicate on two separate blood gas analyzers and CO-oximeters. Arterial blood gas variables included Pa(O(2)), Pa(CO(2)), pH, and calculated alveolar-arterial PO(2) difference (AaPO(2)). CO-oximeter variables were Hb, COHb, MetHb, and Sa(O(2)). Subjects were 18 to 81 yr of age with 166 male and 173 female. Outlier data were excluded from multiple regression analysis, and reference equations were fitted to the data in two ways: (1) best fit using linear, squared, and cross-product terms; (2) simple equations, including only the variables that explained at least 3% of the variance. Two sets of equations were created: (1) using only the sea level data and (2) using the combined data with barometric pressure as an independent variable. Comparisons with earlier studies revealed small but significant differences; the decline in Pa(O(2)) with age at each altitude was consistent with most previous studies. At sea level, the equation that included barometric pressure predicted Pa(O(2)) slightly better than the sea level specific equation. The inclusion of barometric pressure in the equations allows better prediction of blood gas reference values at sea level and at altitudes as high as 1,400 meters.

Differences in spirometry reference values: a statistical comparison of a Mongolian and a Caucasian study.

New reference value studies for spirometry are commonly compared to existing reference value studies using average data derived from existing reference equations. Such comparisons are inherently flawed because they do not account for differences in distributions of the independent and dependent variables and they do not have identical methodologies. This study was undertaken 1) to derive reference equations for forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) for natives of Mongolia and 2) to compare the Mongolian data with data from a 1981 reference study of Caucasians in Salt Lake City, UT, USA. Spirometry was performed on 344 (176 male, 168 female) healthy, nonsmoking urban natives of Mongolia to generate reference equations for FVC, FEV1, and FEV1/FVC. These data were compared with data from a 1981 reference study of Caucasians in Salt Lake City, using both an analysis of covariance of the raw data and parametric and nonparametric comparisons of a matched pair subset. Average measured forced vital capacity and forced expiratory volume in one second in native Mongolians were within 1-2% of the Caucasian predicted values. These small differences are not statistically significant in any of the multiple methods of comparisons. Power analysis suggests that, if real differences exist, the differences in forced vital capacity are <155 mL for males, <105 mL for females, and the differences in forced expiratory volume in one second are <107 mL for males and <76 mL for females.

Effect of altitude on hand-held peak flowmeters.

OBJECTIVE: To quantify the effect of altitude on the operational characteristics of hand-held peak flowmeters. DESIGN: Altitude simulation within a hypobaric chamber combined with five constant simulated peak flows delivered from a computerized pump were used to test commercially available peak flowmeters. SETTING: F.G. Hall Hyperbaric/Hypobaric facilities located at Duke University School of Medicine. MEASUREMENTS: Two each of nine models of commercially available hand-held peak flowmeters and a volume spirometer were tested at six simulated altitudes (100, 500, 1,000, 1,500, 2,000, and 3,000 m) using five target peak flows. Each peak flow was injected into each meter twice. Forward stepwise regression was used to check for nonlinear relationships between altitude and peak expiratory flowmeter readings. Linear regression equations were fit to the data at each target flow across altitude. Effect of absolute peak flow was tested by analysis of covariance. RESULTS: For these altitudes, linear relationships were found between altitude and measured peak flow. For all meters tested, the average decrease in peak flow ranged from -8.7% at the lowest target flow (123 L/min) to -6.5% at the highest target flow (702 L/min) for each 100 mm Hg decrease in barometric pressure (PB). Individual meters ranged from -12.3% at the lowest target flow to -4.4% at the highest target flow for 100 mm Hg decrease in PB. The spirometer had no significant changes associated with changes in PB. In all cases, the magnitude of the altitude effect, measured by percent change, decreased with increasing peak flow. CONCLUSIONS: Peak expiratory flowmeters underread PEF as a function of both increasing altitude and increasing target peak flow.