Longitudinal methods for describing the relationship between pulmonary function, respiratory symptoms and smoking in elderly subjects: the Tucson Study.

In this study recently developed longitudinal techniques are used to examine the relationship between respiratory symptoms, smoking and pulmonary function measures in elderly subjects. The subjects were participants in the Tucson Epidemiological Study of Airways Obstructive Disease, aged > or = 55 yrs at the first survey 1972-1973, who had received pulmonary function testing and completed questionnaires in at least one of the six selected surveys. There were 633 males and 891 females, with up to 14 yrs follow-up included in the analysis. Based on their questionnaire responses, subjects were classified according to their respiratory symptoms and smoking habits at each survey. The pulmonary function testing included forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and their ratio (FEV1/FVC). The pulmonary function data were analysed gender specific, with and without stratifying on vital status. The results indicate that respiratory symptoms are generally associated with lower levels of lung function, and that the impairment associated with chronic cough was observed predominantly in male subjects. The negative association of smoking was apparent in most measures, but was largest and most progressive in the FEV1/FVC ratios. Ex-smokers, in all cases, had better lung function values than current smokers, but their mean curves were always significantly below the values of nonsmokers.

Continuous longitudinal regression equations for pulmonary function measures.

The data from a longitudinal population study in Tucson, Arizona, were used to describe the development and decline of maximal expiratory flow-volume (MEFV) measures with age. On the basis of their answers to self-administered questionnaires, in 9 of the first 10 surveys (1972-1988) and having performed at least one MEFV test, 930 nonsmoking healthy subjects were selected, providing 3,848 individual observations. The data were analysed using statistical methods that yield continuous piecewise linear regression equations and allow subjects to have repeated measures which are unequally spaced and at different times for different subjects. In addition, the age intervals for the piecewise linear line segments are estimated for each of the MEFV indices, as part of the modelling procedure. The resulting predicted values are compared between sexes and to previously published cross-sectional results from the same population. All MEFV measures in healthy subjects have an early increase in the rate of development corresponding to the onset of the adolescent growth spurt. This rapid growth period is followed by a plateau phase which lasts around 10 yrs for forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) in males, in which growth continues, but at a much lower rate. The plateau phase, is followed by a constant rate of decline which lasts throughout adulthood. In contrast, flow measures did not have a detectable plateau period, but did have points of increased rates of decline much later in life.

Characteristics of asthma among elderly adults in a sample of the general population.

This article describes the characteristics and course of asthma among subjects who were older than 65 years at the time of enrollment in a longitudinal study of a general population sample. It was present in 3.8 percent of men and 7.1 percent of women. An additional 4.1 percent of men reported having "asthma," but they also had seen a physician for "emphysema" and had smoked significantly; their "asthma" diagnosis is regarded as highly questionable. They did not show the elevated rate of allergy skin test reactivity of high serum IgE levels that were characteristic of other asthmatics. Many of the elderly asthmatics (mean age, 72 years) had severe disease with marked ventilatory impairment. There was a close relationship between the severity of wheezing complaints and impairment of the FEV1. Of the 46 patients, 48 percent reported an onset before age 40 years. There was no relationship between severity and age of onset or duration of disease. A second diagnosis of "chronic bronchitis" was reported by 46 percent of the asthmatics, but this did not delineate a distinctive group with late-onset, smoking-related disease. Death rates in the asthmatics tended to be higher than in nonasthmatics (odds ratio, 1.9; CI, 0.998 to 3.70, after stratifying by sex). Over a mean follow-up of 7.44 years, most symptoms as well as the FEV1 remained relatively stable. Chronic productive cough did tend to remit (p less than 0.01), but this was noted in the nonasthmatics as well. We estimate that no more than 19 percent of the asthmatics went into complete remission during follow-up. Most of these had mild initial symptoms; there were no remissions in subjects with severe disease at the time of entry. We concluded that asthma in the elderly is not a rare disease and may be associated with severe symptoms and chronic airways obstruction. If severe, it rarely goes into complete remission but tends to remain a severe, disabling disorder.

Smoking and symptom effects on the curves of lung function growth and decline.

Numerous studies have examined the natural time course of human lung function growth and decline throughout life. In most of these studies the investigators used statistical models that required a priori assumptions concerning the underlying form or structure of the lung function data, thus introducing possible biases. In this study we used recently developed nonparametric regression (spline) techniques to describe the evolution of lung function measures with age. This procedure yields an optimally fitted smooth curve through the data and estimates of the process velocity and does not require assumptions concerning the underlying shape of the data curves. The lung function growth-velocity curves are used to estimate the age of growth cessation. This technique was applied to the FVC, FEV1, and the FEV1/FVC ratios of 1,295 females and 1,230 males who were tested in at least one of the first nine surveys of the Tucson epidemiologic study of airway obstructive diseases. Data were analyzed stratified according to gender, smoking status, and respiratory symptoms or diseases. The results indicate large differences between the fitted FEV1 and FEV1/FVC smoothed curves of the various subgroups compared with asymptomatic nonsmokers. These differences were most pronounced in the adult symptomatic smokers, who had higher rates of lung function loss that also began at earlier ages, for both sexes. No significant differences were observed between asymptomatic and symptomatic nonsmokers, most likely because of the reduced number of symptomatic nonsmokers, particularly among the males.

Expiratory computed tomography for assessment of suspected pulmonary emphysema.

Results of computed tomography of the lung performed at two levels in upper lung zones at full inspiration and full expiration were compared with results of tests of ventilatory function, lung mechanics, and single breath carbon monoxide diffusing capacity in 64 subjects, many of whom had some form of airflow obstruction. From the CT scans, the mean percentage of pixels in the range -900 to -1,024 Hounsfield units, or pixel index, was determined for each subject. The highest correlations of pixel index with physiologic variables consistent with a diagnosis of emphysema were observed for CT taken at full expiration. In some subjects, the inspiratory CT would give a "false positive" for emphysema when the hyperaeration observed at inspiration was not observed at expiration. We believe that the CT scan taken at full expiration can effectively reveal the abnormal permanent enlargement of airspaces which defines emphysema and provides a noninvasive method of assessing lung morphology in the living human subject.

Methodology for generating continuous prediction equations for pulmonary function measures.

A mathematical procedure is described for fitting piecewise linear equations constrained to join at estimable multiple junctions or breakpoints. The model parameters, a combination of both linear and nonlinear, are estimated using a "Separable Least Squares" algorithm. In this algorithm the linear parameters, estimated using the General Linear Model, are nested within the iterations of a nonlinear optimization routine. This formulation allows additional covariates to be included in the model and can be easily expanded to include any number of line segments, both linear and nonlinear. The procedure is demonstrated by estimating continuous lung function reference equations for healthy normal subjects. Comparison of these reference equations with previously published equations derived for the same subjects, illustrates the advantages of having continuous equations throughout the age range of the data.

Single breath carbon monoxide transfer factor in different forms of chronic airflow obstruction in a general population sample.

The single breath transfer factor for carbon monoxide (TLCO), TLCO/alveolar volume (VA), and standard spirometric indices were measured in a survey of the randomly selected population sample of 1174 subjects enrolled in the Tucson epidemiological study of airways obstructive disease. Subjects were subdivided according to whether the FEV1/FVC ratio was under 65%, 65-75%, or over 75%. The influence of smoking on TLCO was accounted for by expressing TLCO as a percentage of the expected value-that is, of the value expected from the reported cigarette consumption. The 63 subjects who gave a history of physician confirmed asthma in reply to a questionnaire tended to have high values for TLCO, even when FEV1/FVC was reduced. In the absence of a given diagnosis of asthma, however, TLCO and TLCO/VA were reduced when the FEV1/FVC ratio was reduced, whether or not a clinical diagnosis of emphysema had been reported. This suggests that these subjects may have undiagnosed emphysema. This cross sectional analysis of our survey data suggests that subjects in our sample with spirometric evidence of chronic airflow obstruction have different forms of disease, characterised by different physiological features, in addition to the different risk factors and clinical courses reported earlier.

The effects of cigarette smoking and smoking cessation on the carbon monoxide diffusing capacity of the lung in asymptomatic subjects.

The single-breath carbon monoxide diffusing capacity (DL) was measured together with standard spirometry as part of a survey of a randomly selected community population sample. Based on answers to a self-administered questionnaire, subjects free of respiratory symptoms or disease were identified. Data from subjects who had never regularly smoked cigarettes had been used to derive reference equations for the test variables, and data from the remaining subjects who had smoked were examined to determine the effect of smoking and smoking cessation on the DL. From this cross-sectional analysis, it is apparent that cigarette smoking is associated with a decrease in DL that occurs very soon after beginning the cigarette habit. There is an irreversible decrease in DL with cumulative cigarette consumption, but also a reversible phenomenon that leads to rapid improvement in DL on smoking cessation.

Subclinical effects of cigarette smoking. A five-year follow-up of physiologic comparisons of healthy middle-aged smokers and nonsmokers.

Measurements of ventilatory function, lung elastic recoil, diffusing capacity, and distribution of ventilation were obtained on healthy middle-aged cigarette smokers and nonsmokers on two occasions five years apart in order to assess the effects of smoking and the change which may occur over this five-year interval. Subjects were drawn from a randomly selected sample of the population of Tucson, AZ. Exactly the same protocol, methods, and equipment were employed in both studies. Although very few of these healthy subjects had abnormal function, there were significant differences in most indices of function between smokers and nonsmokers. However, we could discern no difference between smokers and nonsmokers in change in function over five years. It appears that, in smokers who remain free of serious respiratory trouble, there are subtle changes which accumulate over the years and which are too gradual to detect over a five-year interval.

A reexamination of risk factors for ventilatory impairment.

Previous cross-sectional analyses of data from the Tucson Epidemiological Study of Airways Obstructive Diseases have shown significant relationships of ventilatory impairment to a variety of risk factors, including smoking, chronic productive cough, a history of childhood respiratory illnesses, atopy, blood eosinophilia, and serum immunoglobulin E (IgE). In the present report, we reexamine these relationships in subjects 40 to 74 yr of age to determine the effect of excluding known asthmatics who, as a group, have markedly impaired lung function. After exclusion of asthmatics, atopy, eosinophilia, and IgE no longer appear to be significant risk factors for ventilatory impairment, and nonasthmatic nonsmokers show almost no remaining ventilatory impairment. In current smokers, quantitative relationships of FEV1 to pack-years of cigarette consumption and to chronic productive cough are changed little by excluding asthmatics. In nonasthmatic ex-smokers, however, age at quitting smoking adds significantly to prediction of FEV1 after accounting for pack-years. Young ex-smokers closely resemble nonsmokers, but they become increasingly similar to current smokers as their age at quitting increases. A history of respiratory trouble before 16 yr of age continues to appear to increase susceptibility to smoking effects, even after exclusion of asthmatics. But, as in previous studies, the possible bias of preferential recall of childhood illnesses by impaired subjects limits interpretations of this observation. On the other hand, present findings suggest that such factors as atopy, eosinophilia, and elevated serum IgE may well be risk factors for persistent asthma, but they have no relationship to nonasthmatic forms of chronic obstructive pulmonary disease (COPD).(ABSTRACT TRUNCATED AT 250 WORDS)

Physiologic characteristics of subjects exhibiting accelerated deterioration of ventilatory function.

From a randomly selected community population sample followed with sequential surveys since 1972, 13 subjects who exhibited a mean annual decline in FEV1 greater than 60 ml/yr were drawn for detailed studies of lung function. These subjects had developed clinically significant airway obstruction during this period of follow-up. Clinical evaluation was not successful in characterizing the nature of the disorder. None of the subjects had alpha-1-antitrypsin deficiency. In a small proportion of subjects, elevated total serum immunoglobulin E may have played a role in the obstructive airway disorder. Some subjects exhibited loss of lung elastic recoil and diminished carbon monoxide diffusing capacity suggestive of developing emphysema. Others appeared to have intrinsic airway disease involving large and/or small airways, which may be fixed in some and responsive to bronchodilator in others. Thus, neither the site nor the nature of the disorder inferred from results of physiologic tests was uniform, illustrating the heterogeneous nature of chronic obstructive lung disease.

Longitudinal study of pulmonary function development in childhood, adolescence, and early adulthood. Development of pulmonary function.

The growth of pulmonary function between 5.5 and 25 yr of age was determined using 1,511 observations over time on 353 subjects from a representative population sample of white non-Mexican-Americans in Tucson. There was an average of 8.8 yr of follow-up, with a maximum of 12. The method used was shown to be robust for span of follow-up from 3 to 12 yr (3 to 7 observations), and the results were verified by standard statistical methods. The standard error of the estimate decreased linearly with follow-up, indicating the need for longitudinal evaluation. Respiratory symptoms and diagnoses had the biggest negative impact on growth of lung function, using FVC, FEV1, Vmax50, and size-compensated flows (Vmax50/FVC). Smoking had the next biggest negative impact. Smoking cessation was shown to have a positive impact on growth of pulmonary function. Using a second linear model to adjust for individual variability and the random variability over surveys, individual growth showed similar trends. Further negative impacts were due to parental smoking, especially as it interacts with active smoking and respiratory disease. Flows at end of follow-up (Vmax50, Vmax50/FVC) were more sensitive than FEV1 to the effects of concurrent disease and smoking, and more persistent effects of these factors in early adulthood.

The "horse-racing effect" and predicting decline in forced expiratory volume in one second from screening spirometry.

Longitudinal spirometric data on adults in a general population sample confirmed an overall relationship between rate of change in FEV1 (delta FEV1) and mean FEV1/Ht3. This relationship between FEV1 "slope" and "level" has been called a "horse-racing effect" and is the basis for the widely accepted concept that detecting a low FEV1 will predict a rapid decline in FEV1 and the development of clinically significant COPD. However, when both age and smoking habits were taken into account, the effect persisted only in male smokers. Even in them, it was dependent on the inclusion of part of the delta FEV1 in calculation of the mean FEV1 value. While neither a low initial FEV1/Ht3 nor percent predicted FEV1 significantly predicted a subsequent rapid fall in FEV1, presumably because of regression toward the mean, other initial spirometric variables proved better predictors, at least among male smokers. In them, a low FEV1/FVC ratio on entry was almost uniformly associated with a high rate of decline in FEV1. This was not seen in ex-smokers with similar initial spirometric findings. Also, delta FEV1 could not be predicted with any precision in women regardless of their smoking status. The findings strongly support the concept that detection of early airway disease by spirometric screening will identify those male smokers who are likely to develop clinically significant illness if they continue to smoke and that smoking cessation, even at this point, can markedly improve the prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Longitudinal changes in forced expiratory volume in one second in adults. Effects of smoking and smoking cessation.

Longitudinal changes in FEV1 (delta FEV1) in relationship to smoking habits were examined in 1,705 adults enrolled in a prospective study of a general population sample. In both men and women, there were excessive rates of decline in FEV1 in smokers, at least in those smoking more than 10 cigarettes per day. The excess decline of smokers was age dependent, particularly in men, with much of the excess loss of function occurring between 50 and 70 yr of age. Effects of smoking on delta FEV1, observed minus expected delta FEV1 and observed minus expected percent delta FEV1, were greater in men than in women even when controlled for current cigarette dose. Ex-smokers show delta FEV1 values similar to those of nonsmokers. In subjects younger than 35 yr of age, quitting smoking during follow-up was associated with an actual increase in FEV1. In men 50 to 70 yr of age, smoking cessation early in the study appeared to lead to a relatively prompt return to normal rates of functional decline. Thus, the findings suggest relatively prompt beneficial effect of smoking cessation even in late middle age.

The single-breath carbon monoxide diffusing capacity. Reference equations derived from a healthy nonsmoking population and effects of hematocrit.

Measurements of the single-breath carbon monoxide diffusing capacity (DL) were obtained on a randomly selected sample representative of the white non-Mexican-American population of Tucson, Arizona. Methods of measurement followed the guidelines set forth in the ATS-sponsored Epidemiology Standardization Project. There were 228 healthy nonsmokers who had duplicate tests that met the criteria for being acceptable. On the basis of data from these subjects, reference equations were derived for DL, alveolar volume (VA), and DL/VA. The data demonstrate the effects of growth and development, height, and age on these variables. Because a significant proportion of women, but not of men, had low hematocrit values, an effect of hematocrit on DL and DL/VA could be demonstrated only in females in this population sample.

Longitudinal changes in forced expiratory volume in one second in adults. Methodologic considerations and findings in healthy nonsmokers.

Longitudinal changes in FEV1 (delta FEV1) have been examined in a sample of the general population of Tucson, Arizona. Adults with satisfactory spirometric tests in all 7 surveys performed over a period of 11 yr showed some between-survey differences in mean FEV1. Although small in absolute magnitude, such survey biases (which would be impossible to detect unless multiple spirometric tests were carried out on a relatively large group of subjects) could have a marked effect on calculated changes in FEV1 and may explain the widely divergent delta FEV1 values reported in the literature. After adjusting for survey biases, the relationships of delta FEV1 to age, sex, and body size were examined in "healthy" nonsmokers in the population who were followed for an average of 9.6 yr. The FEV1 showed an accelerating decline with age, and delta FEV1 was best explained by a model of proportional change in which it is a function of Age X Height3. Longitudinally determined delta FEV1 showed much less decline in function and a later apparent age of onset of decline than suggested by cross-sectional analyses. While small "learning effects" in longitudinal calculations cannot be excluded, most of the cross-sectional versus longitudinal differences are probably ascribable to past events that have adversely affected the FEV1 in older adults, thereby increasing cross-sectional age effects. Present findings also suggest that generally applicable "prediction equations" for delta FEV1 probably cannot be developed and that delta FEV1 values should only be compared between groups studied in an identical manner within a given study.(ABSTRACT TRUNCATED AT 250 WORDS)

Vectorcardiographic and blood pressure correlates of obstructive pulmonary diseases in a community population.

Vectorcardiography was performed on 2,449 subjects, aged six years and older, in the Tucson (Ariz) Epidemiological Study of Airway Obstructive Diseases (AOD), 95 percent of the white non-Mexican Americans in the stratified cluster population sample. The objectives were to confirm previous relationships and to determine if hypothesized changes in the vectorcardiogram (VCG) could predict AOD. Trained nurse technicians performed the VCGs, which were read and interpreted by a cardiologist. Vectorcardiographic results were broadly interpreted for abnormalities. Also, calculated vector means and angles were compared to standard questionnaire responses for medical history, to maximum expiratory flow-volume variables, and to values for blood pressure; these were all corrected for sex, age, height, weight, and the ponderal index. Values were expressed as percentages of predicted. Over 80 percent of the VCGs were found to be normal. Measured hypertrophy was related to disease; there were significantly more abnormalities in those with histories of heart disease, hypertension, arteriosclerosis, and AOD, when examined by types of ventricular hypertrophy and VCG-identified heart disease or hypertension; findings of AOD and heart disease were also correlated significantly. Of all the ventricular hypertrophy, right ventricular hypertrophy (RVH), type C, was confirmed to be the predominant type associated with decreased pulmonary function in all smoking groups. Systolic blood pressure was related to RVH, type A, and diastolic 4 and 5 blood pressure with RVH, types A and B. The vectors' magnitude and angles were related to abnormality of pulmonary function in those with and without heart disease and AOD.

The aging respiratory system.

In this review article, the effects of old age on lung structure and function are discussed. Changes in lung morphology and biochemistry are correlated with changes in lung mechanics and gas exchange, as well as with the respiratory system's adaptability to the stresses of exercise and sleep. The effects of aging on the lungs' defense mechanisms are related to pulmonary diseases of the elderly.

Frequency dependent phase and amplitude differences between simulated mouth and pleural pressures during panting. Demonstration with a mechanical model.

A mechanical model was employed to examine phase and amplitude relationships between simulated pleural and mouth pressures during panting at different frequencies with and without lower airway obstruction and with rigid or flaccid extrathoracic airways. Results confirm the hypothesis that, in the presence of lower airways obstruction, compliant extrathoracic airways act as a shunt impedance. Consequently, mouth pressure changes may be out of phase with and underestimate changes in pleural pressure, affecting the measurement of thoracic gas volume.