The beta-agonist dilemma.
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Administration, Inhalation↗
Biomedical subjects
B Burrows
Publications and source records attributed to B Burrows.
Relationships of bronchial responsiveness assessed by methacholine to serum IgE, lung function, symptoms, and diagnoses in 11-year-old New Zealand children.
The relationship of bronchial responsiveness (BR), assessed by methacholine challenge, to serum IgE, baseline ventilatory function, and symptoms or diagnoses suggesting an atopic disorder were examined in 522 11-year-old New Zealand children. BR was assessed by the presence or absence of a PC20 25 mg/ml or less and by calculating a continuous index of the decline of the FEV1 during the methacholine test. The latter facilitated multivariate analyses and revealed significant relationships to predictor variables even in those considered "nonresponsive" by PC20 criteria. There was a close relationship of BR to the baseline FEV1/vital capacity ratio, seen even in patients with known asthma, but this relationship was seen only in subjects with at least moderate levels of serum IgE. There was a less close relation of BR to percent predicted FEV1, but this persisted even after accounting for the FEV1/vital capacity ratio and was present regardless of the level of serum IgE. Reported asthma was associated with increased BR independent of all other factors, but other diagnoses and symptoms contributed relatively little to the prediction of BR once the serum IgE and lung function were taken into account. The overall results are compatible with the concept that IgE is a critical factor in the development of bronchial responsiveness in childhood.
Asthma↗
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.
Adult↗
Increased incidence of asthma in children of smoking mothers.
The relationship between parental smoking and both subsequent development of asthma and subsequent lung function (before age 12) was studied in more than 700 children enrolled before age 5. Children of mothers with 12 or fewer years of education and who smoked 10 or more cigarettes per day were 2.5 times more likely (95% confidence interval 1.42 to 4.59; P = .0018) to develop asthma and had 15.7% lower maximal midexpiratory flow (P less than .001) than children of mothers with the same education level who did not smoke or smoked fewer than 10 cigarettes per day. These relationships were independent of self-reported respiratory symptoms in parents. There was no association between maternal smoking and subsequent incidence of asthma or maximal midexpiratory flow among children of mothers with more than 12 years of education. It is concluded that children of lower socioeconomic status may be at considerable risk of developing asthma if their mothers smoke 10 or more cigarettes per day. It is speculated that recently reported increases in prevalence of childhood asthma may be in part related to the increased prevalence of smoking among less educated women.
Asthma↗
Validation of markers of lung destruction.
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Biological Assay↗
Relation between airway responsiveness and serum IgE in children with asthma and in apparently normal children.
BACKGROUND: Although asthma diagnosed by a physician is known to be related to serum IgE levels, it is not known whether there is a relation between the level of IgE and airway hyperresponsiveness to a methacholine challenge. The characteristics of asymptomatic persons that predispose them to airway hyperresponsiveness are also unknown. METHODS: We studied the relation between the serum total IgE level and airway hyperresponsiveness in the presence or absence of asthma and other atopic diseases in a birth cohort of children. Data from a questionnaire regarding respiratory symptoms, plus measurements of the serum total IgE level and airway responsiveness to inhaled methacholine, were obtained for 562 11-year-olds in New Zealand. RESULTS: The boys had a higher prevalence than the girls of current diagnosed asthma (13 percent vs. 6 percent), current symptoms of wheezing (22 percent vs. 15 percent), and airflow obstruction at base line (6 percent vs. 1 percent) and had a wider distribution of IgE levels, although mean IgE levels (120.8 IU per milliliter in the boys and 98.1 IU per milliliter in the girls) did not differ significantly between the sexes. The prevalence of diagnosed asthma was strongly related to the serum IgE level (P for trend less than 0.0001). No asthma was reported in children with IgE levels less than 32 IU per milliliter, whereas 36 percent of those with IgE levels greater than or equal to 1000 IU per milliliter were reported to have asthma. This relation with the serum IgE level was not explained by a concomitant diagnosis of allergic rhinitis or eczema. Airway hyperresponsiveness to a methacholine challenge also correlated very highly (P less than 0.0001) with the serum IgE level. This relation remained significant even after the exclusion of children with diagnosed asthma (P less than 0.0001) and of all children with a history of wheezing, allergic rhinitis, or eczema (P less than 0.0001). CONCLUSIONS: Even in children who have been asymptomatic throughout their lives and have no history of atopic disease, airway hyperresponsiveness appears to be closely linked to an allergic diathesis, as reflected by the serum total IgE level.
Asthma↗
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.
Adolescent↗
Findings before diagnoses of asthma among the elderly in a longitudinal study of a general population sample.
Forty elderly subjects who denied ever having asthma or emphysema on enrollment in a longitudinal epidemiologic study later reported consulting a doctor for asthma when they were older than 60 years of age. The average age at which the diagnosis was reported was 70.8 years, after a mean follow-up of 8.5 years. Findings on enrollment in the newly diagnosed subjects with asthma are compared with findings in the 1145 subjects who provided follow-up information when they were older than age 60 years but had never developed asthma. At the time of enrollment, most subjects later diagnosed as having asthma already had wheezing symptoms, suggesting at least a mild asthmatic state, and many subjects had impaired ventilatory function, a positive allergy skin test (especially in association with rhinitis), and blood eosinophilia. Thirty-five percent of the subjects recalled "respiratory trouble before age 16" despite denying prior asthma. The likelihood of a new asthma label was very closely related to the age-sex-standardized serum-IgE level before diagnosis. Newly diagnosed subjects with asthma demonstrated much greater rates of decline in FEV1 than control subjects or than subjects who already had known asthma on enrollment. We conclude that (1) symptoms suggesting asthma are usually present for many years before the diagnosis of the disease in elderly subjects, (2) the serum-IgE level is closely related to the likelihood of a subsequent asthma diagnosis, even in this age group, and (3) a rapid fall in lung function often occurs around the time of initial diagnosis.
Age Factors↗
Epidemiologic evidence for different types of chronic airflow obstruction.
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Airway Obstruction↗
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.
Body Height↗
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.
Aged↗
A longitudinal study of respiratory symptoms in a community population sample. Correlations with smoking, allergen skin-test reactivity, and serum IgE.
Chronic cough and/or phlegm, wheeze in the absence of colds, and rhinitis attributed to allergies are three of the most common respiratory symptoms encountered in community populations. In this study, we have determined the prevalence of these complaints in a random population sample (n = 1,109) using standardized questionnaires at two points in time, eight years apart. Cross-sectional prevalence and changes in symptom occurrence have been correlated with smoking status, allergen skin test reactivity, and total serum IgE levels. Our objective was to determine the individual and combined influence of these three variables on symptom prevalence. Initially, 19.2 percent of the population admitted to wheeze, 17.9 percent to cough, and 44.1 percent to allergic rhinitis. Cough and wheeze prevalence changed little over the eight-year period, while rhinitis increased 11 percent by the second survey. The occurrence of chronic cough was strongly correlated with smoking, and was not further influenced by either allergen skin reactivity or IgE level. Conversely, rhinitis prevalence was related to skin test reactivity with no additional association with smoking or IgE level. The occurrence of wheeze in the absence of colds was associated with both smoking and allergen skin reactivity. Among smokers, the prevalence was over 30 percent and was similar in both skin test positive (STP) and skin test negative (STN) individuals. However, on both surveys, STP ex-smokers and nonsmokers had significantly more wheeze than those who were STN. While the prevalence of wheeze in STN nonsmokers was low (6.8 percent), an IgE-wheeze relationship was also suggested on the second survey. In addition to these cross-sectional symptom relationships, changes in either smoking status or allergen skin reactivity during the study period were associated with changes in the prevalence of each symptom.
Adult↗
Problems in defining normal limits for serum IgE.
Recommended "normal limits" for serum IgE generally assume that a single upper limit of normal can be applied to all adults. The present article describes the distribution of IgE levels in 2657 subjects in a general population sample in Tucson, Ariz. Limits of IgE defining the lower 5%, 10%, 25%, 50%, 75%, 90%, and 95% in 1569 subjects with negative allergy skin tests and without current asthma, considered a reference group, are provided by age and sex. These cutoffs are then used to compare groups with asthma and with positive allergy skin tests with the reference population. Distributions of IgE levels in these groups are vastly different, but defining an upper "limit of normal" for serum IgE is of doubtful clinical value because there is no single level of IgE that distinguishes different groups with any precision. The spread of IgE values is extremely wide in subjects with and without known allergic diseases.
Adolescent↗
Airways obstructive diseases: pathogenetic mechanisms and natural histories of the disorders.
There has been a long-standing controversy concerning the risk factors and pathogenetic mechanisms involved in the development of chronic airflow obstruction (CAO). This asthmatic constitution consisted of a predisposition to allergy, airways hyperresponsiveness, and possibly eosinophilia. Other investigators, however, regarded CAO as simply the late stage of chronic bronchitis. The term chronic obstructive lung disease (COLD) was developed to resolve what was largely a semantic difference. In subsequent years, the term chronic obstructive pulmonary disease (COPD) has come to be used more often than COLD to describe these patients. This article discusses the differences between these terms and defines the causes and risk factors associated with each.
Asthma↗
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.
Adult↗
Methacholine responsiveness among working populations. Relationship to smoking and airway caliber.
It has been suggested that the development of bronchial hyperresponsiveness (BHR) in some smokers may be an intermediate event in the progression to chronic obstructive pulmonary disease in this group. If this is true, prevalence data on BHR in a general population should show an independent association between BHR and smoking status. To test this, we analyzed BHR to inhaled methacholine in 654 white men without known asthma, in relation to smoking, skin-test reactivity, type of work (office versus industrial), and indicators of baseline airway caliber (FEV1 % predicted and FEV1/FVC). BHR was measured in the traditional way (PC20) and as the slope of FEV1 versus the methacholine concentration (linear scale). A PC20 of less than 16 mg/ml was considered "responsive" for analyses of this outcome. We found that although a positive skin test, smoking, and being an industrial worker all appeared to be significant predictors of increased BHR (p less than 0.05), once FEV1 (% predicted) and FEV1/FVC% were taken into account, none of these variables alone remained significantly associated with BHR. The strongest predictors of BHR were prechallenge FEV1 and FEV1/FVC (both p less than 0.01). The combination of smoking, atopy, and work groups, which identified a small subgroup of atopic smokers who were office workers, also remained significantly associated with increased BHR. We also used a regression model that allowed for comparison of predictors for BHR between the most responsive subset of the population (n = 84) and the remainder of the study population.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Differential diagnosis of chronic obstructive pulmonary disease.
If one includes all types of chronic generalized airways obstruction under the heading of "COPD," diagnosis of this condition requires only the demonstration of an obstructive ventilatory impairment on spirometric testing that persists despite maximum medical therapy. However, as generally used, the term COPD implies that upper airways obstruction and "specific" lung diseases that can produce an obstructive type of physiologic abnormality have been excluded. Examples of these exclusions include silicosis, sarcoidosis, and even advanced tuberculous disease. It is more difficult to determine the type of disease that is causing the chronic airways obstruction in patients with COPD as defined above. A severe and persistent form of asthma, sometimes called "chronic asthmatic bronchitis," can mimic the typical emphysematous form of COPD that is characteristic of heavy cigarette smokers. Since these types of chronic airflow obstruction differ in regard to their clinical courses, prognoses, and treatments, their distinction is clinically important. One should not be discouraged by the fact that some patients appear to have a mixed type of disorder. Features that help differentiate the various forms of chronic airways obstruction are described in this report, and recommendations are offered to help guide the practitioner in the workup indicated for patients thought to have any type of chronic airways obstruction. It is also emphasized that patients vary markedly in regard to the relative importance of readily reversible bronchospasm, airways inflammation, and mucus hypersecretion in producing their disability. Assessment of these factors is critical in determining clinical management.
Diagnosis, Differential↗
Epidemiology of chronic obstructive pulmonary disease.
Morbidity and mortality rates for chronic obstructive pulmonary disease (COPD) have been increasing over time. Epidemiologic investigators of COPD have been exploring the reasons for these increases through prevalence surveys and longitudinal studies. This article examines some of the recent findings.
Air Pollution↗