Host factors and environmental determinants associated with skin test reactivity and eosinophilia in a community-based population study.

We examined the relationship of host factors (age, gender) and environmental determinants (smoking status, area of residence) to indicators of allergy (skin test reactivity and eosinophil count) in a random population sample in the Netherlands. Positive skin test reactivity was associated with age (decreasing with increasing age), with male gender (versus female gender), and with urban residence (versus rural residence). Positive skin test reactivity was not associated with smoking. Elevated eosinophil counts were associated with male gender (versus female gender), with urban residence (versus rural residence), and with current smoking (versus never smoking). Elevated eosinophil counts were not clearly associated with age (if adjusted for the age-related effects of skin test reactivity). Additionally, this study specifically demonstrates that skin test reactivity increases with increasing eosinophil count and vice versa, indicating that the two traits are interrelated. Furthermore, this interrelationship was demonstrated to be age-dependent (decreasing with increasing age).

Long-term variability of bronchial responsiveness to histamine in a random population sample of adults.

Long-term variability of bronchial responsiveness has been studied in a random population sample of adults. During a follow-up period of 18 yr, 2,216 subjects contributed 5,012 observations to the analyses. Each subject could have as many as seven observations. Bronchial responsiveness was assessed with a histamine challenge test. The threshold value was defined as the concentration of histamine that caused a decrease in FEV1 of 10% of more (PC10). After a 3-yr interval, a change of the threshold value with two or more doubling concentrations occurred in 21% of the subjects. This proportion increased to 43% if the time between two measurements increased to 18 yr. Of all subjects with multiple observations, 41% were always nonresponders (PC10 > or = 32 mg/ml), 11% were always responders (PC10 < or = 16 mg/ml), and 48% changed responder status. Of the subjects with greater than three observations, 65% changed responder status. Regression analyses, stratified by symptom status, sex, and smoking habit, were used to estimate intraclass correlation coefficients (ICC) as a measure of variability of responsiveness. On average, ICC values were low (0.40), also indicating considerable variability. With adjustment for FEV1, age, area of residence, and eosinophil count, the ICC values decreased slightly. This indicated that with adjustment, the total variability decreased more than the within-subject variability. ICC values did not differ significantly between asymptomatic and symptomatic subjects. Analyses of responsiveness as a binary variable revealed similar results.

Factors associated with bronchial responsiveness to histamine in a population sample of adults.

The association of age, gender, number of eosinophils, area of residence, cigarette smoking, respiratory symptom prevalence, and FEV1 with the level of bronchial responsiveness was studied in a random sample of 2,216 subjects aged 15 to 72 yr. Subjects participated in the Dutch longitudinal study on chronic obstructive pulmonary disease. In 18 yr of follow-up, 5,012 observations were collected. Interviewers used a standardized questionnaire to assess the presence of respiratory symptoms. Bronchial responsiveness was measured by a histamine challenge test. Because multiple measurements within a subject are correlated, multivariate regression methods for correlated outcome were used. A greater number of eosinophils, skin test positivity, and living in a rural area (Vlagtwedde) were associated with increased responsiveness, independently of the level of FEV1 and the presence of respiratory symptoms. Older age was associated with increased responsiveness, and this was even more so in subjects with symptoms. Cigarette smokers were more responsive than nonsmokers, but this association was not significant if the level of FEV1 was taken into account. Hyperresponsiveness was more likely to be present if the amount of cigarettes smoked per day was greater. The level of responsiveness did not differ significantly between males and females. For the same degree of obstruction, however, expressed as the FEV1/VC ratio, males tended to be less responsive than females. The analyses were repeated using the dose-response slope as a continuous measure of responsiveness and by applying a method to adjust for censoring the responsiveness data. These analyses yielded identical results.

Relationship of skin test reactivity and eosinophilia to level of pulmonary function in a community-based population study.

We studied the relationship of skin test reactivity (sumscore greater than or equal to 3) and eosinophilia (greater than or equal to 275 cells/mm3 blood), separately and combined, to the level of FEV1 in a community cohort. We used the regression analysis technique, adjusting for age and area of residence, and stratifying by gender and cigarette smoking. Eosinophilia, among men, was associated with lower levels of FEV1 in skin test negative subjects with moderate cigarette smoking (greater than or equal to 10 pack-yr: beta = -250 ml, p = 0.02; greater than or equal to 10 pack-yr: beta = -234 ml, p less than 0.01) and in skin test positive subjects who either never smoked (beta = -228 ml, p = 0.06) or had only a brief history of smoking (beta = -428 ml, p less than 0.01). Eosinophilia, among women, was significantly associated with lower levels of FEV1 in never smokers (beta = -95 ml, p less than 0.01), especially if subjects were skin test positive as well (beta = -289 ml, p less than 0.01). Moderate cigarette smoking was uncommon in women. These data suggest an association of indices of inflammation (eosinophilia alone) and allergic inflammation (eosinophilia combined with skin test reactivity) with lower levels of FEV1, independent of the effect of cigarette smoking.

The relationship of eosinophilia and positive skin test reactivity to respiratory symptom prevalence in a community-based population study.

We studied the relationship of the prevalence of a variety of respiratory symptoms to positive skin test reactivity (skin test index greater than or equal to 3) and/or eosinophilia (greater than or equal to 275 eosinophilic cells per cubic millimeter of blood) in a community-based population sample (N = 2805), adjusting for age, gender, area of residence, and cigarette smoking. We considered subjects with neither positive skin test reactivity nor eosinophilia to be the reference group. Positive skin test reactivity without eosinophilia (N = 487; 17.3%) was significantly associated with persistent wheeze (odds ratio value (OR) = 1.6; 95% confidence interval of the odds ratio value (CI) = 1.0 to 2.6) and with asthmatic attacks (OR = 3.2; CI = 2.0 to 5.3). Positive skin test reactivity in combination with eosinophilia (N = 92; 3.3%) was also significantly associated with persistent wheeze (OR = 2.7; CI = 1.2 to 6.0) and with asthmatic attacks (OR = 10.4; CI = 5.3 to 20.2), however, with a stronger association than in subjects with positive skin test reactivity alone. Finally, eosinophilia without positive skin test reactivity (N = 170; 6.1%) was significantly associated with chronic cough (OR = 1.8; CI = 1.2 to 2.7), bronchitis episodes (OR = 2.1; CI = 1.4 to 3.2), dyspnea grade greater than or equal to III (OR = 1.7; CI = 1.0 to 2.8), and asthmatic attacks (OR = 3.0; CI = 1.5 to 6.6).(ABSTRACT TRUNCATED AT 250 WORDS)

The distribution of bronchial responsiveness to histamine in symptomatic and in asymptomatic subjects. A population-based analysis of various indices of responsiveness.

The distribution of bronchial responsiveness (BR) and the place of symptomatic subjects in this distribution was investigated in a random population sample of 339 subjects who participated in the 1984 survey of the Vlagtwedde/Vlaardingen Study. BR was assessed by a histamine provocation test. The following indices of BR were used: (1) a histamine threshold both at 10 and at 20% decreases in FEV1 (PC10 and PC20); (2) the concentration causing a 10 or a 20% decrease estimated by linear interpolation (IPC10 and IPC20), and by linear regression of all data points (PD10 and PD20); (3) the slope of the linear regression line through all data points (SAP) and the slope of the line through the origin and the last data point (SOL). Disease was defined as the self-reported presence of respiratory symptoms from a respiratory symptom questionnaire. Bronchial challenge was considered as a test to predict symptom prevalence. Receiver-operator characteristic curves were applied to define optimal cutoff points for each of the indices used to define a positive and a negative test. For each index, sensitivity, specificity, predictive value of a positive and negative test, and efficiency rate of the test were calculated. The overall distribution of BR in this population appeared to be log normal for the different continuous indices. Subjects with symptoms were on the more responsive tail of the distribution. After adjusting for age, sex, smoking habit, and level of pulmonary function, the mean log-transformed values of PD10, PD20, SAP, and SOL for the various symptom groups differed significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

The relationship between airway responsiveness to histamine and pulmonary function level in a random population sample.

The association of nonspecific bronchial responsiveness (BR) with pulmonary function level has been studied in a random population sample of 2,156 male and female subjects 15 to 64 yr of age participating in the Vlagtwedde-Vlaardingen field survey on chronic obstructive pulmonary disease (COPD) being conducted in the Netherlands. About 25% of the subjects responded with a decrease in baseline FEV1 of 10% or more after challenge with histamine in a concentration of 16 mg/ml or less inhaled over 30 s (PC10). In a stratified analysis, pulmonary function level appeared to be associated with BR in a dose-response relationship. The mean %FEV1 was consistently lower in the more responsive subjects. This relationship was confirmed in linear regression analyses, adjusting for age, sex, area of residence, and smoking habits. Exclusion of subjects with %FEV1 less than 80% diminished but did not change the association between FEV1 and BR. The magnitude of the effect of responsiveness on level of pulmonary function was considerable and statistically significant. In the subjects older than 21 yr of age, male responders (PC10 at less than or equal to 16 mg/ml) on average had an adjusted FEV1 of 32.5 centiliters less than nonresponders, and female responders had an adjusted FEV1 of 30.5 centiliters less (p less than 0.001). BR appeared to be an independent predictor of pulmonary function level after adjustment for age, sex, area of residence, respiratory symptom prevalence, and cigarette smoking. The effect of cigarette smoking on pulmonary function level in this population sample was significant only in men older than 21 yr of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Respiratory symptoms and the maximum expiratory flow-volume curve; a multivariate approach.

Information on the size and shape of about 8500 maximum expiratory flow-volume (MEFV) curves was related multivariately to respiratory symptoms to construct a sensitive measure of airflow limitation. The data were obtained in an epidemiological follow-up study of a normal population in The Netherlands. Using non-linear canonical correlation analysis, thirteen variables from each curve yielded two uncorrelated variates which were optimally related to two variates simultaneously derived from all respiratory data. Curves with different size and shape may yield the same probability for respiratory symptoms. In this context the scores of individuals on the scales of the two curve-derived variates do not have to be corrected for body or lung size. Using FEV1 and standing height about half as much of the variability in respiratory symptoms is explained as when using the whole MEFV-curve. Moreover, the distribution of the scores for the MEFV-curves allows the differentiation between three patterns of airflow limitation graphically. These three types suggest different pathophysiological mechanisms related to airways resistance and lung elastic recoil and may be used to characterize individual curves. One type relates to subjects with symptoms of 'asthma', one to airflow limitation as found among people with dyspnoea and elderly subjects and another to bronchitic symptoms. In females, the association of the MEFV-curve with 'asthma' is stronger than in males but much weaker with bronchitic symptoms. Curves found to be more related to 'asthma' or bronchitic symptoms, but not to dyspnoea, are more prevalent among current than among never smokers in males.

The association of airways responsiveness to respiratory symptom prevalence and to pulmonary function in a random population sample.

In a random population sample of 1905 subjects we studied the occurrence of respiratory symptoms in relation to airways responsiveness. Responders (PC10 FEV1 to histamine at 16 mg.ml-1 or less) had crude prevalence rates two to three times higher than nonresponders. In logistic regression analysis, odds ratios were estimated for each threshold value, compared to the reference value (greater than 32 mg.ml-1), controlling for age, sex, area of residence, and smoking habit. Odds ratios increased with decreasing threshold values in a dose-response relationship for all symptoms, except for bronchitis periods. We analysed the association of airways responsiveness to pulmonary function level by multiple linear regression, controlling for age, sex, height, area of residence, and smoking habit. There was an inverse relationship of FEV1 level to threshold value. Male subjects within a threshold value of 1 mg.ml-1 had a mean adjusted FEV1 of 1170 ml less than males with a threshold value of greater than 32 mg.ml-1. The relationship of responsiveness to decline of FEV1 with time was studied in 186 male subjects who took part in five consecutive surveys from 1967 to 1981. The greatest mean adjusted yearly decline was noted in responding smokers: 35.3 ml per yr, compared to nonreactive nonsmokers: 10.9 ml per yr. Regression analysis of the yearly decline in 169 subjects with at least two pairs of two consecutive threshold tests revealed that the more positive tests subjects had, the greater was their mean adjusted yearly decline. It is concluded that airways responsiveness may be an important factor in the development of chronic obstructive pulmonary disease.

The relationship of nonspecific bronchial responsiveness to respiratory symptoms in a random population sample.

The relationship of airway responsiveness to respiratory symptom prevalence has been studied in a cross-sectional analysis of a random subpopulation from a large-scale population study on chronic obstructive pulmonary disease (COPD) being conducted in the Netherlands. In 1,905 subjects with complete data on age, sex, area of residence, smoking habits, and respiratory symptom prevalence, airway responsiveness was assessed by a histamine challenge test. Subjects with a decrease in FEV1 of greater than or equal to 10% at a histamine concentration of less than or equal to 16 mg/ml were considered to be responders. Bronchial hyperresponsiveness appeared to be age dependent, with the proportion of responders increasing from 13% in those 14 to 24 yr of age to 40% in those 55 to 64 yr of age (p less than 0.001). Respiratory symptom outcomes included chronic cough, chronic phlegm, dyspnea, bronchitic episodes, persistent wheeze, and asthmatic attacks. Respiratory symptom prevalence rates were significantly higher in responders (p less than 0.001 for all symptoms). Cigarette smoking is known to be related to respiratory symptom prevalence and possibly to bronchial responsiveness. Because of these associations, we examined the relationship of bronchial responsiveness to respiratory symptoms within cigarette smoking categories. For all respiratory symptoms, it was found that, regardless of smoking category, responders were more likely to be symptomatic than were nonresponders. Odds ratios ranged from 1.7 for chronic cough to 4.4 for asthmatic attacks.(ABSTRACT TRUNCATED AT 250 WORDS)

Epidemiology of chronic obstructive pulmonary disease (COPD).

Epidemiology can contribute in the fight against COPD by: providing information necessary for planning and management of health care; contributing to the knowledge of natural history and etiology, which is important for treatment and prevention; providing information for early detection and for clinical decision making.

Indoor air pollution and its effect on pulmonary function of adult non-smoking women: II. Associations between nitrogen dioxide and pulmonary function.

The association between nitrogen dioxide levels in homes and pulmonary function of 97 non-smoking adult women was investigated in a rural area in the Netherlands. The study population was a sub-sample of a longitudinal field study on chronic non-specific lung diseases which was started in 1965. Pulmonary function tests were performed at three-yearly intervals. NO2 was measured for one week in the winter in kitchen, living room and bedroom of each home. Cross-sectional analyses showed negative associations between NO2 exposure and several pulmonary function parameters as measured in the 1982 study. No significant association could be found between NO2 exposure and pulmonary function decline since the start of the study.

Indoor air pollution and its effect on pulmonary function of adult non-smoking women: III. Passive smoking and pulmonary function.

The association between pulmonary function and exposure to tobacco smoke in the home was investigated in a sample of adult, non-smoking women living in a rural area. The women were all participants in a large longitudinal survey on the natural history and determinants of chronic non-specific lung disease. On cross-sectional analysis, several pulmonary function parameters were found to be significantly associated with exposure to tobacco smoke in the home. There was no association between exposure and pulmonary function decline.