The relationship between atopy and non-specific bronchial responsiveness

Atopy is often regarded as a risk factor for the development of asthma, particularly childhood asthma and occupational asthma. This could reflect an association with non-specific bronchial responsiveness (NSBR), though atopy could influence asthma independently. We have evaluated the possible relationship between atopy and NSBR (PD20FEV1 to methacholine) in the siblings of 59 probands with atopic asthma. Thirty-four (58%) were atopic (greater than or equal to 1 prick test with weal diameter greater than or equal to that of a 0.1% histamine control) and 28 (47%) showed NSBR. Atopy and NSBR occurred together more frequently than would be expected by chance (P less than 0.05); both variables being observed in 20 subjects, neither in 17, and only one in 22. A significant association was also noted when atopy was defined by a serum total IgE greater than 150 IU (or greater than 50 IU), but when atopy was defined by other commonly used criteria (greater than or equal to 2 prick tests with weal diameter greater than or equal to histamine control; or weal diameter 2 mm or more greater than a saline control), no significant association was demonstrated. Furthermore, linear logistic regression and multiple regression analyses showed that both the presence and the degree of NSBR were influenced much more by the baseline level of FEV1 than by atopic status. At best, atopy accounted for 10% of the variance of the PD20 measurements. We conclude that atopy is associated with NSBR but not strongly; that the relationship may be readily obscured according to the defining criteria used for atopy; and that atopy should not be used as a marker for NSBR.     

Relationship of asthma, atopy, and bronchial responsiveness to serum eosinophil cationic proteins in early childhood

BACKGROUND: The relationship between atopy, asthma, and eosinophilic inflammation is less clear in early childhood than later in life. OBJECTIVE: We sought to determine the relationships between asthma, atopy, and serum eosinophil cationic protein (ECP), a biomarker of eosinophil activation, in 6-year-old children. METHODS: Serum ECP levels were available from 968 six-year-old children who were part of a longitudinal birth cohort being assessed for asthma and atopy. Detailed clinical history and examination, lung function testing, methacholine challenge, and skin prick testing to 4 common allergens were undertaken. Subgroups of the children were compared by using t tests, ANOVA, chi 2 tests, and regression analysis. RESULTS: One hundred ninety-one (19.7%) children had current asthma, with 114 (59.7%) of these being atopic. The mean serum ECP level for the entire group was 18.0 mug/L (range, 2.0-146.0 mug/L), with no difference between male and female patients. Serum ECP was higher in atopic children (20.5 +/- 18.4), those with asthma (22.4 +/- 19.6), and those with asthma and atopy (26.6 +/- 22.4; all P < .001 compared with children with no asthma or atopy [16.1 +/- 15.9]). Serum ECP levels were highest in children with severe asthma ( P < .001), especially in those with concurrent atopy. Severity of atopy, judged on the basis of wheal size or derived variables combining wheal size and the number of positive skin tests, was a major determinant of serum ECP. Heightened methacholine responsiveness was not associated with increased serum ECP levels. CONCLUSION: The higher serum ECP levels seen in 6-year-old children with current asthma and more severe atopy suggest that atopy and eosinophilic inflammation are important in driving this clinical phenotype and that this might represent asthma that persists.     

Associations between asthma history, atopy, and non-specific bronchial responsiveness in young adults

In 105 subjects taken from a student population and aged between 15 and 30 there was a strong positive association between the presence of the atopic state, defined by skin tests, and a high level of non-specific bronchial responsiveness to methacholine (χ²= 10·5, d.f. = 2, P= 0·01). Regression analysis showed a history of asthma, and the symptom of wheeze, to be predominantly predicted by the degree of bronchial responsiveness (R²= 31%), with only a minor independent contribution from the degree of atopy (R² a furthur 5%). The genetic or other reasons for the association between bronchial responsiveness and atopy may have importance in understanding the aetiology of allergic asthma.     

Relationship between bronchial responsiveness to hyperventilation with cold and methacholine in asthma

Twenty-seven subjects with asthma and normal baseline lung function were challenged with aerosols of methacholine (M) and by isocapnic hyperventilation with cold air (HV). Stimulus-effect relationships were determined for each provocational technique on separate days and were expressed as the dose required to produce a 20% fall in forced expired volume in 1 sec (FEV₁) obtained by linear interpolation from log stimulus vs. response curves (PD₂₀). Each stimulus was applied with a sufficient intensity to produce a 20% or greater fall in FEV₁ in each subject. The PD₂₀ for M correlated significantly with the PD₂₀ for HV (p < 0.001) when the latter was expressed in liters per minute. The correlation between cumulative M PD₂₀ and HV PD₂₀ expressed as a percent of maximal voluntary ventilation was significant but less strong. We conclude that the airway response to HV reflects nonspecific bronchial hyperresponsiveness and that the dose of HV is best determined as the absolute level of ventilation.     

Positive allergy prick tests associated with bronchial histamine responsiveness in an unselected population

Bronchial responsiveness to histamine and skin prick test reactions to airborne allergens were measured in a random population sample of 891 adults and 1293 schoolchildren. Total serum IgE concentrations were measured in a subset of 389 adults. The prevalence of bronchial histamine responsiveness (BHR) in the adults increased from 5.8% in those who did not respond to allergen prick tests to 22.2% in those who responded to all five allergen groups (p less than 0.00001). Similarly, the prevalence of BHR in the children increased progressively from 3.5% to 35.3% as the number of positive allergen responses increased from zero through five (p less than 0.0001). In adults for whom IgE data were also available, those with BHR had a significantly higher total serum IgE concentration (p less than 0.002).     

Atopy and bronchial responsiveness in random population sample of 527 children and adolescents.

The relationship between bronchial responsiveness, lung function, and results of skin prick testing was studied in 527 children and adolescents from Copenhagen. All participants completed a questionnaire concerning allergic symptoms (asthma, rhinitis, atopic dermatitis, and urticaria). Furthermore, skin prick test reactivity to nine common aeroallergens, lung function, serum IgE and bronchial responsiveness to histamine and exercise were measured. A total of 53 subjects were atopic, (skin prick 3+), 105 subjects had moderate skin reactivity (1-2+), and 366 subjects had no signs of atopic disease (prick test negative); 58% of the subjects with skin test reactivity (1-3+) were asymptomatic. Increasing degree of atopy was correlated significantly with symptoms such as asthma, rhinitis, dermatitis, and urticaria (P less than .001); increasing level of IgE (P less than .001); month of birth (P = .001); and family history of allergic diseases (P less than .05). The most important markers for the degree of bronchial responsiveness to inhaled histamine were the presence of respiratory symptoms (P less than .001), the degree of atopy (P = .001), a history of asthma in at least two first degree relatives (P less than .01), and the skin reactivity to house dust mites (P = .001), horse epithelium (P = .01), Alternaria iridis, and dog epithelium (P less than .05). In contrast, the degree of bronchial responsiveness to exercise was significantly correlated with asthma (P less than .001), the level of IgE (P less than .05), month of birth (P less than .001), and birth weight (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of asthmatic and rhinitic symptomatology duration on bronchial responsiveness to histamine

Our Study aimed to investigate the influence of the time in years elapsed from the onset of symptoms on bronchial nonspecific responsiveness in rhinitic and asthmatic patients. The study was performed on 83 asthmatic patients and on 46 patients with allergic rhinopathy. The beginning of the symptoms and years of asthmatic or rhinitic history were particularly investigated. A histamine challenge was performed. The dose of histamine producing at 20% change in FEV1 (forced expiratory volume in one second) was calculated from the individual semilogarithmic dose-response curve (PD20). Bronchial responsiveness to histamine showed wide variability in subjects of two groups, and an overlap of the distribution curves was observed between asthmatic and rhinitic patients. A significant relationship (p less than 0.01) between the years elapsed from the onset of symptoms and bronchial responsiveness to histamine was observed in each group of patients. We noticed that the number of the years passed heightened the bronchial responsiveness to histamine in both groups of patients.     

The distribution of bronchial responsiveness to histamine and exercise in 527 children and adolescents

The aim of the study was to describe the bronchial responsiveness to inhaled histamine and exercise in a randomly selected group of 527 children and adolescents from Copenhagen, aged between 7 to 16 years. The distribution of the bronchial responsiveness was described as (1) the provoking concentration that causes a 20% reduction in FEV1 (2) the dose-response slope (DRS), that is, the linear slope of the dose-response curve, and (3) reduction in FEV1 after 6 minutes of exercise on a treadmill. The distribution of the concentration that causes a 20% reduction in FEV1 in the responsive range was not significantly different from a unimodal distribution, although the findings were skewed toward the less responsive end of the range (p greater than 0.05). The subjects with asthma represented a subgroup within the responsive distribution tail rather than a separate distribution peak. In asymptomatic individuals, the values of DRS were distributed symmetrically on a logarithmic scale. The deviation from normal was such that the standard deviation only slightly underestimated the "normal" range. The distribution of the bronchial response to exercise was found to be significantly different from a normal distribution. However, a significant relationship was found between the bronchial response to inhaled histamine and exercise (p less than 0.0001). We conclude that there is a log-normal distribution of the bronchial response to inhaled histamine in a random sample of children and adolescents.     

Relationship between nasal and bronchial responsiveness in perennial allergic rhinitic patients with asthma

BACKGROUND: The nasal and bronchial mucosa present similarities and most patients with asthma also have rhinitis, suggesting the concept of 'one airway one disease'. Although many studies may suggest the relationship between nasal and bronchial responsiveness in patients with allergic rhinitis and asthma, few studies have been published which address this question directly. The aim of this study is to investigate whether the relationship between nonspecific nasal and bronchial responsiveness exists in perennial allergic rhinitic patients with asthma. METHODS: Fifty-one perennial allergic rhinitic patients with the definitive or suspected asthma underwent methacholine bronchial provocation tests and nasal histamine challenge tests. A slope of the absolute changes in nasal symptoms score/log concentrations of histamine was calculated by linear regression analysis. A ratio of the final absolute change in nasal symptoms score to the sum of all the doses of histamine given to the subject was also calculated. The degree of bronchial responsiveness to methacholine was categorized as positive bronchial hyperresponsiveness (BHR) if PC(20) (provocative concentration of methacholine resulting in 20% fall in FEV(1)) was <4 mg/ml, borderline BHR if PC(20) was >or=4 but 16 mg/ml. Another index of bronchial responsiveness (BRindex) was calculated as the log [(% decline in FEV(1)/log final methacholine concentration as mg/dl) + 10]. RESULTS: The geometric means of the slope (4.47 vs. 2.95, p < 0.05) and the ratio (1.68 vs. 0.54, p < 0.01) were higher in patients with positive BHR (n = 23) than in patients with negative BHR (n = 19), respectively. The geometric means of the slope (3.50) and the ratio (1.13) in patients with borderline BHR (n = 9) were between the two groups, respectively. In all patients, the log-slope (r = 0.48, p < 0.001) and the log-ratio (r = 0.51, p < 0.001) were correlated well with the BRindex, respectively. Even in allergic rhinitic patients with definitive asthma, the log-slope was correlated with the BRindex (r = 0.39, p < 0.05) or log-PC(20) (r = -0.36, p < 0.05). CONCLUSIONS: The nonspecific nasal responsiveness may be related to the nonspecific bronchial responsiveness in patients with allergic rhinitis and asthma, which may support the viewpoint that allergic rhinitis and asthma represent a continuum of inflammation involving one common airway.     

Release of histamine from leucocytes and its determinants in vitro in rotation to bronchial responsiveness to inhaled histamine and exercise in vivo

The hypothesis studied is that increased responsiveness in asthma is not limited to the airways. Forty asthmatic children were analysed for their bronchial responsiveness (BR) to exercise. Twenty patients revealed bronchial obstruction after exercise while the remainder did not. These observations were compared with the responsiveness of leucocytes, which was determined by their histamine ‘releasability’. Twenty healthy children served as controls. Release of histamine induced by calcium ionophore-aided calcium influx was significantly higher in both groups of asthmatics than in the healthy children (P < 0.005). Similar findings were obtained by induction of microtubule aggregation due to deuterium oxide (D₂O). The S-shaped dose-response relationship with D₂O was shifted to the left in the patients with BR to exercise compared to patients without (P < 0.025). The slope was increased in both patient groups compared with the healthy children (P < 0.01). It is concluded that the mean ‘releasability’ of histamine release due to both stimulants correlated well (P < 0.01). This suggests that the ‘releasability’ is determined by the responsiveness of the microtubules. This may also apply to allergen-induced histamine release, as was revealed from studies with anti-IgE. The differences in histamine release found in relation to BR due to exercise were also present if the patients were divided according to BR due to histamine. A significant relationship existed between the degree of BR to histamine and the responsiveness of the microtubules (P < 0.02).     

Allergen-induced increase in bronchial responsiveness to histamine: relationship to the late asthmatic response and change in airway caliber

Allergen-induced late asthmatic responses are associated with an increase in bronchial responsiveness to histamine. We have examined the relationship between the magnitude of the late asthmatic response and the magnitude and duration of increased histamine responsiveness. Allergen inhalation tests were carried out in 12 asthmatic subjects to induce a mild early asthmatic response (16% to 40% reduction in FEV₁ in the first hour after allergen inhalation); the response was followed over 8 hr to identify the occurrence and magnitude of any late asthmatic response (maximum fall in FEV₁ from baseline between 3 and 8 hr). The provocation concentration of histamine causing a decrease in FEV₁ of 20% (PC₂₀) was measured before and after inhalation of allergen. The magnitude of decrease in PC₂₀ correlated with the magnitude of the late asthmatic response as measured by the percent fall in FEV₁ (r = 0.8, p < 0.002). The duration of decrease in PC₂₀ was from 2 to 74 days and this also correlated with the magnitude of the late response (r = 0.53, p < 0.05). Total lung capacity (TLC), residual volume (RV), FEV₁, maximal expiratory flow-volume curves (on air and He-O₂), and histamine responsiveness were also measured before and at intervals after allergen inhalation. Four of seven subjects still had a reduction in PC₂₀ when the TLC, RV, FEV₁, maximal expiratory flow-volume rates on air (V?₅₀air) and He-O₂ (V?₅₀He-O₂) (measured at an absolute volume corresponding plus 50% of control vital capacity) and ratio of V?₅₀He-O₂ to V?₅₀air were back t preallergen inhalation levels. In two of these subjects volume of isoflow was also back to ±10% of preallergen inhalation levels when the PC₂₀ was still significantly reduced. The results suggest that allergen-induced late asthmatic responses can be associated with an increase in bronchial responsiveness to histamine by mechanisms other than a reduction in baseline airway caliber alone.     

Rhinoconjunctivitis,bronchial responsiveness,and atopy as determinants for incident non-work-related asthma symptoms in apprentices exposed to high-molecular-weight allergens

OBJECTIVE: The aim of this study was to explore the role of rhinoconjunctivitis (RC), taking into account atopy and the level of bronchial responsiveness to methacholine, on the incidence of respiratory symptoms and in the development and/or worsening of asthma. METHODS: We examined data from a prospective study in 769 students starting exposure to high-molecular-weight occupational allergens and who were serially followed for up to 44 months. RESULTS: The presence of RC symptoms at baseline was significantly associated with an increased risk of developing shortness of breath and wheezing in atopic subjects regardless of PC20 level and in subjects with a PC20 相似文献   

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.     

Exposure to a sensitizing occupational agent can cause a long-lasting increase in bronchial responsiveness to histamine in the absence of significant changes in airway caliber

A 58-year-old subject with a history of occupational asthma to red-cedar sawdust underwent specific inhalation challenges with this product. Significant increases in airway responsiveness to histamine (tenfold fall in PC20 FEV1) were documented 7 hours after exposure for 5 minutes to red cedar while baseline spirometry remained unchanged. A dual asthmatic reaction was induced during the following days by exposing the subject to red-cedar sawdust for 30 minutes and plicatic acid for 7 minutes. After recovery of PC20, the subject was reexposed to plicatic acid for 15 and 30 seconds on 2 consecutive days. No significant changes in FEV1, forced vital capacity, and residual volume were demonstrated in the following 8 hours, although minimal changes in forced expiratory flow rate between 25% and 75% of FVC were observed. PC20 dropped significantly and required 2 weeks to recover. This example illustrates that bronchial hyperresponsiveness to histamine can precede the changes in airway caliber after an antigen challenge. It also demonstrates that such changes can persist for up to 2 weeks after the challenge, even when no significant changes in FEV1 are induced.     

The relationship between bronchial histamine reactivity and atopic status

It has been proposed that increased production of IgE, a feature of atopy, is a cause of the non-specific bronchial hyper-reactivity that is characteristic of asthma. This hypothesis was examined by selecting groups of subjects with asthma or rhinitis and a group of healthy control subjects and studying the relationship between their bronchial histamine reactivity and their atopic status. In none of the groups tested was there a significant association between the degree of bronchial histamine reactivity and either the serum level of total IgE or the number of extracts of aero-allergens giving positive prick test reactions.     

Effect of vitamin C on histamine bronchial responsiveness of patients with allergic rhinitis

The effect of acute oral administration of 2 g vitamin C on bronchial responsiveness to inhaled histamine in 16 patients with allergic rhinitis was compared with placebo on two consecutive days in a double-blind, crossover design. The PC15FEV1 was significantly increased one hour after treatment with vitamin C but not after placebo.     

Bronchial responsiveness to inhaled histamine and exercise.

Bronchial responsiveness to inhaled histamine and exercise was measured in 19 asthmatics. Histamine aerosol was inhaled to determine the provocative concentration producing a 20% fall in forced expired volume in one second (FEV1) (PC20). Exercise was performed on a treadmill and a cycle ergometer; following each procedure the percent fall in the FEV1 (delta FEV1) and the exercise lability (percent rise in FEV1 plus percent fall in FEV1) were calculated. Delta FEV1 and exercise lability after both forms of exercise were similar. PC20 correlated with delta FEV1 and exercise lability in both forms of exercise; however, the correlation with exercise lability was better. PC20 was more sensitive in demonstrating bronchial hyperresponsiveness. The close correlation between the level of bronchial responsiveness to histamine and exercise supports the view that release of endogenous chemical mediators is an important determinant of exercise-induced asthma. The treadmill exercise and cycle ergometry protocols were equally effective in producing exercise-induced asthma.     

Relationship between bronchial asthma and mite

We studied the relationship between bronchial asthma and mite as an antigen by reviewing previous reports. The incidence of the bronchial asthma has been increasing and it is estimated to be more than 2% of the total population. The main components of the antigen in the house dust (H, D.), which has been considered to be an important antigen of the perennial asthma, are Dermatophagoides farinae (D, f.) and Dermatophagoides pteronyssinus (D, p.) in H, D. The housing environment in recent years have become favorable for the reproduction of D, f. and D, p. It is considered that environmental pollution increases the incidence of asthma, especially infants.