Exercise provocation test in the diagnosis of bronchial asthma and detection of airway responsiveness]

Exercise provocation test was performed on a bicycle ergometer in 110 asthmatics, 15 allergic rhinitis patients, 10 patients with moderate chronic bronchitis and 22 healthy subjects. 87.5% (21/24) of atypical asthmatics revealed positive exercise induced asthma (EIA), with the overall positive rate of asthmatics being 90% (99/110). There was a close negative linear correlation between the maximal reduction rate in FEV1 induced by exercise (delta FEV1%) and the inhaled histamine dose needed to reduce FEV1 by 20% (PD20FEV1) (r = -0.59, P less than 0.01). None of the healthy subjects, one of 15 allergic rhinitis patients and one of 10 patients with moderate chronic bronchitis showed positive response to exercise test. In contrast, seven of 18 allergic rhinitis patients and all nine patients with moderate chronic bronchitis had positive response to histamine bronchial provocation test. Therefore, exercise provocation test is a reliable method for diagnosing EIA and detecting airway responsiveness and it may possess higher specificity than histamine provocation test in diagnosing bronchial asthma, particularly in atypical bronchial asthma.     

Course and severity of bronchial asthma and chronic bronchitis in a local Swedish population sample.

A population sample between 35 and 54 years of age with chronic obstructive lung disease was investigated. The material consisted of 86 persons with bronchial asthma (without chronic bronchitis), 69 with chronic bronchitis (without asthma) and 30 with a combination of chronic bronchitis and bronchial asthma. Of the 116 asthmatics 51 had reaginic bronchial allergy. Twenty-three subjects developed bronchoconstriction on exercise testing: 14 of these had asthma, one bronchitis and eight had a combination of the two. Onset of disease before 15 years of age was unusual in pure bronchitis (9%), although more common in pure asthma and in asthma with bronchitis (23-29%). The mean number of days of incapacity during the preceding 12 months was only 6, both in pure asthma and pure bronchitis, but it was more frequent, 22-26, in asthma with bronchitis and in exercise-induced bronchoconstriction. In asthma the multiple regression analyses showed that impaired spirometric values before or after taking a bronchodilating drug were correlated with the duration of incapacity in days and with exercise-induced bronchoconstriction. In bronchitis, impaired spirometric values were found to be correlated with the number of symptomatic days (during the preceding 12 months) and with smoking.     

Ventilatory capacity, working capacity and exercise-induced bronchoconstriction in a population sample of subjects with bronchial asthma or chronic bronchitis.

We have studied a representative population sample comprising 185 persons, aged 35-54 years, having certain respiratory symptoms and considered to have chronic bronchitis and/or bronchial asthma. There were 86 with bronchial asthma (without chronic bronchitis), 69 with chronic bronchitis (without asthma) and 30 with both chronic bronchitis and bronchial asthma. Fifty-one of the 116 asthmatics had reaginic bronchial allergy. In the groups with chronic bronchitis or bronchial asthma, the mean ventilatory capacities were slightly below the normal, being 89 and 91%, respectively, of the predicted values for FEV1 and 85 and 87% of those for MVV40. In the group of persons with both diseases, the mean FEV1 was 77% and the mean MVV40 84% of that predicted. Of the 21 persons with a mean FEV1 below 70% of that predicted 10 had both asthma and bronchitis. Exercise-induced bronchoconstriction, defined as a 15% fall of PEF after exercise, occurred in 22 of the 116 asthmatics and in one of the 69 persons with chronic bronchitis without bronchial asthma. In the asthmatics there was a significant correlation between resting PEF or the difference in PEF before and after orciprenaline inhalation on the one hand, and exercise-induced bronchoconstriction on the other hand. This was taken as an indication of increased bronchial hyperreactivity.     

对慢性喘息型支气管炎气道反应性特点及其本质的探讨

目的 研究慢性喘息型支气管炎对乙酰甲胆碱和运动激发试验的气道反应性特点,并对其本质进行初步探讨。方法 对诊断明确的支气管哮喘患者,单纯型慢性支气管炎患者及慢性喘息型支气管炎患者分别进行乙酰甲胆碱吸入激发和运动激发试验,观察血嗜酸嗜酸粒细胞计数,血ＩｇＥ水平并测定慢性喘息型支气管炎患者血肖嗜酸细胞阳离子蛋白含量。     

支气管激发试验联合血清IgE检测对咳嗽变异型哮喘的诊断价值

目的：探讨支气管激发试验联合激发前后血清ＴＩｇＥ检测对咳嗽变异型哮喘（ＣＶＡ）诊断的特异性和敏感性。方法将咳嗽变异型哮喘与急性支气管炎和无支气管疾病的患者进行比较,分别进行检测ＦＥＶ１／ＦＶＣ、支气管激发试验,以化学发光法分别检测每例患者支气管激发试验前后的ＴＩｇＥ水平,结果ＣＶＡ组气道高反应性的阳性率为９６．７％,显著高于急性支气管炎组和对照缄。ＣＶＡ患者激发前和激发后的ＴＩｇＥ水平分别为（１５     

Evaluation of the relationship between cockroach sensitivity and house-dust-mite sensitivity in Turkish asthmatic patients

Exposure to cockroach has been identified as an important source of indoor allergens in patients with asthma and allergic rhinitis. We evaluated the relationship between cockroach sensitivity and other allergens in patients with asthma. A total of 114 patients, defined asthma according to GINA, were enrolled in this study. A questionnaire including age, sex, duration of asthma, history of cockroach presence at home, and total IgE, blood eosinophil count, pulmonary function tests, standard skin prick test additional cockroach and shrimp allergen were performed. There were 84 (73.7%) female and 30 (26.3%) male patients with a mean age of 38.1+10.1 years. The average duration of asthma was 7.7+7.2 years. Sixty five (57%) patients were determined atopic and 49 (43%) nonatopic. Pollen allergen was the most common allergen in 59 (51.8%) patients with asthma, and second common allergen was mite allergen in 43 (37.7%) patients. Cockroach sensitivity were detected in 23 (20.2%) of 114 all asthmatics and 23 (35%) of atopic asthmatics. High rates of house-dust-mite allergy (73.9%) was determined in patients with cockroach sensitivity (P<0.05), while we found no relationship with other allergens. There was no difference for cockroach sensitivity between rural and urban population. Cockroach sensitivity was more common in mild bronchial asthmatics and a female predominance was observed. In addition, there was no association between shrimp and cockroach sensitivity. As a result, a high rate of cockroach sensitivity alone or with mite sensitivity was seen in patients with bronchial asthma in Turkish population. Because of cross-reactivity between mites and cockroach, cockroach sensitivity should be investigated in patients with house-dust-mite allergy. In addition, a high rate of cockroach sensitivity, in terms of IgE sensitization, may be important for the development of new sensitizations.     

Bronchial provocation tests with RAST-standardized allergens and dosimetric technique

58 patients with proven allergic asthma (positive prick and RAST) were challenged with allergen extracts dosed in RAST arbitrary units; 14 of them were rechallenged after some months to evaluate the reproducibility of results; 41 underwent also a nonspecific challenge with methacholine. The results of the specific bronchial provocation test were well reproducible, with similar coefficients of variation for both early and late reactions. The specific bronchial provocation test was found to be more related to the allergic status, as reflected by specific IgE levels, than to nonspecific bronchial hyperreactivity, as reflected by response to methacholine.     

Interactions of smoking and immunologic factors in relation to airways obstruction

The relationships of smoking, allergy skin test reactivity, and serum IgE to ventilatory function have been analyzed in 1,182 subjects from a general population sample. The study group consisted of subjects aged 35 or more who deny previous lung surgery, old tuberculosis, or a current diagnosis of heart disease in the absence of chronic bronchitis or emphysema. Impairment of the forced expiratory volume in one second (FEV1) shows a definite relationship to total serum IgE. However, this relationship is significant only for a low FEV1 which is accompanied by symptoms suggesting asthmatic or a chronic bronchitis type disease. Allergy skin test reactivity to a battery of common aeroallergens shows no overall relationship to FEV1. However, after accounting for total serum IgE, positive allergy skin tests tend to be associated with high rather than low FEV1 values. The findings suggest that some type of IgE which is not specific for aeroallergens but which is associated with smoking, may be important in the pathogenesis of the "chronic asthmatic bronchitis" syndrome.     

Clearance in small ciliated airways in allergic asthmatics after bronchial allergen provocation

BACKGROUND: Asthma tends to affect mucociliary clearance, as assessed from measurements in large airways. However, there is no knowledge about clearance in the smallest airways of the tracheobronchial region in acute exacerbation of asthma. OBJECTIVE: The aim of the study was to investigate clearance from the bronchiolar region in patients with allergic asthma in a situation resembling a mild acute exacerbation of the disease. We also aimed to compare clearance data with corresponding data found for healthy subjects and asthmatics on therapy. METHODS: Tracheobronchial clearance was studied twice in 9 patients with mild asthma of the allergic type after inhalation of 6 microm (aerodynamic diameter) monodisperse Teflon particles labelled with 111In. At one exposure, inhalation was performed 4 h after bronchial provocation with an allergen the patients were allergic to. The second exposure was a control measurement. The particles were inhaled at an extremely slow flow, 0.05 liter/s, which gives deposition mainly in the small ciliated airways (bronchioles). Lung retention was measured at 0, 24, 48 and 72 h. RESULTS: All patients demonstrated an early asthmatic reaction of varying degree after bronchial provocation. There was significant clearance of radioaerosol in each 24-hour period for both exposures, with the possible exception of the period between 24 and 48 h for the provocation exposure, with similar fractions of retained particles at all points of time. The retained fractions were significantly larger compared to a group of healthy subjects and asthmatics on regular treatment with anti-inflammatory drugs. CONCLUSIONS: Our results indicate that in allergic asthmatics a bronchial allergen provocation with an early asthmatic reaction does not significantly influence overall clearance from the bronchiolar region. However, in the present group of patients, retention in small ciliated airways was significantly higher compared to healthy subjects and asthmatics on regular treatment.     

Bronchial reactivity to inhaled polymyxin B in subjects with asthma and chronic obstructive bronchitis

Bronchial challenge with polymyxin B was performed in 85 patients with asthma and 23 patients with chronic bronchitis. Eighty-five percent of the asthmatics exhibited a significant decline of FEV_1.0 after polymyxin B concentrations of 0.5 – 5 mg/ml. None of the bronchitics responded to such concentrations. Only three bronchitics reacted to 10, 15, and 20 mg/ml polymyxin B. In 21 patients with hay fever, reactivity to polymyxin B paralleled changes in clinical state. The authors discuss the relationship between polymyxin B-induced changes in bronchial reactivity and the interval between provocation and manifestation of allergy.     

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.     

Elevation of total serum immunoglobulin E is associated with asthma in nonallergic individuals.

Elevated serum immunoglobulin (Ig)E is the hallmark of atopy, and contributes to asthma and bronchial hyperresponsiveness in atopic individuals. In contrast, the significance of IgE in nonallergic subjects is less clear. The aim of the present study is to clarify a potential association of IgE and asthma in absence of clinical allergy. To this purpose 1,219 consecutive patients of a pulmonary practice were evaluated. Nonallergic patients were defined by negative skin prick test, history of atopy and specific IgE, 509 subjects (42%) were nonallergic. Among these, 80 patients (16%) had elevated total IgE levels (>150 U x mL(-1)). Prevalence and severity of asthma in nonallergic subjects with IgE>150 U x mL(-1) were compared with subjects with normal IgE levels, and lung function parameters were correlated with serum IgE in all nonallergic subjects and asthmatics. Asthma was more prevalent in nonallergic subjects with elevated IgE levels than in nonallergic subjects with normal IgE (39% versus 14%; p<0.001). Lung function values of nonallergic asthmatics were lower for forced expiratory volume in one second (FEV1)% predicted (66+20% versus 83+/-17%; p<0.001), FEV1% forced vital capacity (FVC) (70+/-14% versus 81+/-8%; p<0.001) and forced mid expiratory flow (FEF25-75) (1.7+/-0.9 L x s(-1) versus 2.8+/-0.9 L x s(-1); p=0.002) in patients with high IgE compared to asthmatics with normal IgE, and were negatively correlated with log IgE levels in all nonallergic asthmatics. (FEVI % pred: r=-0.5, p<0.001; FEV1% FVC: r=-0.53, p<0.001; FEF25-75: r=-0.52, p<0.001). In the whole study population, multivariate analysis showed a greater than fivefold asthma risk for nonallergic individuals with serum IgE>150 U x mL(-1). These data support the role of IgE as risk factor for asthma independent of allergy, and they further challenge the definition of intrinsic asthma as "non-IgE mediated" entity.     

Safety and cellular assessment of bronchial brushing in airway diseases.

Bronchial brushing is a useful method for morphological and functional studies of bronchial epithelial cells (BECs) in various diseases. This technique has been found to be generally safe, but its safety in asthma and chronic bronchitis has not been fully assessed. The purpose of this study was to determine 1, whether bronchial brushing is a safe method in asthmatic and chronic bronchitis patients of differing severity and 2, to characterize the BECs obtained in terms of number, viability and purity. We evaluated 25 asthmatics of variable severity, 19 chronic bronchitis patients and 26 normal volunteers. Bronchoscopy and bronchial brushing were performed in a standardized manner by the same investigator. Safety was assessed by clinical follow-up of all subjects; continuous monitoring of arterial oxygen saturation during the procedure with a digital oximeter was carried out in a subsample of subjects. No complications were observed clinically during the procedure. There was a minimal fall in arterial oxygen saturation without a significant difference between the three groups of subjects. A consistent number of BECs was recovered and their viability, assessed by the trypan blue exclusion test, in asthmatics and chronic bronchitis patients was significantly lower than in controls (P < 0.05). Bronchial brushing is well tolerated and may be a valuable method of obtaining BECs in asthmatic and chronic bronchitis patients.     

Role of Animal Danders as Inhalant Allergens in Bronchial Asthma in India

The etiological significance of animal danders in Indian patients with nasobronchial disorders has not yet been investigated. In the present study, the role of animal danders in the etiology of bronchial asthma was studied. Extracts of danders from 6 animals along with guinea pig whole pelt were prepared. Intradermal and bronchial provocation tests with these extracts were performed on (i) 68 asthmatics and (ii) 20 nonallergic healthy volunteers. In patients, significant positive skin reactions (2+ to 4+) ranged from 1.4% each with guinea pig whole pelt and ox dander to 8.8% with dog dander extracts. None of the healthy volunteers elicited such a response. On bronchial provocation, 20% and 53.8% of the tests were positive in asthmatics showing 1 +and 2+skin reactivity, respectively. All the patients as well as controls eliciting negative intradermal responses demonstrated uniformly negative bronchial provocation tests to different dander extracts. Analysis of various clinical features of asthmatics with respect to skin positivity to dander/pelt extract was also carried out. Radioallergosorbent tests (RASTs) were performed to estimate dander-specific IgE levels in the sera of patients showing different grades of skin response to dander extracts of dog, horse, and goat. Sixty percent of sera from the patients showing 2+ to 4+ skin reactivity to various animal dander extracts showed positive RASTs. RAST positivity as well as RAST ratio increased with increase in the intensity of skin response. All the patients with positive cutaneous as well as positive bronchial responses also showed positive RASTs. Similarly, all the patients with positive skin and positive RASTs showed positive bronchoprovocation tests. These results suggested that animal danders play an important role in the etiology of bronchial asthma. Some of the clinical characteristics of asthmatics, such as (i) early age at onset of asthma, (ii) positive family history, and (iii) asthma with associated allergies, have significant bearing on the cutaneous response to various dander extracts.     

Effects of PAF antagonist, BN52021, on the PAF-, methacholine-, and allergen-induced bronchoconstriction in asthmatic children

Platelet-activating factor (PAF) is an inflammatory mediator capable of inducing protracted inflammation of the airways and bronchial hyperreactivity. Twenty-one asthmatic children were evenly divided into three groups and each group performed a double-blind, placebo-controlled and crossover study on the effect of aerosolized BN52021, a PAF antagonist, on the bronchoconstriction induced by PAF, methacholine, or specific allergen, respectively. One group of healthy children was included for comparison. Total WBC, neutrophils, and eosinophils were counted before and after PAF challenge. The results showed the following: (1) six of seven asthmatics and one of seven normal subjects gave a positive bronchial provocation with PAF; (2) in asthmatics, prior inhalation of BN52021 could inhibit the bronchoconstriction induced by PAF (6/6) and allergen (3/7), but not by methacholine; and (3) 5 min after inhalation of PAF, there was a marked decrease of peripheral blood eosinophils and neutrophils that could be inhibited by prior inhalation of BN52021 in normal subjects but not in asthmatics. These findings support the idea that PAF may be involved in the pathogenesis of bronchial asthma and PAF antagonist may have a role in the prevention and treatment of this disease.     

Coagulation activity in the airways of asthmatic patients]

Fibrin deposition in the mucus plugs of asthmatic patients has long been known, and asthmatic sputum has been held to be important in the pathogenesis of bronchial obstruction. We examined the coagulation activity in the airways of asthmatic patients. Albumin as an index of plasma leakage into the bronchial lumen, thrombin antithrombin III complex (TAT), tissue factor, FDP, D-dimer and the TAT/D-dimer ratio as indices of coagulation and fibrinolytic markers were determined in expectorated or hypertonic saline-induced sputum from patients with acute and stable asthma, and with chronic bronchitis, and from normal control subjects. Patients with acute asthma, in comparison with patients with stable asthma or chronic bronchitis and normal control subjects, had significantly higher levels of albumin, TAT and TAT/D-dimer. The fibrin antigen was more positively stained immunohistochemically in sputum from acute asthmatics than in other sputa. In both patients with acute asthma and those with stable asthma, there was a significant positive correlation between albumin and TAT or albumin and TAT/D-dimer in the sputum. However, in normal control subjects, there was no correlation between these markers. These results suggest that the coagulation system in the airways of acute asthmatic patients is activated, that this favors fibrin deposition in the bronchial lumen and that coagulation pathways in the bronchial compartment and the degree of plasma exudation into the airways are dependently regulated in patients with asthma but not in normal control subjects.     

武汉地区支气管哮喘患儿过敏原特异性IgE分析

目的：探讨武汉地区支气管哮喘儿童特异性过敏原分布及规律。方法：应用德国欧蒙公司生产过敏原特异性IgE检测试剂盒（中国组合）,采用免疫印迹法对216例武汉地区支气管哮喘儿童进行吸入性和食入性过敏原的血清学检测;并按年龄分为婴幼儿组（52例）和儿童组（164例）。对各组过敏原状况进行分析比较。结果：216例患儿中吸入性过敏原呈阳性162例（75％）。其中尘螨152例（70．3％）最高,屋尘89例（41．2％）、真菌组合78例（36．1％）分列其后;儿童组对吸入性过敏原及3种常见吸入性过敏原的阳性率比婴幼儿组高（P〈0．05）。食入性过敏原呈阳性52例（24％）,以虾蟹34例（15．7％）、海鱼26例（12％）、淡水鱼18例（8．3％）分居前3。不同年龄组阳性率差异无统计学意义。结论：过敏是哮喘发病重要因素,引起武汉地区儿童支气管哮喘的过敏原以吸入性过敏原为主并且阳性率随年龄增长而升高;尘螨是最重要的过敏原,食物性过敏原对哮喘的影响亦需重视。     

Allergologic study of allergic asthma and therapeutic implications

The diagnosis of allergic asthma is based on a number of clinical and paraclinical findings which should allow the appropriate therapeutic decisions to be taken. The following diagnostic procedures are available to the clinician: the clinical history which is always of prime importance, skin tests, second stage of diagnosis, total serum and specific IgE (RAST) concentrations demonstrate an IgE dependent mechanism, the human basophil degranulation test (HBDT) to assess cellular sensitivity, bronchial or nasal provocation tests which finally demonstrate the responsibility of the causative allergen. In practice, the clinical history, skin tests and the RAST are sufficient to establish the diagnosis of allergy and to take the appropriate therapeutic measures: eviction, antidegranulation therapy or specific immunotherapy.     

Differences in airway responsiveness to acetaldehyde and methacholine in asthma and chronic bronchitis.

Inhaled acetaldehyde may induce bronchoconstriction in asthmatic subjects and provides a new method to investigate airway responsiveness. The objective of the study was to determine whether acetaldehyde was a more specific stimulus than methacholine in differentiating asthma from chronic bronchitis with or without airflow limitation. Bronchial provocation challenges with methacholine and acetaldehyde were performed in 62 asthmatics and in 59 smokers with chronic bronchitis (32 with chronic bronchitis alone and 27 with chronic bronchitis and coexisting chronic obstructive pulmonary disease (COPD)). The response to both bronchoconstrictor agents was measured by the provocative concentration required to produce a 20% fall in forced expiratory volume in one second (FEV1; PC20). The two types of challenge yielded a similarly high level of sensitivity (100% for methacholine and 92% for acetaldehyde) in revealing airway hyperresponsiveness in asthma. However, bronchoprovocation with acetaldehyde yielded considerably greater specificity (95%) than bronchoprovocation with methacholine (24%) in separating asthma from chronic bronchitis. In subjects with asthma, methacholine and acetaldehyde responsiveness were weakly but significantly correlated (r=0.42, p=0.001) but no correlation was found between airway responsiveness to acetaldehyde and baseline FEV1 (r=0.13, p=0.33). These findings suggest that the demonstration of bronchoconstriction in response to acetaldehyde may be a more specific test than methacholine in the differentiation of asthma from chronic bronchitis. Furthermore, methacholine and acetaldehyde hyperresponsiveness are not reflecting the same pathophysiological process in the airways.     

Sensitivity and exposure to indoor allergens in adults with differing asthma severity.

In asthma, it is uncertain whether there is an association between degrees of exposure to domestic allergens and asthma severity. The pattern of sensitivity and exposure to common indoor allergens was examined in subjects with differing asthma severity. Sensitivity to house dust mite, dog and cat allergen and exposure to Der p 1, Can f 1 and Fel d 1 were assessed by skin prick tests and settled dust analysis in 28 subjects with severe asthma and 28 age- and sex-matched subjects with mild asthma (two declined skin prick test). All severe asthmatic subjects had at least one positive skin test and 20 of the 28 subjects were positive to all three allergens. Fourteen of the 26 subjects with mild asthma who took skin prick tests were positive to at least one, and one of these subjects was positive to the three allergens tested. Except for bedroom Fel d 1, the proportion of severe asthmatics both sensitized and exposed to each allergen at each site was significantly greater than the proportion sensitized and exposed in the mild asthma group. The geometric mean allergen concentrations, with the exception of bedroom Fel d 1, were greater in sensitized severe asthmatics than the sensitized mild asthmatics, which was significant for Der p 1 in bedroom samples and Can f 1 in bedroom and living room samples. These results support an association between the degrees of domestic allergen exposure in sensitized individuals and asthma severity.