Comparison of four different measures of bronchial responsiveness in asthmatic children

Although several tests are available to assess the presence and severity of bronchial hyperresponsiveness (BHR), there is no agreement on the most appropriate stimulus. The most commonly used stimuli are methacholine, histamine, and exercise. Daily peak expiratory flow (PEF) variation has been reported to correlate with the severity of BHR, and in recent years this has been widely used because of its noninvasiveness and ease of performance. This study was carried out to determine the relationship among these four commonly used measures of bronchial responsiveness in asthmatic children. For this purpose, 12 asthmatic children of varying disease severity were recruited. Subjects underwent three challenges on 3 separate days in 1 week. During the week preceding the challenges (methacholine, histamine, and exercise), patients recorded PEF three times a day. All patients had PC₂₀ less than 8 mg/ml with methacholine and histamine. Patients with PC₂₀ greater than 3.5 mg/ml for both methacholine or histamine had negative exercise challenges. The strongest correlation was between histamine and methacholine ( r =0.95). Exercise-induced bronchospasm had substantial and significant correlation with the other three measures. No significant correlation was observed between PEF variability and histamine or methacholine. The varying degrees of relationships among the four commonly used measures suggests that each method yields information on different but related phenomena. More than one measure may be required to detect the different aspects of asthmatic bronchial responsiveness.     

Comparison of the effects on bronchial hyperresponsiveness of antiallergic agents and beclomethasone dipropionate in long-term bronchial asthma

The effect of antiallergic agents (DSCG (disodium cromoglycate), ketotifen, and ibudilast) and beclomethasone dipropionate inhaler (BDI) on bronchial hyperresponsiveness to histamine inhalation was retrospectively assessed in 72 asthmatic patients with more than a year's duration of the disease. Decrease in bronchial hyperresponsiveness to histamine was observed in 10 out of the 33 (30%) antiallergic-agents-treated patients (group A, mean duration = 7.8 months), in 12 of 19 (63.2%) BDI-treated patients (group B, 6.2 months), but only 2 of the 20 (10%) control patients (group C, 7.8 months). Improvement of histamine PC₂₀ was from 310 to 597 μg/ml ( P <0.01) in group A, from 308 to 1622 μg/ml ( P <0.0005) in group B, and from 575 to 525 μg/ml (NS) in group C. A significant decrease in the peripheral eosinophil count was observed only in group B. The improvement in bronchial hyperresponsiveness was parallel with that of asthmatic symptoms; the percentage of patients becoming symptom-free rose from 12 to 42%, 5 to 89%, and 5 to 20% in groups A, B, and C, respectively. Out of 11 unimproved patients in group A, 7 showed a significant improvement in their histamine PC₂₀ by BDI treatment (mean PC₂₀: 311 → 1828 μg/ml). These results suggest that BDI might be more effective than antiallergic agents in the treatment of patients with long-standing bronchial asthma.     

Exercise and isocapnic hyperventilation-induced bronchoconstriction in asthma: relevance of circulating basophils to measurements of plasma histamine

The relationship of airway cooling during exercise to changes in airway caliber, plasma histamine levels, and circulating basophils was investigated in eight allergic asthmatic and eight normal subjects. In asthma matched RHE during exercise and ICH produced almost identical bronchoconstriction with maximum falls in SGaw of 61.0 +/- 4.5% and 57.9 +/- 5.2%, respectively. A similar RHE in normal subjects was associated with a 7.9 +/- 3.3% fall in SGaw. The resting plasma-histamine levels were higher in the asthmatic (0.52 +/- 0.06 ng/ml) than in the normal (0.31 +/- 0.07 ng/ml, p less than 0.05) subjects. No significant change in plasma histamine occurred after exercise in either group nor in the asthmatic subjects with ICH. In contrast, exercise but not ICH stimulated an increase in leukocytes, basophils, and total blood histamine in parallel with the airway response that reached a maximum at 2 to 5 min in both normal and asthmatic subjects. There was a positive correlation between basal plasma and total blood-histamine levels (r = 0.67, p less than 0.01) in normal and asthmatic subjects suggesting that basophils contribute significantly to plasma histamine. The spontaneous basophil release of histamine was greater in asthmatic (13.4 +/- 2%) than in normal subjects (6.46 +/- 7%, p less than 0.005), which is consistent with the higher resting plasma-histamine levels in the asthmatic subjects. These findings suggest that plasma-histamine changes with exercise in asthma but not ICH may be related to the associated basophilia and sample handling rather than intrapulmonary mast cell degranulation.     

Cytomorphological variations and blood histamine in bronchial asthma.

The absolute counts on basophil and eosinophil leucocytes, percentage of vacuolated eosinophil cells and whole blood histamine were determined in 30 controls and 34 patients with bronchial asthma. The basophil counts rose from the quiescent to pre-attack stage and then fell in the acute stage of bronchial asthma. The eosinophil counts, the percentage of vacuolated eosinophils and the blood histamine content increased significantly during an asthmatic attack. An attack of bronchial asthma was precipitated if the blood histamine rose to or above 200 ng/ml or a 50% rise occurred from its quiescent level. The inter-relationship between cytomorphological variations and blood histamine content in various stages of bronchial asthma is discussed.     

Allergen-induced changes in airway responsiveness are related to baseline airway responsiveness

In the literature, bronchial allergen challenge is usually reported to result in an increase in histamine-induced airway responsiveness (AR). The present study investigated the relation between baseline AR and allergen-induced changes in AR. The effect of allergen challenge on AR was investigated in 21 atopic asthmatic patients. Allergen challenge resulted in a significant decrease in PC₂₀ histamine after 24 h. When the group was divided into three subgroups according to baseline PC₂₀ histamine, a significant decrease in PC₂₀ histamine was found only in patients with relatively high baseline PC₂₀ histamine (groups 1 and 2). A significant inverse correlation was found between baseline PC₂₀ and allergen-induced PC₂₀ histamine. The effect of repeated allergen challenge on AR was studied in eight patients. The first allergen challenge resulted in a significant decrease in PC₂₀ histamine; no further decrease in mean PC₂₀ histamine was seen after the second allergen challenge. These results suggest that allergen-induced changes in AR occur mainly in patients with relatively high baseline PC₂₀ values. Once an increase in AR is induced, further allergen challenge does not always result in further increase in AR.     

Eosinophil activity markers in peripheral blood have high predictive value for bronchial hyperreactivity in patients with suspected mild asthma

The present study aimed to evaluate the predictive value of eosinophils and markers of their activity for bronchial hyperreactivity (BHR) in a population of patients with recently developed clinical symptoms of asthma. The activation of eosinophils was estimated by measuring eosinophil cationic protein (ECP) in serum. In addition, flow cytometry was used to measure the expression of the EG2-epitope on intracellular ECP in eosinophils from peripheral blood. Twenty-eight consecutive patients with clinical history of asthma were studied. Of the 28 patients, 18 had a positive bronchial challenge test measured as PD₂₀≤ 1600 μg histamine. A significantly higher concentration of eosinophils and a trend to higher ECP in the peripheral blood was found in the hyperreactive group than in the nonreactive group. However, the intracellular expression of ECP did not correlate with the PD₂₀ value, and no significant difference between the groups was found. With one eosinophil activity marker, either serum ECP or EG2, BHR could be predicted in 70% of the patients. If we combined any two of the activity markers (serum ECP, EG2, or the percentage of eosinophils), the predictive value increased to 100%. We conclude that the blood eosinophil concentration, as well as, to some extent, serum ECP, has a high specificity for BHR in patients with recently developed clinical symptoms of asthma. Despite normal bronchial reactivity, some patients had signs of activated eosinophils, i.e., high serum ECP and increased EG2 expression. Thus, these markers may reflect early stages in the development of BHR. Our results also indicate that a combined evaluation of percentage of eosinophils and of eosinophil activity markers is of clinical value to predict BHR.     

Emergence of basophils at sites of local allergic reactions using a skin vesicle test

Vesicular exudate, produced by the application of cantharides plaster over normal skin and sites of intradermal allergen injection, was examined for the presence of basophils and eosinophils in normal subjects and patients with bronchial asthma. In comparison with the normals, the asthmatic group demonstrated a high rate of basophil appearance in vesicular fluid derived from areas of untreated skin. Basophil appearance was even more prominent in vesicular fluid from skin injected intradermally with various allergens. Modest numbers of basophils appeared at skin sites injected with house dust, but relatively large numbers appeared in areas injected with Candida, ragweed or tuberculin extracts. Patients with severe, intractable asthma frequently demonstrated large numbers of basophils in vesicular exudates. Intradermal injections of anti-IgE caused the greatest number of basophils to appear in the vesicular fluid, The numbers of eosinophils migrating into such vesicular lesions were not statistically significant though their numbers were proportional to those of the basophils. A significant correlation was shown to exist between both basophil and eosinophil blood counts and the numbers of these cells appearing in cutaneous vesicular fluid. This study demonstrates that basophil leukocytes, together with eosinophils, migrate from blood into extravascular tissues at sites of allergic reaction—especially reaginic hypersensitivity. The skin vesicle technique described is simpler than the skin window technique and may be of use in detection of allergens and evaluation of allergic disease states.     

Leukotriene EM4 plasma levels in adult asthmatic patients with variable disease severity

Chavis C, van Vyve T, Chanez P, Farce M, Bousquet J, Michel FB, Godard P. Leukotriene E4 plasma levels in adult asthmatic patients with variable disease severity.
Cysteinyl leukotrienes 'C-LTs' are local inflammatory mediators involved in bronchial asthma. Seventeen asthmatic patients 'FEV₁ ranging from 41 to 99.8% of predicted values' and 11 healthy subjects were studied. The clinical severity of asthma was assessed by the Aas score. Plasma C-LTs were measured by enzyme immunoassay 'EIA' after sample purification by solid-phase extraction 'SPE', to investigate whether differences may exist between asthmatic and control subjects and whether leukotriene E₄'LTE₄' levels were related to the severity of disease. LT measurements showed that 87.6±1.2% was recovered as LTE₄ and 9.4±1.3% as LTC4. In asthmatic subjects, LTE₄ plasma levels were found to be significantly higher than those in the control group '1.073±0.133 and 0.53±0.19 ng/ml of plasma, respectively; P < 0.002'. Moreover, there was a significant correlation between LTE₄ plasma levels and the Aas clinical score ' P < 0.005'. These data suggest that plasma LTE₄ levels might be used to assess the severity of asthma.     

Inhaled lysine acetylsalicylate (L-ASA) attenuates histamine-induced bronchoconstriction in asthma

When administered by inhalation, histamine provokes dose-related bronchoconstriction in asthmatic subjects mainly by a direct activation of histamine H1-receptors on airway smooth muscle. However, little is known of the change in airway responsiveness to histamine after cyclooxygenase blockade. The aim of the study was to investigate the effect of the potent cyclooxygenase inhibitor, lysine acetylsalicylate (L-ASA), administered by inhalation on histamine-induced bronchoconstriction in a group of 16 asthmatic subjects. The subjects studied attended the laboratory on four separate occasions to receive nebulized L-ASA (solution of 90 mg/ml) or matched placebo (glycine solution of 30 mg/ml) 15 min before bronchoprovocation tests with histamine and methacholine in a randomized, double-blind order. Changes in airway caliber were followed as forced expiratory volume in 1 s (FEV₁), and agonist responsiveness was expressed as the provocative concentration causing a 20% fall in FEV₁ from baseline (PC₂₀). Administration of both L-ASA and glycine solution caused a small but significant acute fall in FEV₁ from baseline, which returned to normal within 15 min. When compared to placebo, inhaled L-ASA reduced the airway responsiveness to histamine in 13 of the 16 subjects studied, the geometric mean (range) values for PC₂₀ histamine increasing significantly ( P < 0.001) from 1.72 (0.13–5.49) mg/ml to 3.31 (0.36–12.00) mg/ml after placebo and L-ASA, respectively. No significant change in airway responsiveness to methacholine was recorded after L-ASA. Acute administration of L-ASA by inhalation protects the asthmatic airways against histamine-induced bronchoconstriction, thus suggesting that endogenous prostaglandins may play a contributory role in the airways response to histamine in human asthma.     

Double-blind trial of house-dust mite immunotherapy in asthmatic children resident at high altitude

Twenty-three Dermatophagoides pteronyssinus (Dpt)-sensitive asthmatic children aged 7–14 years entered a double-blind, placebo-controlled trial of standardized immunotherapy (IT) (Alpare) while resident at high altitude. Dpt sensitivity was evaluated by skin prick tests at different allergen concentrations at the enrollment and after 6 and 12 months of treatment. Bronchial hyperreactivity was evaluated at the same time points, and on each occasion, histamine challenge and, the following day, Dpt bronchial challenge were performed. All patients, irrespective of active treatment, improved clinically and in lung function with increased PC₂₀ and Dpt-PD₂₀. Alpare-treated patients had a significantly decreased sensitivity on Dpt skin testing (P ≤0.009) and felt that their asthma had improved (P ≤0.001) compared with placebo-treated subjects, but there was no difference between the treatment groups in lung function or bronchial challenge response. IT neither increased nor decreased bronchial histamine sensitivity. Our results indicate that Dpt IT benefits asthmatic children, but improvement by allergen avoidance at high altitude is even greater.     

The magnitude of the spontaneous production of histamine-releasing factor (HRF) by lymphocytes in vitro correlates with the state of bronchial hyperreactivity in patients with asthma

In our previous studies we reported that lymphocytes from patients with asthma spontaneously produce histamine-releasing factor (HRF) in vitro. In an effort to examine whether spontaneous HRF production (SpHRF) by lymphocytes from patients with asthma is related to the state of bronchial hyperreactivity (BHR), 20 patients with mild to severe asthma were studied. Peripheral blood lymphocytes were cultured alone in a serum-free medium for 24 hours, and culture supernatant was assayed for HRF activity in two separate histamine-release tests with autologous basophils and normal basophils from known healthy donors. BHR was measured as bronchial reactivity to inhaled histamine and was expressed as a provocation concentration of histamine required to induce a 20% fall in FEV1 (PC20). The result of this study demonstrated that lymphocyte supernatant from all patients with asthma released significant amount of histamine from both autologous and normal basophils. Very high histamine release was usually induced by lymphocyte supernatant from severely ill patients who had PC20 less than 2 mg/ml. Statistical analysis demonstrated that the magnitude of the SpHRF significantly correlated (r = -0.86; p less than 0.001) with PC20. Since mast cell- and basophil-derived mediators have been implicated in the pathogenesis of BHR, high correlation between PC20 and SpHRF by lymphocytes suggests that the latter may contribute to the development of BHR. Further studies are required to disclose the exact relationship between SpHRF and BHR.     

Airway inflammation in asthma and perennial allergic rhinitis. Relationship with nonspecific bronchial responsiveness and maximal airway narrowing

BACKGROUND: Eosinophilic airway inflammation is the hallmark of asthma, but it has also been reported in other conditions such as allergic rhinitis. We have tested whether the analysis of cells and chemicals in sputum can distinguish between patients with mild allergic asthma, those with allergic rhinitis, and healthy controls. The relationship between inflammation markers in sputum and nonspecific bronchial hyperresponsiveness to methacholine (BHR) (PD20 and maximal response plateau [MRP] values) was also evaluated. METHODS: We selected 31 mild asthmatics and 15 rhinitis patients sensitized to house-dust mite. As a control group, we studied 10 healthy subjects. Every subject underwent the methacholine bronchial provocation test (M-BPT) and sputum induction. Blood eosinophils and serum ECP levels were measured. Sputum cell differentials were assessed, and eosinophil cationic protein (ECP), tryptase, albumin, and interleukin (IL)-5 levels were measured in the entire sputum supernatant. RESULTS: Blood eosinophils and serum ECP levels were higher in asthma patients and rhinitis than in healthy controls, but no difference between asthma patients and rhinitis patients was found. Asthmatics had higher eosinophil counts and higher ECP and tryptase levels in sputum than rhinitis patients or control subjects. Sputum albumin levels were higher in asthmatics than in controls. Rhinitis patients exhibited higher sputum eosinophils than healthy controls. An association between sputum eosinophil numbers and MPR values (r= -0.57) was detected, and a trend toward correlation between sputum ECP levels and PD20 values (r= -0.47) was found in the rhinitis group, but not in asthmatics. No correlation between blood eosinophilic inflammation and lung functional indices was found. CONCLUSIONS: Induced sputum is an accurate method to study bronchial inflammation, allowing one to distinguish between rhinitis patients and mildly asthmatic patients. The fact that no relationship was detected between sputum inflammation and BHR suggests that other factors, such as airway remodeling, may be at least partly responsible for BHR in asthma.     

Decrease of T-lymphocyte proliferation in exercise-induced asthma

The present study was designed to examine the effect of physical exercise on T-lymphocyte proliferation in patients with exercise-induced asthma (EIA). Indeed, a decrease in different immune functions is described in normal man after exercise. Thirty subjects (10 normal and 20 asthmatic subjects with or without EIA) underwent a submaximal exercise test on an electrically driven treadmill. Before and after this test, ventilatory variables were measured, and venous blood was taken to study plasma histamine (RIA) and spontaneous and phytohemagglutinin (PHA)-pulsed T-lymphocyte proliferation (mononuclear cells isolated on Ficoll-Hypaque; tritiated thymidine incorporation). Ten minutes after the end of the exercise, there was a significant FEV₁ decrease only in asthmatic subjects with EIA (mean: 24 ± 5%). In the same group, the mean plasma histamine level was 0.31 ng/ml 1 (± 0.06) before the challenge. It rose to 0.62ng/ml^-1 (± 0.14) 10 min after the end of the exercise ( P < 0.05), and returned to normal limits 20 min after the test. In this group, there was also a significant decrease (by about 35%) of spontaneous and PHA-pulsed T-lymphocyte proliferation 2 and 4 h after the exercise. By contrast, exercise challenge had no effect on either plasma histamine level or T-lymphocyte proliferation in the normal group. Our results show a rapid and transient increase in plasma histamine in EIA. This was followed 2 and 4 h later by a significant decrease of T-lymphocyte proliferation. A possible relationship between these two phenomena is discussed.     

Bronchial hyperresponsiveness in two populations of Australian schoolchildren. I. Relation to respiratory symptoms and diagnosed asthma

In order to explore the relationship between bronchial hyperresponsiveness (BHR) to inhaled histamine, respiratory symptoms and diagnosed asthma in children, we undertook a cross-sectional study of 2363 Australian schoolchildren aged 8–11 years. The methods used included a self-administered questionnaire to parents, which was shown to have a high degree of repeatability, and a histamine inhalation test to measure bronchial responsiveness (BR). The study showed that 17.9% of children had BHR, defined as a 20% fall in FEV₁ at a provoking dose of histamine (PD₂₀ FEV₁) of less than 7.8 μmol. The distribution of PD₂₀ FEV₁ appeared to be continuous. Most children with PD₂₀ FEV₁ values < 1.0μmol had symptoms of asthma. However, 6.7% of children had BHR without symptoms or a previous diagnosis of asthma and 5.6% had had a diagnosis of asthma but had no BHR. Although there was a good association between BHR and respiratory symptoms, questionnaire data of wheeze and diagnosed asthma do not reflect accurately the level of BHR in the community. We conclude that cross-sectional studies of BR to identify children with BHR probably do not reflect the prevalence of asthma in populations of children. However, the strong association between BHR and symptoms, particularly in children with severe and moderate BHR, suggests that measurements of BR in populations are useful for defining a group of children whose airways behave differently from those of the majority. Prospective studies are needed to define the level of BHR that is associated with important sequelae.     

Spontaneous and non-specific release of histamine and PGD2 by bronchoalveolar lavage cells from asthmatic and normal subjects: effect of nedocromil sodium

Mast cells have been implicated in the pathogenesis of allergic asthma but their role in non-allergic asthma remains to be elucidated. The spontaneous and non-specific release of histamine by suboptimal doses of calcium ionophore A23187 was studied in bronchoalveolar lavage cells obtained from nine asthmatic and seven healthy individuals. Bronchoalveolar lavage was performed with saline, and total cells were incubated without any secretagogue (spontaneous histamine release) or after addition of 1.25, 2.5 and 5 μ m of A23187 for 30 min (net maximal release). Histamine was titrated by using a very sensitive radioimmunoassay using a monoclonal antibody against acylated histamine. The spontaneous release was similar in asthmatic (20.6±8.2%) and healthy individuals (17.4±8.4%). The net maximal release of histamine was significantly greater in asthmatic patients (28.1±17.4%) than in normal subjects (10.3±8.9%). The release of histamine was significantly correlated to the release of PGD₂ measured by enzyme immunoassay using a polyclonal antibody against methoxamine-PGD₂ (Spearman rank test: 0.78, P <0.01). In eight subjects, the release of histamine by A23187 was studied in the presence of nedocromil sodium and it was observed that this drug significantly ( P <0.05) decreased the net maximal release of histamine. This study shows that mast cells from asthmatic individuals have a greater releasability than those of normal subjects.     

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.     

Spontaneous histamine release and histamine content in normal subjects and subjects with asthma

Spontaneous histamine release (SHR) from basophils by simple incubation at 37 degrees C for 60 minutes and histamine content of basophils were assessed in normal subjects, patients with asthma, and methacholine-sensitive subjects without asthma (NAMS). SHR from basophils of normal subjects did not exceed 10% of the total histamine. A significantly higher SHR was observed in basophils from subjects with asthma than from normal subjects (p less than 0.002). Basophil SHR in patients with asthma not receiving medication was significantly greater than that in patients with asthma receiving medication (p less than 0.05). SHR from basophils in NAMS subjects was similar to that in normal subjects. SHR was highly dependent on temperature and Ca++ and Mg++ ions and appeared to be a slower event than anaphylactic release. The mean histamine content per basophil from normal subjects was 1.48 +/- 0.13 pg (mean +/- SEM). Basophils from subjects with asthma contained significantly less histamine than basophils from normal subjects (p less than 0.002). Histamine content per basophil from NAMS subjects was slightly lower than histamine content per normal basophil. No apparent relationship was found between the magnitude of SHR and the histamine content per basophil in the patients with asthma not receiving medication. Hypersensitivity to food or exercise does not appear to be essential for high SHR. High SHR appears to bear little, if any, relationship to cell damage or cell death. High SHR may be a factor that could serve as a marker for bronchial asthma. Further studies are needed to define the clinical relationship and pathophysiologic mechanism of SHR.     

Effect of ethanol on airway caliber and nonspecific bronchial responsiveness in patients with alcohol-induced asthma

No study has investigated the effects of ethanol on bronchial responsiveness in patients with alcohol-induced asthma, although acetaldehyde, which is a metabolite of ethanol and is thought to be a main factor in alcohol-induced asthma, causes both bronchoconstriction and bronchial hyperresponsiveness. The purpose of this study was to investigate the direct action of ethanol on the airway in patients with alcohol-induced asthma. First, we investigated the bronchial response to inhalation of ascending doses (5, 10, and 20%) of ethanol in nine patients with alcohol-induced asthma. Then, the bronchial responsiveness to methacholine was measured in 14 patients who were pretreated with saline or 20% ethanol in a double-blind, randomized, placebo-controlled, crossover fashion. Ascending doses of inhaled ethanol caused no significant changes in FEV₁. The methacholine concentrations producing a 20% fall in FEV₁ (PC₂₀-MCh) after 20% ethanol (0.769 mg/ml, GSEM 1.514) were significantly ( P = 0.0357) higher than those after saline (0.493 mg/ml, GSEM 1.368). This indicates that ethanol has a reducing effect on nonspecific bronchial responsiveness in patients with alcohol-induced asthma; this paper is the first report on the effects of ethanol on bronchial responsiveness.     

Appearance of basophils in the sputum of patients with bronchial asthma

A total of 108 samples of sputum obtained from twenty patients with bronchial asthma were examined for appearance of basophils and eosinophils. Both cell types are present in sputum during an asthmatic attack and disappear at the conclusion of the attack. Their presence correlates with the severity of the disease. It has previously been demonstrated that the blood basophils count falls during attacks of bronchial asthma, and the present study suggests that basophils move from the blood stream into bronchial tissue during the acute phase of an asthmatic attack.     

Relationship Between Atopy and Bronchial Hyperresponsiveness

Both atopy and bronchial hyperresponsiveness (BHR) are characteristic features of asthma. They are also found among non-asthmatic subjects, including allergic rhinitis patients and the general population. Atopy and BHR in asthma are closely related. Atopy induces airway inflammation as an IgE response to a specific allergen, which causes or amplifies BHR. Moreover, significant evidence of the close relationship between atopy and BHR has been found in non-asthmatic subjects. In this article, we discuss the relationship between atopy and BHR in the general population, asthmatic subjects, and those with allergic rhinitis. This should widen our understanding of the pathophysiology of atopy and BHR.