[Case of bronchial asthma complicated with Takotsubo cardiomyopathy after frequent epinephrine medication].

A 62-year-old man with non-topic severe persistent asthma and chronic obstructive disease suffered severe asthma exacerbation. Epinephrine was repeatedly injected subcutaneously (0.3mg x 8 times in four hours) in addition to intravenous methylprednisolone for his severe asthma. Despite these treatments, his symptoms steadily deteriorated and thus he was transferred to our hospital. He did not have chest pain or a sensation of compression, while ECG on admission demonstrated ST elevation, loss of R-wave progression, negative T waves and QT interval prolongation, suggesting ischemic heart disease. Nonetheless creatine kinase and its MB isozyme were within normal range and myosin light chain I and troponin T were only mildly elevated. Echocardiography demonstrated apical dyskinesia and hypersystole in the basal region of the heart. Finally this case was diagnosed as Takotsubo cardiomyopathy, probably due to catecholamine-mediated myocardial stunning by overuse of epinephrine for acute severe asthma exacerbation. Abnormal findings of ECG and echocardiography became normal without any specific treatments for the heart.

[Questionnaire survey of the relationship between the common cold and acute asthma exacerbation].

Using questionnaires for 281 healthy subjects and 139 asthmatic patients in 5 medical institutes, we investigated the relationship between the common cold and acute asthma. The frequency of the common cold, duration to recovery and absences from work were slightly higher in asthmatics than healthy subjects. Acute asthma occurred in a few days following common cold and subsided at the end of or after the common cold. Evaluation of the types of common cold revealed that the cold, which causes upper respiratory symptoms, frequently induced acute asthma. Bronchodilators seemed to be less effective for cold-induced asthma. Collectively, these results suggested that the common cold induces acute asthma not through virus-induced direct inflammatory responses but through indirect immunological responses. Through these questionnaires, we realized that it is important to prevent the common cold, a trigger of asthma attacks. As the guidelines of asthma therapy recommended, the use of corticosteroid must be considered when acute asthma attacks occur.

Polymorphisms in the CYP1A2 gene and theophylline metabolism in patients with asthma.

BACKGROUND: Cytochrome p450 (CYP) 1A2 gene polymorphisms are thought to be involved in theophylline metabolism. OBJECTIVE: We analyzed the effect of genetic polymorphisms in the 5'-flanking region to the first intron of the CYP1A2 gene on theophylline metabolism in 75 Japanese patients with asthma and 159 healthy Japanese volunteers. METHODS: Genetic polymorphisms were detected at 4 sites of the CYP1A2 gene, -2964(G/A) and -1569(T/del) in the 5'-flanking region and 155(T/G) and 731(A/C) in the first intron. RESULTS: There were no significant differences in the distribution of gene polymorphisms between the asthmatic and control groups. Among asthmatic patients, theophylline clearance was significantly lower in patients with the polymorphism at site -2964(G/A) whose genotype was G/A (0.029 +/- 0.001 L x h(-1) x kg(-1)) or A/A (0.029 +/- 0.002 L x h(-1) x kg(-1)) than in those whose genotype was G/G (0.034 +/- 0.001 L x h(-1) x kg(-1)) (P <.01 and P <.05, respectively). High theophylline clearance levels significantly correlated with age in the G/G subgroup of site -2964(G/A) (P <.05, r = -0.35) but not in the G/A or A/A subgroup. CONCLUSION: Given its potential side effects, theophylline may need to be used with care in patients with the A allele at site -2964(G/A) in the CYP1A2 gene, because theophylline metabolism levels are lower in such patients, particularly in young asthmatic individuals.

[Clinical evaluation of bronchial asthma complicated with sarcoidosis].

The clinical features of 25 asthma cases complicated with sarcoidosis were evaluated retrospectively. In our department, 8 patients (6%) out of 134 with sarcoidosis had asthma. The complication was found more frequently in females than in males, and the age of onset of the asthma extended from 2 to 63 years. Neither the severity nor the type of asthma showed any distinct pattern. In terms of chest radiographs of sarcoidosis, stage II was more common in our cases, while stage I was more common in the reported cases. In our cases, the severity of the asthma remained stable irrespective of the activity of the sarcoidosis. In the reported cases, the two diseases showed similar courses. The deterioration of each disease was associated in few cases with improvement in the other. In summary, the present study suggests that inflammation of the airways in asthma and sarcoidosis probably affect their course so that the two diseases improve or deteriorate together.

[A case of pulmonary involvement of malignant lymphoma with diffuse ground-glass opacity in chest CT].

A chest CT of an 82-year-old woman suffering from general fatigue revealed ground-glass opacities in both lower lung fields. Antibiotics were administered, but the ground-glass opacities developed into air-space consolidation with air-bronchogram. Hematuria was observed and abdominal CT showed multiple retroperitoneal masses, suggesting malignant lymphoma. The case was diagnosed histopathologically as malignant lymphoma (non-Hodgkins) of the diffuse, medium-sized B cell type on the basis of a right inguinal lymph node biopsy. Autopsy results suggested that the malignant lymphoma may have developed from the left adrenal gland. In the lungs, lymphoma cells infiltrated mainly into the interstitial spaces, but also into some alveolar spaces. The ground-glass opacities found in this case may have reflected the infiltration of lymphoma cells into the pulmonary interstitial spaces.

[Two cases of asthmatic exacerbation caused by parainfluenza virus 3 infection].

Although viral respiratory tract infections are considered to be the most frequent causes of asthmatic exacerbation, respiratory viruses can rarely be detected in the adult population. We describe 2 cases, in a 43-yr-old man with severe atopic asthma and in a 69-yr-old man with moderate non-atopic asthma. After the onset of nasal discharge, sore throat and fever, the asthma had become exacerbated in both cases during the summer of 2002. In both cases, parainfluenza virus (PIV) 3 viral RNA could be detected from oral gargling by RT-PCR, and the serum viral antibody titer against PIV 3 increased significantly. These cases were therefore diagnosed as undergoing asthmatic exacerbation caused by PIV 3 infection and were successfully treated with systemic steroids. During summer, 2002, in our outpatient clinic, PIV 3 infection was demonstrated in approximately half of the asthmatic exacerbations associated with upper respiratory symptoms, including the present cases. Collectively, PIV 3 seems to represent an important viral cause of asthma exacerbation in summer.

[A case of pulmonary Mycobacterium gordonae infection with pleural effusion].

A 65-year-old woman, treated with prednisolone (5 mg daily) for rheumatoid arthritis, visited our hospital because of right chest pain. Chest CT showed small nodular shadows in the right lung accompanied with right pleural effusion. A pulmonary Mycobacterium gordonae infection was diagnosed, since M. gordonae was identified twice from her sputum. She was treated with rifampicin, ethambutol and streptomycin for two months, and then streptomycin was replaced with clarithromycin. Three months after the initial treatment, M. gordonae was eradicated from her sputum. Pleural puncture revealed bloody, exudative, lymphocytotic pleural effusion, but no malignant cells were identified. Although pathological diagnosis by thoracoscopic pleural biopsy could not be performed, it is likely that the pleural effusion was associated with the pulmonary M. gordonae infection in the present case.

[Two cases of allergic bronchopulmonary mycosis caused by Schizophyllum commune in young asthmatic patients].

We report on two patients, a 27-year-old and a 33-year-old woman, with allergic bronchopulmonary mycosis (ABPM) caused by the basidiomycetous fungus Schizophyllum commune (S. commune). Each patient had bronchial asthma. Both were admitted to our institution for further examination of cough, sputum, and abnormal chest shadows. ABPM was strongly suspected, because they showed eosinophilia in both peripheral blood and sputum, and increased serum IgE levels. A mold was isolated from their sputum, but identification was not possible. Systemic corticosteroid therapy relieved their symptoms and chest abnormal shadows. Later, S. commune, a basidiomycetous fungus, was detected from further examination of their sputum cultures, and serum anti-S. commune IgG was elevated. Finally, both cases were diagnosed as ABPM caused by S. commune. It is reported that this syndrome typically develops in women in middle age, but our patients were young women. It is important to take into account the possibility of ABPM caused by S. commune even in young patients when Aspergillus species are not isolated.

Effects of anti-inflammatory therapies on recurrent and low-grade respiratory syncytial virus infections in a murine model of asthma.

BACKGROUND: Recurrent and subclinical viral respiratory tract infections could immunologically exacerbate allergic airway inflammation. However, the most appropriate treatment for virus-induced asthma exacerbation is yet to be established. The effects of glucocorticoids in virus-induced acute asthma are controversial. OBJECTIVE: To determine the effects of representative anti-inflammatory therapies for asthma--glucocorticoids and leukotriene receptor antagonists (LTRAs)--in mite allergen-sensitized and repeatedly low-grade respiratory syncytial virus (RSV)--infected mice. METHODS: Dermatophagoides farinae-sensitized mice were inoculated twice with low-grade RSV and subcutaneously injected with either a glucocorticoid or an LTRA for 4 consecutive days. Lung inflammation, cytokine profiles, LT production, and viral RNA in lung tissues were compared in 5 groups of 8 mice each: controls, D farinae allergen sensitized, D farinae sensitized and RSV infected, D farinae sensitized and RSV infected with dexamethasone, and D farinae sensitized and RSV infected with pranlukast, an LTRA. RESULTS: Allergic airway inflammation in D farinae mice was significantly enhanced by recurrent and low-grade RSV infections (RLRIs). The glucocorticoid attenuated allergic airway inflammation, which was associated with interleukin 5 (IL-5) and interferon-gamma (IFN-gamma) suppression in lung-draining lymph nodes without affecting viral quantity. The LTRA also attenuated allergic airway inflammation in D farinae-RSV mice with concomitant inhibition of IL-5 but not IFN-gamma. Dermatophagoides farinae allergen sensitization significantly increased LTs in the airway, whereas RLRIs did not further enhance LT production. CONCLUSIONS: Glucocorticoids and LTRAs significantly inhibit RLRI-induced exacerbation of allergic airway inflammation by distinct pathways. Dexamethasone suppressed nonspecific cytokines, whereas viral RNA did not increase via suppression of immunity. In contrast, pranlukast specifically inhibited IL-5 but not IFN-gamma.

Naturally occurring parainfluenza virus 3 infection in adults induces mild exacerbation of asthma associated with increased sputum concentrations of cysteinyl leukotrienes.

BACKGROUND: Viral respiratory tract infections represent the most frequent cause of asthma exacerbation in both children and adults, but the precise mechanism of such exacerbation remains unknown. OBJECTIVES: To determine the critical mediator of naturally occurring parainfluenza virus (PIV) 3-induced mild asthma exacerbations in adults. METHODS: The study subjects were 19 adult asthmatics with mild asthma exacerbation (peak expiratory flow = 60-80% of predicted before bronchodilator use and >80% of predicted after initial bronchodilator treatment). Differential cell counts and concentrations of inflammatory markers including eosinophil cationic protein (ECP), cysteinyl leukotrienes (cysLTs), interleukin (IL)-5, IL-10 and IL-12 were measured in the induced sputum obtained from adults with PIV3- (n = 9) and non-cold-induced (n = 10) exacerbation of asthma during both acute and convalescent phases. RESULTS: PIV3 infection was confirmed by the presence of viral RNA in nasopharyngeal aspirates. Mild exacerbation of asthma was not associated with significant changes in sputum differential cell counts. Concentrations of sputum ECP and cytokines were comparable between PIV3 and non-cold-induced patients. In contrast, PIV3 infection was associated with a significant increase in sputum cysLTs during the acute phase of mild asthma exacerbation. CONCLUSIONS: Our results identified cysLTs as a critical mediator of PIV3-induced acute asthma exacerbation.

Salivary IgA and oral candidiasis in asthmatic patients treated with inhaled corticosteroid.

BACKGROUND: Inhaled corticosteroids are used for the treatment of bronchial asthma. Systemic side effects are rare, but local problems, such as oral candidiasis, can occur. Only a proportion of patients encounter this problem, and the mechanism of oral candidiasis induced by inhaled corticosteroids remains obscure. According to reports in immunodeficient patients, oral candidiasis is related to deficiencies in topical immunity, such as salivary IgA. OBJECTIVES: We evaluated differences in salivary IgA between asthmatics in whom Candida was detected or not detected from the pharynges, respectively. METHODS: Saliva was collected from 18 healthy controls and 37 asthmatic patients treated with inhaled corticosteroids. The amounts of total IgA and the Candida-specific IgA of the saliva were measured. Fungal culture of the pharyngeal wall was also performed. RESULTS: There were no differences in salivary total IgA and Candida-specific IgA between healthy controls and culture-negative asthmatic patients. Salivary total IgA of Candida-positive asthmatic patients was significantly lower than that of Candida-negative patients. However, there was no difference in Candida-specific IgA levels between these two groups. CONCLUSIONS: Our results suggest that inhaled corticosteroids can potentially decrease salivary total IgA but that host factors are also important in the development of oral candidiasis.

Evaluation of theophylline or pranlukast, a cysteinyl leukotriene receptor 1 antagonist, as add-on therapy in uncontrolled asthmatic patients with a medium dose of inhaled corticosteroids.

A few studies compared the additional effects of oral controller medicines on pulmonary function in asthmatic patients on a moderate dose of inhaled steroids. The aim of this study was to compare the additional effects of two oral asthma controllers, a leukotriene receptor antagonist and a sustained released theophylline (Theo), with a moderate dose of inhaled steroid on peak expiratory flow (PEF) and asthma-related symptoms. A total of 67 adult asthmatic patients with PEF < 80% predicted during a 2-week run-in period with 800 microg/day of beclomethasone dipropionate were randomized to receive either pranlukast, 450 mg/day (n = 33), or sustained released Theo, 200 mg/day (n = 34), for 4 weeks. Pranlukast and Theo did not significantly alter the symptom scores, use of rescue beta2-agonist, and daily PEF variability. However, both agents significantly increased both morning and evening PEF compared with the run-in periods. The effects of both medications were comparable. For asthmatic patients even on a moderate dose of inhaled steroids, the addition of either leukotriene receptor antagonist or sustained released Theo does not improve asthma-related symptoms but significantly and equally increases PEF.

Pranlukast, a leukotriene receptor antagonist, inhibits interleukin-5 production via a mechanism distinct from leukotriene receptor antagonism.

BACKGROUND: Pranlukast, a cysteinyl leukotriene receptor 1 (CysLTR1) antagonist, inhibits not only airway smooth muscle contraction, but also allergic inflammation. The aim of this study was to determine the mechanism of pranlukast-induced interleukin-5 (IL-5) inhibition in allergic inflammation. METHODS: Surgically resected human lung tissue was passively sensitized in vitro with mite-allergen-sensitized sera, followed by stimulation with mite allergen after pretreatment of the tissue with pranlukast, dexamethasone, or both. The IL-5 protein level in the culture medium was measured, and in situ hybridization of IL-5 and CysLTR1 mRNA was performed using lung tissues. RESULTS: Pretreatment of lung tissues with pranlukast alone significantly decreased the amount of IL-5 protein in the culture medium by 40%. The combination of pranlukast and dexamethasone synergistically enhanced this effect. Quantitative in situ hybridization with image analysis revealed abundant expression of IL-5 mRNA in eosinophils, lymphocytes, and mast cells in sensitized and allergen-stimulated lung tissues. CysLTR1 mRNA was detected in macrophages, smooth muscle cells, eosinophils, and mast cells, but was less expressed in lymphocytes. Pranlukast-induced inhibition of IL-5 mRNA expression was noted in various cells, irrespective of their CysLTR1 mRNA expression status. In addition, cysteinyl leukotrienes per se failed to upregulate the IL-5 production. CONCLUSION: Our results indicate that pranlukast inhibits IL-5 synthesis via a mechanism distinct from CysLTR1 antagonism.

Effects of antiasthmatic agents on the functions of peripheral blood monocyte-derived dendritic cells from atopic patients.

BACKGROUND: Dendritic cells (DCs), the antigen-presenting cells in the airway, play a critical role in asthma. Nevertheless, there is little information on the effects of antiasthmatic agents on DCs. OBJECTIVES: The purpose of the present study was to determine the effects of representative antiasthmatic agents, including cysteinyl leukotriene (cysLT) 1 receptor antagonists, corticosteroid, and tacrolimus, on DCs in inducing allergy. METHODS: Human peripheral blood monocyte-derived DCs (MoDCs) generated from atopic and healthy subjects were pulsed with Dermatophagoides farinae allergen in the presence of medium alone, pranlukast, montelukast, dexamethasone, or tacrolimus. The mRNA expressions of cysLT receptor, cysLTs producing enzymes, and various surface markers on MoDCs, as well as the concentrations of cysLTs, IL-10, and IL-12 in cultured supernatants, were determined. MoDCs were also cocultured in vitro with autologous CD4(+) T cells, and IL-5 and IFN-gamma production was measured. RESULTS: MoDCs of atopic patients expressed mRNAs of cysLT1 receptor and cysLT-producing enzymes, and allergen pulsing significantly increased cysLT production. MoDCs of atopic patients showed a T(H)2-favoring phenotype and induced T(H)2-skewed cytokine production from autologous CD4(+) T cells. Dexamethasone and tacrolimus inhibited allergen-pulsed MoDC-induced cytokine production by autologous CD4(+) T cells without and with IL-10 inhibition, respectively. CysLT1 receptor antagonists had no effect on MoDC functions. CONCLUSION: Our results indicate that MoDCs of atopic patients induce a T(H)2 reaction. Corticosteroid and tacrolimus, but not cysLT1 receptor antagonists, inhibit T(H)2 reactions, and this effect is probably mediated through different pathways.

Acetaldehyde induces granulocyte macrophage colony-stimulating factor production in human bronchi through activation of nuclear factor-kappa B.

Acetaldehyde, a metabolite of alcohol and primary mediator of alcohol-induced asthma, causes bronchoconstriction via histamine release from airway mast cells. Acetaldehyde also is found in cigarette smoke and may cause airway inflammation. The purpose of this study was to determine the effect of acetaldehyde on cytokine production and nuclear factor kappa B (NF-kappa B) activation in human bronchial tissues. Human bronchi were prepared from normal parts of lung tissues resected for lung cancer (n = 11). The bronchi were cultured in the presence of 5 x 10(-4) M of acetaldehyde for 24 hours and the concentrations of eotaxin, granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin-5, interleukin-8, and regulated on activation, normal T cells expressed and secreted in cultured supernatants were determined by enzyme-linked immunosorbent assay. Tissues also were immunohistochemically stained for NF-kappa Bp65. Acetaldehyde significantly increased GM-CSF production from human bronchi and nuclear translocation of NF-kappa Bp65 in airway epithelium but had no effects on other cytokines. Our findings suggest that acetaldehyde potentially causes airway inflammation via increased GM-CSF production through nuclear translocation of NF-kappa B.

Cysteinyl leukotrienes regulate dendritic cell functions in a murine model of asthma.

Dendritic cells (DCs) act as APCs in the airway and play a critical role in allergy. Cysteinyl leukotrienes (cysLTs) synthesized from arachidonic acid are primary mediators of immediate asthmatic reaction. The aim of this study was to investigate the effects of cysLTs on Dermatophagoides farinae (Der f)-pulsed mouse myeloid DCs in inducing allergic airway inflammation in vitro and in vivo. Control DC (medium-pulsed), Der f-pulsed DC, cysLT-pulsed DC, Der f- and cysLT-pulsed DC, and Der f-pulsed and cysLT receptor antagonist (LTRA)-treated DC were prepared from murine bone marrow, and the production of cytokines ws compared. Subsequently, these DCs were intranasally instilled into another group of naive mice, followed by intranasal Der f challenge to induce allergic airway inflammation in vivo. Der f-pulsed DC produced significantly higher amounts of IL-10 and IL-12 compared with control DC. Der f- and cysLT-pulsed DC further increased IL-10 production compared with Der f-pulsed DC. In contrast, treatment of Der f-pulsed DC with LTRA increased IL-12 and decreased IL-10. Intranasal instillation of Der f-pulsed DC resulted in airway eosinophilia associated with a significant rise in IL-5 levels in the airway compared with control DC. Pulmonary eosinophilia and excess IL-5 were further enhanced in Der f- and cysLT-pulsed DC-harboring mice. In contrast, Der f-pulsed and LTRA-treated DC significantly inhibited airway eosinophilia, reduced IL-5, and increased IFN-gamma in the airway. Our results suggest that cysLTs play an important role in the development of allergic airway inflammation by regulating the immunomodulatory functions of DCs.

Regulation of mite allergen-pulsed murine dendritic cells by respiratory syncytial virus.

Dendritic cells (DCs) are the only antigen-presenting cells that determine T-cell differentiation and play an important role in both allergy and viral infection. Respiratory syncytial virus (RSV) can infect DCs and affect their functions. The aim of this study was to determine the interaction between RSV infection and Dermatophagoides farinae allergen (D. farinae) sensitization on the development of allergy at the DC level. Murine bone marrow-derived DCs were prepared and treated as: control; D. farinae-pulsed DCs (D. farinae-DCs); ultraviolet-inactivated RSV challenged; RSV-infected, D. farinae-pulsed plus ultraviolet-inactivated RSV-challenged; and D. farinae-pulsed plus RSV-infected. In in vitro experiments, we compared the expression of costimulatory molecules and cytokine production between the six groups of DCs. Another group of naive mice were then intranasally inoculated with these DCs, after which intranasal challenge with D. farinae was performed to develop allergic airway inflammation in vivo. In comparison with D. farinae-DCs, D. farinae-pulsed plus RSV-infected DCs showed helper T cell (Th) 1-favored expression of costimulatory molecules and cytokine production. Allergic airway inflammation induced by intranasal instillation of D. farinae-DCs was abrogated when infected with RSV, which was associated with a concomitant suppression of Th2 response in the lung. Our results indicated that RSV suppresses D. farinae-DCs to induce Th2 response both in vitro and in vivo through regulation of expression of surface markers and production of immunoregulatory cytokines.

Tacrolimus reduces urinary excretion of leukotriene E(4) and inhibits aspirin-induced asthma to threshold dose of aspirin.

BACKGROUND: The exact mechanism of aspirin-induced asthma is not clear. It has been postulated that precipitation of asthma attacks by aspirin is linked to inhibition of COX activity and massive release of cysteinyl leukotriene into the airway. Tacrolimus, a macrolide-derived immunosuppressant, is used for immunosuppression in organ transplantation and also for allergic diseases such as atopic dermatitis. OBJECTIVE: We evaluated the effects of tacrolimus in aspirin-induced asthma by using a double-blind, crossover study design. METHODS: Twelve patients with aspirin-induced asthma (male:female, 3:9; mean age +/- SD, 36.7 +/- 7.2 years) received either tacrolimus (0.1 mg/kg) or placebo 2 hours before the threshold dose of oral aspirin. RESULTS: In the placebo arm, oral aspirin significantly decreased FEV 1 concomitant with significant increases in sputum eosinophilic cationic protein and urinary leukotriene E(4) levels. Tacrolimus significantly inhibited bronchoconstriction and abrogated aspirin-induced increase in both sputum eosinophilic cationic protein and urinary leukotriene E(4) levels. CONCLUSION: The current study suggested that tacrolimus inhibited bronchoconstriction to a threshold dose of aspirin by inhibition of cysteinyl leukotriene excretion.

The position of pranlukast, a cysteinyl leukotriene receptor antagonist, in the long-term treatment of asthma. 5-year follow-up study.

BACKGROUND: Adverse effects, tachyphylaxis, and the position of pranlukast, a cysteinyl leukotriene receptor antagonist, in asthma treatment have not been fully established. OBJECTIVES AND METHODS: To address these questions, adverse effects and long-term efficacy of pranlukast were evaluated in 82 patients [28 patients with moderate asthma (group I), 27 with severe persistent asthma not on oral corticosteroid (OCS; group II) and 27 with severe persistent asthma on OCS (group III)] at 4 and 16 weeks. In the following, pranlukast was either withdrawn 1 year after the start of therapy, or if that was not possible due to reappearance of symptoms, the dose of OCS or inhaled corticosteroid (ICS) was reduced. The efficacy of pranlukast was evaluated during 5 years by peak expiratory flow rate (PEFR), and symptom and treatment scores. RESULTS: Adverse reactions appeared in 4 patients (4.9%; diarrhea, dizziness and leg edema). The mean improvement in PEFR on week 16 was 18.5 +/- 2.3, 18.8 +/- 3.2, and 15.2 +/- 3.8% in groups I-III, respectively (p < 0.01, for all groups). However, increases in PEFR in 29 of 72 patients (40.3%) were less than 15%. Pranlukast could not be withdrawn in 28 of 42 responders (66.7%), but their dose of ICS was reduced by 363 +/- 97 microg/day (group II) and that of OCS by 3.4 +/- 0.7 mg/day (group III). Tachyphylaxis was not recognized during the 5-year period. CONCLUSION: Pranlukast is safe when taken for up to 5 years, and is effective irrespective of asthma severity. In the majority of patients with persistent asthma, pranlukast may help to control the disease in the long term.

Acetaldehyde induces histamine release from human airway mast cells to cause bronchoconstriction.

BACKGROUND: Approximately half of the Japanese asthmatics experience exacerbation of asthma after alcohol consumption. We previously reported that this phenomenon is probably caused by histamine release from mast cells by acetaldehyde stimulation. However, no reports have described the effects of acetaldehyde on human airway mast cells. The purpose of the present study was to demonstrate acetaldehyde-induced histamine release from human airway mast cells with subsequent airway smooth muscle contraction and to investigate the ensuing mechanisms. METHODS: Human tissue samples were prepared from the lungs resected from patients with lung cancer. The effect of acetaldehyde on airway muscle tone and the concentration of chemical mediators released in the organ bath were measured before and after acetaldehyde stimulation. Mast cells were prepared from lung parenchyma by the immunomagnetic method and then stimulated with acetaldehyde to determine the chemical mediators released. RESULTS: Acetaldehyde (>3 x 10(-4) M) increased airway muscle tone, which was associated with a significant increase in the release of histamine, but not thromboxane B2 or cysteinyl-leukotrienes. A histamine (H1 receptor) antagonist completely inhibited acetaldehyde-induced bronchial smooth muscle contraction. Acetaldehyde also induced a significant histamine release from human lung mast cells and degranulation of mast cells. CONCLUSIONS: The present results strongly suggest that acetaldehyde stimulates human airway mast cells to release histamine, which may be involved in bronchial smooth muscle contraction following alcohol consumption.