[Case of allergic bronchopulmonary aspergillosis complicated with lung abscess which developed into a bronchopleural fistula].

We report a case of bronchopleural fistula in a patient with allergic bronchopulmonary aspergillosis. A 25-year-old man was admitted with high fever and chest pain. Although his chest CT in a previous hospital showed pulmonary infiltrate suggesting the existence of a mucous plug, a mass shadow in the right upper lobe was recognized on admission to our hospital. Based on the presence of eosinophilia, elevated levels of total IgE and Aspergillus-specific IgE, positive precipitating antibody to Aspergillus, and detection of A. fumigatus in bronchial washing fluid, we diagnosed this case as ABPA complicated with lung abscess. Although we treated by antibiotics and antifungal drugs, the lung abscess did not improve and led to bronchopleural fistula. After addition of nebulised liposomal amphotericin B, his symptoms improved and treatment was successful.

[Characteristics of shrimp allergy from childhood to adulthood in Japan].

OBJECTIVE: We examined profiles and clinical symptoms of shrimp allergy patients and investigated the correlation of shrimp-specific IgE to crustaceans-specific IgE, mollusks-specific IgE and shellfish-specific IgE. In addition, symptoms when eating crustaceans other than shrimp, mollusks and shellfish were examined, because they shared tropomyosin as a major allergen. METHODS: We examined 99 definitive shrimp allergy cases with questionnaire. RESULTS: Their onset started during either childhood or young adulthood. Symptoms appeared within an hour after ingestion of shrimp in 87.9% cases. The most common symptoms were skin symptoms, followed by oral allergic syndrome (OAS) like symptoms, respiratory symptoms. Anaphylaxis were observed in 61 cases including 2 anaphylactic shock cases. Among 99 shrimp allergy cases, 44 cases (64.7%) showed positive reaction to crabs out of 68 cases experiencing crab ingestion. Only 11 cases (17.5%) reacted against squid out of 63 cases with the experience in squid ingestion. Crab-specific IgE (C.I. 0.954, p < 0.001) and squid-specific IgE (C.I. 0.582, p > 0.001) were strongly correlated with shrimp-specific IgE. CONCLUSION: We conclude that a lot of cases with shrimp allergy react to crabs clinically, and which seem to be different from the reaction against mollusk and shellfish intake in spite of sharing tropomyosin as a major allergen among them.

Polymorphisms in the prostaglandin E2 receptor subtype 2 gene confer susceptibility to aspirin-intolerant asthma: a candidate gene approach.

Aspirin-intolerant asthma (AIA) is a subtype of bronchial asthma characterized by development of bronchoconstriction evoked by non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs inhibit the cyclooxygenase pathway, leading to enhancement of the lipoxygenase pathway. We evaluated allelic association of 370 single nucleotide polymorphisms (SNPs) of 63 candidate genes, mostly from the arachidonic acid metabolic cascade, with AIA. After two rounds of screening with 198 AIA patients, multiple SNPs in the prostaglandin E(2) receptor subtype 2 (EP2) gene were associated with AIA (P<0.05). Among the 77 SNPs identified in the EP2 gene, we selected 17 SNPs on the basis of linkage disequilibrium and allelic frequencies (minor allele frequency >0.1) for further association study. SNPs in the promoter region of the EP2 gene, uS5, uS5b, and uS7, were significantly associated with AIA (permutation P=0.039-0.001). Analysis of haplotypes constructed according to the LD pattern showed a significant association with AIA (permutation P=0.001). The most significantly associated SNP, uS5, located in the regulatory region of the EP2 gene, was in a STATs-binding consensus sequence [AIA 31.1% versus control 22.1% (permutation P=0.0016) or versus aspirin-tolerant asthma 22.2% (permutation P=0.0017)]. Although STAT1 binding was not observed in gel mobility shift assay with HeLa nuclear extract, an unidentified protein was specifically bound to the allelic sequence. In in vitro reporter assay in HCT116 cells, the site containing the uS5 allele showed reduced transcription activity. Taken together, these results suggest that uS5 allele serves as a target of a transcription repressor protein. A functional SNP of the EP2 gene associated with risk of AIA should decrease the transcription level, resulting in reduction of the PGE(2) braking mechanism of inflammation and involvement in the molecular mechanism underlying AIA.

Influence of inhaled corticosteroids on community-acquired pneumonia in patients with bronchial asthma.

OBJECTIVE: The aim of the present study was to evaluate the influence of inhaled corticosteroids (ICS) on community-acquired pneumonia (CAP) in patients with asthma. PATIENTS AND METHODS: All asthmatic patients who required hospitalization for CAP from the beginning of 1989 through December 2001 were enrolled in this retrospective study. Patients who used oral corticosteroids daily were excluded. Patients were divided into two groups based on whether or not they used ICS, and we analyzed clinical characteristics of the pneumonia. Sixty-two patients (28 males, 34 females; mean age, 54.5 years) were enrolled in this study. Thirty-seven of 62 patients used ICS, with the mean dosage being 777.9 microg/day. RESULTS: We found no significant differences between the two groups with regard to mean age, serum albumin level, duration of asthma, pulmonary function and frequency of intravenous infusion of corticosteroids in the outpatient department. There were no significant differences in body temperature, white blood cell count, and CRP value upon admission between the two groups. Differences were not significant in the period of resolution of the pneumonia or in the frequency of pathogens identified between the two groups. CONCLUSION: ICS therapy appears to have no influence on CAP in patients with asthma. We recommend that ICS should be continued to control asthma with adequate antibiotic therapy when asthmatic patients have CAP.

[A case of eosinophilic gastroenteritis: observation of serum IL-5 and sIL-2R levels before and after remission].

56 years-old man was admitted to our hospital because of severe diarrhea and hypereosinophilia. There was tenderness in the middle part of his abdomen. Laboratory examination revealed elevation of serum IL-5 and serum IL-2R value. No pathogens were detected from his stool specimen. An abdominal CT showed neither ascites nor thickening of intestinal wall. Pathological finding showed marked eosinophil infiltration in gastric and colonic mucosa. Eosinophilic gastroenteritis was diagnosed. His symptom was gradually improved spontaneously at the point of diagnosis. But administration of suplatast tosilate was stared because patients with this disease often relapse. Abdominal symptom was completely disappeared and value of serum IL-5 and sIL-2R was decreased at the end of September. This finding may imply pathogenesis of this disease.

Lipopolysaccharide-induced c-Jun NH2-terminal kinase activation in human neutrophils: role of phosphatidylinositol 3-Kinase and Syk-mediated pathways.

Polymorphonuclear leukocytes (neutrophils) respond to lipopolysaccharide (LPS) through the up-regulation of several pro-inflammatory mediators. We have recently shown that LPS-stimulated neutrophils express monocyte chemoattractant protein 1 (MCP-1), an AP-1-dependent gene, suggesting that LPS activates the c-Jun N-terminal kinase (JNK) pathway in neutrophils. Previously, we have shown the activation of p38 MAPK, but not JNK, in suspended neutrophils stimulated with LPS but have recently shown activation of JNK by TNF-alpha in an adherent neutrophil system. We show here that exposure to LPS activates JNK in non-suspended neutrophils and that LPS-induced MCP-1 expression, but not tumor necrosis factor-alpha (TNF-alpha) or interleukin-8 (IL-8), is dependent on JNK activation. In addition, LPS stimulation of non-suspended neutrophils activates Syk and phosphatidylinositol 3-kinase (PI3K). Inhibition of Syk with piceatannol or PI3K with wortmannin inhibited LPS-induced JNK activation and decreased MCP-1 expression after exposure to LPS, suggesting that both Syk and PI3K reside in a signaling pathway leading to LPS-induced JNK activation in neutrophils. This Syk- and PI3K-dependent pathway leading to JNK activation after LPS exposure in non-suspended neutrophils is specific for JNK, because inhibition of neither Syk nor PI3K decreased p38 activation after LPS stimulation. Furthermore we show that PI3K inhibition decreased LPS-induced Syk activation suggesting that PI3K resides upstream of Syk in this pathway. Finally, we show that Syk associates with Toll-like receptor 4 (TLR4) upon LPS stimulation further implicating Syk in the LPS-induced signaling pathway in neutrophils. Overall our data suggests that LPS induces JNK activation only in non-suspended neutrophils, which proceeds through Syk- and PI3K-dependent pathways, and that JNK activation is important for LPS-induced MCP-1 expression but not for TNF-alpha or IL-8 expression.

[Clinical properties of community-acquired pneumonia in patients with asthma].

PURPOSE: Many reports were found on the clinical properties of community-acquired pneumonia. The clinical properties of community-acquired pneumonia in patients with asthma have not been elucidated, and we therefore investigated such properties. MATERIALS AND METHODS: Asthmatic patients who required hospitalization for community-acquired pneumonia from the beginning of 1989 through the end of 2001 were enrolled in this study. We performed the study in a retrospective manner. Patients were divided into two groups based on severity of their asthma (mild to moderate asthma vs severe asthma), and we studied the clinical properties of the pneumonia. RESULT: No significant difference was seen in body temperature, white blood cell counts, or CRP value on admission between the two groups. No significant difference was seen in the resolving period of the pneumonia. The frequency of common pathogens (Streptococcus pneumoniae + Haemophilus influenzae) was lower in patients with severe asthma. Asthmatic patients not taking daily oral corticosteroids were divided into two groups based on whether or not they were using a inhaled corticosteroid, and we examined the frequency of pathogendetection. The percentage of common pathogens was almost the same in the two groups. CONCLUSION: The frequency of common pathogens was lower in patients with severe asthma than in those with mild to moderate asthma. This fact is worth considering when empiric therapy for pneumonia is performed in patients with asthma. Inhaled corticosteroid therapy seems to have no influence on the pathogens of pneumonia in patients with asthma.

Effects of suplatast tosilate on allergic eosinophilic airway inflammation in patients with mild asthma.

BACKGROUND: Bronchial asthma is a chronic inflammatory disease characterized mainly by infiltration of the airway mucosa by various inflammatory cells, notably eosinophils. T(H)2-type cytokines are suggested to be deeply involved in the pathogenesis of asthma. OBJECTIVE: We sought to determine the suppressive effects of suplatast tosilate, an inhibitor of T(H)2-type cytokines, on eosinophilic inflammation of the bronchial mucosa in patients with mild asthma. METHODS: Airway hyperresponsiveness tests, pulmonary function tests, eosinophil measurements in induced sputum, and bronchial mucosa biopsies were performed before and after treatment with suplatast tosilate for 6 weeks in 15 patients with mild asthma and in 13 control patients with mild asthma not receiving suplatast tosilate. This study was performed as a case-controlled open study. RESULTS: In the treatment group a significant improvement in the provocation concentration of histamine was observed (P <.05). Improvements in peak expiratory flow (P <.01) and in symptom score (P <.05) were also noted in the suplatast tosilate-treated group. Moreover, the average number of infiltrating eosinophils and EG2(+) cells significantly decreased (both P <.05), as did the ratios of eosinophils and EG2(+) cells in sputum (both P <.01). The average number of CD4(+) and CD25(+) T lymphocytes also decreased (both P <.05). CONCLUSION: Suplatast tosilate appears to inhibit allergic airway inflammation mediated by T(H)2-type cytokine and to improve clinical symptoms in patients with mild asthma.

[Management of patients with bronchial asthma received general anesthesia and surgical intervention].

Stimulation to bronchial mucosa is one of the major risk factor of asthma attack. When patients receive surgical intervention and general anesthesia, they are always exposed to stimulation to bronchial mucosa. Prevention method of bronchial asthma attack during surgical intervention is not established yet. We investigated that clinical course of patients with bronchial asthma who received general anesthesia and surgical intervention. Seventy-six patients with bronchial asthma were received general anesthesia and surgical intervention from 1993 to 1998. Twenty-four patients were mild asthmatic patients, 39 were moderate asthmatic patients and 13 were severe asthmatic patients. Preoperative treatment for preventing asthma attack was as follows; Eight patients were given intravenous infusion of aminophylline before operation. Fifty-two patients were given intravenous infusion of aminophylline and hydrocortisone before operation. Three patients were given intravenous infusion of hydrocortisone for consecutive 3 days before operation. Thirteen patients were given no treatment for preventing asthma attack. One patient was suffered from asthma attack during operation. She was given no preventing treatment for asthma attack before operation. Three patients were suffered from asthma attack after operation. No wound dehiscence was observed in all patients. To prevent asthma attack during operation, intravenous infusion of steroid before operation is recommended, when patients with asthma receive general anesthesia and surgical intervention.