Esophageal candidiasis as a side effect of inhaled fluticasone propionate dry powder: recovery by switching over to hydrofluoroalkane-134a beclomethasone dipropionate (HFA-BDP).

BACKGROUND: Esophageal candidiasis is one of the local side effects of inhaled corticosteroid treatment, and it is difficult to prevent this condition. Our previous report indicated that the prevalence of esophageal candidiasis among patients treated with inhaled fluticasone propionate dry powder (FP-dp) reached up to 37% in Japanese patients. Although a reduction in the daily dose of inhaled FP-dp can eliminate this infection, it may lead to asthma not being well-controlled in these patients. OBJECTIVE: The aim of this study was to estimate whether switching to an equal daily dose of inhaled hydrofluoroalkane-134a beclomethasone dipropionate (HFA-BDP), the oropharyngeal deposition of which is very low, can eliminate the infection without deterioration of asthma. METHODS: A total of 10 stable asthmatic patients with esophageal candidiasis, induced by inhaled FP-dp treatment (400 or 800 microg/ day), were enrolled in this study. A second upper GI endoscopy was performed, more than 1 month but less than 3 months after switching to an equal dose of inhaled HFA-BDP with a tube spacer device, Duopacer. The patients' medications were not changed during the study. RESULTS: Esophageal candidiasis was eliminated in 9 of the 10 patients. The degree of candidiasis reduced in another patient. The forced expiratory volume in 1 sec (FEV1.0) did not worsen during the study. CONCLUSION: Switching from FP-dp to HFA-BDP with Duopacer is useful in preventing esophageal candidiasis.

[Successful treatment of bronchial mucoepidermoid carcinoma by bronchoplasty].

A 63-year-old man who was pointed out abnormal shadow on chest X-ray admitted to our hospital. Chest computed tomography (CT) showed a tumor originated from right upper bronchus and grew into right main bronchus. The tumor was diagnosed as mucoepidermoid carcinoma by bronchoscopic biopsy. Fluorodeoxyglucose positron emission tomography (FDG-PET) showed abnormal uptake localized at the tumor. The standardized uptake values of the tumor 60 minutes after injection were 2.86, and 120 minutes after injection, it increased to 3.97. Right upper lobectomy with bronchoplasty by deep wedge resection of right main bronchus at the orifice of right upper bronchus and lymphadenectomy was performed. Pathological diagnosis was high-grade mucoepidermoid carcinoma without lymph nodes metastasis which was compatible with FDG-PET. Postoperative course was uneventful.

[An autopsy case of MPO-ANCA-positive microscopic polyangiitis with manifestations of pulmonary hemorrhage and diffuse alveolar damage].

A 68-year-old woman was admitted to our hospital because of fever of unknown origin and pain in the lower extremities. Six weeks after onset, diffuse infiltrative shadows were observed on chest X-ray films, and marked hypoxemia and progressive renal dysfunction suddenly developed. Corticosteroid therapy (2 courses of pulse therapy, each consisting of methylprednisolone at 500 mg/day for 3 days) was not effective, and the patient died 9 weeks after onset because of respiratory failure. Serologic tests were positive for MPO-ANCA. Histopathologic findings at autopsy disclosed arteriolar fibrinoid necrosis in tissues of the liver, spleen, lungs, and kidneys, thus yielding a diagnosis of microscopic polyangiitis. Lung specimens also demonstrated massive alveolar hemorrhaging in the mid-lung fields and diffuse alveolar damage (DAD) in all lobes. Pulmonary hemorrhage coexistent with DAD worsens the prognosis for microscopic polyangiitis in patients positive for MPO-ANCA.

Elevation of the plasma level of RANTES during asthma attacks.

BACKGROUND: RANTES is considered to play an important role in various immune and allergic disorders since it is a potent chemoattractant for inflammatory cells such as eosinophils, memory T cells, and monocytes. OBJECTIVE: To investigate the possible role of RANTES in the pathogenesis of bronchial asthma. METHODS: The plasma level of RANTES was measured in 12 asthma patients and 15 normal controls by a sandwich enzyme-linked immunosorbent assay. RESULTS: In the patients with asthma, the plasma RANTES level was significantly elevated during acute attacks compared to that in the controls. In addition, it was higher than that during the asymptomatic state in the same patients. Plasma beta-thromboglobulin levels were also elevated in asthma patients during acute attacks and showed a correlation with the RANTES level. CONCLUSION: These findings suggest a role for RANTES in the pathogenesis of asthma and a possible role for platelets in RANTES release in asthma.

Elevated plasma RANTES levels in patients with atopic dermatitis.

Eosinophils and T cells are involved in the pathologic process of atopic dermatitis. To further understand the role of these cells, and the possible involvement of RANTES, in the pathogenesis of atopic dermatitis, we measured the plasma level of RANTES using the sandwich ELISA. The mean plasma level of RANTES in 11 patients with atopic dermatitis was significantly higher than that of 15 normal control subjects. RANTES levels were higher in patients with severe form of atopic dermatitis than that of patients with mild disease. These findings suggest that RANTES may play a role in the recruitment and activation of eosinophils and T cells in atopic dermatitis.

[A case of acute eosinophilic pneumonia: bronchoalveolar lavage findings before and after steroid treatment].

An 18-year-old woman presented with coughing, fever, progressive dyspnea, and diffuse infiltrates on the chest X-ray film. Analysis of bronchoalveolar lavage fluid showed 73% eosinophils. Acute eosinophilic pneumonia was diagnosed. Methylprenisolone, 1 g per day was given for three days and her condition improved dramatically. No relapse was observed. Analysis of bronchoalveolar lavage fluid also showed lymphocytosis, abnormally high concentrations of ECP, GM-CSF, IL-5 and sICAM-1, and hypersegmentation of eosinophil nuclei. After steroid treatment almost all these findings returned to normal; only lymphocytosis remained. Precipitating antibodies against four kinds of fungi, including Trichoderma viridae, were noted in the serum, but the environmental provocation test was negative and those fungi were not detected in the environmental culture growth. Comparison of bronchoalveolar lavage findings obtained before and after steroid treatment can provide information on the mechanism of eosinophil accumulation in the lung. This case also draws attention to the relationship between acute and chronic eosinophilic pneumonia.

Possible low response of C-reactive protein production in eosinophilic pneumonia.

C-reactive protein (CRP) in the patients with eosinophilic pneumonia was examined compared with that of bacterial pneumonia. While no difference between erythrocyte sedimentation rate (ESR) in eosinophilic pneumonia (mean +/- SE: 74.5 +/- 10.6 mm/hr) and that in bacterial pneumonia (86.2 + 7.7 mm/hr) was observed, serum CRP level (3.87 +/- 1.24 mg/dL) and alpha 2-macroglobulin level (182.53 +/- 13.00 mg/dL) in eosinophilic pneumonia were lower in comparison with those in bacterial pneumonia (14.89 +/- 1.34 mg/dL, 315.65 +/- 11.54 mg/dL, respectively), suggesting that the pathogenesis of eosinophilic pneumonia might involve defective secretion of certain cytokine related to the production of acute-phase reactant proteins such as interleukin-6.

Characteristics of bone marrow cells of patients with eosinophilic pneumonia.

Bone marrow features were studied to clarify the pathogenesis of peripheral blood eosinophilia in eosinophilic pneumonia. We observed (1) increases in the number of nucleated cells in patients with this disease as compared with that of control subjects (205,944 +/- 104,253 versus 118,154 +/- 76,306) (P < .05); (2) increases in the myelocyte to erythrocyte ratio (6.95 +/- 4.06 versus 4.02 +/- 1.36) (P < .05) mainly due to a marked increase in the eosinophilic series; and (3) an increase in the eosinophilic series with advance in the maturation process, the degree of increase becoming greater with the increase in eosinophilic maturation. These findings suggest that differentiation and maturation of the precursor cells into mature eosinophils were accelerated in the bone marrow in eosinophilic pneumonia by some lymphokines as eosinophilopoietic growth factors.

Possible induction of intercellular adhesion molecule-1 (ICAM-1) expression on endothelial cells by platelet-activating factor (PAF).

We demonstrated that PAF and IL-1 markedly induce ICAM-1 expression on endothelial cells. These findings suggest that PAF not only modulates inflammation by the attraction and activation of eosinophils or by platelet activation, but also intensifies such phenomena by induction of ICAM-1 expression on endothelial cells.

[A basic study on the plasma and serum levels of eosinophil cationic protein (ECP) in bronchial asthma].

A basic study on the blood eosinophil cationic protein (ECP) as an index for eosinophil activation in bronchial asthma was performed. 1) ECP concentration in the serum collected 2 hours after blood sampling and the peripheral eosinophil count were significantly higher in asthmatic patients than in normal individuals. A correlation between these two parameters was observed in normal controls but not in asthmatic patients. These findings suggest that the degree of eosinophil activation, which is reflected by the blood ECP concentration, varies with the clinical condition in asthmatic patients. 2) The plasma and serum ECP levels were compared. The serum ECP was higher than the plasma ECP in both normal controls and asthmatic patients. In asthmatic patients, however, plasma ECP levels poorly correlated with serum levels: the serum levels were markedly elevated in some cases, and only the plasma levels were significantly elevated during symptomatic periods compared with stable periods. Therefore, attention must be paid not only to the serum ECP concentration, but also to the plasma ECP concentration and the plasma-serum difference. 3) This plasma-serum difference in ECP concentration may be due to the in vitro release of ECP during coagulation after blood sampling rather than the effect of alpha 1-macroglobulin concentration, because supernatants from stimulated platelets elicited ECP release from eosinophils.

Increased releasability of platelet products and reduced heparin-induced platelet factor 4 release from endothelial cells in bronchial asthma.

To determine whether or not platelet activation is involved in the mechanism of exacerbation of bronchial asthma, we evaluated adenosine triphosphate (ATP) release from thrombin-stimulated washed platelets, plasma levels of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4), and plasma beta-TG/PF4 ratios during symptomatic and asymptomatic periods in 15 patients with bronchial asthma compared with 16 normal control subjects. We also measured these parameters during allergen provocation tests and acetylcholine inhalation tests in 6 allergic asthmatics. ATP release, plasma levels of beta-TG and PF4 were significantly increased during symptomatic periods and after the allergen provocations but not after acetylcholine inhalations. However, these findings were not accompanied by the elevation of plasma beta-TG/PF4 ratios. The heparin-induced PF4 release, which is reported to reflect release of PF4 attached on endothelial cells, was significantly reduced in 12 asymptomatic asthmatic patients compared with 11 normal subjects, and it was much more reduced in 7 symptomatic asthmatic patients, suggesting the possibility of the reduced PF4 binding on endothelial cell surface. This finding may represent the prolonged half life of PF4 in asthmatics. We concluded that 1) increased releasability of platelet products and in vivo release of the platelet granular contents are involved in the mechanism of the exacerbation of bronchial asthma, 2) some functional alteration in platelet-endothelial cell interaction may be involved in bronchial asthma, and 3) plasma beta-TG/PF4 ratios are not elevated possibly because of both increased platelet releasability and prolonged half-life of PF4 in the blood in asthmatic patients.

Effect of ozagrel (OKY-046), a thromboxane synthetase inhibitor, on theophylline pharmacokinetics in asthmatic patients.

The effect of ozagrel (OKY-046), a selective thromboxane A2 synthetase inhibitor, on theophylline disposition was studied in 12 asthmatic patients. Ozagrel was administered at a dose of 200 mg twice daily for 24 weeks to 4 outpatients receiving oral theophylline medication. Blood samples were drawn from each patient visiting the hospital at one to four-week intervals. There were no clinical significant changes between the time course profiles of serum theophylline concentration during the treatment and those after the cessation of ozagrel dosing. In addition, another 8 hospitalized patients received a single intravenous infusion of aminophylline (200 mg as theophylline) before and after ozagrel treatment of 200 mg twice daily for 7 days. No statistical significant alteration in elimination half-life, total body clearance or volume of distribution of theophylline was observed by the administration of ozagrel. These results suggest that ozagrel does not inhibit the metabolism of theophylline despite having an imidazole ring in its chemical structure.

[Luminol-dependent chemiluminescence of peripheral neutrophils in asthmatic patients].

To evaluate the role of the neutrophil in the pathophysiology of bronchial asthma, we examined the luminol-dependent chemiluminescence of peripheral neutrophils (CL) in steroid-dependent asthmatic patients during an acute attack (n = 18), during stable period (n = 10), and in normal controls (n = 21). When stimulated with formyl-methionyl-leucyl-phenylalanine (fMLP 0.1 microM), the CL of patients in acute attack was lower than that of normal controls. (5.29 +/- 1.25 vs. 9.29 +/- 0.84 relative light units p less than 0.01) Among 18 patients, we could examine 10 patients during the stable period after receiving steroids. The CL of those 10 patients during the stable period was significantly higher than their CL during acute attacks, when evaluated by the paired t-test (p less than 0.05), and was not very different than in normal controls. When stimulated with opsonized zymosan (5 mg/ml), CL was similar in the three groups. We also examined the CL of peripheral neutrophils of normal persons after the preincubation with serum of patients during acute attack and stable period. When stimulated with fMLP, CL after preincubation with serum of patients during acute attack was lower than CL after preincubation with the serum of patients during the stable period. It was suggested that the respiratory-burst activity of peripheral neutrophils in acute asthmatic attack was reduced to the chemotactic stimulus of fMLP.