Serological analysis of sensitization in allergic bronchopulmonary aspergillosis: a study on allergen components and interspecies relationships.

Background: Serological testing for immunoglobulin (Ig) E or IgG is useful for diagnosing allergic bronchopulmonary aspergillosis (ABPA), as it detects type I and III allergic reactions to Aspergillus species. However, few reports have investigated the allergen component and cross-reactivity among Aspergillus species. We aimed to measure and analyze the levels of IgGs specific to each Aspergillus species and investigate the prevalence of IgEs specific to each allergen component of A. fumigatus (Af) in ABPA patients.Methods: Serum samples were collected from 12 ABPA patients who visited our hospital between February and December 2017, and 16 with Af-sensitized asthma and 41 with Af-unsensitized asthma were controls. Immuno-CAP was performed to analyze the IgEs and IgGs specific to Af, A. niger, A flavus and A. terreus, and IgEs specific to allergen components Asp f 1, 2, 3, 4 and 6.Results: The ABPA group was significantly more frequently sensitized to Asp f 1 and 2 than the control groups. Af-specific IgEs were significantly positively correlated to the IgEs specific to A. flavus, A. niger and A. terreus. Af-specific IgGs were positively correlated to the IgGs specific to all the other species.Conclusions: Tests using allergen components were useful for ABPA diagnosis. Both IgE and IgG were highly cross-reactive among the Aspergillus species. There were many patients apart from asthmatic patients with ABPA, who displayed high Aspergillus IgG values.

Sex differences in use of inhalants by elderly patients with asthma.

BACKGROUND: The number of elderly patients with asthma has been increasing in Japan. Treatment for these patients should be provided based on the condition of individual patients. This study was performed to clarify the relationship between inhalation procedure and sex difference in elderly patients with asthma. METHODS: The inhalation procedure was examined in 155 elderly patients with asthma (male: n=66, average age ± standard deviation: 75.5±5.65 years old; female: n=89, average age ± standard deviation: 78.7±6.87 years old) during a medical examination. RESULTS: For the three items that were common to all devices, the percentages of the 155 patients who could/could not perform the actions were examined by separate Fisher's exact tests for males and females. A statistically significant difference (P=0.007) was observed for "breath holding", and more females than males were not able to hold their breath. Although no significant difference was seen in the "accurate number of times of inhalation", females tended to not be able to inhale accurately compared to males (P=0.072). CONCLUSION: Our results suggest that elderly female patients with asthma have less understanding of inhaled steroid therapy, compared to elderly male patients. Therefore, it is particularly important to confirm that the correct inhalation procedure is used by elderly female patients with asthma.

Long-term monotherapy with suplatast tosilate in patients with mild atopic asthma: a pilot comparison with low-dose inhaled fluticasone.

BACKGROUND AND OBJECTIVE: Suplatast tosilate is a Th2 cytokine inhibitor that is effective for controlling persistent asthma. However, the long-term efficacy of suplatast is unknown. We compared the clinical efficacy of long-term monotherapy with suplatast tosilate with a low dose of inhaled steroids in patients with mild atopic asthma. METHODS: A total of 32 patients with mild atopic asthma were randomly assigned to receive suplatast (n=15) or fluticasone (n=17). In the suplatast group, 100 mg of suplatast was given orally 3 times a day (total daily dose = 300 mg) for 2 years. In the fluticasone group, 100 pg of fluticasone was inhaled twice a day (total daily dose = 200 tg) for 2 years. RESULTS: In the suplatast group, the improvements in peak expiratory flow (PEF) rate and forced expiratory volume in 1 second (FEV1) and the changes in the symptom diary scale and frequency of beta2 stimulant inhalation were generally similar to those in the fluticasone group, and efficacy was maintained for 2 years. Improvements in inflammatory indices, such as the sputum eosinophil cationic protein (ECP) level and exhaled nitric oxide concentration, were comparable in the suplatast and fluticasone groups. The improvement in airway hyperresponsiveness was also similar in the 2 groups. The peripheral blood eosinophil percent change, serum ECP level, and total IgE antibody titer improved only in the suplatast group. CONCLUSIONS: Long-term treatment with suplatast significantly improved symptoms and inflammatory indices in patients with mild atopic asthma. Along with fluticasone, suplatast is considered a useful drug for the management of mild atopic asthma.

[A case of MPO-ANCA positive vasculitis associated with alveolar hemorrhage and progressive glomerulonephritis following propylthiouracil treatment, the interval was 6 years and 4 months].

The patient was a 62-year-old female. In June 1999, thiamazole (MMI) was orally administered under a diagnosis of hyperthyroidism. However, drug exanthema developed. In July, oral administration of propylthiouracil (PTU) was started. On October 20, 2005, palpitation and exertional dyspnea occurred. On November 1, bloody sputum was noted, and the patient consulted our hospital on November 8. In addition to severe anemia, chest X-ray and CT revealed diffuse infiltration in the bilateral lungs. The patient was admitted for detailed examination and treatment. After admission, the myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibody (ANCA) level was 390 EU, suggesting ANCA-associated angitis. PTU was discontinued, and steroid pulse therapy resulted in the disappearance of alveolar hemorrhage and hematuria. Transbronchial lung biopsy suggested alveolar hemorrhage, and kidney biopsy showed glomerular necrosis and interstitial infiltration of inflammatory cells, suggesting PTU-induced ANCA-associated angitis. Posttreatment with prednisolone at 30 mg/day gradually decreased the MPO-ANCA level. There has been no relapse during the 2-years follow-up.

Comparative evaluation of the leukotriene receptor antagonist pranlukast versus the steroid inhalant fluticasone in the therapy of aged patients with mild bronchial asthma.

A comparative study was conducted in elderly subjects with mild bronchial asthma to investigate the clinical usefulness of monotherapy with a leukotriene receptor antagonist in comparison to an inhaled corticosteroid. A total of 41 elderly patients aged 65 years or older with mild bronchial asthma, classified as being in severity step 1 and 2, were randomly assigned to the following two treatment groups: a pranlukast (CAS 103177-37-3, Onon) treatment group of 21 patients and an inhaled corticosteroid treatment group of 20 patients. Patients of the former group received pranlukast 450 mg daily and those of the latter group received fluticasone (CAS 90566-53-3) 200 microg daily for eight weeks. In the reference group, one patient was found to suffer from oral candidiasis 4 weeks after the start of the study. Therefore the evaluation was conducted on the remaining 19 participants. The evaluation parameters examined were obtained by keeping an asthma diary, determinations of PEF (peek expiratory flow), use frequency of beta2 stimulants, changes in symptom scores, and medication compliance. Further, measured before and after therapy were the ratio of peripheral blood eosinophils counts, serum ECP (eosinophils cationic protein), ECP levels induced sputum, and forced expiratory volume in one second (FEV1.0). As a result, in the time-course changes of symptoms scores and morning PEF, swift improvement was noted in the pranlukast group. Further, in the variables such as use frequency of beta2 stimulants, serum ECP levels, ECP levels induced sputum, and FEV1.0, an almost comparable level of improvement to the fluticasone group was demonstrated. From the above results, it was deemed that in elderly patients with mild bronchial asthma classified as steps 1 and 2, the pranlukast monotherapy, with superior medication compliance to inhaled therapy, would produce an equivalent level of clinical efficacy to the monotherapy with inhaled corticosteroid (fluticasone 200 microg daily).

[A patient who sufferred pulmonary tuberculosis with syndrome of inappropriate secretion of antidiuretic hormone, after radiotherapy for pulmonary adenocarcinoma].

A 62-year-old man presented in June 2006 with right thoracic pain, cough, and weight loss, which had persisted for 3 months. Chest X-ray showed a mass-like shadow in the right pulmonary apex, suggesting a stage IIIb adenocarcinoma which was confirmed by biopsy. We gave a total radiation dose of 60 Gy, after this which general malaise and weakness were noted. The results of endocrinological examinations suggested syndrome of inappropriate antidiuretic hormone secretion (SIADH). Thoracic CT showed ground-glass opacity (GGO) in both lungs, and we could not rule out pulmonary tuberculosis. A sputum was positive for acid-fast stain and PCR-Tb, suggesting that SIADH was associated with pulmonary tuberculosis. Water restriction, i.v. physiological saline, and antituberculosis therapy relieved hyponatremia and the symptoms.

[A case of drug-induced pneumonitis due to amiodarone].

An 80-year-old man, who had been taking the antiarrhythmic drug amiodarone for chronic atrial fibrillation since October 2004, developed dyspnea and fever in June 2005, and was admitted to our hospital. Chest X-ray and CT scan showed ground-glass opacities in all lung fields. Arterial blood gas analysis revealed hypoxemia. These findings led to a diagnosis of acute respiratory distress syndrome. Oral amiodarone was discontinued, and steroid pulse therapy was started; however, the disease progressed rapidly, and the patient died on the fourth hospital day. Autopsy showed diffuse alveolar damage, accumulation of edema fluid in the alveolar spaces, and the presence of foamy macrophages, leading to a diagnosis of amiodarone-induced pulmonary damage.

[A couple suffering acute respiratory illness due to waterproofing spray exposure].

The patients were a 28-year-old man and a his 27-year-old wife. The husband smoked a cigarette immediately after using a waterproofing spray, and developed fever, cough, and dyspnea 15 min later. The wife had nausea 2 hours later. Nine hours later, the husband visited a local clinic, and was referred to our hospital because of hypoxemia. In addition, chest CT showed ill-defined areas of increased density, predominantly in the bilateral upper lung fields, with interlobular septal thickening, and he was hospitalized. Although the wife was asymptomatic at the time of examination, she had chest CT findings similar to those of her husband, and was also hospitalized. After admission, the husband received steroid pulse therapy and oxygen inhalation for his symptoms and hypoxemia, with return of arterial blood gas analysis results to normal on the third day. The wife had no symptoms or hypoxemia during her hospital stay. Their chest CT findings improved on the seventh day after admission, and they were discharged. Thus, it appears that the couple suffered from acute respiratory illness due to waterproofing spray exposure, and probably heat degradation products from cigarette smoking caused the husband to have severe symptoms.

Usefulness of HFA-BDP for adult patients with bronchial asthma: randomized crossover study with fluticasone.

In this randomized crossover study, 22 adult patients with moderate-to-severe persistent bronchial asthma were assigned to one of two groups. Patients in group 1 were administered fluticasone dry powder inhaler (DPI) for 8 weeks followed by a 2-week washout period, then hydrofluoroalkane-beclometasone dipropionate (HFA-BDP) for 8 weeks. After a further 2-week washout, they were again administered fluticasone DPI for 8 weeks. Patients in group 2 were assigned HFA-BDP followed by fluticasone PII and finally HFA-BDP over the same time periods. In both groups, no significant difference was observed in use of beta2-agonists and symptom score between the treatment periods; however, markers of pulmonary function were significantly higher when on HFA-BDP versus fluticasone DPI. Significant increases of morning peak expiratory flow (PEF) (p < 0.01), forced expiratory volume in 1 second (FEV1.0) (p < 0.01), V50 (p < 0.05), and V25 (p < 0.01) were observed at 18 weeks in group 1, whereas there were significant decreases of V50 (p < 0.05) at 18 weeks in group 2. No significant difference was noted in circulating eosinophil count and serum ECP between the 2 treatments; however, ECP in induced sputum and nitric oxide in expired gas were significantly lower (p < 0.05 and < 0.01, respectively) when on HFA-BDP versus fluticasone DPI. HFA-BDP might be delivered to small airways more effectively than fluticasone DPI.

[Three cases of spontaneous pneumomediastinum].

We encountered 3 male patients with spontaneous pneumomediastinum. The patients were a 16-year old and a 17-year old and a 24-year old. Predisposing episodes for the development of spontaneous pneumomediastinum could be identified in all 3 patients: throwing a ball during a baseball game in 1, lifting a heavy load during work in 2. However, they were healthy and suddenly developed symptoms in the absence of any underlying disease. The presenting complaint was chest pain in all 3 patients. Chest X-ray films and chest CT images revealed pneumomediastinum. A diagnosis of spontaneous pneumomediastinum was made based on chest X-ray films and chest CT images. After conservative treatment, all 3 patients recovered.

[A case of adult idiopathic chylothorax with transudative ascites].

A 70-year-old woman presented at a local clinic because of shortness of breath. Since she was found to have pleural effusion, she was referred to our hospital for further evaluation. She had no history of trauma or surgery. Pleural effusion examination revealed a milky-white, chylous, odorless fluid with increased triglycerides. Further evaluation led to a diagnosis of idiopathic chylothorax. Althought she was found to have transudative ascites, abdominal ultrasonography and computed tomography revealed no significant findings including cirrhosis of the liver. As a result of intravenous hyperalimentation with fasting, the chylous pleural fluid became serous and decreased. Ascites disappeared simultaneously, suggesting a possible relationship between the chylothorax and transudative ascites.

Clinical effects of long-term administration of pranlukast, a leukotriene receptor antagonist, on adult patients with bronchial asthma.

Eighty-one adult patients with bronchial asthma who suffered from an unstable peak expiratory flow rate (PEFR) and asthmatic attacks that developed at irregular intervals in spite of inhaling beclometasone dipropionate (CAS 5534-09-8, BDP) in excess of 400 micrograms/day were treated with pranlukast (CAS 103177-37-3, Onon) 450 mg/day for 1 to 2 years and the clinical effects of its long-term administration were studied. The patients were divided into 3 groups: Group I with drug effect seen on peak expiratory flow rate (PEFR) in a short-term; Group II showing long term PEFR improvement; and Group III with no sustained improvement in PEFR. Those in the first two groups continued oral medication for 2 years, while those of the third group withdrew from medication after one year and their clinical course was observed. The evaluation parameters were: PEFR, frequency of beta 2-stimulant inhalation, number of night time visits to health service facilities, quantity of inhalation steroids used, amount of oral steroids used at fixed intervals, peripheral eosinophil count, serum eosinophil cationic protein (ECP) concentration and FEV1.0. In Group I, the frequency of beta 2-stimulant inhalation, number of night time visits to health service facilities, quantity of inhalation steroids used, and the amount of oral steroids used at fixed intervals were reduced; and after two years, the frequency of beta 2-stimulant inhalation and quantity of inhalation steroids used were further reduced. In Group II, reductions were seen in the peripheral eosinophil count and serum ECP level. The asthmatic severity shifted from step 3 to 2 in 12 patients and from step 4 to 3 in 4 patients in Group I; and from step 3 to 2 in 3 patients in Group II. In Group III, an increase in the number of night time visits to health service facilities after the medication was interrupted and a rise in the serum ECP concentration were recognized.

[Clinical effects of long-term administration of pranlukast, a leukotriene receptor antagonist, on adult patients with bronchial asthma].

Eighty-one adult patients with bronchial asthma who suffered asthmatic episodes in spite of treatment with 400 mg/day of BDP were placed on pranlukast therapy for 4 weeks. Group I, which showed a 5% or greater increase in PEFR, continued oral pranlukast medication for an additional two years. Those patients who did not show an increase of 5% or greater in PEFR after 4 weeks of pranlukast therapy were instructed to continue the medication for another year. Group II, which exhibited a 5% or greater increase in PEFR after a one-year period continued medication for one more year. Medication was suspended for Group III, which failed to show improvement in PEFR after one year, and the group was placed under observation for the following year. Group I improved significantly in PEFR and exhibited a reduction in the frequency of b2 inhalation, the number of night visits to a medical facility, the amount of steroids inhaled, and the quantity of oral steroids given at regular intervals; and the Group I peripheral eosinophil count, serum ECP level, and FEV1.0 ameliorated. After one year, Group II also showed significant improvement in PEFR and a reduction in both the peripheral eosinophil count and the serum ECP level. This group's PEFR continued to improve after two years. One year after medication was suspended, Group III showed a significant increase in the number of night visits to a medical facility and a rise in the serum ECP level. These findings indicated the efficacy of pranlukast.

Study on the usefulness of seratrodast in the treatment of chronic pulmonary emphysema.

It has been reported that the biosynthesis of thromboxane A2 (TXA2) is enhanced in platelets in the presence of chronic obstructive pulmonary disease (COPD), and 11-dehydro-TXB2, a urinary metabolite of thromboxane, also increases in blood. In the present study, seratrodast (CAS 112665-43-7, Bronica), a TXA2 receptor antagonist, was administered to 14 patients with chronic pulmonary emphysema in the stable phase for 8 weeks. Respiratory distress was evaluated in the attending physicians' judgments using the Hugh-Jones (H-J) classification, and also by the patients themselves using the Borg scale. Respiratory function tests, including forced vital capacity (FVC), percent of one second forced expiratory volume (FEV1.0%), arterial blood gases during respiration of room air, and peak expiratory flows (PEF) (morning and evening), and measurement of plasma 11-denhydro-TXB2 and TXB2 levels were performed before and 8 weeks after the start of administration, as well as at the time of the start of administration. The results revealed significant improvement of respiratory distress, evaluated on both the H-J classification and the Borg scale, at week 8. Although no significant changes were observed in plasma TXB2 levels, the plasma 11-dehydro-TXB2 level significantly decreased at week 8. Among the respiratory function parameters examined, only FVC was significantly improved. These results indicated that seratrodast is useful for the improvement of respiratory distress in patients with chronic pulmonary emphysema in the stable phase.