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.

Japanese guidelines for adult asthma 2020.

Bronchial asthma is characterized by chronic airway inflammation, which manifests clinically as variable airway narrowing (wheezes and dyspnea) and cough. Long-standing asthma may induce airway remodeling and become intractable. The prevalence of asthma has increased; however, the number of patients who die from it has decreased (1.3 per 100,000 patients in 2018). The goal of asthma treatment is to control symptoms and prevent future risks. A good partnership between physicians and patients is indispensable for effective treatment. Long-term management with therapeutic agents and the elimination of the triggers and risk factors of asthma are fundamental to its treatment. Asthma is managed by four steps of pharmacotherapy, ranging from mild to intensive treatments, depending on the severity of disease; each step includes an appropriate daily dose of an inhaled corticosteroid, which may vary from low to high. Long-acting ß2-agonists, leukotriene receptor antagonists, sustained-release theophylline, and long-acting muscarinic antagonists are recommended as add-on drugs, while anti-immunoglobulin E antibodies and other biologics, and oral steroids are reserved for very severe and persistent asthma related to allergic reactions. Bronchial thermoplasty has recently been developed for severe, persistent asthma, but its long-term efficacy is not known. Inhaled ß2-agonists, aminophylline, corticosteroids, adrenaline, oxygen therapy, and other approaches are used as needed during acute exacerbations, by selecting treatment steps for asthma based on the severity of the exacerbations. Allergic rhinitis, eosinophilic chronic rhinosinusitis, eosinophilic otitis, chronic obstructive pulmonary disease, aspirin-exacerbated respiratory disease, and pregnancy are also important conditions to be considered in asthma therapy.

Effectiveness of training patients using DVD in the accurate use of inhalers for the treatment of bronchial asthma.

BACKGROUND: Inhalants are the standard treatment for patients with bronchial asthma. Inaccurate inhaler use leads to inadequate therapeutic effects and unnecessary dosage increases. However, it is a challenge for practitioners to master the various devices available and train patients on the accurate use of inhalers. Thus, establishing a system to instruct patients on how to accurately use inhalers is essential. We prepared a DVD and accompanying user manual explaining the operation of each inhaler device used in Japan. This pilot study aimed to examine the efficacy of these materials. METHODS: The subjects were 33 outpatients with bronchial asthma who received treatment in our facility for asthma and had already received conventional inhalant training. The oral medication and inhalants used by the patients were not changed. The patients were randomly assigned to a DVD viewing group or non-viewing group; various parameters were comparatively examined after 4 weeks. RESULTS: Significant improvements in Asthma Control Test scores, inhalation technique, forced vital capacity, forced expiratory volume in 1 s, impulse oscillometry resonant frequency, and induced sputum eosinophil count were observed in the DVD viewing group at 4 weeks post training. CONCLUSIONS: Pulmonary function and inflammatory parameters improved significantly in the DVD viewing group. These findings suggest that unnecessary step-up of asthma treatment can be avoided, leading to treatment cost reduction. Training patients with asthma in accurate inhaler use improves quality of life and therefore has great clinical significance. Hence, this method should be used more extensively in Japan and worldwide.

Recurrent Staphylococcus aureus abscess and fatal pneumococcal septicemia due to IRAK-4 deficiency.

We describe the case of an infant with recurrent episodes of staphylococcal skin abscess and subsequent lethal pneumococcal meningitis/septicemia due to interleukin-1 receptor-associated kinase 4 (IRAK-4) deficiency. In this case, systemic signs of inflammatory response were poor and delayed. Among all other reported cases of IRAK-4 deficiency, none involved severe viral or fungal disease, and the range of infecting bacteria was narrow.

A prospective study exploring the predictors of response to benralizumab in patients with refractory bronchial asthma.

OBJECTIVE: This study aimed to evaluate the predictors of response to benralizumab therapy in patients with refractory bronchial asthma. METHODS: After 16 weeks of benralizumab therapy, 32 patients with refractory bronchial asthma were assigned to two groups based on the response to treatment as indicated by changes in the asthma control test score (responders and non-responders) and evaluated for clinical characteristics. RESULTS: Overall, 25 responders and 7 non-responders were identified at week 16. Logistic regression analysis identified a peripheral eosinophil count of >300/µL during benralizumab treatment and a maximal peripheral eosinophil count of >300/µL in the past year as predictors of response. CONCLUSIONS: The predictors of response to benralizumab included a peripheral eosinophil count of >300/µL during treatment and a maximal peripheral eosinophil count of >300/µL in the past year. These findings could improve patient selection and reduce medical costs in the future.

Optimal follow-up period after switching to another inhaled corticosteroid/long-acting ß2 agonist in patients with asthma: A retrospective study using Japanese administrative claims data.

Switching inhalation devices is a reasonable option if problems with control, adherence, or inhalation technique occur in patients with asthma treated with inhaled corticosteroid (ICS)/long-acting ß2 agonist (LABA). However, evidence to determine the extent to which the carefully monitored period persists after switching is insufficient. In this study, we aimed to investigate the duration of the carefully monitored period after switching to another ICS/LABA. This retrospective study used claims data from Japanese health insurance associations from May 2014 to April 2019. A total of 1,951 patients who switched to another ICS/LABA during the study period were selected for analysis. The relative risk of the first exacerbation after switching was calculated for each four-week interval after the switch compared with that before the switch in a self-controlled case series design. We further assessed patient background associated with exacerbations during the follow-up period. In the primary analysis, the risk of asthma exacerbation compared to the control period was derived from a conditional logistic regression model, which showed a significant decrease immediately after the switch (1 to 4 weeks, Odds ratio [OR] 0.37, 95% confidence interval [CI] 0.26-0.54). Subsequently, the risk increased again and was not significantly different from the control period until week 32 (OR 0.55, 95% CI 0.29-1.04). In a sensitivity analysis among patients with a history of exacerbations, up to week 20 was the period of no continuous risk reduction (OR 0.84, 95% CI 0.41-1.70). In the secondary analysis, chronic rhinosinusitis, sleep disorders, and a history of asthma exacerbation were significantly associated with asthma exacerbation. The incidence of exacerbation remained high for approximately 4 to 7 months after patients with asthma switched to another ICS/LABA. Therefore, these patients should be carefully monitored for at least 4 to 7 months and should be re-assessed at an earlier point in time, if necessary.

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.

Long-term clinical effects of an inhaler guidance DVD in patients with bronchial asthma.

OBJECTIVES: Erroneous use of inhalers is a serious problem. Given the multitude of devices currently available, it can be difficult to convey the correct methods for their efficient use to patients. We previously generated an educational DVD that visually and audibly explains the proper use of all inhaler types available in Japan to provide inhalation guidance to patients. Herein, we report the 1-year follow-up of patients who received or did not receive the DVD guidance. METHODS: Sixty-nine bronchial asthma patients undergoing outpatient treatment who received inhalation guidance from a pharmacist using a standard package insert were randomly allocated to a DVD group (n=35) or a no-DVD group (n=34). Their current oral or inhalant drug regimens were unchanged. Various parameters were measured 12 months later. Frequencies of aggravation during the 12-month period were also determined. RESULTS: Compared with the no-DVD group, there were significant improvements in asthma control test scores, forced vital capacity, FEV1, impulse oscillometry, resonant frequency, induced sputum eosinophil count, and FeNO in the DVD group after 12 months. Pulmonary function and inflammation parameters improved significantly with the use of the instructive DVD in addition to the package inserts. The frequency of asthma aggravation significantly decreased in the DVD group during the 12-month study period, likely because inhalation procedures were performed accurately. CONCLUSIONS: A DVD that provides accurate inhalation guidance enhances the quality of life of asthma patients and has substantial clinical ramifications. Thus, this tool would be beneficial for patients in Japan and worldwide.

Use of Assist Devices to Actuate Pressurized Metered-Dose Inhalers in Elderly Patients with Asthma.

INTRODUCTION: Some elderly patients experience difficulty when attempting to use pressurized metered-dose inhalers (pMDIs) due to reduced finger muscle strength. However, no studies have investigated the finger muscle strength required for pMDI actuation. Therefore, we created a modified pMDI pinch gauge and examined the finger muscle strength in elderly asthmatic patients with and without the use of a pMDI assist device to push the canister. METHODS: We measured the finger muscle strength (N) required to spray pMDI formulations (Adoair®, Alvesco®, Flutiform®, and Breztri®) using one hand in healthy individuals. We then similarly measured the finger muscle strength when using the modified pinch gauge in older adults aged 65 years or older with bronchial asthma who used pMDI formulations. RESULTS: The finger muscle strength required to actuate these devices was 29.4 N or more in healthy individuals. In the older patients with asthma, the finger muscle strength was 38.45 ± 5.80 N in men and 31.34 ± 9.94 N in women. The finger muscle strength was ≤ 29.4 N in 6.6% of men and 40.0% of women. CONCLUSIONS: Finger muscle strength should be considered when selecting a device for older patients with asthma, and the use of a pMDI assist device to push the canister is recommended in patients with weaker finger muscles.

Evaluation of the pneumococcal urinary antigen test (PUT): a retrospective study.

OBJECTIVES: To determine the usefulness of the pneumococcal urinary antigen test (PUT) and to describe the characteristics of pneumococcal pneumonia. METHODS: In this retrospective study, we examined the effects of prior antibiotic treatment, pneumonia onset period, and sputum quality on the results of PUT. Clinical information was collected via medical records from all adult patients who were hospitalized at the Fujita Health University Bantane Hospital with "pneumonia" as a new diagnosis from April 2015 to March 2018. RESULTS: A total of 482 patients with pneumonia were included, of whom 103 had pneumococcal pneumonia. The frequency of PUT positivity did not differ significantly in patients with a pneumonia onset period of ≥3 days compared with those with a period of ≤2 days (P=0.514). Patients with a history of prior antimicrobial therapy had a significantly lower rate of positive sputum culture vs those with no such history (P=0.005); however, PUT positivity in the two groups did not differ significantly (P=0.367). CONCLUSIONS: Our results showed that urinary antigen testing for pneumococcal pneumonia is useful for diagnosis regardless of prior antibiotic treatment and time since symptom onset.

[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 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.

[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.

[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 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.

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.

[Clinical evaluation of tulobuterol patch in patients with mild or moderate persistent bronchial asthma-effects of long-term treatment on airway inflammation and hypersensitivity].

The tulobuterol transdermal therapeutic system (TTS) is the world's first commercially available transdermal preparation of tulobuterol, a beta-2 stimulant, that can maintain effective blood tulobuterol levels for 24 hours when applied once daily. In the present study, a total of 36 adult patients with mildly persistent (Step 2) or moderately persistent (Step 3) bronchial asthma 19 who were using inhalational steroids and 17 who were not used tulobuterol TTS for one year and underwent measurement of peak expiratory flow (PEF) once daily. Peripheral eosinophil count, serum eosinophil cationic protein (ECP) level and airway responsiveness (Dmin) were evaluated at 6 months and 1 year after the start of the study. PEF exhibited significant improvements at 6 months and 1 year in patients treated with or without inhalational steroids, while serum ECP was improved significantly only in the patients on inhalational steroids. Patients not using inhalational steroids exhibited no significant exacerbation of Dmin at either 6 months or 1 year: One-year treatment with tulobuterol TTS did not appear to cause tachyphylaxis. The significant improvements in Dmin at 6 months and 1 year in the patients using inhalational steroids suggested that inhalational steroids offer beneficial effects in controlling airway inflammation. Tulobuterol TTS is considered quite beneficial in improving quality of life (QOL) in patients with bronchial asthma because its incidence of adverse effects including palpitations and shivering is significantly lower than those of oral preparations, because of its remarkable improvement of pulmonary function and symptoms of airway obstruction without increasing airway responsiveness even after repeated use, and because it is simple to use and offers excellent clinical efficacy.

[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.