Real-world efficacy of anti-IL-5 treatment in patients with allergic bronchopulmonary aspergillosis.

Despite standard treatment with systemic corticosteroids and/or antifungal triazoles, a substantial proportion of patients with allergic bronchopulmonary aspergillosis (ABPA) experience frequent relapses and require long-term treatment despite unfavorable adverse effects. We investigated the efficacy and safety of anti-interleukin (IL)-5/IL-5 receptor α chain (Rα) monoclonal antibodies (mAbs) in patients with ABPA complicated by asthma. ABPA cases treated with anti-IL-5/IL-5Rα mAbs were collected from 132 medical institutes in 2018 and published case reports in Japan. Clinical outcomes, laboratory and physiological data, and radiographic findings during 32 weeks before and after treatment were retrospectively evaluated. We analyzed 29 cases of ABPA: 20 treated with mepolizumab and nine with benralizumab. Treatment with anti-IL-5/IL-5Rα mAbs reduced the frequency of exacerbations (p = 0.03), decreased the dose of oral corticosteroids (p < 0.01), and improved pulmonary function (p = 0.01). Mucus plugs in the bronchi shrank or diminished in 18 patients (82%). Despite the clinical/radiographical improvement, serum levels of total IgE, the key biomarker for the pharmacological response in ABPA, were unchanged. Anti-IL-5/IL-5Rα mAbs that directly target eosinophils are promising candidates for the treatment of patients with ABPA, especially those with mucus plugs in the bronchi.

Pulmonary emphysema is associated with fungal sensitization in asthma.

BACKGROUND: Fungal sensitization is a risk factor for severe asthma. Colonization in the lower respiratory tract is one of the forms of fungal exposure, and it is related to fungal sensitization. Pulmonary emphysema was recently reported to be an underlying disease of fungal colonization. The aim of study was to evaluate the prevalence of pulmonary emphysema in asthmatic patients with and without fungal sensitization. METHODS: We enrolled 108 patients with allergic asthma and divided them into the patients sensitized to Aspergillus and/or Candida (n=56) and those not sensitized to both Aspergillus and Candida (n=52). The presence of pulmonary emphysema on chest CT was evaluated retrospectively. RESULTS: The frequency of pulmonary emphysema was significantly higher in the patients sensitized to Aspergillus and/or Candida compared to the patients not sensitized to both fungi (P=0.0040). The frequency of pulmonary emphysema was also significantly higher in the patients sensitized to either Aspergillus or Candida compared to the patient not sensitized to the fungi (P=0.0398 and P=0.0198, respectively). A multivariate logistic regression analysis demonstrated that the presence of pulmonary emphysema was independently associated with the sensitization to Aspergillus and/or Candida (OR 7.84, 95% CI: 1.20-51.10). CONCLUSIONS: Pulmonary emphysema is associated with sensitization to Aspergillus and/or Candida.

Persistent Asthma from Childhood to Adulthood Presents a Distinct Phenotype of Adult Asthma.

BACKGROUND: In approximately 30% of children with asthma, the condition persists into adulthood. The longer duration of asthma in these patients is a risk factor for poor asthma control. However, the characteristics of adult patients with asthma that has persisted since childhood are not well documented. OBJECTIVE: We sought to compare the clinical characteristics among patients with adult-onset asthma, patients who outgrew childhood asthma but relapsed, and patients with persistent asthma since childhood. METHODS: We conducted a cross-sectional study of adult patients with asthma who visited our hospital. We classified them into 3 groups: those with adult-onset asthma (adult-onset), those who had remitted childhood asthma that relapsed (relapsed), and those who had asthma that had persisted since childhood (persistent). The clinical characteristics of these groups were compared. RESULTS: A total of 1443 patients were enrolled. The persistent group was younger and included fewer patients with a smoking history. There were statistically significant differences among the 3 groups in the percentages of patients with a family history of asthma and comorbidities of allergic rhinitis and atopic dermatitis. The proportion of patients with severe asthma differed among the 3 groups (31% in the adult-onset group, 34% in the relapsed group, and 40% in the persistent group; P = .015). The values of forced expiratory flow at 75% of vital capacity were lower in the persistent group than the relapsed or adult-onset group. A multivariable logistic regression analysis (dependent variable: severe asthma) in each group revealed that the factors associated with severe asthma differed among the adult-onset, relapsed, and persistent groups. When we established an overall model that included interaction terms of cohort-by-other factors, there was a trend that comorbidity of allergic rhinitis affected the severity of asthma differently in the relapsed group compared with the other groups. CONCLUSION: The clinical phenotype of asthma that persists from childhood to adulthood seems to be a distinct phenotype of adult asthma.

The utility of galactomannan antigen in the bronchial washing and serum for diagnosing pulmonary aspergillosis.

BACKGROUND: The diagnosis of pulmonary aspergillosis is difficult because the sensitivity of the conventional methods for the detection of Aspergillus such as culture and cytology, is poor. To improve the sensitivity for Aspergillus detection, the detection of galactomannan antigen has been investigated. The serum galactomannan (GM) antigen has been recognized to be a useful tool for the diagnosis of invasive pulmonary aspergillosis. However, the utility of the galactomannan antigen for the diagnosis of pulmonary aspergillosis other than invasive pulmonary aspergillosis (IPA) has been unclear. METHODS: The GM antigen using serum and bronchial washing (BW) using bronchofiberscopy for the diagnosis of pulmonary aspergillosis other than IPA were measured. RESULTS: In 45 enrolled patients, 7 patients had pulmonary aspergillosis, 5 of these patients had chronic necrotizing pulmonary aspergillosis and 2 patients had allergic bronchopulmonary aspergillosis. The area under the receiver operating characteristic (ROC) curve was 0.89 for the BW GM antigen detection test, and 0.41 for the serum GM antigen detection test, suggesting that the BW GM antigen detection test exhibits a better diagnostic performance than the serum GM antigen detection test. The BW GM antigen detection test had a sensitivity of 85.7% and a specificity of 76.3% at a cut-off level of ≥0.5, which was the optimal cut-off level obtained by the ROC curve. CONCLUSION: The BW GM antigen detection test is thought to be a promising test for the diagnosis of pulmonary aspergillosis other than IPA.

Clinical relevance of plasma miR-106b levels in patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is characterized by both chronic inflammation in the airway and systemic inflammation; however, the molecular mechanism of COPD has not been fully elucidated. By measuring microRNA (miRNA) expression in the plasma of COPD subjects, we aimed to identify the clinical relevance of plasma miRNA levels in these patients. Blood samples were obtained from COPD patients and age-matched normal controls. We initially produced plasma miRNA expression profiles using TaqMan low-density array screening. For further validation, individual qRT-PCRs were performed in 40 COPD patients and 20 healthy subjects. TaqMan low-density array screening showed that 9 miRNAs (miR-29b, miR-483-5p, miR-152, miR-629, miR-26b, miR-101, miR-106b, miR-532-5p and miR-133b) were significantly downregulated in the plasma from COPD patients when compared with normal smokers. Among these miRNAs, we focused on miR-106b. A reduction in the plasma miR-106b levels was evident in COPD ex-smokers and COPD current smokers compared with levels in smokers. There was a negative correlation between the plasma miR-106b level and the duration of disease since diagnosis in COPD ex-smokers and the duration of smoking in COPD current smokers. These findings support the concept that progressive reduction in the plasma miR-106b level may reflect persistent and systemic changes even after the discontinuation of smoking in COPD patients. miR-106b may therefore play an important role in the pathogenesis of COPD.

Histological types and localizations of lung cancers in patients with combined pulmonary fibrosis and emphysema.

BACKGROUND: Most patients with combined pulmonary fibrosis and emphysema (CPFE) are males, and heavy smokers. CPFE is more prevalent than fibrosis in patients with lung cancer, and patients with CPFE usually have a poor prognosis. This study reviewed the differences in the prevalence of lung cancer among patients with normal, fibrosis, emphysema and CPFE via chest computed tomography (CT), and the relationship between histopathology and the localizations of lung cancer. METHODS: Patients that were diagnosed with lung cancer confirmed by pathological examinations between 2003 and 2011 were retrospectively reviewed to obtain clinical, pathological, and radiological data. These patients were categorized into four groups based on chest CT findings: normal, fibrosis, emphysema and CPFE. RESULTS: Two hundred and seventy-four patients with lung cancer were classified into 146 normal, 14 fibrosis, 78 emphysema, and 36 CPFE groups. Combined centriacinar and paraseptal emphysema was common in the CPFE group. The prevalence of squamous cell carcinoma in the CPFE group was significantly higher in comparison to the normal group. The rate of peripheral localization of lung cancer in the CPFE group was significantly higher in comparison to the normal, fibrosis, and emphysema groups. The prevalence of squamous cell carcinoma of peripheral areas in the CPFE group was significantly higher in the normal and emphysema groups. CONCLUSIONS: CPFE patients demonstrated histopathological and radiological differences concerning the histological types and localization of lung cancers.

The relationship between the clinical course and cytokine in a patient with cigarette smoking-induced acute eosinophilic pneumonia - A case report.

A 19-year-old female was admitted to our hospital because of a sudden onset fever and cough, and she was diagnosed to have acute eosinophilic pneumonia (AEP). The cause was thought to be cigarette smoking, because she had started smoking just before the development of AEP and her condition improved after cigarette smoking cessation, without corticosteroid treatment. The cytokines which are thought to be involved in eosinophilic accumulation in the lungs were analyzed using bronchoalveolar lavage fluid (BALF) and serum. Of the analyzed cytokines, only regulated on activation, normal T cell expressed and secreted (RANTES) increased in the serum after the improvement. RANTES is a unique chemokine which attracts not only eosinophils, but also T cells. Interestingly, in this case, the eosinophil count in the blood increased in parallel with the lymphocyte count after the improvement. These findings are interesting because it may help to understand the pathogenesis of AEP and the role of RANTES.

Effects of inhaled tiotropium plus transdermal tulobuterol versus tiotropium alone on impulse oscillation system (IOS)-assessed measures of peripheral airway resistance and reactance, lung function and quality of life in patients with COPD: a randomized crossover study.

BACKGROUND: The addition of transdermal tulobuterol (Tulo) to inhaled tiotropium bromide (Tio) produced beneficial effects on spirometry-assessed parameters of respiratory function, disease-related symptoms and quality of life in patients with chronic obstructive pulmonary disease (COPD). AIM: To compare the effects of Tio plus Tulo versus Tio alone on peripheral airway obstruction and quality of life in Japanese patients with COPD using impulse oscillation system (IOS)-assessed measures. PATIENTS AND METHODS: Patients aged 50-80 years with clinically stable COPD and a forced expiratory volume in 1 s (FEV(1)) that was 30-80% of the predicted value were randomized to receive Tio 18 µg once daily, or combination therapy with Tio 18 µg once daily plus Tulo 2 mg once daily for 4 weeks. Patients then switched treatments for a further 4 weeks. RESULTS: Sixteen patients completed the study. Tio plus Tulo was associated with significantly greater improvements than Tio in IOS-assessed markers of resistance (R5 and R5-R20), reactance and reactance area, from baseline to week 4. Both treatments significantly improved these markers over the 4-week treatment period, with the exception of R20 for which improvements were not significant. Tio plus Tulo improved symptoms of dyspnea to a significantly greater extent than Tio alone. St. George's Respiratory Questionnaire Score-Total was not significantly different between the two groups, but improvement from baseline in the 'impact' component was significantly greater with Tio plus Tulo than with Tio alone. CONCLUSIONS: Coadministration of transdermal Tulo with inhaled Tio, as well as Tio alone, is associated with beneficial effects on IOS-assessed measures of peripheral airway obstruction in patients with COPD.