Clinical characteristics of allergic bronchopulmonary mycosis caused by Schizophyllum commune.

BACKGROUND: Allergic bronchopulmonary mycosis (ABPM) is an allergic disease caused by type I and type III hypersensitivity to environmental fungi. Schizophyllum commune, a basidiomycete fungus, is one of the most common fungi that causes non-Aspergillus ABPM. OBJECTIVE: Herein, we attempted to clarify the clinical characteristics of ABPM caused by S. commune (ABPM-Sc) compared with those of allergic bronchopulmonary aspergillosis (ABPA). METHODS: Patients with ABPM-Sc or ABPA were recruited from a nationwide survey in Japan, a multicenter cohort, and a fungal database at the Medical Mycology Research Center of Chiba University. The definition of culture-positive ABPM-Sc/ABPA is as follows: (1) fulfills five or more of the 10 diagnostic criteria for ABPM proposed by Asano et al., and (2) positive culture of S. commune/Aspergillus spp. in sputum, bronchial lavage fluid, or mucus plugs in the bronchi. RESULTS: Thirty patients with ABPM-Sc and 46 with ABPA were recruited. Patients with ABPM-Sc exhibited less severe asthma and presented with better pulmonary function than those with ABPA (p = 0.008-0.03). Central bronchiectasis was more common in ABPM-Sc than that in ABPA, whereas peripheral lung lesions, including infiltrates/ground-glass opacities or fibrotic/cystic changes, were less frequent in ABPM-Sc. Aspergillus fumigatus-specific immunoglobulin (Ig)E was negative in 10 patients (34%) with ABPM-Sc, who demonstrated a lower prevalence of asthma and levels of total serum IgE than those with ABPM-Sc positive for A. fumigatus-specific IgE or ABPA. CONCLUSIONS: Clinical characteristics of ABPM-Sc, especially those negative for A. fumigatus-specific IgE, differed from those of ABPA.

An effective case of bronchoscopic balloon dilatation for tuberculous bronchial stenosis.

Endobronchial tuberculosis often causes bronchial stenosis. Balloon dilation is a minimally invasive and effective bronchoscopic intervention for bronchial stenosis; however, reports on balloon dilation in older individuals are limited. We present a case of a 77-year-old woman with endobronchial tuberculosis and clarify the efficacy and safety of balloon dilation. She presented with dyspnea, right lung atelectasis, and respiratory failure 55 days after initiation of antituberculosis therapy. We performed bronchoscopic balloon dilatation for the right main bronchial stenosis. Consequently, respiratory failure rapidly improved. Chest computed tomography (CT) showed improved lung atelectasis; however, severe bronchial stenosis and rhonchi persisted. Therefore, we performed a second balloon dilatation. CT 3 months after the first balloon dilation showed right upper bronchial stenosis and right lung middle lobe atelectasis. Restenosis was absent 21 months after third balloon dilatation. Bronchoscopic balloon dilation is effective for restenosis with repeated treatment and can be safely performed in older individuals.

Effects of macrolides on antigen-induced increases in cough reflex sensitivity in guinea pigs.

BACKGROUND: Macrolides are antibiotics that have anti-inflammatory activities. Hence, they are used for both acute and chronic inflammatory airway diseases. However, the effects of these agents on allergic airway disorders presenting with an isolated chronic cough, such as non-asthmatic eosinophilic bronchitis and eosinophilic tracheobronchitis with cough hypersensitivity (atopic cough), still remain to be elucidated. OBJECTIVE: To determine if macrolides are effective in the management of chronic cough caused by eosinophilic airway inflammation. METHODS: The cough reflex sensitivity to inhaled capsaicin was measured at 48h after challenge with an aerosolized antigen in actively sensitized guinea pigs. The 14-, 15- or 16-membered macrolides (erythromycin, azythromycin, or josamycin, respectively) were given intraperitoneally every 12h after the antigen challenge. Bronchoalveolar lavage and the resection of the tracheal tissue were performed immediately after the measurement of the cough response to capsaicin. RESULTS: The antigen-induced increase in the number of coughs elicited by capsaicin inhalation was significantly reduced by treatments with erythromycin and azythromycin, but not with josamycin. Erythromycin dose-dependently inhibited the increases in the substance P, prostaglandin E(2) and leukotriene B(4) levels, but not the histamine levels, in the bronchoalveolar lavage fluid. However, erythromycin did not influence the antigen-induced decrease in the neutral endopeptidase (NEP) activity in the tracheal tissue. CONCLUSIONS: Both 14- and 15-membered, but not 16-membered, macrolides could reduce the antigen-induced cough reflex hypersensitivity by inhibiting the antigen-induced release of the afferent sensory nerve sensitizers. These macrolides may be therapeutically useful for the treatment of isolated chronic cough based on cough reflex hypersensitivity in allergic airway diseases such as non-asthmatic eosinophilic bronchitis and atopic cough.

Evaluation of airway hyperresponsiveness and exhaled nitric oxide as risk factors for airway remodeling in patients with stable asthma.

Chronic eosinophilic airway inflammation, airflow limitation, and airway hyperresponsiveness (AHR) are distinctive features of bronchial asthma. Exhaled nitric oxide (eNO) is a marker of eosinophilic airway inflammation. Airway remodeling due to chronic airway inflammation results in fixed airway obstruction. Asthmatic patients have been reported to have greater declines in forced expiratory volume in 1 second (FEV(1)) over time than nonasthmatic patients. This longitudinal observational study aimed to elucidate outcomes and risk factors for the decline in FEV(1) in patients with stable asthma. Postbronchodilator FEV(1) was measured in 30 outpatients with stable asthma every 6 months for 5 years. We calculated the rate of decline in postbronchodilator FEV(1) (deltaFEV(1)/year) in each subject and adjusted deltaFEV(1)/year with predictive FEV(1). Patients were examined while their asthma was well controlled. In the first observation period, we measured AHR to methacholine (the provocative concentration of methacholine causing a 20% fall in FEV(1) [PC(20)]). In the second observation period (defined as the period over 2 years from start of observation), we measured methacholine PC(20) and eNO. The mean deltaFEV(1)/year (SEM) was -36 +/- 4 mL/year and the adjusted deltaFEV(1)/year (SEM) was -0.015 +/- 0.001/year. Adjusted deltaFEV(1)/year did not correlate with eNO measured during the second observation period or methacholine PC(20) measured during the first observation period. On the other hand, methacholine PC(20) measured during the latter period was correlated significantly with adjusted deltaFEV(1)/year. Persistent AHR may be a risk factor for longitudinal decline in FEV(1) in asthma patients even if their asthma is stable and well controlled by inhaled corticosteroid.

Sputum eosinophilia, airway hyperresponsiveness and airway narrowing in young adults with former asthma.

BACKGROUND: 30-80% of outgrown asthma subjects develop symptoms again later in life. We investigated inflammation and function of lower airway in adolescents with former asthma. METHODS: 326 never-smoking young adults (mean age 24.0 years) were interviewed with special emphasis on history of asthma. Diagnosis of asthma was based on GINA guidelines. Former asthma subjects consisted of ones with a history of physician-diagnosed childhood asthma, who had been free of asthma symptoms without the use of medication for at least 10 years prior to the study. Provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 second (FEV(1))(PC(20)) and eosinophil percentage in induced sputum were measured. RESULTS: 31 subjects were former asthma subjects (FBA), 11 subjects were current asthma subjects (CBA) and 284 subjects had no history of asthma (non-BA). PC(20) and FEV(1)/FVC ratio were significantly lower in the FBA group than in the non-BA group (P < 0.01). Maximal mid-expiratory flow (MMF) was significantly lower in the FBA group than in the non-BA group (P < 0.05). Sputum eosinophil percentage was significantly increased in the FBA group compared with the non-BA group (P < 0.01). PC(20) was significantly lower in the CBA group than in the FBA and non-BA groups (P < 0.01). FEV(1), FEV(1)/FVC ratio and MMF were significantly lower in the CBA group than in the FBA group (P < 0.05, P < 0.05 and P < 0.05, respectively) and the non-BA group (P < 0.01, P < 0.01 and P < 0.05, respectively). Sputum eosinophils were significantly higher in the CBA group than in the FBA and non-BA groups (P < 0.01). CONCLUSIONS: This study shows that subjects with long-term outgrown asthma continue to have airway eosinophilic inflammation, airway hyperresponsiveness and airway narrowing.

Exhaled nitric oxide levels in patients with atopic cough and cough variant asthma.

BACKGROUND AND OBJECTIVE: Atopic cough (AC) is an established clinical entity in Japan, in which patients present with a chronic persistent non-productive cough. Exhaled nitric oxide (NO) is a biomarker of eosinophilic airway inflammation. The present study examined whether exhaled NO levels were increased in AC in comparison with cough variant asthma (CVA) and bronchial asthma (BA). METHODS: Consecutive patients presenting with an isolated cough lasting at least 8 weeks were enrolled in the study. The aetiology of the chronic cough was determined according to the Japanese Respiratory Society guidelines for management of cough. Exhaled NO, capsaicin cough sensitivity (capsaicin concentration eliciting five or more coughs (C5)) and bronchial reversibility were measured at the patients' first visit. Bronchial responsiveness (PC20 to methacholine) was measured at their second visit following a 6-day course of bronchodilator therapy. RESULTS: There were 58 patients recruited and fully investigated; of these 9 and 11 patients were diagnosed with AC and CVA, respectively, as single causes of chronic cough. Ten patients with BA who had not received corticosteroid therapy in the previous 4 weeks and who attended the same clinic in the same time period acted as controls. Exhaled NO levels in patients with AC were significantly lower than those in patients with CVA and BA. There was no significant difference in the exhaled NO levels between patients with CVA and BA. CONCLUSIONS: Exhaled NO may reflect eosinophilic inflammation of peripheral airways and its measurement may be useful in differentiating CVA from AC and other causes of chronic non-productive cough.

A phase II study of combination chemotherapy with docetaxel and carboplatin for patients with advanced or metastatic non-small cell lung cancer.

BACKGROUND: The aim of this phase II study was to evaluate the efficacy of combination chemotherapy consisting of docetaxel and carboplatin in patients with inoperable non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: For this multicenter phase II study, the eligibility criteria included histologically or cytologically proven inoperable NSCLC, measurable lesions, Eastern Cooperative Oncology Group performance status (PS) 0-2, adequate organ and bone marrow functions, and written informed consent. Patients received 60 mg/m2 of docetaxel and carboplatin (target AUC 5.5) on day 1 every 3 weeks until disease progression. The primary end-point of this study was response rate and the secondary end-points were toxicities, time to progression and overall survival. RESULTS: A total of 40 patients were enrolled and 39 patients were eligible. A complete response and partial response were observed in 1 and 13 patients, respectively. An objective response rate was 35.9% (95% confidential interval [CI] 20.8-51.0%). The median time to progression was 5.2 months and the median overall survival was 12.0 months. The 1- and 2-year survival rates were 53.8% and 25.1%, respectively. The major toxicities were leukocytopenia and neutropenia. Grade 3 or 4 thrombocytopenia was rare and non-hematological toxicities were generally mild. Grade 3 non-hematological toxicities were observed in 6 patients (2 with nausea and vomiting, 1 with diarrhea, 1 with elevated transaminase levels, 1 with allergic reaction and 1 with edema). No grade 4 non-hematological toxicities were observed. CONCLUSION: Docetaxel and carboplatin combination chemotherapy was well tolerated and active in Japanese patients with advanced or metastatic NSCLC.

Eosinophilic inflammation, remodeling of lower airway, bronchial responsiveness and cough reflex sensitivity in non-asthmatic subjects with nasal allergy.

BACKGROUND: It has been reported that nasal allergy influences the lower airway inflammation and functions. We elucidated whether nasal allergy would contribute to lower airway inflammation and functions. METHODS: 266 subjects aged 21-39 years were interviewed with special emphasis on history of asthma and nasal allergies (perennial allergic rhinitis (PAR) and seasonal allergic rhinitis (Japanese cedar pollinosis; PO)). Symptomatic subject was defined when nasal symptoms were present during a 3-week study period. Pulmonary function, provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 s (PC20), capsaicin cough threshold defined as capsaicin concentration eliciting 5 or more coughs (C5) and eosinophil percentage in hypertonic saline-induced sputum were measured. RESULTS: Based on the interview, 232 subjects without asthma were divided into symptomatic (n = 25) and asymptomatic (n = 22) PAR, PO on-season (n = 15) and off-season (n = 36), and non-nasal allergy subjects (control) (n = 134). Sputum eosinophils were significantly greater in symptomatic PAR than another four groups (p < 0.01). FEV1/FVC ratio was significantly lower in PAR than control (p < 0.05). Maximum mean expiratory flow was lower in PAR than control (asymptomatic: p < 0.05, symptomatic: p = 0.06). C5 was not different among groups. PAR tended to have a lower PC20 compared to control (symptomatic: p = 0.078; asymptomatic: p = 0.086). CONCLUSIONS: These results suggest that eosinophilic inflammation occurred in symptomatic period of PAR may contribute to development of lower airway remodeling and bronchial hyperresponsiveness. Reversely, PO may not be associated with lower airway eosinophilic inflammation or abnormal bronchial functions. Nasal allergy dose not influence the cough reflex sensitivity.

Primary alveolar hypoventilation syndrome complicated with antiphospholipid syndrome.

A 32-year-old woman was transported to our hospital by ambulance because of loss of consciousness and breathing induced by drug intoxication. After general status was recovered, her arterial blood gas analysis under breathing room air revealed hypercapnia and hypoxemia which were caused by hypoventilation. After exclusion of apparent pulmonary, neuromuscular and central nerve diseases, she was diagnosed with primary alveolar hypoventilation syndrome. She had the complication of antiphospholipid syndrome (APS), suggesting the possibility of small lesions of the brainstem due to APS, which were too small to be detected on CT or MRI; these small lesions could cause injuries to the respiratory center.

Comparison of cough reflex sensitivity after an inhaled antigen challenge between actively and passively sensitized guinea pigs.

BACKGROUND: Late asthmatic response is observed following antigen challenge in actively, but not passively, sensitized guinea pigs. Although cough reflex sensitivity is increased after antigen challenge in actively sensitized guinea pigs, it is unknown whether the antigen-induced increase in cough reflex sensitivity develops in passively sensitized animals. The aim of this study was to compare the cough reflex sensitivity to inhaled capsaicin after an inhaled antigen challenge between actively and passively sensitized guinea pigs. METHODS: Measurement of number of coughs elicited by increasing concentrations of capsaicin (10(-6) and 10(-4) M) and bronchial responsiveness to ascending concentrations of methacholine, and analysis of bronchoalveolar lavage fluid (BALF) were separately performed 24 h after an antigen challenge in actively and passively sensitized guinea pigs. RESULTS: Percentage of eosinophils in BALF and bronchial responsiveness to methacholine were increased 24 h after the antigen challenge in both actively and passively sensitized animals compared with saline-challenged actively and passively sensitized animals, respectively. Absolute number of eosinophils in BALF from actively sensitized and antigen-challenged guinea pigs was significantly greater than that from passively sensitized and antigen-challenged animals. Cough response to capsaicin and concentration of substance P in BALF were increased 24 h after the antigen challenge in actively sensitized guinea pigs, but not in passively sensitized guinea pigs. Bronchial responsiveness, cough reflex sensitivity and substance P concentration and total cells in BALF were increased in actively sensitized and saline challenged guinea pigs compared with passively sensitized and saline challenged animals. CONCLUSION: The results suggest that active sensitization per se increases cough reflex sensitivity accompanied by increased inflammatory cells and substance P level in BALF, and antigen challenge further increases them, while simple IgE- and/or IgG-mediated allergic reaction per se or the low intensity of eosinophil infiltration in the airway itself may not affect cough reflex sensitivity in guinea pigs.