Association Between Patient Preference for Inhaler Medications and Asthma Outcomes.

Purpose: Asthma guidelines recommend considering the patient preference to optimize medication choices. Patient preference for inhaler medication may affect asthma outcomes, but evidence regarding this is lacking. This study investigated the associations between patient preference for inhaler medications and asthma outcomes. Patients and Methods: A multicenter questionnaire survey was conducted among 351 adult patients with asthma treated with regular inhaled corticosteroids. Agreement between patients' preferences and current medication was evaluated using two questions: matched preference was defined as patients answering that the current inhaler medication was the most preferred treatment and they were satisfied with it. Mismatched preference was defined as when patients reported that the current inhaler medication was not the most preferred treatment and/or they were not satisfied with it. We investigated the factors associated with patient preference for asthma inhaler medications. Results: In total, 269 (76.6%) patients were classified into the matched preference group and 82 (23.4%) patients into the mismatched preference group. Multivariate analyses showed that matched preference was independently associated with higher asthma control test scores (P<0.001), fewer exacerbations (P=0.009), less regular oral corticosteroid use (P=0.009), and better inhaler adherence (P=0.006) than the mismatched preference group. In subgroup analysis, younger age was associated with matched preference in patients using dry powder inhalers but not in those using pressurized metered dose inhalers. Conclusion: The use of preference-matched inhaler medication was associated with better asthma outcomes. Evaluation of patients' preference for inhaler medication might provide useful information for individualized treatment with asthma inhaler medications.

[A Case of Lung Cancer Associated with Drug-Induced Immune Thrombocytopenia].

A Stage IV lung adenocarcinoma was diagnosed in the left upper lobe of an 81-year-old man 2.5 years ago. Following another form of chemotherapy, he then received docetaxel as fourth-line therapy. After 21 days of therapy, although his white blood cell count recovered, his platelet count decreased to 20,000/mL and continued to decrease. Subsequently, he was closely monitored without therapy, and eventually, his platelet count returned within the normal range after 112 days. Blood biochemistry and bone marrow paracentesis findings suggested the presence of paraneoplastic syndrome, idiopathic thrombocytopenic purpura, and drug-induced immune thrombocytopenia. It was difficult to distinguish between the presence of myelosuppression, carcinoma with bone marrow invasion, and paraneoplastic syndrome. This is believed to have resulted from a docetaxel-induced immune thrombocytopenia because, although the platelet count decreased after docetaxel chemotherapy, it eventually returned to normal levels without therapy.

Mustard gas exposure and mortality among retired workers at a poisonous gas factory in Japan: a 57-year follow-up cohort study.

OBJECTIVES: Mustard gas (MG) has been the most widely used chemical warfare agent in the past century. However, few but conflicting data exist on the effects of MG exposure on long-term mortality. We investigated MG-related mortality in retired workers at a poisonous gas factory. METHODS: We assessed mortality rates among 2392 male and 1226 female workers, whose vital status could be determined through 31 December 2009, at a poisonous gas factory operating from 1929 to 1945 in Okuno-jima, Japan. The analysis employed standardised mortality ratios (SMRs) calculated using national and prefectural references and a Cox proportional hazard regression model. Applying the Kaplan-Meier method, we compared cumulative death rates in the study cohort stratified by an 'Okuno-jima MG Index' which represented the product of HRs derived for job category and length of service. RESULTS: Among male workers, we found significant excesses in mortality from upper respiratory tract cancer (SMR 3.06), liver cancer (1.67), lung cancer (2.01) and chronic bronchitis/emphysema (4.84) compared with the national population, as well as stomach cancer (1.20) versus the Hiroshima Prefecture population. When stratified into 3 subgroups by the Okuno-jima MG Index, those with a higher Okuno-jima MG Index had significantly higher cumulative rates of death from respiratory cancer and chronic bronchitis/emphysema. CONCLUSIONS: MG exposure significantly increases the long-term risk of death from respiratory cancer and chronic bronchitis/emphysema. The Okuno-jima MG Index may be a useful indicator for estimating cumulative MG exposure.

[Clinical effects of budesonide/formoterol combination drug in elder patients with asthma compared with budesonide plus tulobuterol patch combination treatment].

BACKGROUND AND AIMS: Tulobuterol patch (Tulo) is often used for treatment of elder patient with asthma in Japan. However, there is no evidence either ICS plus Tulo or ICS/LABA combination is better for elder patient. METHODS: Elder patients with asthma (aged≥ 70, n=17) who had treated with budesonide (BUD) 400 µg/day plus Tulo 2 mg/day, were randomly assigned either to change control medication to budesonide/formoterol combination (BUD/FM) 320/9 µg/day or to keep BUD plus Tulo treatment for 12 weeks. RESULTS: At week 4 and week 12, the BUD/FM group showed significant increase in lung function (FEV1, %FEV1) and mini AQLQ score compared with the BUD plus Tulo group. The BUD/FM group also showed decrease in Tumor Necrosis Factor-alpha level in exhaled breath condensate at week 12. No adverse event was observed in both groups. CONCLUSION: In elder patients with asthma, treatment with BUD/FM does not have any clinical disadvantage and may provide better efficacy in lung function, QOL, and possibly anti-inflammation compared with BUD plus Tulo treatment.

Intra-airway administration of small interfering RNA targeting plasminogen activator inhibitor-1 attenuates allergic asthma in mice.

Recent studies suggest that plasminogen activator inhibitor-1 (PAI-1), a major inhibitor of the fibrinolytic system, may promote the development of asthma. To further investigate the significance of PAI-1 in the pathogenesis of asthma and determine the possibility that PAI-1 could be a therapeutic target for asthma, this study was conducted. First, PAI-1 levels in induced sputum (IS) from asthmatic subjects and healthy controls were measured. In asthmatic subjects, IS PAI-1 levels were elevated, compared with that of healthy controls, and were significantly higher in patients with long-duration asthma compared with short-duration asthma. PAI-1 levels were also found to correlate with IS transforming growth factor-ß levels. Then, acute and chronic asthma models induced by ovalbumin were established in PAI-1-deficient mice and wild-type mice that received intra-airway administrations of small interfering RNA against PAI-1 (PAI-1-siRNA). We could demonstrate that eosinophilic airway inflammation and airway hyperresponsiveness were reduced in an acute asthma model, and airway remodeling was suppressed in a chronic asthma model in both PAI-1-deficient mice and wild-type mice that received intra-airway administration of PAI-1-siRNA. These results indicate that PAI-1 is strongly involved in the pathogenesis of asthma, and intra-airway administration of PAI-1-siRNA may be able to become a new therapeutic approach for asthma.

Effect of mustard gas exposure on incidence of lung cancer: a longitudinal study.

Sulfur mustard, an agent used in chemical warfare, is an alkylating substance with carcinogenic potential. However, the precise long-term carcinogenic effects of mustard gas are unclear. Since 1952, the authors have conducted health surveys of former workers who were employed from 1929 to 1945 in a poisonous gas factory in Okuno-jima, Hiroshima, Japan. This prospective study was undertaken from 1952 to 2005 to examine the incidence of lung cancer among the workers who were exposed to mustard gas (n=480), lewisite (n=55), and/or diphenylcyanarsine (n=178), as well as the incidence among unexposed workers (n=969). The stochastic relation between exposure and lung cancer was explored on the basis of multistage carcinogenesis by using an accelerated hazard model with a transformed age scale. Mustard gas exposure was found to transform the age scale for developing lung cancer. One year of exposure in subjects ≤18 or >18 years old at first exposure shifted the age scale down by 4.9 years and 3.3 years, respectively. On the basis of the long-term follow-up of former workers in the poisonous gas factory, the authors concluded that sulfur mustard decreased the age at which people were at risk of developing lung cancer and that the effect declined with aging.

Suppressor of cytokine signaling 1 inhibits pulmonary inflammation and fibrosis.

BACKGROUND: Suppressor of cytokine signaling (SOCS) proteins are inhibitors of cytokine signaling. Our previous study suggested that SOCS1 regulates collagen synthesis by lung fibroblasts, suggesting a role of SOCS1 in the pathophysiology of pulmonary fibrosis. OBJECTIVES: We sought to investigate the role of SOCS1 in pulmonary inflammation and fibrosis in vivo. METHODS: SOCS1-haplodeficient mice treated with bleomycin (BLM) were evaluated for pulmonary inflammation and fibrosis compared with wild-type mice. The human study group was composed of 18 patients with interstitial lung disease. Lung specimens obtained by means of open lung biopsy were investigated to determine whether the severity of fibrosis was associated with decreased SOCS1 expression. Finally, we further analyzed the effect of exogenous SOCS1 on BLM-induced lung injury based on adenoviral SOCS1 gene transfer to the lung. RESULTS: SOCS1-haplodeficient mice treated with BLM showed markedly enhanced pulmonary inflammation and fibrosis compared with wild-type mice. Using human lung specimens, we found that SOCS1 mRNA levels inversely correlated with duration of the disease. SOCS1 expression was significantly less in lung tissue from patients with idiopathic pulmonary fibrosis (IPF) compared with that in non-IPF patients. Moreover, SOCS1 expression was significantly less in severe fibrotic lesions (lower lobe) than in less fibrotic lesions (upper lobe). Adenoviral SOCS1 gene transfer to murine lungs significantly decreased lymphocytic inflammation, pulmonary fibrosis, and mortality because of BLM-induced lung injury. Exogenous SOCS1 inhibited expression of various cytokines, including TNF-alpha, which might play a key role. CONCLUSIONS: These results suggest that SOCS1 might act as a suppressor for pulmonary fibrosis. SOCS1 might be a target of IPF treatment.

[Remission of pulmonary alveolar proteinosis during antituberculosis chemotherapy].

The patient was a 32-year-old man in whom pulmonary tuberculosis had occurred 5 years after the presumptive onset of pulmonary alveolar proteinosis. A diagnosis of pulmonary tuberculosis was made by sputum smears positive for acid-fast bacilli. Computer tomography of the chest showed ground glass opacities, consolidation and cavitation. Rifampicin, isoniazid and ethambutol were given daily, and streptomycin three times a week. Serial chest radiographs revealed progressive clearing not only of the new but also of the old lung infiltrates thought to be due to pulmonary alveolar proteinosis. Serum LDH and CEA returned to normal values. This case indicates the possibility of improving pulmonary alveolar proteinosis by tuberculosis infection or antituberculosis therapy.