Low-dose Fluticasone Propionate in Combination With Salmeterol in Patients With Chronic Obstructive Pulmonary Disease.

Inhaled corticosteroids are widely used in the treatment of chronic obstructive pulmonary disease (COPD). However, their use has been questioned for appropriate dose and a possible increased risk of pneumonia. Here, we reviewed patients with COPD who had received fluticasone-salmeterol combination treatment using data from a linked electronic medical record database. A total of 180 patients received salmeterol with 250 µg fluticasone propionate twice daily and 78 received salmeterol and 100 µg fluticasone propionate twice daily. In both groups, there was no difference in the improved forced expiratory volume in 1 second and COPD assessment test score and the proportion of patients with exacerbations. Although the incidence of common toxicity was approximately equal, that of pneumonia was much higher in the 250 µg group (8.9% vs 1.3%, P=.01). The beneficial effects of inhaled corticosteroids might be obtained at lower doses.

Clinical diagnosis of idiopathic pleuroparenchymal fibroelastosis: A retrospective multicenter study.

BACKGROUND: Although the accurate diagnosis of pleuroparenchymal fibroelastosis (PPFE) requires pathologic evaluation, this diagnosis is often suggested when the radiologic findings are consistent with typical PPFE and when pulmonary apical cap, which radiologically and pathologically mimics PPFE, can be excluded by confirming disease progression. The aim of this study was to evaluate the validity of the clinical diagnosis of idiopathic PPFE. METHODS: We recruited 44 patients with idiopathic PPFE according to our modified diagnostic criteria: 1) a radiologic PPFE pattern (i.e., bilateral subpleural dense consolidation with or without pleural thickening in the upper lobes and less marked or absent involvement of the lower lobes), 2) radiologic confirmation of disease progression, and 3) exclusion of other lung diseases with identifiable etiologies. The patients' baseline characteristics and clinical course were reviewed. RESULTS: The median age was 70 years, and 28 patients were males. The majority revealed emaciation, hypercapnia, and a high ratio of residual volume to total lung capacity. On chest computed tomography, 39 patients showed abnormal shadows in the lower lobes; more than half were classified as having usual interstitial pneumonia (UIP)/possible UIP pattern. Pneumothorax was the most frequent complication (33/44). The median overall survival time after diagnosis was 35.3 months. The presence of lower lobe UIP/possible UIP pattern did not show a significant prognostic impact. CONCLUSIONS: Using our diagnostic criteria, we could recruit relatively many patients with similar characteristics to those of idiopathic PPFE patients in the literature. The possibility of clinical diagnosis of idiopathic PPFE should be further discussed.

Persistent impairment on spirometry in chronic eosinophilic pneumonia: A longitudinal observation study (Shizuoka-CEP study).

BACKGROUND: Chronic eosinophilic pneumonia (CEP) is characterized by the accumulation of eosinophils in the lung with unknown etiology. Although systemic corticosteroid administration leads to dramatic improvement, nearly half the patients with CEP experience relapse and some develop persistent impairment of pulmonary function. However, predictive factors for this persistent impairment have not been determined. OBJECTIVE: To investigate the occurrence of persistent impairment of pulmonary function in CEP and determine its predictive factors. METHODS: This observational study consisted of 133 consecutive patients with CEP who were followed for longer than 1 year. Spirometry was performed at the time of diagnosis and at follow-up. RESULTS: During the observational period (6.1 ± 4.1 years), relapse occurred in 75 patients (56.4%). Remarkably, 42 patients (31.6%) had a persistent pulmonary function defect (27 obstructive, 10 restrictive, and 4 obstructive and restrictive cases) at the last evaluation. Logistic analyses showed that the relapse was associated with neither persistent obstructive nor restrictive defects. Persistent obstructive defect was significantly associated with the comorbidity of asthma and obstructive defect at the initial CEP diagnosis, whereas persistent restrictive defect was significantly related to reticulation at high-resolution computer tomography and restrictive defect at diagnosis. CONCLUSION: Persistent impairment of pulmonary function is common in CEP. Concurrent asthma and obstructive defects at diagnosis were predictors for persistent obstructive impairments, whereas reticulation at high-resolution computer tomography and restrictive defect at diagnosis predicted persistent restrictive impairment. Attention should be paid to these persistent impairments in the management of CEP. TRIAL REGISTRATION: http://www.umin.ac.jp/ctr/index-j.htm Identifier: UMIN000019092 (principal investigator, Takafumi Suda, MD, PhD).

Evaluation of urinary desmosines as a noninvasive diagnostic biomarker in patients with idiopathic pleuroparenchymal fibroelastosis (PPFE).

BACKGROUND: Pleuroparenchymal fibroelastosis (PPFE) is a rare interstitial pneumonia with upper lobe predominance and fibroelastosis. Although definite diagnosis requires surgical lung biopsy (SLB), SLB is often difficult because of its complications such as refractory pneumothorax. OBJECTIVE: To evaluate urinary desmosines (degradation product of mature elastin) as a novel biomarker in patients with PPFE. METHODS: Biopsy-proven patients with PPFE (n = 14) were prospectively enrolled. Levels of urinary desmosines in patients with PPFE were measured with liquid chromatography-tandem mass spectrometry (LC-MS/MS) and compared with those in patients with idiopathic pulmonary fibrosis (IPF), patients with chronic obstructive pulmonary disease (COPD), and controls. RESULTS: Levels of urinary desmosines were significantly higher in patients with PPFE than those in patients with IPF (48.4 vs. 28.6 ng/mg creatinine, p = 0.034), patients with COPD (8.0 ng/mg creatinine, p < 0.001), or controls (17.4 ng/mg creatinine, p < 0.001). Desmosines discriminated between PPFE and IPF (area under the curve [AUC] = 0.708), and between PPFE and controls (AUC = 0.956). However, levels of desmosines were not correlated with physiological parameters in patients with PPFE. CONCLUSIONS: Urinary desmosines may be a useful diagnostic biomarker in patients with PPFE. Measurement of desmosines combined with specific clinical and radiological features of PPFE may lead to an accurate diagnosis without SLB in patients with PPFE.

Step-down treatment from medium-dosage of budesonide/formoterol in controlled asthma.

BACKGROUND: The stepping down of asthma treatment can be considered when asthma symptoms have been well controlled with inhaled corticosteroids (ICSs)/long-acting ß2 adrenergic agonists (LABAs). However, few data are available comparing the efficacy between two step-down strategies, to reduce ICS/LABA dose or to withdraw LABA continuing ICS, in well-controlled asthmatics. METHODS: This was a prospective multicentre randomized, two-arm, controlled study. Ninety-one asthmatic patients controlled by budesonide/formoterol combination (BFC) 320/9 µg twice daily were assigned to 2 stepping-down treatments as follows: the BFC group; BUD/FM 160/4.5 µg twice daily, and the ICS group; ICS (budesonide 400 µg twice daily or equivalent dose of ICS) without LABA, and followed for 12 weeks. The primary outcome was the incidence of asthma exacerbations. Asthma control, pulmonary function tests, and fraction of exhaled nitric oxide (FeNO) were evaluated at the beginning and end of the period. RESULTS: The incidence of exacerbations was 16.3% in the BFC groups and 12.5% in the ICS group, which were not different between the groups (p = 0.766). No significant differences were found in QOL score and FeNO between 0 week and 12 week in the both group. FEV1 and FEV1 percentage of the predicted value were lower at week 12 than at week 0 in the ICS group, but not in the BFC group. CONCLUSIONS: The two step-down strategies for 12 weeks have equal acceptability in well-controlled asthmatics treated with medium-dose of BFC, however, withdrawal of LABA may have potential risk to deteriorate FEV1. CLINICAL TRIAL REGISTRATION: This study was registered to UMIN-CTR (http://www.umin.ac.jp/ctr/), UMIN000010333.

Continuation maintenance therapy with S-1 in chemotherapy-naïve patients with advanced squamous cell lung cancer.

Objectives Maintenance therapy is a standard therapeutic strategy in non-squamous non-small-cell lung cancer. However, there is no consensus regarding the benefit of maintenance therapy for patients with squamous cell lung cancer. We assessed maintenance therapy with S-1, an oral fluoropyrimidine agent, following induction therapy with carboplatin and S-1 in patients with squamous cell lung cancer. Methods In this phase II trial, chemotherapy-naïve patients with squamous cell lung cancer were enrolled to induction therapy with four cycles of carboplatin (at an area under the curve of 5 on day 1) and S-1 (80 mg/m(2)/day on days 1-14) in a 28-day cycle. Patients who achieved disease control after induction therapy received maintenance therapy with S-1 in a 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival after administration of maintenance therapy. Results Fifty-one patients were enrolled in the study. The median progression-free survival from the start of maintenance therapy was 3.0 months (95 % confidence interval, 2.5-3.5). The most common toxicities associated with maintenance therapy were anemia, thrombocytopenia, and fatigue, but they were not severe. Conclusion S-1 maintenance therapy might be a feasible treatment option in patients with squamous cell lung cancer.

Sequential addition of aprepitant in patients receiving carboplatin-based chemotherapy.

Chemotherapy-induced nausea and vomiting is a challenging issue. Although aprepitant is sometimes used as a therapeutic option in patients receiving moderately emetogenic chemotherapy, the potential benefit of sequential addition of aprepitant to dexamethasone and a 5-hydroxytryptamine-3 (5-HT3) receptor antagonist during the second cycle of carboplatin-based chemotherapy remains unclear. Chemo-naïve patients with advanced non-small cell lung cancer (NSCLC) who received carboplatin-based chemotherapy were treated with doublet antiemetic therapy with dexamethasone and a 5-HT3 receptor antagonist during the first cycle of chemotherapy. Aprepitant was then added during the second cycle of chemotherapy. The primary endpoint was overall complete response rate, defined as no vomiting and no rescue therapy during the 120 h after administration of chemotherapy. Sixty-seven patients were enrolled, 63 of whom were eligible after two cycles of chemotherapy. The overall complete response rate was significantly improved in the second cycle [87.3 %, 95 % confidence interval (CI) 76.5-94.4 %] compared with the first cycle (65.1 %, 95 % CI 52.0-76.7 %; p < 0.001). Improvement was observed in the delayed phase, but not in the acute phase. Subsequent addition of aprepitant significantly improved the overall complete response rate in NSCLC patients receiving a second cycle of carboplatin-based chemotherapy.

Maintenance therapy with pemetrexed and bevacizumab versus pemetrexed monotherapy after induction therapy with carboplatin, pemetrexed, and bevacizumab in patients with advanced non-squamous non small cell lung cancer.

OBJECTIVES: Single agent maintenance therapy is widely accepted for advanced non-squamous non small cell lung cancer (NSCLC). However, there is no consensus on the initial and maintenance phase regimens, and the clinical benefit of adding bevacizumab to cytotoxic drugs in the maintenance phase remains unclear. METHODS: Chemotherapy-naïve patients with non-squamous NSCLC were randomly assigned to maintenance therapy with pemetrexed and bevacizumab or pemetrexed alone, after achieving disease control after four cycles of induction therapy with carboplatin (area under the curve = 6), pemetrexed (500 mg/m(2)), and bevacizumab (15 mg/kg). The primary end-point was 1-year progression-free survival (PFS) rate. RESULTS: One hundred ten patients were enrolled in the study, with 55 patients assigned to the two groups. The mean 1-year PFS rate was 43.9% (95% confidence interval [CI]: 29.6-59.2%) in the combination maintenance group and 35.2% (95% CI: 22.1-51.0%) in the pemetrexed maintenance group, and the difference was not significant (p = 0.433). Median PFS measured from enrolment was 11.5 months (95% CI: 7.1-19.0) in the combination maintenance group and 7.3 months (95% CI: 5.7-14.1, hazard ratio: 0.73, 95% CI: 0.44-1.19, log-rank p = 0.198) in the pemetrexed maintenance group. Nasal haemorrhage, hypertension, and proteinuria were significantly more frequent in the combination maintenance group, but they were mild and tolerable. CONCLUSION: Both maintenance therapy with pemetrexed alone and pemetrexed and bevacizumab in combination were feasible in patients with non-squamous NSCLC who have achieved disease control after induction therapy with carboplatin, pemetrexed, and bevacizumab. According to the selection design, differences in the superiority between these maintenance therapies were not demonstrated.

Efficacy of short-term prednisolone treatment in patients with chronic eosinophilic pneumonia.

In patients with chronic eosinophilic pneumonia (CEP), dramatic improvements are seen in response to corticosteroid therapy; however, relapse is common after treatment has ceased. The optimal duration of corticosteroid therapy remains unclear. In a randomised, open-label, parallel group study, eligible patients with CEP received oral prednisolone for either 3 months (3-month group) or 6 months (6-month group), followed by 2 years observation. All patients were treated with an initial dose of prednisolone of 0.5 mg·kg(-1)·day(-1), which was then tapered and discontinued at either 3 or 6 months. The primary end-point was relapse during the follow-up period. In the final analysis, there were 23 patients in the 3-month group and 21 patients in the 6-month group. All patients showed a good response to prednisolone treatment. There were 12 (52.1%) relapses in the 3-month group and 13 (61.9%) relapses in the 6-month group. No significant difference was found in the cumulative rate of relapse (p=0.56). All relapse cases showed improvement upon resumption of prednisolone treatment. No difference was observed in the rate of relapse between the 3- and 6-month prednisolone treatment groups for patients with CEP.

Evaluation of palonosetron and dexamethasone with or without aprepitant to prevent carboplatin-induced nausea and vomiting in patients with advanced non-small-cell lung cancer.

OBJECTIVES: Although antiemetic management has improved, better control of chemotherapy-induced nausea and vomiting (CINV), particularly during the delayed phase, is needed. The benefit of combination therapy using dexamethasone and the second-generation 5-hydroxytryptamine-3 receptor antagonist palonosetron compared with that of other such receptor antagonists in carboplatin-based chemotherapy is unclear. The effectiveness of adding aprepitant for CINV treatment in moderate emetogenic chemotherapy is also unknown. We compared the efficacy and safety of triple antiemetic therapy using aprepitant, palonosetron, and dexamethasone with that of double antiemetic therapy using palonosetron and dexamethasone in patients with advanced non-small-cell lung cancer receiving carboplatin-containing chemotherapy. METHODS: Chemotherapy-naïve patients with non-small-cell lung cancer were enrolled in this prospective controlled study. Eighty patients were randomly assigned to groups receiving either double antiemetic therapy with palonosetron and dexamethasone, or triple antiemetic therapy with aprepitant, palonosetron, and dexamethasone. Complete response rate (no vomiting episode and no rescue therapy) was evaluated as the primary endpoint during the 5-day post-chemotherapy period. RESULTS: The aprepitant add-on and double therapy groups showed overall complete response rates of 80.5% (95% confidence interval [CI]: 68.4-92.6%) and 76.9% (95% CI: 63.7-90.1%; odds ratio [OR]: 0.81; 95% CI; 0.27-2.36; p=0.788), respectively. Complete responses in the acute and delayed phases and overall incidences of treatment-related adverse events were similar between groups. CONCLUSION: According to the selection design, triple antiemetic therapy with aprepitant, palonosetron, and dexamethasone was not considered as an option for further studies.

Quantitative analysis of lung elastic fibers in idiopathic pleuroparenchymal fibroelastosis (IPPFE): comparison of clinical, radiological, and pathological findings with those of idiopathic pulmonary fibrosis (IPF).

BACKGROUND: The pathological appearance of idiopathic pleuroparenchymal fibroelastosis (IPPFE) with hematoxylin-eosin staining is similar to that of usual interstitial pneumonia (UIP) in patients with idiopathic pulmonary fibrosis (IPF). The amount of elastic fibers (EF) and detailed differences between IPPFE and IPF have not been fully elucidated. The aim of this study was to quantify the EF and identify the differences between IPPFE and IPF. METHODS: We evaluated six patients with IPPFE and 28 patients with IPF who underwent surgical lung biopsy or autopsy. The patients' clinical history, physical findings, chest high-resolution computed tomography (HRCT) findings, and pathological features of lung specimens were retrospectively evaluated. The amounts of EF in lung specimens were quantified with Weigert's staining using a camera with a charge-coupled device and analytic software in both groups. RESULTS: Fewer patients with IPPFE than IPF had fine crackles (50.0% vs. 96.4%, p = 0.012). Patients with IPPFE had a lower forced vital capacity (62.7 ± 10.9% vs. 88.6 ± 21.9% predicted, p = 0.009), higher consolidation scores on HRCT (1.7 ± 0.8 vs. 0.3 ± 0.5, p < 0.0001), lower body mass indices (17.9 ± 0.9 vs. 24.3 ± 2.8, p < 0.0001), and more pneumothoraces than did patients with IPF (66.7 vs. 3.6%, p = 0.002). Lung specimens from patients with IPPFE had more than twice the amount of EF than did those from patients with IPF (28.5 ± 3.3% vs. 12.1 ± 4.4%, p < 0.0001). The amount of EF in the lower lobes was significantly lower than that in the upper lobes, even in the same patient with IPPFE (23.6 ± 2.4% vs. 32.4 ± 5.5%, p = 0.048). However, the amount of EF in the lower lobes of patients with IPPFE was still higher than that of patients with IPF (23.6 ± 2.4% vs. 12.2 ± 4.4%, p < 0.0001). CONCLUSION: More than twice the amount of EF was found in patients with IPPFE than in those with IPF. Even in the lower lobes, the amount of EF was higher in patients with IPPFE than in those with IPF, although the distribution of lung EF was heterogeneous in IPPFE specimens.

Aprepitant in patients with advanced non-small-cell lung cancer receiving carboplatin-based chemotherapy.

OBJECTIVES: Chemotherapy-induced nausea and vomiting (CINV) is an unanswered problem in cancer therapy. We evaluated the efficacy and safety of triple antiemetic therapy with aprepitant, a 5-hydroxytryptamine-3 (5-HT(3)) receptor antagonist, and dexamethasone in patients with advanced non-small-cell lung cancer (NSCLC) who received carboplatin-based first-line chemotherapy. METHODS: Chemotherapy-naïve patients with NSCLC were enrolled in this randomized phase-II study. Patients were randomized to standard antiemetic therapy with a 5-HT(3) receptor antagonist and dexamethasone, and aprepitant add-on triple antiemetic therapy. The primary endpoint was the complete response rate (no vomiting and no rescue therapy) during the 120 h post-chemotherapy. RESULTS: A total of 134 patients were assigned randomly to the aprepitant group or the control group. The aprepitant group and the control group showed an overall complete response rate of 80.3% (95% confidence interval (CI), 69.2-88.1%) and 67.2% (95% CI, 55.3-77.2%; odds ratio (OR), 0.50; 95% CI, 0.22-1.10; p = 0.085), respectively. Among patients taking carboplatin and pemetrexed, adding aprepitant significantly improved the complete response rate in the overall phase (83.8% in the aprepitant group and 56.8% in the control group; OR, 0.26; 95% CI, 0.08-0.70; p < 0.01) and the delayed phase (86.5% in the aprepitant group and 59.1% in the control group; OR, 0.23; 95% CI, 0.07-0.65; p < 0.01). CONCLUSION: Carboplatin-based chemotherapy has considerable emetic potential. Triple antiemetic therapy with aprepitant, a 5-HT(3) receptor antagonist, and dexamethasone improved the control of CINV prevention in patients receiving carboplatin and pemetrexed chemotherapy.

[Phaeomycotic cyst caused by Exophiala xenobiotica in a patient with rheumatoid arthritis and lung cancer].

In black fungal infections, Exophiala species are frequently encountered as causative agents of human mycosis, particularly in immunocompromised patients. Among them, Exophiala jenselmei was previously reported as the most common etiological agent. Advances in molecular taxonomy proved this taxon to be heterogeneous, and led to newly introduced or redefined species. Exophiala xenobiotica is one of the novel species differentiated from E. jenselmei on the basis of molecular phylogeny.Here, we report a case of pheomycotic cyst caused by E. xenobiotica, which was well controlled via drainage and local thermotherapy. A 70-year-old man developed a cystic nodular lesion on the dorsum of his right thumb over the previous 3 months. He had been treated with prednisolone and methotrexate for 4 years for rheumatoid arthritis. The patient also had lung cancer with vertebral bone metastasis. Direct microscopic examination of the greenish pus aspirated from the cyst revealed mycelial elements. Culture of the pus on blood and Sabouraud dextrose agar yielded numerous black colonies multiple times. Histopathological examination of a biopsy specimen showed subcutaneous abscess formation surrounded by granulomatous tissues. Faintly pigmented pseudohyphae were seen within the abscess. The presence of melanin in the fungal cells was determined by Fontana-Masson staining. Initial microscopic examination of the isolate revealed annellidic conidiogenous cells, suggestive of E. jenselmei. This strain was further identified as E. xenobiotica by sequence analysis of the internal transcribed spacer (ITS) region of ribosomal RNA, showing a 100% sequence homology with the strain type.Pheomycotic cysts should be considered on identifying a slowly developing chronic subcutaneous abscess in immunocompromised patients. Sequencing is recommended for accurate species identification of causative pathogens.

Maintenance therapy with pemetrexed versus docetaxel after induction therapy with carboplatin and pemetrexed in chemotherapy-naïve patients with advanced non-squamous non-small-cell lung cancer: a randomized, phase II study.

PURPOSE: The optimal strategy for maintenance chemotherapy is controversial. We evaluated the efficacy and safety of continuation maintenance with pemetrexed and switch maintenance with docetaxel in advanced non-squamous non-small-cell lung cancer (NSCLC). METHODS: Chemotherapy-naïve patients with non-squamous NSCLC were enrolled in this randomized phase II study. Patients who achieved disease control after four cycles of induction therapy with carboplatin (AUC 6) and pemetrexed (500 mg/m(2)) were randomized to maintenance therapy with pemetrexed (500 mg/m(2)) or docetaxel (60 mg/m(2)). The primary endpoint was survival without toxicity, defined as the time from the initiation of maintenance therapy to the first date of any grade 3/4 toxicity or death due to any cause. RESULTS: A total of eighty-five patients were enrolled in the induction phase, and 26 patients were assigned to the pemetrexed maintenance therapy and 25 patients were assigned to the docetaxel maintenance therapy. Survival without toxicity was significantly longer in the pemetrexed group (median 20.8 months, 95 % confidence interval (CI) 0.7-not estimable) than in the docetaxel group (median 0.5 months, 95 % CI 0.2-2.0, hazard ratio 0.36, 95 % CI 0.17-0.74). CONCLUSIONS: Continuation maintenance with pemetrexed may be a feasible treatment option for patients with non-squamous NSCLC who have achieved disease control after induction therapy with carboplatin and pemetrexed. Switch maintenance with docetaxel may also be efficacious but frequently causes severe hematologic toxicity.

Idiopathic pleuroparenchymal fibroelastosis: consideration of a clinicopathological entity in a series of Japanese patients.

BACKGROUND: Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a recently reported group of disorders characterized by fibrotic thickening of the pleural and subpleural parenchyma predominantly in the upper lobes. We report five Japanese cases fulfilling the criteria of IPPFE and address whether it should be considered a separate clinicopathologic entity. And this study was an attempt to identify features in common between IPPFE and previously described idiopathic upper lobe fibrosis (IPUF), allowing IPPFE to be considered as a distinct entity in our Japanese series. METHODS: Five consecutive cases of idiopathic interstitial lung disease confirmed as IPPFE by surgical lung biopsy were studied. RESULTS: There were four males and one female, aged 70±2.76 yr. No associated disorder or presumed cause was found in any case. Lung function tests found a restrictive ventilatory defect (4/5) and/or impairment of DLco (4/5). Chest X-ray showed marked apical pleural thickening in all cases. Computed tomography of the chest in all cases mainly showed intense pleural thickening and volume loss associated with evidence of fibrosis, predominantly in the upper lobes. In all cases in this study, markedly thickened visceral pleura and prominent subpleural fibrosis characterized by both elastic tissue and dense collagen were clearly shown. All cases were alive at the last follow-up, 17.6±13.59 months after diagnosis; however, all had deteriorated both clinically and radiologically. CONCLUSIONS: IPPFE deserves to be defined as a separate, original clinicopathologic entity owing to its uniformity and IPPFE has some features in common with previously described idiopathic upper lobe fibrosis (IPUF). Our limited experience with a cohort of 5 subjects suggests that IPPFE can be rapidly progressive.

Ulcerating bronchitis caused by cytomegalovirus in a patient with polymyositis.

We herein report a case of cytomegalovirus (CMV) bronchitis in a 62-year-old woman with polymyositis. She presented with respiratory symptoms and CMV antigenemia while undergoing immunosuppressive therapy with methotrexate (MTX) and prednisolone (PSL). Bronchoscopy was performed, which revealed an ulceration of the left main bronchus. A mucosal biopsy confirmed CMV infection, and the patient was diagnosed with CMV ulcerating bronchitis. The administration of ganciclovir improved the lesion, and the CMV antigenemia disappeared. Endobronchial ulceration should be considered in the differential diagnosis of CMV disease.

Biweekly combination therapy with gemcitabine and carboplatin compared with gemcitabine monotherapy in elderly patients with advanced non-small-cell lung cancer: a randomized, phase-II study.

INTRODUCTION: The strategy of chemotherapy in the elderly is controversial. We wanted to evaluate the efficacy and safety of biweekly gemcitabine and low-dose carboplatin combination therapy in elderly patients with advanced non-small-cell lung cancer (NSCLC). METHODS: In this phase-II trial, chemotherapy-naive elderly patients (aged ≥76 years) with NSCLC were randomly treated with biweekly combination therapy with gemcitabine and carboplatin (1000 mg/m(2) gemcitabine and carboplatin at an area under the curve (AUC) of 3 on days 1 and 15, every 4 weeks) or gemcitabine monotherapy (1000 mg/m(2) on days 1, 8 and 15, every 4 weeks). The primary endpoint was overall response rate and analysis was based on intention-to-treat. RESULTS: Thirty-one patients were randomly assigned combination therapy and 30 were assigned monotherapy. The median age was 79.0 years. Response rate was 22.6% (95% confidence interval (CI): 11.4-39.8%) for biweekly combination therapy and 10.0% (95% CI: 3.5-25.6%) for monotherapy. Median progression-free survival in combination chemotherapy was 3.9 months (95% CI: 0.5-8.5 months), which was significantly longer that that in monotherapy (2.4 months, 95% CI: 0.5-6.7 months). The prevalence of hematological and non-hematological adverse events reaching grade 3/4 was not significantly different between combination therapy and monotherapy. CONCLUSIONS: Biweekly gemcitabine and low-dose carboplatin combination chemotherapy showed acceptable efficacy, toxicity, and tolerability in those aged ≥76 years with NSCLC. Further investigations with a large population are required to confirm our results.

Effect of switching from salmeterol/fluticasone to formoterol/ budesonide combinations in patients with uncontrolled asthma.

BACKGROUND: Combination therapy with an inhaled corticosteroid (ICS) and a long-acting ß(2)-agonist (LABA) in a single inhaler is the mainstay of asthma management and salmeterol/fluticasone combination (SFC) and fixed-dose formoterol/budesonide combination (FBC) are currently available in Japan; however, there is nothing to choose between the two. The purpose of this study was to clarify the effect of switching from SFC to FBC in patients with asthma not adequately controlled under the former treatment regimen. METHODS: This was a prospective, multicenter, open-label, uncontrolled longitudinal study in 87 adult patients with an Asthma Control Questionnaire, 5-item version (ACQ5) score of greater than 0.75 under treatment with SFC 50/250µg one inhalation twice daily (bid). SFC was switched to FBC 4.5/160µg two inhalations bid. Study outcomes included ACQ5 score, peak expiratory flow (PEF), FEV(1), and fractional exhaled nitric oxide (FeNO) at the end of treatment period. RESULTS: Eighty-three patients completed the study. ACQ5 scores improved and exceeded the clinically meaningful difference after 12 weeks of treatment and well-controlled asthma (ACQ5 score ≤0.75) was attained in 37 (44.6%) patients. Minimum and maximum PEF and FEV(1) values improved significantly, but not FeNO values, after switching from SFC to FBC. CONCLUSIONS: Switching ICS/LABA combination therapy is a useful option in the management of asthma that is not optimally controlled.

Epithelial-mesenchymal transition induced by transforming growth factor-beta1 in mouse tracheal epithelial cells.

BACKGROUND AND OBJECTIVE: Epithelial-mesenchymal transition (EMT) is the process by which differentiated epithelial cells undergo a phenotypic transition to mesenchymal cells. This process may occur in certain fibrotic diseases that involve airway remodelling. However, few studies have directly proved the occurrence of EMT in primary cultures of airway epithelial cells. The aim of this study was to clarify whether airway epithelial cells can differentiate into mesenchymal cells through EMT. METHODS: Mouse tracheal epithelial cells (mTEC) were cultured in an air-liquid interface (ALI) culture system, in the presence or absence of transforming growth factor-beta1 (TGF-beta1). The expression of mesenchymal and epithelial cell markers was examined by immunofluorescence staining and western blotting. Secretion of matrix metalloproteinase (MMP)-9 into the culture medium was measured by ELISA. The phenotype of epithelial cells involved in EMT was also examined by immunofluorescence staining. RESULTS: Immunofluorescence staining and western blotting revealed that TGF-beta1 treatment for 14 days induced the expression of the mesenchymal markers, alpha-smooth muscle actin (alpha-SMA) and vimentin, and reduced the expression of the epithelial markers, zonula occludens-1 (Zo-1) and occludin. In addition, alpha-SMA and Zo-1 were colocalized within individual cells treated with TGF-beta1. Concentrations of MMP-9 in the culture medium were significantly higher in TGF-beta1-treated mTEC than in untreated cells. The basal cell markers, cytokeratin-5 and cytokeratin-17, were colocalized within the cells expressing alpha-SMA. CONCLUSIONS: EMT was induced by TGF-beta1 in primary cultures of mTEC, suggesting that airway epithelial cells, possibly the basal cells, may be involved in airway remodelling through EMT.

[Thyroid involvement of sarcoidosis].

A 54-year-old woman was found to have abnormal shadows on her chest radiograph taken on an annual medical examination. The chest radiograph showed multiple nodules in the bilateral middle and lower lung fields accompanied with bilateral hilar lymphadenopathy. A computed tomography of the neck and chest revealed nodules in her right middle lobe and bilateral lower lobes with an enlarged thyroid. A metastatic malignant disease involving both thyroid and lungs was suspected, therefore thyroid and lung biopsies were performed. The histological examination of the thyroid and the lung specimens revealed non-caseating epithelioid cell granulomas which were compatible with sarcoidosis. Although the thyroid involvement of sarcoidosis is rare, it should be included in the differential diagnosis with patients with thyroid swelling.