Real-world effects of two inhaled corticosteroid/long-acting ß2-agonist combinations in the treatment of asthma.

OBJECTIVE: There are several inhaled corticosteroid/long-acting ß2-agonist (ICS/LABA) combinations currently used to treat asthmatic patients, but the differences in the clinical effects of these ICS/LABAs are currently unknown. We herein evaluated the effects of two currently available ICS/LABA combinations in a real-world setting. METHODS: A fluticasone propionate/salmeterol combined Discus inhaler (FP/SM; 250/50 µg bid) was switched to a budesonide/formoterol Turbuhaler inhaler (BUD/FM; 160/4.5 µg two inhalations bid) and FP/SM (500/50 µg bid) was also switched to BUD/FM (160/4.5 µg four inhalations bid) in symptomatic asthmatic patients treated with FP/SM over 20 years of age. RESULTS: Sixty patients were enrolled in this study, and the scores of the asthma control test (ACT) and asthma control questionnaire-5 item version (ACQ5) were significantly improved 4 and 8 weeks after the switch to ICS/LABA treatments, and well-controlled asthma (ACQ5 score <0.75) and good control (ACT score >20) was achieved in 54 (90%) and 40 (66.7%) patients, respectively, at 8 weeks. The spirometric analysis revealed significant improvements of the values of the peak expiratory flow (PEF) and forced expiratory volume in one second (FEV1) after switching from FP/SM to BUD/FM, and significantly improved small airway impairments ([Formula: see text]50 and [Formula: see text]25) were observed in patients treated with high-dose ICS/LABA. These subjective and objective improvements were also seen in patients aged over 65 years old. CONCLUSION: These data demonstrated that changing the combined ICS/LABA inhaler from FP/SM to BUD/FM can lead to more effective management of symptomatic patients with asthma, especially in patients treated with high-dose ICS/LABA.

[Evaluation of the antiemetic effect of aprepitant in lung cancer patients receiving carboplatin-based chemotherapy using the Functional Living Index-Emesis questionnaire].

In the present study, we evaluated the antiemetic effect of aprepitant in combination with 5-hydroxytryptophan(5-HT3) receptor antagonist and dexamethasone for chemotherapy-induced emesis and nausea in lung cancer patients treated with carboplatin-based systemic chemotherapy using the Functional Living Index-Emesis, an emesis- and nausea-specific quality of life(QOL)questionnaire. Patients experiencing emesis and/or nausea during and/or after previous courses of carboplatin-based chemotherapy received aprepitant in the following treatment cycle with the same anti-cancer agent. Emesis- and nausea-specific QOL aspects were significantly improved with the addition of aprepitant to the existing regimen containing dexamethasone and 5-HT3 receptor antagonist. Our result suggests that combined antiemetic treatment with aprepitant, dexamethasone, and 5-HT3 receptor antagonist is more effective in lung cancer patients receiving carboplatin-based systemic chemotherapy than dexamethasone and 5-HT3 receptor antagonist alone.

Phase II trial of erlotinib for Japanese patients with previously treated non-small-cell lung cancer harboring EGFR mutations: results of Lung Oncology Group in Kyushu (LOGiK0803).

OBJECTIVE: Erlotinib has been reported to be useful for treatment of non-small-cell lung cancer harboring mutation of the epidermal growth factor receptor gene EGFR-mt. However, no prospective trial has yet assessed the utility of erlotinib in Japanese patients. METHODS: Patients with EGFR-mt (exon 19/21) non-small-cell lung cancer who had previously received one to two chemotherapy regimens were enrolled in this trial. Erlotinib was initially administered at a dose of 150 mg/day orally until disease progression or unacceptable toxicities occurred. The primary endpoint was the objective response rate. RESULTS: Twenty-six patients were enrolled between February 2009 and January 2011. Objective response was observed in 14 patients (53.8%, 95% confidence interval: 33.4-73.4%), and the disease control rate reached 80.8% (95% confidence interval: 60.7-93.5%). After a median follow-up time of 17.3 months (range: 5.8-29.5 months), the median progression-free survival was 9.3 months (95% confidence interval: 7.6-11.6 months). The median survival time is yet to be determined. Major toxicities were skin disorder and liver dysfunction; most episodes were grade 2 or less, and all were tolerable. Only one patient with grade 3 skin rash discontinued the study. No patients developed interstitial lung disease, and there were no treatment-related deaths. CONCLUSIONS: This prospective study is the first to have investigated the usefulness of erlotinib in Japanese patients with previously treated EGFR-mt non-small-cell lung cancer. Although this trial could not meet the primary endpoint, erlotinib was well tolerated and showed clinical benefit such as promising disease control rate or progression-free survival in this population, similar to gefitinib.

[Case of primary lymphoplasmacytic lymphoma limited to the paratracheal mediastinum].

A 54 year old Japanese man was introduced to Saiseikai General hospital for an evaluation of an abnormal chest X-ray film. Abnormal soft tissue area was observed in the mediastinum surrounding anterior area of the trachea on chest CT. Because the mediastinal tumor showed slow enlargement after temporal decrease and surgical resection of the tumor was performed 3 years after the first visit. Pathologically, diffuse proliferation of oval-shaped plasmacytic or small lymphocytic cells with eccentrically-located nuclei with rough chromatin were observed in the tumor. Immunohistochemically, these cells were positive for CD20, weakly positive for IgM, negative for CD3, CD5, CD10, suggesting lymphoplasmacytic lymphoma (LPL). The patient was treated with rituximab after the surgical treatment, and showed no exacerbation for 3.5 years after surgery. LPL localized to the paratracheal mediastinum is rare, and a surgical approach is important for prompt and proper diagnosis.

[Efficacy and safety of moxifloxacin in patients with nursing and healthcare-associated pneumonia].

Moxifloxacin (MFLX) is a respiratory quinolone, and is effective against not only Gram-positive and negative bacteria but also anaerobes. There has been no prospective studies evaluating the efficacy and safety of MFLX in patients with nursing and healthcare-associated pneumonia (NHCAP). Therefore, we assessed the efficacy and safety of MFLX in patients with NHCAP. NHCAP patients with mild and moderate severity assessed by the A-DROP system in community-acquired pneumonia guideline proposed by Japan Respiratory Society visited our hospitals from April 2011 to March 2012. Clinical symptoms, chest X-ray films and/or computed tomography, peripheral white and red blood cell and platelet counts, serum CRP, AST, ALT, BUN, creatinine were evaluated. Forty patients were eventually evaluated, and average age was 74.1 years old, male/female were 21/19, 92.5% (37/40) of them had one or more comorbidities. Median duration of MFLX administration was 7.1 days (4-15 days). The efficacy of MFLX in all patients was 87.5% (35/40). The efficacies in each age group were 87.9% (aged over 65 years old), 85.7% (aged under 64 years old), and in each pneumonia severity group by the A-DROP system were 91.7% (mild), 85.7% (moderate). Diarrhea and swelling of the breast were observed in one patient (2.5%) after starting MFLX administration. Mild elevated transaminases were observed in three patients (7.5%), and mild renal dysfunction was observed in two patients (5.0%). All abnormally increased levels of transaminases and serum creatinine were recovered after a cessation of MFLX. MFLX is effective and safe in patients with NHCAP.

Intrathoracic Rosai-Dorfman disease with spontaneous remission: a clinical report and a review of the literature.

Rosai-Dorfman disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy, is a rare non-neoplastic disease that is characterized by a proliferation of histiocytes mostly in lymph nodes. However, the etiological mechanism of RDD still remains unclear. Intrathoracic manifestations of RDD are only observed in 2% of patients with RDD. Spontaneous remission was reported in about 20% of patients with RDD; however, there are no reports of an intrathoracic manifestation of RDD that showed a spontaneous remission within a short period of time. A 64-year-old Japanese female with dry cough and left chest pain was introduced to our hospital, and computed tomography revealed a pulmonary nodular lesion and enlarged mediastinal lymph nodes. The bronchial specimen obtained from the abnormal mucosal lesion showed massive infiltration of histiocytes underneath the bronchial epithelium and emperipolesis, a typical pathological finding in RDD, which is characterized by the presence of histiocyte-like cells engulfing intact lymphocytes. These histiocytes were positive for S-100 (one of the known positive markers of RDD) and for CD68 (a marker for various cells of the macrophage lineage). All these findings are consistent with the diagnosis of RDD. These radiological and endoscopic findings spontaneously resolved within four months without any treatment. In conclusion, clinicians should be aware of this disease as one of differential diagnoses of pulmonary nodules in combination with mediastinal lymph node enlargements, especially in order to differentiate it from primary lung cancer.

[A case of rhabdomyolysis caused by saw palmetto of healthy foods].

An 82-year-old man visited our hospital when he developed a fever of over 38 degrees C after having consumed 5 types of health foods. He had previously been treated for chronic obstructive pulmonary disease, hypertension and hyperuricemia. Blood examination on admission revealed renal dysfunction, marked elevation of C-reactive protein, and an elevated level of serum creatine kinase. According to the laboratory data and his clinical history, rhabdomyolysis complicated by acute renal failure was suspected, but his condition improved and his fever was reduced with fluid infusion. As a drug lymphocyte stimulation test was positive for only saw palmetto in the 5 health foods, we diagnosed the case as rhabdomyolysis induced by saw palmetto. We believe that this is the first case of a health food being the cause of rhabdomyolysis.

Diagnosis of fulminant pneumonia caused by Legionella pneumophila serogroup 8 with the sequence analysis of the 16S rRNA gene.

Pneumonia is the fourth leading cause of death in Japan. Accurate and rapid detection of the causative pathogen(s) is necessary and important for appropriate antimicrobial treatment, especially in patients with rapidly progressive pneumonia or immunocompromised patients. Conventional methods, such as cultivations, detection of urinary antigens or PCR amplification of specific genes, inevitably require the precise presumption of potential pathogens in each case, and pneumonia caused by unanticipated microorganisms might lead to inadequate antimicrobial treatments and unfortunate consequences. We herein report an immunocompromised female patient (69 years old) with fulminant pneumonia caused by Legionella (L.) pneumophila serogroup 8. Ordinary cultivation methods and urinary antigen detection failed to identify the causative organisms. Accordingly, DNA was extracted from the bronchoalveolar lavage fluid and used for the PCR-based cloning of the bacterial 16S rRNA gene. Sequencing analysis of the isolated clones revealed the predominance of L. pneumophila. Based on this information, the patient received an appropriate and successful antimicrobial treatment. In addition, L. pneumophila serogroup 8 was identified with culturing the bronchoalveolar lavage fluid and serotyping with L. pneumophila antisera. The 16S rRNA gene sequencing analysis can reveal the potential pathogens without any presumption about the organism, and can evaluate the kinds and ratio of bacterial species in each specimen. In conclusion, this cultivation-independent method is a potential diagnostic modality for pneumonia, especially in patients with rapidly progressive pneumonia or those who are immunocompromised.

[A case of acute chronic respiratory failure due to fat embolism syndrome after the left femoral neck fracture].

A 78 year old Japanese woman was transferred to our hospital for the treatment of a fracture of the left femoral neck in April, 2010. She had been taking oral corticosteroid (prednisolone 5 mg/day) for the treatment of idiopathic interstitial pneumonia since 2003, and had been treated by home oxygen therapy since 2007. She fell in the restroom at home and hurt herself, and was transferred to our hospital for treatment of a left femoral neck fracture in April, 2010. Her respiratory status was stable just after the transfer; however, she was transferred to the intensive care unit and started to receive mechanical ventilation due to rapidly progressive respiratory failure on the fourth day after admission. Chest X-ray and computed tomography revealed rapid progression of bilateral ground-glass attenuations, and acute exacerbation of interstitial pneumonia was clinically suspected. However, the elevation of D-dimer over time and characteristic findings of petechial hemorrhagic lesions on her palpebral conjunctivae and neck with microscopic findings of phagocytized lipid in alveolar macrophages in her endobronchial secretion led to the diagnosis of fat embolism syndrome. She was successfully treated with high-dose corticosteroid and sivelestat sodium, and she was discharged on the 21st day after admission. Although a differential diagnosis of acute exacerbation of interstitial pneumonia and fat embolism syndrome was necessary and difficult in the present case, characteristic findings of petechial hemorrhagic lesions of skin, palpebral conjunctiva and lipid-laden alveolar macrophages in endotracheal aspirate were useful for the accurate and prompt diagnosis of fat embolism syndrome.

[Retrospective analysis of the safety of four hours administration of liposomal amphotericin B in patients with chronic necrotizing pulmonary aspergillosis].

We have retrospectively analyzed the safety of 4 hours administration of liposomal amphotericin B (L-AMB) compared to less than or equal to 3 hours administration in patients with chronic necrotizing pulmonary aspergillosis (CNPA). The elevation of serum creatinine in the group with 4 hours administration of L-AMB in patients with CNPA was equal to the group with shorter administration time (less than or equal to three hours). During the administration of L-AMB, the group with 4 hours administration of LAMB had significantly a safer profile in relation to hypokalemia during L-AMB treatment than the group with shorter administration time. Additionally, white cell counts, platelet counts, serum creatinine, AST, ALT were not significantly different between L-AMB 4 hours administration group and less than or equal to 3 hours administration group. As the group with 4 hours administration of L-AMB had significantly a safer profile in relation to hypokalemia during L-AMB treatment, this modality can be one of the safer ways in the treatment of CNPA. As L-AMB is one of the fungicidal agents, 4 hours administration of L-AMB can be an optimal way of treating CNPA.

[Efficacy and safety of sitafloxacin for lower respiratory tract infections].

We investigated the efficacy and safety of sitafloxacin (STFX) in patients with mild to moderate community-acquired pneumonia or secondary infections of chronic respiratory tract diseases. The results showed that the efficacy rate was 96.5% (111/115) in patients analyzed for efficacy. The efficacy rate by STFX administration method was 93.9% (46/49) at 50mg b.i.d., 100% (37/37) at 100 mg q.d. and 96.6% (28/29) at 100mg b.i.d. In chest X-rays, the image improvement rate in 102 patients with shadows before treatment was 94.1% (96/102). The image improvement rate by STFX administration method was 90.5% (38/42) at 50 mg b.i.d., 97.1% (33/34) at 100mg q.d. and 96.2% (25/26) at 100mg b.i.d. Side effects occurred in five out of 115 patients (4.3%). Abnormalities in hepatic function test values appeared in two patients and abnormalities in renal function test values appeared in three patients. In four cases, the abnormalities were very mild and STFX administration was continued without any treatment. In the other patient, the abnormal value rapidly returned to normal after STFX administration was discontinued. These findings indicated that STFX can be used safety in routine practice by adjusting the administration within the approved dose based on patient characteristics. Good therapeutic effects can be expected in patients with respiratory tract infections.

[A case of rapidly progressive metastatic pulmonary amelanotic malignant melanoma 16 years after resection of melanoma].

An 80-year-old Japanese male was admitted to our hospital because of bloody sputum. He had a history of malignant melanoma of the left fourth digit, which was surgically excised 16 years previously. On hospital admission, chest computed tomography revealed several nodules in the lower lobes. He underwent thoracoscopic lung biopsy and amelanotic malignant melanoma was histologically diagnosed by immunohistochemical staining. The staining pattern with several antibodies was similar to that of the melanoma excised 16 years previously. Therefore, we concluded that the nodules in the lung were metastases of the malignant melanoma of the digit. Despite treatment with interferon, the nodules progressed rapidly, and the patient died 4 months later. This case suggests that the risk of recurrence with rapidly progressive distant metastasis should be considered in patients with malignant melanoma, even after a long disease-free interval. In addition, this case suggests that immunohistochemical stains with several antibodies are useful in the diagnosis of malignant melanoma.

[A case of multicentric Castleman disease with massive infiltration of plasmacytes presenting IgG4].

A 42-year-old Japanese woman was referred to our university hospital due to progressive anemia and bilateral hilar lymphadenopathy with diffuse ground-glass attenuation on chest computed tomography in December 2009. She had suffered from exertional dyspnea and fatigue for several months. Laboratory findings on admission demonstrated leukocytosis (10,950/ul), elevation of C-reactive protein (4.7 mg/dl), IL-6 (19.9 pg/ml), IgG4 (567 mg/dl) and polyclonal hyper gamma-globulinemia. Chest computed tomography represented mediastinal and bilateral hilar lymphadenopathy with diffuse centrilobular fine nodules and intralobular septal thickening. Histopathological findings of the specimens obtained by thoracoscopic lung and mediastinal lymph node biopsies revealed massive infiltration of IgG4-positive plasma cells in lung tissue and lymph nodes. Pathological findings and high levels of C-reactive protein and interleukin-6 suggested a diagnosis of multicentric Castleman's disease (MCD). In addition, pathological findings of peribronchiolar infiltration of IgG4-positive plasma cells and lymphoid follicles with infiltration of IgG4-positive plasma cells with a high level of IgG4 were indicative of the complication of IgG4-related lung disease. Radiological and serological findings improved rapidly soon after the initiation of oral corticosteroid treatment. It was speculated that this case indicated the close relationship between MCD and IgG4-related lung disease.

Pneumonia and empyema caused by Streptococcus intermedius that shows the diagnostic importance of evaluating the microbiota in the lower respiratory tract.

The bacterial species in the Streptococcus anginosus group (S. constellatus, S. anginosus, S. intermedius) are important causative pathogens of bacterial pneumonia, pulmonary abscesses and empyema. However, the bacteria in this group are primarily oral resident bacteria and unable to grow significantly on ordinary aerobic culture media. We experienced a case of pneumonia and empyema caused by Streptococcus intermedius detected using a 16S rRNA gene sequencing analysis of bronchoalveolar lavage fluid and pleural effusion, but not sputum. Even when applying the molecular method, sputum samples are occasionally unsuitable for identifying the causative pathogens of lower respiratory tract infections.

Discrepancy between the Clinical Image and Pathological Findings of Non-Small Cell Lung Cancer Harboring an Epidermal Growth Factor Receptor Gene Mutation That Was Surgically Resected after Gefitinib Treatment.

We herein describe a discrepancy between the clinical image and pathological findings in a non-small cell lung cancer patient with an epidermal growth factor receptor (EGFR) mutation who underwent surgical resection after gefitinib treatment. The patient was a 66-year-old female with c-stage IIIA lung adenocarcinoma harboring an EGFR gene mutation; she was surgically treated after receiving gefitinib. The pathological examination revealed adenocarcinoma, and the pathologically therapeutic effect was considered to be slight or of no response. EGFR T790M mutation and MET amplification were not present. The pathologically therapeutic effect is generally well correlated with the response rate after induction therapy. In this case, there was a discrepancy between the clinical image and pathological findings. Our findings, therefore, raise questions about the role of surgery after EGFR-tyrosine kinase inhibitor treatment.

Pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma with multiple thin-walled pulmonary cysts: a case report and review of the literature.

We herein report a rare case of pulmonary mucosa-associated lymphoid tissue (p-MALT) lymphoma with multiple cystic lesions. A previously healthy 58-year-old Japanese woman visited our hospital for an evaluation of abnormal chest computed tomography (CT) findings. Chest CT revealed multiple cystic lesions in both lungs, and she was diagnosed as having p-MALT lymphoma based on the pathological findings. The patient had no underlying autoimmune diseases. She has not received any chemotherapy and has been stable for two years. This case suggests that, although rare, the possibility of p-MALT lymphoma should be considered in patients with multiple cystic lung diseases.

Significance of anaerobes and oral bacteria in community-acquired pneumonia.

BACKGROUND: Molecular biological modalities with better detection rates have been applied to identify the bacteria causing infectious diseases. Approximately 10-48% of bacterial pathogens causing community-acquired pneumonia are not identified using conventional cultivation methods. This study evaluated the bacteriological causes of community-acquired pneumonia using a cultivation-independent clone library analysis of the 16S ribosomal RNA gene of bronchoalveolar lavage specimens, and compared the results with those of conventional cultivation methods. METHODS: Patients with community-acquired pneumonia were enrolled based on their clinical and radiological findings. Bronchoalveolar lavage specimens were collected from pulmonary pathological lesions using bronchoscopy and evaluated by both a culture-independent molecular method and conventional cultivation methods. For the culture-independent molecular method, approximately 600 base pairs of 16S ribosomal RNA genes were amplified using polymerase chain reaction with universal primers, followed by the construction of clone libraries. The nucleotide sequences of 96 clones randomly chosen for each specimen were determined, and bacterial homology was searched. Conventional cultivation methods, including anaerobic cultures, were also performed using the same specimens. RESULTS: In addition to known common pathogens of community-acquired pneumonia [Streptococcus pneumoniae (18.8%), Haemophilus influenzae (18.8%), Mycoplasma pneumoniae (17.2%)], molecular analysis of specimens from 64 patients with community-acquired pneumonia showed relatively higher rates of anaerobes (15.6%) and oral bacteria (15.6%) than previous reports. CONCLUSION: Our findings suggest that anaerobes and oral bacteria are more frequently detected in patients with community-acquired pneumonia than previously believed. It is possible that these bacteria may play more important roles in community-acquired pneumonia.

Detection of MALT1 gene rearrangements in BAL fluid cells for the diagnosis of pulmonary mucosa-associated lymphoid tissue lymphoma.

BACKGROUND: Mucosa-associated lymphoid tissue (MALT) lymphoma constitutes approximately 90% of primary pulmonary lymphoma, and the diagnosis of pulmonary MALT lymphoma often requires invasive methods such as surgical lung biopsy. Chromosomal rearrangements involving MALT lymphoma translocation gene 1 (MALT1) have been reported to be specific for MALT lymphoma. The combination of BAL and cytologic approaches with molecular methods is useful for the diagnosis of lymphoproliferative disorders. Therefore, we examined the detection of MALT1 gene rearrangements in BAL fluid (BALF) cells for the diagnosis of MALT lymphoma. METHODS: We determined the percentage of BALF cells with MALT1 gene rearrangements by using the fluorescence in situ hybridization (FISH) method in 10 patients suspected to have pulmonary MALT lymphoma. RESULTS: MALT1 gene rearrangements in BALF cells were found in four of five cases with pulmonary MALT lymphoma (percentage of BALF cells with MALT1 gene rearrangements: 21.8% ± 6.8%). On the other hand, MALT1 gene rearrangements in BALF cells were negative in the five cases without pulmonary MALT lymphoma and one case with pulmonary MALT lymphoma. CONCLUSION: These results suggest that the detection of MALT1 gene rearrangements in BALF cells is useful for the diagnosis of pulmonary MALT lymphoma, as it is a specific method that is less invasive than surgical biopsy. Because of the small number of patients in this study, further investigations are necessary to evaluate the detection rate of MALT1 gene rearrangements in BALF cells from patients with pulmonary MALT lymphoma.

Two cases of primary ciliary dyskinesia with different responses to macrolide treatment.

We herein report two cases of primary ciliary dyskinesia (PCD) with different responses to macrolides. Case 1: a 17-year-old Japanese man with Pseudomonas aeruginosa infection and combined defect of both inner and outer dynein arms in the cilia was unsuccessfully treated with long-term macrolides (clarithromycin, erythromycin, and azithromycin). Case 2: a 70-year-old Japanese man with deficiency of only the inner dynein arm was successfully treated with clarithromycin. Though the reasons for the different responses to macrolides are unclear, differences of ultrastructural abnormalities of the cilia might be one of the predictive factors in PCD just as in Pseudomonas aeruginosa infection.

A case of successful treatment with polymyxin B-immobilized fiber column direct hemoperfusion in acute respiratory distress syndrome after influenza A infection.

We report a case of acute respiratory distress syndrome (ARDS) after influenza A infection who was successfully treated with combined treatment including direct hemoperfusion with polymyxin B-immobilized fiber (PMX-DHP) column. A 56-year-old Japanese man was admitted to our hospital in January 2010 because of progressive dyspnea, hypoxemia, fever and bilateral diffuse infiltration on chest radiograph after pandemic influenza A infection. His chest computed tomography showed diffuse and patchy bilateral ground-glass opacities, and we diagnosed ARDS after influenza A infection. The patient was successfully treated with PMX-DHP in addition to the treatment with oseltamivir, corticosteroid, sivelestat and antibiotics with mechanical ventilation, and the patient recovered with only minor pulmonary fibrotic change. Although the efficacy of PMX-DHP treatment in patients with acute lung injury (ALI)/ARDS after influenza virus infection is not well established, this treatment could be a possible therapeutic modality in treating the patients with this disease.