Search

A 66-year-old woman rheumatoid arthritis was treated with methotrexate and tocilizumab. Chest radiography revealed bilateral consolidation of an upper lesion in the lung. Laboratory data indicated a hepatic disorder and increased eosinophils. Transbronchial lung biopsy specimens showed organizing pneumonia. Infection was unfavorable based on culture and PCR. Drug lymphocyte stimulation test showed positive results both for methotrexate and tocilizumab. We were concerned that her pneumonitis was drug-induced. And the symptoms appeared after the infusion of tocilizumab. Here, we report a case of tocilizumab-induced organizing pneumonia.

The present study was designed to prospectively evaluate the clinical efficacy of gefitinib readministration in patients with advanced non-small cell lung cancer who responded well to initial gefitinib, followed by cytotoxic chemotherapy. Twenty subjects were enrolled, and 3 and 6 patients achieved partial response and stable disease, respectively. These findings provide valuable information for the management of previous gefitinib responders. Introduction: Salvage treatment for acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitor in patients with non-small-cell lung cancer is a matter of clinical concern. Several retrospective reports have indicated the usefulness of epidermal growth factor receptor tyrosine kinase inhibitor readministration; however, there have been few prospective studies. Materials and Methods: This study was designed to prospectively evaluate the clinical efficacy of gefitinib readministration in patients with advanced or metastatic non-small-cell lung cancer who responded well to initial gefitinib treatment. The subjects received at least 1 regimen of cytotoxic chemotherapy after progressive disease with the initial gefitinib therapy. Gefitinib administration (250 mg/d, orally) was started after progressive disease with the previous chemotherapeutic regimen. The primary endpoint in the present study was the response rate. Results: Twenty patients were enrolled between April 2007 and May 2011. Three patients achieved partial response, and 6 showed stable disease. Thus, the overall response rate and disease control rate of gefitinib readministration were 15% (95% Cl, 3.21-37.9) and 45% (95% Cl, 23.1-68.5), respectively. Median progression-free survival and overall survival from the start of gefitinib readministration were 2.0 months (95% Cl, 0.9-3.1 months) and 12.0 months (95% Cl, 8.0-16.0 months), respectively. Conclusion: These results suggest that gefitinib readministration may be an option, albeit with a low res

A 43-year-old-man was diagnosed as having primary mediastinal nonseminomatous germ cell tumor based on pericutaneous biopsy and an elevated serum concentration of alpha-fetoprotein (AFP). Although AFP decreased after chemotherapy, the mass size grew and developed tracheal compression by the tumor. The patient was treated with mechanical ventilation and subsequent stent implantation for keeping airway patency. After three cycles of chemotherapy and normalization of AFP, the increased mass was successfully resected and the pathological examination demonstrated a mature teratoma. This case showed a rare clinical manifestation of mediastinal growing teratoma syndrome and successful outcome by multimodal therapies.

Sherpas comprise a population of Tibetan ancestry in the Himalayan region that is renowned for its mountaineering prowess. The very small amount of available genetic information for Sherpas is insufficient to explain their physiological ability to adapt to high-altitude hypoxia. Recent genetic evidence has indicated that natural selection on the endothelial PAS domain protein 1 (EPAS1) gene was occurred in the Tibetan population during their occupation in the Tibetan Plateau for millennia. Tibetan-specific variations in EPAS1 may regulate the physiological responses to high-altitude hypoxia via a hypoxia-inducible transcription factor pathway. We examined three significant tag single-nucleotide polymorphisms (SNPs, rs13419896, rs4953354, and rs4953388) in the EPAS1 gene in Sherpas, and compared these variants with Tibetan highlanders on the Tibetan Plateau as well as with non-Sherpa lowlanders. We found that Sherpas and Tibetans on the Tibetan Plateau exhibit similar patterns in three EPAS1 significant tag SNPs, but these patterns are the reverse of those in non-Sherpa lowlanders. The three SNPs were in strong linkage in Sherpas, but in weak linkage in non-Sherpas. Importantly, the haplotype structured by the Sherpa-dominant alleles was present in Sherpas but rarely present in non-Sherpas. Surprisingly, the average level of serum erythropoietin in Sherpas at 3440 m was equal to that in non-Sherpas at 1300 m, indicating a resistant response of erythropoietin to high-altitude hypoxia in Sherpas. These observations strongly suggest that EPAS1 is under selection for adaptation to the high-altitude life of Tibetan populations, including Sherpas. Understanding of the mechanism of hypoxia tolerance in Tibetans is expected to provide lights to the therapeutic solutions of some hypoxia-related human diseases, such as cardiovascular disease and cancer.

Although rare, gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. The asynchronous occurrence of other malignancies in patients with GIST during the clinical course is relatively common. However, the synchronous coexistence of GIST and lung cancer has only rarely been reported. We experienced a case of coincidental primary lung adenocarcinoma and intestinal GIST. The present case is not only of interest due to the rare coincidence of GIST and lung cancer, but also because there was an epidermal growth factor receptor gene mutation in the lung cancer and a c-kit mutation in the GIST.

The present study was designed to evaluate inflammatory changes in collapsed lungs during one-lung ventilation using the assistance of a bronchoscopic microsampling probe. Serial albumin and interleukin (IL)-8 concentrations in epithelial lining fluid (ELF) were measured in seven patients undergoing resection of lung tumors. The samples were taken after induction of anesthesia (baseline), 30 min after one-lung ventilation was started (point 2), just before resuming two-lung ventilation (point 3), and 30 min after two-lung ventilation was restarted (point 4). The albumin and IL-8 concentrations in ELF were significantly increased at point 2 and point 3, respectively, and remained to be high, compared to the baseline. The increase in IL-8 at point 3 was correlated with the interval of one-lung ventilation; however, none developed specific acute lung injury. These findings suggest that inflammatory changes can occur on the epithelium of a collapsed lung even in patients who underwent successful and standard thoracic surgery.

A 66-year-old man was diagnosed with autoimmune pancreatitis in February 2009 and started 40 mg of oral prednisolone followed by a maintenance dose of 5 mg daily. The patient developed a cough in October 2010 and visited our division. He had a high serum concentration of immunoglobulin (Ig) G4 and his chest computed tomography showed airway stenosis without bilateral hilar lymphadenopathy (BHL). The bronchial biopsy specimens revealed lymphoplasmacytic infiltrations with IgG4-positive/IgG-positive plasma cells of more than 50%. Thus, we diagnosed the airway lesion with IgG4-related airway involvement. This is the first report of a patient with IgG4-related airway involvement without BHL.

The present study was performed to compare the effects of high frequency oscillatory ventilation (HFOV) with conventional mechanical ventilation (CMV) on pulmonary inflammatory responses in a rat acid-induced lung injury model. Anesthetized rats were instilled intratracheally with HCl (0.1 N, 2 mL/kg) and then randomly divided into three mechanical ventilation settings: HFOV (an oscillatory frequency of 15 Hz, mean airway pressure (MAP) of 9 cmH(2)O), CMV at tidal volume of 12 and 6 mL/kg for 5 h. After HCl instillation, HFOV significantly attenuated the increases in neutrophil infiltration and TNF-alpha concentration in bronchoalveolar lavage fluid compared with the CMV groups. During HFOV, there was an inhibition of an increase in TNF-alpha mRNA expression and a decrease in SP-A mRNA expression induced by acid instillation. This animal study demonstrates that HFOV is a suitable form of mechanical ventilation to prevent inflammatory responses in acid-induced lung injury.

Yoshiaki Kitaguchi1,*, Yoshimichi Komatsu1,*, Keisaku Fujimoto2, Masayuki Hanaoka1, Keishi Kubo1 1First Department of Internal Medicine, Shinshu University School of Medicine, 2Department of Biomedical Laboratory Sciences, Shinshu University School of Health Sciences, Matsumoto, Japan *These authors contributed equally to this workBackground: Chronic obstructive pulmonary disease (COPD) and asthma may overlap and converge in older people (overlap syndrome). It was hypothesized that patients with overlap syndrome may have different clinical characteristics such as sputum eosinophilia, and better responsiveness to treatment with inhaled corticosteroid (ICS).Methods: Sixty-three patients with stable COPD (forced expiratory volume in 1 second [FEV1] ≤80%) underwent pulmonary function tests, including reversibility of airflow limitation, arterial blood gas analysis, analysis of inflammatory cells in induced sputum, and chest high-resolution computed tomography. The inclusion criteria for COPD patients with asthmatic symptoms included having asthmatic symptoms such as episodic breathlessness, wheezing, cough, and chest tightness worsening at night or in the early morning (COPD with asthma group). The clinical features of COPD patients with asthmatic symptoms were compared with those of COPD patients without asthmatic symptoms (COPD without asthma group).Results: The increases in FEV1 in response to treatment with ICS were significantly higher in the COPD with asthma group. The peripheral eosinophil counts and sputum eosinophil counts were significantly higher. The prevalence of patients with bronchial wall thickening on chest high-resolution computed tomography was significantly higher. A significant correlation was observed between the increases in FEV1 in response to treatment with ICS and sputum eosinophil counts, and between the increases in FEV1 in response to treatment with ICS and the grade of bronchial wall thickening. Receiver operating characteristic curv

Objective The purpose of this study was to clarify the differences in physiological properties of the airways between asthma and COPD using an impulse oscillation system (IOS). Patients and Methods Subjects comprised 95 stable COPD patients, 52 never-smoker asthma patients and 29 healthy never-smokers > 60 years old, all matched for age, in whom respiratory impedance was examined by IOS. Results In both asthma and COPD patients, a significant increase in respiratory resistance (Rrs5) and more negative value of respiratory reactance (Xrs5) at 5 Hz of oscillatory frequency with an increase in resonant frequency (fres) were observed when compared with healthy never-smokers. In asthma, a significant increase in respiratory resistance at 20 Hz (Rrs20) was also observed when compared with healthy never-smokers and COPD. The increases in Rrs5 and relative changes of Xrs5 to more negative were remarkable with increasing severity of COPD. On the other hand, among patients with asthma, these changes in Rrs5 and Xrs5 were also observed in asthmatics with normal FEV1/FVC. Interestingly, Xrs5 showed further changes to more negative in expiration of tidal breath in severe COPD, whereas no significant changes in Xrs5 to more negative in expiration was observed in healthy never-smokers and asthmatics with and without normal FEV1/FVC. Conclusion IOS may be useful for detecting pathophysiological changes of respiratory system in accordance with severity of COPD and even in asthmatics with normal FEV1/FVC. The larger within-breath changes of Xrs5 to more negative in severe COPD may represent easy collapsibility of small airways in expiration of tidal breath. These properties may help to analyze airway mechanics and to identify abnormalities of the airways that cannot be found by spirometry alone.

Background and objective: Patients with combined pulmonary fibrosis and emphysema (CPFE) are sometimes seen, and we speculate that these patients have some different clinical characteristics from COPD patients. This study clarifies the clinical characteristics of CPFE patients. Methods: This was a retrospective study of 47 stable patients with concurrent emphysema and diffuse parenchymal lung disease with fibrosis, based on the findings of chest CT (CPFE patients). The clinical characteristics of CPFE patients were compared with those of emphysema-dominant COPD patients without parenchymal lung disease (COPD patients). Results: Forty-six of the 47 CPFE patients were male. Paraseptal emphysema was particularly common in the CPFE group. Honeycombing, ground-glass opacities and reticular opacities were present in 75.6%, 62.2% and 84.4% of CPFE patients, respectively. Twenty-two of the 47 CPFE patients (46.8%) had lung cancer. Pulmonary function tests showed that the CPFE group had milder airflow limitation and lower diffusing capacity than the COPD group. Desaturation during 6-min walking test in CPFE patients tended to be more severe than in COPD patients, if the level of FEV1 or 6MWD was equal. Conclusions: CPFE patients had some different clinical characteristics in comparison with COPD patients and may also have a high prevalence of lung cancer., The definitive version is available at www.blackwell-synergy.com

The present study was performed to investigate the role of exogenous surfactant on hydrochloric acid (HCL) - induced lung injury in rats. Six-week-old male Sprague-Dawley rats were anesthetized by intraperitoneal injection of pentobarbital sodium (40 mg/kg) and HCL (0.1 N, 2 mL/kg) or normal saline (NS, 2 mL/kg) was instilled into the trachea. Thirty minutes after HCL instillation, surfactant at a dose of 60 mg (=2 mL)/body or NS (2 mL) was instilled into the rat lungs. Animals in another experimental group were also treated with the same dose of surfactant supplement 2 hours after the first administration. Bronchoalveolar lavage fluid (BALF) was obtained 5 hours after HCL instillation. In BALF, increases in total nuclear cell counts, neutrophil counts, optical density at 412 nm as an indicator Of Pulmonary hemorrhage, neutrophil elastase activity, concentrations of albumin and cytokine-induced neutrophil chemoattractant (CINC) induced by HCL instillation were significantly attenuated by surfactant treatment. The wet-to-dry weight (W/D) ratio in the lung and partial oxygen tension (P-O2) were also estimated; surfactant treatment significantly attenuated the W/D ratio and improved deteriorated P-O2 induced by HCL Additional surfactant supplementation did not show further beneficial effects on HCL-induced lung injury compared with a single treatment. These results suggest that surfactant shows an anti-inflammatory effect on acid lung injury in rats but the beneficial effects may be dose limited.

Here, we describe a case of colonic sarcoidosis that developed over a 7-year period of observation of intrathoracic sarcoidosis. The patient was asymptomatic, but colonoscopy showed multiple elevated lesions mimicking submucosal tumors in several areas of the colon. The specimens obtained by biopsy showed non-caseating granuloma, suggesting sarcoidosis. The observations in the present case indicate that colonic involvement should be considered in patients with sarcoidosis. Furthermore, the macroscopic appearance of multiple submucosal tumor-like lesions in colonic sarcoidosis is extremely rare.

The present study was designed to examine the combined effects of a synthetic protease inhibitor, gabexate mesilate, with a specific neutrophil elastase inhibitor, sivelestat sodium, on acid-induced lung injury. Adult male Sprague-Dawley rats weighing 300-350 g were anaesthetised intraperitoneally with pentobarbitone sodium and the right jugular vein was cannulated. Following tracheostomy, rats were ventilated mechanically and underwent intratracheal instillation of hydrochloric acid (HCl, 0.1 N 1.5 ml/kg) or normal saline. Gabexate mesilate (10 mg/kg, i.p.) and/or sivelestat sodium (10 mg/kg/h, i.v.) were administered 30 min before HCl instillation. Bronchoalveolar lavage fluid samples were obtained 5 h after HCl instillation. in bronchoalveolar lavage fluid, the HCl-induced increases in total nucleated cell counts, neutrophil counts, optical density at 412 nm as an index of pulmonary haemorrhage, concentrations of albumin and cytokine-induced neutrophil chemoattractant (CINC) were significantly attenuated by either gabexate mesilate or sivelestat sodium treatment. Gabexate mesilate or sivelestat sodium treatment also significantly attenuated the wet to dry weight ratio induced by HCl. However, combined treatment with both gabexate mesilate and sivelestat sodium did not show additive effects on HO-induced lung injury, compared with single treatments. These findings suggested that gabexate mesilate and sivelestat sodium each exhibited protective effects on acid-induced lung injury, but that synergistic effects of both agents are limited in this acid-induced lung injury model.

Keisaku Fujimoto1, Yoshiaki Kitaguchi2, Shintaro Kanda2, Kazuhisa Urushihata2, Masayuki Hanaoka2, Keishi Kubo21Department of Biomedical Laboratory Sciences, 2First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Nagano, JapanBackground: The purpose of this study was to clarify the association between morphological phenotypes according to the predominance of emphysema and efficacy of long-acting muscarinic antagonist and β2 agonist bronchodilators in patients with chronic obstructive pulmonary disease (COPD).Methods: Seventy-two patients with stable COPD treated with tiotropium (n = 41) or salmeterol (n = 31) were evaluated for pulmonary function, dynamic hyperinflation following metronome-paced incremental hyperventilation, six-minute walking distance, and St George’s Respiratory Questionnaire (SGRQ) before and 2–3 months following treatment with tiotropium or salmeterol. They were then visually divided into an emphysema dominant phenotype (n = 25 in the tiotropium-treated group and n = 22 in the salmeterol-treated group) and an emphysema nondominant phenotype on high-resolution computed tomography, and the efficacy of the two drugs in each phenotype was retrospectively analyzed.Results: Tiotropium significantly improved airflow limitation, oxygenation, and respiratory impedance in both the emphysema dominant and emphysema nondominant phenotypes, and improved dynamic hyperinflation, exercise capacity, and SGRQ in the emphysema dominant phenotype but not in the emphysema nondominant phenotype. Salmeterol significantly improved total score for SGRQ in the emphysema phenotype, but no significant effects on other parameters were found for either of the phenotypes.Conclusion: These findings suggest that tiotropium is more effective than salmeterol for airflow limitation regardless of emphysema dominance, and also can improve dynamic hyperinflation in the emphysema dominant phenotype, which results in further