Takemasa Matsumoto

Nationwide surveillance of bacterial respiratory pathogens conducted by the Japanese Society of Chemotherapy in 2007: general view of the pathogens' antibacterial susceptibility.

For the purpose of nationwide surveillance of the antimicrobial susceptibility of bacterial respiratory pathogens collected from patients in Japan, the Japanese Society of Chemotherapy conducted a third year of nationwide surveillance during the period from January to April 2008. A total of 1,097 strains were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections. Susceptibility testing was evaluable with 987 strains (189 Staphylococcus aureus, 211 Streptococcus pneumoniae, 6 Streptococcus pyogenes, 187 Haemophilus influenzae, 106 Moraxella catarrhalis, 126 Klebsiella pneumoniae, and 162 Pseudomonas aeruginosa). A total of 44 antibacterial agents, including 26 β-lactams (four penicillins, three penicillins in combination with β-lactamase inhibitors, four oral cephems, eight parenteral cephems, one monobactam, five carbapenems, and one penem), three aminoglycosides, four macrolides (including a ketolide), one lincosamide, one tetracycline, two glycopeptides, six fluoroquinolones, and one oxazolidinone were used for the study. Analysis was conducted at the central reference laboratory according to the method recommended by the Clinical and Laboratory Standard Institute (CLSI). The incidence of methicillin-resistant S. aureus (MRSA) was as high as 59.8%, and those of penicillin-intermediate and penicillin-resistant S. pneumoniae (PISP and PRSP) were 35.5 and 11.8%, respectively. Among H. influenzae, 13.9% of them were found to be β-lactamase-non-producing ampicillin (ABPC)-intermediately resistant (BLNAI), 26.7% to be β-lactamase-non-producing ABPC-resistant (BLNAR), and 5.3% to be β-lactamase-producing ABPC-resistant (BLPAR) strains. A high frequency (76.5%) of β-lactamase-producing strains was suspected in Moraxella catarrhalis isolates. Four (3.2%) extended-spectrum β-lactamase-producing K. pneumoniae were found among 126 strains. Four isolates (2.5%) of P.aeruginosa were found to be metallo β-lactamase-producing strains, including three (1.9%) suspected multidrug-resistant strains showing resistance to imipenem, amikacin, and ciprofloxacin. Continual national surveillance of the antimicrobial susceptibility of respiratory pathogens is crucial in order to monitor changing patterns of susceptibility and to be able to update treatment recommendations on a regular basis.

Pleuroparenchymal fibroelastosis as a manifestation of chronic lung rejection

To the Editor: Idiopathic pleuroparenchymal fibroelastosis is a peculiar pulmonary fibrosis proposed by Frankel et al . [1] in 2003 and is almost the same concept as idiopathic pulmonary upper lobe fibrosis proposed by Amitani et al. [2]. There are no known causes for fibrosis in idiopathic pleuroparenchymal fibroelastosis. Sometimes, pleuroparenchymal fibroelastosis (PPFE) has underlying diseases or conditions, such as collagen vascular diseases, anti-cancer chemotherapy, irradiation, asbestos exposure and bone-marrow transplantation [3]. Herein, we report the case of a female who received living-donor lung transplantation and died of pulmonary fibrosis, which was pathologically compatible with PPFE in addition to constrictive bronchiolitis, which is a manifestation of chronic lung allograft dysfunction (CLAD) [4]. A 30-yr-old female suffering from idiopathic pulmonary arterial hypertension underwent living-donor lung transplantation surgery and received a right lower lobe from her younger sister and a left lower lobe from her mother in December 2003. 20 months after the lung transplantation she had dyspnoea and a chest radiograph disclosed bilateral ground-glass shadows. 1 month later, right open lung biopsy was performed and a diagnosis of interstitial pneumonia was obtained. Pulse therapy with methylprednisolone slightly improved her condition and prednisolone was administered after the pulse therapy. However, bilateral interstitial opacities gradually deteriorated (fig. 1) with increased dyspnoea. 49 months after the lung transplantation, her daily life had worsened to almost whole-day bed rest. 18 days prior to her death she …

Impaired host defence against Mycobacterium avium in mice with chronic granulomatous disease

Patients with chronic granulomatous disease (CGD), an inherited disorder of phagocytic cells, often contract recurrent life‐threatening bacterial and fungal infections. CGD is considered to arise from a functional defect of the O2‐generating nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in phagocytes. To determine whether or not NADPH oxidase is crucial to the host defence against Mycobacterium avium, we investigated the response against M. avium using CGD model mice (gp91‐phox‐) of C57BL/6 strain. A tracheal injection of 1 × 107 colony‐forming units (CFU)/head of M. avium strain FN into the CGD mice resulted in a pulmonary infection, while also increasing the mortality rate. In contrast, normal C57BL/6 mice injected with same dose of the organisms did not develop severe pulmonary infection and were able to survive through 2 months of observation. The macrophages obtained from the CGD mice were observed to have a higher burden of the bacterial growth than macrophages from normal C57BL/6 mice. These results suggest that the defect of the NADPH oxidase function impairs the host defence against M. avium infection.

Efficacy of aprepitant in patients with advanced or recurrent lung cancer receiving moderately emetogenic chemotherapy

AIMS AND BACKGROUND To evaluate the efficacy of a combination of aprepitant and conventional antiemetic therapy in patients with advanced or recurrent lung cancer receiving moderately emetogenic chemotherapy (MEC). METHODS Patients with advanced or recurrent lung cancer who were treated with MEC regimens at the Department of Respiratory Medicine, Fukuoka University Hospital, were included and classified into the following groups: control group (treatment: 5-HT3 receptor antagonists + dexamethasone) and aprepitant group (treatment: 5-HT3 receptor antagonists + dexamethasone + aprepitant). The presence or absence of chemotherapy-induced nausea and vomiting (CINV) was evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0; patients with grade 1 or above were considered positive for CINV. Food intake per day, completion of planned chemotherapy, and progression-free survival (PFS) achieved by chemotherapy were investigated. RESULTS The complete suppression rate of nausea in the aprepitant group was significantly higher than that in the control group (p = 0.0043). Throughout the study, the food intake in the aprepitant group was greater than that in the control group, with the rate being significantly higher, in particular, on day 5 (p = 0.003). The completion rate of planned chemotherapy was also higher in the aprepitant group (p = 0.042). PFS did not differ significantly, but tended to be improved in the aprepitant group. CONCLUSIONS The aprepitant group showed significantly higher complete suppression of nausea, food intake on day 5, and completion of planned chemotherapy than the control group.

Histological findings of the computed tomography halo in pulmonary sarcoidosis

In 1974, Sahn et al. 1 described a patient with sarcoidosis who presented with a fine acinar rosette pattern of infiltrate on chest radiograph and alveolar filling with mononuclear cells in the biopsied specimen. In 1978, Shigematsu et al. 2 reported the presence of noncaseating epithelioid granulomas in the alveolar spaces in patients with radiographic findings similar to the previous report. They considered these lesions to represent the early stage of sarcoidosis. Although there seems to be no definite relationship between the stage of sarcoidosis and the anatomical extent of the granulomas, sarcoid granulomas in the alveoli are rarely found. Nowadays, in the era of high-resolution computed tomography (HRCT), ground-glass attenuations are sometimes found in sarcoidosis that could fit the “acinar pattern” proposed by Sahn et al. 1 and Shigematsu et al. 2. In 2004, Marten et al. 3 described the presence of ground-glass attenuation around solid nodules, the halo sign, on computed tomography (CT) of a patient with sarcoidosis. Herein, we report a case of sarcoidosis presenting a CT halo sign that was surgically biopsied. The pathological/radiological correlation of sarcoidosis with the halo sign is discussed. A 69-yr-old female noticed general fatigue. She had a past history of left lower lobectomy due to adenocarcinoma of the lung 8 yrs prior to admission. She was admitted to our hospital (Fukuoka University School of Medicine, Fukuoka, Japan) …

Critical role of tumor necrosis factor receptor 1 in the pathogenesis of pulmonary emphysema in mice

COPD is a major cause of chronic morbidity and mortality throughout the world. Although tumor necrosis factor-α (TNF-α) has a critical role in the development of COPD, the role of different TNF receptors (TNFRs) in pulmonary emphysema has not been resolved. We aimed to clarify the role of TNFRs in the development of pulmonary emphysema. TNF-α transgenic mice, a murine model of COPD in which the mice spontaneously develop emphysema with a large increase in lung volume and pulmonary hypertension, were crossed with either TNFR1-deficient mice or TNFR2-deficient mice. After 6 months, the gross appearance of the lung, lung histology, and pulmonary and cardiac physiology were determined. In addition, the relationship between apoptosis and emphysema was investigated. Pulmonary emphysema-like changes disappeared with deletion of TNFR1. However, slight improvements were attained with deletion of TNFR2. Apoptotic cells in the interstitium of the lung were observed in TNF-α transgenic mice. The apoptotic signals through TNFR1 appear critical for the pathogenesis of pulmonary emphysema. In contrast, the inflammatory process has a less important role for the development of emphysema.

Chronic Pseudomonas aeruginosa infection-induced chronic bronchitis and emphysematous changes in CCSP-deficient mice.

The club cell secretory protein (CCSP) is a regulator of lung inflammation following acute respiratory infection or lung injury. Recently, the relationship between CCSP and COPD has been reported. Since COPD results from an abnormal inflammatory response, we hypothesized that CCSP could have a protective role against chronic inflammation-induced lung damage. To address this issue, the pathophysiology of chronic lung inflammation induced by Pseudomonas aeruginosa in CCSP-deficient mice was determined. A tube of 5 mm in length was soaked in a fluid containing P. aeruginosa (PAO01 strain) for 1 week and inserted into the trachea of CCSP-deficient mice. One week later, P. aeruginosa was administered into the trachea. Five weeks after insertion of tube, the mice were sacrificed. Bronchoalveolar lavage fluids were collected to determine the bacterial growth, and the lung histology and physiology were also examined. P. aeruginosa was continuously detected in bronchoalveolar lavage fluids during the study. Neutrophils were increased in the bronchoalveolar lavage fluids from the CCSP-deficient mice in comparison to wild-type mice. A histological study demonstrated chronic inflammation around bronchus, serious bronchial stenosis, and alveolar enlargement in the CCSP-deficient mice. The lung physiology study demonstrated an increase in the lung compliance of the CCSP-deficient mice. Chronic P. aeruginosa inflammation resulted in chronic bronchitis and emphysematous changes in the CCSP-deficient mice. CCSP could play an important role in protecting the host from the chronic inflammation-induced lung damage.

Adenoid Cystic Carcinoma of the Lung with an EGFR Mutation.

An 80-year-old woman was referred to our hospital due to the presence of a mass that was identified on a chest X-ray. A further investigation demonstrated advanced adenoid cystic carcinoma of the lungs. Anti-cancer chemotherapy with docetaxel was carried out and the lesion remained as stable disease. Subsequently, pleural effusion was detected, and an investigation of the pleural effusion revealed the existence of malignant cells with an epidermal growth factor (EGFR) mutation. Gefitinib was administered and the pleural effusion resolved. This is the first case of a positive EGFR mutation of adenoid cystic carcinoma of the lung with a favorable response to an EGFR-tyrosine kinase inhibitor.

Treatment outcome of the two-part semi-rigid oral appliance in obstructive sleep apnea

Abstract Aim The aim of this study was to assess the effectiveness of the two-part semi-rigid oral appliance, Silensor ® (Erkodent, Tuttlingen, Germany) which prevents the mandible from retracting during mouth opening. Materials and methods Ten patients with mild or moderate obstructive sleep apnea (2 males and 8 females; mean age=62.5±10.0 years) were recruited and lateral cephalometric radiographs were taken. The patients underwent polysomnography before and after 3 months of receiving treatment with the Silensor ® . The relationship between the improvement in the polysomnographic variables after the therapy and the cephalometric features was analyzed. Results A significant difference was observed in the apnea–hypopnea index after 3 months of Silensor ® therapy (1st (baseline), 17.1±5.5; 2nd (therapy of Silensor ® ), 11.0±7.2, p =0.011). Furthermore there was a significant positive correlation between the improvement in the degree of slow wave sleep (%) and the mandibular plane angle ( R =0.662, p =0.037), as well as between the improvement in degree of slow wave sleep (%) and the lower face height ( R =0.845, p =0.002). A significant negative correlation was observed between the improvement in degree of sleep efficiency (%) and the soft palate area ( R =−0.809, p =0.005). Conclusion These results suggested that keeping the nasopharyngeal airway space during mouth opening improves apnea–hypopnea index of some patients with mild or moderate obstructive sleep apnea and quality of sleep in obstructive sleep apnea patients with a long lower face height and a small soft palate.

Doxycycline Attenuated Mycobacterium avium Induced Inflammation in Mice

Mycobacterium avium causes chronic and progressive respiratory infection. A therapeutic regimen including clarithromycin, rifampin and ethambutol has been commonly employed, however, the effect of such antibacterial therapy is often unsatisfactory. Doxycycline is an antibiotic known to have immuno-modulating effects as well as antibacterial activity. In this study, we investigated the effect of doxycycline administration on M. avium infection in mice. The administration of doxycycline attenuated lung inflammation caused by M. avium according to the results from a histology analysis and the number of inflammatory cells from BAL fluids. Moreover, doxycycline improved the survival rate in TNF-R1 KO mice infected with M. avium. However, doxycycline did not affect the colony number of M. avium in the lungs. These results suggest that doxycycline may have protective effects against M. avium induced inflammation in mice. The effects of doxycycline may be due to its biological effect apart from its antimicrobial function.