Takeharu Koga

Increased circulating 92 kDa matrix metalloproteinase (MMP-9) activity in exacerbations of asthma

Background: The 72 kDa matrix metalloproteinase 2 (MMP-2) and the 92 kDa matrix metalloproteinase 9 (MMP-9) are type IV collagenases implicated in various aspects of inflammation including accumulation of inflammatory cells, tissue injury, and development of remodelling. The role of these enzymes in the pathogenesis of asthma exacerbations is unknown. Methods: Circulating levels of MMP-2 and MMP-9 proteins and the expression of their inhibitor, tissue inhibitor of metalloproteinase 1 (TIMP-1), were measured in 21 patients experiencing an asthma exacerbation and 21 age matched patients with stable asthma. Circulating gelatinolytic activity was compared during the asthma exacerbation and during subsequent convalescence by gelatin zymography in the same individuals. In addition, MMP-9 specific activity was quantified with a colorimetric assay which uses an artificial proenzyme containing a specific domain recognised by MMP-9 in the same paired samples. Results: A significant increase in the circulating level of MMP-9 was seen in patients with an asthma exacerbation compared with patients with stable asthma (202.9 (22.0) v 107.7 (9.9) ng/ml, p=0.0003). There were no significant differences in the circulating levels of MMP-2 or TIMP-1. Gelatin zymography identified two major circulating gelatinolytic activities corresponding to MMP-2 and MMP-9, and showed that asthma exacerbations are characterised by markedly increased MMP-9 activity with no significant change in MMP-2 activity compared with the activities during convalescence in the same individuals. Direct measurement showed that MMP-9 specific activity is significantly increased during asthma exacerbations compared with subsequent convalescence (269.6 (31.7) v 170.4 (12.6) ng/ml, p=0.0099). Conclusions: Asthma exacerbations are characterised by increased circulating MMP-9 activity. This increased activity may be related to exaggerated airway inflammation and airway remodelling.

Chronic pulmonary scedosporiosis simulating aspergillosis

Abstract:  Scedosporium apiospermum, a ubiquitously distributed saprophyte, is emerging as an important pathogen in immunocompromised patients. We describe a 72‐year‐old patient with chronic S. apiospermum infection of the lung simulating aspergilloma. His medical history was unremarkable except that he had undergone partial lung resection as a treatment for pulmonary tuberculosis several decades previously. He had no underlying immunosuppressive conditions. This patient illustrates that pulmonary scedosporiosis is not confined to immunocompromised patients and that the clinical presentation may be indistinguishable from that of aspergilloma.

Giant cell interstitial pneumonia in two hard metal workers: The role of bronchoalveolar lavage in diagnosis

Two cases of hard metal lung disease and pathological findings of giant cell interstitial pneumonia are reported. The cases worked in different factories manufacturing hard metal parts from tungsten carbide and cobalt. Pathological specimens were obtained by percutaneous thoracoscopy and transbronchial lung biopsy. X‐ray microanalysis detected only tungsten carbide in the lung specimen of one case. Bronchoalveolar lavage showed diagnostic bizarre macrophages in the lavage fluid.

Determinants of bronchodilator responsiveness in patients with controlled asthma.

Short-term bronchodilator responsiveness to an inhaled β 2 adrenergic agonist was assessed by changes in forced expiratory volume in 1 second (FEV1) in nonsmoking adults with controlled asthma (mild disease, 20 patients; moderate disease, 20 patients; severe disease, 18 patients). Responsiveness correlated significantly with age and with percent of predicted FEV1 (%FEV1) except in patients with severe asthma, who showed significantly less responsiveness than others. Thus, responsiveness is closely associated with degree of airflow limitation in patients with controlled asthma and is significantly influenced by severity of disease and by aging.

Gordonia iterans sp. nov., isolated from a patient with pneumonia.

A second novel clinical actinobacterial strain, designated IFM 10348(T), was isolated from the sputum of the same Japanese patient with bacterial pneumonia from whom the type strain of Gordonia araii had been isolated. The strains differed in phylogenetic position and drug-resistance profiles. The taxonomic position of strain IFM 10348(T) was clarified by phenotypic, chemotaxonomic and phylogenetic studies. Phylogenetic analyses based on 16S rRNA gene sequences clearly demonstrated that strain IFM 10348(T) occupied a distinct clade within the genus Gordonia and was related closely to Gordonia malaquae DSM 45064(T) and Gordonia hirsuta DSM 44140(T) (97.3 and 97.1% similarities, respectively). Strain IFM 10348(T) was also clearly differentiated from G. malaquae DSM 45064(T) and G. hirsuta DSM 44140(T) based on gyrB and secA1 gene sequence similarity values. Strain IFM 10348(T) had MK-9(H2) as the predominant menaquonine, contained meso-diaminopimelic acid, arabinose, galactose and glucosamine as cell-wall components, and contained C18:1ω9c, summed feature 3 (C16:1ω7c and/or C16:1ω6c) and C16:0 as the major cellular fatty acids. Mycolic acids were present. The DNA G+C content of strain IFM 10348(T) was 68.0 mol%. DNA-DNA relatedness data coupled with the combination of genotypic and phenotypic data indicated that strain IFM 10348(T) represents a novel species of the genus Gordonia, for which the name Gordonia iterans sp. nov. is proposed. The type strain is IFM 10348(T) ( = CCTCC M2011245(T) = NCCB 100436(T)).

Dengue hemorrhagic fever in a Japanese traveler with pre-existing Japanese encephalitis virus antibody.

An adult Japanese man who had just returned from Thailand developed dengue hemorrhagic fever (DHF). A primary infection of dengue virus (DENV) was confirmed, specifically DENV serotype 2 (DENV-2), on the basis of the detection of the virus genome, a significant increase in the neutralizing antibody and the isolation of DENV-2. DHF is often observed following a secondary infection from another serotype of dengue virus, particularly in children, but this case was a primary infection of DENV. Japan is a non-endemic country for dengue disease. In fact, only Japanese encephalitis (JE) is known to be a member of the endemic flavivirus family. In this study, IgG antibody against Japanese encephalitis virus (JEV) was detected. JEV belongs to the family of dengue virus and prevails in Japan, particularly Kyushu. Among many risk factors for the occurrence of DHF, a plausible candidate could be a cross-reactive antibody-dependent enhancement (ADE) mechanism caused by JEV antibody. This indicates that most Japanese travelers who living in dengue non-endemic areas, particularly Kyushu, should be aware of the occurrence of DHF.

Effect of add-on therapy of tiotropium in COPD treated with theophylline

Background Although combination therapy with bronchodilators is recommended for chronic obstructive pulmonary disease (COPD), there is insufficient evidence for the efficacy of some combinations of long-acting bronchodilators. Objective We investigated the effects of a combination therapy with tiotropium and theophylline in COPD patients. Methods In a 12-week, open-labeled, parallel-group randomized study, pulmonary functions and dyspnea scores were compared between the combination and theophylline alone therapy at baseline, and 4 and 8 weeks after randomization in COPD. Results Sixty-one COPD patients completed the trial (31 combination therapy, 30 theophylline alone; mean age 70 years; 58 males; mean dyspnea score 2.0 and forced expiratory volume in one second (FEV1) 1.5 L [62.5% predicted]). FEV1 in the combination group, but not in the theophylline alone, was significantly increased at 4 (1.56 ± 0.13 L, p < 0.001) and 8 weeks (1.60 ± 0.13 L, p < 0.001) from the baseline (1.40 ± 0.12 L). In the combination group, but not the theophylline alone group, the dyspnea score was significantly improved after 4 (p < 0.01) and 8 weeks (p < 0.05) compared with baseline. In 17 patients who did not receive theophylline at screening, treatment with 4 or 8 weeks of theophylline alone did not improve dyspnea score or FEV1. Conclusion Addition of tiotropium therapy to theophylline treatment can improve dyspnea and pulmonary function in COPD. Although this study did not assess whether there was any benefit of adding theophylline to patients treated with tiotropium, tiotropium can be a useful addition in COPD already treated with theophylline.

Phase II Study of Irinotecan and Ifosfamide in Patients with Advanced Non-Small Cell Lung Cancer

Objectives: This phase II study was conducted to investigate the efficacy and safety of irinotecan (CPT-11) and ifosfamide as first-line chemotherapy for advanced non-small cell lung cancer (NSCLC). Methods: Eligibility criteria included histologically or cytologically confirmed NSCLC (stage IIIb or IV), no prior treatment, and measurable or evaluable disease. CPT-11 (80 mg/m2) was administered intravenously on days 1, 8, and 15, while ifosfamide (1.5 g/m2) was given on days 1 through 3 every 4 weeks. Results: Forty-four patients (31 men) with a median age of 65 years (range 43–75) and a median ECOG performance status of 1 (range 0–2) were enrolled. The response rate was 29.5% [95% CI: 16.7–45.2%], with 13 partial responses. The median survival was 12.5 months, the median time to progression was 5.3 months, and the 1 and 2-year survival rates were 52.3 and 11.3%, respectively. Toxicity was generally mild; WHO grade 3–4 neutropenia was recorded in 38.6% of the patients, grade 3 diarrhea in 6.8%, and grade 3–4 nausea/vomiting in 0%. Conclusions: CPT-11 combined with ifosfamide demonstrated anti-tumor activity in advanced NSCLC, with response and survival rates similar to those of cisplatin-based chemotherapy but with a more favorable toxicity profile.

Complex Cystic Lung Lesion Presenting in a 41-Year-Old Woman

A 41-year-old woman presented to the hospital because of a cough that had lasted for 10 days. The patient had been well until she noticed a sore throat 2 weeks previously and then started to cough. The sore throat subsided in a week. She did not smoke, did not regularly drink, and denied abuse of drugs. Her medical history included arrhythmia at the age of 33 years, for which she was taking medications, and myoma uteri, for which only check-ups were required, at 41 years of age. She was born normally and resided in the same area where she had been born. She was working as a veterinarian. Her familial history was not remarkable. Physical characteristics on examination were as follows: height, 161.5 cm; weight, 51.1 kg; body temperature, 36.7°C; pulse rate, 60 min; BP, 106 82 mm Hg; respiratory rate, 18 min; oxygen saturation, 98% while breathing room air. Oral cavity and neck were not remarkable. Percussion of the thorax revealed an increased resonance over the right lung, where breath sounds were diminished on auscultation. Heart sounds were not remarkable. Laboratory test results showed WBC, 5,300 m L; hemoglobin, 13.1 g dL; platelets, 191,000 m L; aspartate aminotransferase, 26 U L; alanine aminotransferase, 18 U L; BUN, Complex Cystic Lung Lesion Presenting in a 41-Year-Old Woman

Pulmonary vascular involvement in neoplastic angioendotheliosis.

Neoplastic angioendotheliosis has rarely been described as a respiratory disease. A patient is described with pulmonary vascular involvement induced by neoplastic angioendotheliosis in pulmonary vessels.