Background: In 2007, the American Thoracic Society (ATS) and Infectious Disease Society of America (IDSA) published new diagnostic guidelines for nontuberculous mycobacterial (NTM) disease. Bacteriological criteria have become simpler compared to the 1997 ATS diagnostic criteria. Objective: For assessing the impact of the 2007 ATS/IDSA diagnostic criteria, we compared the diagnosis rate and time to diagnosis of NTM lung disease using the 1997 and 2007 ATS guidelines. Methods: Sixty-four patients who had excreted Mycobacterium intracellulare, M. avium, M. abscessus or M. kansasii at least one time in their respiratory specimens at Chonnam National University Hospital were reviewed. The 1997 ATS and 2007 ATS/IDSA guidelines were applied to these patients. Results: Thirty-seven of 64 patients (57.8%) were diagnosed with NTM lung disease by the 1997 ATS criteria. When the 2007 ATS/IDSA criteria were applied, 6 patients were newly diagnosed with NTM lung disease. The diagnosis rate significantly increased from 57.8 to 67.2% (p < 0.001). The time to diagnosis in the 1997 ATS and 2007 ATS/IDSA guidelines was 46.4 ± 53.0 and 36.2 ± 38.5 days, respectively (p = 0.002). Conclusion: These data suggest that we can shorten the time to diagnose NTM lung disease and diagnose more simply by using the 2007 ATS/IDSA guidelines. Further study will be needed to assess that these changes affect the management of NTM disease.

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Introduction: EGFR-TIKs showed about twenty percent of response rate in refractory non-small cell lung cancer. Clinical trials of cytotoxic drugs and EGFR-TIKs failed to show improved survival compared to platinum based doublets. An antagonism between EGFR-TKIs and cytotoxic chemotherapy drugs was raised as a possible explanation for the negative results. Materials and Methods: The antiproliferative effects and cell cycle distributions after treatments with EGFR-TKIs(gefitinib and erlotinib) and cytotoxic drugs(Docetaxel, Paclitaxel, Gemcitabine) were studied using a cell line(NCI-H1975, adenocarcinoma of lung) harboring T790M mutation in exon 20 of EGFR gene. The cell viability assay and cell cycle analysis were performed with MTT assay and flow cytometry. EGFR-TKIs and cytotoxic drugs were treated in different sequences to observe sequence dependent effect. Calcusyn software(Biosoft, Cambridge, UK) was used to calculate combination index(CI). Results: Various combinations of cytotoxic drugs and EGFR-TKIs showed different antiproliferative effects on NCI-H1975 cell line. Antagonisms(CI>1) were observed when EGFR-TKIs were treated before cytotoxic drugs(EC sequence), while synergisms(CI<1) were observed when cytotoxic drugs were pre-treated before EGFR-TKIs(CE sequence). Treatment in EC sequence arrested the cells in G0/G1 phase and decreased the apoptotic fraction. However, treatment in CE sequence arrested the cells in G2/M phase and higher fractions of apoptotic cell death were observed. Conclusion:To combine EGFR-TKIs and cytotoxic drugs, sequence dependent anti-proliferative effects should be considered.

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patients were treated with gefitinib 250 mg/day orally until disease progression. The primary endpoint was response rate. The secondary endpoints were disease control rate, overall survival, progression-free survival, and toxicity. Results: Thirty-one patients were enrolled in this study from December 2004 to December 2005. One patient was ineligible because of IIIA disease. Of the 30 eligible patients, the median age was 78.5 years, 16 patients were female, and 14 patients had no smoking history. We observed no CR, 7 PR, 8 SD, 13 PD, and 2 NE (unconfirmed extramurally). The response rate was 23% and the disease control rate was 50%. The median overall survival was 11.9 months and the median progression-free survival was 3.2 months. In never-smokers, the response rate was 43%, the disease control rate was 57%, the median overall survival was 15.0 months, and the median progression-free survival was 7.1 months. The common grade 3 to 4 toxicities were rash (7%), diarrhea (3%), anorexia (7%), fatigue (3%), AST (7%), and ALT (7%). We encountered one acute myocardial infarction (grade 4) that was considered as therapy-unrelated. There was no interstitial lung disease and no treatment-related death. Conclusions: Single-agent gefitinib is active and well tolerated in chemotherapy-naïve elderly patients with lung adenocarcinoma. Gefitinib may become a new standard treatment characterized by less toxicity, especially in never-smokers. Further investigation is warranted in Asia.