Hee-Jung Ban

Differences in classification of COPD group using COPD assessment test (CAT) or modified Medical Research Council (mMRC) dyspnea scores: a cross-sectional analyses

BackgroundThe GOLD 2011 document proposed a new classification system for COPD combining symptom assessment by COPD assessment test (CAT) or modified Medical Research Council (mMRC) dyspnea scores, and exacerbation risk. We postulated that classification of COPD would be different by the symptom scale; CAT vs mMRC.MethodsOutpatients with COPD were enrolled from January to June in 2012. The patients were categorized into A, B, C, and D according to the GOLD 2011; patients were categorized twice with mMRC and CAT score for symptom assessment, respectively. Additionally, correlations between mMRC scores and each item of CAT scores were analyzed.ResultsClassification of 257 patients using the CAT score vs mMRC scale was as follows. By using CAT score, 60 (23.3%) patients were assigned to group A, 55 (21.4%) to group B, 21 (8.2%) to group C, and 121 (47.1%) to group D. On the basis of the mMRC scale, 97 (37.7%) patients were assigned to group A, 18 (7.0%) to group B, 62 (24.1%) to group C, and 80 (31.1%) to group D. The kappa of agreement for the GOLD groups classified by CAT and mMRC was 0.510. The mMRC score displayed a wide range of correlation with each CAT item (r = 0.290 for sputum item to r = 0.731 for dyspnea item, p < 0.001).ConclusionsThe classification of COPD produced by the mMRC or CAT score was not identical. Care should be taken when stratifying COPD patients with one symptom scale versus another according to the GOLD 2011 document.

Retreatment of gefitinib in patients with non-small-cell lung cancer who previously controlled to gefitinib: a single-arm, open-label, phase II study.

Most patients with non-small-cell lung cancer (NSCLC) who initially respond to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) eventually experience progression of disease. Based on previous trials which showed second response after switching to another EGFR-TKI, we hypothesized that the reintroduction of gefitinib would lead to disease control rate (DCR) in more than 30% of patients. This was a single-arm, open-label, prospective, phase II trial of gefitinib for the treatment of advanced or metastatic NSCLC. Eligible patients had previously responded to, or had experienced disease stabilization with, initial gefitinib treatment for at least 3 months. Prior to retreatment, progressive disease (PD) should be observed, with at least one cytotoxic treatment following initial gefitinib failure. Twenty-three patients were recruited and defined as the intention to treat (ITT) group. Most of the enrolled patients were female (86.9%), never-smokers (91.3%), and adenocarcinoma patients (95.7%). Responses to initial gefitinib were partial response (PR) in 10 cases (43.5%) and stable disease (SD) in 13 cases (56.5%). PR and DCR were observed in 21.7% (5 patients) and 65.2% (15 patients) in the ITT group. Among 14 DNA samples, 13 cases had either exon 19 deletion or L858R point mutation, whereas one patient evidenced the wild-type EGFR gene. Re-initiation of EGFR-TKI can be considered as an option after failure of chemotherapy for those patients who previously controlled to EGFR-TKI treatment.

Plasma proGRP Concentration is Sensitive and Specific for Discriminating Small Cell Lung Cancer from Nonmalignant Conditions or Non-small Cell Lung Cancer

To date, most clinical data on pro-gastrin-releasing peptide (proGRP) have been based on serum concentrations. This study evaluated the agreement between proGRP levels in fresh serum and plasma in patients with various lung diseases. Pairs of serum and EDTA plasma were collected from 49 healthy individuals. At the same time, EDTA plasma of 118 lung cancer patients and 23 patients with benign pulmonary diseases were prospectively collected. Compared to serum, plasma proGRP concentrations were higher by an average of 103.3%. Plasma proGRP was higher in malignancy (336.4 ± 925.4 pg/mL) than in benign conditions (40.1 ± 11.5 pg/mL). Small cell lung cancer (SCLC) patients showed higher levels of proGRP (1,256.3 ± 1,605.6 pg/mL) compared to other types of lung cancer. Based on the ROC curve analyses at a specificity of 95%, the diagnostic sensitivity of plasma proGRP was estimated to be 83.8% in distinguishing SCLC from all the other conditions, and 86.5% for discriminating SCLC from the nonmalignant cases. Among the SCLC cases, limited stage disease had lower levels of plasma proGRP than extensive disease. When measuring circulating levels of proGRP, the use of plasma is preferred over serum. Plasma proGRP has a potential marker for discriminating SCLC from nonmalignant conditions or non-small cell lung cancer.

The Impact of the 2007 ATS/IDSA Diagnostic Criteria for Nontuberculous Mycobacterial Disease on the Diagnosis of Nontuberculous Mycobacterial Lung Disease

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.

Disease-free survival of patients after surgical resection of non-small cell lung carcinoma and correlation with excision repair cross-complementation group 1 expression and genotype

Background and objective:  Expression of excision repair cross‐complementation group 1 (ERCC1) is recognized as a favourable prognostic marker in patients who have undergone surgical resection of non‐small cell lung cancer (NSCLC). However, in patients treated with adjuvant chemotherapy after surgical resection, ERCC1 correlated with poor prognosis. Class III beta tubulin (TUBB3) is also known to be a predictive marker of the efficacy of treatment with taxanes or vinorelbine.

Temozolomide-Associated Bronchiolitis Obliterans Organizing Pneumonia Successfully Treated with High-Dose Corticosteroid

Temozolomide is an oral alkylating agent with clinical activity against glioblastoma multiforme (GM). It is generally well-tolerated and has few pulmonary side effects. We report a case of temozolomide-associated brochiolitis obliterans organizing pneumonia (BOOP) requiring very high-dose corticosteroid treatment. A 56-yr-old woman presented with a 2-week history of exertional dyspnea. For the treatment of GM diagnosed 4 months previously, she had undergone surgery followed by chemoradiotherapy, and then planned adjuvant chemotherapy with temozolomide. After the 1st cycle, progressive dyspnea was gradually developed. Chest radiograph showed diffuse patchy peribronchovascular ground-glass opacities in both lungs. Conventional dose of methylprednisolone (1 mg/kg/day) was begun for the possibility of BOOP. Although transbronchial lung biopsy findings were compatible with BOOP, the patients clinical course was more aggravated until hospital day 5. After the dose of methylprednisolone was increased (500 mg/day for 5 days) radiologic findings were improved dramatically.

Predictive factors for survival and correlation to toxicity in advanced Stage III non-small cell lung cancer patients with concurrent chemoradiation.

OBJECTIVE Concurrent chemoradiotherapy is the standard treatment for locally advanced Stage III non-small cell lung cancer in patients with a good performance status and minimal weight loss. This study aimed to define subgroups with different survival outcomes and identify correlations with the radiation-related toxicities. METHODS We retrospectively reviewed 381 locally advanced Stage III non-small cell lung cancer patients with a good performance status or weight loss of <10% who received concurrent chemoradiotherapy between 2004 and 2011. Three-dimensional conformal radiotherapy was administered once daily, combined with weekly chemotherapy. The Kaplan-Meier method was used for survival comparison and Cox regression for multivariate analysis. Multivariate analysis was performed using all variables with P values <0.1 from the univariate analysis. RESULTS Median survival of all patients was 24 months. Age > 75 years, the diffusion lung capacity for carbon monoxide ≤80%, gross tumor volume ≥100 cm(3) and subcarinal nodal involvement were the statistically significant predictive factors for poor overall survival both in univariate and multivariate analyses. Patients were classified into four groups according to these four predictive factors. The median survival times were 36, 29, 18 and 14 months in Groups I, II, III and IV, respectively (P < 0.001). Rates of esophageal or lung toxicity ≥Grade 3 were 5.9, 14.1, 12.5 and 22.2%, respectively. The radiotherapy interruption rate differed significantly between the prognostic subgroups; 8.8, 15.4, 22.7 and 30.6%, respectively (P = 0.017). CONCLUSION Severe toxicity and interruption of radiotherapy were more frequent in patients with multiple adverse predictive factors. To maintain the survival benefit in patients with concurrent chemoradiotherapy, strategies to reduce treatment-related toxicities need to be deeply considered.

Different characteristics associated with intensive care unit transfer from the medical ward between patients with acute exacerbations of chronic obstructive pulmonary disease with and without pneumonia.

BACKGROUND The rate of hospitalization due to acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is increasing. Few studies have examined the clinical, laboratory and treatment differences between patients in general wards and those who need transfer to an intensive care unit (ICU). METHODS We retrospectively reviewed clinical, laboratory, and treatment characteristics of 374 patients who were initially admitted to the general ward at Chonnam National University Hospital in South Korea due to AECOPD (pneumonic, 194; non-pneumonic, 180) between January 2008 and March 2015. Of these patients, 325 were managed at the medical ward during their hospitalization period (ward group), and 49 required ICU transfer (ICU group). We compared the clinical, laboratory, and treatment characteristics associated with ICU transfer between patients with AECOPD with and without pneumonia. RESULTS Male patients were 86.5% in the ward group and 79.6% in the ICU group. High glucose levels [median 154.5 mg/dL, interquartile range (IQR) 126.8-218.3 in ICU group vs. median 133.0, IQR 109.8-160.3 in ward group], high pneumonia severity index scores (median 100.5, IQR 85.5-118.5 vs. median 86.0, IQR 75.0-103.5), low albumin levels (median 2.9 g/dL, IQR 2.6-3.6 vs. median 3.4, IQR 3.0-3.7), and anemia (73.3% vs. 43.3%) independently increased the risk of ICU transfer in the pneumonic AECOPD group. High PaCO2 levels (median 53.1 mmHg in ICU group, IQR 38.5-84.6 vs. median 39.7, IQR 34.2-48.6 in ward group) independently increased the risk of ICU transfer in the non-pneumonic AECOPD group. Treatment with systemic corticosteroids (≥30 mg of daily prednisolone) during hospitalization in the medical ward independently reduced the risk of ICU transfer in both groups. CONCLUSIONS The characteristics associated with ICU transfer differed between the pneumonic and non-pneumonic AECOPD groups, and systemic corticosteroids use was associated with lower rate of ICU transfer in both groups.

Repeated favorable responses to epidermal growth factor receptor-tyrosine kinase inhibitors in a case of advanced lung adenocarcinoma.

The presence of epidermal growth factor receptor (EGFR) mutation is a prognostic and predictive marker for EGFR-tyrosine kinase inhibitor (TKI) therapy. However, inevitably, relapse occurs due to the development of acquired resistance, such as T790M mutation. We report a case of repeated responses to EGFR-TKIs in a never-smoked woman with adenocarcinoma. After six cycles of gemcitabine and cisplatin, the patient was treated by gefitinib for 4 months until progression. Following the six cycles of third-line pemetrexed, gefitinib retreatment was initiated and continued with a partial response for 6 months. After progression, she was recruited for an irreversible EGFR inhibitor trial, and the time to progression was 11 months. Although EGFR direct sequencing on the initial diagnostic specimen revealed a wild-type, we performed a rebiopsy from the progressed subcarinal node at the end of the trial. The result of peptide nucleic acid clamping showed L858R/L861Q.

Response to gemcitabine–platinum chemotherapy by single nucleotide polymorphisms of RRM1 and ERCC1 genes in patients with non-small-cell lung cancer

Background:  RRM1, the regulatory subunit of ribonucleotide reductase, is involved in carcinogenesis and the response to gemcitabine. Two single nucleotide polymorphisms (SNP) in the RRM1 gene (RR37 and RR524) impact promoter activity and are associated with prognosis. The excision repair cross‐complementation group 1 protein (ERCC1) is associated with platinum resistance. A SNP of the ERCC1 gene (T19007C) has been reported as a prognostic marker in platinum‐treated non‐small‐cell lung cancer (NSCLC).