Clinical Features of Chronic Obstructive Pulmonary Disease with High Fractional Exhaled Nitric Oxide / 결핵및호흡기질환

Background@#The fractional exhaled nitric oxide (FENO) test is useful in asthma patients. However, a few studies on its usefulness in chronic obstructive pulmonary disease (COPD) patients have been reported. We analyzed the FENO level distribution and clinical characteristics according to the FENO level in COPD patients. @*Methods@#From December 2014 to June 2019, COPD patients who underwent pulmonary function and FENO tests at Chonnam National University Hospital were retrospectively evaluated for FENO, comorbidities, asthma history, blood eosinophil, and pulmonary function test. The high FENO group was defined as those with FENO level>25 parts per billion (ppb). @*Results@#A total of 849 COPD patients (mean age, 70.3±9.4 years) were included. The mean forced expiratory volume at 1 second was 66.5±21.7% and the mean FENO level was 24.3±20.5 ppb. Patients with FENO ≤25 ppb were 572 (67.4%) and those with FENO >25 ppb were 277 (32.6%). Blood eosinophil percentage was significantly higher (4.2±4.8 vs. 2.7±2.5, p3% (46.9% vs. 34.8%, p=0.001) and asthma history (25.6% vs. 8.6%, p3%, and positive bronchodilator response (BDR) were independent risk factors for the high FENO level (adjusted odds ratio [aOR], 3.85; p<0.001; aOR, 1.46; p=0.017; and aOR, 1.57, p=0.034, respectively) in the multivariable analysis. @*Conclusion@#The FENO level distribution varied in COPD patients and the mean FENO value was slightly elevated. Asthma history, eosinophil percent, and positive BDR were independent risk factors for the high FENO level.

Adherence to the GOLD Guideline in COPD Management of South Korea: Findings from KOCOSS Study 2011–2018 / 전남의대학술지

The guidelines for chronic obstructive pulmonary disease (COPD) treatment are important for the management of the disease. However, studies regarding the treatment adherence to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines have been scarce in Korea. Therefore, to examine the adherence to the GOLD guidelines, we examined the patterns of prescribed medication in COPD patients from 2011 to 2018. Patients were classified as having been appropriately and inappropriately treated (overtreatment or undertreatment) for the GOLD group. Appropriate medical therapy was defined as using the first choice or alternative choice drug recommended in the GOLD guidelines. Inappropriate therapy was classified as overtreatment or undertreatment in accordance with the categorization in the GOLD guidelines. According to treatment of 2011 GOLD guidelines, there was inappropriate treatment in 52.3% in group A, 47.3% in group B, 56.3% in group C, and 17.8% in group D. According to treatment of 2017 GOLD guidelines, there was inappropriate treatment in 66.7% in group A, 45.3% in group B, 14.3% in group C, and 24.0% in group D. The common type of inappropriate COPD treatment is overtreatment, with inhaled corticosteroid (ICS) containing regimens. In conclusions, adherence to the GOLD guideline by the pulmonologist in clinical practice is still low in Korea. Therefore, we need better strategies to both optimize the use of the guidelines and adhere to the guidelines as well.

Clinical Characteristics of Korean Patients with Lung Cancer Who Have Programmed Death-Ligand 1 Expression / 결핵

BACKGROUND: Programmed death-ligand 1 (PD-L1), a transmembrane protein, binds to the programmed death-1 (PD-1) receptor, and anti-PD-1 therapy enables immune responses against tumors. This study aimed to assess clinical characteristics of PD-L1 expression using immunohistochemistry among Korean patients with lung cancer. METHODS: We retrospectively reviewed the data of patients with pathologically proven lung cancer from a single institution. PD-L1 expression determined by Tumor Proportion Score (TPS) was detected using 22C3 pharmDx (Agilent Technologies) and SP263 (Ventana Medical Systems) assays. RESULTS: From July 2016 to July 2017, 267 patients were enrolled. The main histologic type was adenocarcinoma (69.3%). Most participants were smokers (67.4%) and had clinical stage IV disease (60.7%). In total, 116 (42%) and 58 (21%) patients had TPS ≥1% and ≥50%, respectively. The patients were significantly older in TPS ≥1% group than in TPS <1% group (64.83±9.38 years vs. 61.73±10.78 years, p=0.014), not in TPS ≥50% cutoff value (64.69 ± 9.39 vs. 62.36 ± 10.51, p= 0.178). Regarding histologic grade, higher proportions of poorly differentiated tumor were observed in the TPS ≥1% (40.8% vs. 25.8%, p=0.020) and TPS ≥50% groups (53.2% vs. 27.2%, p=0.004). Among 34 patients examined with 22C3 and SP263 assays, 27 had positive results in both assays, with a cutoff of TPS ≥1% (r=0.826; 95% confidence interval, 0.736–0.916). CONCLUSION: PD-L1 expression, defined as TPS ??%, was related to older age and poorly differentiated histology. There was a similar distribution of PD-L1 expression in both 22C3 and SP263 results.

Clinical Characteristics of Korean Patients with Lung Cancer Who Have Programmed Death-Ligand 1 Expression / 결핵및호흡기질환

BACKGROUND@#Programmed death-ligand 1 (PD-L1), a transmembrane protein, binds to the programmed death-1 (PD-1) receptor, and anti-PD-1 therapy enables immune responses against tumors. This study aimed to assess clinical characteristics of PD-L1 expression using immunohistochemistry among Korean patients with lung cancer.@*METHODS@#We retrospectively reviewed the data of patients with pathologically proven lung cancer from a single institution. PD-L1 expression determined by Tumor Proportion Score (TPS) was detected using 22C3 pharmDx (Agilent Technologies) and SP263 (Ventana Medical Systems) assays.@*RESULTS@#From July 2016 to July 2017, 267 patients were enrolled. The main histologic type was adenocarcinoma (69.3%). Most participants were smokers (67.4%) and had clinical stage IV disease (60.7%). In total, 116 (42%) and 58 (21%) patients had TPS ≥1% and ≥50%, respectively. The patients were significantly older in TPS ≥1% group than in TPS <1% group (64.83±9.38 years vs. 61.73±10.78 years, p=0.014), not in TPS ≥50% cutoff value (64.69 ± 9.39 vs. 62.36 ± 10.51, p= 0.178). Regarding histologic grade, higher proportions of poorly differentiated tumor were observed in the TPS ≥1% (40.8% vs. 25.8%, p=0.020) and TPS ≥50% groups (53.2% vs. 27.2%, p=0.004). Among 34 patients examined with 22C3 and SP263 assays, 27 had positive results in both assays, with a cutoff of TPS ≥1% (r=0.826; 95% confidence interval, 0.736–0.916).@*CONCLUSION@#PD-L1 expression, defined as TPS ??%, was related to older age and poorly differentiated histology. There was a similar distribution of PD-L1 expression in both 22C3 and SP263 results.

Cutaneous adverse drug reactions in patients with peripheral blood eosinophilia during antituberculosis treatment

BACKGROUND/AIMS@#Peripheral eosinophilia during tuberculosis (TB) treatment is common, but has not been fully evaluated. The aim of this study was to determine the prevalence and clinical significance of peripheral blood eosinophilia in patients undergoing anti-TB treatment.@*METHODS@#We retrospectively reviewed the clinical and laboratory data of patients who received anti-TB treatment and had peripheral blood eosinophilia (> 5% of the total white blood cell count) at the Chonnam National University Hospital between January 2010 and December 2014.@*RESULTS@#Of all 2,234 patients with TB who received anti-TB treatment, 397 (17.8%) had peripheral blood eosinophilia. Of the 397 with eosinophilia, we reviewed the data of 262 (66%), and cutaneous adverse drug reactions (CADRs) were observed in 161 (61.5%). Of the 161 with CADRs, itching (47.2%) and skin rash (47.8%) were common. Older age, abnormal liver function, and higher peak blood eosinophil percentage were associated with CADRs in multivariate analysis. There was a significant relationship between increased peak eosinophil counts and the degree of severity of CADRs.@*CONCLUSIONS@#Peripheral blood eosinophilia is a relatively common occurrence during anti-TB treatment. Peripheral blood eosinophil counts were higher according to the degree of severity of CADRs.

Efficacy of Afatinib in a Previously-Treated Patient with Non-Small Cell Lung Cancer Harboring HER2 Mutation: Case Report

Human epidermal growth factor receptor 2 (HER2) mutation in non-small cell lung cancer (NSCLC) is an oncogenic driver that possibly becomes a druggable target to HER2-targeted therapy. The benefit of HER2-targeted therapy is much less defined especially in eastern populations. We provide evidence of clinical benefit of afatinib in a 50-year-old Asian woman with HER2-mutant NSCLC who previously failed cytotoxic chemotherapy and gefitinib treatment. Next-generation sequencing of the tumor tissue revealed a HER2 exon 20 mutation (c.2437A > G), which has never been reported. The patient was treated with afatinib for more than four months. She showed rapid radiologic response within a month, and maintained stable state until the last dose of afatinib.

Review of Sarcoidosis in a Province of South Korea from 1996 to 2014 / 결핵및호흡기질환

BACKGROUND: Since the introduction of endobronchial ultrasound (EBUS)–guided transbronchial needle aspiration (TBNA) of mediastinal lymph nodes, the incidence of histopathologically-confirmed sarcoidosis has increased. METHODS: The electronic medical records of Chonnam National University (CNU) Hospital and CNU Hwasun Hospital (CNUHH) were searched for confirmed cases of sarcoidosis diagnosed between 1996 and 2014. Cases were selected using a combination of clinical, radiological, and pathological evidence. Of 115 cases with the relevant disease codes, 16 cases were excluded, as they had not been confirmed pathologically or had no definitive clinical features of sarcoidosis. RESULTS: Among 99 cases of confirmed sarcoidosis, only nine patients were diagnosed with sarcoidosis before 2008; the rest were diagnosed from 2008 onward, after the introduction of EBUS-TBNA. EBUS-TBNA was used in 75.8% of patients, open surgical biopsy in 13.2%, and mediastinoscopic biopsy in 5.1%. At the time of diagnosis, 42.4% of sarcoidosis cases were at stage I, 55.6% at stage II, and 2% at stage III. Spontaneous remission of sarcoidosis was observed in 33.3% of cases, and stable disease in 37.4%; systemic steroid treatment was initiated in 23.2% of cases. Of the patients treated with systemic steroids, 69.6% showed improvement. The median duration of steroid treatment was 5 months. CONCLUSION: Following the introduction of EBUS-TBNA, the number of newly diagnosed sarcoidosis patients has increased. Clinical features of sarcoidosis were similar to those previously reported. Spontaneous remission occurred in about one-third of patients, while one-fourth of patients required systemic steroid treatment.

Once-Daily OROS Hydromorphone for Management of Cancer Pain: an Open-Label, Multi-Center, Non-Interventional Study

Extended-release osmotic extended-release oral delivery system (OROS) hydromorphone is a strong synthetic opioid designed to maintain a constant blood concentration by once daily dosing. The objective of this observational study was to investigate the clinical usefulness of OROS hydromorphone in patients with cancer pain of moderate to severe intensity. Patients with cancer pain who required strong opioids were administered with OROS hydromorphone for 4 weeks. We assessed changes in pain intensity using a numerical rating scale (NRS) as well as levels of sleep disturbance, breakthrough pain, end-of-dose failure, patient satisfaction, and overall assessment of drug effectiveness based on investigator evaluation. Of the 648 enrolled patients, 553 patients were included in the full analysis set. The mean pain intensity was significantly decreased from the NRS value of 5.07 ± 1.99 to 2.75 ± 1.94 (mean % change of 42.13 ± 46.53, P < 0.001). The degree of sleep disturbance significantly improved (mean NRS change of 1.61 ± 2.57, P < 0.001), and the incidence of breakthrough pain was significantly decreased (mean NRS change of 1.22 ± 2.30, P < 0.001). The experience of end-of-dose failure also significantly decreased from 4.60 ± 1.75 to 3.93 ± 1.70, P = 0.007). The patient satisfaction rate was 72.7%, and 72.9% of investigators evaluated the study drug as effective. OROS hydromorphone was an effective and tolerable agent for cancer pain management. It effectively lowered pain intensity as well as improved sleep disturbance, breakthrough pain, and end-of-dose failure (Identifier: NCT 01273454).

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 patient's 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.

Bacterial Pathogens of Ventilator Associated Pneumonia in a Tertiary Referral Hospital / 결핵및호흡기질환

BACKGROUND: This study evaluates the bacterial pathogens of Ventilator-associated pneumonia (VAP) in a tertiary referral hospital. METHODS: A total of 109 bacterial pathogens from 91 adult patients with VAP, who were admitted to the medical intensive care unit from January 2008 to December 2009, were examined. Clinical characteristics, bacterial pathogens, and resistance profiles were analyzed. RESULTS: Staphylococcus aureus (44%) was the most frequently isolated. Acinetobacter baumanii (30%), Pseudomonas aeruginosa (12%), Stenotrophomonas maltophilia (7%), Klebsiella pneumoniae (6%), and Serratia marcescens (2%) were isolated from the transtracheal aspirates or bronchoalveolar lavage in patients with VAP. There was no significant difference of bacterial pathogens between early and late onset VAP. All isolated S. aureus were methicillin resistant S. aureus; the imipenem resistance rate of A. baumanii was 69%. CONCLUSION: The two most frequent pathogens of VAP were S. aureus and A. baumanii. There were no pathogenic differences between early and late onset VAP.

Bacterial Pathogens of Ventilator Associated Pneumonia in a Tertiary Referral Hospital / 결핵및호흡기질환

BACKGROUND: This study evaluates the bacterial pathogens of Ventilator-associated pneumonia (VAP) in a tertiary referral hospital. METHODS: A total of 109 bacterial pathogens from 91 adult patients with VAP, who were admitted to the medical intensive care unit from January 2008 to December 2009, were examined. Clinical characteristics, bacterial pathogens, and resistance profiles were analyzed. RESULTS: Staphylococcus aureus (44%) was the most frequently isolated. Acinetobacter baumanii (30%), Pseudomonas aeruginosa (12%), Stenotrophomonas maltophilia (7%), Klebsiella pneumoniae (6%), and Serratia marcescens (2%) were isolated from the transtracheal aspirates or bronchoalveolar lavage in patients with VAP. There was no significant difference of bacterial pathogens between early and late onset VAP. All isolated S. aureus were methicillin resistant S. aureus; the imipenem resistance rate of A. baumanii was 69%. CONCLUSION: The two most frequent pathogens of VAP were S. aureus and A. baumanii. There were no pathogenic differences between early and late onset VAP.

Comparison of Therapeutic Efficacy of Gefitinib and Erlotinib in Patients with Squamous Cell Lung Cancer / 결핵및호흡기질환

BACKGROUND: Gefitinib and erlotinib are useful, molecular targeted agents in patients with non-small-cell lung cancer (NSCLC) who failed previous chemotherapy. We compared the efficacy and toxicity of two drugs in patients with squamous cell lung cancer, most of whom are male smokers. METHODS: We retrospectively reviewed the clinical information on patients with NSCLC who were treated with gefitinib or erlotinib treatment at Chonnam National University Hwasun Hospital between July 2002 and November 2009. The overall response rate (ORR), overall survival (OS) and progression-free survival (PFS) were compared between the two drugs. RESULTS: A total of 182 (100 gefitinib vs. 82 erlotinib) of 584 patients treated by targeted agents had squamous histology. Of the 182 patients, 167 (91.7%) were male and 159 (87.4%) were smokers. The ORR and disease control rate (DCR) were 4.9% and 40.6%, and there was no significant difference between gefitinib and erlotinib (ORR, 5.0% vs 4.8%; p=0.970; DCR, 40.0% vs 41.4%; p=0.439). The median OS in the gefitinib group was 12.1 months, and that in the erlotinib was 12.7 months (hazard ratio [HR], 1.282; 95% confidence interval [CI], 0.771~2.134; p=0.339). The median PFS for the gefitinib group was 1.40 months, compared with 1.37 months for the erlotinib group (HR, 1.092; 95% CI, 0.809~1.474; p=0.564). Skin rash > or =grade 3 was more common in erlotinib (12.2%) than gefitinib (1.0%, p=0.003) groups. CONCLUSION: This retrospective study showed that the two drugs appear to have similar antitumor efficacy and toxicity except for skin rash.

Influence of Diaphragmatic Mobility on Hypercapnia in Patients with Chronic Obstructive Pulmonary Disease

A reduction in diaphragm mobility has been identified in patients with chronic obstructive pulmonary disease (COPD) and has been associated with a decline in pulmonary function parameters. However, little information exists regarding the potential role of diaphragm mobility on hypercapnia in COPD. A new method of assessing the mobility of the diaphragm, using ultrasound, has recently been validated. The purpose of the present study was to investigate the relationship between diaphragm mobility and pulmonary function parameters, as well as that between arterial blood gas values and diaphragm mobility, in COPD patients. Thirty seven COPD patients were recruited for pulmonary function test, arterial blood gas analysis and diaphragm mobility using ultrasound to measure the craniocaudal displacement of the left branch of the portal vein. There were significant negative correlations between diaphragmatic mobility and PaCO2 (r = -0.373, P = 0.030). Diaphragmatic mobility correlated with airway obstruction (FEV1, r = 0.415, P = 0.011) and with ventilatory capacity (FVC, r = 0.302, P = 0.029; MVV, r = 0.481, P = 0.003). Diaphragmatic mobility also correlated significantly with pulmonary hyperinflation. No relationship was observed between diaphragm mobility and PaO2 (r = -0.028, P = 0.873). These findings support a possibility that the reduction in diaphragm mobility relates to hypercapnia in COPD patients.

Mortality and Prognostic Factors in Acute Respiratory Distress Syndrome due to Tuberculosis / 대한내과학회지

BACKGROUND/AIMS: Acute respiratory distress syndrome (ARDS) due to tuberculosis (TB) is a rare disease, but its mortality is believed to be high. The aim of this study was to evaluate the mortality rate and prognostic factors of ARDS. METHODS: We retrospectively reviewed the demographic, clinical, radiologic, and laboratory data of 19 patients with ARDS due to active pulmonary TB at Chonnam National University Hospital between January 2000 and December 2010. RESULTS: The median age of patients was 71.1 (interquartile range [IQR] 51-74) years. None had a history of TB treatment. The most common symptoms were dyspnea (90%), fever (68%), and cough (53%). The overall in-hospital mortality was 73%. The median acute physiologic assessment and chronic health evaluation (APACHE) III score and pneumonia severity index (PSI) were 81.9 (IQR 59.0-92.0) and 111.0 (IQR 77.0-131.0), respectively. The PSI was significantly higher in non-survivors than in survivors (55.0 vs. 122.0; p = 0.016). The rate of TB treatment before admission was significantly higher in survivors than in non-survivors (75% vs. 13%; p = 0.037). The time from admission to treatment initiation was significantly longer in non-survivors than in survivors (3 vs. 0 days; p = 0.049). The median duration of mechanical ventilation was 11 days (IQR 5-16 days). The most common cause of death was a refractory shock (53%). CONCLUSIONS: The overall mortality rate of ARDS due to pulmonary TB was high. A high PSI score and delay of TB treatment may be risk factors for a poor outcome of ARDS due to pulmonary TB.

A Case of Pulmonary Alveolar Microlithiasis

Pulmonary alveolar microlithiasis (PAM) is a rare disease with unknown etiology and pathogenesis. It is characterized by diffuse, innumerable, and minute calculi, called microlithiasis in the alveoli. More than half of reported cases are asymptomatic at the time of diagnosis. We describe the first case of PAM in Korea. A 19-yr-old man without respiratory symptoms presented with interstitial thickening on the chest radiograph. His chest high resolution CT scan showed diffusely scattered, ill defined tiny micronodules and interstitial thickening. Open lung biopsy confirmed the diagnosis of PAM. He was followed up for 6 months without treatment, and no progression was noticed.

A Case of Ischemic Colitis Associated with Paclitaxel Loaded Polymeric Micelle (Genexol-PM(R)) Chemotherapy / 결핵및호흡기질환

Paclitaxel has been widely used for treating many solid tumors. Although colonic toxicity is an unusual complication of paclitaxel-based chemotherapy, the reported toxicities include pseudomembranous colitis, neutropenic enterocolitis and on rare occasions ischemic colitis. Genexol-PM(R), which is a recently developed cremophor-free, polymeric micelle-formulated paclitaxel, has shown a more potent antitumor effect because it can increase the usual dose of paclitaxel due to that Genexol-PM(R) does not include the toxic cremophor compound. We report here on a case of a 57-year-old man with advanced non-small cell lung cancer and who developed ischemic colitis after chemotherapy with Genexol-PM(R) and cisplatin. He complained of hematochezia with abdominal pain on the left lower quadrant. Colonoscopy revealed diffuse mucosal hemorrhage and edema from the sigmoid colon to the splenic flexure. After bowel rest, he recovered from his symptoms and the follow-up colonoscopic findings showed that the mucosa was healing. Since then, he was treated with pemetrexed monotherapy instead of a paclitaxel compound and platinum.