Soo-Jung Um

Role of the Neutrophil-Lymphocyte Count Ratio in the Differential Diagnosis between Pulmonary Tuberculosis and Bacterial Community-Acquired Pneumonia

Background Differential diagnosis between pulmonary tuberculosis (TB) and bacterial community-acquired pneumonia (CAP) is often challenging. The neutrophil-lymphocyte count ratio (NLR), a convenient marker of inflammation, has been demonstrated to be a useful biomarker for predicting bacteremia. We investigated the usefulness of the NLR for discriminating pulmonary TB from bacterial CAP in an intermediate TB-burden country. Methods We retrospectively analyzed the clinical and laboratory characteristics of 206 patients suspected of having pulmonary TB or bacterial CAP from January 2009 to February 2011. The diagnostic ability of the NLR for differential diagnosis was evaluated and compared with that of C-reactive protein. Results Serum NLR levels were significantly lower in patients with pulmonary TB than in patients with bacterial CAP (3.67±2.12 vs. 14.64±9.72, P<0.001). A NLR <7 was an optimal cut-off value to discriminate patients with pulmonary TB from patients with bacterial CAP (sensitivity 91.1%, specificity 81.9%, positive predictive value 85.7%, negative predictive value 88.5%). The area under the curve for the NLR (0.95, 95% confidence interval [CI], 0.91-0.98) was significantly greater than that of C-reactive protein (0.83, 95% CI, 0.76-0.88; P=0.0015). Conclusions The NLR obtained at the initial diagnostic stage is a useful laboratory marker to discriminate patients with pulmonary TB from patients with bacterial CAP in an intermediate TB-burden country.

Four Cases of a Cerebral Air Embolism Complicating a Percutaneous Transthoracic Needle Biopsy

A percutaneous transthoracic needle biopsy is a common procedure in the practice of pulmonology. An air embolism is a rare but potentially fatal complication of a percutaneous transthoracic needle biopsy. We report four cases of a cerebral air embolism that developed after a percutaneous transthoracic needle biopsy. Early diagnosis and the rapid application of hyperbaric oxygen therapy is the mainstay of therapy for an embolism. Prevention is the best course and it is essential that possible risk factors be avoided.

Absolute Leukocyte Telomere Length in HIV-Infected and Uninfected Individuals: Evidence of Accelerated Cell Senescence in HIV-Associated Chronic Obstructive Pulmonary Disease

Combination antiretroviral therapy (cART) has extended the longevity of human immunodeficiency virus (HIV)-infected individuals. However, this has resulted in greater awareness of age-associated diseases such as chronic obstructive pulmonary disease (COPD). Accelerated cellular senescence may be responsible, but its magnitude as measured by leukocyte telomere length is unknown and its relationship to HIV-associated COPD has not yet been established. We measured absolute telomere length (aTL) in peripheral leukocytes from 231 HIV-infected adults. Comparisons were made to 691 HIV-uninfected individuals from a population-based sample. Subject quartiles of aTL were assessed for relationships with measures of HIV disease severity, airflow obstruction, and emphysema severity on computed tomographic (CT) imaging. Multivariable regression models identified factors associated with shortened aTL. Compared to HIV-uninfected subjects, the mean aTL in HIV-infected patients was markedly shorter by 27 kbp/genome (p<0.001); however, the slopes of aTL vs. age were not different (p=0.469). Patients with longer known durations of HIV infection (p=0.019) and lower nadir CD4 cell counts (p=0.023) had shorter aTL. Shorter aTL were also associated with older age (p=0.026), smoking (p=0.005), reduced forced expiratory volume in one second (p=0.030), and worse CT emphysema severity score (p=0.049). HIV-infected subjects demonstrate advanced cellular aging, yet in a cART-treated cohort, the relationship between aTL and age appears no different from that of HIV-uninfected subjects.

Phase I study of autologous dendritic cell tumor vaccine in patients with non-small cell lung cancer

BACKGROUND A dendritic cell vaccine has been developed as a novel strategy for generating antitumor immunity in the treatment of cancer. The purpose of this study was to assess the maximal tolerated dose, safety, and immunologic response of a new dendritic cell vaccine (DC-Vac) into which tumor lysate was loaded by electroporation and pulse in patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS Fifteen patients with inoperable stage III or IV NSCLC were assigned to cohorts that received 3, 6, or 12 × 10(6) DC-Vac intradermally 3 times at 2 week intervals. We also evaluated immunologic and tumor responses. RESULTS The maximum dose of DC-Vac (12 × 10(6)) was shown to be safe. In 5 of 9 patients, the vaccine resulted in increased interferon (IFN)-γ production by CD8+ cells after exposure to tumor lysate. Additionally, there were mixed responses which do fulfill progressive disease definition but demonstrate some clinical benefit in two patients. CONCLUSION The administration of tumor lysate-loaded autologous dendritic cells by electroporation and pulse was non-toxic and induced immunologic responses to tumor antigens. The two mixed tumor responses which were achieved may represent a potential benefit of this new DC-Vac.

Association of the Neutrophil-to-Lymphocyte Ratio with Lung Function and Exacerbations in Patients with Chronic Obstructive Pulmonary Disease.

Background The ratio of neutrophils to lymphocytes (NLR) is a widely available marker of inflammation. Several types of inflammatory cells and mediators have been found to be involved in the progression of chronic obstructive pulmonary disease (COPD). We sought to evaluate the association of the NLR with severity of airflow limitation and disease exacerbations in a COPD population. Methods We analyzed 885 patients from the Korean COPD Subtype Study cohort that recruited subjects with COPD from 44 referral hospitals. We determined the relationship of NLR levels to severity of lung function using a linear regression model. In addition, we analyzed the experiences of COPD exacerbation according to the NLR quartiles. Results NLR levels were inversely associated with severity of airflow limitation as measured by FEV1% predicted and absolute values after adjustments for age, gender, body mass index, pack-years of smoking, and the use of inhaled corticosteroid (P<0.001, respectively). In the multivariate binary regression model, the NLR 4th quartile (vs. 1st quartile) was found to be a significant predictor of exacerbations during 1-year follow-up (OR = 2.05, 95% CI = 1.03 to 4.06, P = 0.041). Adding an NLR to FEV1 significantly improved prediction for exacerbations during 1-year follow-up as measured by the net reclassification improvement (NRI = 7.8%, P = 0.032) and the integrated discrimination improvement (IDI = 0.014, P = 0.021). Conclusions The NLR showed a significant inverse relationship to airflow limitation and was a prognostic marker for future exacerbations in patients with COPD.

Choice between Levofloxacin and Moxifloxacin and Multidrug-Resistant Tuberculosis Treatment Outcomes

RATIONALE We previously showed that the choice of levofloxacin or moxifloxacin for the treatment of patients with fluoroquinolone-sensitive multidrug-resistant tuberculosis (MDR-TB) did not affect sputum culture conversion at 3 months of treatment. OBJECTIVES To compare final treatment outcomes between patients with MDR-TB randomized to levofloxacin or moxifloxacin. METHODS A total of 151 participants with MDR-TB who were included for the final analysis in our previous trial were followed through the end of treatment. Treatment outcomes were compared between 77 patients in the levofloxacin group and 74 in the moxifloxacin group, based on the 2008 World Health Organization definitions as well as 2013 revised definitions of treatment outcomes. In addition, the time to culture conversion was compared between the two groups. MEASUREMENTS AND MAIN RESULTS Treatment outcomes were not different between the two groups, based on 2008 World Health Organization definitions as well as 2013 definitions. With 2008 definitions, cure was achieved in 54 patients (70.1%) in the levofloxacin group and 54 (73.0%) in the moxifloxacin group (P = 0.72). Treatment success rates, including cure and treatment completed, were not different between the two groups (87.0 vs. 81.1%, P = 0.38). With 2013 definitions, cure rates (83.1 vs. 78.4%, P = 0.54) and treatment success rates (84.4 vs. 79.7%, P = 0.53) were also similar between the levofloxacin and moxifloxacin groups. Time to culture conversion was also not different between the two groups (27.0 vs. 45.0 d, P = 0.11 on liquid media; 17.0 vs. 42.0 d, P = 0.14 on solid media). Patients in the levofloxacin group had more adverse events than those in the moxifloxacin group (79.2 vs. 63.5%, P = 0.03), especially musculoskeletal ones (37.7 vs. 14.9%, P = 0.001). CONCLUSIONS The choice of levofloxacin or moxifloxacin made no difference to the final treatment outcome among patients with fluoroquinolone-sensitive MDR-TB. Clinical trial registered with www.clinicalrials.gov (NCT01055145).

An Aortoesophageal Fistula in Patient with Lung Cancer after Chemo-Irradiation and Subsequent Esophageal Stent Implantation

An aortoesophageal fistula (AEF) is uncommon but is frequently fatal. Most cases are attributable to a thoracic aortic aneurysm. Other common causes include malignant intrathoracic neoplasm, foreign body ingestion, endovascular stent graft repair for thoracic aortic disease, and esophageal surgery. We report a case of an AEF that developed after chemo-irradiation and subsequent esophageal stent implantation in patient with non-small cell lung cancer. The patient underwent self expanding metallic esophageal stent implantation for an esophageal stricture after chemotherapy and radiotherapy. However, 1 month later, he presented with hematemesis. Chest computed tomography and aortography revealed a fistula from the descending thoracic aorta to the stented esophagus. The patient expired 36 hours after initial hematemesis. To our knowledge, this is the first confirmed report of an AEF in patient with a nonesophageal malignancy that had undergone chemo-irradiation and subsequent esophageal stent implantation. We recommend that special caution be exercised when performing esophageal stent implantation in patients who have received prior radiotherapy to the thorax including the esophagus.

Drug reaction with eosinophilia and systemic symptoms syndrome is not uncommon and shows better clinical outcome than generally recognised

BACKGROUND Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare disease which can cause severe morbidity and mortality. The aim of this study is to evaluate the clinical manifestation and course of DRESS syndrome. METHODS We conducted a retrospective analysis of prospectively collected data in 45 patients with DRESS syndrome diagnosed between September 2009 and August 2011. RESULTS The most common causative drug group was antibiotics (n=13, 28.9%), followed by anticonvulsants (n=12, 26.7%), antituberculosis drugs (n=6, 13.3%), non-steroidal anti-inflammatory drugs (n=4, 8.9%), undetermined agents (n=4, 8.9%), allopurinol (n=3, 6.7%), and others (n=3, 6.7%). The latency period ranged from 2 to 120 days, with a mean of 20.2 ± 24.3 days. The longest latency period was noted for the antituberculosis drug group, at 46.5 ± 29.9 days. Eosinophilia in peripheral blood examination was noted in 35 subjects (77.8%). Atypical lymphocytosis was noted in 16 patients (35.6%), and thrombocytopenia in seven patients (15.6%). Hepatic involvement was noted in 39 (86.7%) study patients, kidney in eight (17.8%), lung in four (8.9%), and central nervous system in one (2.3%). Systemic corticosteroids were administered to 10 patients (22.2%). Forty-three patients (95.6%) showed complete recovery, while two patients had poor outcomes. CONCLUSIONS DRESS syndrome was not more uncommon than generally recognised. Antibiotics were the most frequently implicated drug group, followed by anticonvulsants. Most patients with this disease showed a better clinical outcome than that which had been generally expected.

Absence of Hyper-Responsiveness to Methacholine after Specific Bronchial Provocation Tests in a Worker With Hydroxyapatite-Induced Occupational Asthma

Hydroxyapatite is commonly used as a filler to replace amputated bone or as a coating to promote bone ingrowth into prosthetic implants. Many modern implants, such as hip replacements and dental implants, are coated with hydroxyapatite. We report a patient with occupational asthma due to hydroxyapatite, proven by a specific inhalation challenge, who experienced an early asthmatic reaction after exposure to hydroxyapatite, without increased airway responsiveness to methacholine despite an increased eosinophil count in the peripheral blood. A 38-year-old male dental implant worker visited our allergy department for the evaluation of occupational asthma. He had treated dental implant titanium surfaces with hydroxyapatite for 1.5 years. One year after starting his employment, he noticed symptoms of rhinorrhea, paroxysmal cough, and chest tightness. His symptoms were aggravated during and shortly after work and subsided several hours after work. When he stopped working for 2 months because of his chest symptoms, he became asymptomatic. After restarting his work, his symptoms reappeared and were aggravated. A methacholine bronchial challenge test had a negative response. The following day, a specific bronchial provocation test with wheat powder was negative. On the third day, a specific bronchial provocation test with hydroxyapatite powder produced an early asthmatic response. On the fourth day, a methacholine bronchial challenge test was negative. Further studies are needed to evaluate the exact pathogenetic mechanism of hydroxyapatite-induced occupational asthma.

Fatal interstitial lung disease after erlotinib administration in a patient with radiation fibrosis

Introduction:  Although gefitinib used for the treatment of non‐small‐cell lung cancer is a well‐known cause of interstitial lung disease (ILD), few case reports on erlotinib‐induced ILD have been issued. The common risk factor of both of these two drug‐induced ILDs is idiopathic interstitial pneumonia, but ILD in a patient with radiation fibrosis has not been previously reported.