Ki Hwan Jung

Comparison of levofloxacin versus moxifloxacin for multidrug-resistant tuberculosis.

RATIONALE Levofloxacin (LFX) and moxifloxacin (MXF) are the two most frequently recommended fluoroquinolones for treatment of patients with multidrug-resistant tuberculosis (MDR-TB). However, studies comparing the effectiveness of LFX and MXF among patients with MDR-TB are lacking. OBJECTIVES To compare the effectiveness of LFX and MXF in terms of culture conversion after 3 months of treatment for MDR-TB. METHODS In this prospective multicenter randomized open label trial, we randomly assigned 182 patients with MDR-TB (sensitive to LFX and MXF) to receive either LFX (750 mg/day; 90 patients) or MXF (400 mg/day; 92 patients) with a background drug regimen. The primary outcome was the proportion of patients who achieved sputum culture conversion at 3 months of treatment. Secondary outcomes were time to culture conversion and time to smear conversion, with data censored at 3 months, and the proportions of adverse drug reactions. MEASUREMENTS AND MAIN RESULTS At 3 months of treatment, 68 (88.3%) of the 77 patients in the LFX group and 67 (90.5%) of the 74 in the MXF group showed conversion to negative sputum cultures (odds ratio for LFX compared with MXF, 0.78; 95% confidence interval, 0.27-2.20). Adverse drug reactions were reported in six patients (7.7%) in the LFX group and four (5.2%) in the MXF group (P = 0.75). CONCLUSIONS The choice of LFX or MXF for treatment of patients with MDR-TB may not affect sputum culture conversion at 3 months of treatment. Clinical trial registered with www.clinicaltrials.gov (NCT 01055145).

Asthma-Like Symptoms are Increased in the Metabolic Syndrome

Background. The prevalence of obesity and asthma has been increasing during the last several decades. Obesity has been reported to be associated with asthma. Obesity, especially abdominal obesity, is the main component of the metabolic syndrome. Objectives. We thus hypothesized that metabolic syndrome is an important contributing factor for the development of asthma-like symptoms. Methods. The Korean Health and Genome Study started in 2001 as an ongoing population-based study of Korean adults 40 to 69 years of age. The prevalence of asthma-like symptoms in the previous 12 months was obtained by a questionnaire, and spirometric testing was conducted. Results. Among the 10,038 participants, the data from 9,942 individuals (4,716 men and 5,226 women) was available. Asthma-like symptoms (wheeze [p = 0.0006], resting dyspnea [p = 0.0062], and post-exercise dyspnea [p < 0.0001]) were increased in the subjects of the metabolic syndrome group. Subjects with asthma-like symptoms had a decreased lung function compared to subjects without asthma-like symptoms. Among the components of the metabolic syndrome, abdominal obesity and hypertension were the risk factors for asthma-like symptoms. Conclusions. Metabolic syndrome is associated with asthma-like symptoms. Among the components of metabolic syndrome, abdominal obesity and hypertension are the risk factors for asthma-like symptoms.

Inflammatory and transcriptional roles of poly (ADP-ribose) polymerase in ventilator-induced lung injury

IntroductionPoly (ADP-ribose) polymerase (PARP) participates in inflammation by cellular necrosis and the nuclear factor-kappa-B (NF-κB)-dependent transcription. The purpose of this study was to examine the roles of PARP in ventilator-induced lung injury (VILI) in normal mice lung.MethodsMale C57BL/6 mice were divided into four groups: sham tracheostomized (sham), lung-protective ventilation (LPV), VILI, and VILI with PARP inhibitor PJ34 pretreatment (PJ34+VILI) groups. Mechanical ventilation (MV) settings were peak inspiratory pressure (PIP) 15 cm H2O + positive end-expiratory pressure (PEEP) 3 cm H2O + 90 breaths per minute for the LPV group and PIP 40 cm H2O + PEEP 0 cm H2O + 90 breaths per minute for the VILI and PJ34+VILI groups. After 2 hours of MV, acute lung injury (ALI) score, wet-to-dry (W/D) weight ratio, PARP activity, and dynamic compliance (CD) were recorded. Tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), myeloperoxidase (MPO) activity, and nitrite/nitrate (NOX) in the bronchoalveolar lavage fluid and NF-κB DNA-binding activity in tissue homogenates were measured.ResultsThe VILI group showed higher ALI score, W/D weight ratio, MPO activity, NOX, and concentrations of TNF-α and IL-6 along with lower CD than the sham and LPV groups (P < 0.05). In the PJ34+VILI group, PJ34 pretreatment improved all histopathologic ALI, inflammatory profiles, and pulmonary dynamics (P < 0.05). NF-κB activity was increased in the VILI group as compared with the sham and LPV groups (P < 0.05) and was decreased in the PJ34+VILI group as compared with the VILI group (P = 0.009). Changes in all parameters were closely correlated with the PARP activity (P < 0.05).ConclusionOveractivation of PARP plays an important role in the inflammatory and transcriptional pathogenesis of VILI, and PARP inhibition has potentially beneficial effects on the prevention and treatment of VILI.

Hyaluronic acid pulmonary embolism: a critical consequence of an illegal cosmetic vaginal procedure

The materials used for cosmetic procedures by physicians as well as illegally by non-medical personnel can cause non-thrombotic pulmonary embolism (NTPE). The case history is presented of a woman with acute respiratory failure after an illegal cosmetic vaginal procedure using hyaluronic acid (HA) dermal filler by an unlicensed medical practitioner on the day of symptom onset. Histopathological examination of a video-assisted thoracoscopic lung biopsy specimen showed a granulomatous foreign body reaction with multinucleated giant cells around amorphous basophilic materials in the pulmonary vessels and lung parenchyma, suggesting NTPE by HA. HA is approved for dermal implantation for the correction of facial wrinkles and folds. All other uses are considered off label. Although HA is supposedly devoid of immunological reactions, localised complications with granulomatous foreign body reactions by HA injection have been reported after cosmetic facial procedures. However, the case of a typical NTPE syndrome has not yet been reported. This is the first reported biopsy-proven case of a patient developing NTPE caused by HA.

Determining optimal sleep position in patients with positional sleep-disordered breathing using response surface analysis.

A lateral position (LP) during sleep is effective in reducing sleep disorder symptoms in mild or moderate sleep apnea patients. However, the effect of head and shoulder posture in LP on reducing sleep disorders has not been reported. In this study, effective sleeping positions and a combination of sleep position determinants were evaluated with respect to their ability to reduce snoring and apnea. The positions evaluated included the following: cervical vertebrae support with head tilting (CVS‐HT), scapula support (SS), and LP. A central composite design was applied for response surface analysis (RSA). Sixteen patients with mild or moderate positional sleep apnea and snoring who underwent polysomnography for two nights were evaluated. Based on an estimated RSA equation, LP (with a rotation of at least 30°) had the most dominant effect [P = 0.0057 for snoring rate, P = 0.0319 for apnea–hypopnea index (AHI)]. In addition, the LP was found to interact with CVS‐HT (P = 0.0423) for snoring rate and CVS‐HT (P = 0.0310) and SS (P = 0.0265) for AHI. The optimal sleep position reduced mild snoring by more than 80% (i.e. snoring rate in the supine position was <20%) and the snoring rate was approximately zero with a 40° rotation. To achieve at least 80% reduction of AHI, LP and SS should be >30° and/or 20 mm respectively. To determine an effective sleep position, CVS‐HT and SS, as well as the degree of the LP, should be concurrently considered in patients with positional sleep apnea or snoring.

A Case of Pulmonary Lymphomatoid Granulomatosis Successfully Treated by Combination Chemotherapy with Rituximab

Lymphomatoid granulomatosis (LYG) is a rare angiocentric and angiodestructive lymphoproliferative disease characterized by Epstein-Barr virus-positive B cells admixed with reactive T cells. LYG most commonly affects the lung but can also involve other extrapulmonary sites. Pulmonary LYG usually presents as multiple pulmonary nodules with rapid progression and excavation. It can mimic various infectious diseases, vasculitis or metastatic malignancy and is difficult to be diagnosed clinically. Standard treatment for LYG has not yet been established. Despite combination chemotherapy, the overall prognosis is poor. Recently, anti-CD20 monoclonal antibody, rituximab, has been used to treat LYG. We report the case of a 70-year-old male patient with pulmonary LYG, who showed rapid remission of the disease after combination chemotherapy with rituximab.

Relation of Epidermal Growth Factor Receptor Expression to Mucus Hypersecretion in Diffuse Panbronchiolitis

STUDY OBJECT Diffuse panbronchiolitis (DPB) is a hypersecretory airway disease, and the mechanism of mucus hypersecretion in DPB is poorly understood. Moreover, mucin synthesis in the airways has been reported to be regulated by neutrophilic inflammation-induced epidermal growth factor receptor (EGFR) expression, and the degranulation of goblet cells is known to be mediated by neutrophilic elastase. In this study, we examined the relationship between EGFR expression in the bronchiolar epithelium with neutrophilic inflammation and mucus hypersecretion in the tissues of DPB patients. DESIGN The tissue specimens of 13 DPB patients and 6 healthy control subjects were examined by alcian blue/periodic acid-Schiff (AB/PAS) staining for mucous glycoconjugates, and by immunohistochemical staining for MUC5AC, EGFR, tumor necrosis factor-alpha, and CD16 on neutrophils. RESULTS Neutrophilic inflammation was significantly higher in the tissue of DPB patients than in that of control subjects (p = 0.002). In the bronchiolar epithelium, goblet cell metaplasia, by AB/PAS staining and mucin MUC5AC expression, was significantly higher than that in control subjects (p = 0.001 and p = 0.002, respectively). In addition, the morphometric quantification of intraluminal mucus secretion showed that the areas of the bronchiolar lumen occupied by mucus secretion were significantly increased in the tissue of DPB patients (p = 0.001), suggesting goblet cell degranulation. EGFR expression was observed in the bronchiolar epithelium of DPB patients, but not in that of control subjects. CONCLUSIONS In DPB, we suggest that mucus hypersecretion due to goblet cell metaplasia is closely associated with neutrophilic inflammation and the expression of EGFR. The study also shows that intraluminal secretion due to the degranulation of goblet cells degranulation is related to neutrophilic inflammation.

Increased cell-free DNA concentrations in patients with obstructive sleep apnea

Aim:  Blood concentrations of cell‐free DNA, which is considered to be released during apoptosis, are elevated under some pathological conditions such as cardiovascular disease and cancer. The association between obstructive sleep apnea (OSA) and cell‐free DNA concentrations has not been reported so far. The purpose of the present study was to examine the association between OSA and plasma DNA concentrations.

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).

Mycobacterium avium lung disease combined with a bronchogenic cyst in an immunocompetent young adult

We report a very rare case of a bronchogenic cyst combined with nontuberculous mycobacterial pulmonary disease in an immunocompetent patient. A 21-year-old male was referred to our institution because of a cough, fever, and worsening of abnormalities on his chest radiograph, despite anti-tuberculosis treatment. Computed tomography of the chest showed a large multi-cystic mass over the right-upper lobe. Pathological examination of the excised lobe showed a bronchogenic cyst combined with a destructive cavitary lesion with granulomatous inflammation. Microbiological culture of sputum and lung tissue yielded Mycobacterium avium. The patient was administered anti-mycobacterial treatment that included clarithromycin.