Hye Yun Park

What is asthma−COPD overlap syndrome? Towards a consensus definition from a round table discussion

Patients with asthma–chronic obstructive pulmonary disease overlap syndrome (ACOS) have been largely excluded from pivotal therapeutic trials and, as a result, its treatment remains poorly defined and lacking firm evidence. To date, there is no universally accepted definition of ACOS, which has made it difficult to understand its epidemiology or pathophysiology. Despite many uncertainties, there is emerging agreement that some of the key features of ACOS include persistent airflow limitation in symptomatic individuals 40 years of age and older, a well-documented history of asthma in childhood or early adulthood and a significant exposure history to cigarette or biomass smoke. In this perspective, we propose a case definition of ACOS that incorporates these key features in a parsimonious algorithm that may enable clinicians to better diagnose patients with ACOS and most importantly enable researchers to design therapeutic and clinical studies to elucidate its epidemiology and pathophysiology and to ascertain its optimal management strategies. We propose that asthma-COPD overlap syndrome be defined based on three major criteria and one minor criterion http://ow.ly/3rOU304aTNm

Repeated derecruitments accentuate lung injury during mechanical ventilation.

OBJECTIVES The aim of our study was to assess whether repeated derecruitments induced by the repetitive withdrawal of high positive end-expiratory pressure could induce lung injury in a swine model. DESIGN Prospective, randomized, experimental animal study. SETTING University laboratory. SUBJECTS Specific pathogen-free pigs (Choong-Ang Laboratory Animals, Seoul, Korea) weighing around 30 kg. INTERVENTIONS After lung injury was induced by repeated saline lavage, pigs were ventilated in pressure-limited mode with the highest possible positive end-expiratory pressure with a tidal volume of 8 mL/kg and maximum inspiratory pressure of 30 cm H2O. With this initial ventilator setting, the control group (n = 5) received ventilation without derecruitments for 4 hours, and in the derecruitment group (n = 5), derecruitments were repeatedly induced by intentional disconnection of the ventilatory circuit for 30 seconds every 5 minutes for 4 hours. MEASUREMENTS AND MAIN RESULTS After the initial increase in positive end-expiratory pressure, the PaO2 increased to greater than 450 mm Hg in both groups. The PaO2 remained at greater than 450 mm Hg in the control group persistently, but in the derecruitment group, PaO2 significantly decreased to 427.7 mm Hg (adjusted p = 0.03) after 2 hours and remained significant for the rest of the study. PaCO2, oxygenation index, and alveolar-arterial oxygen gradient also significantly increased after 2 hours compared with the control group. However, the variables of respiratory mechanics except for minute volume at 2-hour point showed no difference between the two groups for the duration of the study. Histologically, significant bronchiolar injury was observed in the dependent portion of the derecruitment group compared with the controls (p = 0.03), but not in the nondependent area of the lung. CONCLUSIONS Repeated derecruitments exacerbated lung injury, particularly at the bronchiolar level in the dependent portion. Strategies to minimize this type of injury should be incorporated when designing optimal ventilator strategies in acute respiratory distress syndrome patients.Objectives:The aim of our study was to assess whether repeated derecruitments induced by the repetitive withdrawal of high positive end-expiratory pressure could induce lung injury in a swine model. Design:Prospective, randomized, experimental animal study. Setting:University laboratory. Subjects:Specific pathogen-free pigs (Choong–Ang Laboratory Animals, Seoul, Korea) weighing around 30 kg. Interventions:After lung injury was induced by repeated saline lavage, pigs were ventilated in pressure-limited mode with the highest possible positive end-expiratory pressure with a tidal volume of 8 mL/kg and maximum inspiratory pressure of 30 cm H2O. With this initial ventilator setting, the control group (n = 5) received ventilation without derecruitments for 4 hours, and in the derecruitment group (n = 5), derecruitments were repeatedly induced by intentional disconnection of the ventilatory circuit for 30 seconds every 5 minutes for 4 hours. Measurements and Main Results:After the initial increase in positive end-expiratory pressure, the PaO2 increased to greater than 450 mm Hg in both groups. The PaO2 remained at greater than 450 mm Hg in the control group persistently, but in the derecruitment group, PaO2 significantly decreased to 427.7 mm Hg (adjusted p = 0.03) after 2 hours and remained significant for the rest of the study. PaCO2, oxygenation index, and alveolar-arterial oxygen gradient also significantly increased after 2 hours compared with the control group. However, the variables of respiratory mechanics except for minute volume at 2-hour point showed no difference between the two groups for the duration of the study. Histologically, significant bronchiolar injury was observed in the dependent portion of the derecruitment group compared with the controls (p = 0.03), but not in the nondependent area of the lung. Conclusions:Repeated derecruitments exacerbated lung injury, particularly at the bronchiolar level in the dependent portion. Strategies to minimize this type of injury should be incorporated when designing optimal ventilator strategies in acute respiratory distress syndrome patients.

Intermittent Antibiotic Therapy for Nodular Bronchiectatic Mycobacterium avium Complex Lung Disease

RATIONALE Although intermittent, three-times-weekly therapy is recommended for the initial treatment of noncavitary nodular bronchiectatic Mycobacterium avium complex (MAC) lung disease, supporting data are limited. OBJECTIVES To evaluate the clinical efficacy of intermittent therapy compared with daily therapy for nodular bronchiectatic MAC lung disease. METHODS A retrospective cohort study of 217 patients with treatment-naive noncavitary nodular bronchiectatic MAC lung disease. All patients received either daily (n = 99) or intermittent therapy (n = 118) that included clarithromycin or azithromycin, rifampin, and ethambutol. MEASUREMENTS AND MAIN RESULTS Modification of the initial antibiotic therapy occurred more frequently in the daily therapy group than in the intermittent therapy group (46 vs. 21%; P < 0.001); in particular, ethambutol was more frequently discontinued in the daily therapy group than in the intermittent therapy group (24 vs. 1%; P ≤ 0.001). However, the rates of symptomatic improvement, radiographic improvement, and sputum culture conversion were not different between the two groups (daily therapy vs. intermittent therapy: 75 vs. 82%, P = 0.181; 68 vs. 73%, P = 0.402; 76 vs. 67%, P = 0.154, respectively). In addition, the adjusted proportion of sputum culture conversion was similar between the daily therapy (71.3%; 95% confidence interval, 59.1-81.1%) and the intermittent therapy groups (73.6%; 95% confidence interval, 62.9-82.2%; P = 0.785). CONCLUSIONS These results suggest that intermittent three-times-weekly therapy with a macrolide, rifampin, and ethambutol is a reasonable initial treatment regimen for patients with noncavitary nodular bronchiectatic MAC lung disease. Clinical trial registered with www.clinicaltrials.gov (NCT 00970801).

Endobronchial Ultrasound versus Mediastinoscopy for Mediastinal Nodal Staging of Non-Small-Cell Lung Cancer

Introduction: Correct mediastinal staging is critical for determination of the most appropriate management strategy in patients with non–small-cell lung cancer (NSCLC). The purpose of this study was to compare the diagnostic performance of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) with that of mediastinoscopy in patients with NSCLC. Methods: A prospective trial was conducted in a tertiary referral center in Korea. Patients with histologically proven NSCLC and suspicion for N1, N2, or N3 metastasis were enrolled. Each patient underwent EBUS-TBNA followed by mediastinoscopy. Surgical resection and complete lymph node dissection were conducted in patients for whom no evidence of mediastinal metastasis was apparent after mediastinoscopy. Results: In total, 138 patients underwent EBUS-TBNA and 127 completed both EBUS-TBNA and mediastinoscopy. N2/N3 disease was confirmed in 59.1% of the patients. The diagnostic sensitivity, specificity, accuracy, positive predictive value, and negative predictive value (NPV) of EBUS-TBNA on a per-person analysis were 88.0%, 100%, 92.9%, 100%, and 85.2%, respectively. The diagnostic sensitivity, specificity, accuracy, positive predictive value, and NPV of mediastinoscopy on a per-person analysis were 81.3%, 100%, 89.0%, 100%, and 78.8%, respectively. Significant differences in the sensitivity, accuracy, and NPV were evident between EBUS-TBNA and mediastinoscopy (p < 0.005). Conclusions: EBUS-TBNA was superior to mediastinoscopy in terms of its diagnostic performance for mediastinal staging of cN1–3 NSCLC. Because EBUS-TBNA is both less invasive and affords superior diagnostic sensitivity, it should be the first-line procedure performed in patients with NSCLC.

Treatment of Refractory Mycobacterium avium Complex Lung Disease with a Moxifloxacin-Containing Regimen

ABSTRACT Moxifloxacin (MXF) has in vitro and in vivo activity against Mycobacterium avium complex (MAC) in experimental models. However, no data are available concerning its treatment effect in patients with MAC lung disease. The aim of this study was to evaluate the clinical efficacy of an MXF-containing regimen for the treatment of refractory MAC lung disease. Patients with MAC lung disease who were diagnosed between January 2002 and December 2011 were identified from our hospital database. We identified 41 patients who received MXF for ≥4 weeks for the treatment of refractory MAC lung disease. A total of 41 patients were treated with an MXF-containing regimen because of a persistent positive culture after at least 6 months of clarithromycin-based standardized antibiotic therapy. The median duration of antibiotic therapy before MXF administration was 410 days (interquartile range [IQR], 324 to 683 days). All patients had culture-positive sputum when MXF treatment was initiated. The median duration of MXF administration was 332 days (IQR, 146 to 547 days). The overall treatment success rate was 29% (12/41), and the median time to sputum conversion was 91 days (IQR, 45 to 190 days). A positive sputum acid-fast-bacillus smear at the start of treatment with MXF-containing regimens was an independent predictor of an unfavorable microbiological response. Our results indicate that MXF may improve treatment outcomes in about one-third of patients with persistently culture-positive MAC lung disease who fail to respond to clarithromycin-based standardized antibiotic treatment. Prospective studies are required to assess the clinical efficacy of MXF treatment for refractory MAC lung disease.

Mycobacterial Characteristics and Treatment Outcomes in Mycobacterium abscessus Lung Disease

Background. Treatment outcomes of patients with Mycobacterium abscessus subspecies abscessus lung disease are poor, and the microbial characteristics associated with treatment outcomes have not been studied systematically. The purpose of this study was to identify associations between microbial characteristics and treatment outcomes in patients with M. abscessus lung disease. Methods. Sixty-seven consecutive patients with M. abscessus lung disease undergoing antibiotic treatment for ≥12 months between January 2002 and December 2012 were included. Morphotypic and genetic analyses were performed on isolates from 44 patients. Results. Final sputum conversion to culture negative occurred in 34 (51%) patients. Compared to isolates from 24 patients with persistently positive cultures, pretreatment isolates from 20 patients with final negative conversion were more likely to exhibit smooth colonies (9/20, 45% vs 2/24, 8%; P = .020), susceptibility to clarithromycin (7/20, 35% vs 1/24, 4%; P = .015), and be of the C28 sequevar with regard to the erm(41) gene (6/20, 30% vs 1/24, 4%; P = .035). Mycobacterium abscessus lung disease recurred in 5 (15%) patients after successful completion of antibiotic therapy. Genotypic analysis revealed that most episodes (22/24, 92%) of persistently positive cultures during antibiotic treatment and all cases of microbiologic recurrence after treatment completion were caused by different M. abscessus genotypes within a patient. Conclusions. Precise identification to the subspecies level and analysis of mycobacterial characteristics could help predict treatment outcomes in patients with M. abscessus lung disease. Treatment failures and recurrences are frequently associated with multiple genotypes, suggesting reinfection. Clinical Trials Registration. NCT00970801.

Standardized Combination Antibiotic Treatment of Mycobacterium avium Complex Lung Disease

Purpose The optimal treatment regimen for Mycobacterium avium complex (MAC) lung disease has not yet been fully established. We evaluated the efficacy of standardized combination antibiotic therapy and the factors that might affect unfavorable microbiologic responses in patients with MAC pulmonary disease. Materials and Methods This retrospective study reviewed data from 96 patients (56 females; median age 59 years) treated with newly diagnosed MAC lung disease between January 2003 and December 2006. Results All patients received standardized combination antibiotic therapy, consisting of clarithromycin, rifampicin, and ethambutol. Streptomycin was additionally given in 72 patients (75%) for a median duration of 4.5 months. The overall favorable microbiologic response rate was 79% (76/96); 20 patients (21%) had unfavorable microbiologic responses, including failure to sputum conversion (n = 13), relapse (n = 3), and MAC-related death (n = 4). A positive sputum acid-fast bacillus smear at the start of treatment was an independent predictor of an unfavorable microbiologic response. Conclusion Standardized combination antibiotic therapy consisting of clarithromycin, rifampicin, and ethambutol with or without initial use of streptomycin is effective in treating patients with newly diagnosed MAC lung disease.

Lung function, coronary artery calcification, and metabolic syndrome in 4905 Korean males

BACKGROUND Impaired lung function is an independent predictor of cardiovascular mortality. We assessed the relationships of lung function with insulin resistance (IR), metabolic syndrome (MetS), systemic inflammation and coronary artery calcification score (CACS) measured by computed tomography (CT) scan an indicator of coronary atherosclerosis. METHODS We identified 4905 adult male patients of the Health Promotion Center in Samsung Medical Center between March 2005 and February 2008 and retrospectively reviewed the following data for these patients: pulmonary function, CT-measured CACS, anthropometric measurement, fasting glucose, insulin, lipid profiles, serum C-reactive protein (CRP) and homeostatic model assessment (HOMA-IR). MetS was defined according to the AHA/NHLBI criteria. RESULTS When the subjects were divided into four groups according to quartiles of FVC or FEV(1) (% pred), serum CRP level, HOMA-IR, prevalence of MetS and CACS significantly increased as the FVC or FEV(1) (% pred) decreased. The odds ratios (ORs) for MetS in the lowest quartiles of FVC and FEV(1) (% pred) were 1.85 (95% CI, 1.49-2.30; p<0.001) and 1.47 (95% CI, 1.20-1.81; p<0.001) respectively. The ORs for the presence of coronary artery calcification in the lowest quartiles of FVC and FEV(1) (% pred) were 1.31 (95% CI, 1.09-1.58; p=0.004) and 1.22 (95% CI, 1.02-1.46; p=0.029) respectively. Obesity, CRP, HOMA-IR, and the presence of coronary artery calcium were independent risk predictors for impaired lung function. CONCLUSION Metabolic syndrome, insulin resistance, coronary atherosclerosis, and systemic inflammation are closely related to the impaired lung function.

Early initiation of low-dose corticosteroid therapy in the management of septic shock: a retrospective observational study

IntroductionThe use of low-dose steroid therapy in the management of septic shock has been extensively studied. However, the association between the timing of low-dose steroid therapy and the outcome has not been evaluated. Therefore, we evaluated whether early initiation of low-dose steroid therapy is associated with mortality in patients with septic shock.MethodsWe retrospectively analyzed the clinical data of 178 patients who received low-dose corticosteroid therapy for septic shock between January 2008 and December 2009. Time-dependent Cox regression models were used to adjust for potential confounding factors in the association between the time to initiation of low-dose corticosteroid therapy and in-hospital mortality.ResultsThe study population consisted of 107 men and 71 women with a median age of 66 (interquartile range, 54 to 71) years. The 28-day mortality was 44% and low-dose corticosteroid therapy was initiated within a median of 8.5 (3.8 to 19.1) hours after onset of septic shock-related hypotension. Median time to initiation of low-dose corticosteroid therapy was significantly shorter in survivors than in non-survivors (6.5 hours versus 10.4 hours; P = 0.0135). The mortality rates increased significantly with increasing quintiles of time to initiation of low-dose corticosteroid therapy (P = 0.0107 for trend). Other factors associated with 28-day mortality were higher Simplified Acute Physiology Score (SAPS) 3 (P < 0.0001) and Sequential Organ Failure Assessment (SOFA) scores (P = 0.0007), dose of vasopressor at the time of initiation of low-dose corticosteroid therapy (P < 0.0001), need for mechanical ventilation (P = 0.0001) and renal replacement therapy (P < 0.0001), while the impaired adrenal reserve did not affect 28-day mortality (81% versus 82%; P = 0.8679). After adjusting for potential confounding factors, the time to initiation of low-dose corticosteroid therapy was still significantly associated with 28-day mortality (adjusted odds ratio (OR) 1.025, 95% confidence interval (CI) 1.007 to 1.044, P = 0.0075). The early therapy group (administered within 6 hours after the onset of septic shock, n = 66) had a 37% lower mortality rate than the late therapy group (administered more than 6 hours after the onset of septic shock, n = 112) (32% versus 51%, P = 0.0132).ConclusionsEarly initiation of low-dose corticosteroid therapy was significantly associated with decreased mortality.

Asthma–COPD overlap syndrome (ACOS): A diagnostic challenge

Asthma–chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) is characterized by persistent airflow limitation with several features usually associated with asthma and several features usually associated with COPD. ACOS may be a special phenotype of a spectrum of chronic obstructive airway diseases, in which asthma and COPD are at the two opposite ends. The prevalence of ACOS varies considerably due to differing criteria being applied for diagnosis. Patients with ACOS utilize a large proportion of medical resources. They are associated with more frequent adverse outcomes than those with asthma or COPD alone. ACOS is currently a diagnostic challenge for physicians because there are no specific biomarkers to differentiate ACOS from asthma or COPD. The approach to diagnosing ACOS depends on the population from which the patient originated. The management of ACOS should be individualized to ensure the most effective treatment with minimal side effects. In this paper, we review the diagnostic criteria of ACOS used in previous studies, propose practical approaches to diagnosing and managing ACOS and raise some research questions related to ACOS.