COVID-19 Vaccine-Associated Pneumonitis in the Republic of Korea:A Nationwide Multicenter Survey

Background@#Recent reports have suggested that pneumonitis is a rare complication following vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).However, its clinical features and outcomes are not well known. The aim of this study was to identify the clinical characteristics and outcomes of patients with vaccine-associated pneumonitis following vaccination against SARS-CoV-2. @*Methods@#In this nationwide multicenter survey study, questionnaires were distributed to pulmonary physicians in referral hospitals. They were asked to report cases of development or exacerbation of interstitial lung disease (ILD) associated with the coronavirus disease 2019 vaccine. Vaccine-associated pneumonitis was defined as new pulmonary infiltrates documented on chest computed tomography within 4 weeks of vaccination and exclusion of other possible etiologies. @*Results@#From the survey, 49 cases of vaccine-associated pneumonitis were identified between February 27 and October 30, 2021. After multidisciplinary discussion, 46 cases were analyzed. The median age was 66 years and 28 (61%) were male. The median interval between vaccination and respiratory symptoms was 5 days. There were 20 (43%), 17 (37%), and nine (19%) patients with newly identified pneumonitis, exacerbation of pre-diagnosed ILD, and undetermined pre-existing ILD, respectively. The administered vaccines were BNT162b2 and ChAdOx1 nCov-19/AZD1222 each in 21 patients followed by mRNA-1273 in three, and Ad26.COV2.S in one patient. Except for five patients with mild disease, 41 (89%) patients were treated with corticosteroid. Significant improvement was observed in 26 (57%) patients including four patients who did not receive treatment. However, ILD aggravated in 9 (20%) patients despite treatment. Mortality was observed in eight (17%) patients. @*Conclusion@#These results suggest pneumonitis as a potentially significant safety concern for vaccines against SARS-CoV-2. Clinical awareness and patient education are necessary for early recognition and prompt management. Additional research is warranted to identify the epidemiology and characterize the pathophysiology of vaccine-associated pneumonitis.

Identification of Biomarkers for the Diagnosis of Sepsis-Associated Acute Kidney Injury and Prediction of Renal Recovery in the Intensive Care Unit

Purpose@#Acute kidney injury (AKI) following sepsis is associated with higher mortality; however, reliable biomarkers for AKI development and recovery remain to be elucidated. @*Materials and Methods@#Patients with sepsis admitted to the medical intensive care unit (ICU) of Severance Hospital between June 2018 and May 2019 were prospectively analyzed. Patients were divided into those with and without AKI within 48 hours. Patients with septic AKI were subdivided into AKI-recovery and non-recovery groups based on whether their kidney injury recovered within 7 days. @*Results@#A total of 84 patients were enrolled. The baseline creatinine (2.9 mg/dL vs. 0.8 mg/dL vs. 1.2 mg/dL, p<0.001), Charlson Comorbidity Index (4.5 vs. 2.0 vs. 3.0, p=0.002), Sequential Organ Failure Assessment (10.0 vs. 6.5 vs. 8.0, p<0.001), and Acute Physiology and Chronic Health Evaluation II scores (32.0 vs. 21.5 vs. 30.5, p=0.004) were higher in the non-recovery AKI group compared to the non-AKI and AKI-recovery groups. The Kaplan-Meier curves revealed that non-recovery from AKI was associated with lower survival (p<0.001). High-lactate (p≤0.05) and kynurenine levels (p≤0.05) were associated with non-recovery of renal function following AKI. The areas under the curve for predicting non-recovery from AKI were 0.693 and 0.721 for lactate and kynurenine, respectively. The survival rate was lower in the high-kynurenine (p=0.040) and high-lactate (p=0.010) groups. @*Conclusion@#The mortality of patients who recovered from AKI was comparable to that of patients without AKI. Lactate and kynurenine could be useful biomarkers for the diagnosis and recovery of AKI following sepsis.

The Assessment and Outcomes of Crossmatching in Lung Transplantation in Korean Patients

Background@#In lung transplantation, human leukocyte antigen (HLA) compatibility is not included in the lung allocation score system or considered when placing donor allografts.However, HLA matching may affect the outcomes of lung transplantation. This study evaluated the current assessment status, prevalence, and effects of HLA crossmatching in lung transplantation in Korean patients using nationwide multicenter registry data. @*Methods@#Two hundred and twenty patients who received lung transplantation at six tertiary hospitals in South Korea between March 2015 and December 2019 were retrospectively reviewed. Clinical data, including general demographic characteristics, primary diagnosis, and pretransplant status of the recipients and donors registered by the Korean Organ Transplant Registry, were retrospectively analyzed. Survival analysis was performed using the Kaplan-Meier method with log-rank tests. @*Results@#Complement-dependent cytotoxic crossmatch (CDC-XM) was performed in 208 patients (94.5%) and flow cytometric crossmatch (flow-XM) was performed in 125 patients (56.8%). Among them, nine patients (4.1%) showed T cell- and/or B cell-positive crossmatches. The incidences of postoperative complications, including primary graft dysfunction, acute rejection, and chronic allograft dysfunction in positively crossmatched patients, were not significant compared with those in patients without mismatches.Moreover, Kaplan-Meier analyses showed poorer 1-year survival in patients with positive crossmatch according to CDC-XM (P < 0.001) and T lymphocyte XM (P = 0.002) than in patients without mismatches. @*Conclusion@#Positive CDC and T lymphocyte crossmatching results should be considered in the allocation of donor lungs. If unavailable, the result should be considered for postoperative management in lung transplantation.

The Association between Behavioral Risk Factors and Nontuberculous Mycobacterial Pulmonary Disease

Purpose@#We aimed to determine the relationship between environmental exposure and nontuberculous mycobacterial pulmonary disease (NTM-PD) in Korea. @*Materials and Methods@#A group of 150 patients with NTM-PD and a control group of 217 patients with other respiratory diseases were prospectively enrolled between June 2018 and December 2020 in Seoul, Korea. They were surveyed with a standardized questionnaire, and their medical records were reviewed. Odds ratio (OR) and 95% confidence intervals (CI) were calculated with multivariate logistic regression analysis. @*Results@#The mean ages of the NTM-PD and control groups were similar (63.8±9.2 years vs. 63.5±10.0 years; p=0.737), and most patients were female (76.0% vs. 68.7%; p=0.157) and nonsmokers (82.0% vs. 72.8%; p=0.021). Mycobacterium avium (49.3%) was the most commonly identified strain among NTM-PD patients, followed by M. intracellulare (32.0%) and M. abscessus subspecies massiliense (12.7%). There were no differences in housing type or frequency of soil- or pet-related exposure between the case and the control groups. However, in subgroup analysis excluding patients with M. intracellulare infection, more case patients frequently visited public baths ≥1 time/week (35.3% vs. 19.4%, p=0.003); this remained significant after multivariate analysis (OR, 2.84; 95% CI, 1.58–5.17). @*Conclusion@#Frequent exposure to water at public baths might affect the odds of contracting NTM-PD, excluding individuals infected with M. intracellulare strains.

The Association between Behavioral Risk Factors and Nontuberculous Mycobacterial Pulmonary Disease

Purpose@#We aimed to determine the relationship between environmental exposure and nontuberculous mycobacterial pulmonary disease (NTM-PD) in Korea. @*Materials and Methods@#A group of 150 patients with NTM-PD and a control group of 217 patients with other respiratory diseases were prospectively enrolled between June 2018 and December 2020 in Seoul, Korea. They were surveyed with a standardized questionnaire, and their medical records were reviewed. Odds ratio (OR) and 95% confidence intervals (CI) were calculated with multivariate logistic regression analysis. @*Results@#The mean ages of the NTM-PD and control groups were similar (63.8±9.2 years vs. 63.5±10.0 years; p=0.737), and most patients were female (76.0% vs. 68.7%; p=0.157) and nonsmokers (82.0% vs. 72.8%; p=0.021). Mycobacterium avium (49.3%) was the most commonly identified strain among NTM-PD patients, followed by M. intracellulare (32.0%) and M. abscessus subspecies massiliense (12.7%). There were no differences in housing type or frequency of soil- or pet-related exposure between the case and the control groups. However, in subgroup analysis excluding patients with M. intracellulare infection, more case patients frequently visited public baths ≥1 time/week (35.3% vs. 19.4%, p=0.003); this remained significant after multivariate analysis (OR, 2.84; 95% CI, 1.58–5.17). @*Conclusion@#Frequent exposure to water at public baths might affect the odds of contracting NTM-PD, excluding individuals infected with M. intracellulare strains.

Basiliximab Induction with Delayed Calcineurin Inhibitors for High-Risk Lung Transplant Candidates

Purpose@#Calcineurin inhibitor (CNI) use has improved lung transplantation outcomes. However, significant perioperative complications in patients receiving CNI can deteriorate the early course of lung transplantation. To date, there is no consensus regarding the optimal agent for the induction regimen after lung transplantation. We aimed to determine the efficacy of basiliximab induction with delayed CNI initiation in the prevention of acute complications without compromising immunosuppression in high-risk patients. @*Materials and Methods@#Between January 2013 and December 2019, 236 patients at a single lung transplant center were retrospectively reviewed. Forty-one patients (17.4%) received basiliximab induction, and 195 patients (82.6%) received a routine triple-drug regimen without induction. The primary endpoint was postoperative acute kidney injury with several other postoperative outcomes as secondary end-points. @*Results@#Preoperatively, the induction group had a higher proportion of patients who were admitted before transplantation (95.1% vs. 47.7%, p<0.001) and received intensive unit care (90.2% vs. 33.8%, p<0.001) and extracorporeal membrane oxygenation (ECMO) (87.8% vs. 20.0%, p<0.001) compared to the non-induction group. No significant differences were observed in the incidence of acute rejection between groups (p=0.657), although lower incidence of postoperative complications, including acute kidney injuries or culture-proven infections, were observed in the induction group. However, the differences were not statistically significant. A subgroup analysis of high-risk and preoperative ECMO support groups showed similar results. @*Conclusion@#Basiliximab induction with delayed CNI initiation for high-risk patients might decrease the incidence of perioperative complications, including acute renal failure, without increasing the risk of acute rejection.

Characteristics and risk factors associated with missed diagnosis in patients with smear-negative pulmonary tuberculosis

Background/Aims@#Delayed diagnosis and treatment of smear-negative pulmonary tuberculosis (TB) are major concerns for TB control. We evaluated characteristics of patients with smear-negative pulmonary TB who received a delayed diagnosis and identified risk factors that may have contributed to this delay. @*Methods@#We reviewed medical records of patients with smear-negative culture-positive pulmonary TB treated at a tertiary care hospital in South Korea between January 2017 and December 2018. Patients who initiated anti-TB treatment after positive cultures were included in the missed TB group, and those who initiated empirical treatment before positive cultures were included in the control group. @*Results@#Of 220 patients included, 117 (53.2%) and 103 (46.8%) were in the missed TB and control groups, respectively. Patients in the missed TB group were older (p = 0.001) and had a higher mean body mass index (BMI) (p = 0.019). Comorbidities (66.9% vs. 46.6%, p = 0.003) and immunocompromised patients (33.1% vs. 20.4%, p = 0.035) were more common in the missed TB group than in the control group. Old age (odds ratio [OR], 1.030; 95% confidence interval [CI], 1.012 to 1.048; p = 0.001), high BMI (OR, 1.114; 95% CI, 1.004 to 1.237; p = 0.042), and negative polymerase chain reaction (PCR) results (OR, 9.551; 95% CI, 4.925 to 18.521; p < 0.001) were associated with delayed diagnosis. @*Conclusions@#In more than half of patients with smear-negative pulmonary TB, the diagnosis was delayed. Patients with delayed TB diagnosis were older, had higher BMI, and negative PCR results.

Risk Factors for Predicting Hypoxia in Adult Patients Undergoing Bronchoscopy under Sedation / 결핵및호흡기질환

Background@#Flexible bronchoscopy is one of the essential procedures for the diagnosis and treatment of pulmonary diseases. The purpose of this study was to identify the risk factors associated with the occurrence of hypoxia in adults undergoing flexible bronchoscopy under sedation. @*Methods@#We retrospectively analyzed 2,520 patients who underwent flexible bronchoscopy under sedation at our tertiary care university hospital in South Korea January 1, 2013–December 31, 2014. Hypoxia was defined as more than 5%-point reduction in the baseline percutaneous oxygen saturation (SpO2) or SpO2 1 minute during the procedure. @*Results@#The mean age was 64.7±13.5, and 565 patients developed hypoxia during the procedure. The mean sedation duration and midazolam dose for sedation were 31.1 minutes and 3.9 mg, respectively. The bivariate analysis showed that older age, a low forced expiratory volume in one second (FEV1), use of endobronchial ultrasound, the duration of sedation, and the midazolam dose were associated with the occurrence of hypoxia during the procedure, while the multivariate analysis found that age >60 (odds ratio [OR], 1.32), a low FEV1 (OR, 0.99), and a longer duration of sedation (>40 minutes; OR, 1.33) were significant risk factors. @*Conclusion@#The findings suggest that patients older than age 60 and those with a low FEV1 tend to develop hypoxia during the bronchoscopy under sedation. Also, longer duration of sedation (>40 minutes) was a significant risk factor for hypoxia.

Incidental Lung Cancer of Explanted Lungs from Lung Transplant Recipients:Incidence, Characteristics, and 5-Year Survival

Purpose@#Recent history of malignancy without 5-year disease-free interval is an absolute contraindication for lung transplantation (LTx). However, in rare cases, lung cancer may be incidentally diagnosed in the explanted lung of recipients. We evaluated the prevalence, 5-year survival, and prognosis of incidental lung cancer after LTx. @*Materials and Methods@#Medical records of patients who underwent LTx at Severance Hospital between January 1, 2012 and June 30, 2019 were reviewed. Patients with incidental lung cancer were included, and those with histologically proven pre-transplant lung cancer were excluded. @*Results@#Of the 247 patients who underwent LTx, 6 (2.4%) were diagnosed with incidental lung cancer. Interstitial lung disease (ILD) was the underlying lung disease in all patients. The median interval from the last preoperative computed tomography (CT) screening to LTx was 26 days. The most common histological type of incidental lung cancer was adenocarcinoma (n=4, 66.7%).All Stage IV cases were misdiagnosed as fibrosis on preoperative chest CT. Patients with incidental lung cancer showed lower 5-year survival than those without malignancy (median survival: 8.5 months vs. not reached, p=0.047, respectively). Patients with Stage III or IV demonstrated lower 5-year survival than those with Stage I or II and those without malignancy (median survival: 5 months, 19 months, and not reached, respectively, p=0.011). @*Conclusion@#Multidisciplinary preoperative screening and serial imaging studies within short intervals are required to differentiate lung malignancy from fibrotic foci. Furthermore, active pathologic examination of suspicious lung lesions is required in patients at high risk for lung cancer.

Panel-Reactive and Donor-Specific Antibodies before Lung Transplantation can Affect Outcomes in Korean Patients Receiving Lung Transplantation

Purpose@#Data on the distribution and impact of panel reactive antibodies (PRA) and donor specific antibodies (DSA) before lung transplantation in Asia, especially multi-center-based data, are limited. This study evaluated the prevalence of and effects of PRA and DSA levels before lung transplantations on outcomes in Korean patients using nationwide multicenter registry data. @*Materials and Methods@#This study included 103 patients who received a lung transplant at five tertiary hospitals in South Korea between March 2015 and December 2017. Mortality, primary graft dysfunction (PGD), and bronchiolitis obliterans syndrome (BOS) were evaluated. @*Results@#Sixteen patients had class I and/or class II PRAs exceeding 50%. Ten patients (9.7%) had DSAs with a mean fluorescence intensity (MFI) higher than 1000, six of whom had antibodies with a high MFI (≥2000). DSAs with high MFIs were more frequently observed in patients with high-grade PGD (≥2) than in those with no or low-grade (≤1) PGD. In the 47 patients who survived for longer than 9 months and were evaluated for BOS after the transplant, BOS was not related to DSA or PRA levels. One-year mortality was more strongly related to PRA class I exceeding 50% than that under 50% (0% vs. 16.7%, p=0.007). @*Conclusion@#Preoperative DSAs and PRAs are related to worse outcomes after lung transplantation. DSAs and PRAs should be considered when selecting lung transplant recipients, and recipients who have preoperative DSAs with high MFI values and high PRA levels should be monitored closely after lung transplantation.

Characteristics and Treatment Outcomes of Isoniazid Mono-Resistant Tuberculosis:A Retrospective Study

Purpose@#Isoniazid (INH) mono-resistant tuberculosis (Hr-TB) is a highly prevalent type of drug-resistant TB, possibly associated with unfavorable treatment outcomes. However, definitive guidelines on an optimal treatment regimen and duration for Hr-TB are currently under discussion. We evaluated the characteristics and treatment outcomes of Hr-TB patients. @*Materials and Methods@#We retrospectively reviewed the medical records of Hr-TB patients treated at a South Korean tertiary referral hospital from January 2005 to December 2018. @*Results@#We included 195 Hr-TB patients. 113 (57.9%) were male, and the median age was 56.6 [interquartile range, 40.2–68.6] years. Mutations in katG were the most frequent [54 (56.3%)], followed by those in the inhA [34 (35.4%)]. Favorable and unfavorable outcomes were noted in 164 (84.1%) and 31 (15.9%) patients, respectively. Smoking history [odds ratio (OR)=5.606, 95% confidence interval (CI): 1.695–18.543, p=0.005], low albumin level (OR=0.246, 95% CI: 0.104–0.578, p=0.001), and positive acid-fast bacilli culture at 2 months (OR=7.853, 95% CI: 1.246–49.506, p=0.028) were associated with unfavorable outcomes. @*Conclusion@#A tailored strategy targeting high-risk patients is imperative for improved treatment outcomes. Further research on the rapid and accurate detection of resistance to INH and other companion drugs is warranted.

Age- and sex-related characteristics of the increasing trend of nontuberculous mycobacteria pulmonary disease in a tertiary hospital in South Korea from 2006 to 2016

Background/Aims@#The incidence rate of nontuberculous mycobacterial pulmonary disease (NTM-PD) is increasing worldwide. However, data regarding the age- and sex-specific epidemiology of NTM-PD are limited. This study aimed to investigate the long-term epidemiologic trends of NTM-PD within the recent 11- year period in a tertiary referral hospital in Korea. @*Methods@#We retrospectively reviewed the medical records of the patients diagnosed with NTM-PD between January 2006 and December 2016 at Severance Hospital, South Korea. @*Results@#There were 1,017 incident cases with NTM-PD during the study period. The mean age was 62.7 years, and 41.2% were men. Women were younger than men (59.9 years vs. 66.7 years, p < 0.001) and a higher proportion of women had bronchiectasis (88.6% vs. 77.1%, p < 0.001). The incidence rates of NTM-PD annually increased by 14% (95% confidence interval, 10% to 19%) from 1.2 in 2006 to 4.8 in 2016 (per 100,000 patients-year). The peak incidence rate was in the 50s for women and in the 70s for men, except for those aged ≥ 80 years. Mycobacterium avium complex was the most common causative species of NTM-PD (63.6%). @*Conclusions@#The incidence rate of NTM-PD in a tertiary referral hospital in South Korea continued to increase from 2006 to 2016. Furthermore, there were age- and sex-related differences in the clinical characteristics, which might contribute to understanding the nature of the disease and inherited and acquired host factors.

Clinical significance of postoperative atrial arrhythmias in patients who underwent lung transplantation

Background/Aims@#Atrial arrhythmia (AA) occasionally occurs after lung transplantation (LT); however, risk factors for AA and their impact on clinical outcomes are inconsistent. We aimed to investigate the incidence, predisposing factors, and clinical outcomes of AA after LT. @*Methods@#We retrospectively evaluated 153 consecutive patients who underwent LT between January 2010 and August 2016. An AA episode was defined as a documented atrial fibrillation (AF), atrial flutter, or atrial tachycardia on 12-lead electrocardiography or episodes lasting ≥ 30 seconds on telemetry monitoring. @*Results@#The mean follow-up time was 22.0 ± 19.1 months. Postoperative AA occurred in 46 patients (30.1%) after LT. Patients with postoperative AA were older, had larger body surface area, and had an increased incidence of paroxysmal AF prior to transplantation, idiopathic pulmonary fibrosis, and postoperative tracheostomy than patients without AA. Preoperative right atrial pressure (RAP) (odds ratio [OR], 1.19; p = 0.005) and longer periods of mechanical ventilation (OR, 1.03; p = 0.008) were found to be independent risk factors for AA after surgery. Development of AA was a significant predictor of long-term overall mortality (hazard ratio, 2.75; p = 0.017). @*Conclusions@#Patients with elevated preoperative RAP and long-term ventilator care had a higher risk of AA after LT. Further, AA after LT was associated with poor long-term survival.

The Effects of Retinoic Acid and MAPK Inhibitors on Phosphorylation of Smad2/3 Induced by Transforming Growth Factor β1 / 결핵및호흡기질환

BACKGROUND: Transforming growth factor β (TGF-β), retinoic acid (RA), p38 mitogen-activated protein kinase (MAPK), and MEK signaling play critical roles in cell differentiation, proliferation, and apoptosis. We investigated the effect of RA and the role of these signaling molecules on the phosphorylation of Smad2/3 (p-Smad2/3) induced by TGF-β1. METHODS: A549 epithelial cells and CCD-11Lu fibroblasts were incubated and stimulated with or without all-trans RA (ATRA) and TGF-β1 and with MAPK or MEK inhibitors. The levels of p-Smad2/3 were analyzed by western blotting. For animal models, we studied three experimental mouse groups: control, bleomycin, and bleomycin+ATRA group. Changes in histopathology, lung injury score, and levels of TGF-β1 and Smad3 were evaluated at 1 and 3 weeks. RESULTS: When A549 cells were pre-stimulated with TGF-β1 prior to RA treatment, RA completely inhibited the p-Smad2/3. However, when A549 cells were pre-treated with RA prior to TGF-β1 stimulation, RA did not completely suppress the p-Smad2/3. When A549 cells were pre-treated with MAPK inhibitor, TGF-β1 failed to phosphorylate Smad2/3. In fibroblasts, p38 MAPK inhibitor suppressed TGF-β1-induced p-Smad2. In a bleomycin-induced lung injury mouse model, RA decreased the expression of TGF-β1 and Smad3 at 1 and 3 weeks. CONCLUSION: RA had inhibitory effects on the phosphorylation of Smad induced by TGF-β1 in vitro, and RA also decreased the expression of TGF-β1 at 1 and 3 weeks in vivo. Furthermore, pre-treatment with a MAPK inhibitor showed a preventative effect on TGF-β1/Smad phosphorylation in epithelial cells. As a result, a combination of RA and MAPK inhibitors may suppress the TGF-β1-induced lung injury and fibrosis.

Korean Guidelines for Diagnosis and Management of Interstitial Lung Diseases: Part 2. Idiopathic Pulmonary Fibrosis / 결핵

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial pneumonia, which presents with a progressive worsening dyspnea, and thus a poor outcome. The members of the Korean Academy of Tuberculosis and Respiratory Diseases as well as the participating members of the Korea Interstitial Lung Disease Study Group drafted this clinical practice guideline for IPF management. This guideline includes a wide range of topics, including the epidemiology, pathogenesis, risk factors, clinical features, diagnosis, treatment, prognosis, and acute exacerbation of IPF in Korea. Additionally, we suggested the PICO for the use of pirfenidone and nintendanib and for lung transplantation for the treatment of patients with IPF through a systemic literature review using experts' help in conducting a meta-analysis. We recommend this guideline to physicians, other health care professionals, and government personnel in Korea, to facilitate the treatment of patients with IPF.

Validation of Voriconazole Therapeutic Drug Monitoring in Lung Transplant Recipients Receiving Voriconazole alone for Treatment of Invasive Aspergillosis

BACKGROUND: Invasive aspergillosis (IA) is associated with high morbidity and mortality, particularly among immunocompromised patients, such as lung transplant recipients. Voriconazole, the first-line therapy for IA, shows a non-linear pharmacokinetic profile and has a narrow therapeutic range. Careful and appropriate administration is necessary, primarily because it is used for critically ill patients; however, the clinical usefulness of therapeutic drug monitoring (TDM) has not been sufficiently verified. Therefore, in this study, we validated the safety and efficacy of voriconazole TDM in lung transplant recipients receiving only voriconazole for IA treatment. METHODS: The electronic medical records of lung transplant recipients (≥19 years of age) administered only voriconazole for > 7 days for treatment of IA from June 1, 2013 to May 31, 2018 were analyzed retrospectively. RESULTS: Among the 54 patients, 27 each were allocated to TDM and non-TDM groups, respectively. There were no significant differences in patient characteristics between the two groups except for ICU-hospitalization status. Of the TDM group patients, 81.5% needed adjustment of voriconazole dosage because the levels were out of target range. Comparison of two groups showed that treatment response was higher throughout treatment and switching rates of second-line agents were significantly lower in the TDM group, but it was insufficient to confirm safety improvements through voriconazole TDM. CONCLUSION: Considering that the treatment response tended to be higher and the rates of switching to second-line antifungal agents were lower in the TDM group, voriconazole TDM may increase the therapeutic effect on IA in lung transplant patients.

Korean Guidelines for Diagnosis and Management of Interstitial Lung Diseases: Part 2. Idiopathic Pulmonary Fibrosis / 결핵및호흡기질환

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial pneumonia, which presents with a progressive worsening dyspnea, and thus a poor outcome. The members of the Korean Academy of Tuberculosis and Respiratory Diseases as well as the participating members of the Korea Interstitial Lung Disease Study Group drafted this clinical practice guideline for IPF management. This guideline includes a wide range of topics, including the epidemiology, pathogenesis, risk factors, clinical features, diagnosis, treatment, prognosis, and acute exacerbation of IPF in Korea. Additionally, we suggested the PICO for the use of pirfenidone and nintendanib and for lung transplantation for the treatment of patients with IPF through a systemic literature review using experts' help in conducting a meta-analysis. We recommend this guideline to physicians, other health care professionals, and government personnel in Korea, to facilitate the treatment of patients with IPF.

Preoperative Corticosteroid Use and Early Postoperative Bronchial Anastomotic Complications after Lung Transplantation

BACKGROUND: Airway anastomotic complications are a leading cause of mortality after lung transplantation. Among the factors that cause airway complications, preoperative steroid use has been considered to be related with postoperative airway healing. We analyzed the influence of preoperative steroid use on postoperative airway complications. METHODS: The medical records of 66 double-lung transplant recipients from January 2014 to December 2015 were reviewed. Forty patients were prescribed steroids preoperatively. The daily steroid dose was standardized using the patient’s body mass index (BMI). Patients who received preoperative steroids were sub-divided into high-dose (HD) and low-dose (LD) groups (cut-off value, 1.6 mg/BMI/day). RESULTS: Thirteen patients suffered from airway complications postoperatively (bronchopulmonary fistula, 9; bronchial stenosis, 4). There was a tendency for early development of airway complications in the steroid use group compared to the non-steroid use group, but it was not significant (percentage free from airway complications in year 1: non-steroid group, 90.9% vs. steroid group, 79.2%; p=0.43). The percentage of patients in the LD and HD groups who were free from airway complications in year 1 was not significantly different (84.0% vs. 77.8%, p=0.39). CONCLUSION: The airway complication rate did not vary significantly according to steroid use. Additionally, in patients who received preoperative steroids, the dose did not affect the rate of development of airway complications.

Factors Associated with Lung Function Recovery at the First Year after Lung Transplantation

PURPOSE: Post-operative pulmonary function is an important prognostic factor for lung transplantation. The purpose of this study was to identify factors affecting recovery of forced expiratory volume in 1 second (FEV1) at the first year after lung transplantation. MATERIALS AND METHODS: We retrospectively reviewed the medical records of lung transplantation patients between October 2012 and June 2016. Patients who survived for longer than one year and who underwent pulmonary function test at the first year of lung transplantation were enrolled. Patients were divided into two groups according to whether they recovered to a normal range of FEV1 (FEV1 ≥80% of predicted value vs. < 80%). We compared the two groups and analyzed factors associated with lung function recovery. RESULTS: Fifty-eight patients were enrolled in this study: 28 patients (48%) recovered to a FEV1 ≥80% of the predicted value, whereas 30 patients (52%) did not. Younger recipients [odds ratio (OR), 0.92; 95% confidence interval (CI), 0.87–0.98; p=0.010], longer duration of mechanical ventilator use after surgery (OR, 1.14; 95% CI, 1.03–1.26; p=0.015), and high-grade primary graft dysfunction (OR, 8.08; 95% CI, 1.67–39.18; p=0.009) were identified as independent risk factors associated with a lack of full recovery of lung function at 1 year after lung transplantation. CONCLUSION: Immediate postoperative status may be associated with recovery of lung function after lung transplantation.

Utility of Conventional Culture and MALDI-TOF MS for Identification of Microbial Communities in Bronchoalveolar Lavage Fluid in Comparison with the GS Junior Next Generation Sequencing System

BACKGROUND: Diverse microbiota exist in the lower respiratory tract. Although next generation sequencing (NGS) is the most widely used microbiome analysis technique, it is difficult to implement NGS in clinical microbiology laboratories. Therefore, we evaluated the performance of conventional culture methods together with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) in identifying microbiota in bronchoalveolar lavage (BAL) fluid. METHODS: BAL fluid samples (n=27) were obtained from patients undergoing diagnostic bronchoscopy for lung mass evaluation. Bacterial and fungal culture was performed with conventional media used in clinical microbiology laboratories. On an average, 20 isolated colonies were picked from each agar plate and identified by MALDI-TOF MS. Microbiome analysis using 16S rRNA NGS was conducted for comparison. RESULTS: Streptococcus spp. and Neisseria spp. were most frequently cultured from the BAL fluid samples. In two samples, Enterobacteriaceae grew predominantly on MacConkey agar. Actinomyces and Veillonella spp. were commonly identified anaerobes; gut bacteria, such as Lactobacillus, Bifidobacterium, and Clostridium, and fungi were also isolated. NGS revealed more diverse bacterial communities than culture, and Prevotella spp. were mainly identified solely by NGS. Some bacteria, such as Staphylococcus spp., Clostridium spp., and Bifidobacterium spp., were identified solely by culture, indicating that culture may be more sensitive for detecting certain bacteria. CONCLUSIONS: Culture and NGS of BAL fluid samples revealed common bacteria with some different microbial communities. Despite some limitations, culture combined with MALDI-TOF MS might play a complementary role in microbiome analysis using 16S rRNA NGS.