Prospective direct comparison of biologic treatments for severe eosinophilic asthma: Findings from the PRISM study.

BACKGROUND: Although various monoclonal antibodies have been used as add-on therapy for severe eosinophilic asthma (SEA), to the best of our knowledge, no direct head-to-head comparative study has evaluated their efficacy. OBJECTIVE: To compare the efficacy of reslizumab, mepolizumab, and dupilumab in patients with SEA. METHODS: This was a multicenter, prospective observational study in patients with SEA who had received 1 of these biologic agents for at least 6 months. Cox proportional hazard models were used to compare the risk of the first exacerbation event, adjusting for sputum or blood eosinophils and common asthma-related covariates. The annual exacerbation rate was analyzed using a negative binomial model, and a mixed-effect model was used to analyze changes in forced expiratory volume in 1 second and asthma control test score over time. RESULTS: A total of 141 patients with SEA were included in the analysis; 71 (50%) received dupilumab; 40 (28%) received reslizumab, and 30 (21%) received mepolizumab. During the 12-month follow-up, 27.5%, 43.3%, and 38.0% of patients in the reslizumab, mepolizumab, and dupilumab groups, respectively, experienced at least 1 exacerbation. However, after adjusting for confounding factors, the dupilumab and mepolizumab groups showed similar outcomes in time-to-first exacerbation, exacerbation rate, forced expiratory volume in 1 second, and asthma control test score to those of the reslizumab group. CONCLUSION: In patients with SEA, treatment with reslizumab, mepolizumab, and dupilumab resulted in comparable clinical outcomes within a 12-month period. TRIAL REGISTRATION: The cohort protocol was sanctioned by the Institutional Review Board of each study center (clinicaltrial.gov identifier NCT05164939).

Predictors of Early and Late Lung Function Improvement in Severe Eosinophilic Asthma on Type2-Biologics in the PRISM Study.

BACKGROUND: The determinants linked to the short- and long-term improvement in lung function in patients with severe eosinophilic asthma (SEA) on biological treatment (BioT) remain elusive. OBJECTIVE: We sought to identify the predictors of early and late lung function improvement in patients with SEA after BioT. METHODS: 140 adult patients with SEA who received mepolizumab, dupilumab, or reslizumab were followed up for 6 months to evaluate improvement in forced expiratory volume in one second (FEV1). Logistic regression was used to determine the association between potential prognostic factors and improved lung function at 1 and 6 months of treatment. RESULTS: More than a third of patients with SEA using BioT showed early and sustained improvements in FEV1 after 1 month. A significant association was found between low baseline FEV1 and high blood eosinophil count and sustained FEV1 improvement after 1 month (0.54 [0.37-0.79] and 1.88 [1.28-2.97] odds ratios and 95% confidence interval, respectively). Meanwhile, among patients who did not experience FEV1 improvement after 1 month, 39% exhibited improvement at 6 months follow-up. A high ACT score measured at this visit was the most reliable predictor of late response after 6 months of treatment (OR and 95% CI 1.75 [1.09-2.98]). CONCLUSION: Factors predicting the efficacy of biological agents that improve lung function in SEA vary according to the stage of response.

WITHDRAWN: Prospective direct comparison of biological treatments on severe eosinophilic asthma: Findings from the PRISM study.

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Prognostic marker for severe acute exacerbation of chronic obstructive pulmonary disease: analysis of diffusing capacity of the lung for carbon monoxide (DLCO) and forced expiratory volume in one second (FEV1).

BACKGROUND: It is important to assess the prognosis of patients with chronic obstructive pulmonary disease (COPD) and acute exacerbation of COPD (AECOPD). Recently, it was suggested that diffusing capacity of the lung for carbon monoxide (DLCO) should be added to multidimensional tools for assessing COPD. This study aimed to compare the DLCO and forced expiratory volume in one second (FEV1) to identify better prognostic factors for admitted patients with AECOPD. METHODS: We retrospectively analyzed 342 patients with AECOPD receiving inpatient treatment. We classified 342 severe AECOPD patients by severity of DLCO and FEV1 (≤ vs. > 50% predicted). We tested the association of FEV1 and DLCO with the following outcomes: in-hospital mortality, need for mechanical ventilation, need for intensive care unit (ICU) care. We analyzed the prognostic factors by multivariate analysis using logistic regression. In addition, we conducted a correlation analysis and receiver operating characteristic (ROC) curve analysis. RESULTS: In multivariate analyses, DLCO was associated with mortality (odds ratio = 4.408; 95% CI 1.070-18.167; P = 0.040) and need for mechanical ventilation (odds ratio = 2.855; 95% CI 1.216-6.704; P = 0.016) and ICU care (odds ratios = 2.685; 95% CI 1.290-5.590; P = 0.008). However, there was no statistically significant difference in mortality rate when using FEV1 classification (P = 0.075). In multivariate linear regression analyses, DLCO (B = - 0.542 ± 0.121, P < 0.001) and FEV1 (B = - 0.106 ± 0.106, P = 0.006) were negatively associated with length of hospital stay. In addition, DLCO showed better predictive ability than FEV1 in ROC curve analysis. The area under the curve (AUC) of DLCO was greater than 0.68 for all prognostic factors, and in contrast, the AUC of FEV1 was less than 0.68. CONCLUSION: DLCO was likely to be as good as or better prognostic marker than FEV1 in severe AECOPD.

Variation of clinical manifestations according to culprit drugs in DRESS syndrome.

PURPOSE: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare but serious condition that systematically damages various internal organs through T-cell-mediated immunological drug reactions. We aimed to investigate whether clinical manifestations of DRESS syndrome differ according to culprit drugs. METHODS: We retrospectively analyzed data from 123 patients with probable/definite DRESS syndrome based on the RegiSCAR criteria (January 2011 to July 2016). The data were obtained from the Korean Severe Cutaneous Adverse Reaction Registry. Causality was assessed using the World Health Organization-Uppsala Monitoring Centre criteria. The culprit drugs were categorized as allopurinol, carbamazepine, anti-tuberculosis drug, vancomycin, cephalosporins, dapsone, and nonsteroidal anti-inflammatory drugs. RESULTS: Differences were observed among culprit drugs regarding the frequencies of hepatitis (P < 0.01), renal dysfunction (P < 0.0001), lymphadenopathy (P < 0.01), and atypical lymphocyte (P < 0.01). Latency period differed among culprit drugs (P < 0.0001), being shorter in vancomycin and cephalosporin. In terms of clinical severity, admission duration (P < 0.01) and treatment duration (P < 0.05) differed among culprit drugs, being longer in vancomycin and anti-tuberculosis drugs, respectively. CONCLUSIONS: Based on the findings, clinical manifestations, including latency period and clinical severity, may differ according to culprit drugs in DRESS syndrome.

Clinical Features of Hereditary Angioedema in Korean Patients: A Nationwide Multicenter Study.

BACKGROUND: Hereditary angioedema (HAE) is a genetically heterogeneous autosomal dominant disorder characterized by recurrent episodes of nonpruritic, nonpitting edema increasing after puberty. It can be fatal due to laryngeal or gastrointestinal (GI) involvement with varied and changing frequency of mortality according to studies published from the Western countries. Epidemiological and clinical data of HAE in Asian countries are sparse. We sought to examine the clinical characteristics of HAE patients in Korea. METHODS: Patients diagnosed with HAE at 15 tertiary hospitals across the country until 2016 were retrospectively reviewed. RESULTS: A total of 65 patients diagnosed with HAE by 2016 were identified. The prevalence of HAE was estimated at 1.3/1,000,000 in Korea. Of the 65 patients, 21 (32.3%) were males. A total of 90.8% patients had type I HAE, while the remaining 9.2% patients had type II HAE. The first symptom developed after 20 years in 73.8% of patients, with a mean age 28.4 ± 14.1 years. The age at diagnosis was 36.5 ± 15.8 years, with a mean time delay of 7.8 ± 10.5 years. While the face (82.3%) and extremities (upper 71.0%, lower 62.9%) were the most frequently involved, the GI tract was affected in 40.5% of Korean HAE patients. Prophylaxis was maintained in 62.5% of patients. There was no reported case of death from HAE so far. CONCLUSIONS: The clinical manifestation and severity of HAE may vary according to ethnicity. HAE is more infrequent and GI involvement is less likely in Korea compared with Western countries.

Prognostic Factors and Skeletal-Related Events in Patients with Small Cell Lung Cancer with Bone Metastases at the Time of Diagnosis.

BACKGROUND/OBJECTIVE: The aim of this study was to evaluate the characteristics and prognostic factors of small cell lung cancer (SCLC) with bone metastases. We also investigated the characteristics and predictive factors of skeletal-related events (SREs) in these patients. MATERIALS AND METHODS: Sixty-one patients who were first diagnosed with SCLC with bone metastases at our institution were included in this retrospective analysis. RESULTS: The overall survival (OS) of patients with bone metastases was shorter than that of patients without bone metastases (4.13 vs. 6.17 months, p = 0.015). Poor Eastern Cooperative Oncology Group (ECOG) performance status (PS; ≥2) and higher serum alkaline phosphatase (ALP; above upper normal limit × 2) were independent poor prognostic factors (p = 0.027 for ECOG PS, p = 0.002 for ALP). More than 1 SRE occurred in 21 patients (34.4%). Cervical spine metastasis, thoracic spine metastasis, pelvic bone metastasis, more than 5 bone metastatic regions and higher serum lactate dehydrogenase were correlated with the occurrence of SREs. Thoracic spinal metastasis was a strong predictive factor for the occurrence of SREs (odds ratio = 5.475; 95% CI: 1.080-27.755). CONCLUSION: Our study demonstrates the poor prognosis of SCLC patients with bone metastases. Physicians should treat SCLC patients with bone metastases with caution.

The effect of an IκB-kinase-ß(IKKß) inhibitor on tobacco smoke-induced pulmonary inflammation.

PURPOSE OF THE STUDY: Inactivation of NF-κB with IKKß knockout mice reduces tobacco smoke-induced pulmonary inflammation. In this study, we investigated whether the IKKß inhibitor PS-1145 could attenuate the pulmonary inflammation induced by tobacco smoke. MATERIALS AND METHODS: We divided 30 mice into three groups: a control group, a smoking group, and a PS-1145 group. Mice from the smoking and PS-1145 groups were exposed for 2 weeks to tobacco smoke. PS-1145 was injected intraperitoneally before every tobacco smoke exposure. After 2 weeks, bronchoalveolar lavage (BAL) was performed for cell counting and measuring of inflammatory chemokines. We analyzed the correlation between NF-κB and NF-κB-regulated chemokines in BAL fluid and measured the neutrophils and macrophages by immunostaining in lung tissues. RESULTS: The PS-1145 group showed a significant reduction in the number of total cells, neutrophils, and macrophages, as well as the KC and MCP-1 level, in the BAL fluid compared to the smoking group. There was no significant difference in the level of MIP-1α. The level of NF-κB in BAL fluid was significantly positively correlated with KC and MCP-1 levels, but not with MIP-1α level. The PS-1145 group also showed a significant fewer neutrophils and macrophages in the lung tissue. CONCLUSIONS: We conclude that the IKKß inhibitor PS-1145 suppressed the NF-κB signaling pathway and reduced the recruitment of inflammatory cells and chemokines in pulmonary inflammation induced by tobacco smoke. IKKß inhibition offers a potential therapeutic target for tobacco smoke-induced pulmonary inflammation.

Comparison of the Efficacy between Pemetrexed plus Platinum and Non-Pemetrexed plus Platinum as First-Line Treatment in Patients with Wild-Type Epidermal Growth Factor Receptor Nonsquamous Non-Small Cell Lung Cancer: A Retrospective Analysis.

BACKGROUND: Despite the development of molecular research and targeted therapy, patients with wild-type epidermal growth factor receptor (EGFR) non-small cell lung cancer (NSCLC) still receive platinum doublet chemotherapy as the standard first-line treatment. We investigated the efficacy of first-line regimens in patients with wild-type EGFR nonsquamous NSCLC. METHODS: We retrospectively analyzed the efficacy of various platinum doublet regimens as first-line treatments. Between 2007 and 2013, a total of 165 patients with wild-type EGFR nonsquamous NSCLC were included in this study. RESULTS: Seventy-one (43.0%) patients were treated with pemetrexed plus platinum (PP) and 94 (57.0%) with non-pemetrexed plus platinum (NPP). The overall response rate was not different between the PP- and NPP-treated groups (26.8 vs. 28.7%, respectively; p = 0.78). The median progression-free survival (PFS) and overall survival (OS) also showed no differences between the two treatment groups (p = 0.12 for PFS, p = 0.42 for OS). The median PFS and OS for the PP group were 4.6 months (95% CI, 3.8-5.4) and 18.7 months (95% CI, 11.7-25.8), respectively, and for the NPP group, they were 4.2 months (95% CI, 3.4-5.0) and 12.2 months (95% CI, 10.3-14.1), respectively. In the subgroup analysis, most subgroups showed no significant difference in PFS and OS between the two treatment groups. CONCLUSION: Our data showed that the efficacy of various platinum doublet regimens was similar in patients with wild-type EGFR nonsquamous NSCLC.

Biological and genetic markers in occupational asthma.

Occupational asthma (OA) is a complex disease that is often hard to diagnose due to difficulties in detecting relevant exposure, along with inherent differences in disease susceptibility. Numerous studies have attempted to identify relevant biological and genetic markers for OA and to devise tools capable of detecting exposure to the causative agent. Immunological markers, including skin prick test reactivity and specific IgE and IgG antibodies can be used to detect high-molecular-weight allergens in cases of baker's asthma. For OA induced by low-molecular-weight agents, such as isocyanate, potential biomarkers include serum-specific IgE and IgG antibodies to isocyanate-HSA conjugate and IgG to cytokeratin 19 and transglutaminase-2. For protein-based markers, ferritin/transferrin and vitamin D-binding protein levels have been suggested for isocyanate-OA. Genetic markers of susceptibility to isocyanate-OA include human leukocyte antigen and CTNNA3. Further investigations will be needed to identify better biomarkers for OA, which may be used to inform clinical decision.

Effects of transglutaminase 2 inhibition on ventilator-induced lung injury.

This study was performed to examine the role of transglutaminase 2 (TG2) in ventilator-induced lung injury (VILI). C57BL/6 mice were divided into six experimental groups: 1) control group; 2) lipopolysaccharide (LPS) group; 3) lung protective ventilation (LPV) group; 4) VILI group; 5) VILI with cystamine, a TG2 inhibitor, pretreatment (Cyst+VILI) group; and 6) LPV with cystamine pretreatment (Cyst+LPV) group. Acute lung injury (ALI) score, TG2 activity and gene expression, inflammatory cytokines, and nuclear factor-κB (NF-κB) activity were measured. TG2 activity and gene expression were significantly increased in the VILI group (P < 0.05). Cystamine pretreatment significantly decreased TG2 activity and gene expression in the Cyst+VILI group (P < 0.05). Inflammatory cytokines were higher in the VILI group than in the LPS and LPV groups (P < 0.05), and significantly lower in the Cyst+VILI group than the VILI group (P < 0.05). NF-κB activity was increased in the VILI group compared with the LPS and LPV groups (P < 0.05), and significantly decreased in the Cyst+VILI group compared to the VILI group (P = 0.029). The ALI score of the Cyst+VILI group was lower than the VILI group, but the difference was not statistically significant (P = 0.105). These results suggest potential roles of TG2 in the pathogenesis of VILI.

New targets for type 2-low asthma.

Asthma is characterized by airway obstruction and inflammation, and presents significant diagnostic and treatment challenges. The concept of endotypes has improved understanding of the mechanisms of asthma and has stimulated the development of effective treatment strategies. Sputum profiles may be used to classify asthma into two major inflammatory types: type 2-high (T2H) and type 2-low (T2L) asthma. T2H, characterized by elevated type 2 inflammation, has been extensively studied and several effective biologic treatments have been developed. However, managing T2L is more difficult due to the lack of reliable biomarkers for accurate diagnosis and classification. Additionally, conventional anti-inflammatory therapy does not completely control the symptoms of T2L; therefore, further research is needed to identify effective biologic treatments. This review provides new insights into the clinical characteristics and underlying mechanisms of severe T2L and investigates potential therapeutic approaches to control the disease.

Rapid Progression of Acute Interstitial Pneumonia in a Patient with Low MDA-5 Antibody Titer.

BACKGROUND Melanoma differentiation associated gene-5 antibody (MDA-5 Ab) is one of the diagnostic autoantibodies that appears in idiopathic inflammatory myopathies (IIMs). Unlike when other autoantibodies are positive, when this antibody is positive, there is less characteristic muscle involvement. However, this MDA-5 Ab-positive myopathy presents extremely rapid progression of interstitial lung disease, resulting in a high mortality rate. Previous studies reported that the prognosis of this lung disease will be determined by the titer and suggest that low titers of MDA-5 antibody can indicate a good prognosis in associated interstitial lung disease. CASE REPORT Our case describes a 55-year-old woman who presented with acute respiratory symptoms and dyspnea. After hospitalization, symptoms and chest imaging worsened rapidly, and the radiology image of lung disease featured interstitial changes not seen in typical infections. We treated the patient with a high-flow oxygen nasal cannula, empirical antibiotics, and a systemic steroid. While treatment for a disease of unknown cause was continued, low titer of MDA-5 antibody was identified. CONCLUSIONS This case suggests 2 points to consider about non-infectious interstitial changes with acute respiratory distress syndrome. First, when treating rapidly progressing interstitial pneumonia of an unknown cause, it is recommended to consider lung involvement of MDA-5 Ab dermatomyositis. Second, a low titer of MDA-5 Ab can be associated with better prognosis in this MDA-5 Ab dermatomyositis-related lung disease.

Mechanical ventilation in patients with idiopathic pulmonary fibrosis in Korea: a nationwide cohort study.

BACKGROUND/AIMS: The prognosis of patients with idiopathic pulmonary fibrosis (IPF) and respiratory failure requiring mechanical ventilation is poor. Therefore, mechanical ventilation is not recommended. Recently, outcomes of mechanical ventilation, including those for patients with IPF, have improved. The aim of this study was to investigate changes in the use of mechanical ventilation in patients with IPF and their outcomes over time. METHODS: This retrospective, observational cohort study used data from the National Health Insurance Service database. Patients diagnosed with IPF between January 2011 and December 2019 who were placed on mechanical ventilation were included. We analyzed changes in the use of mechanical ventilation in patients with IPF and their mortality using the Cochran- Armitage trend test. RESULTS: Between 2011 and 2019, 1,227 patients with IPF were placed on mechanical ventilation. The annual number of patients with IPF with and without mechanical ventilation increased over time. However, the ratio was relatively stable at approximately 3.5%. The overall hospital mortality rate was 69.4%. There was no improvement in annual hospital mortality rate. The overall 30-day mortality rate was 68.7%, which did not change significantly. The overall 90-day mortality rate was 85.3%. The annual 90-day mortality rate was decreased from 90.9% in 2011 to 83.1% in 2019 (p = 0.028). CONCLUSION: Despite improvements in intensive care and ventilator management, the prognosis of patients with IPF receiving mechanical ventilation has not improved significantly.

Serum MRGPRX2 as a Long-term Biomarker for Iodinated Contrast Media-Induced Anaphylaxis.

The diagnosis of anaphylaxis is based on the clinical history. The utility of tryptase measurements in clinical setting is limited. Mas-related G protein-coupled receptor-X2 (MRGPRX2) is expressed in mast cells and is involved in the degranulation of these cells. We evaluated the potential of MRGPRX2 as a diagnostic biomarker in patients with iodinated contrast media (ICM)-induced immediate hypersensitivity reactions (IHRs). A total of 173 patients with documented ICM-induced IHR within 4 months from registration were enrolled and skin tests for the culprit ICM were performed. The time interval was evaluated as the duration between the onset of ICM-induced IHR and the measurement of serum MRGPRX2 levels. Serum MRGPRX2 concentration was determined using an enzyme-linked immunosorbent assay kit. Of the 173 patients, 33 and 140 were included in the anaphylaxis and non-anaphylaxis groups, respectively. Serum MRGPRX2 levels were significantly higher in the anaphylaxis than in the non-anaphylaxis group (29.9 ± 24.1 vs. 20.7±17.5, P = 0.044). Serum MRGPRX2 showed a moderate predictive ability for anaphylaxis, with an area under the curve of 0.61 (P = 0.058). When groups were classified based on the time interval, T1(0-2months) and T2 (2-4months), patients with anaphylaxis had higher MRGPRX2 levels compared to the non-anaphylaxis group in the T2 group (36.5±19.2 vs. 20.5±19.0, P = 0.035). This pilot study shows that serum MRGPRX2 is a potential long-term biomarker for predicting anaphylaxis, particularly ICM-induced anaphylaxis. Further studies are needed to determine the role of MRGPRX2 in anaphylaxis in a larger population of patients with various drug-induced IHRs.

Skin Test-Guided Strategy to Select Alternative Iodinated Contrast Media in Patients With Immediate Hypersensitivity Reaction: A Prospective Confirmative Study.

BACKGROUND: Iodinated contrast media (ICM) are a common cause of drug-induced immediate hypersensitivity reaction (IHR). Repeated use of ICM is often necessary; therefore, a standardized protocol to prevent recurrence of IHR is required. OBJECTIVE: We aimed to propose an intradermal skin test (IDT)-guided strategy for previous reactors to prevent recurrence of IHR. METHODS: We conducted a prospective multicenter study from May 2018 to December 2020 and recruited patients who had experienced IHR to ICM. Once enrolled, the participants underwent IDT with a causative ICM. The alternatives for reexposure were selected using the following protocol: (1) if the IDT with the culprit ICM was positive, further skin tests with other available ICM were conducted to choose IDT-negative agents as alternatives, and (2) if the IDT with the culprit ICM was negative, a randomly changed ICM was used without additional skin tests. The recurrence and severity of hypersensitivity were assessed in subsequent computed tomography examinations. Premedication was administered according to the severity of the index event in all cases. RESULTS: A total of 496 participants were enrolled, and 299 were reexposed to ICM. Among 269 participants who followed the protocol, 228 (84.8%) completed computed tomography examinations without adverse reactions, and IHR recurred in 16 of 30 participants (53.3%) who did not follow the protocol (P < .001). In addition, application of the protocol reduced the severity of IHR in recurred cases (P = 0.003). CONCLUSIONS: Our IDT-guided strategy not only reduced recurrence of IHR to ICM but also mitigated the severity in recurred cases. This provides evidence for recommending an IDT to diagnose ICM allergy and find safe alternatives.

Effect of interleukin-18 gene polymorphisms on sensitization to wheat flour in bakery workers.

Lower respiratory symptoms in bakery workers may be induced by wheat flour and endotoxins. We hypothesized that endotoxins from wheat flour may stimulate innate immunity and that interleukin-18 (IL-18) gene polymorphisms may affect their regulatory role in innate immune responses to endotoxins. To investigate the genetic contribution of IL-18 to sensitization to wheat flour, we performed a genetic association study of IL-18 in Korean bakery workers. A total of 373 bakery workers undertook a questionnaire regarding work-related symptoms. Skin prick tests with common and occupational allergens were performed and specific antibodies to wheat flour were measured by ELISA. Three polymorphisms of the IL-18 gene (-607A/C, -137G/C, 8674C/G) were genotyped, and the functional effects of the polymorphisms were analyzed using the luciferase reporter assay. Genotypes of -137G/C (GC or CC) and haplotype ht3 [ACC] showed a significant association with the rate of sensitization to wheat flour. Luciferase activity assay indicated ht3 [AC] as a low transcript haplotype. In conclusion, the regulatory role of IL-18 in lipopolysaccharide-induced responses in bakery workers may be affected by this polymorphism, thus contributing to the development of sensitization to wheat flour and work-related respiratory symptoms.

Cardiac Dysfunction Is Not Associated with Increased Reintubation Rate in Patients Treated with Post-extubation High-Flow Nasal Cannula.

BACKGROUND: Cardiac dysfunction patients have long been considered at high risk of reintubation. However, it is based on past studies in which only conventional oxygen therapy was applied after extubation. We investigated association between cardiac dysfunction and reintubation rate in situation where high-flow nasal cannula (HFNC) was widely used during post-extubation period. METHODS: We conducted a retrospective observational cohort study of patients treated with HFNC after planned extubation in medical intensive care unit of single tertiary center. Patients were divided into normal function group (ejection fraction [EF] ≥45%) and cardiac dysfunction group (EF <45%). The primary outcome was reintubation rate within 72 hours following extubation. RESULTS: Of 270 patients, 35 (13%) had cardiac dysfunction. Baseline characteristics were similar in both groups. There were no differences in the changes in vital signs between the two groups during the first 12 hours after extubation except diastolic blood pressure. The reintubation rates were 20% and 17% for cardiac dysfunction group and normal function group, respectively (p=0.637). In a multivariate Cox regression analysis, cardiac dysfunction was not associated with an increased risk of reintubation within 72 hours following extubation (hazard ratio, 1.56; p=0.292). CONCLUSION: Cardiac dysfunction was not associated with increased reintubation rate within 72 hours when HFNC is immediately applied after planned extubation.