Differential response to roflumilast in patients with chronic obstructive pulmonary disease: real-world evidence.

Background: Roflumilast is effective in reducing acute exacerbation in patients with chronic obstructive pulmonary disease (COPD) at high risk of severe exacerbation. Clinical traits related to the benefits of roflumilast need to be evaluated in patients with COPD. Methods: A longitudinal observational study in patients newly diagnosed with COPD was conducted using claims data from the Health Insurance Review and Assessment Service in South Korea from 2012-2020 after a 2-year washout period. The primary outcome was to estimate the ratio of hazard ratio (RHR) of roflumilast for moderate-to-severe exacerbation in prespecified subgroups. A time-dependent Cox regression model was used to estimate the hazard ratio (HR) for moderate-to-severe exacerbations. Results: Among 823,862 patients with COPD, 0.6% used roflumilast. The adjusted HR of roflumilast for moderate-to-severe exacerbations was reduced when treated for ≥3 months (RHR =0.558). Interaction effects of the variables on the HR of roflumilast for moderate-to-severe exacerbation were identified. The adjusted HR of roflumilast for moderate-to-severe exacerbation was significantly reduced in several subgroups: older age (65 years > age ≥50 years, RHR =0.838; age ≥65 years, RHR =0.818), a higher Charlson comorbidity index (1, RHR =0.832; 2, RHR =0.798; ≥3, RHR =0.790), history of exacerbation (RHR =0.886), bronchiectasis (RHR =0.774), chronic bronchitis (RHR =0.793), inhaled therapy [mono-bronchodilator, RHR =0.824; inhaled corticosteroid (ICS)/long-acting beta-agonist (LABA), RHR =0.591; LABA/long-acting muscarinic antagonist (LAMA), RHR =0.822; ICS/LABA/LAMA, RHR =0.570], methylxanthine (RHR =0.853), and statin (RHR =0.888). Conclusions: The benefit of roflumilast in moderate-to-severe exacerbations was estimated to be greater in specific subgroups of patients with COPD. Personalised approaches to roflumilast based on clinical phenotypes would be effective for COPD.

Acute Exacerbation and Longitudinal Lung Function Change of Preserved Ratio Impaired Spirometry.

Background: Preserved ratio impaired spirometry (PRISm) is a heterogeneous disease entity. Limited data are available regarding its prevalence, clinical course, or prognosis. We aimed to evaluate the longitudinal clinical course of patients with PRISm compared with chronic obstructive pulmonary disease (COPD). Methods: A retrospective study enrolled PRISm and COPD patients who underwent chest computed tomography and longitudinal pulmonary function tests between January 2013 and December 2020. We compared the incidence of acute exacerbations and lung function changes between PRISm and COPD patients. Results: Of the 623 patients, 40 and 583 had PRISm and COPD, respectively. Compared to COPD patients, PRISm patients were younger, more likely to be female and have a history of tuberculosis, and less likely to be smokers. They also had less severe comorbidities, lower forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO). The clinical course was not significantly different between the PRISm and COPD patients in terms of the risk of moderate-to-severe acute exacerbations or proportion of frequent exacerbators. During follow-up, PRISm patients had a significantly slower annual decline of forced expiratory volume in 1 second, FVC, and DLCO than COPD patients. Conclusion: PRISm patients had no significant difference in the risk of acute exacerbations, but a significantly slower decline of lung function during longitudinal follow-up, compared with COPD patients.

Diffusing capacity as an independent predictor of acute exacerbations in chronic obstructive pulmonary disease.

A weak correlation between diffusing capacity of the lung for carbon monoxide (DLCO) and emphysema has been reported. This study investigated whether impaired DLCO in chronic obstructive pulmonary disease (COPD) is associated with increased risk of acute exacerbation independent of the presence or extent of emphysema. This retrospective cohort study included patients with COPD between January 2004 and December 2019. The participants were divided into four groups based on visually detected emphysema and impaired DLCO. Among 597 patients with COPD, 8.5% had no emphysema and impaired DLCO whereas 36.3% had emphysema without impaired DLCO. Among the four groups, patients with impaired DLCO and emphysema showed a higher risk of moderate-to-severe or severe exacerbation than those with normal DLCO. Impaired DLCO was an independent risk factor for severe exacerbation (hazard ratio, 1.524 [95% confidence interval 1.121-2.072]), whereas the presence of emphysema was not. The risk of moderate-to-severe or severe exacerbation increases with the severity of impaired DLCO. After propensity-score matching for the extent of emphysema, impaired DLCO was significantly associated with a higher risk of moderate-to-severe (p = 0.041) or severe exacerbation (p = 0.020). In patients with COPD and heterogeneous parenchymal abnormalities, DLCO can be considered an independent biomarker of acute exacerbation.

Combined effect of changes in NO2, O3, PM2.5, SO2 and CO concentrations on small airway dysfunction.

BACKGROUND AND OBJECTIVE: When multiple complex air pollutants are combined in real-world settings, the reliability of estimating the effect of a single pollutant is questionable. This study aimed to investigate the combined effects of changes in air pollutants on small airway dysfunction (SAD). METHODS: We analysed Korea National Health and Nutrition Examination Survey (KNHANES) V-VIII database from 2010 to 2018 to elucidate the associations between annual changes in air pollutants over a previous 5-year period and small airway function. We estimated the annual concentrations of five air pollutants: NO2, O3, PM2.5, SO2 and CO. Forced expiratory flow between 25% and 75% of vital capacity (FEF25%-75%) <65% was defined as SAD. Using the quantile generalized-Computation (g-Computation) model, the combined effect of the annual changes in different air pollutants was estimated. RESULTS: A total of 29,115 individuals were included. We found significant associations between SAD and the quartiles of annual changes in NO2 (OR = 1.10, 95% CI = 1.08-1.12), O3 (OR = 1.03, 95% CI = 1.00-1.05), PM2.5 (OR = 1.03, 95% CI = 1.00-1.05), SO2 (OR = 1.04, 95% CI = 1.02-1.08) and CO (OR = 1.16, 95% CI = 1.12-1.19). The combined effect of the air pollutant changes was significantly associated with SAD independent of smoking (OR = 1.31, 95% CI = 1.26-1.35, p-value <0.001), and this trend was consistently observed across the entire study population and various subgroup populations. As the estimated risk of SAD, determined by individual-specific combined effect models, increased and the log odds for SAD increased linearly. CONCLUSION: The combined effect of annual changes in multiple air pollutant concentrations were associated with an increased risk of SAD.

Clinical outcomes of long-term inhaled combination therapies in patients with bronchiectasis and airflow obstruction.

BACKGROUND AND OBJECTIVES: Few studies have reported which inhaled combination therapy, either bronchodilators and/or inhaled corticosteroids (ICSs), is beneficial in patients with bronchiectasis and airflow obstruction. Our study compared the efficacy and safety among different inhaled combination therapies in patients with bronchiectasis and airflow obstruction. METHODS: Our retrospective study analyzed the patients with forced expiratory volume in 1 s (FEV1)/forced vital capacity < 0.7 and radiologically confirmed bronchiectasis in chest computed tomography between January 2005 and December 2021. The eligible patients underwent baseline and follow-up spirometric assessments. The primary endpoint was the development of a moderate-to-severe exacerbation. The secondary endpoints were the change in the annual FEV1 and the adverse events. Subgroup analyses were performed according to the blood eosinophil count (BEC). RESULTS: Among 179 patients, the ICS/long-acting beta-agonist (LABA)/long-acting muscarinic antagonist (LAMA), ICS/LABA, and LABA/LAMA groups were comprised of 58 (32.4%), 52 (29.1%), and 69 (38.5%) patients, respectively. ICS/LABA/LAMA group had a higher severity of bronchiectasis and airflow obstruction, than other groups. In the subgroup with BEC ≥ 300/uL, the risk of moderate-to-severe exacerbation was lower in the ICS/LABA/LAMA group (adjusted HR = 0.137 [95% CI = 0.034-0.553]) and the ICS/LABA group (adjusted HR = 0.196 [95% CI = 0.045-0.861]) compared with the LABA/LAMA group. The annual FEV1 decline rate was significantly worsened in the ICS/LABA group compared to the LABA/LAMA group (adjusted ß-coefficient=-197 [95% CI=-307--87]) in the subgroup with BEC < 200/uL. CONCLUSION: In patients with bronchiectasis and airflow obstruction, the use of ICS/LABA/LAMA and ICS/LABA demonstrated a reduced risk of exacerbation compared to LABA/LAMA therapy in those with BEC ≥ 300/uL. Conversely, for those with BEC < 200/uL, the use of ICS/LABA was associated with an accelerated decline in FEV1 in comparison to LABA/LAMA therapy. Further assessment of BEC is necessary as a potential biomarker for the use of ICS in patients with bronchiectasis and airflow obstruction.

Association between timed up-and-go test and subsequent pneumonia: A cohort study.

BACKGROUND: Sarcopenia is a risk factor for pneumonia in the elderly, and the timed up-and-go test (TUG) can be used as a screening tool for sarcopenia in this population. This study aimed to evaluate the association between TUG test results and future pneumonia or ventilator care. MATERIALS AND METHODS: From the National Health Insurance Service-Senior Cohort database, we identified 19,804 people without neurological diseases who underwent the TUG test in the National Screening Program for Transitional Ages at the age of 66 years during 2007-2008. Gait abnormality was defined as taking 10 s or longer to perform the TUG test. Pneumonia occurrence was defined using the International Classification of Diseases 10th Revision (ICD-10) code for pneumonia (J12-J18, J69), and ventilator care was defined by procedure codes (M5830, M5850, M5867, M5858, M5860, M5859) according to the Healthcare Common Procedure Coding system codes from 2007 to 2015. RESULTS: The mean follow-up period was 7.4 years (standard error, SE 0.02). The incidence rates of pneumonia in the normal and slow TUG groups were 38 and 39.5/1000 person-years, respectively. The slow TUG group did not show a higher risk of pneumonia (adjusted hazard ratio [aHR], 1.042; 95% confidence interval [95% CI], 0.988-1.107]). Regarding ventilator care, the incidence was 4.7 and 5.2 cases per 1,000 person-years in the normal and slow TUG groups, respectively. Slow TUG groups also did not show an increased risk of ventilator occurrence (aHR, 1.136, [95% CI = 0.947-1.363]). CONCLUSION: The TUG test result was not associated with future pneumonia or ventilator care and may not be useful for predicting pneumonia in community-dwelling elderly individuals. Further studies are needed to identify additional functional tools for sarcopenia associated with future pneumonia occurrences.

Association between successful weaning from nasogastric tube feeding and thoracic muscle mass in patients with aspiration pneumonia.

Nasogastric tube feeding is often used to provide optimal nutrition and hydration in patients with aspiration pneumonia. However, evidence regarding radiologic indicators for successful nasogastric tube weaning is lacking. We investigated whether thoracic skeletal muscle assessment can be useful for predicting successful weaning from nasogastric tube feeding in patients with aspiration pneumonia. This longitudinal, observational study included subjects with aspiration pneumonia who underwent a videofluoroscopic swallowing study (VFSS) and chest computed tomography (CT) in Boramae Medical Center, from January 2012 to December 2019. We estimated the area under the receiver operating characteristics curve (AUC) to evaluate the predictive performance of skeletal muscle and visceral fat parameters and VFSS results for successful weaning from nasogastric tube feeding. A board-certified radiologist measured muscle and fat areas. Muscle and fat volumes were segmented and measured using an externally validated convolutional neural network model. Among the 146 included patients, nasogastric tube feeding was successfully transitioned to oral feeding in 46.6%. After adjusting for covariables related to successful weaning, skeletal muscle areas, indices, and volume indices were positively associated with successful nasogastric tube weaning. Although VFSS results and skeletal muscle parameters alone showed suboptimal performance for predicting successful weaning, a prediction model combining skeletal muscle index at the T4 level and VFSS results improved the prediction performance to an acceptable level (AUC ≥ 0.7). Skeletal muscle index measured at the T4 level may be a useful supplementary indicator for predicting successful weaning from nasogastric tube feeding in patients with aspiration pneumonia.

Validation of the Rome proposal for severity of acute exacerbation of chronic obstructive pulmonary disease.

BACKGROUND: The Rome proposal provides an objective assessment tool for severity of acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) but requires validation. OBJECTIVES: We aimed to evaluate the predictive performance of the Rome proposal in patients with AE-COPD. DESIGN: This observational study assessed the patients who visited the emergency room (ER) or were hospitalized due to AE-COPD between January 2010 and December 2020. METHODS: We compared the performance of the Rome Proposal with that of the DECAF score or GesEPOC 2021 criteria in predicting intensive care unit (ICU) admission, need for non-invasive ventilation (NIV) or invasive mechanical ventilation (IMV), and in-hospital mortality. RESULTS: A total of 740 events of ER visit or hospitalization due to AE-COPD were reviewed and classified into mild (30.9%), moderate (58.6%), or severe (10.4%) group according to the Rome proposal. The severe group had a higher rate of ICU admission, required more NIV or IMV, and had a higher in-hospital mortality than the mild and moderate groups. The predictive performance of the Rome proposal was significantly better for ICU admission [area under the receiver operating characteristic curve (AU-ROC) = 0.850 versus 0.736, p = 0.004] and need for NIV or IMV (AU-ROC = 0.870 versus 0.770, p = 0.004) than that of the GesEPOC 2021 criteria but better than that of the DECAF score only in female patients. There was no significant difference in predicting the in-hospital mortality between the Rome proposal and DECAF score or GesEPOC 2021 criteria. CONCLUSION: External validation of the Rome Proposal in Korean patients demonstrated excellent performance for ICU admission and need for NIV or IMV and an acceptable performance for in-hospital mortality.

The Incidence of Brain-Dead Donors Based on Screening and Management Led by Intensivists.

BACKGROUND This study aimed to compare the incidence of brain-dead (BD) donors and potential brain-dead (PBD) donors before vs after the introduction of intensivists. MATERIAL AND METHODS This longitudinal retrospective study was performed between January 2012 and December 2020 at Seoul Metropolitan Government-Seoul National University Boramae Medical Center. Four dedicated intensivists were introduced in January 2016. The periods before and after introduction of the intensivists were defined as the pre-introduction period (2012-2015) and post-introduction period (2016-2020), respectively. RESULTS During the study period, there were 2872 discharges in the Intensive Care Unit, of which there were a total of 113 PBD (3.93%) and 36 BD (1.25%) donors. The number of PBD and BD donors increased in the post-introduction period compared in the pre-introduction period (PBD, 47.84 vs 27.14 per 1000 discharges; BD, 13.59 vs 11.03 per 1000 discharges). Poisson regression analysis showed the annual incidence rate of PBD donors significantly increased post-introduction (PBD, 27.53% vs 48.11%, P=0.044), while those of BD donors were similar between the 2 groups (BD, 11.41% vs 13.9%; P=0.743). The annual incidence rate of the total number of organ donations, multi-organ donations (>3 organs), and donation of organs (heart, lung, and kidney) increased in the post-introduction period compared to that in the pre-introduction period. CONCLUSIONS Our findings suggest a beneficial role of a dedicated intensivist, not only in improving actual organ donation and discovering PBD donors, but also in affecting the yield of the heart and lung transplantation in actual organ donation compared to donors without a dedicated intensivist.

The factors associated with mortality and progressive disease of nontuberculous mycobacterial lung disease: a systematic review and meta-analysis.

This systematic review and meta-analysis aimed to comprehensively evaluate the factors associated with mortality and progressive disease in NTM-LD patients. We conducted a literature search to identify the eligible studies, dated between January 1, 2007, and April 12, 2021. Forty-one studies with total 10,452 patients were included. The overall all-cause mortality rate was 20% (95% CI 17-24%). The overall rates of clinical and radiographic progressive disease were 46% (95% CI 39-53%) and 43% (95% CI 31-55%), respectively. Older age, male sex, history of TB, diabetes, chronic heart disease, malignancy, systemic immunosuppression, chronic liver disease, presence of cavity, consolidative radiologic features, acid-fast bacillus (AFB) smear positivity, hypoalbuminemia, anemia, increasing platelet count, high CRP, and high ESR were significantly associated with increased all-cause mortality, whereas increasing body mass index (BMI), hemoptysis, and treatment with rifamycin regimen (in M. xenopi) were significantly associated with decreased all-cause mortality in multivariable analysis. History of TB, Aspergillus co-infection, cough, increased sputum, weight loss, presence of cavity, and AFB smear positivity were significantly associated with increased clinical progression with treatment, while older age and low BMI were significantly associated with decreased clinical progression in multivariable analysis. Older age, interstitial lung disease, presence of cavity, consolidative radiologic feature, anemia, high CRP, and leukocytosis were significantly associated with increased radiographic progression after adjusting for covariates. Older age, history of tuberculosis, presence of cavity, consolidative radiologic features, AFB smear positivity, anemia, and high C-reactive protein were common significant factors associated with the all-cause mortality and clinical or radiographic progressive disease of NTM-LD. These factors are thought to directly affect NTM-LD related mortality. The future prediction models for the prognosis of NTM-LD should be established considering these factors.

New prognostic scoring system for mortality in idiopathic pulmonary fibrosis by modifying the gender, age, and physiology model with desaturation during the six-minute walk test.

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease (ILD) with variable and heterogeneous clinical course. The GAP (gender, age, and physiology) model had been used to predict mortality in patients with IPF, but does not contain exercise capacity. Therefore, our aim in this study was to develop new prognostic scoring system in the Korea IPF Cohort (KICO) registry. Materials and methods: This is a retrospective study of Korean patients with IPF in KICO registry from June 2016 to August 2021. We developed new scoring system (the GAP6) based on the GAP model adding nadir saturation of percutaneous oxygen (SpO2) during six-minute walk test (6MWT) in the KICO registry and compared the efficacy of the GAP and the GAP6 model. Results: Among 2,412 patients in KICO registry, 966 patients were enrolled. The GAP6 model showed significant prognostic value for mortality between each stage [HR Stage II vs. Stage I = 2.89 (95% CI = 2.38-3.51), HR Stage III vs. Stage II = 2.68 (95% CI = 1.60-4.51)]. In comparison the model performance with area under curve (AUC) using receiver operating characteristic (ROC) curve analysis, the GAP6 model showed a significant improvement for predicting mortality than the GAP model (AUC the GAP vs. the GAP6, 0.646 vs. 0.671, p < 0.0019). Also, the C-index values slightly improved from 0.674 to 0.691 for mortality. Conclusion: The GAP6 model adding nadir SpO2 during 6WMT for an indicator of functional capacity improves prediction ability with C-index and AUC. Additional multinational study is needed to confirm these finding and validate the applicability and accuracy of this risk assessment system.

Rapid FEV1/FVC Decline Is Related With Incidence of Obstructive Lung Disease and Mortality in General Population.

BACKGROUND: Forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) naturally decreases with age; however, an excessive decline may be related with increased morbidity and mortality. This study aimed to evaluate the FEV1/FVC decline rate in the Korean general population and to identify whether rapid FEV1/FVC decline is a risk factor for obstructive lung disease (OLD) and all-cause and respiratory mortality. METHODS: We evaluated individuals aged 40-69 years who underwent baseline and biannual follow-up spirometric assessments for up to 18 years, excluding those with airflow limitations at baseline. Based on the quartiles of the annual FEV1/FVC decline rate, the most negative FEV1/FVC change (1st quartile of annual FEV1/FVC decline rate) was classified as rapid FEV1/FVC decline. We investigated the risk of progression to OLD and all-cause and respiratory mortality in individuals with rapid FEV1/FVC decline. RESULTS: The annual FEV1/FVC decline rate in the eligible 7,768 patients was 0.32 percentage point/year. The incidence rate of OLD was significantly higher in patients with rapid FEV1/FVC decline than in those with non-rapid FEV1/FVC decline (adjusted incidence rate, 2.119; 95% confidence interval [CI], 1.932-2.324). Rapid FEV1/FVC decline was an independent risk factor for all-cause mortality (adjusted hazard [HR], 1.374; 95% CI, 1.105-1.709) and respiratory mortality (adjusted HR, 1.353; 95% CI, 1.089-1.680). CONCLUSION: The annual FEV1/FVC decline rate was 0.32%p in the general population in Korea. The incidence rate of OLD and the hazards of all-cause and respiratory mortality were increased in rapid FEV1/FVC decliners.

Systemic corticosteroid use and cardiovascular risk in patients hospitalized for pneumonia.

BACKGROUND: Limited data are available concerning cardiovascular risk with respect to adjunctive corticosteroid use in patients with pneumonia. We aimed to assess the associations between systemic corticosteroid use and the occurrence of major adverse cardiovascular events (MACEs) in patients hospitalized for pneumonia. METHODS: Among study participants enrolled via surveillance for severe acute respiratory infection from July 2016 to January 2017, the clinical course of patients with pneumonia was retrospectively investigated until December 2019. We evaluated the occurrence of in-hospital and after-discharge MACEs according to steroid use during hospitalization. RESULTS: Of the 424 patients hospitalized for pneumonia, 118 (28.8%) received systemic corticosteroids during hospitalization. The most common reason for steroid use was acute exacerbation of chronic lung disease (75.4%). Systemic steroid use was significantly associated with an increased risk of in-hospital MACEs; it was not associated with after-discharge MACEs. The risk of in-hospital MACEs was significantly greater in patients with more comorbidities, more severe pneumonia, and a higher inflammatory marker level; moreover, it was positively associated with duration and cumulative dose of steroid treatment. CONCLUSION: Systemic corticosteroid use was associated with an increased risk of in-hospital MACEs in patients hospitalized for pneumonia.

Artificial Intelligence Solution for Chest Radiographs in Respiratory Outpatient Clinics: Multicenter Prospective Randomized Clinical Trial.

Rationale: Artificial intelligence (AI)-assisted diagnosis imparts high accuracy to chest radiography (CXR) interpretation; however, its benefit for nonradiologist physicians in detecting lung lesions on CXR remains unclear. Objectives: To investigate whether AI assistance improves the diagnostic performance of physicians for CXR interpretation and affects their clinical decisions in clinical practice. Methods: We randomly allocated eligible patients who visited an outpatient clinic to the intervention (with AI-assisted interpretation) and control (without AI-assisted interpretation) groups. Lung lesions on CXR were recorded by seven nonradiologists with or without AI assistance. The reference standard for lung lesions was established by three radiologists. The primary and secondary endpoints were the physicians' diagnostic accuracy and clinical decision, respectively. Results: Between October 2020 and May 2021, 162 and 161 patients were assigned to the intervention and control groups, respectively. The area under the receiver operating characteristic curve was significantly larger in the intervention group than in the control group for the CXR level (0.840 [95% confidence interval (CI), 0.778-0.903] vs. 0.718 [95% CI, 0.640-0.796]; P = 0.017) and lung lesion level (0.800 [95% CI, 0.740-0.861] vs. 0.677 [95% CI, 0.605-0.750]; P = 0.011). The intervention group had higher sensitivity in terms of both CXR and lung lesion level and a lower false referral rate for the lung lesion level. AI-assisted CXR interpretation did not affect the physicians' clinical decisions. Conclusions: AI-assisted CXR interpretation improves the diagnostic performance of nonradiologist physicians in detecting abnormal lung findings. Clinical trial registered with Clinical Research Information Service of the Republic of Korea (KCT 0005466).

Different treatment response to systemic corticosteroids according to white blood cell counts in severe COVID-19 patients.

BACKGROUND: Limited data are available in COVID-19 patients on the prediction of treatment response to systemic corticosteroid therapy based on systemic inflammatory markers. There is a concern whether the response to systemic corticosteroid is different according to white blood cell (WBC) counts in COVID-19 patients. We aimed to assess whether WBC count is related with the clinical outcomes after treatment with systemic corticosteroids in severe COVID-19. METHODS: We conducted a retrospective cohort study and analysed the patients hospitalised for severe COVID-19 and received systemic corticosteroids between July 2020 and June 2021. The primary endpoint was to compare the composite poor outcome of mechanical ventilation, extracorporeal membrane oxygenation, and mortality among the patients with different WBC counts. RESULTS: Of the 585 COVID-19 patients who required oxygen supplementation and systemic corticosteroids, 145 (24.8%) belonged to the leukopoenia group, 375 (64.1%) belonged to the normal WBC group, and 65 (11.1%) belonged to the leukocytosis group. In Kaplan-Meier curve, the composite poor outcome was significantly reduced in leukopoenia group compared to leukocytosis group (log-rank p-value < 0.001). In the multivariable Cox regression analysis, leukopoenia group was significantly associated with a lower risk of the composite poor outcome compared to normal WBC group (adjusted hazard ratio [aHR] = 0.32, 95% CI 0.14-0.76, p-value = 0.009) and leukocytosis group (aHR = 0.30, 95% CI = 0.12-0.78, p-value = 0.013). There was no significant difference in aHR for composite poor outcome between leukocytosis and normal WBC group. CONCLUSION: Leukopoenia may be related with a better response to systemic corticosteroid therapy in COVID-19 patients requiring oxygen supplementation.KEY MESSAGESIn severe COVID-19 treated with systemic corticosteroids, patients with leukopoenia showed a lower hazard for composite poor outcome compared to patients with normal white blood cell counts or leukocytosis.Leukopoenia may be a potential biomarker for better response to systemic corticosteroid therapy in COVID-19 pneumonia.

Cereblon Deficiency Contributes to the Development of Elastase-Induced Emphysema by Enhancing NF-κB Activation.

Cereblon (CRBN) has been shown to play an essential role in regulating inflammatory response and endoplasmic reticulum stress, thus mediating the development of various diseases. However, little is known about the roles of CRBN in chronic obstructive pulmonary disease (COPD) pathogenesis. We found that the protein levels of CRBN in lung homogenates from patients with COPD were lower than those from never smokers and smokers. The CRBN protein level was positively correlated with the forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC). To investigate the role of CRBN in modulating elastase-induced emphysema, we used Crbn knockout (KO) mice. Elastase-induced emphysematous changes were significantly aggravated in Crbn KO mice. Neutrophil infiltration, lung cell injury, and protein leakage into the bronchoalveolar space were more severe in Crbn KO mice than in wild-type (WT) mice. Furthermore, Crbn KO resulted in the elevated release of neutrophilic chemokines and inflammatory cytokines in lung epithelial cells and macrophages. The transcriptional activity of nuclear factor-κB (NF-κB) was significantly increased in Crbn knocked-down cells. In conclusion, Crbn deficiency might be involved in the development of emphysema by enhancing NF-κB activation, suggesting that targeting CRBN might be an effective therapeutic approach for the treatment of COPD.

Radiographic Phenotypes Affect the Risk of Inhaled Corticosteroid-Associated Pneumonia in Patients with COPD.

Purpose: Few studies have reported the association between the radiographic characteristics and the development of pneumonia in patients with chronic obstructive pulmonary disease (COPD) treated with inhaled corticosteroids (ICSs). Our study aimed to assess the effect of radiographic phenotypes on the risk of pneumonia in patients treated with ICSs. Patients and Methods: This study retrospectively analysed all patients with COPD treated with ICSs in a subset of the Korea Chronic Obstructive Pulmonary Disorders Subgroup Study registry between January 2017 and December 2019. The association between radiographic phenotypes including the presence and severity of emphysema, airway wall thickening, or bronchiectasis on chest computed tomography were determined visually/qualitatively and the risk of pneumonia was analyzed using the Cox regression model. Results: Among the 90 patients with COPD treated with ICSs, 41 experienced pneumonia more than once during the median follow-up of 29 (interquartile range, 8-35) months. In univariate Cox regression analysis, older age, longer use of ICSs, use of fluticasone propionate or metered dose inhaler, and severe exacerbation events increased the risk of pneumonia. In multivariate analysis, the presence of emphysema (adjusted hazard ratio [aHR]=3.73, P=0.033), severity measured using the visual sum score (mild-to-moderate, aHR=8.58, P=0.016; severe, aHR=3.58, P=0.042), Goddard sum score (mild-to-moderate, aHR=3.31, P=0.058; severe, aHR=5.38, P=0.014), and the upper lobe distribution of emphysema (aHR=3.76, P=0.032) were associated with a higher risk of pneumonia. Subtypes of centrilobular and panlobular emphysema had a higher risk of pneumonia compared with paraseptal emphysema (aHR=3.98, P=0.033; HR=3.91, P=0.041 vs HR=2.74, P=0.304). The presence of bronchiectasis (aHR=2.41, P=0.02) and emphysema/bronchiectasis overlap phenotype (aHR=2.19, P=0.053) on chest CT was a risk factor for pneumonia in this population. However, severity of bronchiectasis and the presence or severity of bronchial wall thickening according to the visual sum score were not associated with the risk of pneumonia. Conclusion: Among patients with COPD treated with ICSs, radiographic phenotypes including the presence of emphysema, bronchiectasis or emphysema/bronchiectasis overlap phenotype, severity with emphysema, subtypes of centrilobular or panlobular emphysema, and upper lobe distribution of emphysema may help predict the risk of pneumonia.

Association between oxygen saturation level during bronchoscopy and post-bronchoscopy adverse events: a retrospective cohort study.

BACKGROUND: Flexible bronchoscopy is widely used to diagnose and treat various respiratory diseases. However, caution is warranted for post-bronchoscopy adverse events. Although desaturation frequently occurs during bronchoscopy, its clinical impact and the optimal oxygen saturation level during the procedure remain unclear. This study aimed to investigate whether the percutaneous oxygen saturation (SpO2) level during bronchoscopy is associated with the development of post-bronchoscopy respiratory adverse events. METHODS: In this single-center retrospective cohort study conducted from March 2020 to February 2021, 569 patients were classified into high or low oxygen saturation groups based on the SpO2 level during bronchoscopy. The primary outcome was post-bronchoscopy respiratory adverse events, and secondary outcomes were other post-bronchoscopy adverse events and clinical outcomes. RESULTS: Among 569 patients, 458 and 111 patients were classified into the high oxygen saturation (SpO2 > 96%) and low oxygen saturation (SpO2 ≤ 94%) groups, respectively. After propensity score matching, the low oxygen saturation group had more post-bronchoscopy respiratory and febrile adverse events than the high oxygen saturation group. In the multivariable regression analysis, low SpO2 level during bronchoscopy was an independent risk factor for post-bronchoscopy respiratory adverse events (odds ratio = 3.16 [95% confidence interval 1.37-7.30]). In the low oxygen saturation group, the high-risk subgroups for post-bronchoscopy respiratory adverse events were the elderly, women, current smokers, and patients with chronic obstructive pulmonary disease or acute decompensated heart failure before bronchoscopy. There was no significant difference in the length of hospital stay, intensive care unit admission, or mortality between the high and low oxygen saturation groups. CONCLUSIONS: Close monitoring is recommended for patients with SpO2 ≤ 94% during bronchoscopy due to the increased risk of respiratory adverse events after the procedure.

Clinical Deterioration and Lung Function Change in Patients With Concomitant Asthma and Bronchiectasis.

BACKGROUND: Only limited data are available regarding the effects of bronchiectasis on the clinical course of asthma. OBJECTIVE: This study evaluated longitudinal clinical outcomes according to bronchiectasis status in patients with asthma. METHODS: This retrospective study included patients with asthma who underwent chest computed tomography and pulmonary function tests between January 2013 and December 2019. The annual incidence of episodes of moderate-to-severe acute clinical deterioration (exacerbations) and longitudinal changes in lung function were evaluated. RESULTS: Of 667 patients with asthma, 251 had bronchiectasis. Patients with bronchiectasis had significantly more history of tuberculosis and nontuberculous mycobacterial lung disease, and lower forced expiratory volume in 1 second and forced vital capacity, compared with patients without bronchiectasis, although there was no difference in smoking intensity and inhaled corticosteroid treatment. Bronchiectasis was significantly associated with higher annual rates of severe and moderate-to-severe acute exacerbations; it was also associated with greater risk of acute exacerbation during follow-up. The severity and progression of bronchiectasis were independent risk factors for acute exacerbation. There were no significant differences in annual decline of lung function according to bronchiectasis status or bronchiectasis progression. CONCLUSIONS: In patients with asthma, the presence and progression of bronchiectasis were significantly associated with increased risk of moderate-to-severe acute exacerbation, but they were not associated with longitudinal changes in lung function.

Rapid FEV1 Decline and Lung Cancer Incidence in South Korea.

BACKGROUND: Impaired lung function is associated with a higher risk of developing lung cancer. However, lung function is a dynamic variable and must be evaluated longitudinally. This study reports on the relationship between accelerated lung function decline and development of lung cancer. RESEARCH QUESTION: Is accelerated lung function decline associated with the development of lung cancer? STUDY DESIGN AND METHODS: A longitudinal, observational study was performed by using epidemiologic data from two population-based studies comprising subjects assessed biannually from 2001 to 2019 in South Korea. Eligible subjects were between 40 and 69 years of age and were followed up by using spirometry. Spirometry measurements were made at each follow-up. Patients with a decline in FEV1 > 60 mL per year were defined as rapid FEV1 decliners. The relationship between lung cancer and rapid FEV1 decline was evaluated by using adjusted Cox regression models with covariates, including age, sex, smoking history, FEV1/FVC, and WBC count. RESULTS: Among the 8,549 eligible subjects, 1,287 (15.1%) had rapid FEV1 decline, and 48 (0.6%) had newly developed lung cancer. The risk of lung cancer development was increased in the subjects aged ≥ 45 years and those with ≥ 30 pack-years of smoking, low baseline FEV1/FVC, low forced expiratory flow between 25% and 75% of vital capacity, rapid FEV1 decline, and increased WBC count. Rapid FEV1 decline was an independent risk factor for lung cancer development (adjusted hazard ratio, 2.34; 95% CI, 1.28-4.28; P = .006). Time-dependent net reclassification improvement showed a benefit of FEV1 decline rate in determining subjects at risk of lung cancer when added to conventional practice (categorical, 0.32 [95% CI, 0.00-0.64]; continuous, 0.83 [95% CI, 0.14-1.25]). INTERPRETATION: The FEV1 decline rate may be a potential biomarker for lung cancer development. Further study is needed to identify whether patients with rapid FEV1 decline warrant lung cancer assessment or screening.