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 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.

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.

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.

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.

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.

The Effect of the Timing of Dexamethasone Administration in Patients with COVID-19 Pneumonia.

BACKGROUND: Despite the proven benefits of dexamethasone in hospitalized coronavirus disease 2019 (COVID-19) patients, the optimum time for the administration of dexamethasone is unknown. We investigated the progression of COVID-19 pneumonia based on the timing of dexamethasone administration. METHODS: A single-center, retrospective cohort study based on medical record reviews was conducted between June 10 and September 21, 2020. We compared the risk of severe COVID-19, defined as the use of a high-flow nasal cannula or a mechanical ventilator, between groups that received dexamethasone either within 24 hours of hypoxemia (early dexamethasone group) or 24 hours after hypoxemia (late dexamethasone group). Hypoxemia was defined as room-air SpO2 <90%. RESULTS: Among 59 patients treated with dexamethasone for COVID-19 pneumonia, 30 were in the early dexamethasone group and 29 were in the late dexamethasone group. There was no significant difference in baseline characteristics, the time interval from symptom onset to diagnosis or hospitalization, or the use of antiviral or antibacterial agents between the two groups. The early dexamethasone group showed a significantly lower rate of severe COVID-19 compared to the control group (75.9% vs. 40.0%, p=0.012). Further, the early dexamethasone group showed a significantly shorter total duration of oxygen supplementation (10.45 days vs. 21.61 days, p=0.003) and length of stay in the hospital (19.76 days vs. 27.21 days, p=0.013). However, extracorporeal membrane oxygenation and in-hospital mortality rates were not significantly different between the two groups. CONCLUSION: Early administration of dexamethasone may prevent the progression of COVID-19 to a severe disease, without increased mortality.

Clinical implication and risk factor of pneumonia development in mild coronavirus disease 2019 patients.

BACKGROUND/AIMS: Although a majority of coronavirus disease 2019 (COVID-19) cases were characterized as mild, data assessing the development of pneumonia in mild COVID-19 patients are limited. We aimed to examine the effect of pneumonia development on the clinical course of mild COVID-19 in hospitalized patients. METHODS: A retrospective cohort study was conducted via medical record review between February 25, 2020 and April 11, 2020 at a single center. The impact of pneumonia development on the time to viral clearance in mild COVID-19 patients was evaluated. Risk factors associated with the development of pneumonia were also identified. RESULTS: Chest radiographs revealed the development of pneumonia in 26.8% of mild COVID-19 patients. The time to pneumonia development was a median of 8.0 days from the onset of symptoms and 3.5 days after hospital admission. A multivariate analysis for predicting pneumonia development identified age ≥ 65 years (odds ratio [OR], 3.15; 95% confidence interval [CI], 1.14 to 8.73), cough (OR, 2.18; 95% CI, 1.29 to 3.68), dyspnea (OR, 3.58; 95% CI, 1.10 to 11.69), and diarrhea (OR, 2.69; 95% CI, 1.51 to 4.78) as significant variables. The time to negative conversion was longer in mild COVID-19 patients who developed pneumonia (23.6 days vs. 18.4 days, p = 0.003). In Kaplan-Meier estimation and multivariate Cox regression analyses, newly developed pneumonia was significantly related with delayed time to negative conversion (log-rank test, p = 0.02; hazard ratio, 2.90; 95% CI, 1.06 to 7.97). CONCLUSION: The development of pneumonia delayed viral clearance in patients with mild COVID-19. Elderly patients or those suffering from diarrhea should be closely monitored, given the increased risk of developing pneumonia.

A population-based observational study of patients with pulmonary disorders in intensive care unit.

BACKGROUND/AIMS: Only a few epidemiologic studies on the patients with pulmonary disorders admitted to intensive care unit exist. We investigated the characteristics and clinical outcomes of the patients with severe pulmonary disorders. METHODS: The sample cohort database of National Health Insurance Sharing Service from 2006 to 2015 was used. Operational definition of critically ill patients was adults who were either admitted to intensive care unit for at least 3 days or expired within first 2 days in the unit. The pulmonary disorder group comprised of critically ill patients with respiratory disease as the main diagnosis. RESULTS: Among the 997,173 patients, 12,983 (1.3%) in 383 intensive care units were categorized as critically ill. Patients in the pulmonary disorder group tended to have more comorbidities or disabilities. The length of hospital stay and duration of mechanical ventilation were longer in the pulmonary disorder group. Overall mortality and re-admission were higher in the pulmonary disorder group, with adjusted incidence rate ratios of 1.22 (95% confidence interval, 1.18 to 1.27) and 1.26 (95% confidence interval, 1.17 to 1.36), respectively. After adjustment by Cox regression, the pulmonary disorder group was an independent risk factor for in-hospital mortality. CONCLUSION: In critically ill patients with pulmonary disorder, the use of healthcare resources was higher, and their clinical outcomes were significantly worse than the non-pulmonary disorder group.

Delayed diagnosis of allergic bronchopulmonary aspergillosis due to absence of asthmatic symptoms.

Allergic bronchopulmonary aspergillosis (ABPA) is a pulmonary disease with small prevalence. Exposure to aspergillus mold causes immunologic hypersensitivity and may cause ranges of symptoms from minimal to detrimental outcomes. Diagnosing and treating the disease before the development of bronchiectasis may save the patient from poor outcomes. This report presents a case of recurrent ABPA without any symptom of asthma, which impeded the correct diagnosis even after numerous hospitalizations.