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Background: Forced expiratory volume in 1 second (FEV 1 )/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 FEV 1 /FVC decline rate in the Korean general population and to identify whether rapid FEV 1 /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 FEV 1 /FVC decline rate, the most negative FEV 1 /FVC change (1 st quartile of annual FEV 1 /FVC decline rate) was classified as rapid FEV 1 /FVC decline. We investigated the risk of progression to OLD and all-cause and respiratory mortality in individuals with rapid FEV 1 /FVC decline., Results: The annual FEV 1 /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 FEV 1 /FVC decline than in those with non-rapid FEV 1 /FVC decline (adjusted incidence rate, 2.119; 95% confidence interval [CI], 1.932-2.324). Rapid FEV 1 /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 FEV 1 /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 FEV 1 /FVC decliners., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

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 FEV 1 > 60 mL per year were defined as rapid FEV 1 decliners. The relationship between lung cancer and rapid FEV 1 decline was evaluated by using adjusted Cox regression models with covariates, including age, sex, smoking history, FEV 1 /FVC, and WBC count., Results: Among the 8,549 eligible subjects, 1,287 (15.1%) had rapid FEV 1 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 FEV 1 /FVC, low forced expiratory flow between 25% and 75% of vital capacity, rapid FEV 1 decline, and increased WBC count. Rapid FEV 1 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 FEV 1 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 FEV 1 decline rate may be a potential biomarker for lung cancer development. Further study is needed to identify whether patients with rapid FEV 1 decline warrant lung cancer assessment or screening., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: The impact of reflux esophagitis on the decline of lung function has been rarely reported. This study was performed to evaluate the association between erosive reflux esophagitis and lung function changes., Methods: We included patients with normal lung function who underwent esophagogastroduodenoscopy for health screening from a health screening center. Patients with persistent erosive reflux esophagitis on two discrete endoscopic examinations were designated as the erosive reflux esophagitis group. We also selected patients without erosive reflux esophagitis and matched them 1:4 with patients from the erosive reflux esophagitis group. We estimated annual forced expiratory volume in 1 second (FEV₁) and forced vital capacity (FVC) changes from baseline and compared these estimates by the linear mixed regression model. We also estimated the biannual incidence of chronic obstructive pulmonary disease (COPD)., Results: In total, 1,050 patients (210 patients with erosive reflux esophagitis, and 840 matched controls) were included. The median follow-up duration for spirometry was six years. In patients with erosive reflux esophagitis, mild reflux esophagitis (A grade) was most common (165 patients, 78.6%). The adjusted annual FEV₁ change in patients with erosive reflux esophagitis was -51.8 mL/yr, while it decreased by 46.8 mL/yr in controls ( P = 0.270). The adjusted annual FVC decline was similar between the two groups (-55.8 vs. -50.5 mL/yr, P = 0.215). The estimated COPD incidence during the follow-up period was not different between the erosive reflux esophagitis and control groups., Conclusion: In patients with normal lung function, the presence of erosive reflux esophagitis did not affect the annual declines in FEV₁ or FVC., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2021 The Korean Academy of Medical Sciences.)

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.

Background: Methylxanthines and leukotriene receptor antagonists (LTRA) are not a first-line medical treatment for chronic obstructive pulmonary disease (COPD) but are frequently prescribed despite limited evidence. We aimed to elucidate the real prescribing status and clinical impacts of these agents in early COPD patients., Methods: Patients with mild-to-moderate COPD (FEV 1 >50%) were selected from the Korean National Health and Nutrition Examination Survey data between 2007 and 2012. Besides analyzing the prescription status of methylxanthines and LTRA and the contributing factors to the prescription, we evaluated the clinical impacts of these drugs on the exacerbation, hospitalization, and medical costs., Results: Of 2269 patients with mild-to-moderate COPD, 378 patients (16.7%) were under medical treatments, and the users of methylxanthines and/or LTRA were 279 patients (12.3%); however, only 139 patients (6.1%) were inhaler users. The contributing factors for the prescription of methylxanthines were a comorbidity of asthma or allergic disease, poor lung function, low quality of life, prescribing doctor from the specialty of internal medicine, and an institution type of private hospital. The prescription of LTRA was associated with the comorbidity of allergic disease. The methylxanthine and/or LTRA users had more hospital utilization but did not have significant differences in acute exacerbations and medical cost for hospital utilization, compared with the non-users., Conclusion: Methylxanthines and LTRA were used in a significant proportion of patients with mild-to-moderate COPD in real fields without favorable impacts on the exacerbations, hospitalizations, or medical costs. The use of more effective inhaled medications should be encouraged., Competing Interests: C.K.R reports personal fees from MSD, AstraZeneca, GSK, Novartis, Takeda, Mundipharma, Boehringer-Ingelheim, Teva, and Bayer, outside of the submitted work. The authors report no other conflicts of interest in this work., (© 2019 Lee et al.)

Background and Objective: There are limited data on pulmonary arterial hypertension (PAH) in patients with tuberculosis-destroyed lung (TDL), a sequela of pulmonary tuberculosis. We identified the risk factors for PAH and their effects on acute exacerbation and mortality in patients with TDL, as well as the clinical differences in patients with chronic obstructive pulmonary disease (COPD) and PAH., Methods: A retrospective cohort study was conducted from 2010 through 2015 in a municipal referral hospital in South Korea. PAH was defined when echocardiographic pulmonary arterial pressure (PAP) was >40 mmHg. The clinical features and course of TDL patients with or without PAH were evaluated and differences between patients with COPD and PAH were analyzed., Results: Among the 195 patients with TDL, echocardiographic data were available in 53 patients, and their mean PAP was 50.72±23.99 mmHg. The PAH group (n=37) had a smaller lung volume (forced vital capacity % predicted, 51.55% vs 72.37%, P <0.001) and more extensively destroyed lungs (3.27 lobes vs 2 lobes, P <0.001) than those in the non-PAH group (n=16). A higher PAP was significantly correlated with a higher frequency of acute exacerbation ( r =0.32, P =0.02). Multivariate analyses did not reveal any significant risk factors contributing to PAH in patients with TDL. Compared to COPD patients with PAH, TDL patients with PAH have smaller lung volume but a less severe airflow limitation. Tricuspid regurgitation and a D-shaped left ventricle during diastole were more frequently observed in TDL patients. The risk of exacerbation was not different between patients with PAH in COPD and TDL., Conclusion: PAH in patients with TDL was associated with severity of lung destruction but risk of exacerbation and mortality did not significantly differ between patients with PAH and without PAH., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Linezolid, an oxazolidinone, substantially improves treatment outcomes of multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis. We started a trial to test whether the use of linezolid instead of ethambutol could increase the rate of sputum culture conversion as of 8 weeks of treatment in patients with drug-susceptible tuberculosis., Methods/design: This is a phase II, multicenter, randomized study with three arms. We are enrolling patients with pulmonary tuberculosis without rifampicin resistance screened by the Xpert MTB/RIF® assay. The standard treatment arm uses isoniazid (6 months), rifampicin (6 months), pyrazinamide (2 months), and ethambutol (2 months). Experimental arm 1 uses linezolid (600 mg/day) for 4 weeks instead of ethambutol. Experimental arm 2 uses linezolid (600 mg/day) for 2 weeks instead of ethambutol. The primary outcome is the sputum culture conversion rate on liquid media after 2 months of treatment. Secondary outcomes include the sputum culture conversion rate on solid media after 2 months of treatment, time to sputum culture conversion on liquid and solid media, cure rate, and treatment success rate. The frequencies of total adverse events (AEs) and serious AEs will be described and documented. Based on an α = 0.05 level of significance, a power of 85%, a 15% difference in the culture conversion rate after 2 months between the control arm and experimental arm 1 (75% vs. 90%), a 10% default (loss to follow-up) rate, and a 10% culture failure, the required number per arm was calculated to be 143 (429 in total)., Discussion: This trial will reveal the effectiveness and safety of 2 or 4 weeks of use of linezolid instead of ethambutol for patients with drug-susceptible pulmonary tuberculosis. If a new regimen including linezolid shows a higher culture conversion rate by week 8, and is safe, it could be tested as a 4-month antituberculosis treatment regimen in the future., Trial Registration: ClincalTrials.gov, NCT01994460 . Registered on 13 November 2013.

Background: Limited studies have examined the association between lung cancer and bronchiectasis (BE). This study evaluated the regional association between BE and lung cancer by analyzing the lobar location of lung cancer in patients with underlying BE., Methods: This clustered multi-level study enrolled patients who had underlying BE and were newly diagnosed with lung cancer between January 1, 2010 and May 30, 2013 in two referral hospitals in South Korea. By analyzing the presence of lung cancer and underlying BE as event variables at the level of lung lobes on chest computed tomography (CT), we evaluated the association of BE and lung cancer by the locations of the diseases., Results: Eighty-one patients with BE and combined lung cancer were enrolled. Within 486 lung lobes of the patients, combined BE and lung cancer in the same lobe was found in 11 lobes (2.3 %). Using the general estimating equation assuming BE as a risk factor of lung cancer, the results indicated that the prevalence of lung cancer was significantly lower in the lobes with pre-existing BE (β = -1.09, p-value = 0.001)., Conclusions: Regionally, pre-existing BE was associated with a lower risk of the occurrence of lung cancer in the same lobe.