Pulmonary hypertension (PH) is a condition of increased blood pressure in the pulmonary arteries and is diagnosed with an increased a mean pulmonary artery pressure ≥25 mm Hg. This condition may be associated with multiple clinical situations. Based on pathophysiological mechanisms, clinical presentation, hemodynamic profiles, and treatment strategies, the patients were classified into five clinical groups. Although there have been major advances in the management of PH, it is still associated with significant morbidity and mortality. The diagnosis and treatment of PH have been performed mainly by following European guidelines, even in Korea because the country lacks localized PH guidelines. European treatment guidelines do not reflect the actual status of Korea. Therefore, the European diagnosis and treatment of PH have not been tailored well to suit the needs of Korean patients with PH. To address this issue, we developed this guideline to facilitate the diagnosis and treatment of PH appropriately in Korea, a country where the consensus for the diagnosis and treatment of PH remains insufficient. This is the first edition of the guidelines for the diagnosis and treatment of PH in Korea, and it is primarily based on the '2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension.' with the acceptance and adaptation of recent publications of PH.

Background: In asthma, consistent control of chronic airway inflammation is crucial, and the use of asthma-controller medication has been emphasized. Our purpose in this study is to compare the incidence of acute exacerbation and healthcare costs related to the use of asthma-controller medication.
Methods: By using data collected by the National Health Insurance Review and Assessment Service, we compared one-year clinical outcomes and medical costs from July 2014 to June 2015 (follow-up period) between two groups of patients with asthma who received different prescriptions for recommended asthma-controller medication (inhaled corticosteroids or leukotriene receptor antagonists) at least once from July 2013 to June 2014 (assessment period).
Results: There were 51,757 patients who satisfied our inclusion criteria. Among them, 13,702 patients (26.5%) were prescribed a recommended asthma-controller medication during the assessment period. In patients using a recommended asthma-controller medication, the frequency of acute exacerbations decreased in the follow-up period, from 2.7% to 1.1%. The total medical costs of the controller group decreased during the follow-up period compared to the assessment period, from $3,772,692 to $1,985,475. Only 50.9% of patients in the controller group used healthcare services in the follow-up period, and the use of asthma-controller medication decreased in the follow-up period.
Conclusion: Overall, patients using a recommended asthma-controller medication showed decreased acute exacerbation and reduced total healthcare cost by half.

Background: Neutrophilic asthma (NeuA) is usually resistant to corticosteroids. Tiotropium bromide (TIO) is a bronchodilator that is used as an add-on therapy to inhaled corticosteroid and long-acting β2 agonist in asthma treatment. However, the role of TIO in NeuA is not fully known. Thus, the aim of this study was to evaluate the effect of TIO on NeuA compared to that of corticosteroids.
Methods: C57BL/6 female mice were sensitized with ovalbumin and lipopolysaccharide to induce neutrophilic inflammation. Dexamethasone (DEX) was administered on days 14, 17, 20, and 23. TIO was inhaled on days 21, 21, and 23. On day 24, mice were sacrificed. Airway hyper-responsiveness, levels of cytokines in bronchoalveolar lavage (BAL) and lung homogenates, and lung tissue histopathology were compared between the two groups.
Results: Neutrophil counts, T helper 2 cells (TH2)/TH17 cytokines, and pro-inflammatory cytokine in BAL fluids were elevated in the NeuA group. TIO group showed lower total cells, neutrophil counts, and eosinophil counts in BAL fluids than the DEX group (p<0.001, p<0.05, and p<0.001, respectively). Airway resistance was attenuated in the TIO group but elevated in the NeuA group (p<0.001). Total protein, interleukin (IL)-5, and IL-17A levels in BAL fluids were lower in the TIO group than in the NeuA group (all p<0.05).
Conclusion: TIO showed more potent effects than DEX in improving airway inflammation and attenuating airway resistance in NeuA.

Background: Only a few studies directly compared the therapeutic efficacy and safety of two pressurized metereddose inhalers (pMDIs) in asthma. We analyzed the asthma treatment outcomes, safety, and patient preferences using formoterol/beclomethasone (FORM/BDP), a pMDI with extra-fine particles, compared with formoterol/budesonide (FORM/BUD), another pMDI with non-extra-fine particles.
Methods: In this randomized, double-blind, double-dummy parallel group study, 40 adult asthmatics were randomized to FORM/BDP group (n=18; active FORM/BDP and placebo FORM/BUD) or FORM/BUD group (n=22; active FORM/BUD and placebo FORM/BDP). During the two visits (baseline and end of 8-week treatment), subjects were asked to answer questionnaires including asthma control test (ACT), asthma control questionnaires (ACQ), and Quality of Life Questionnaire for Adult Korean Asthmatics (QLQAKA). Lung function, compliance with inhaler, and inhaler-handling skills were also assessed.
Results: Ten subjects in the FORM/BDP group and 14 in the FORM/BUD group completed follow-up visits. ACT, ACQ, QLQAKA (a primary outcome), and adverse events did not differ between two groups. We found that the increase in forced expiratory volume in 1 second/forced vital capacity and forced expiratory flow at 25% to 75% of the pulmonary volume in the FORM/BDP group was higher than in the FORM/BUD group. Regarding preference, subjects responded that the flume velocity of FORM/BDP was higher, but more adequate than that of FORM/BUD. They also answered that FORM/BDP reached the trachea and bronchus and irritated them significantly more than FORM/BUD.
Conclusion: The use of pMDI with extra-fine particles may relieve small airway obstruction more than the one with non-extra-fine particles despite no significant differences in overall treatment outcomes. Some asthmatics have a misconception about the adequacy of high flume velocity of pMDIs.

Background: Although respiratory tract infection is one of the most important factors triggering acute exacerbation of chronic obstructive pulmonary disease (AE-COPD), limited data are available to suggest an epidemiologic pattern of microbiology in South Korea.
Methods: A multicenter observational study was conducted between January 2015 and December 2018 across 28 hospitals in South Korea. Adult patients with moderate-to-severe acute exacerbations of COPD were eligible to participate in the present study. The participants underwent all conventional tests to identify etiology of microbial pathogenesis. The primary outcome was the percentage of different microbiological pathogens causing AE-COPD. A comparative microbiological analysis of the patients with overlapping asthma-COPD (ACO) and pure COPD was performed.
Results: We included 1,186 patients with AE-COPD. Patients with pure COPD constituted 87.9% and those with ACO accounted for 12.1%. Nearly half of the patients used an inhaled corticosteroid-containing regimen and one-fifth used systemic corticosteroids. Respiratory pathogens were found in 55.3% of all such patients. Bacteria and viruses were meldetected in 33% and 33.2%, respectively. Bacterial and viral coinfections were found in 10.9%. The most frequently detected bacteria were Pseudomonas aeruginosa (9.8%), and the most frequently detected virus was influenza A (10.4%). Multiple bacterial infections were more likely to appear in ACO than in pure COPD (8.3% vs. 3.6%, p=0.016).
Conclusion: Distinct microbiological patterns were identified in patients with moderate-to-severe AE-COPD in South Korea. These findings may improve evidence-based management of patients with AE-COPD and represent the basis for further studies investigating infectious pathogens in patients with COPD.

Background: We evaluated the long-term effects of domiciliary noninvasive positive-pressure ventilation (NIPPV) used to treat patients with chronic obstructive pulmonary disease (COPD).
Methods: Databases were searched to identify randomized controlled trials of COPD with NIPPV for longer than 1 year. Mortality rates were the primary outcome in this meta-analysis. The eight trials included in this study comprised data from 913 patients.
Results: The mortality rates for the NIPPV and control groups were 29% (118/414) and 36% (151/419), suggesting a statistically significant difference (risk ratio [RR], 0.79; 95% confidence interval [CI], 0.65-0.95). Mortality rates were reduced with NIPPV in four trials that included stable COPD patients. There was no difference in admission, acute exacerbation and quality of life between the NIPPV and control groups. There was no significant difference in withdrawal rates between the two groups (RR, 0.99; 95% CI, 0.72-1.36; p=0.94).
Conclusion: Maintaining long-term nocturnal NIPPV for more than 1 year, especially in patients with stable COPD, decreased the mortality rate, without increasing the withdrawal rate compared with long-term oxygen treatment.

Background: Because the etiologies of bronchiectasis and related diseases vary significantly among different regions and ethnicities, this study aimed to develop a diagnostic bundle for bronchiectasis in South Korea.
Methods: A modified Delphi method was used to develop expert consensus statements on a diagnostic bundle for bronchiectasis in South Korea. Initial statements proposed by a core panel, based on international bronchiectasis guidelines, were discussed in an online meeting and two email surveys by a panel of experts (≥70% agreement).
Results: The study involved 21 expert participants, and 30 statements regarding a diagnostic bundle for bronchiectasis were classified as recommended, conditional, or not recommended. The consensus statements of the expert panel were as follows: A standardized diagnostic bundle is useful in clinical practice; diagnostic tests for specific diseases, including immunodeficiency and allergic bronchopulmonary aspergillosis, are necessary when clinically suspected; initial diagnostic tests, including sputum microbiology and spirometry, are essential in all patients with bronchiectasis, and patients suspected with rare causes such as primary ciliary dyskinesia should be referred to specialized centers.
Conclusion: Based on this Delphi survey, expert consensus statements were generated including specific diagnostic, laboratory, microbiological, and pulmonary function tests required to manage patients with bronchiectasis in South Korea.

Background: Bronchiectasis patients with neutrophilic airway inflammation develop symptoms of chronic cough, sputum production, and recurrent exacerbations. Roflumilast has anti-inflammatory actions via decreased neutrophilic airway inflammation. The effectiveness of roflumilast to reduce bronchiectasis exacerbation has never been evaluated.
Methods: We conducted a double-blinded, randomized, placebo-controlled trial. Our primary objective was to assess the effect of roflumilast compared with that of a placebo in reducing exacerbation rates in bronchiectasis patients. The secondary objectives were the changes in forced expiratory volume in 1 second (FEV1) and St. George's Respiratory Questionnaire (SGRQ). Bronchiectasis patients older than 18 years who had had two exacerbations during the previous 12 months were randomly assigned to receive either 500 μg of either roflumilast or a placebo once daily for 6 months in a 1:1 ratio.
Results: Forty bronchiectasis patients who had experienced exacerbations were screened. Thirty patients completed the study after 6 months of treatment: roflumilast group (n=15) and placebo group (n=15). The rates of exacerbations were 0.57 and 0.59 per patient in the roflumilast and placebo groups, respectively. Prebronchodilator FEV1 increased by 0.07 L from baseline in the roflumilast group and decreased by 0.015 L in the placebo group, but the difference was not significant. No significant differences were observed in the change of SGRQ scores between the roflumilast and placebo groups. Roflumilast had significant side effects, including loss of appetite and headache.
Conclusion: Roflumilast did not significantly affect the rate of exacerbations or quality of life. However, FEV1 tended to improve more in the roflumilast group than in the placebo group.

Background: The effect of underlying chronic obstructive pulmonary disease (COPD) on coronavirus disease 2019 (COVID-19) during a pandemic is controversial. The purpose of this study was to examine the prognosis of COVID-19 according to the underlying COPD.
Methods: COVID-19 patients were assessed using nationwide health insurance data. Comorbidities were evaluated using the modified Charlson Comorbidity Index (mCCI) which excluded COPD from conventional CCI scores. Baseline characteristics were assessed. Univariable and multiple logistic and linear regression analyses were performed to determine effects of variables on clinical outcomes. Ages, sex, mCCI, socioeconomic status, and underlying COPD were selected as variables.
Results: COPD patients showed older age (71.3±11.6 years vs. 47.7±19.1 years, p<0.001), higher mCCI (2.6±1.9 vs. 0.8±1.3, p<0.001), and higher mortality (22.9% vs. 3.2%, p<0.001) than non-COPD patients. The intensive care unit admission rate and hospital length of stay were not significantly different between the two groups. All variables were associated with mortality in univariate analysis. However, underlying COPD was not associated with mortality unlike other variables in the adjusted analysis. Older age (odds ratio [OR], 1.12; 95% confidence interval [CI], 1.11-1.14; p<0.001), male sex (OR, 2.29; 95% CI, 1.67-3.12; p<0.001), higher mCCI (OR, 1.30; 95% CI, 1.20-1.41; p<0.001), and medical aid insurance (OR, 1.55; 95% CI, 1.03-2.32; p=0.035) were associated with mortality.
Conclusion: Underlying COPD is not associated with a poor prognosis of COVID-19.

Background: Although it is known that inhaled corticosteroid (ICS) use may increase the risk of respiratory infection, its influence on the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains unknown. Thus, the aim of this study was to investigate the association between ICS use and the positivity of SARS-CoV-2 infection among patients with chronic respiratory diseases.
Methods: Nationwide data of 44,968 individuals with chronic respiratory diseases tested for SARS-CoV-2 until May 15, 2021 were obtained from the Ministry of Health and Welfare and Health Insurance Review and Assessment Service in Korea. The positivity of SARS-CoV-2 infection was retrospectively analysed according to the prescription, type, and dose of ICS taken one year before SARS-CoV-2 test.
Results: Among 44,968 individuals tested, 931 (2.1%) were positive for SARS-CoV-2. A total of 7,019 patients (15.6%) were prescribed ICS one year prior to being tested for SARS-CoV-2. Low, medium, and high doses of ICS were prescribed in 7.5%, 1.6%, and 6.5% of total cases, respectively. Among types of ICS, budesonide, fluticasone, beclomethasone, and ciclesonide were prescribed in 3.7%, 8.9%, 2.3%, and 0.6% of total cases, respectively. A multivariate analysis showed no significant increase in infection with ICS use (odds ratio, 0.84; 95% confidence interval, 0.66-1.03). Moreover, there were no associations between the positivity of infection and the dose or type of ICS prescribed.
Conclusion: Prior ICS use did not increase the positivity for SARS-CoV-2 infection. Moreover, different doses or types of ICS did not affect this positivity.