Adverse drug reactions of montelukast and pranlukast: Analysis of the Korea database.

BACKGROUND: Leukotriene receptor antagonists are recommended to treat asthma and allergic rhinitis. Although they had been used for a long time, recent studies have reported neuropsychiatric adverse drug reactions are associated with montelukast. OBJECTIVE: This study analyzed the adverse drug reactions of montelukast and pranlukast, which are the two most frequently prescribed leukotriene receptor antagonists, respectively in Korea. METHODS: This study retrospectively reviewed ADRs of 5,426 montelukast and 1,146 pranlukast reported in the Korea Adverse Event Reporting System between January 2014 and December 2018. RESULTS: When both drugs are classified by system organ class, the most adverse drug reactions were related to the gastro-intestinal system, followed by psychiatric events. The reported adverse drug reactions for both drugs were more common in women, and the ratio of adverse drug reactions to prescriptions was highest in the elderly. Women aged 19 to 64 years reported more than twice as many adverse drug reactions than men of the same age, and more than 5 times in insomnia. CONCLUSIONS: When prescribing montelukast and pranlukast, attention would need to digestive and sleep disorders, especially women aged 19 to 64. After prescribing montelukast, physicians would need to pay more attention to agitation (5/396378 vs 0/82475), bad or vivid dreams (6/396378 vs 0/82475), anxiety (11/396378 vs 0/82475), depression (14/396378 vs 1/82475), tremor (53/396378 vs 7/82475), irritability (5/396378 vs 1/82475), insomnia (159/396378 vs 25/82475), and headache (68/396378 vs 10/82475), compared to when prescribing pranlukast. Further prospective research needs to elucidate the relationship between neuropsychiatric events and montelukast.

Discontinuation of inhaled corticosteroids in patients with controlled asthma: The DISCO (Discontinuation of Inhaled Steroid in Controlled asthmatics Over 6 months) study.

BACKGROUND: Although inhaled corticosteroids (ICSs) are the recommended first-line therapy for asthma, determining whether to continue or discontinue ICS treatment in patients with mild asthma remains challenging for clinicians. Several studies have revealed that patients with mild-persistent asthma maintained a well-controlled state after ICS withdrawal. However, the long-term outcomes of ICS withdrawal have not yet been determined. OBJECTIVE: To determine the possible clinical outcomes of the discontinuation of ICS in patients with well-controlled mild asthma. METHODS: We investigated the clinical outcomes of discontinuing ICSs in patients with well-controlled mild asthma and compared the time to loss of control (LOC) between patients who stopped ICS treatment (ICS withdrawal group, IWG) and those who continued treatment for 3 years (continuous ICS group, CIG). RESULTS: A significant difference in the time to LOC was observed between the IWG and CIG (hazard ratio, 2.56; 95% confidence interval, 1.52-4.33; P < .001). Increasing fractional exhaled nitric oxide levels (P = 0.008) and sputum eosinophil counts (%) (P = 0.015) revealed a weak but significant association with LOC risk in the CIG. The sputum eosinophil counts (P = 0.039) and serum total immunoglobulin E levels (P = 0.014) were significantly higher in the LOC group than in the non-LOC group of the CIG. CONCLUSION: Our results suggest that the maintenance of ICS treatment may help keep patients' asthma under control. Furthermore, patients with LOC had significantly higher sputum eosinophil counts in the CIG than those in the non-LOC group. Therefore, continuous ICS use by patients with mild, well-controlled asthma could be associated with good clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: KCT0002234.

Impact of asthma, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap on the prognosis of coronavirus disease 2019.

Background: The effects of asthma, chronic obstructive pulmonary disease (COPD), or asthma-COPD overlap (ACO) on coronavirus disease 2019 (COVID-19) remain unclear. Objective: We aimed to investigate the effects of chronic obstructive airway diseases such as asthma, COPD, and ACO on COVID-19. Methods: In total, 5625 hospitalized patients with COVID-19 were divided into asthma, COPD, ACO, and control groups. A multivariate logistic regression analysis was performed to identify factors affecting the COVID-19 mortality rate. To find out whether chronic obstructive airway diseases such as asthma, COPD, and ACO affect COVID-19 mortality, 1:4 matching was performed, except for the ACO group alone due to a small number of patients. Results: The mortality rates of asthma, COPD, and ACO groups were about 2.3, 4.8, and 5.5 times higher than that of the control group, respectively. Although not statistically significant, the survival probability tended to decrease (asthma, COPD, and combined groups of asthma and ACO, hazard ratio [HR]: 1.84, 1.31, and 1.89, respectively). The survival probability of the combined groups of COPD, ACO, and asthma and the combined groups of COPD and ACO was significantly lower than that of the matched control group (HR: 3.00 and 1.99, respectively). Conclusion: Compared to patients with COVID-19 without chronic obstructive airway disease, patients with these comorbidities are more likely to require oxygen and mechanical ventilators and have a higher mortality rate, which can be considered when classifying and monitoring patients in the era of COVID-19. Therefore, further studies are needed to evaluate the effect of chronic obstructive airway disease, especially ACO, on COVID-19 mortality.

Clinical predictors of treatment response to tiotropium add-on therapy in adult asthmatic patients: From multicenter real-world cohort data in Korea.

Background: Tiotropium, a long-acting muscarinic antagonist, is recommended for add-on therapy to inhaled corticosteroids (ICS)-long-acting beta 2 agonists (LABA) for severe asthma. However, real-world studies on the predictors of response to tiotropium are limited. We investigated the real-world use of tiotropium in asthmatic adult patients in Korea and we identified predictors of positive response to tiotropium add-on. Methods: We performed a multicenter, retrospective, cohort study using data from the Cohort for Reality and Evolution of Adult Asthma in Korea (COREA). We enrolled asthmatic participants who took ICS-LABA with at least 2 consecutive lung function tests at 3-month intervals. We compared tiotropium users and non-users, as well as tiotropium responders and non-responders to predict positive responses to tiotropium, defined as 1) increase in forced expiratory volume in 1 s (FEV1) ≥ 10% or 100 mL; and 2) increase in asthma control test (ACT) score ≥3 after 3 months of treatment. Results: The study included 413 tiotropium users and 1756 tiotropium non-users. Tiotropium users had low baseline lung function and high exacerbation rate, suggesting more severe asthma. Clinical predictors for positive response to tiotropium add-on were 1) positive bronchodilator response (BDR) [odds ratio (OR) = 6.8, 95% confidence interval (CI): 1.6-47.4, P = 0.021] for FEV1 responders; 2) doctor-diagnosed asthma-chronic obstructive pulmonary disease overlap (ACO) [OR = 12.6, 95% CI: 1.8-161.5, P = 0.024], and 3) initial ACT score <20 [OR = 24.1, 95% CI: 5.45-158.8, P < 0.001] for ACT responders. FEV1 responders also showed a longer exacerbation-free period than those with no FEV1 increase (P = 0.014), yielding a hazard ratio for the first asthma exacerbation of 0.5 (95% CI: 0.3-0.9, P = 0.016). Conclusions: The results of this study suggest that tiotropium add-on for uncontrolled asthma with ICS-LABA would be more effective in patients with positive BDR or ACO. Additionally, an increase in FEV1 following tiotropium may predict a lower risk of asthma exacerbation.