Inhaled Tranexamic Acid: A Therapeutic Option For Hemoptysis

Abstract

mally symptomatic patients, and the addition of long-acting anticholinergics for more symptomatic patients.1 Severe cases warrant the use of systemic glucocorticoids to control COPD exacerbations. The benefits of smoking cessation, vaccinations, antibiotic therapy, and pulmonary rehabilitation are well established.1 Multiple researchers have linked the use of aspirin to the overall improvement in mortality in COPD.2–5 It reduces the need for mechanical ventilation and hospital stay, and it has also been linked to a reduction in the progression of emphysema.2–6 Pavasani et al5 carried out a meta-analysis of 5 observational studies and concluded that there is a decrease in mortality rate associated with the use of aspirin at different phases of COPD, in both the outpatient and inpatient settings. Schwameis et al7 carried out a randomized, double-blinded, single-center study, to evaluate the addition of aspirin to the standard treatment. In the study, 40 patients (sufficient power) were randomized to either aspirin therapy or to placebo, with the primary endpoint of FEV1 and secondary endpoints of changes in mean peak expiratory flow and SGRQ scores, but no statistically significant differences were identified in the 12-week observation period.7 Because the existing medications to treat COPD and its exacerbations only produce modest improvements despite combinations, new therapies are being evaluated.8 Harrison et al4 found that thrombocytosis (>400×109 cells/mm3) was associated with a 137% increase in the risk of inpatient mortality and a 53% increase in 1-year mortality for COPD, and that antiplatelet therapy with aspirin or clopidogrel led to a 3-fold reduction in the 1-year mortality.4 In the current observational cohort study, Fawzy et al2 reported a novel correlation between aspirin use and several morbidities, such as acute exacerbation of COPD, respiratory symptoms, and quality of life. They followed-up patients aged 40 to 80 years, across 12 clinical sites in the United States, for up to 36 months. The primary outcome of interest was the number of moderate and severe acute exacerbations, while secondary outcomes included baseline COPD status using the mMRC scale, SGRQ, and 6-minute walk test. As this was an observational cohort study, a propensity score–matched analysis was required.2 Of the 1843 initial participants, a total of 1698 had consistent follow-up and acute exacerbation data. A total of 764 (45%) reported using aspirin daily at baseline, but, after matching, 503 pairs of participants with balanced baseline characteristics between aspirin users and nonusers were identified.2 The participants were on average 66.5 years old, with postbronchodilator FEV1 of 62% predicted, of male sex, white, and with fewer than 2 cardiovascular comorbidities.2 At baseline, the sample consisted of 30% current smokers and 23% home oxygen users, 43% statin users, 48% inhaled corticosteroid users, and 58% long-acting bronchodilator users during the previous 3 months. In adjusted analysis, aspirin users had about a 22% lower incidence of total acute exacerbations, with an incidence rate ratio (IRR) of 0.78, while reduction in moderate acute exacerbations IRR was 0.75. There was no statistically significant difference in severe exacerbations, with an IRR of 0.86. Baseline cross-sectional analysis of 1044 participants showed that aspirin users had 3 points lower SGRQ scores [95% confidence interval (CI), −4.9 to −1.1], with a 34% lower odds of reporting moderate-severe dyspnea on the basis of mMRC score (≥ 2) with adjusted odds ratio of 0.66 and 95% CI of 0.49-0.90, and lower total COPD assessment test (CAT) score (β, −1.1; 95% CI, −1.9 to −0.2). There was no association between aspirin use and 6-minute walk distance.2 In summary, daily aspirin intake was associated with reduced rates of acute exacerbations, a better quality of life, and improvement of dyspnea. A recent study6 showed the attenuation of emphysema progression with aspirin, but there was a lack of follow-up scans. Elevated thromboxane A2 from activated platelets has been detected in COPD, and this pathway is irreversibly inhibited by aspirin.2 Aspirin treatment also decreases proinflammatory cytokines in bronchoalveolar lavage.2 Despite good design and power, this study had several limitations. Aspirin use was self-reported, and dose and adherence were not ascertained.2 It did not investigate the effects of aspirin on mild exacerbations. Other factors such as physical activity, trigger avoidance, medication, and vaccination adherence were not well accounted for.2 This study used SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study), which was not designed to assess aspirin use.2 Therefore, at the end of the day, this is an observational study, and we should take the observations with a grain of salt; a blinded randomized control study is required to confidently claim a definitive correlation and causation.