Abstract
Purpose: Gender differences exist in the prevalence of asthma and allergic diseases, partially due to the effects of sex hormones on the development of allergic manifestations. Women, compared with men, are more prone to suffer allergic asthma, experience difficulties in controlling asthma symptoms, and show adverse responses to drugs. However, there are knowledge gaps on the effectiveness of anti-leukotrienes drugs on lung function, symptoms, and pulmonary and systemic inflammation in adult asthmatic women compared with men. We conducted a prospective cohort study to characterize the effectiveness of an anti-leukotrienes drug, montelukast (MS), in asthmatic adult women and men. Methods: Twenty-one asthmatic subjects (11 women and 10 men), who were on low-dose inhaled corticosteroids (ICS), were treated with MS. The optimal control of the symptoms was achieved in both groups according to the Global Initiative for Asthma guidelines. At enrollment, and after 13 weeks from the beginning of MS, pulmonary function tests and asthma control tests were performed, and the fraction of exhaled nitric oxide and blood eosinophils levels were measured. Results: From baseline until the end of the study, women treated with MS + ICS had better control of the asthmatic symptoms, defined as higher asthma control test (ACT) score (17.00 ± 1.07 to 23.36 ± 0.45; p < 0.0015), improved pulmonary function [with higher forced expiratory volume in 1 s (from 77.25 ± 6.79 to 103.88 ± 6.24; p < 0.0077)], and forced vital capacity (from 91.95 ± 6.81 to 113.17 ± 4.79; p < 0.0183) compared with men. Interestingly, MS + ICS-treated women had significantly lower levels of blood eosinophils (from 5.27 ± 0.30 to 3.30 ± 0.31; p < 0.0449) and exhaled nitric oxide (from 44.70 ± 7.30 to 25.20 ± 3.90; p < 0.0294) compared with men. Conclusion: The treatment with MS, added to ICS, in women leads to better control of symptoms, better management of lung function, and decreased inflammation levels compared with ICS + MS treatment in men.
Highlights
Asthma, a highly prevalent chronic inflammatory disease of the airways, is characterized by a variable degree of airflow obstruction (D’Agostino et al, 2010) and bronchial hyperresponsiveness (Locksley, 2010; Roviezzo et al, 2016), caused by chronic exposition to allergens (Hamid and Tulic, 2009; Spaziano et al, 2015) or associated to other diseases such as gastroesophageal reflux (Gallelli et al, 2017; Rouget et al, 2004; D’Agostino et al, 2005)
Asthmatic women treated with MS + ICS showed a better control of symptoms compared with men treated with the same dose and therapeutic approach (Figure 1C)
This is the first prospective cohort study that documents a higher effectiveness of MS treatment on lung function, symptoms, and readouts of inflammation in asthmatic women compared with men, suggesting a sex-dependent effect of the treatment with MS in asthma
Summary
A highly prevalent chronic inflammatory disease of the airways, is characterized by a variable degree of airflow obstruction (D’Agostino et al, 2010) and bronchial hyperresponsiveness (Locksley, 2010; Roviezzo et al, 2016), caused by chronic exposition to allergens (Hamid and Tulic, 2009; Spaziano et al, 2015) or associated to other diseases such as gastroesophageal reflux (Gallelli et al, 2017; Rouget et al, 2004; D’Agostino et al, 2005). During inflammatory reactions, androgens influence 5-lipoxygenase (5-LO)-mediated cellular events (Sessa et al, 2018), inducing lower LT biosynthesis in men compared with women (Rossi et al, 2019) Based on this evidence, some study suggested that the gender could play a role on the effectiveness of anti-asthmatic pharmacological treatments, such as montelukast (MS). Some study suggested that the gender could play a role on the effectiveness of anti-asthmatic pharmacological treatments, such as montelukast (MS) It is unknown whether gender differences could have an effect on the asthmatic symptoms, pulmonary function, and biomarkers associated with the severity of asthma [e.g., eosinophils and exhaled nitric oxide (FeNO)] (Sessa et al, 2018) in the adult population. Given the major role of LTs in the female biology, the gender differences should be taken in consideration when evaluating the therapeutic potential of anti-LT drugs as well as the efficacy of LT inhibitors in asthma
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