Can Leukotriene Receptor Antagonist Therapy Improve the Control of Patients with Severe Asthma on Biological Therapy and Coexisting Bronchiectasis? A Pilot Study

Abstract

Introduction: Asthma and bronchiectasis appear to be two related diseases and in their complex inflammatory interaction, the cysteinyl leukotriene/cysteinyl leukotriene receptor 1 (cysLT/cysLTR1) axis appears to play an important role given its involvement also in the neutrophilic pathway. To our knowledge, few studies have been conducted so far to evaluate the role of the leukotriene cysLT/cysLTr1 axis in the management of clinical and inflammatory outcomes within a population of patients with severe asthma and bronchiectasis. The aim of our study was to verify in this population the effect of leukotriene receptor antagonist (LTRA) therapy in clinical and inflammatory control before and after 6 months of introduction of biologic therapy. Methods: We retrospectively enrolled, from eight different severe asthma centers’ outpatients, 36 atopic patients with the simultaneous presence of non-cystic fibrosis (non-CF) and non-allergic bronchopulmonary aspergillosis (non-ABPA) bronchiectasis and severe asthma. The first biological injection was performed at baseline (T0 time). Patients who were already taking LTRA therapy at time T0 were recorded, and no new prescriptions were made. We observed our population over a 6-month period (T1 time). At the baseline we collected the following data: baseline characteristics, clinical history, high resolution computed tomography and bronchiectasis-related parameters and skin prick test. At both times T0 and T1 we collected the following data: asthma control test (ACT), asthma control questionnaire (ACQ), immunoglobulin E (IgE) level, blood count, fractional exhaled nitric oxide 50 (FeNO 50) and flow-volume spirometry. The study was retrospectively registered. Results: Our population had a mean age of 59.08 ± 11.09 and 50% were female. At T1, patients on LTRA therapy had a significantly lower FeNO value (33.03 ± 23.61 vs. 88.92 ± 77.96; p = 0.012). We assessed that the value of ΔFeNO (FeNO 50 T1 − FeNO 50 T0) and the number of unplanned specialist visits allowed a discrimination of 66.7% in the presence of LTRA therapy. We also verified how low FeNO values at time T1 were statistically significant predictors of LTRA therapy (ODD = 9.96 (0.94–0.99); p = 0.032). Conclusion: The presence of LTRA in therapy in a population of severe asthmatics with coexisting non-ASBPA bronchiectasis and non-cystic fibrosis, acting simultaneously on the T helper type 2 (TH2) pathway and probably on the neutrophilic component of bronchiectasis, would allow a further amplification of the beneficial effects of biological therapy, leading to a reduction in the number of unplanned visits to specialists.

Bronchial Asthma as a Cardiovascular Risk Factor: A Prospective Observational Study

“…In our group, anti-IgE therapy led to a reduction in the need for systemic corticosteroids and a reduction in the number of exacerbations, as well as a gradual improvement in fitness and a return to physical activities, but the persistent overweight from the period before the initiation of anti-IgE therapy seems to be one of the possible reasons for the higher risk of CVD in some patients, in addition to the severity of the disease. The effect of LTRA therapy on improving control in patients with severe asthma on biological therapy was investigated by Quaranta et al [ 79 ].…”

Blood eosinophil percentage as a predictor of response to inhaled corticosteroid in bronchiectasis

“…Another unplanned post hoc analysis of a randomised, double‐blind, controlled study also suggested that 6‐month treatment with inhaled fluticasone propionate in adults with bronchiectasis significantly improved quality of life with a trend of lower exacerbation rate among those with a blood eosinophil count ≥3% or ≥150 cells/μL compared with control 21 . Nonetheless, post hoc analysis of another randomised, double‐blind, parallel‐group trial of 40 patients with bronchiectasis revealed no significant change in quality of life after 6 months of inhaled budesonide treatment in the subgroup with baseline blood eosinophil count of at least 3% and 150 cells/μL 22 …”

“…21 Nonetheless, post hoc analysis of another randomised, double-blind, parallel-group trial of 40 patients with bronchiectasis revealed no significant change in quality of life after 6 months of inhaled budesonide treatment in the subgroup with baseline blood eosinophil count of at least 3% and 150 cells/μL. 22 The role of ICS in preventing bronchiectasis exacerbation remained controversial. Despite the evidence from earlier reports, this was challenged by subsequent Cochrane review and European guidelines.…”

“…To provide personalised treatment, phenotyping of airway diseases is crucial, 10–16 and blood eosinophil count is one of the most commonly used biomarkers in phenotyping 14–16 . Eosinophilic phenotype is also reported in bronchiectasis, 17–20 and it may play a role in the therapeutic options in bronchiectasis, 21,22 especially on ICS treatment 23,24 . Blood eosinophil count may also predict the preferential localisation of bronchiectasis in patients with severe asthma, and type 2 inflammation was postulated to have causative role in the development of bronchiectasis among severe asthma patients 25,26 …”

Role of Leukotriene Antagonists in the Treatment of Asthma Exacerbations

“…In different types of asthma included in the study, like aspirin-exacerbated, elderly asthma, smoking asthma, obesity associated asthma along with asthma comorbid with allergic rhinitis, LTRA therapy proved to be advantageous because of the reduction of FeNO biomarker. LTRA therapy acts on both eosinophilic and neutrophilic inflammatory pathway to control asthma exacerbation [11].…”