Recent Insights into the Management of Inflammation in Asthma

Abstract

The present prevailing inflammatory paradigm in asthma is of T2-high inflammation orchestrated by key inflammatory cells like Type 2 helper lymphocytes, innate lymphoid cells group 2 and associated cytokines. Eosinophils are key components of this T2 inflammatory pathway and have become key therapeutic targets. Real-world evidence on the predominant T2-high nature of severe asthma is emerging. Various inflammatory biomarkers have been adopted in clinical practice to aid asthma characterization including airway measures such as bronchoscopic biopsy and lavage, induced sputum analysis, and fractional exhaled nitric oxide. Blood measures like eosinophil counts have also gained widespread usage and multicomponent algorithms combining different parameters are now appearing. There is also growing interest in potential future biomarkers including exhaled volatile organic compounds, micro RNAs and urinary biomarkers. Additionally, there is a growing realisation that asthma is a heterogeneous state with numerous phenotypes and associated treatable traits. These may show particular inflammatory patterns and merit-specific management approaches that could improve asthma patient outcomes. Inhaled corticosteroids (ICS) remain the mainstay of asthma management but their use earlier in the course of disease is being advocated. Recent evidence suggests potential roles for ICS in combination with long-acting beta-agonists (LABA) for as needed use in mild asthma whilst maintenance and reliever therapy regimes have gained widespread acceptance. Other anti-inflammatory strategies including ultra-fine particle ICS, leukotriene receptor antagonists and macrolide antibiotics may show efficacy in particular phenotypes too. Monoclonal antibody biologic therapies have recently entered clinical practice with significant impacts on asthma outcomes. Understanding of the efficacy and use of those agents is becoming clearer with a growing body of real-world evidence as is their potential applicability to other treatable comorbid traits. In conclusion, the evolving understanding of T2 driven inflammation alongside a treatable traits disease model is enhancing therapeutic approaches to address inflammation in asthma.

Phenotyping, Precision Medicine, and Asthma

“…Urinary leukotriene-E4 (LTE4) can delineate pathways driving aspirin exacerbated respiratory disease in a subpopulation of patients with type 2 asthma. 31,67 These markers continue to be utilized primarily in research studies and have not gained favor as clinically relevant biomarkers.…”

“…Furthermore, therapeutic interventions have an impact on the currently available biomarkers which renders them less useful after treatment is initiated. Our current non-invasive biomarkers provide important insights into disease biology without the need for invasive procedures such as airway biopsy 31 which has provided significant advantages and has enhanced our ability to subdivide patients into phenotypic groups, moving us closer to realizing our goal of implementing precision medicine in asthma care.…”

Recent Insights into the Management of Inflammation in Asthma [Letter]

“…Recently, Rupani et al 1 released a paper in the Journal of Inflammation Research, entitled “Recent Insights into the Management of Inflammation in Asthma.” The results mentioned in the original paper 1 are incomplete due to the fact that the authors did not take into account aerosols of expectorants that can optimize the patency of the respiratory tract for corticosteroids in obstructive bronchitis. Essentially an article by Rupani et al 1 is devoted to substantiating the importance of anti-inflammatory drugs in the treatment of patients with asthma, to eliminate curable signs of this heterogeneous disease and the need to continue the study of inflammatory pathways for new therapeutic purposes. The authors showed that inhaled corticosteroids (ICS) remain the basis of asthma treatment.…”

Role of Th17 Cytokines in Airway Remodeling in Asthma and Therapy Perspectives

“…In contrast, T2 high asthma is more commonly associated with response to steroids. Additionally, patients with T2 high severe asthma have now access to effective biotherapies that have emerged over the last decade, based on monoclonal antibodies targeting Th2 cytokines and immunoglobulins E (26). Although involvement of non-T2 pathways in asthma remains not fully understood, recent works have highlighted the role of Th17-driven inflammation in T2 low asthma (27)(28)(29).…”