Figures
- FIGURE 1
Type 2-low asthma pathways and potential therapeutic targets. MMP: matrix metalloprotease; LTB: leukotriene B; IL: interleukin; Th: T-helper cell; INF: interferon; TNF: tumour necrosis factor; ILC: innate lymphoid cells.
Tables
- TABLE 1
Differential diagnostic characteristics of type 2 (T2)-low versus T2-high asthma
T2-low asthma T2-high asthma Onset Late Early Symptoms Mostly significant May be significant Obesity Often present May be present Smoking Often present May be present Response to inhaled corticosteroids Often poor Usually good Severity of asthma Often difficult to treat Mild to severe Asthma control Often poor Variable Sputum eosinophils Absent Normal or high levels Sputum neutrophils Frequently present May be present Exhaled nitric oxide Usually normal Elevated or normal Airways Often present May be present - TABLE 2
Overview of the major biologic approaches currently in development for type 2 low asthma management
Studied biomarker Biologic Drug type Sponsor Main effects [Ref.] Add-on therapy in severe uncontrolled neutrophilic asthma IL-8 SCH527123/navarixin CXCR2 antagonist AstraZeneca Reduction in sputum neutrophils and in blood neutrophils
No improvement in clinical outcomes and exacerbation rates[81–83] Add-on therapy in uncontrolled moderate-to-severe asthma IL-17 Brodalumab Human anti-IL-17 receptor A monoclonal antibody Leo Pharma Did not improve ACQ score, lung function or asthma symptoms [84] Add-on therapy in severe uncontrolled neutrophilic asthma PDE4 PRL-554 CHF6001 (inhaled) Dual phosphodiesterase PDE3 and PDE4 inhibitors Verona Pharma, Chiesi Farmaceutici Bronchodilatatory and anti-inflammatory effect [85, 86] Severe and mild asthma
Severe, refractory, or steroid-resistant asthmaTNF-α Etanercept, golimumab Human monoclonal antibody against TNF-α Pfizer, Janssen Biologics Treatment was associated with substantial adverse reactions such as infections and malignancies [87, 88] Add-on therapy in severe uncontrolled neutrophilic asthma IL-1 Anakinra Human IL-1 receptor antagonist Swedish Orphan Biovitrum Reduced neutrophilic airway inflammation and sputum levels of IL-1β, IL-6 and IL-8 [89] Severe neutrophilic asthma p38 MAPK tyrosine kinase Losmapimod, AZD7624, masitinib, imatinib Protein kinase inhibitors, MAPK inhibitors, tyrosine kinase inhibitors GlaxoSmithKline, AstraZeneca, AB Science, Novartis Reduced exacerbations
Reduced inflammatory biomarkers from blood (IL-6, neutrophil percentage and CRP) and sputum (IL-6 and IL-8)
Improved asthma control[90–92] Severe uncontrolled asthma
Severe neutrophilic asthmaPI3-kinase Nemiralisib, IPI-145, RV-1729 (duvelisib) PI3-kinase inhibitors GlaxoSmithKline No discernible difference in trough FEV1 and ACT score
Attenuation of airway inflammation, promotion of bronchodilation and reversal of β2-adrenoreceptor tachyphylaxis[93–96] IL: interleukin; ACQ: Asthma Control Questionnaire; PDE: phosophdiesterase; TNF: tumour necrosis factor; MAPK: mitogen-activated protein kinase; CRP: C-reactive protein; PI3: phosphoinositide 3; FEV1: forced expiratory volume in 1 s; ACT: Asthma Control Test.
Vol 7 Issue 2
Table of Contents
Identification and treatment of T2-low asthma in the era of biologics
