Figures
- FIGURE 1
Classification of asthma phenotypes and disease severity based on T-helper cell type 2 (Th2) and non-Th2 characteristics. LPS: lipopolysaccharide.
- FIGURE 2
A microRNA (miR)-21/phosphoinositide 3-kinase (PI3K)/histone deacetylase (HDAC)2 axis drives severe steroid-resistant asthma and may be targeted using miR-21-specific inhibitors (such as antagomiR (Ant)-21) and/or PI3K inhibitors (such as LY294002). AAD: allergic airway disease; PTEN: phosphatase and tensin homologue.
- FIGURE 3
Role of the NLRP3 inflammasome in severe steroid-resistant asthma. An infection and/or allergen promotes NLRP3 inflammasome-mediated cleavage of pro-caspase-1 into caspase-1 (CASP1), which then cleaves pro-interleukin (IL)-1β into active IL-1β, which drives steroid-resistant asthma. Neutralising anti (α)-IL-1β antibodies, a CASP1-specific inhibitor (YVAD) and a potent and highly specific NLRP3 inflammasome inhibitor (MCC950) may have therapeutic utility in severe steroid-resistant asthma. PAMPs: pathogen-associated molecular patterns; DAMPs: damage-associated molecular patterns; ASC: adaptor protein apoptosis-associated speck-like containing a caspase recruitment domain; PYD: pyrin domain; CARD: caspase recruitment domain.
Tables
- TABLE 1
Role of infections in the pathogenesis of severe steroid-resistant asthma and their response to steroid therapy
Pathogen Asthma endotype Immune response Steroid resistance [Ref.] AHR Inflammation Chlamydia Neutrophilic SSRAAD ↑Th1/Th17 and ↓Th2 Yes Yes [52] Haemophilus Neutrophilic SSRAAD ↑Th17 and ↓Th2 Yes Yes [51] Influenza A virus Eosinophilic SSRAAD ↑Th1 and ↔Th2 Yes Intermediate [60] Respiratory syncytial virus Eosinophilic SSRAAD ↑Th1 and ↔Th2 Yes Yes [61] AHR: airway hyperresponsiveness; SSRAAD: severe steroid-resistant allergic airway disease; Th: T-helper cell; ↑: increased; ↓: decreased; ↔: no change.
