Table 4.
Representative Therapeutics in Use or under Investigation for Noneosinophilic Asthma
| Target | Treatment | Studies | Patient Population | Outcomes |
|---|---|---|---|---|
| Muscarinic receptors | Tiotropium* (long-acting muscarinic antagonist) | Iwamoto et al., 2008 (137) | Severe asthma (n = 17) | Improvement in lung function with increasing sputum neutrophils |
| Bacteria | Clarithromycin (macrolide antibiotic) | Simpson et al., 2008 (156) | Severe refractory asthma (n = 45) | Improved QOL scores in NEA |
| Azithromycin (macrolide antibiotic) | Brusselle et al., 2013 (157) | Severe asthma (n = 109) | Fewer exacerbations and lower respiratory infections in NEA only | |
| HMG-CoA reductase | Atorvastatin | Braganza et al., 2011 (158) | Smokers with asthma with NEA (n = 71) | Improved QOL at 4 wk but not 8 wk |
| PPARγ | Rosiglitazone (PPARγ agonist) | Spears et al., 2009 (159) | Smokers with mild to moderate asthma (n = 46) | Improvement in lung function at 28 d |
| Pioglitazone (PPARγ agonist) | Dixon et al., 2015 (160) | Obese patients with asthma (n = 23) | No improvement; weight gain | |
| PDE | Theophylline* (nonselective PDE inhibitor) | Spears et al., 2009 (161) | Smokers with asthma with NEA (n = 68) | Improved symptoms and peak flow at 4 wk |
| Roflumilast (PDE4 inhibitor) | Gauvreau et al., 2011 (162) | Mild allergic asthma (n = 25) | Inhibits allergen-induced increase in sputum neutrophils and eosinophils | |
| Meltzer et al., 2015 (163) | Pooled analysis of 9 randomized studies on moderate to severe asthma (n = 4,873) | Improved asthma symptom control and lung function | ||
| CXCR2 | SCH527123 (CXCR2 antagonist) | Nair et al., 2012 (164) | Severe asthma with sputum neutrophilia > 40% (n = 34) | Fewer mild exacerbations |
| IL-17 receptor | Brodalumab (anti–IL-17RA antibody) | Busse et al., 2013 (165) | Moderate to severe asthma (n = 302) | No improvement |
| TNF | Etanercept (soluble TNF-α receptor blocker) | Berry et al., 2006 (166) | Mild to severe asthma (n = 30) | Improvement in QOL, lung function, and bronchial hyperreactivity |
| Holgate et al., 2011 (167) | Moderate to severe asthma (n = 132) | No benefit | ||
| Golimumab (anti–TNF-α antibody) | Wenzel et al., 2009 (168) | Severe asthma (n = 309) | Discontinued early; unfavorable risk | |
| IL-1 | Anakinra (IL-1R antagonist) | www.clinicaltrials.gov |
— | |
| IL-6 | Sirukumab (anti–IL-6 antibody) | www.clinicaltrials.gov |
— | |
| Protein kinases | Phosphoinositide 3 kinase inhibitors | Preclinical | — | — |
| Tyrosine kinase inhibitors | ||||
Definition of abbreviations: CXCR2 = chemokine receptor 2; HMG-CoA = 3-hydroxy-3-methylglutaryl-coenzyme A; NEA = noneosinophilic asthma; PDE = phosphodiesterase; PPARγ = peroxisome proliferator-activated receptor-γ; QOL = quality of life; TNF = tumor necrosis factor.
*
U.S. Food and Drug Administration approved at time of article submission for treatment of asthma.