Table 1.

Compounds tested in LPS model and development progression

Compounds	Administration route of IMP	LPS model	Effects on inflammatory markers	Progression to Phase III	Sources
Prednisolone	Oral	Inhaled	No effect on lung inflammation; significant reduction in CRP	Yes, successful NDA	13
Cilomilast (PDE4I, GlaxoSmithKline)	Oral	Inhaled	No effect on lung inflammation, reduction in CRP (P = 0.09)	Yes, development terminated due to lack of efficacy	13
Fluticasone	Inhaled	Inhaled	Significant reduction in neutrophils and eosinophils; no effect on soluble inflammatory markers	Yes, successful NDA	16
Roflumilast (PDE4I, Nycomed)	Oral	Segmental	Significant reduction in neutrophils and eosinophils; no effect on soluble inflammatory markers in bronchoalveolar lavage	Yes, successful NDA and Market Authorization Application	15
Simvastatin	Oral	Inhaled	Reduction in neutrophils, MPO, TNFα, MMP-7, -8, and -9 in the BALF; reduction in plasma CRP	Two Phase II clinical trials are ongoing in acute lung injury; 4 large RCTs in COPD are ongoing	62

Abbreviations: LPS, lipopolysaccharide; IMP, investigational medicinal product; CRP, C-reactive protein; NDA, new drug application; PDE4I, phosphodiesterase type 4 inhibitor; MPO, myeloperoxidase; TNF, tumor necrosis factor; MMP, matrix metalloproteinase; BALF, bronchoalveolar lavage fluid; RCTs, randomized controlled trials; COPD, chronic obstructive pulmonary disorder.