AZD9668 (Alvelestat, AstraZeneca)34 and BAY 85-8501 (Bayer HealthCare)35 are two potent HNE inhibitors, belonging to the third and fifth generations of HNE inhibitors31, respectively, that have recently reached Phase II of clinical trials for COPD, CF, and BE (Figure 1). This evidence concerns the gene ELANE and cystic fibrosis.