Table 1.

Overview of clinical trials undertaken using protease inhibitors in patients with muco-obstructive lung diseases including CF, COPD, and bronchiectasis.

Target Protease	Inhibitor	Disease	Stage	Outcome
NE	A1-AT	CF	II	Reduced inflammation, no effect on lung function [189,190]
		Bronchiectasis	I	Results unpublished [191]
		COPD/A1-AT deficiency	II/III	Reduced serine protease levels, reduces elastin degradation in the lung, reduced inflammation [192,193,194]
	AZD9668	CF	II	Reduced inflammation, no effect on lung function [195]
		COPD	II	No changes in lung function or inflammation [196,197]
		Bronchiectasis	II	Improved lung function and reduced sputum inflammatory biomarkers [198]
	AZD6553	COPD	I	Terminated due to emerging PK profile that could not be aligned to the known pharmaceutical properties of the IMP [199]
	Alvelestat	COPD	II	Currently recruiting [200]
	POL6014	CF	I	No serious adverse effects noted [201,202]
	CHF6333	CF + non-CF bronchiectasis	I	Results unpublished [203]
	BI 1323495	Bronchiectasis	I	Currently recruiting [204]
	BAY85-8501	Bronchiectasis	II	No changes in lung function or inflammation [205,206]
MMP-9/-12	AZD1236	COPD	II	No clinical efficacy observed [207]
Cathepsin C	Brensocatib	Bronchiectasis	II	Improved clinical outcomes with reduced NE activity, reduced time to first exacerbation [208]