Pathological Mechanism and Targeted Drugs of COPD

Figures & data

Table 1 Antioxidants

Drugs	Type	Clinical Outcomes
NAC	Controlling oxidative stress	ClinicalTrials.gov, NCT01136239 (1-year high-dose NAC improved small airway function in COPD and reduced the frequency of exacerbations) ClinicalTrials.gov, NCT01739790 (The trial was 8 weeks and did not find that high-dose NAC improved respiratory clinical outcomes in COPD)
Sulforaphane	Targeting the Nrf2 gene	Clinicaltrials.gov, NCT01335971 (4 weeks of sulforaphane in COPD patients was not found to stimulate Nrf2 gene expression and was not found to improve inflammatory marker levels)

Table 2 Cytokine-Targeted Drugs

Drugs	Type	Clinical Outcomes
Infliximab	TNF-α inhibitor	ClinicalTrials.gov, NCT00056264 (In the treatment of COPD, infliximab has a higher probability of causing lung malignancy) ClinicalTrials.gov, NCT00244192 (6 weeks of treatment in COPD patients, had not any evidence pointed that it can improve clinical outcomes)
Etanercept	TNF-α inhibitor	ClinicalTrials.gov, NCT00789997 (It can improve lung function in COPD patients, it was less compared to prednisolone)
Mepolizumab	IL-5 inhibitor	ClinicalTrials.gov, NCT02105948, NCT02105961 (It can reduce COPD exacerbation with elevated eosinophils)
Benralizumab	IL-5 inhibitor	ClinicalTrials.gov, NCT02138916, NCT02155660 (Addition of benralizumab does not reduce annual exacerbation rates in patients with moderate or severe COPD with a history of frequent exacerbations)
MK-7123	CXCR2 inhibitor	ClinicalTrials.gov NCT01006616 (It can significantly improves lung function in COPD patients treated by 50mg dose)

Table 3 Enzyme Inhibitors

Drugs	Tpye	Clinical Outcomes
AZD9668	NE inhibitor	ClinicalTrials.gov NCT01054170 (After 12 weeks of treatment with 60 mg dose of AZD9668, not found of that CT airway structure were improved in COPD patients) ClinicalTrials.gov, NCT01023516 (AZD9668 three months treatment, no significant improvement in lung function found in COPD patients)
AZD1236	MMP-9, MMP-12 inhibitors	6 weeks of AZD1236 in COPD patients, had not found any valuable clinical outcomes^Citation81
RPL554	PED3/4 inhibitors	ClinicalTrials.gov, NCT02542254, NCT03028142 (Combined with that standard bronchodilators, it improves peak FEV1 in COPD patients)
Roflumilast	PED4 inhibitor	ClinicalTrials.gov, NCT00313209, NCT00424268 (Can improve lung function in COPD patients, but has the side effect of headache)

Table 4 Signaling Pathway Inhibitors

Drugs	Type	Clinical Outcomes
Verproside	NF-κB inhibitor	ClinicalTrials.gov, NCT02272634 (It blocked TNF-α/ NF-κB pathway in human airway epithelial cells NCI-H292)
SB-681323	p38MAPK inhibitor	ClinicalTrials.gov, NCT00380133 (Reduced TNF-α levels in COPD patients)
PH-797804	p38MAPK inhibitor	ClinicalTrials.gov, NCT00559910 (Improved lung function in patients with moderate to severe COPD)
GSK2269557 (nemiralisib)	PI3K inhibitor	ClinicalTrials.gov, NCT02294734 (Improved FEV1 in patients with moderate to severe COPD), ClinicalTrials.gov, NCT02130635 (Inhaled GSK2269557 can effectively reduce IL-6 and IL-8 levels in COPD patients) ClinicalTrials.gov, NCT02522299 (Altered sputum neutrophil transcription and improved neutrophil migration phenotype) ClinicalTrials.gov, NCT03345407 (12 weeks of treatment had not found that can improved clinical outcomes in acute exacerbations of COPD)

Ntontsi P, Detta A, Bakakos P, Loukides S, Hillas G. Experimental and investigational phosphodiesterase inhibitors in development for asthma. Expert Opin Investig Drugs. 2019;28(3):261–266. doi:10.1080/13543784.2019.1571582

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