47. CXCR2 ANTOGONIST
● CXCR2 is a potent neutrophil chemotactic factor and considered to be
involved in neutrophil migration to sites of inflammation.
● Antagonists of the human CXCR2 receptors target neutrophil trafficking
in inflammatory pathway.
● MK-7123, a CXCR2 antagonist, is undergoing trials and has shown
significant improvement in FEV1 compared to placebo in COPD patients.
48. P38 MITOGEN-ACTIVATED PROTEIN KINASE
(P38 MAPK) INHIBITORS
● P38 mitogen-activated protein kinase (P38 MAPK) pathway involves a
signaling cascade that controls the cellular responses to cytokines and
stress.
● P38 MAPK pathway is upregulated in COPD.
49. MATRIX METALLOPROTEINASES INHIBITORS
● Protease and antiprotease imbalance plays a significant role in COPD.
● Antagonizing matrix metalloproteinases (MMP) using selective MMP
inhibitors provided an option to revert back thebalance.
50. HUMANIZED MABTARGETEDTO ALPHA SUBUNIT IL-5 R
● Humanized monoclonal antibodies targeted to alpha subunit of the
interleukin (IL)-5 receptor (IL-5Ra) selectively blocks IL-5.
● This action is considered to be beneficial in management of asthmatic
inflammation as well as COPD exacerbations.
51. ANTIHUMAN IL-17 R ANTIBODIES
● Interlukin (IL)-17 is an important cytokine for regulating mucosal defense
● Aberrant expression or overexpression of IL-17 cytokines contributes to a
number of pathological outcomes.
● IL-17A induce neutrophilic inflammation by releasing CXCL1, CXCL8, and
GM-CSF from airway epithelial cells and smooth-muscle cells.
● Antihuman IL-17R antibodies including
Ixekizumab,
Brodalumab, and
Ustekinumab are investigated in asthma and COPD.
52. PHOSPHOINOSITIDE3-KINASES INHIBITORS
● Phosphoinositide 3-kinase (PI3K) signaling is upregulated in COPD and
correlates with an increased susceptibility of patients to lung infections.
● PDE 3-kinases inhibitors prevent recruitment of inflammatory.
● Inhalation resulted in suppression of sputum, IL-8 and IL-6 levels; with a
potential therapeutic benefit in chronically inflamed COPD patients.
● PDE 3-kinases inhibitors - GSK2269557-Inhalational route.
53. AUTOLOGOUS STEM CELLTHERAPY
● Stem cell- based therapies that have being investigated in the management of COPD.
● Stem cells deliver signals to host cells, inducing a regenerative mechanism against alveolar
destruction in the COPD lung.
● They also contribute to tissue maintenance and repair due to their inherent anti-
inflammatory properties.
● Mesenchymal stem cells (MSCs) reduce airway inflammation and regenerate the alveolus in
cigarette- and elastase-induced COPD.
● Stem cell therapy is still in the early stages of implementation, no phase III randomized
controlled trials and no US FDA approval.
54. CONCLUSION
● SABA and SAMA are appropriate for use as rescue medication.
● LABA and LAMA are first-line maintenance (daily) treatment in COPD
patients.
● Ultra-LAMA and ultra-LABA appear tempting due to once daily
convenience and lesser adverse reactions as claimed by their developers
● their availability in many countries still an issue.
55. ● The patients with Asthma-COPD Overlap Syndrome may respond better with a
combination of LABA + IS. Raised blood eosinophils can provide indications for
using inhaled corticosteroids.
● Patients with COPD Group D may require triple-inhaler therapy including LABA +
LAMA + ICS.
● COPD patients with recurrent exacerbations, those with lower respiratory tract
bacterial colonization, or those with coexistent bronchiectasis may have beneficial
efficacy with selective PDE4 inhibitor and/or long-term antibiotic prophylaxis.
