Novel Anti-Inflammatory Approaches to COPD

Abstract

Airway inflammation, driven by different types of inflammatory cells and mediators, plays a fundamental role in COPD and its progression. Neutrophils, eosinophils, macrophages, and CD4⁺ and CD8⁺ T lymphocytes are key players in this process, although the extent of their participation varies according to the patient’s endotype. Anti-inflammatory medications may modify the natural history and progression of COPD. However, since airway inflammation in COPD is relatively resistant to corticosteroid therapy, innovative pharmacological anti-inflammatory approaches are required. The heterogeneity of inflammatory cells and mediators in annethe different COPD endo-phenotypes requires the development of specific pharmacologic agents. Indeed, over the past two decades, several mechanisms that influence the influx and/or activity of inflammatory cells in the airways and lung parenchyma have been identified. Several of these molecules have been tested in vitro models and in vivo in laboratory animals, but only a few have been studied in humans. Although early studies have not been encouraging, useful information emerged suggesting that some of these agents may need to be further tested in specific subgroups of patients, hopefully leading to a more personalized approach to treating COPD.

Keywords:

• anti-inflammatory drugs
• COPD
• inflammation
• treatment

Abbreviations

AAT, α1-antitrypsin, AATD, AAT deficiency; ACT, α-1-antichymotrypsin; AECOPD, acute exacerbations of COPD; AR, adrenoceptor; BALF, bronchoalveolar lavage fluid; BEC, blood eosinophil count; cAMP, cyclic adenosine monophosphate; cGMP, cyclic guanosine monophosphate; CS corticosteroid; COPD, chronic obstructive pulmonary disease; CXCR, CXC chemokine receptor; DC, dendritic cell; DPP1, dipeptidyl peptidase 1; ECM, extracellular matrix; FEV₁, forced expiratory volume in the first second; GR, glucocorticoid receptor; HDAC. Histone deacetylase; HRQoL, health-related quality of life; ICS, inhaled corticosteroid; Ig, immunoglobulin; IL, interleukin; IL-4Rα, interleukin-4 receptor subunit α; IL-5Rα, interleukin-5 receptor subunit α; IL-17RA, IL-17 receptor A; IL-33^ox, IL-33 oxidated form; IL-33^red, IL-33 reduced form; LABA, long-acting β₂-agonist; LAMA, long-acting muscarinic antagonist; LPS, lipopolysaccharide; mAb, monoclonal antibody; MAPK, mitogen-activated protein kinase; MMP, matrix metalloprotease; NE, neutrophil elastase; NETs, neutrophil extracellular traps; PDE, phosphodiesterase; PI3K, phosphoinositide 3-kinase; RCT, randomized controlled trial; Rfh, recombinant form of human fragments; sAC, soluble adenylyl cyclase; SP, surfactant protein; Syk, spleen tyrosine kinase; ST2, tumor suppressor protein 2; sST2, soluble version of ST2; T, type; TNF-α, tumor necrosis factor-α; TSLP, thymic stromal lymphopoietin.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

M.C. participated as a faculty member and advisor in scientific meetings and courses under the sponsorship of Abdi Ibrahim, Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, Cipla, Edmond Pharma, GlaxoSmithKline, Glenmark, Lallemand, Mankind Pharma, Menarini Group, Mundipharma, Novartis, Pfizer, Sanofi, Teva, Verona Pharma, and Zambon and is or was a consultant to ABC Farmaceutici, AstraZeneca, Chiesi Farmaceutici, Edmond Pharma, Lallemand, Novartis, Ockham Biotech, Verona Pharma, and Zambon. N.A.H. received honoraria for serving as advisor or consultant for GSK, AstraZeneca, Sanofi, Regeneron, Boehringer Ingelheim, Verona, Amgen, Genentech, Novartis and Teva. His institution received research grant support of his behalf from GSK, Genentech, Sanofi, Teva, Novartis, and Astra Zeneca. C.P.P. has acted as a consultant to Eurodrug, Recipharm, Glycosynnovation and PrEP Biopharma. C.P.P. also holds equity in Verona Pharma. M.G.M. participated as a faculty member and advisor in scientific meetings and courses under the sponsorship of ABC Farmaceutici, Almirall, AstraZeneca, Chiesi Farmaceutici, GlaxoSmithKline, and Novartis and was a consultant to Chiesi Farmaceutici and GlaxoSmithKline. Her department was funded by GlaxoSmithKline and Novartis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in, or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.