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Chronic Obstructive Pulmonary Disease: Molecular Basis of Pathogenesis and Targeted Therapeutic Approaches

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Targeting Cellular Signalling Pathways in Lung Diseases

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Abstract

Chronic obstructive pulmonary disease (COPD) is a heterogeneous inflammatory disorder that is strongly associated with cigarette smoking. Its prominent symptoms include chronic bronchitis, dyspnea, and emphysema. Goblet cell-mediated mucus hypersecretion and chronic inflammation in the respiratory tract lead to the congestion and narrowing of small airways and alveolar wall destruction (emphysema). Increased number of alveolar macrophages, cytotoxic T lymphocyte, and neutrophils along with upregulated multiple inflammatory mediators (cytokines, chemokines, growth factors, etc.) cause the exaggerated inflammatory reaction. Sustained oxidative stress additionally amplifies this inflammatory cascade. Moreover, increased elastolysis by several elastolytic enzymes, including serine, proteases, cathepsins, and matrix metalloproteinases, causes the alveolar wall destruction. Besides this, various genetic and epigenetic factors are also responsible for the early onset of COPD. This inflammatory disorder, in marked contrast to asthma, is resistant to corticosteroid therapy. Different physiological activities along with bronchodilator therapy, antioxidant intake, and oxygen supplementation can effectively subdue the disease outcome and improve the quality of life of COPD patients.

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Abbreviations

BTVA:

Bronchoscopic thermal vapour ablation

CHARGE:

Cohorts for Heart and Aging Research in Genomic Epidemiology

DEFB1:

Defensin beta 1

ENA-78:

Epithelial neutrophil activating protein of 78 kDa

G-CSF:

Granulocyte colony-stimulating factor

GM-CSF:

Granulocyte-macrophage colony-stimulating factor

GRO-α:

Growth-related oncoprotein

HAT:

Histone acetylate

HDAC:

Histone deacetylase

IL:

Interleukin

IP-10:

Interferon gamma-induced protein-10

I-TAC:

Interferon-inducible T-cell alpha-chemoattractant

LTB-4:

Leukotriene B4

LVR:

Lung volume reduction

MCP-1:

Monocyte chemoattractant protein-1

MIG:

Monokine induced by gamma interferon

NE:

Neutrophil elastase

PCNA:

Proliferative cell nuclear antigen

PS:

Phosphatidylserine

SOD:

Superoxide dismutase

TLD:

Targeted lung denervation

TNF:

Tumour necrosis factor

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Authors and Affiliations

  1. Division of Molecular Medicine, Bose Institute, Kolkata, West Bengal, India

    Sushweta Mahalanobish, Sayanta Dutta & Parames C. Sil

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  1. Sushweta Mahalanobish
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  2. Sayanta Dutta
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  3. Parames C. Sil
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  1. Graduate School of Health, Discipline of Pharmacy, University of Technology Sydney, Sydney, NSW, Australia

    Kamal Dua

  2. Drug Development and Innovation Centre, University of Alberta, Edmonton, AB, Canada

    Raimar Löbenberg

  3. Haematology and Hemotherapy Center, State University of Campinas, Campinas, São Paulo, Brazil

    Ângela Cristina Malheiros Luzo

  4. Graduate School of Health, Discipline of Pharmacy, University of Technology Sydney, Sydney, NSW, Australia

    Shakti Shukla

  5. School of Pharmaceutical Sciences & Division of Research & Development, Lovely Professional University, Phagwara, Punjab, India

    Saurabh Satija

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Mahalanobish, S., Dutta, S., Sil, P.C. (2021). Chronic Obstructive Pulmonary Disease: Molecular Basis of Pathogenesis and Targeted Therapeutic Approaches. In: Dua, K., Löbenberg, R., Malheiros Luzo, Â.C., Shukla, S., Satija, S. (eds) Targeting Cellular Signalling Pathways in Lung Diseases. Springer, Singapore. https://doi.org/10.1007/978-981-33-6827-9_7

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