Vol.:(0123456789) 1 3 Infammation Research (2019) 68:59–74 https://doi.org/10.1007/s00011-018-1191-2 REVIEW A review of infammatory mechanism in airway diseases Parya Aghasafari 1  · Uduak George 1,2  · Ramana Pidaparti 1 Received: 16 February 2018 / Revised: 12 September 2018 / Accepted: 27 September 2018 / Published online: 10 October 2018 © Springer Nature Switzerland AG 2018 Background Infammation in the lung is the body’s natural response to injury. It acts to remove harmful stimuli such as pathogens, irritants, and damaged cells and initiate the healing process. Acute and chronic pulmonary infammation are seen in diferent respiratory diseases such as; acute respiratory distress syndrome, chronic obstructive pulmonary disease (COPD), asthma, and cystic fbrosis (CF). Findings In this review, we found that infammatory response in COPD is determined by the activation of epithelial cells and macrophages in the respiratory tract. Epithelial cells and macrophages discharge transforming growth factor-β (TGF-β), which trigger fbroblast proliferation and tissue remodeling. Asthma leads to airway hyper-responsiveness, obstruction, mucus hyper-production, and airway-wall remodeling. Cytokines, allergens, chemokines, and infectious agents are the main stimuli that activate signaling pathways in epithelial cells in asthma. Mutation of the CF transmembrane conductance regulator (CFTR) gene results in CF. Mutations in CFTR infuence the lung epithelial innate immune function that leads to exagger- ated and inefective airway infammation that fails to abolish pulmonary pathogens. We present mechanistic computational models (based on ordinary diferential equations, partial diferential equations and agent-based models) that have been applied in studying the complex physiological and pathological mechanisms of chronic infammation in diferent airway diseases. Conclusion The scope of the present review is to explore the infammatory mechanism in airway diseases and highlight the infuence of aging on airways’ infammation mechanism. The main goal of this review is to encourage research collaborations between experimentalist and modelers to promote our understanding of the physiological and pathological mechanisms that control infammation in diferent airway diseases. Keywords Infammation · Infammaging · Airway disease · Computational modeling Introduction Infammation is the body’s natural defense mechanism to remove harmful stimuli such as pathogens, irritants and damaged cells and initiate the healing process. In general, infammation is classifed as acute or chronic infammation [1]. Acute infammation is a benefcial process that helps to immobilize the injured region and lets the rest of the immune system mobilize to heal injuries [2]. Chronic infammation, on the other hand, turns into a problem rather than a solution to the injuries. Chronically infamed tissues typically pro- ceed to evoke immune cells from the bloodstream to amplify the infammatory response. They can destroy healthy tissues in a misdirected attempt at initiating the healing process [3]. In general, infammatory mechanisms employ a group of pattern recognition receptors (PRRs) to recognize molecular patterns expressed by the invading pathogens. These recep- tors may either be on the membrane surface e.g., Toll-Like receptors (TLRs) and C-type Lectin Receptors (CLRs) or inside the cytoplasm, e.g., Nod-Like Receptors (NLRs) and RIG-I-Like Receptors (RLRs) [4]. Next, the resolution pro- cess, which involves apoptosis and subsequent clearance of activated infammatory cells, will initiate [5, 6]. Then, the process of tissue repair starts to retrieve damaged tissue [7]. Airway infammation is usually caused by pathogens or by exposure to toxins, pollutants, irritants, and allergens [8]. TLRs recognize molecular patterns shared by patho- gens and activate infammatory cells like nuclear factor Inflammation Research Responsible Editor: Andrew Roberts. Parya Aghasafari and Uduak George have equally contributed. * Ramana Pidaparti rmparti@uga.edu 1 College of Engineering, University of Georgia, Athens, GA, USA 2 Department of Mathematics and Statistics, San Diego State University, San Diego, CA, USA