Drugs Used in the Treatment of Viral Infections for the Prevention of Airway Remodeling in Asthma
This article is part of Special Issue:
Joanna Wieczfinska,
Rafal Pawliczak,
Joanna Wieczfinska
Department of Immunopathology , Medical Faculty , Medical University of Lodz , Lodz , Poland , umed.pl
Search for more papers by this authorCorresponding Author
Rafal Pawliczak
Department of Immunopathology , Medical Faculty , Medical University of Lodz , Lodz , Poland , umed.pl
Search for more papers by this authorJoanna Wieczfinska,
Rafal Pawliczak,
Joanna Wieczfinska
Department of Immunopathology , Medical Faculty , Medical University of Lodz , Lodz , Poland , umed.pl
Search for more papers by this authorCorresponding Author
Rafal Pawliczak
Department of Immunopathology , Medical Faculty , Medical University of Lodz , Lodz , Poland , umed.pl
Search for more papers by this authorFirst published: 24 July 2025
Academic Editor: Mirella Giovarelli
Abstract
One of the main causes of the exacerbation of chronic airway inflammatory diseases is respiratory virus infections. The most prevalent viruses that can infect humans multiple times a year are rhinovirus (RV) and respiratory syncytial virus (RSV). Because remodeling factors like matrix metalloproteinases (MMPs), which are released by infiltrating neutrophils, are present. Airway remodeling is a characteristic of the pathology of airway diseases such as bronchial asthma. In these circumstances, viral infections may result in increased neutrophilic activation, which would exacerbate asthma symptoms and modify the airway. Although a connection between viral infections and acute exacerbations of chronic inflammatory respiratory diseases has been established, anti-inflammatory medications are frequently used in conjunction with antiviral medications to treat viral infections. Although their modes of action differ, they all lessen inflammation, which is essential for the development of airway remodeling. This review addresses the potential role of anti-inflammatory and antiviral drugs in preventing airway remodeling.
Conflicts of Interest
The authors declare no conflicts of interest.
Open Research
Data Availability Statement
Data sharing is not applicable to this article as no new data were created or analyzed in this study.
References
- 1 Tan K. S., Lim R. L., and Liu J., et al.Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium, Frontiers in Cell and Developmental Biology. (2020) 8, https://doi.org/10.3389/fcell.2020.00099, 99.
- 2 Moheimani F., Shahdab N., Cummings S., Hansbro P. M., and Ward C., Key Role of Dysregulated Airway Epithelium in Response to Respiratory Viral Infections in Asthma, ERJ Open Research. (2022) 8, no. 3, https://doi.org/10.1183/23120541.00314-2022, 00314.
- 3 Pace E., Di Vincenzo S., Ferraro M., Lanata L., and Scaglione F., Role of Airway Epithelium in Viral Respiratory Infections: Can Carbocysteine Prevent or Mitigate Them?, Immunology. (2024) 172, no. 3, 329–342, https://doi.org/10.1111/imm.13762.
- 4 Varricchi G., Ferri S., and Pepys J., et al.Biologics and Airway Remodeling in Severe Asthma, Allergy. (2022) 77, no. 12, 3538–3552, https://doi.org/10.1111/all.15473.
- 5 Banno A., Reddy A. T., Lakshmi S. P., and Reddy R. C., Bidirectional Interaction of Airway Epithelial Remodeling and Inflammation in Asthma, Clinical Science. (2020) 134, no. 9, 1063–1079, https://doi.org/10.1042/CS20191309.
- 6 Holtzman M. J., Morton J. D., and Shornick L. P., et al.Immunity, Inflammation, and Remodeling in the Airway Epithelial Barrier: Epithelial-Viral-Allergic Paradigm, Physiological Reviews. (2002) 82, no. 1, 19–46, https://doi.org/10.1152/physrev.00020.2001, 2-s2.0-0036079897.
- 7 Olczyk P., Mencner L., and Komosinska-Vassev K., The Role of the Extracellular Matrix Components in Cutaneous Wound Healing, Biomed Research International. (2014) 2014, https://doi.org/10.1155/2014/747584, 2-s2.0-84897495506, 747584.
- 8 Mostaco-Guidolin L. B., Osei E. T., and Ullah J., et al.Defective Fibrillar Collagen Organization by Fibroblasts Contributes to Airway Remodeling in Asthma, American Journal of Respiratory and Critical Care Medicine. (2019) 200, no. 4, 431–443, https://doi.org/10.1164/rccm.201810-1855OC, 2-s2.0-85070984110.
- 9 Reeves S. R., Kolstad T., and Lien T. Y., et al.Asthmatic Airway Epithelial Cells Differentially Regulate Fibroblast Expression of Extracellular Matrix Components, Journal of Allergy and Clinical Immunology. (2014) 134, no. 3, 663–670.e1, https://doi.org/10.1016/j.jaci.2014.04.007, 2-s2.0-84906944952.
- 10 Defnet A. E., Huang W., and Polischak S., et al.Effects of ATP-Competitive and Function-Selective ERK Inhibitors on Airway Smooth Muscle Cell Proliferation, The FASEB Journal. (2019) 33, no. 10, 10833–10843, https://doi.org/10.1096/fj.201900680R, 2-s2.0-85072718532.
- 11 Hill M. R., Philp C. J., and Billington C. K., et al.A Theoretical Model of Inflammation- and Mechanotransduction-Driven Asthmatic Airway Remodelling, Biomechanics and Modeling in Mechanobiology. (2018) 17, no. 5, 1451–1470, https://doi.org/10.1007/s10237-018-1037-4, 2-s2.0-85049555271.
- 12 Yuan L., Liu H., and Du X., et al.Airway Epithelial ITGB4 Deficiency Induces Airway Remodeling in a Mouse Model, Journal of Allergy and Clinical Immunology. (2023) 151, no. 2, 431–446.e16, https://doi.org/10.1016/j.jaci.2022.09.032.
- 13 Kurowska-Stolarska M., Stolarski B., and Kewin P., et al.IL-33 Amplifies the Polarization of Alternatively Activated Macrophages that Contribute to Airway Inflammation, The Journal of Immunology. (2009) 183, no. 10, 6469–6477, https://doi.org/10.4049/jimmunol.0901575, 2-s2.0-75549085516.
- 14 Wang Q., Hong L., and Chen M., et al.Targeting M2 Macrophages Alleviates Airway Inflammation and Remodeling in Asthmatic Mice via miR-378a-3p/GRB2 Pathway, Frontiers in Molecular Biosciences. (2021) 8, https://doi.org/10.3389/fmolb.2021.717969, 717969.
- 15 Jartti T. and Gern J. E., Role of Viral Infections in the Development and Exacerbation of Asthma in Children, Journal of Allergy and Clinical Immunology. (2017) 140, no. 4, 895–906, https://doi.org/10.1016/j.jaci.2017.08.003, 2-s2.0-85031844868.
- 16 XuChen X., Weinstock J., and Arroyo M., et al.Airway Remodeling Factors During Early-Life Rhinovirus Infection and the Effect of Premature Birth, Frontiers in Pediatrics. (2021) 9, https://doi.org/10.3389/fped.2021.610478, 610478.
- 17 Beppu A. K., Zhao J., and Yao C., et al.Epithelial Plasticity and Innate Immune Activation Promote Lung Tissue Remodeling Following Respiratory Viral Infection, Nature Communications. (2023) 14, no. 1, https://doi.org/10.1038/s41467-023-41387-3, 5814.
- 18 Spector C., De Sanctis C. M., PanettieriR. A.Jr., and Koziol-White C. J., Rhinovirus Induces Airway Remodeling: What are the Physiological Consequences?, Respiratory Research. (2023) 24, no. 1, https://doi.org/10.1186/s12931-023-02529-9, 238.
- 19 Yamaya M. and Sasaki H., Rhinovirus and Asthma, Viral Immunology. (2003) 16, no. 2, 99–109, https://doi.org/10.1089/088282403322017857, 2-s2.0-0038043469.
- 20 Radzikowska U., Eljaszewicz A., and Tan G., et al.Rhinovirus-Induced Epithelial RIG-I Inflammasome Suppresses Antiviral Immunity and Promotes Inflammation in Asthma and COVID-19, Nature Communications. (2023) 14, no. 1, https://doi.org/10.1038/s41467-023-37470-4, 2329.
- 21 Wang Q., Miller D. J., and Bowman E. R., et al.MDA5 and TLR3 Initiate pro-Inflammatory Signaling Pathways Leading to Rhinovirus-Induced Airways Inflammation and Hyperresponsiveness, PLoS Pathogens. (2011) 7, no. 5, https://doi.org/10.1371/journal.ppat.1002070, 2-s2.0-79958062793, e1002070.
- 22 Liu X., Zhao Z., Shi X., Zong Y., and Sun Y., The Effects of Viral Infections on the Molecular and Signaling Pathways Involved in the Development of the PAOs, Viruses. (2024) 16, no. 8, https://doi.org/10.3390/v16081342, 1342.
- 23 Beale J., Jayaraman A., and Jackson D. J., et al.Rhinovirus-Induced IL-25 in Asthma Exacerbation Drives Type 2 Immunity and Allergic Pulmonary Inflammation, Science Translational Medicine. (2014) 6, no. 256, https://doi.org/10.1126/scitranslmed.3009124, 2-s2.0-84908374296, 256ra134.
- 24 Message S. D., Laza-Stanca V., and Mallia P., et al.Rhinovirus-Induced Lower Respiratory Illness Is Increased in Asthma and Related to Virus Load and Th1/2 Cytokine and IL-10 Production, Proceedings of the National Academy of Sciences. (2008) 105, no. 36, 13562–13567, https://doi.org/10.1073/pnas.0804181105, 2-s2.0-51649109114.
- 25 Jackson D. J., The Role of Rhinovirus Infections in the Development of Early Childhood Asthma, Current Opinion in Allergy & Clinical Immunology. (2010) 10, no. 2, 133–138, https://doi.org/10.1097/ACI.0b013e3283352f7c, 2-s2.0-77950988249.
- 26 Shariff S., Shelfoon C., and Holden N. S., et al.Human Rhinovirus Infection of Epithelial Cells Modulates Airway Smooth Muscle Migration, American Journal of Respiratory Cell and Molecular Biology. (2017) 56, no. 6, 796–803, https://doi.org/10.1165/rcmb.2016-0252OC, 2-s2.0-85020180696.
- 27 Leigh R., Oyelusi W., and Wiehler S., et al.Human Rhinovirus Infection Enhances Airway Epithelial Cell Production of Growth Factors Involved in Airway Remodeling, Journal of Allergy and Clinical Immunology. (2008) 121, no. 5, 1238–1245.e4, https://doi.org/10.1016/j.jaci.2008.01.067, 2-s2.0-42749091669.
- 28 Liu P., Jamaluddin M., Li K., Garofalo R. P., Casola A., and Brasier A. R., Retinoic Acid-Inducible Gene I Mediates Early Antiviral Response and Toll-Like Receptor 3 Expression in Respiratory Syncytial Virus-Infected Airway Epithelial Cells, Journal of Virology. (2007) 81, no. 3, 1401–1411, https://doi.org/10.1128/JVI.01740-06, 2-s2.0-33846554134.
- 29 Klouwenberg P. K., Tan L., Werkman W., van Bleek G. M., and Coenjaerts F., The Role of Toll-Like Receptors in Regulating the Immune Response against Respiratory Syncytial Virus, Critical Reviews in Immunology. (2009) 29, no. 6, 531–550, https://doi.org/10.1615/CritRevImmunol.v29.i6.40.
- 30 Marzec J., Cho H.-Y., High M., McCaw Z. R., Polack F., and Kleeberger S. R., Toll-Like Receptor 4-Mediated Respiratory Syncytial Virus Disease and Lung Transcriptomics in Differentially Susceptible Inbred Mouse Strains, Physiological Genomics. (2019) 51, no. 12, 630–643, https://doi.org/10.1152/physiolgenomics.00101.2019.
- 31
Zhao Z.,
Liu X.,
Zong Y.,
Shi X., and
Sun Y., Cellular Processes Induced by HSV-1 Infections in Vestibular Neuritis, Viruses. (2024) 16, no. 1, https://doi.org/10.3390/v16010012, 12.
10.3390/v16010012 Google Scholar
- 32 Habibi M. S., Thwaites R. S., and Chang M., et al.Neutrophilic Inflammation in the Respiratory Mucosa Predisposes to RSV Infection, Science. (2020) 370, no. 6513, https://doi.org/10.1126/science.aba9301, eaba9301.
- 33 McNamara P. S., Ritson P., Selby A., Hart C. A., and Smyth R. L., Bronchoalveolar Lavage Cellularity in Infants With Severe Respiratory Syncytial Virus Bronchiolitis, Archives of Disease in Childhood. (2003) 88, no. 10, 922–926, https://doi.org/10.1136/adc.88.10.922, 2-s2.0-0141636306.
- 34 Griffiths C., Drews S. J., and Marchant D. J., Respiratory Syncytial Virus: Infection, Detection, and New Options for Prevention and Treatment, Clinical Microbiology Reviews. (2017) 30, no. 1, 277–319, https://doi.org/10.1128/CMR.00010-16, 2-s2.0-85007227794.
- 35 DeVincenzo J. P., Wilkinson T., and Vaishnaw A., et al.Viral Load Drives Disease in Humans Experimentally Infected With Respiratory Syncytial Virus, American Journal of Respiratory and Critical Care Medicine. (2010) 182, no. 10, 1305–1314, https://doi.org/10.1164/rccm.201002-0221OC, 2-s2.0-78349243640.
- 36 Leigh R. and Proud D., Virus-Induced Modulation of Lower Airway Diseases: Pathogenesis and Pharmacologic Approaches to Treatment, Pharmacology & Therapeutics. (2015) 148, 185–198, https://doi.org/10.1016/j.pharmthera.2014.12.005, 2-s2.0-84923278931.
- 37 PeeblesR. S.Jr. and Aronica M. A., Proinflammatory Pathways in the Pathogenesis of Asthma, Clinics in Chest Medicine. (2019) 40, no. 1, 29–50, https://doi.org/10.1016/j.ccm.2018.10.014, 2-s2.0-85060465907.
- 38 Inoue D., Yamaya M., and Kubo H., et al.Mechanisms of Mucin Production by Rhinovirus Infection in Cultured Human Airway Epithelial Cells, Respiratory Physiology & Neurobiology. (2006) 154, no. 3, 484–499, https://doi.org/10.1016/j.resp.2005.11.006, 2-s2.0-33751006156.
- 39 Zhu L., Lee P.-K., Lee W.-M., Zhao Y., Yu D., and Chen Y., Rhinovirus-Induced Major Airway Mucin Production Involves a Novel TLR3-EGFR-Dependent Pathway, American Journal of Respiratory Cell and Molecular Biology. (2009) 40, no. 5, 610–619, https://doi.org/10.1165/rcmb.2008-0223OC, 2-s2.0-65349121396.
- 40 Hewson C. A., Haas J. J., and Bartlett N. W., et al.Rhinovirus Induces MUC5AC in a Human Infection Model and in Vitro via NF-KappaB and EGFR Pathways, European Respiratory Journal. (2010) 36, no. 6, 1425–1435, https://doi.org/10.1183/09031936.00026910, 2-s2.0-78049280936.
- 41 Skevaki C. L., Psarras S., and Volonaki E., et al.Rhinovirus-Induced Basic Fibroblast Growth Factor Release Mediates Airway Remodeling Features, Clinical and Translational Allergy. (2012) 2, no. 1, https://doi.org/10.1186/2045-7022-2-14, 2-s2.0-85006319293, 14.
- 42 Lewis T. C., Metitiri E. E., and Mentz G. B., et al.Community Action Against Asthma Steering C, Influence of Viral Infection on the Relationships between Airway Cytokines and Lung Function in Asthmatic Children, Respiratory Research. (2018) 19, no. 1, https://doi.org/10.1186/s12931-018-0922-9, 2-s2.0-85056915010, 228.
- 43 Williams T., McCaw J. M., and Osborne J. M., Accounting for the Geometry of the Respiratory Tract in Viral Infections, Epidemics. (2025) 51, https://doi.org/10.1016/j.epidem.2025.100829, 100829.
- 44 Han M., Rajput C., and Hong J. Y., et al.The Innate Cytokines IL-25, IL-33, and TSLP Cooperate in the Induction of Type 2 Innate Lymphoid Cell Expansion and Mucous Metaplasia in Rhinovirus-Infected Immature Mice, The Journal of Immunology. (2017) 199, no. 4, 1308–1318, https://doi.org/10.4049/jimmunol.1700216, 2-s2.0-85027320410.
- 45
Minor D.,
Traves S., and
Proud D., Induction of Human Airway Epithelial to Mesenchymal Transition upon Rhinovirus Infection, Allergy, Asthma & Clinical Immunology. (2014) suppl.1, A53.
10.1186/1710-1492-10-S1-A53 Google Scholar
- 46 Kumar N., Sharma S., and Kumar R., et al.Host-Directed Antiviral Therapy, Clinical Microbiology Reviews. (2020) 33, no. 3, https://doi.org/10.1128/CMR.00168-19.
- 47 Billiau A., Anti-Inflammatory Properties of Type I Interferons, Antiviral Research. (2006) 71, no. 2-3, 108–116, https://doi.org/10.1016/j.antiviral.2006.03.006, 2-s2.0-33747115709.
- 48 Shi X., Liu X., and Sun Y., The Pathogenesis of Cytomegalovirus and Other Viruses Associated With Hearing Loss: Recent Updates, Viruses. (2023) 15, no. 6, https://doi.org/10.3390/v15061385, 1385.
- 49 Checconi P., De Angelis M., and Marcocci M. E., et al.Redox-Modulating Agents in the Treatment of Viral Infections, International Journal of Molecular Sciences. (2020) 21, no. 11, https://doi.org/10.3390/ijms21114084, 4084.
- 50 Song P., Li W., Xie J., Hou Y., and You C., Cytokine Storm Induced by SARS-CoV-2, Clinica Chimica Acta. (2020) 509, 280–287, https://doi.org/10.1016/j.cca.2020.06.017.
- 51 Kamzeeva P. N., Aralov A. V., Alferova V. A., and Korshun V. A., Recent Advances in Molecular Mechanisms of Nucleoside Antivirals, Current Issues in Molecular Biology. (2023) 45, no. 8, 6851–6879, https://doi.org/10.3390/cimb45080433.
- 52 Yip A. J. W., Low Z. Y., Chow V. T. K., and Lal S. K., Repurposing Molnupiravir for COVID-19: The Mechanisms of Antiviral Activity, Viruses. (2022) 14, no. 6, https://doi.org/10.3390/v14061345, 1345.
- 53 Aboul-Fotouh S., Mahmoud A. N., Elnahas E. M., Habib M. Z., and Abdelraouf S. M., What Are the Current Anti-COVID-19 Drugs? From Traditional to Smart Molecular Mechanisms, Virology Journal. (2023) 20, no. 1, https://doi.org/10.1186/s12985-023-02210-z, 241.
- 54 Coultas J. A., Cafferkey J., Mallia P., and Johnston S. L., Experimental Antiviral Therapeutic Studies for Human Rhinovirus Infections, Journal of Experimental Pharmacology. (2021) 13, 645–659, https://doi.org/10.2147/JEP.S255211.
- 55 Hayden F. G., Herrington D. T., and Coats T. L., et al.Efficacy and Safety of Oral Pleconaril for Treatment of Colds due to Picornaviruses in Adults: Results of 2 Double-Blind, Randomized, Placebo-Controlled Trials, Clinical Infectious Diseases. (2003) 36, no. 12, 1523–1532, https://doi.org/10.1086/375069, 2-s2.0-0038548251.
- 56 Uwe S., Anti-Inflammatory Interventions of NF-κB Signaling: Potential Applications and Risks, Biochemical Pharmacology. (2008) 75, no. 8, 1567–1579, https://doi.org/10.1016/j.bcp.2007.10.027, 2-s2.0-40949144895.
- 57 Zhao J., He S., Minassian A., Li J., and Feng P., Recent Advances on Viral Manipulation of NF-κB Signaling Pathway, Current Opinion in Virology. (2015) 15, 103–111, https://doi.org/10.1016/j.coviro.2015.08.013, 2-s2.0-84942118676.
- 58 Zalman L. S., Brothers M. A., and Dragovich P. S., et al.Inhibition of Human Rhinovirus-Induced Cytokine Production by AG7088, a Human Rhinovirus 3C Protease Inhibitor, Antimicrobial Agents and Chemotherapy. (2000) 44, no. 5, 1236–1241, https://doi.org/10.1128/AAC.44.5.1236-1241.2000, 2-s2.0-0034050610.
- 59 Hayden F. G., Treanor J. J., and Fritz R. S., et al.Use of the Oral Neuraminidase Inhibitor Oseltamivir in Experimental Human Influenza: Randomized Controlled Trials for Prevention and Treatment, JAMA. (1999) 282, no. 13, 1240–1246, https://doi.org/10.1001/jama.282.13.1240, 2-s2.0-0033530264.
- 60 Bassetti M., Castaldo N., and Carnelutti A., Neuraminidase Inhibitors as a Strategy for Influenza Treatment: Pros, Cons and Future Perspectives, Expert Opinion on Pharmacotherapy. (2019) 20, no. 14, 1711–1718, https://doi.org/10.1080/14656566.2019.1626824, 2-s2.0-85072546130.
- 61 Jin Y., Liu X., Chen S., Xiang J., Peng Z., and Sun Y., Analysis of the Results of Cytomegalovirus Testing Combined with Genetic Testing in Children With Congenital Hearing Loss, Journal of Clinical Medicine. (2022) 11, no. 18, https://doi.org/10.3390/jcm11185335, 5335.
- 62 Chow E. J., Doyle J. D., and Uyeki T. M., Influenza Virus-Related Critical Illness: Prevention, Diagnosis, Treatment, Critical Care. (2019) 23, no. 1, https://doi.org/10.1186/s13054-019-2491-9, 2-s2.0-85068183307, 214.
- 63 Li Z., Li L., and Zhao S., et al.Re-Understanding Anti-Influenza Strategy: Attach Equal Importance to Antiviral and Anti-Inflammatory Therapies, Journal of Thoracic Disease. (2018) 10, no. S9, S2248–S2259, https://doi.org/10.21037/jtd.2018.03.169, 2-s2.0-85050687028.
- 64 Gilzad-Kohan H. and Jamali F., Anti-Inflammatory Properties of Drugs Used to Control COVID-19 and Their Effects on the Renin-Angiotensin System and Angiotensin-Converting Enzyme-2, Journal of Pharmacy & Pharmaceutical Sciences. (2020) 23, 259–277, https://doi.org/10.18433/jpps31346.
- 65 Akhvlediani T., Bernard-Valnet R., Dias S. P., Eikeland R., Pfausler B., and Sellner J., Infectious Disease Panel of the European Academy of N, Neurological Side Effects and Drug Interactions of Antiviral Compounds Against SARS-CoV-2, European Journal of Neurology. (2023) 30, no. 12, 3904–3912, https://doi.org/10.1111/ene.16017.
- 66 Kausar S., Said Khan F., and Ishaq Mujeeb Ur Rehman M., et al.A Review: Mechanism of Action of Antiviral Drugs, International Journal of Immunopathology and Pharmacology. (2021) 35, https://doi.org/10.1177/20587384211002621, 20587384211002621.
- 67 Yang J.-W., Yang L., Luo R.-G., and Xu J.-F., Corticosteroid Administration for Viral Pneumonia: COVID-19 and Beyond, Clinical Microbiology and Infection. (2020) 26, no. 9, 1171–1177, https://doi.org/10.1016/j.cmi.2020.06.020.
- 68 Nawasreh M. M., Alzyoud E. I., Al-Mazaydeh Z. A., Rammaha M. S., Yasin S. R., and Tahtamouni L. H., Biological Activity and Apoptotic Signaling Pathway of C(11)-Functionalized Cephalostatin 1 Analogues, Steroids. (2020) 158, https://doi.org/10.1016/j.steroids.2020.108602, 108602.
- 69 Deploey N., Van Moortel L., Rogatsky I., Peelman F., and De Bosscher K., The Biologist’s Guide to the Glucocorticoid Receptor’s Structure, Cells. (2023) 12, no. 12, https://doi.org/10.3390/cells12121636, 1636.
- 70 Martinez G. J., Appleton M., Kipp Z. A., Loria A. S., Min B., and HindsT. D.Jr, Glucocorticoids, Their Uses, Sexual Dimorphisms, and Diseases: New Concepts, Mechanisms, and Discoveries, Physiological Reviews. (2024) 104, no. 1, 473–532, https://doi.org/10.1152/physrev.00021.2023.
- 71 Barnes P. J., How Corticosteroids Control Inflammation: Quintiles Prize Lecture 2005, British Journal of Pharmacology. (2006) 148, no. 3, 245–254, https://doi.org/10.1038/sj.bjp.0706736, 2-s2.0-33744477341.
- 72 Roche N., Yorgancioglu A., and Cruz A. A., et al.Systematic Literature Review of Traits and Outcomes Reported in Randomised Controlled Trials of Asthma With Regular Dosing of Inhaled Corticosteroids With Short-Acting Beta(2)-Agonist Reliever, as-Needed ICS/Formoterol, or ICS/Formoterol Maintenance and Reliever Therapy, Respiratory Medicine. (2024) 221, https://doi.org/10.1016/j.rmed.2023.107478, 107478.
- 73 Ramphul M., Increased Inhaled Corticosteroids for Treating Acute Asthma Exacerbations, Clinical & Experimental Allergy. (2023) 53, no. 4, 388–391, https://doi.org/10.1111/cea.14306.
- 74 Barnes P. J., Inhaled Corticosteroids, Pharmaceuticals (Basel). (2010) 3, no. 3, 514–540, https://doi.org/10.3390/ph3030514, 2-s2.0-77950395088.
- 75 Jen R., Rennard S. I., and Sin D. D., Effects of Inhaled Corticosteroids on Airway Inflammation in Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis, International Journal of Chronic Obstructive Pulmonary Disease. (2012) 7, 587–595, https://doi.org/10.2147/COPD.S32765, 2-s2.0-84872236803.
- 76 Van Ly D., King N. J., Moir L. M., Burgess J. K., Black J. L., and Oliver B. G., Effects of Beta(2) Agonists, Corticosteroids, and Novel Therapies on Rhinovirus-Induced Cytokine Release and Rhinovirus Replication in Primary Airway Fibroblasts, Journal of Allergy. (2011) 2011, https://doi.org/10.1155/2011/457169, 457169.
- 77 Skevaki C. L., Christodoulou I., and Spyridaki I. S., et al.Budesonide and Formoterol Inhibit Inflammatory Mediator Production by Bronchial Epithelial Cells Infected With Rhinovirus, Clinical & Experimental Allergy. (2009) 39, no. 11, 1700–1710, https://doi.org/10.1111/j.1365-2222.2009.03307.x, 2-s2.0-70350330313.
- 78 Domingo C., Mirapeix R. M., Gonzalez-Barcala F. J., Forne C., and Garcia F., Omalizumab in Severe Asthma: Effect on Oral Corticosteroid Exposure and Remodeling. A Randomized Open-Label Parallel Study, Drugs. (2023) 83, no. 12, 1111–1123, https://doi.org/10.1007/s40265-023-01905-5.
- 79 Stewart A. G., Fernandes D., and Tomlinson P. R., The Effect of Glucocorticoids on Proliferation of Human Cultured Airway Smooth Muscle, British Journal of Pharmacology. (1995) 116, no. 8, 3219–3226, https://doi.org/10.1111/j.1476-5381.1995.tb15127.x, 2-s2.0-0029595274.
- 80
Nayak A. P.,
Deshpande D. A., and
Penn R. B., New Targets for Resolution of Airway Remodeling in Obstructive Lung Diseases, F1000Research. (2018) 7, https://doi.org/10.12688/f1000research.14581.1, 2-s2.0-85048175792, 680.
10.12688/f1000research.14581.1 Google Scholar
- 81 Nayak A. P., Glucocorticoids and Airway Smooth Muscle: A Few More Answers, Still More Questions, American Journal of Respiratory Cell and Molecular Biology. (2019) 61, no. 1, 9–10, https://doi.org/10.1165/rcmb.2019-0089ED, 2-s2.0-85068326849.
- 82 Henderson I., Caiazzo E., McSharry C., Guzik T. J., and Maffia P., Why Do Some Asthma Patients Respond Poorly to Glucocorticoid Therapy?, Pharmacological Research. (2020) 160, https://doi.org/10.1016/j.phrs.2020.105189, 105189.
- 83 Olivieri D., Chetta A., and Del Donno M., et al.Effect of Short-Term Treatment With Low-Dose Inhaled Fluticasone Propionate on Airway Inflammation and Remodeling in Mild Asthma: A Placebo-Controlled Study, American Journal of Respiratory and Critical Care Medicine. (1997) 155, no. 6, 1864–1871, https://doi.org/10.1164/ajrccm.155.6.9196087, 2-s2.0-0030958324.
- 84 Yamaya M., Nishimura H., Nadine L., Kubo H., and Nagatomi R., Formoterol and Budesonide Inhibit Rhinovirus Infection and Cytokine Production in Primary Cultures of Human Tracheal Epithelial Cells, Respiratory Investigation. (2014) 52, no. 4, 251–260, https://doi.org/10.1016/j.resinv.2014.03.004, 2-s2.0-84903751692.
- 85 Wang Y., Ninaber D. K., van Schadewijk A., and Hiemstra P. S., Tiotropium and Fluticasone Inhibit Rhinovirus-Induced Mucin Production via Multiple Mechanisms in Differentiated Airway Epithelial Cells, Frontiers in Cellular and Infection Microbiology. (2020) 10, https://doi.org/10.3389/fcimb.2020.00278, 278.
- 86 Volonaki E., Psarras S., Xepapadaki P., Psomali D., Gourgiotis D., and Papadopoulos N. G., Synergistic Effects of Fluticasone Propionate and Salmeterol on Inhibiting Rhinovirus-Induced Epithelial Production of Remodelling-Associated Growth Factors, Clinical & Experimental Allergy. (2006) 36, no. 10, 1268–1273, https://doi.org/10.1111/j.1365-2222.2006.02566.x, 2-s2.0-33749338671.
- 87 Obase Y., Rytila P., and Metso T., et al.Effects of Inhaled Corticosteroids on Metalloproteinase-8 and Tissue Inhibitor of Metalloproteinase-1 in the Airways of Asthmatic Children, International Archives of Allergy and Immunology. (2010) 151, no. 3, 247–254, https://doi.org/10.1159/000242362, 2-s2.0-70349422692.
- 88
Beigel J. H.,
Tomashek K. M., and
Dodd L. E., et al.Remdesivir for the treatment of Covid-19, New England Journal of Medicine, 2020, 383, 1813–1826, https://doi.org/10.1056/NEJMoa2007764.
10.1056/NEJMoa2007764 Google Scholar
- 89 Sterne J. A., Murthy S., and Diaz J. V., et al.Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-Analysis, JAMA. (2020) 324, no. 13, 1330–1341, https://doi.org/10.1001/jama.2020.17023.
- 90 Koshi E. J., Young K., Mostales J. C., Vo K. B., and Burgess L. P., Complications of Corticosteroid Therapy: A Comprehensive Literature Review, Journal of Pharmacy Technology. (2022) 38, no. 6, 360–367, https://doi.org/10.1177/87551225221116266.
- 91 Mihaescu G., Chifiriuc M. C., and Filip R., et al.Role of Interferons in the Antiviral Battle: From Virus-Host Crosstalk to Prophylactic and Therapeutic Potential in SARS-CoV-2 Infection, Frontiers in Immunology. (2024) 14, https://doi.org/10.3389/fimmu.2023.1273604, 1273604.
- 92 McNab F., Mayer-Barber K., Sher A., Wack A., and O’Garra A., Type I Interferons in Infectious Disease, Nature Reviews Immunology. (2015) 15, no. 2, 87–103, https://doi.org/10.1038/nri3787, 2-s2.0-84923000335.
- 93 Scheu S., Ali S., and Mann-Nuttel R., et al.Interferon β-Mediated Protective Functions of Microglia in Central Nervous System Autoimmunity, International Journal of Molecular Sciences. (2019) 20, no. 1, https://doi.org/10.3390/ijms20010190, 2-s2.0-85059795810, 190.
- 94 Sharif M. N., Tassiulas I., Hu Y., Mecklenbrauker I., Tarakhovsky A., and Ivashkiv L. B., IFN-α Priming Results in a Gain of Proinflammatory Function by IL-10: Implications for Systemic Lupus Erythematosus Pathogenesis, The Journal of Immunology. (2004) 172, no. 10, 6476–6481, https://doi.org/10.4049/jimmunol.172.10.6476.
- 95 Erb A., Zissler U. M., Oelsner M., Chaker A. M., Schmidt-Weber C. B., and Jakwerth C. A., Genome-Wide Gene Expression Analysis Reveals Unique Genes Signatures of Epithelial Reorganization in Primary Airway Epithelium Induced by Type-I, -II and -III Interferons, Biosensors (Basel). (2022) 12, no. 11, https://doi.org/10.3390/bios12110929, 929.
- 96 Gusella G. L., Musso T., Bosco M. C., Espinoza-Delgado I., Matsushima K., and Varesio L., IL-2 up-Regulates but IFN-Gamma Suppresses IL-8 Expression in Human Monocytes, The Journal of Immunology. (1993) 151, no. 5, 2725–2732, https://doi.org/10.4049/jimmunol.151.5.2725.
- 97 Schnyder-Candrian S., Strieter R. M., Kunkel S. L., and Walz A., Interferon-α and Interferon-γ Down-Regulate the Production of Interleukin-8 and ENA-78 in Human Monocytes, Journal of Leukocyte Biology. (1995) 57, no. 6, 929–935, https://doi.org/10.1002/jlb.57.6.929, 2-s2.0-0029055412.
- 98 Cassatella M. A., Guasparri I., Ceska M., Bazzoni F., and Rossi F., Interferon-Gamma Inhibits Interleukin-8 Production by Human Polymorphonuclear Leucocytes, Immunology. (1993) 78, no. 2, 177–184.
- 99 Mayer-Barber K. D., Andrade B. B., and Oland S. D., et al.Host-Directed Therapy of Tuberculosis Based on Interleukin-1 and Type I Interferon Crosstalk, Nature. (2014) 511, no. 7507, 99–103, https://doi.org/10.1038/nature13489, 2-s2.0-84903750131.
- 100 Mayer-Barber K. D., Andrade B. B., and Barber D. L., et al.Innate and Adaptive Interferons Suppress IL-1α and IL-1β Production by Distinct Pulmonary Myeloid Subsets During Mycobacterium tuberculosis Infection, Immunity. (2011) 35, no. 6, 1023–1034, https://doi.org/10.1016/j.immuni.2011.12.002, 2-s2.0-84255162073.
- 101 Huang Y., Blatt L. M., and Taylor M. W., Type 1 Interferon as an Antiinflammatory Agent: Inhibition of Lipopolysaccharide-Induced Interleukin-lβ and Induction of Interleukin-1 Receptor Antagonist, Journal of Interferon & Cytokine Research. (1995) 15, no. 4, 317–321, https://doi.org/10.1089/jir.1995.15.317, 2-s2.0-0028901912.
- 102 Ryoo S., Koh D. H., and Yu S. Y., et al.Clinical Efficacy and Safety of Interferon (Type I and Type III) Therapy in Patients With COVID-19: A Systematic Review and Meta-Analysis of Randomized Controlled Trials, PLOS ONE. (2023) 18, no. 3, https://doi.org/10.1371/journal.pone.0272826, e0272826.
- 103 Panchal N. K. and Prince Sabina E., Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): A Current Insight Into Its Molecular Mechanism Eliciting Organ Toxicities, Food and Chemical Toxicology. (2023) 172, https://doi.org/10.1016/j.fct.2022.113598, 113598.
- 104 D’haens G., Dubinsky M., and Kobayashi T., et al.Mirikizumab as Induction and Maintenance Therapy for Ulcerative Colitis, New England Journal of Medicine. (2023) 388, no. 26, 2444–2455, https://doi.org/10.1056/NEJMoa2207940.
- 105
Garegnani L.,
Oltra G., and
Burgos M. A., et al.Proton Pump Inhibitors for the Prevention of Non-Steroidal Anti-Inflammatory Drug-Induced Ulcers and Dyspepsia, Cochrane Database of Systematic Reviews. (2025) 2025, no. 5, https://doi.org/10.1002/14651858.CD014585.pub2, CD014585.
10.1002/14651858.CD014585.pub2 Google Scholar
- 106 Balachander B., Mondal N., and Bhat V., et al.Comparison of Efficacy of Oral Paracetamol versus Ibuprofen for PDA Closure in Preterms—A Prospective Randomized Clinical Trial, The Journal of Maternal-Fetal & Neonatal Medicine. (2020) 33, no. 9, 1587–1592, https://doi.org/10.1080/14767058.2018.1525354, 2-s2.0-85055691592.
- 107 Kiruthiga N., Alagumuthu M., Selvinthanuja C., Srinivasan K., and Sivakumar T., Molecular Modelling, Synthesis and Evaluation of Flavone and Flavanone Scaffolds as Anti-Inflammatory Agents, Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry. (2021) 20, no. 1, 20–38, https://doi.org/10.2174/1871523019666200102112017.
- 108 Tanaka K.-I., Suemasu S., Ishihara T., Tasaka Y., Arai Y., and Mizushima T., Inhibition of Both COX-1 and COX-2 and Resulting Decrease in the Level of Prostaglandins E2 Is Responsible for Non-Steroidal Anti-Inflammatory Drug (NSAID)-Dependent Exacerbation of Colitis, European Journal of Pharmacology. (2009) 603, no. 1–3, 120–132, https://doi.org/10.1016/j.ejphar.2008.11.058, 2-s2.0-58249103210.
- 109 Zheng W., Fan W., and Zhang S., et al.Naproxen Exhibits Broad Anti-Influenza Virus Activity in Mice by Impeding Viral Nucleoprotein Nuclear Export, Cell Reports. (2019) 27, no. 6, 1875–1885.e5, https://doi.org/10.1016/j.celrep.2019.04.053, 2-s2.0-85064933610.
- 110 Amici C., Di Caro A., and Ciucci A., et al.Indomethacin Has a Potent Antiviral Activity Against SARS Coronavirus, Antiviral Therapy. (2006) 11, no. 8, 1021–1030, https://doi.org/10.1177/135965350601100803.
- 111
Sills J. and
FitzGerald G. A., Misguided Drug Advice for COVID-19, Science. (2020) 367, no. 6485, https://doi.org/10.1126/science.abb8034.
10.1126/science.abb8034 Google Scholar
- 112 Chamkouri N., Absalan F., Koolivand Z., and Yousefi M., Nonsteroidal Anti-Inflammatory Drugs in Viral Infections Disease, Specially COVID-19, Advanced Biomedical Research. (2023) 12, no. 1, https://doi.org/10.4103/abr.abr_148_21, 20.
- 113 Shirey K. A., Lai W., and Pletneva L. M., et al.Role of the Lipoxygenase Pathway in RSV-Induced Alternatively Activated Macrophages Leading to Resolution of Lung Pathology, Mucosal Immunology. (2014) 7, no. 3, 549–557, https://doi.org/10.1038/mi.2013.71, 2-s2.0-84891899101.
- 114 Tam V. C., Quehenberger O., and Oshansky C. M., et al.Lipidomic Profiling of Influenza Infection Identifies Mediators that Induce and Resolve Inflammation, Cell. (2013) 154, no. 1, 213–227, https://doi.org/10.1016/j.cell.2013.05.052, 2-s2.0-84879935264.
- 115 Shirey K. A., Pletneva L. M., and Puche A. C., et al.Control of RSV-Induced Lung Injury by Alternatively Activated Macrophages is IL-4Rα-, TLR4-, and IFN-β-Dependent, Mucosal Immunology. (2010) 3, no. 3, 291–300, https://doi.org/10.1038/mi.2010.6, 2-s2.0-77951447568.
- 116 Kelleni M. T., ACEIs, ARBs, Ibuprofen Originally Linked to COVID-19: The Other Side of the Mirror, Inflammopharmacology. (2020) 28, no. 6, 1477–1480, https://doi.org/10.1007/s10787-020-00755-x.
- 117 Fang L., Karakiulakis G., and Roth M., Antihypertensive Drugs and Risk of COVID-19? - Authors’ Reply, The Lancet Respiratory Medicine. (2020) 8, no. 5, e32–e33, https://doi.org/10.1016/S2213-2600(20)30159-4.
- 118 Leth M. F., Bukhari S., and Laursen C. C. W., et al.Risk of Serious Adverse Events Associated With Non-Steroidal Anti-Inflammatory Drugs in Orthopaedic Surgery. A Protocol for a Systematic Review, Acta Anaesthesiologica Scandinavica. (2022) 66, no. 10, 1257–1265, https://doi.org/10.1111/aas.14140.
- 119 Brusselle G., Himpe U., and Fievez P., et al.Evolving to a Single Inhaler Extrafine LABA/LAMA/ICS - Inhalation Technique and Adherence at the Heart of COPD Patient Care (TRIVOLVE), Respiratory Medicine. (2023) 218, https://doi.org/10.1016/j.rmed.2023.107368, 107368.
- 120 Malerba M., Foci V., and Patrucco F., et al.Single Inhaler LABA/LAMA for COPD, Frontiers in Pharmacology. (2019) 10, https://doi.org/10.3389/fphar.2019.00390, 2-s2.0-85068409919, 390.
- 121 Morales D. R., LABA Monotherapy in Asthma: An Avoidable Problem, British Journal of General Practice. (2013) 63, no. 617, 627–628, https://doi.org/10.3399/bjgp13X675250, 2-s2.0-84888811360.
- 122 Boulet L. P., Abbott C., and Brusselle G., et al.Baseline Characteristics and ICS/LAMA/LABA Response in Asthma: Analyses From the CAPTAIN Study, The Journal of Allergy and Clinical Immunology: In Practice. (2024) 12, no. 5, 1244–1253.e8, https://doi.org/10.1016/j.jaip.2024.01.039.
- 123 Bucher H., Duechs M. J., Tilp C., Jung B., and Erb K. J., Tiotropium Attenuates Virus-Induced Pulmonary Inflammation in Cigarette Smoke-Exposed Mice, The Journal of Pharmacology and Experimental Therapeutics. (2016) 357, no. 3, 606–618, https://doi.org/10.1124/jpet.116.232009, 2-s2.0-84974622446.
- 124 Yang N., Singhera G. K., and Yan Y. X., et al.Olodaterol Exerts Anti-Inflammatory Effects on COPD Airway Epithelial Cells, Respiratory Research. (2021) 22, no. 1, https://doi.org/10.1186/s12931-021-01659-2, 65.
- 125 Matera M. G., Rinaldi B., and Calabrese C., et al.The Effect of Combining an Inhaled Corticosteroid and a Long-Acting Muscarinic Antagonist on Human Airway Epithelial Cells in Vitro, Respiratory Research. (2024) 25, no. 1, https://doi.org/10.1186/s12931-024-02710-8, 104.
- 126 Bochkov Y. A., Busse W. W., and Brockman-Schneider R. A., et al.Budesonide and Formoterol Effects on Rhinovirus Replication and Epithelial Cell Cytokine Responses, Respiratory Research. (2013) 14, no. 1, https://doi.org/10.1186/1465-9921-14-98, 2-s2.0-84884942387, 98.
- 127 Tacon C. E., Newton R., Proud D., and Leigh R., Rhinovirus-Induced MMP-9 Expression is Dependent on Fra-1, Which Is Modulated by Formoterol and Dexamethasone, The Journal of Immunology. (2012) 188, no. 9, 4621–4630, https://doi.org/10.4049/jimmunol.1101666, 2-s2.0-84860320293.
- 128 Yamaya M., Nishimura H., and Deng X., et al.Inhibitory Effects of Glycopyrronium, Formoterol, and Budesonide on Coronavirus HCoV-229E Replication and Cytokine Production by Primary Cultures of Human Nasal and Tracheal Epithelial Cells, Respiratory Investigation. (2020) 58, no. 3, 155–168, https://doi.org/10.1016/j.resinv.2019.12.005.
- 129 Samajdar S. S., Mukherjee S., Moitra S., Pal J., Joshi S., and Tripathi S. K., Effectiveness of Budesonide Formoterol Fixed-Dose Combination MDI in Reducing Cough Symptoms in COVID-19 Patients: A Real-World Evidence Study, Lung India. (2023) 40, no. 2, 107–111, https://doi.org/10.4103/lungindia.lungindia_268_22.
- 130 Qin J., Wang G., and Han D., Benefits of LAMA in Patients With Asthma-COPD Overlap: A Systematic Review and Meta-Analysis, Clinical Immunology. (2022) 237, https://doi.org/10.1016/j.clim.2022.108986, 108986.
- 131 Teh B. W., Worth L. J., Harrison S. J., Thursky K. A., and Slavin M. A., Risks and Burden of Viral Respiratory Tract Infections in Patients With Multiple Myeloma in the Era of Immunomodulatory Drugs and Bortezomib: Experience at an Australian Cancer Hospital, Supportive Care in Cancer. (2015) 23, no. 7, 1901–1906, https://doi.org/10.1007/s00520-014-2550-3, 2-s2.0-84929947636.
- 132 Flandre T. D., Piaia A., and Cary M. G., Biologic Immunomodulatory Drugs and Infection in the Respiratory Tract of Nonhuman Primates, Toxicologic Pathology. (2021) 49, no. 2, 397–407, https://doi.org/10.1177/0192623320946705.
- 133 Li Y., Wang L., and Si H., et al.Influenza Virus Glycoprotein-Reactive Human Monoclonal Antibodies, Microbes and Infection. (2020) 22, no. 6-7, 263–271, https://doi.org/10.1016/j.micinf.2020.06.003.
- 134 Li G., Hilgenfeld R., Whitley R., and De Clercq E., Therapeutic Strategies for COVID-19: Progress and Lessons Learned, Nature Reviews Drug Discovery. (2023) 22, no. 6, 449–475, https://doi.org/10.1038/s41573-023-00672-y.
- 135
Group RC, Baricitinib in Patients Admitted to Hospital with COVID-19 (RECOVERY): A Randomised, Controlled, Open-Label, Platform Trial and Updated Meta-Analysis, The Lancet. (2022) 400, no. 10349, 359–368, https://doi.org/10.1016/S0140-6736(22)01109-6.
10.1016/S0140-6736(22)01109-6 Google Scholar
- 136 Riccio A. M., Mauri P., and De Ferrari L., et al.Galectin-3: An Early Predictive Biomarker of Modulation of Airway Remodeling in Patients With Severe Asthma Treated with Omalizumab for 36 months, Clinical and Translational Allergy. (2017) 7, no. 1, https://doi.org/10.1186/s13601-017-0143-1, 2-s2.0-85015174747, 6.
- 137 Zastrzezynska W., Bazan-Socha S., and Przybyszowski M., et al.Effect of Omalizumab on Bronchoalveolar Lavage Matrix Metalloproteinases in Severe Allergic Asthma, Journal of Asthma. (2022) 59, no. 6, 1087–1094, https://doi.org/10.1080/02770903.2021.1903917.
- 138 Riccio A. M., Dal Negro R. W., and Micheletto C., et al.Omalizumab Modulates Bronchial Reticular Basement Membrane Thickness and Eosinophil Infiltration in Severe Persistent Allergic Asthma Patients, International Journal of Immunopathology and Pharmacology. (2012) 25, no. 2, 475–484, https://doi.org/10.1177/039463201202500217, 2-s2.0-84863698582.
- 139 Zastrzezynska W., Przybyszowski M., and Bazan-Socha S., et al.Omalizumab May Decrease the Thickness of the Reticular Basement Membrane and Fibronectin Deposit in the Bronchial Mucosa of Severe Allergic Asthmatics, Journal of Asthma. (2020) 57, no. 5, 468–477, https://doi.org/10.1080/02770903.2019.1585872, 2-s2.0-85063258833.
- 140 Sverrild A., Hansen S., and Hvidtfeldt M., et al.The Effect of Tezepelumab on Airway Hyperresponsiveness to Mannitol in Asthma (UPSTREAM), European Respiratory Journal. (2021) 59, no. 1, https://doi.org/10.1183/13993003.01296-2021, 2101296.
- 141 Diver S., Khalfaoui L., and Emson C., et al.Effect of Tezepelumab on Airway Inflammatory Cells, Remodelling, and Hyperresponsiveness in Patients With Moderate-to-Severe Uncontrolled Asthma (CASCADE): A Double-Blind, Randomised, Placebo-Controlled, Phase 2 Trial, The Lancet Respiratory Medicine. (2021) 9, no. 11, 1299–1312, https://doi.org/10.1016/S2213-2600(21)00226-5.
- 142 Baldo B. A., Immune- and Non-Immune-Mediated Adverse Effects of Monoclonal Antibody Therapy: A Survey of 110 Approved Antibodies, Antibodies (Basel). (2022) 11, no. 1, https://doi.org/10.3390/antib11010017, 17.
- 143 BrittR. D.Jr., Ruwanpathirana A., Ford M. L., and Lewis B. W., Macrophages Orchestrate Airway Inflammation, Remodeling, and Resolution in Asthma, International Journal of Molecular Sciences. (2023) 24, no. 13, https://doi.org/10.3390/ijms241310451, 10451.
- 144 Antar S. A., Ashour N. A., Marawan M. E., and Al-Karmalawy A. A., Fibrosis: Types, Effects, Markers, Mechanisms for Disease Progression, and Its Relation with Oxidative Stress, Immunity, and Inflammation, International Journal of Molecular Sciences. (2023) 24, no. 4, https://doi.org/10.3390/ijms24044004, 4004.
- 145 Mack M., Inflammation and Fibrosis, Matrix Biology. (2018) 68-69, 106–121, https://doi.org/10.1016/j.matbio.2017.11.010, 2-s2.0-85036652665.
- 146 Piedimonte G., Contribution of Neuroimmune Mechanisms to Airway Inflammation and Remodeling During and After Respiratory Syncytial Virus Infection, The Pediatric Infectious Disease Journal. (2003) 22, no. S1, S66–S75, https://doi.org/10.1097/01.inf.0000053888.67311.1d.
- 147 Wieczfinska J. and Pawliczak R., Relaxin Affects Airway Remodeling Genes Expression through Various Signal Pathways Connected With Transcription Factors, International Journal of Molecular Sciences. (2022) 23, no. 15, https://doi.org/10.3390/ijms23158413, 8413.
- 148 Miller M., Cho J. Y., and McElwain K., et al.Corticosteroids Prevent Myofibroblast Accumulation and Airway Remodeling in Mice, American Journal of Physiology-Lung Cellular and Molecular Physiology. (2006) 290, no. 1, L162–L169, https://doi.org/10.1152/ajplung.00252.2005, 2-s2.0-33644791777.
- 149 Williams D. M., Clinical Pharmacology of Corticosteroids, Respir Care, Respiratory Care. (2018) 63, no. 6, 655–670, https://doi.org/10.4187/respcare.06314, 2-s2.0-85054866649.
- 150 Pauwels R. A., Pedersen S., and Busse W. W., et al.Early Intervention With Budesonide in Mild Persistent Asthma: A Randomised, Double-Blind Trial, The Lancet. (2003) 361, no. 9363, 1071–1076, https://doi.org/10.1016/S0140-6736(03)12891-7, 2-s2.0-0037471787.
- 151 Covar R. A., Fuhlbrigge A. L., Williams P., and Kelly H. W., The Childhood Asthma Management Program (CAMP): Contributions to the Understanding of Therapy and the Natural History of Childhood Asthma, Current Respiratory Care Reports. (2012) 1, no. 4, 243–250, https://doi.org/10.1007/s13665-012-0026-9.
- 152 Jackson D. J., Heaney L. G., and Humbert M., et al.Reduction of Daily Maintenance Inhaled Corticosteroids in Patients With Severe Eosinophilic Asthma Treated With Benralizumab (SHAMAL): A Randomised, Multicentre, Open-Label, Phase 4 Study, The Lancet. (2024) 403, no. 10423, 271–281, https://doi.org/10.1016/S0140-6736(23)02284-5.
- 153 Baraket M., Oliver B. G., Burgess J. K., Lim S., King G. G., and Black J. L., Is Low Dose Inhaled Corticosteroid Therapy as Effective for Inflammation and Remodeling in Asthma? A Randomized, Parallel Group Study, Respiratory Research. (2012) 13, no. 1, https://doi.org/10.1186/1465-9921-13-11, 2-s2.0-84856446250, 11.
- 154 Ghandi V., Li D., and Weinkauf J., et al.Systemic Corticosteroids for Outpatient Respiratory Viral Infections in Lung Transplant Recipients, Transplant Infectious Disease. (2023) 25, no. 6, https://doi.org/10.1111/tid.14181, e14181.
- 155 Stumm C. L., Wettlaufer S. H., Jancar S., and Peters-Golden M., Airway Remodeling in Murine Asthma Correlates With a Defect in PGE2 Synthesis by Lung Fibroblasts, American Journal of Physiology-Lung Cellular and Molecular Physiology. (2011) 301, no. 5, L636–644, https://doi.org/10.1152/ajplung.00158.2011, 2-s2.0-80055117381.
- 156 Gans M. D. and Gavrilova T., Understanding the Immunology of Asthma: Pathophysiology, Biomarkers, and Treatments for Asthma Endotypes, Paediatric Respiratory Reviews. (2020) 36, 118–127, https://doi.org/10.1016/j.prrv.2019.08.002.
- 157 Gong Y., Sui Z., Lv Y., Zheng Q., and Li L., LABA/LAMA versus LABA/ICS Fixed-Dose Combinations in the Prevention of COPD Exacerbations: A Modeling Analysis of Literature Aggregate Data, European Journal of Clinical Pharmacology. (2023) 79, no. 10, 1321–1332, https://doi.org/10.1007/s00228-023-03543-y.
- 158 Ferguson G. T., Darken P., and Ballal S., et al.Efficacy of Budesonide/Glycopyrronium/Formoterol Fumarate Metered Dose Inhaler (BGF MDI) Versus Other Inhaled Corticosteroid/Long-Acting Muscarinic Antagonist/Long-Acting β2-Agonist (ICS/LAMA/LABA) Triple Combinations in COPD: A Systematic Literature Review and Network Meta-analysis, Advances in Therapy. (2020) 37, no. 6, 2956–2975, https://doi.org/10.1007/s12325-020-01311-3.
- 159
Buhl R.,
Miravitlles M.,
Anzueto A., and
Brunton S., Long-Acting Muscarinic Antagonist and Long-Acting β 2 -Agonist Combination for the Treatment of Maintenance Therapy–Naïve Patients With Chronic Obstructive Pulmonary Disease: A Narrative Review, Therapeutic Advances in Respiratory Disease. (2024) 18, https://doi.org/10.1177/17534666241279115, 17534666241279115.
10.1177/17534666241279115 Google Scholar
- 160 Kaszubowska L., Foerster J., Kaczor J. J., Karnia M. J., and Kmiec Z., Anti-Inflammatory Klotho Protein Serum Concentration Correlates With Interferon Gamma Expression Related to the Cellular Activity of Both NKT-Like and T Cells in the Process of Human Aging, International Journal of Molecular Sciences. (2023) 24, no. 9, https://doi.org/10.3390/ijms24098393, 8393.
- 161 Finotto S., Jartti T., and Johnston S. L., Editorial: Type I and Type III Interferon Immune Responses in Asthma, Frontiers in Immunology. (2022) 12, https://doi.org/10.3389/fimmu.2021.826363, 826363.
- 162 Guo-Parke H., Linden D., Weldon S., Kidney J. C., and Taggart C. C., Deciphering Respiratory-Virus-Associated Interferon Signaling in COPD Airway Epithelium, Medicina (Kaunas). (2022) 58, no. 1, https://doi.org/10.3390/medicina58010121, 121.
- 163 Domvri K., Tsiouprou I., and Bakakos P., et al.Effect of Mepolizumab in Airway Remodeling in Patients With Late-Onset Severe Asthma With an Eosinophilic Phenotype, Journal of Allergy and Clinical Immunology. (2025) 155, no. 2, 425–435, https://doi.org/10.1016/j.jaci.2024.10.024.
- 164 Akhmetzyanova I., Aaron T., and Galbo P., et al.Tissue-Resident Macrophages Promote Early Dissemination of Multiple Myeloma via IL-6 and TNF alpha, Blood Advances. (2021) 5, no. 18, 3592–3608, https://doi.org/10.1182/bloodadvances.2021005327.
- 165 Tang R., Wang H., and Tang M., Roles of Tissue-Resident Immune Cells in Immunotherapy of Non-Small Cell Lung Cancer, Frontiers in Immunology. (2023) 14, https://doi.org/10.3389/fimmu.2023.1332814, 1332814.
- 166 Rhee C. K., Park J.-W., Park H.-W., Noh H., Msihid J., and Cho Y. S., Long-Term Safety and Efficacy of Dupilumab in Patients With Uncontrolled, Moderate-to-Severe Asthma Recruited From Korean Centers: A Subgroup Analysis of the Phase 3 LIBERTY ASTHMA TRAVERSE Trial, Allergy, Asthma & Immunology Research. (2024) 16, no. 4, 372–386, https://doi.org/10.4168/aair.2024.16.4.372.
- 167
Zhang Q.,
Zhong N., and
Dhooria S., et al.Dupilumab Efficacy and Safety in Patients With Persistent Asthma: Asia-Pacific Region, Clinical & Experimental Allergy. (2025) https://doi.org/10.1111/cea.70005.
10.1111/cea.70005 Google Scholar
- 168 Edwards M. R., Walton R. P., and Jackson D. J., et al.The Potential of Anti-Infectives and Immunomodulators as Therapies for Asthma and Asthma Exacerbations, Allergy. (2018) 73, no. 1, 50–63, https://doi.org/10.1111/all.13257, 2-s2.0-85038583973.
- 169 Sobieraj D. M., Baker W. L., and Nguyen E., et al.Association of Inhaled Corticosteroids and Long-Acting Muscarinic Antagonists With Asthma Control in Patients With Uncontrolled, Persistent Asthma: A Systematic Review and Meta-Analysis, JAMA. (2018) 319, no. 14, 1473–1484, https://doi.org/10.1001/jama.2018.2757, 2-s2.0-85045184802.
- 170 Lo P.-C., Tsai Y.-T., Lin S.-K., and Lai J.-N., Risk of Asthma Exacerbation Associated With Nonsteroidal Anti-Inflammatory Drugs in Childhood Asthma: A Nationwide Population-Based Cohort Study in Taiwan, Medicine (Baltimore). (2016) 95, no. 41, https://doi.org/10.1097/MD.0000000000005109, 2-s2.0-85011971670, e5109.
- 171 Takeuchi Y., Ando T., Ishiguro C., and Uyama Y., Risk of Acute Asthma Attacks Associated With Nonsteroidal Anti-Inflammatory Drugs: A Self-Controlled Case Series, Therapeutic Innovation & Regulatory Science. (2017) 51, no. 3, 332–341, https://doi.org/10.1177/2168479016679865, 2-s2.0-85018418079.
- 172 Kim L. H. Y., Saleh C., Whalen-Browne A., O’Byrne P. M., and Chu D. K., Triple Vs Dual Inhaler Therapy and Asthma Outcomes in Moderate to Severe Asthma: A Systematic Review and Meta-Analysis, JAMA. (2021) 325, no. 24, 2466–2479, https://doi.org/10.1001/jama.2021.7872.
- 173 Plaza V., Dominguez-Ortega J., Gonzalez-Segura Alsina D., Lo Re D., and Sicras-Mainar A., Comprehensive Observational Study in a Large Cohort of Asthma Patients after Adding LAMA to ICS/LABA, Pharmaceuticals (Basel). (2023) 16, no. 11, https://doi.org/10.3390/ph16111609, 1609.
- 174 Rich H. E., Antos D., Melton N. R., Alcorn J. F., and Manni M. L., Insights Into Type I and III Interferons in Asthma and Exacerbations, Frontiers in Immunology. (2020) 11, https://doi.org/10.3389/fimmu.2020.574027, 574027.
- 175 Tliba O., Damera G., and Banerjee A., et al.Cytokines Induce an Early Steroid Resistance in Airway Smooth Muscle Cells: Novel Role of Interferon Regulatory Factor-1, American Journal of Respiratory Cell and Molecular Biology. (2008) 38, no. 4, 463–472, https://doi.org/10.1165/rcmb.2007-0226OC, 2-s2.0-41449101856.
- 176 Nolasco S., Crimi C., and Campisi R., Personalized Medicine in Asthma: Current Approach and Future Perspectives, Journal of Personalized Medicine. (2023) 13, no. 10, https://doi.org/10.3390/jpm13101459, 1459.
- 177 Lee I. T. and Yang C. M., Inflammatory Signalings Involved in Airway and Pulmonary Diseases, Mediators of Inflammation. (2013) 2013, https://doi.org/10.1155/2013/791231, 2-s2.0-84877262734, 791231.
