Aspirin-exacerbated respiratory disease (AERD) is an asthma phenotype characterized by nasal polyps, chronic hypertrophic eosinophilic sinusitis, asthma, and sensitivity to aspirin. Unawareness of this disease by patients and their physicians may have serious consequences because of the risk of near-fatal asthma. Its confirmative diagnosis can be established only by provocative aspirin challenge, which represents a potential risk for patient health. Purpose: Because CCL4 plays an important role in several pulmonary conditions, we tested its immunoreactivity in nasal lavages and sera from control subjects, and from aspirin-sensitive and non-aspirin-sensitive patients. Method: Immunoreactivity of CCL4 was measured in serum and nasal lavages from 30 healthy controls (HC), 23 patients with AERD, and 20 patients with aspirin-tolerant asthma (ATA). Additionally, a serum biobank contained sera from 90 HC, 83 patients with AERD, and 69 patients with ATA was employed. Results: The serum immunoreactivity of CCL4 could distinguish both types of asthma phenotypes. Conclusion: CCL4 may play an unexpected role in thephysiopathology of AERD.
KeywordsAERDCCL4Asthma
Lee, R.U. and Stevenson, D.D. (2011) Aspirin-Exacerbated Respiratory Disease: Evaluation and Management. Allergy, Asthma & Immunology Research, 3, 3-10. https://doi.org/10.4168/aair.2011.3.1.3
Wenzel, S.E. (2006) Asthma: Defining of the Persistent Adult Phenotypes. Lancet, 368, 804-813. https://doi.org/10.1016/S0140-6736(06)69290-8
Babu, K.S. and Salvi, S.S. (2000) Aspirin and Asthma. Chest, 118, 1470-1476. https://doi.org/10.1378/chest.118.5.1470
Walgama, E.S. and Hwang, P.H. (2017) Aspirin-Exacerbated Respiratory Disease. Otolaryngologic Clinics of North America, 50, 83-94. https://doi.org/10.1016/j.otc.2016.08.007
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Kupczyk, M., Kurmanowska, Z., Kuprys-Lipinska, I., Bochenska-Marciniak, M. and Kuna, P. (2010) Mediators of Inflammation in Nasal Lavage from Aspirin Intolerant Patients after Aspirin Challenge. Respiratory Medicine, 104, 1404-1409. https://doi.org/10.1016/j.rmed.2010.04.017
Menten, P., Wuyts, A. and Van, D.J. (2002) Macrophage Inflammatory Protein-1. Cytokine & Growth Factor Reviews, 13, 455-481. https://doi.org/10.1016/S1359-6101(02)00045-X
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Adams, D.H., Hubscher, S., Fear, J., Johnston, J., Shaw, S. and Afford, S. (1996) Hepatic Expression of Macrophage Inflammatory Protein-1 Alpha and Macrophage Inflammatory Protein-1 Beta after Liver Transplantation. Transplantation, 61, 817-825. https://doi.org/10.1097/00007890-199603150-00024
O’Grady, N.P., Tropea, M., Preas, H.L., Reda, D., Vandivier, R.W., Banks, S.M., et al. (1999) Detection of Macrophage Inflammatory Protein (MIP)-1 Alpha and MIP-1 Beta during Experimental Endotoxemia and Human Sepsis. The Journal of Infectious Diseases, 179, 136-141. https://doi.org/10.1086/314559
Reape, T.J. and Groot, P.H. (1999) Chemokines and Atherosclerosis. Atherosclerosis, 147, 213-225.
Capelli, A., Di, S.A., Gnemmi, I., Balbo, P., Cerutti, C.G., Balbi, B., et al. (1999) Increased MCP-1 and MIP-1 Beta in Bronchoalveolar Lavage Fluid of Chronic Bronchitics. The European Respiratory Journal, 14, 160-165. https://doi.org/10.1034/j.1399-3003.1999.14a27.x
Emad, A. and Emad, V. (2007) Elevated Levels of MCP-1, MIP-Alpha and MIP-1 Beta in the Bronchoalveolar Lavage (BAL) Fluid of Patients with Mustard Gas-Induced Pulmonary Fibrosis. Toxicology, 240, 60-69.
Brennan, S., Sly, P.D., Gangell, C.L., Sturges, N., Winfield, K., Wikstrom, M., et al. (2009) Alveolar Macrophages and CC Chemokines Are Increased in Children with Cystic Fibrosis. The European Respiratory Journal, 34, 655-661. https://doi.org/10.1183/09031936.00178508
Odum, N., Bregenholt, S., Eriksen, K.W., Skov, S., Ryder, L.P., Bendtzen, K., et al. (1999) The CC-Chemokine Receptor 5 (CCR5) Is a Marker of, But Not Essential for the Development of Human Th1 Cells. Tissue Antigens, 54, 572-577. https://doi.org/10.1034/j.1399-0039.1999.540606.x
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Grob, M., Schmid-Grendelmeier, P., Joller-Jemelka, H.I., Ludwig, E., Dubs, R.W., Grob, P.J., et al. (2003) Altered Intracellular Expression of the Chemokines MIP-1 Alpha, MIP-1 Beta and IL-8 by Peripheral Blood CD4+ and CD8+ T Cells in Mild Allergic Asthma. Allergy, 58, 239-245. https://doi.org/10.1034/j.1398-9995.2003.00035.x
Moon, H.G., Tae, Y.M., Kim, Y.S., Gyu, J.S., Oh, S.Y., Song, G.Y., et al. (2010) Conversion of Th17-Type into Th2-Type Inflammation by Acetyl Salicylic Acid via the Adenosine and Uric Acid Pathway in the Lung. Allergy, 65, 1093-1103. https://doi.org/10.1111/j.1398-9995.2010.02352.x
Lee, R.U. and Stevenson, D.D. (2011) Aspirin-Exacerbated Respiratory Disease: Evaluation and Management. Allergy, Asthma & Immunology Research, 3, 3-10. https://doi.org/10.4168/aair.2011.3.1.3
Wenzel, S.E. (2006) Asthma: Defining of the Persistent Adult Phenotypes. Lancet, 368, 804-813. https://doi.org/10.1016/S0140-6736(06)69290-8
Babu, K.S. and Salvi, S.S. (2000) Aspirin and Asthma. Chest, 118, 1470-1476. https://doi.org/10.1378/chest.118.5.1470
Velazquez, J.R. and Teran, L.M. (2013) Aspirin-Intolerant Asthma: A Comprehensive Review of Biomarkers and Pathophysiology. Clinical Reviews in Allergy & Immunology, 45, 75-86. https://doi.org/10.1007/s12016-012-8340-0
Walgama, E.S. and Hwang, P.H. (2017) Aspirin-Exacerbated Respiratory Disease. Otolaryngologic Clinics of North America, 50, 83-94. https://doi.org/10.1016/j.otc.2016.08.007
Szczeklik, A. (1992) Aspirin-Induced Asthma: Pathogenesis and Clinical Presentation. Allergy Proceedings, 13, 163-173. https://doi.org/10.2500/108854192778817211
Kupczyk, M., Kurmanowska, Z., Kuprys-Lipinska, I., Bochenska-Marciniak, M. and Kuna, P. (2010) Mediators of Inflammation in Nasal Lavage from Aspirin Intolerant Patients after Aspirin Challenge. Respiratory Medicine, 104, 1404-1409. https://doi.org/10.1016/j.rmed.2010.04.017
Menten, P., Wuyts, A. and Van, D.J. (2002) Macrophage Inflammatory Protein-1. Cytokine & Growth Factor Reviews, 13, 455-481. https://doi.org/10.1016/S1359-6101(02)00045-X
Afford, S.C., Fisher, N.C., Neil, D.A., Fear, J., Brun, P., Hubscher, S.G., et al. (1998) Distinct Patterns of Chemokine Expression Are Associated with Leukocyte Recruitment in Alcoholic Hepatitis and Alcoholic Cirrhosis. The Journal of Pathology, 186, 82-89. https://doi.org/10.1002/(SICI)1096-9896(199809)186:1 3.0.CO;2-D
Adams, D.H., Hubscher, S., Fear, J., Johnston, J., Shaw, S. and Afford, S. (1996) Hepatic Expression of Macrophage Inflammatory Protein-1 Alpha and Macrophage Inflammatory Protein-1 Beta after Liver Transplantation. Transplantation, 61, 817-825. https://doi.org/10.1097/00007890-199603150-00024
O’Grady, N.P., Tropea, M., Preas, H.L., Reda, D., Vandivier, R.W., Banks, S.M., et al. (1999) Detection of Macrophage Inflammatory Protein (MIP)-1 Alpha and MIP-1 Beta during Experimental Endotoxemia and Human Sepsis. The Journal of Infectious Diseases, 179, 136-141. https://doi.org/10.1086/314559
Reape, T.J. and Groot, P.H. (1999) Chemokines and Atherosclerosis. Atherosclerosis, 147, 213-225.
Capelli, A., Di, S.A., Gnemmi, I., Balbo, P., Cerutti, C.G., Balbi, B., et al. (1999) Increased MCP-1 and MIP-1 Beta in Bronchoalveolar Lavage Fluid of Chronic Bronchitics. The European Respiratory Journal, 14, 160-165. https://doi.org/10.1034/j.1399-3003.1999.14a27.x
Emad, A. and Emad, V. (2007) Elevated Levels of MCP-1, MIP-Alpha and MIP-1 Beta in the Bronchoalveolar Lavage (BAL) Fluid of Patients with Mustard Gas-Induced Pulmonary Fibrosis. Toxicology, 240, 60-69.
Brennan, S., Sly, P.D., Gangell, C.L., Sturges, N., Winfield, K., Wikstrom, M., et al. (2009) Alveolar Macrophages and CC Chemokines Are Increased in Children with Cystic Fibrosis. The European Respiratory Journal, 34, 655-661. https://doi.org/10.1183/09031936.00178508
Odum, N., Bregenholt, S., Eriksen, K.W., Skov, S., Ryder, L.P., Bendtzen, K., et al. (1999) The CC-Chemokine Receptor 5 (CCR5) Is a Marker of, But Not Essential for the Development of Human Th1 Cells. Tissue Antigens, 54, 572-577. https://doi.org/10.1034/j.1399-0039.1999.540606.x
Boot, J.D., Chandoesing, P., de Kam, M.L., Mascelli, M.A., Das, A.M., Gerth van, W.R., et al. (2008) Applicability and Reproducibility of Biomarkers for the Evaluation of Anti-Inflammatory Therapy in Allergic Rhinitis. Journal of Investigational Allergology and Clinical Immunology, 18, 433-442.
Grob, M., Schmid-Grendelmeier, P., Joller-Jemelka, H.I., Ludwig, E., Dubs, R.W., Grob, P.J., et al. (2003) Altered Intracellular Expression of the Chemokines MIP-1 Alpha, MIP-1 Beta and IL-8 by Peripheral Blood CD4+ and CD8+ T Cells in Mild Allergic Asthma. Allergy, 58, 239-245. https://doi.org/10.1034/j.1398-9995.2003.00035.x
Moon, H.G., Tae, Y.M., Kim, Y.S., Gyu, J.S., Oh, S.Y., Song, G.Y., et al. (2010) Conversion of Th17-Type into Th2-Type Inflammation by Acetyl Salicylic Acid via the Adenosine and Uric Acid Pathway in the Lung. Allergy, 65, 1093-1103. https://doi.org/10.1111/j.1398-9995.2010.02352.x