Clinical Significance of Combined Detection of CCL22 and IL-1 as Potential New Bronchial Inflammatory Mediators in Children's Asthma
Lei Cui,
Xiaozhen Song,
Yanping Peng,
Min Shi,
Lei Cui
Department of Pediatrics, People's Hospital of Xiangxi Tujia and Miao Autonomous Prefecture, First Affliated Hospital of Jishou University, Jishou, China
Search for more papers by this authorXiaozhen Song
Department of Pediatrics, People's Hospital of Xiangxi Tujia and Miao Autonomous Prefecture, First Affliated Hospital of Jishou University, Jishou, China
Search for more papers by this authorYanping Peng
Department of Pediatrics, People's Hospital of Xiangxi Tujia and Miao Autonomous Prefecture, First Affliated Hospital of Jishou University, Jishou, China
Search for more papers by this authorCorresponding Author
Min Shi
Department of Pediatrics, People's Hospital of Xiangxi Tujia and Miao Autonomous Prefecture, First Affliated Hospital of Jishou University, Jishou, China
Correspondence: Min Shi ([email protected])
Search for more papers by this authorLei Cui,
Xiaozhen Song,
Yanping Peng,
Min Shi,
Lei Cui
Department of Pediatrics, People's Hospital of Xiangxi Tujia and Miao Autonomous Prefecture, First Affliated Hospital of Jishou University, Jishou, China
Search for more papers by this authorXiaozhen Song
Department of Pediatrics, People's Hospital of Xiangxi Tujia and Miao Autonomous Prefecture, First Affliated Hospital of Jishou University, Jishou, China
Search for more papers by this authorYanping Peng
Department of Pediatrics, People's Hospital of Xiangxi Tujia and Miao Autonomous Prefecture, First Affliated Hospital of Jishou University, Jishou, China
Search for more papers by this authorCorresponding Author
Min Shi
Department of Pediatrics, People's Hospital of Xiangxi Tujia and Miao Autonomous Prefecture, First Affliated Hospital of Jishou University, Jishou, China
Correspondence: Min Shi ([email protected])
Search for more papers by this authorFirst published: 07 November 2024
ABSTRACT
Backgrounds
Severe asthma is a significant health burden because children with severe asthma are vulnerable to medication-related side effects, life-threatening deterioration, and impaired quality of life. However, there is a lack of data to elucidate the role of inflammatory variables in asthma. This study aimed to compare the levels of inflammatory factors in serum and sputum in children with acute and stable asthma to those in healthy children and the ability to predict clinical response to azithromycin therapy.
Methods
This study recruited 95 individuals aged 1−3 years old and collected data from January 2018 to 2020. We examined serum and sputum inflammatory factors and constructed the least absolute shrinkage and selection operator (LASSO) model. Predictive models were constructed through multifactor logistic regression and presented in the form of column-line plots. The performance of the column-line diagrams was measured by subject work characteristics (ROC) curves, calibration plots, and decision curve analysis (DCA). Then, filter-paper samples were collected from 45 children with acute asthma who were randomly assigned to receive either azithromycin (10 mg/kg, n = 22) or placebo (n = 23). Pretreatment levels of immune mediators were then analyzed and compared with clinical response to azithromycin therapy.
Results
Of the 95 eligible participants, 21 (22.11%) were healthy controls, 29 (30.53%) had stable asthma, and 45 (47.37%) had acute asthma. The levels of interferon-γ (IFN-γ), tumor necrosis factor-a (TNF-α), chemokine CCL22 (CCL22), interleukin 12 (IL-12), chemokine CCL4 (CCL4), chemokine CCL2 (CCL2), and chemokine CCL13 (CCL13）were significantly higher in the acute asthma group than in the stable asthma group. A logistic regression analysis was performed using CCL22 and IL-1 as independent variables. Additionally, IFN-γ, TNF-α, IL-1, IL-13, and CCL22 were identified in the LASSO model. Finally, we found that CCL22 and IL-1 were more responsive in predicting the response to azithromycin treatment.
Conclusion
Our results show that CCL22 and IL-1 are both representative markers during asthma symptom exacerbations and an immune mediator that can predict response to azithromycin therapy.
Conflicts of Interest
The authors declare no conflicts of interest.
Open Research
Data Availability Statement
The data used to support the findings of this study are included in the article.
Supporting Information
| Filename | Description |
|---|---|
| iid370043-sup-0001-STROBE_checklist_v4_combined.doc84.5 KB | Supporting information. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1M. D. Gans and T. Gavrilova, “Understanding the Immunology of Asthma: Pathophysiology, Biomarkers, and Treatments for Asthma Endotypes,” Paediatric Respiratory Reviews 36 (2020): 118–127, https://doi.org/10.1016/j.prrv.2019.08.002.
- 2J. R. Pleis, J. W. Lucas, and B. W. Ward, “Summary Health Statistics for US Adults; National Health Interview Survey, 2008,” Vital and Health Statistics Series 10, no. 242 (2009): 1–157.
- 3L. P. Boulet and M. È. Boulay, “Asthma-Related Comorbidities,” Expert Review of Respiratory Medicine 5, no. 3 (2011): 377–393, https://doi.org/10.1586/ers.11.34.
- 4T. D. Wu, E. P. Brigham, and M. C. McCormack, “Asthma in the Primary Care Setting,” Medical Clinics of North America 103, no. 3 (2019): 435–452, https://doi.org/10.1016/j.mcna.2018.12.004.
- 5P. Ntontsi, A. Photiades, E. Zervas, G. Xanthou, and K. Samitas, “Genetics and Epigenetics in Asthma,” International Journal of Molecular Sciences 22, no. 5 (2021): 2412, https://doi.org/10.3390/ijms22052412.
- 6J. W. Mims, “Asthma: Definitions and Pathophysiology,” International Forum of Allergy & Rhinology 5, no. S1 (2015): S2–S6, https://doi.org/10.1002/alr.21609.
- 7J. H. Kwah and A. T. Peters, “Asthma in Adults: Principles of Treatment,” Allergy and Asthma Proceedings 40, no. 6 (2019): 396–402, https://doi.org/10.2500/aap.2019.40.4256.
- 8M. Sockrider and L. Fussner, “What Is Asthma,” American Journal of Respiratory and Critical Care Medicine 202, no. 9 (2020): P25–P26, https://doi.org/10.1164/rccm.2029P25.
- 9A. Banno, A. T. Reddy, S. P. Lakshmi, and R. C. Reddy, “Bidirectional Interaction of Airway Epithelial Remodeling and Inflammation in Asthma,” Clinical Science 134, no. 9 (2020): 1063–1079, https://doi.org/10.1042/cs20191309.
- 10L. Fang, Q. Sun, and M. Roth, “Immunologic and Non-Immunologic Mechanisms Leading to Airway Remodeling in Asthma,” International Journal of Molecular Sciences 21, no. 3 (2020): 757, https://doi.org/10.3390/ijms21030757.
- 11K. Malmström, A. S. Pelkonen, and M. J. Mäkelä, “Remodeling, Inflammation and Airway Responsiveness in Early Childhood Asthma,” Current Opinion in Allergy & Clinical Immunology 13, no. 2 (2013): 203–210, https://doi.org/10.1097/ACI.0b013e32835e122c.
- 12A. Moeller, K. H. Carlsen, P. D. Sly, et al., “Monitoring Asthma in Childhood: Lung Function, Bronchial Responsiveness and Inflammation,” European Respiratory Review 24, no. 136 (2015): 204–215, https://doi.org/10.1183/16000617.00003914.
- 13M. W. Pijnenburg and L. Fleming, “Advances in Understanding and Reducing the Burden of Severe Asthma in Children,” Lancet Respiratory Medicine 8, no. 10 (2020): 1032–1044, https://doi.org/10.1016/s2213-2600(20)30399-4.
- 14R. F. Lemanske Jr., “Inflammation in Childhood Asthma and Other Wheezing Disorders,” Pediatrics 109, no. S2 (2002): 368–372.
- 15J. A. Castro-Rodriguez, S. Saglani, C. E. Rodriguez-Martinez, M. A. Oyarzun, L. Fleming, and A. Bush, “The Relationship Between Inflammation and Remodeling in Childhood Asthma: A Systematic Review,” Pediatric Pulmonology 53, no. 6 (2018): 824–835, https://doi.org/10.1002/ppul.23968.
- 16K. M. Lebold, D. B. Jacoby, and M. G. Drake, “Inflammatory Mechanisms Linking Maternal and Childhood Asthma,” Journal of Leukocyte Biology 108, no. 1 (2020): 113–121, https://doi.org/10.1002/jlb.3mr1219-338r.
- 17A. K. Saikumar Jayalatha, L. Hesse, M. E. Ketelaar, G. H. Koppelman, and M. C. Nawijn, “The Central Role of IL-33/IL-1RL1 Pathway in Asthma: From Pathogenesis to Intervention,” Pharmacology & Therapeutics 225 (2021): 107847, https://doi.org/10.1016/j.pharmthera.2021.107847.
- 18H. Bowen, A. Kelly, T. Lee, and P. Lavender, “Control of Cytokine Gene Transcription in Th1 and Th2 Cells,” Clinical & Experimental Allergy 38, no. 9 (2008): 1422–1431, https://doi.org/10.1111/j.1365-2222.2008.03067.x.
- 19K. R. Bartemes and H. Kita, “Innate and Adaptive Immune Responses to Fungi in the Airway,” Journal of Allergy and Clinical Immunology 142, no. 2 (2018): 353–363, https://doi.org/10.1016/j.jaci.2018.06.015.
- 20S. T. Holgate, “Innate and Adaptive Immune Responses in Asthma,” Nature Medicine 18, no. 5 (2012): 673–683, https://doi.org/10.1038/nm.2731.
- 21M. Kubo, “Innate and Adaptive Type 2 Immunity in Lung Allergic Inflammation,” Immunological Reviews 278, no. 1 (2017): 162–172, https://doi.org/10.1111/imr.12557.
- 22H. Hammad, M. Plantinga, K. Deswarte, et al., “Inflammatory Dendritic Cells: Not Basophils: Are Necessary and Sufficient for Induction of Th2 Immunity to Inhaled House Dust Mite Allergen,” Journal of Experimental Medicine 207, no. 10 (2010): 2097–2111, https://doi.org/10.1084/jem.20101563.
- 23P. S. Arunachalam, M. K. D. Scott, T. Hagan, et al., “Systems Vaccinology of the BNT162b2 mRNA Vaccine in Humans,” Nature 596, no. 7872 (2021): 410–416, https://doi.org/10.1038/s41586-021-03791-x.
- 24G. Drazdauskaitė, J. A. Layhadi, and M. H. Shamji, “Mechanisms of Allergen Immunotherapy in Allergic Rhinitis,” Current Allergy and Asthma Reports 21, no. 1 (2020): 2, https://doi.org/10.1007/s11882-020-00977-7.
- 25B. N. Lambrecht and H. Hammad, “The Airway Epithelium in Asthma,” Nature Medicine 18, no. 5 (2012): 684–692, https://doi.org/10.1038/nm.2737.
- 26I. Schmudde, Y. Laumonnier, and J. Köhl, “Anaphylatoxins Coordinate Innate and Adaptive Immune Responses in Allergic Asthma,” Seminars in Immunology 25, no. 1 (2013): 2–11, https://doi.org/10.1016/j.smim.2013.04.009.
- 27L. Y. Drake and H. Kita, “IL-33: Biological Properties, Functions, and Roles in Airway Disease,” Immunological Reviews 278, no. 1 (2017): 173–184, https://doi.org/10.1111/imr.12552.
- 28S. J. Galli, N. Gaudenzio, and M. Tsai, “Mast Cells in Inflammation and Disease: Recent Progress and Ongoing Concerns,” Annual Review of Immunology 38 (2020): 49–77, https://doi.org/10.1146/annurev-immunol-071719-094903.
- 29H. Hawlisch, “The Anaphylatoxins Bridge Innate and Adaptive Immune Responses in Allergic Asthma,” Molecular Immunology 41, no. 2–3 (2004): 123–131, https://doi.org/10.1016/j.molimm.2004.03.019.
- 30M. E. Kirtland, D. C. Tsitoura, S. R. Durham, and M. H. Shamji, “Toll-Like Receptor Agonists as Adjuvants for Allergen Immunotherapy,” Frontiers in Immunology 11 (2020): 599083, https://doi.org/10.3389/fimmu.2020.599083.
- 31D. Y. M. Leung, E. Berdyshev, and E. Goleva, “Cutaneous Barrier Dysfunction in Allergic Diseases,” Journal of Allergy and Clinical Immunology 145, no. 6 (2020): 1485–1497, https://doi.org/10.1016/j.jaci.2020.02.021.
- 32S. K. Panda and M. Colonna, “Innate Lymphoid Cells in Mucosal Immunity,” Frontiers in Immunology 10 (2019): 861, https://doi.org/10.3389/fimmu.2019.00861.
- 33J. Stokholm, B. L. Chawes, N. H. Vissing, et al., “Azithromycin for Episodes With Asthma-Like Symptoms in Young Children Aged 1-3 Years: A Randomised, Double-Blind, Placebo-Controlled Trial,” Lancet Respiratory Medicine 4, no. 1 (2016): 19–26, https://doi.org/10.1016/s2213-2600(15)00500-7.
- 34A. Kicic, E. N. Sutanto, P. T. Stevens, D. A. Knight, and S. M. Stick, “Intrinsic Biochemical and Functional Differences in Bronchial Epithelial Cells of Children With Asthma,” American Journal of Respiratory and Critical Care Medicine 174, no. 10 (2006): 1110–1118, https://doi.org/10.1164/rccm.200603-392OC.
- 35S. M. van Schaik, D. A. Tristram, I. S. Nagpal, K. M. Hintz, R. C. Welliver, and R. C. Welliver, “Increased Production of IFN-γ and Cysteinyl Leukotrienes in Virus-Induced Wheezing,” Journal of Allergy and Clinical Immunology 103, no. 4 (1999): 630–636, https://doi.org/10.1016/s0091-6749(99)70235-6.
- 36J. de Blic, F. Midulla, A. Barbato, et al., “Bronchoalveolar Lavage in Children. ERS Task Force on Bronchoalveolar Lavage in Children. European Respiratory Society,” European Respiratory Journal 15, no. 1 (2000): 217–231, https://doi.org/10.1183/09031936.00.15121700.
- 37Y. Lu, H. Kared, S. W. Tan, et al., “Dynamics of Helper CD4 T Cells During Acute and Stable Allergic Asthma,” Mucosal Immunology 11, no. 6 (2018): 1640–1652, https://doi.org/10.1038/s41385-018-0057-9.
- 38K. A. Holden, D. Roland, K. G. Welsh, and E. A. Gaillard, “Comparison of Blood Eosinophil Numbers Between Acute Asthma and Stable Disease in Children With Preschool Wheeze,” Pediatric Allergy, Immunology, and Pulmonology 30, no. 4 (2017): 210–217, https://doi.org/10.1089/ped.2017.0802.
- 39F. Wang, X. Y. He, K. J. Baines, et al., “Different Inflammatory Phenotypes in Adults and Children With Acute Asthma,” European Respiratory Journal 38, no. 3 (2011): 567–574, https://doi.org/10.1183/09031936.00170110.
- 40C. J. Carlsson, M. A. Rasmussen, S. B. Pedersen, et al., “Airway Immune Mediator Levels During Asthma-Like Symptoms in Young Children and Their Possible Role in Response to Azithromycin,” Allergy 76, no. 6 (2021): 1754–1764, https://doi.org/10.1111/all.14651.
- 41H. Bisgaard, N. H. Vissing, C. G. Carson, et al., “Deep Phenotyping of the Unselected COPSAC2010 Birth Cohort Study,” Clinical & Experimental Allergy 43, no. 12 (2013): 1384–1394, https://doi.org/10.1111/cea.12213.
- 42N. V. Følsgaard, B. L. Chawes, M. A. Rasmussen, et al., “Neonatal Cytokine Profile in the Airway Mucosal Lining Fluid Is Skewed by Maternal Atopy,” American Journal of Respiratory and Critical Care Medicine 185, no. 3 (2012): 275–280, https://doi.org/10.1164/rccm.201108-1471OC.
- 43H. M. Wolsk, B. L. Chawes, N. V. Følsgaard, M. A. Rasmussen, S. Brix, and H. Bisgaard, “Siblings Promote a Type 1/Type 17-Oriented Immune Response in the Airways of Asymptomatic Neonates,” Allergy 71, no. 6 (2016): 820–828, https://doi.org/10.1111/all.12847.
- 44A. H. Thysen, M. A. Rasmussen, E. Kreiner-Møller, et al., “Season of Birth Shapes Neonatal Immune Function,” Journal of Allergy and Clinical Immunology 137, no. 4 (2016): 1238–1246.e13, https://doi.org/10.1016/j.jaci.2015.08.041.
- 45J. L. Simpson, M. Carroll, I. A. Yang, et al., “Reduced Antiviral Interferon Production in Poorly Controlled Asthma Is Associated With Neutrophilic Inflammation and High-Dose Inhaled Corticosteroids,” Chest 149, no. 3 (2016): 704–713, https://doi.org/10.1016/j.chest.2015.12.018.
- 46H. Bisgaard, C. B. Pipper, and K. Bønnelykke, “Endotyping Early Childhood Asthma by Quantitative Symptom Assessment,” Journal of Allergy and Clinical Immunology 127, no. 5 (2011): 1155–1164.e2, https://doi.org/10.1016/j.jaci.2011.02.007.
- 47A. C. Kidd, M. McGettrick, S. Tsim, D. L. Halligan, M. Bylesjo, and K. G. Blyth, “Survival Prediction in Mesothelioma Using a Scalable Lasso Regression Model: Instructions for Use and Initial Performance Using Clinical Predictors,” BMJ Open Respiratory Research 5, no. 1 (2018): e000240, https://doi.org/10.1136/bmjresp-2017-000240.
- 48J. Xing, L. Min, S. Zhu, et al., “Factors Associated With Gastric Adenocarcinoma and Dysplasia in Patients With Chronic Gastritis: A Population-Based Study,” Chinese Journal of Cancer Research 29, no. 4 (2017): 341–350, https://doi.org/10.21147/j.issn.1000-9604.2017.04.07.
- 49V. P. Balachandran, M. Gonen, J. J. Smith, and R. P. DeMatteo, “Nomograms in Oncology: More Than Meets the Eye,” Lancet Oncology 16, no. 4 (2015): e173–e180, https://doi.org/10.1016/s1470-2045(14)71116-7.
- 50A. J. Vickers, A. M. Cronin, E. B. Elkin, and M. Gonen, “Extensions to Decision Curve Analysis, a Novel Method for Evaluating Diagnostic Tests, Prediction Models and Molecular Markers,” BMC Medical Informatics and Decision Making 8 (2008): 53, https://doi.org/10.1186/1472-6947-8-53.
- 51Y. Huang, C. Liang, L. He, et al., “Development and Validation of a Radiomics Nomogram for Preoperative Prediction of Lymph Node Metastasis in Colorectal Cancer,” Journal of Clinical Oncology 34, no. 18 (2016): 2157–2164, https://doi.org/10.1200/jco.2015.65.9128.
- 52A. L. Voskamp, T. G. Kormelink, R. G. van Wijk, et al., “Modulating Local Airway Immune Responses to Treat Allergic Asthma: Lessons From Experimental Models and Human Studies,” Seminars in Immunopathology 42, no. 1 (2020): 95–110, https://doi.org/10.1007/s00281-020-00782-4.
- 53M. Colaneri, M. De Filippo, A. Licari, et al., “COVID Vaccination and Asthma Exacerbation: Might There be a Link,” International Journal of Infectious Diseases: IJID: Official Publication of the International Society for Infectious Diseases 112 (2021): 243–246, https://doi.org/10.1016/j.ijid.2021.09.026.
- 54A. Kozik and Y. J. Huang, “Ecological Interactions in Asthma: From Environment to Microbiota and Immune Responses,” Current Opinion in Pulmonary Medicine 26, no. 1 (2020): 27–32, https://doi.org/10.1097/mcp.0000000000000632.
- 55C. Pilette, J. N. Francis, S. J. Till, and S. R. Durham, “CCR4 Ligands Are Up-Regulated in the Airways of Atopic Asthmatics After Segmental Allergen Challenge,” European Respiratory Journal 23, no. 6 (2004): 876–884, https://doi.org/10.1183/09031936.04.00102504.
- 56R. Bonecchi, G. Bianchi, P. P. Bordignon, et al., “Differential Expression of Chemokine Receptors and Chemotactic Responsiveness of Type 1 T Helper Cells (Th1s) and Th2s,” Journal of Experimental Medicine 187, no. 1 (1998): 129–134, https://doi.org/10.1084/jem.187.1.129.
- 57C. A. Weston, B. M. J. Rana, and D. J. Cousins, “Differential Expression of Functional Chemokine Receptors on Human Blood and Lung Group 2 Innate Lymphoid Cells,” Journal of Allergy and Clinical Immunology 143, no. 1 (2019): 410–413.e9, https://doi.org/10.1016/j.jaci.2018.08.030.
- 58B. N. Lambrecht, H. Hammad, and J. V. Fahy, “The Cytokines of Asthma,” Immunity 50, no. 4 (2019): 975–991, https://doi.org/10.1016/j.immuni.2019.03.018.
- 59J. A. Gonzalo, Y. Pan, C. M. Lloyd, et al., “Mouse Monocyte-Derived Chemokine Is Involved in Airway Hyperreactivity and Lung Inflammation,” Journal of Immunology 163, no. 1 (1999): 403–411.
- 60H. Hammad, B. N. Lambrecht, P. Pochard, et al., “Monocyte-Derived Dendritic Cells Induce a House Dust Mite-Specific Th2 Allergic Inflammation in the Lung of Humanized SCID Mice: Involvement of CCR7,” Journal of Immunology 169, no. 3 (2002): 1524–1534, https://doi.org/10.4049/jimmunol.169.3.1524.
- 61J. M. Subramaniam, G. Whiteside, K. McKeage, and J. C. Croxtall, “Mogamulizumab: First Global Approval,” Drugs 72, no. 9 (2012): 1293–1298, https://doi.org/10.2165/11631090-000000000-00000.
- 62S. N. Georas, J. E. Cumberland, T. F. Burke, R. Chen, U. Schindler, and V. Casolaro, “Stat6 Inhibits Human Interleukin-4 Promoter Activity in T Cells,” Blood 92, no. 12 (1998): 4529–4538.
- 63M. Ritter, R. Göggel, N. Chaudhary, et al., “Elevated Expression of TARC (CCL17) and MDC (CCL22) in Models of Cigarette Smoke-Induced Pulmonary Inflammation,” Biochemical and Biophysical Research Communications 334, no. 1 (2005): 254–262, https://doi.org/10.1016/j.bbrc.2005.06.084.
- 64C. Cayrol and J. P. Girard, “Interleukin-33 (IL-33): A Nuclear Cytokine From the IL-1 Family,” Immunological Reviews 281, no. 1 (2018): 154–168, https://doi.org/10.1111/imr.12619.
- 65I. Mahmutovic Persson, M. Menzel, S. Ramu, S. Cerps, H. Akbarshahi, and L. Uller, “IL-1β Mediates Lung Neutrophilia and IL-33 Expression in a Mouse Model of Viral-Induced Asthma Exacerbation,” Respiratory Research 19, no. 1 (2018): 16, https://doi.org/10.1186/s12931-018-0725-z.
- 66R. Y. Kim, J. W. Pinkerton, A. T. Essilfie, et al., “Role for NLRP3 Inflammasome-Mediated, IL-1β-Dependent Responses in Severe, Steroid-Resistant Asthma,” American Journal of Respiratory and Critical Care Medicine 196, no. 3 (2017): 283–297, https://doi.org/10.1164/rccm.201609-1830OC.
- 67W. Wei, J. Huang, Y. Ma, et al., “IL-1 Signaling Pathway Molecules as Key Markers in Childhood Asthma,” Pediatric Allergy and Immunology 32, no. 2 (2021): 305–313, https://doi.org/10.1111/pai.13388.
- 68E. T. Osei, C. A. Brandsma, W. Timens, I. H. Heijink, and T. L. Hackett, “Current Perspectives on the Role of Interleukin-1 Signalling in the Pathogenesis of Asthma and COPD,” European Respiratory Journal 55, no. 2 (2020): 1900563, https://doi.org/10.1183/13993003.00563-2019.
- 69N. Röhrle, M. M. L. Knott, and D. Anz, “CCL22 Signaling in the Tumor Environment,” Advances in Experimental Medicine and Biology 1231 (2020): 79–96, https://doi.org/10.1007/978-3-030-36667-4_8.
- 70C. Baer, S. Kimura, M. S. Rana, et al., “CCL22 Mutations Drive Natural Killer Cell Lymphoproliferative Disease by Deregulating Microenvironmental Crosstalk,” Nature Genetics 54, no. 5 (2022): 637–648, https://doi.org/10.1038/s41588-022-01059-2.
- 71G. Ren, N. Al-Jezani, P. Railton, J. N. Powell, and R. J. Krawetz, “CCL22 Induces Pro-Inflammatory Changes in Fibroblast-Like Synoviocytes,” iScience 24, no. 1 (2021): 101943, https://doi.org/10.1016/j.isci.2020.101943.
- 72C. Y. Chiu, K. W. Su, M. H. Tsai, et al., “Low Mother-to-Child CCL22 Chemokine Levels Are Inversely Related to Mite Sensitization and Asthma in Early Childhood,” Scientific Reports 8, no. 1 (2018): 6043, https://doi.org/10.1038/s41598-018-24523-8.
- 73T. Balamugesh, D. Behera, A. Bhatnagar, and S. Majumdar, “Inflammatory Cytokine Levels in Induced Sputum and Bronchoalveolar Lavage Fluid in Pulmonary Sarcoidosis,” Indian Journal of Chest Diseases & Allied Sciences 48, no. 3 (2006): 177–181.
- 74E. Osika, J. Cavaillon, K. Chadelat, et al., “Distinct Sputum Cytokine Profiles in Cystic Fibrosis and Other Chronic Inflammatory Airway Disease,” European Respiratory Journal 14, no. 2 (1999): 339–346, https://doi.org/10.1034/j.1399-3003.1999.14b17.x.
- 75H. Ali, J. Douwes, J. Burmanje, et al., “Sputum Inflammatory, Neural, and Remodeling Mediators in Eosinophilic and Noneosinophilic Asthma,” Annals of Allergy, Asthma & Immunology: Official Publication of the American College of Allergy, Asthma, & Immunology 130, no. 6 (2023): 776–783, https://doi.org/10.1016/j.anai.2023.03.015.
- 76A. Tanaka, H. Sato, K. Akimoto, T. Matsunaga, and H. Sagara, “Spontaneous Sputum Discriminates Inflammatory Phenotypes in Patients With Asthma,” Annals of Allergy, Asthma & Immunology: Official Publication of the American College of Allergy, Asthma, & Immunology 126, no. 1 (2021): 54–60, https://doi.org/10.1016/j.anai.2020.06.017.
- 77Y. P. Tsang, J. M. Marchant, A. M. Li, and A. B. Chang, “Stability of Sputum Inflammatory Phenotypes in Childhood Asthma During Stable and Exacerbation Phases,” Pediatric Pulmonology 56, no. 6 (2021): 1484–1489, https://doi.org/10.1002/ppul.25347.
- 78P. G. Gibson, I. A. Yang, J. W. Upham, et al., “Effect of Azithromycin on Asthma Exacerbations and Quality of Life in Adults With Persistent Uncontrolled Asthma (AMAZES): A Randomised, Double-Blind, Placebo-Controlled Trial,” Lancet 390, no. 10095 (2017): 659–668, https://doi.org/10.1016/s0140-6736(17)31281-3.
- 79S. L. Taylor, L. E. X. Leong, F. M. Mobegi, et al., “Long-Term Azithromycin Reduces Haemophilus influenzae and Increases Antibiotic Resistance in Severe Asthma,” American Journal of Respiratory and Critical Care Medicine 200, no. 3 (2019): 309–317, https://doi.org/10.1164/rccm.201809-1739OC.
- 80J. J. Ghimire, K. R. Jat, J. Sankar, et al., “Azithromycin for Poorly Controlled Asthma in Children,” Chest 161, no. 6 (2022): 1456–1464, https://doi.org/10.1016/j.chest.2022.02.025.
- 81L. Liu, G. Z. Wang, D. Han, and M. X. Li, “Effectiveness and Safety of Azithromycin in the Treatment of Bronchial Asthma: A Meta-Analysis,” Nan fang yi ke da xue xue bao = Journal of Southern Medical University 35, no. 1 (2015): 83–87.
- 82B. P. Tian, N. Xuan, Y. Wang, G. Zhang, and W. Cui, “The Efficacy and Safety of Azithromycin in Asthma: A Systematic Review,” Journal of Cellular and Molecular Medicine 23, no. 3 (2019): 1638–1646, https://doi.org/10.1111/jcmm.13919.
