Intraepithelial neutrophils in pediatric severe asthma are associated with better lung function

Journal of Allergy and Clinical Immunology

Volumn 139, Issue 6, 2017, Pages 1819-1829.e11

  Andersson, Cecilia K ^a   Adams, Alexandra ^a,b   Nagakumar, Prasad ^a,b   Bossley, Cara ^b   Gupta, Atul ^b   De Vries, Daphne ^a   Adnan, Afiqah ^a   Bush, Andrew ^b   Saglani, Sejal ^a,b   Lloyd, Clare M ^a  

^a NATIONAL HEART AND LUNG INSTITUTE   (United Kingdom)

^b ROYAL BROMPTON AND HAREFIELD NHS FOUNDATION TRUST   (United Kingdom)

Author keywords

IL 17A; IL 17A receptor; neutrophils; Pediatric asthma; severe therapy resistant asthma

Indexed keywords

BUDESONIDE; FIBROBLAST GROWTH FACTOR 2; FIBRONECTIN; GAMMA INTERFERON; GAMMA INTERFERON INDUCIBLE PROTEIN 10; INTERLEUKIN 13; INTERLEUKIN 17; INTERLEUKIN 22; INTERLEUKIN 6; INTERLEUKIN 8; MDC PROTEIN; MONOCYTE CHEMOTACTIC PROTEIN 1; PROTEIN; UNCLASSIFIED DRUG; IL17A PROTEIN, HUMAN; IL17RA PROTEIN, HUMAN; INTERLEUKIN 17 RECEPTOR; INTERLEUKIN DERIVATIVE; INTERLEUKIN-22;

ADOLESCENT; ARTICLE; ASTHMA; BACTERIUM CULTURE; BASEMENT MEMBRANE; BRONCHUS BIOPSY; BRONCHUS EPITHELIUM; CHILD; CONTROLLED STUDY; CYTOKINE RELEASE; DISEASE SEVERITY; EOSINOPHIL; FEMALE; FIBEROPTIC BRONCHOSCOPY; FORCED EXPIRATORY VOLUME; GENE EXPRESSION; HUMAN; HUMAN CELL; HUMAN TISSUE; INTRAEPITHELIAL NEUTROPHIL; LUNG FUNCTION; LUNG LAVAGE; MAJOR CLINICAL STUDY; MALE; MONONUCLEAR CELL; NEUTROPHIL; NEUTROPHIL COUNT; POLYMERASE CHAIN REACTION; POLYMORPHONUCLEAR CELL; PRIORITY JOURNAL; PROTEIN EXPRESSION; BIOPSY; BRONCHOALVEOLAR LAVAGE FLUID; BRONCHOSCOPY; CYTOLOGY; IMMUNOLOGY; INFANT; LUNG; PATHOLOGY; PATHOPHYSIOLOGY; PRESCHOOL CHILD; RESPIRATORY MUCOSA;

ADOLESCENT; ASTHMA; BIOPSY; BRONCHOALVEOLAR LAVAGE FLUID; BRONCHOSCOPY; CHILD; CHILD, PRESCHOOL; FEMALE; HUMANS; INFANT; INTERLEUKIN-17; INTERLEUKINS; LUNG; MALE; NEUTROPHILS; RECEPTORS, INTERLEUKIN-17; RESPIRATORY MUCOSA;

EID: 85006932870     PISSN: 00916749     EISSN: 10976825     Source Type: Journal    
DOI: 10.1016/j.jaci.2016.09.022     Document Type: Article

References (64)

1. Wenzel, S.E., Asthma phenotypes: the evolution from clinical to molecular approaches. Nat Med 18 (2012), 716–725.
2. Wu, W., Bleecker, E., Moore, W., Busse, W.W., Castro, M., Chung, K.F., et al. Unsupervised phenotyping of Severe Asthma Research Program participants using expanded lung data. J Allergy Clin Immunol 133 (2014), 1280–1288.
3. Moore, W.C., Bleecker, E.R., Asthma heterogeneity and severity—why is comprehensive phenotyping important?. Lancet Respir Med 2 (2014), 10–11.
4. Bush, A., Saglani, S., Management of severe asthma in children. Lancet 376 (2010), 814–825.
5. Bossley, C.J., Fleming, L., Gupta, A., Regamey, N., Frith, J., Oates, T., et al. Pediatric severe asthma is characterized by eosinophilia and remodeling without T(H)2 cytokines. J Allergy Clin Immunol 129 (2012), 974–982.e13.
6. Moore, W.C., Hastie, A.T., Li, X., Li, H., Busse, W.W., Jarjour, N.N., et al. Sputum neutrophil counts are associated with more severe asthma phenotypes using cluster analysis. J Allergy Clin Immunol 133 (2014), 1557–1563.e5.
7. Wenzel, S.E., Schwartz, L.B., Langmack, E.L., Halliday, J.L., Trudeau, J.B., Gibbs, R.L., et al. Evidence that severe asthma can be divided pathologically into two inflammatory subtypes with distinct physiologic and clinical characteristics. Am J Respir Crit Care Med 160 (1999), 1001–1008.
8. Al-Ramli, W., Prefontaine, D., Chouiali, F., Martin, J.G., Olivenstein, R., Lemiere, C., et al. T(H)17-associated cytokines (IL-17A and IL-17F) in severe asthma. J Allergy Clin Immunol 123 (2009), 1185–1187.
9. Barczyk, A., Pierzchala, W., Sozanska, E., Interleukin-17 in sputum correlates with airway hyperresponsiveness to methacholine. Respir Med 97 (2003), 726–733.
10. Bullens, D.M., Truyen, E., Coteur, L., Dilissen, E., Hellings, P.W., Dupont, L.J., et al. IL-17 mRNA in sputum of asthmatic patients: linking T cell driven inflammation and granulocytic influx?. Respir Res, 7, 2006, 135.
11. Molet, S., Hamid, Q., Davoine, F., Nutku, E., Taha, R., Page, N., et al. IL-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokines. J Allergy Clin Immunol 108 (2001), 430–438.
12. Agache, I., Ciobanu, C., Agache, C., Anghel, M., Increased serum IL-17 is an independent risk factor for severe asthma. Respir Med 104 (2010), 1131–1137.
13. Chesne, J., Braza, F., Mahay, G., Brouard, S., Aronica, M., Magnan, A., IL-17 in severe asthma. Where do we stand?. Am J Respir Crit Care Med 190 (2014), 1094–1101.
14. Willis, C.R., Siegel, L., Leith, A., Mohn, D., Escobar, S., Wannberg, S., et al. IL-17RA signaling drives airway inflammation and bronchial hyper reactivity in allergic asthma. Am J Respir Cell Mol Biol 53 (2015), 810–821.
15. Kudo, M., Melton, A.C., Chen, C., Engler, M.B., Huang, K.E., Ren, X., et al. IL-17A produced by alphabeta T cells drives airway hyper-responsiveness in mice and enhances mouse and human airway smooth muscle contraction. Nat Med 18 (2012), 547–554.
16. Onishi, R.M., Gaffen, S.L., Interleukin-17 and its target genes: mechanisms of interleukin-17 function in disease. Immunology 129 (2010), 311–321.
17. Ye, P., Rodriguez, F.H., Kanaly, S., Stocking, K.L., Schurr, J., Schwarzenberger, P., et al. Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense. J Exp Med 194 (2001), 519–527.
18. Huang, W., Na, L., Fidel, P.L., Schwarzenberger, P., Requirement of interleukin-17A for systemic anti-Candida albicans host defense in mice. J Infect Dis 190 (2004), 624–631.
19. Farfariello, V., Amantini, C., Nabissi, M., Morelli, M.B., Aperio, C., Caprodossi, S., et al. IL-22 mRNA in peripheral blood mononuclear cells from allergic rhinitic and asthmatic pediatric patients. Pediatr Allergy Immunol 22 (2011), 419–423.
20. Taube, C., Tertilt, C., Gyulveszi, G., Dehzad, N., Kreymborg, K., Schneeweiss, K., et al. IL-22 is produced by innate lymphoid cells and limits inflammation in allergic airway disease. PLoS One, 6, 2011, e21799.
21. Eyerich, S., Eyerich, K., Pennino, D., Carbone, T., Nasorri, F., Pallotta, S., et al. Th22 cells represent a distinct human T cell subset involved in epidermal immunity and remodeling. J Clin Investig 119 (2009), 3573–3585.
22. Chung, K.F., Wenzel, S.E., Brozek, J.L., Bush, A., Castro, M., Sterk, P.J., et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J 43 (2014), 343–373.
23. Bracken, M., Fleming, L., Hall, P., Van Stiphout, N., Bossley, C., Biggart, E., et al. The importance of nurse-led home visits in the assessment of children with problematic asthma. Arch Dis Child 94 (2009), 780–784.
24. Zijlstra, G.J., Ten Hacken, N.H., Hoffmann, R.F., van Oosterhout, A.J., Heijink, I.H., Interleukin-17A induces glucocorticoid insensitivity in human bronchial epithelial cells. Eur Respir J 39 (2012), 439–445.
25. Hymowitz, S.G., Filvaroff, E.H., Yin, J.P., Lee, J., Cai, L., Risser, P., et al. IL-17s adopt a cystine knot fold: structure and activity of a novel cytokine, IL-17F, and implications for receptor binding. EMBO J 20 (2001), 5332–5341.
26. McAllister, F., Henry, A., Kreindler, J.L., Dubin, P.J., Ulrich, L., Steele, C., et al. Role of IL-17A, IL-17F, and the IL-17 receptor in regulating growth-related oncogene-alpha and granulocyte colony-stimulating factor in bronchial epithelium: implications for airway inflammation in cystic fibrosis. J Immunol 175 (2005), 404–412.
27. McKinley, L., Alcorn, J.F., Peterson, A., Dupont, R.B., Kapadia, S., Logar, A., et al. TH17 cells mediate steroid-resistant airway inflammation and airway hyperresponsiveness in mice. J Immunol 181 (2008), 4089–4097.
28. Cao, J., Ren, G., Gong, Y., Dong, S., Yin, Y., Zhang, L., Bronchial epithelial cells release IL-6, CXCL1 and CXCL8 upon mast cell interaction. Cytokine 56 (2011), 823–831.
29. Manni, M.L., Trudeau, J.B., Scheller, E.V., Mandalapu, S., Elloso, M.M., Kolls, J.K., et al. The complex relationship between inflammation and lung function in severe asthma. Mucosal Immunol 7 (2014), 1186–1198.
30. Bruijnzeel, P.L., Uddin, M., Koenderman, L., Targeting neutrophilic inflammation in severe neutrophilic asthma: can we target the disease-relevant neutrophil phenotype?. J Leukocyte Biol 98 (2015), 549–556.
31. Colgan, S.P., Comerford, K.M., Lawrence, D.W., Epithelial cell-neutrophil interactions in the alimentary tract: a complex dialog in mucosal surveillance and inflammation. Sci World J 2 (2002), 76–88.
32. de Blic, J., Tillie-Leblond, I., Emond, S., Mahut, B., Dang Duy, T.L., Scheinmann, P., High-resolution computed tomography scan and airway remodeling in children with severe asthma. J Allergy Clin Immunol 116 (2005), 750–754.
33. Kelly, M.N., Kolls, J.K., Happel, K., Schwartzman, J.D., Schwarzenberger, P., Combe, C., et al. Interleukin-17/interleukin-17 receptor-mediated signaling is important for generation of an optimal polymorphonuclear response against Toxoplasma gondii infection. Infect Immun 73 (2005), 617–621.
34. Klesney-Tait, J., Keck, K., Li, X., Gilfillan, S., Otero, K., Baruah, S., et al. Transepithelial migration of neutrophils into the lung requires TREM-1. J Clin Invest 123 (2013), 138–149.
35. Zemans, R.L., Colgan, S.P., Downey, G.P., Transepithelial migration of neutrophils: mechanisms and implications for acute lung injury. Am J Respir Cell Mol Biol 40 (2009), 519–535.
36. Staley, J.T., Konopka, A., Measurement of in situ activities of nonphotosynthetic microorganisms in aquatic and terrestrial habitats. Annu Rev Microbiol 39 (1985), 321–346.
37. Hilty, M., Burke, C., Pedro, H., Cardenas, P., Bush, A., Bossley, C., et al. Disordered microbial communities in asthmatic airways. PLoS One, 5, 2010, e8578.
38. Chung, K.F., Asthma phenotyping: a necessity for improved therapeutic precision and new targeted therapies. J Intern Med 279 (2016), 192–204.
39. Fitzpatrick, A.M., Higgins, M., Holguin, F., Brown, L.A., Teague, W.G., et al., National Institutes of Health/National Heart, Lung and Blood Institute's Severe Asthma Research Program. The molecular phenotype of severe asthma in children. J Allergy Clin Immunol 125 (2010), 851–857.e18.
40. Cosmi, L., Maggi, L., Santarlasci, V., Capone, M., Cardilicchia, E., Frosali, F., et al. Identification of a novel subset of human circulating memory CD4(+) T cells that produce both IL-17A and IL-4. J Allergy Clin Immunol 125 (2010), 222–230.e1-4.
41. Choy, D.F., Hart, K.M., Borthwick, L.A., Shikotra, A., Nagarkar, D.R., Siddiqui, S., et al. TH2 and TH17 inflammatory pathways are reciprocally regulated in asthma. Sci Transl Med, 7, 2015, 301ra129.
42. Nagata, T., McKinley, L., Peschon, J.J., Alcorn, J.F., Aujla, S.J., Kolls, J.K., Requirement of IL-17RA in Con A induced hepatitis and negative regulation of IL-17 production in mouse T cells. J Immunol 181 (2008), 7473–7479.
43. Nanzer, A.M., Chambers, E.S., Ryanna, K., Richards, D.F., Black, C., Timms, P.M., et al. Enhanced production of IL-17A in patients with severe asthma is inhibited by 1alpha,25-dihydroxyvitamin D3 in a glucocorticoid-independent fashion. J Allergy Clin Immunol 132 (2013), 297–304.e3.
44. Brandt, E.B., Kovacic, M.B., Lee, G.B., Gibson, A.M., Acciani, T.H., Le Cras, T.D., et al. Diesel exhaust particle induction of IL-17A contributes to severe asthma. J Allergy Clin Immunol 132 (2013), 1194–1204.e2.
45. Wilson, R.H., Whitehead, G.S., Nakano, H., Free, M.E., Kolls, J.K., Cook, D.N., Allergic sensitization through the airway primes Th17-dependent neutrophilia and airway hyperresponsiveness. Am J Respir Crit Care Med 180 (2009), 720–730.
46. Zhao, J., Lloyd, C.M., Noble, A., Th17 responses in chronic allergic airway inflammation abrogate regulatory T-cell-mediated tolerance and contribute to airway remodeling. Mucosal Immunol 6 (2013), 335–346.
47. Busse, W.W., Holgate, S., Kerwin, E., Chon, Y., Feng, J., Lin, J., et al. Randomized, double-blind, placebo-controlled study of brodalumab, a human anti-IL-17 receptor monoclonal antibody, in moderate to severe asthma. Am J Respir Crit Care Med 188 (2013), 1294–1302.
48. Hauber, H.P., Daigneault, P., Frenkiel, S., Lavigne, F., Hung, H.L., Levitt, R.C., et al. Niflumic acid and MSI-2216 reduce TNF-alpha-induced mucin expression in human airway mucosa. J Allergy Clin Immunol 115 (2005), 266–271.
49. Nguyen, L.T., Lim, S., Oates, T., Chung, K.F., Increase in airway neutrophils after oral but not inhaled corticosteroid therapy in mild asthma. Respir Med 99 (2005), 200–207.
50. Prause, O., Laan, M., Lotvall, J., Linden, A., Pharmacological modulation of interleukin-17-induced GCP-2-, GRO-alpha- and interleukin-8 release in human bronchial epithelial cells. Eur J Pharmacol 462 (2003), 193–198.
51. Saglani, S., Lui, S., Ullmann, N., Campbell, G.A., Sherburn, R.T., Mathie, S.A., et al. IL-33 promotes airway remodeling in pediatric patients with severe steroid-resistant asthma. J Allergy Clin Immunol 132 (2013), 676–685.e13.
52. Saglani, S., Payne, D.N., Zhu, J., Wang, Z., Nicholson, A.G., Bush, A., et al. Early detection of airway wall remodeling and eosinophilic inflammation in preschool wheezers. Am J Respir Crit Care Med 176 (2007), 858–864.
53. Bossley, C.J., Fleming, L., Gupta, A., Regamey, N., Frith, J., Oates, T., et al. Pediatric severe asthma is characterized by eosinophilia and remodeling without T(H)2 cytokines. J Allergy Clin Immunol 129 (2012), 974–982.e13.
54. Bossley, C.J., Saglani, S., Kavanagh, C., Payne, D.N., Wilson, N., Tsartsali, L., et al. Corticosteroid responsiveness and clinical characteristics in childhood difficult asthma. Eur Respir J 34 (2009), 1052–1059.
55. Bush, A., Saglani, S., Management of severe asthma in children. Lancet 376 (2010), 814–825.
56. Bracken, M., Fleming, L., Hall, P., Van Stiphout, N., Bossley, C., Biggart, E., et al. The importance of nurse-led home visits in the assessment of children with problematic asthma. Arch Dis Child 94 (2009), 780–784.
57. Schatz, M., Sorkness, C.A., Li, J.T., Marcus, P., Murray, J.J., Nathan, R.A., et al. Asthma Control Test: reliability, validity, and responsiveness in patients not previously followed by asthma specialists. J Allergy Clin Immunol 117 (2006), 549–556.
58. Nathan, R.A., Sorkness, C.A., Kosinski, M., Schatz, M., Li, J.T., Marcus, P., et al. Development of the asthma control test: a survey for assessing asthma control. J Allergy Clin Immunol 113 (2004), 59–65.
59. Miller, M.R., Hankinson, J., Brusasco, V., Burgos, F., Casaburi, R., Coates, A., et al. Standardisation of spirometry. Eur Respir J 26 (2005), 319–338.
60. Pellegrino, R., Viegi, G., Brusasco, V., Crapo, R.O., Burgos, F., Casaburi, R., et al. Interpretative strategies for lung function tests. Eur Respir J 26 (2005), 948–968.
61. American Thoracic Society. European Respiratory Society. ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide. Am J Respir Crit Care Med 2005:171 (2005), 912–930.
62. Chang, Y., Al-Alwan, L., Risse, P.A., Halayko, A.J., Martin, J.G., Baglole, C.J., et al. Th17-associated cytokines promote human airway smooth muscle cell proliferation. FASEB J 26 (2012), 5152–5160.
63. Johnson, J.R., Nishioka, M., Chakir, J., Risse, P.A., Almaghlouth, I., Bazarbashi, A.N., et al. IL-22 contributes to TGF-beta1-mediated epithelial-mesenchymal transition in asthmatic bronchial epithelial cells. Respir Res, 14, 2013, 118.
64. Pociask, D.A., Scheller, E.V., Mandalapu, S., McHugh, K.J., Enelow, R.I., Fattman, C.L., et al. IL-22 is essential for lung epithelial repair following influenza infection. Am J Pathol 182 (2013), 1286–1296.