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Review article: Biomedical intelligence

Vol. 149 No. 2728 (2019)

Chronic rhinosinusitis in unified airway disease: surfactant proteins as mediators of respiratory immunity

  • George T. Noutsios
  • Saurabh Sharma
DOI
https://doi.org/10.4414/smw.2019.20104
Cite this as:
Swiss Med Wkly. 2019;149:w20104
Published
14.07.2019

Summary

PURPOSE OF REVIEW

The aim of this review is to describe the co-occurrence of chronic rhinosinusitis (CRS) with other inflammatory illnesses of the lower respiratory system characterised by airway obstruction and hyperresponsiveness, such as asthma, cystic fibrosis (CF), and chronic obstructive pulmonary disease (COPD) in the context of the unified airway disease (UAD). We also sought to discuss the novel role of surfactant proteins as mediators of innate immunity in the sinonasal epithelium and their potential as therapeutic interventions.

RECENT FINDINGS

Different epidemiological and physiological studies in CRS and asthma have outlined that there are common clustering patterns in the phenotypes/endotypes of both diseases, reinforcing the notion of the UAD. Also, surfactant proteins A (SP-A) and SP-D have now emerged as novel innate immunity molecules in bacterial sinusitis and allergic fungal sinusitis patients, respectively.

SUMMARY

CRS and asthma coexist and are interconnected. Therefore, management of CRS and asthma must be jointly carried out as one functional entity. SP-A and SP-D bridge the innate and adaptive immunity mechanisms of the sinonasal epithelium to bring together a well-orchestrated mechanism that effectively fights pathogens. The use of SP-A to ameliorate the innate immune responses in CRS is a new concept and is likely to lead to new horizons in CRS therapeutic regimens.

References

  1. Bhattacharyya N. The economic burden and symptom manifestations of chronic rhinosinusitis. Am J Rhinol. 2003;17(1):27–32. doi:.https://doi.org/10.1177/194589240301700106
  2. Barnett SB, Nurmagambetov TA. Costs of asthma in the United States: 2002-2007. J Allergy Clin Immunol. 2011;127(1):145–52. doi:.https://doi.org/10.1016/j.jaci.2010.10.020
  3. Corren J. Allergic rhinitis and asthma: how important is the link? J Allergy Clin Immunol. 1997;99(2):S781–6. doi:.https://doi.org/10.1016/S0091-6749(97)70127-1
  4. Guerra S, Sherrill DL, Baldacci S, Carrozzi L, Pistelli F, Di Pede F, et al. Rhinitis is an independent risk factor for developing cough apart from colds among adults. Allergy. 2005;60(3):343–9. doi:.https://doi.org/10.1111/j.1398-9995.2005.00717.x
  5. Krouse JH, Krouse HJ. Asthma, rhinitis, and the unified airway. ORL Head Neck Nurs. 2013;31(4):6–10.
  6. Krouse JH. The unified airway. Facial Plast Surg Clin North Am. 2012;20(1):55–60. doi:.https://doi.org/10.1016/j.fsc.2011.10.006
  7. Kocevar VS, Bisgaard H, Jönsson L, Valovirta E, Kristensen F, Yin DD, et al. Variations in pediatric asthma hospitalization rates and costs between and within Nordic countries. Chest. 2004;125(5):1680–4. doi:.https://doi.org/10.1378/chest.125.5.1680
  8. Stachler RJ. Comorbidities of asthma and the unified airway. Int Forum Allergy Rhinol. 2015;5(1, Suppl 1):S17–22. doi:.https://doi.org/10.1002/alr.21615
  9. Guerra S, Sherrill DL, Martinez FD, Barbee RA. Rhinitis as an independent risk factor for adult-onset asthma. J Allergy Clin Immunol. 2002;109(3):419–25. doi:.https://doi.org/10.1067/mai.2002.121701
  10. Jacobs SE, Lamson DM, St George K, Walsh TJ. Human rhinoviruses. Clin Microbiol Rev. 2013;26(1):135–62. doi:.https://doi.org/10.1128/CMR.00077-12
  11. Gavala ML, Bertics PJ, Gern JE. Rhinoviruses, allergic inflammation, and asthma. Immunol Rev. 2011;242(1):69–90. doi:.https://doi.org/10.1111/j.1600-065X.2011.01031.x
  12. Foxman EF, Iwasaki A. Genome-virome interactions: examining the role of common viral infections in complex disease. Nat Rev Microbiol. 2011;9(4):254–64. doi:.https://doi.org/10.1038/nrmicro2541
  13. Doctor TH, Trivedi SS, Chudasama RK. Pulmonary function test in healthy school children of 8 to 14 years age in south Gujarat region, India. Lung India. 2010;27(3):145–8. doi:.https://doi.org/10.4103/0970-2113.68317
  14. Gupta S, Siddiqui S, Haldar P, Raj JV, Entwisle JJ, Wardlaw AJ, et al. Qualitative analysis of high-resolution CT scans in severe asthma. Chest. 2009;136(6):1521–8. doi:.https://doi.org/10.1378/chest.09-0174
  15. Jensen SP, Lynch DA, Brown KK, Wenzel SE, Newell JD. High-resolution CT features of severe asthma and bronchiolitis obliterans. Clin Radiol. 2002;57(12):1078–85. doi:.https://doi.org/10.1053/crad.2002.1104
  16. Van Zele T, Claeys S, Gevaert P, Van Maele G, Holtappels G, Van Cauwenberge P, et al. Differentiation of chronic sinus diseases by measurement of inflammatory mediators. Allergy. 2006;61(11):1280–9. doi:.https://doi.org/10.1111/j.1398-9995.2006.01225.x
  17. Akdis CA, Bachert C, Cingi C, Dykewicz MS, Hellings PW, Naclerio RM, et al. Endotypes and phenotypes of chronic rhinosinusitis: a PRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology. J Allergy Clin Immunol. 2013;131(6):1479–90. doi:.https://doi.org/10.1016/j.jaci.2013.02.036
  18. Zhang N, Van Zele T, Perez-Novo C, Van Bruaene N, Holtappels G, DeRuyck N, et al. Different types of T-effector cells orchestrate mucosal inflammation in chronic sinus disease. J Allergy Clin Immunol. 2008;122(5):961–8. doi:.https://doi.org/10.1016/j.jaci.2008.07.008
  19. Smith TL, Litvack JR, Hwang PH, Loehrl TA, Mace JC, Fong KJ, et al. Determinants of outcomes of sinus surgery: a multi-institutional prospective cohort study. Otolaryngol Head Neck Surg. 2010;142(1):55–63. doi:.https://doi.org/10.1016/j.otohns.2009.10.009
  20. Wenzel SE. Asthma phenotypes: the evolution from clinical to molecular approaches. Nat Med. 2012;18(5):716–25. doi:.https://doi.org/10.1038/nm.2678
  21. Lötvall J, Akdis CA, Bacharier LB, Bjermer L, Casale TB, Custovic A, et al. Asthma endotypes: a new approach to classification of disease entities within the asthma syndrome. J Allergy Clin Immunol. 2011;127(2):355–60. doi:.https://doi.org/10.1016/j.jaci.2010.11.037
  22. Noutsios GT, Floros J. Childhood asthma: causes, risks, and protective factors; a role of innate immunity. Swiss Med Wkly. 2014;144:w14036. doi:.https://doi.org/10.4414/smw.2014.14036
  23. Hinks TS, Brown T, Lau LC, Rupani H, Barber C, Elliott S, et al. Multidimensional endotyping in patients with severe asthma reveals inflammatory heterogeneity in matrix metalloproteinases and chitinase 3-like protein 1. J Allergy Clin Immunol. 2016;138(1):61–75. doi:.https://doi.org/10.1016/j.jaci.2015.11.020
  24. Moore WC, Meyers DA, Wenzel SE, Teague WG, Li H, Li X, et al.; National Heart, Lung, and Blood Institute’s Severe Asthma Research Program. Identification of asthma phenotypes using cluster analysis in the Severe Asthma Research Program. Am J Respir Crit Care Med. 2010;181(4):315–23. doi:.https://doi.org/10.1164/rccm.200906-0896OC
  25. Haldar P, Pavord ID, Shaw DE, Berry MA, Thomas M, Brightling CE, et al. Cluster analysis and clinical asthma phenotypes. Am J Respir Crit Care Med. 2008;178(3):218–24. doi:.https://doi.org/10.1164/rccm.200711-1754OC
  26. Tomassen P, Vandeplas G, Van Zele T, Cardell LO, Arebro J, Olze H, et al. Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers. J Allergy Clin Immunol. 2016;137(5):1449–1456.e4. doi:.https://doi.org/10.1016/j.jaci.2015.12.1324
  27. Nakayama T, Yoshikawa M, Asaka D, Okushi T, Matsuwaki Y, Otori N, et al. Mucosal eosinophilia and recurrence of nasal polyps - new classification of chronic rhinosinusitis. Rhinology. 2011;49(4):392–6.
  28. Schlosser RJ, London SD, Gwaltney JM, Jr, Gross CW. Microbiology of chronic frontal sinusitis. Laryngoscope. 2001;111(8):1330–2. doi:.https://doi.org/10.1097/00005537-200108000-00004
  29. Soler ZM, Hyer JM, Ramakrishnan V, Smith TL, Mace J, Rudmik L, et al. Identification of chronic rhinosinusitis phenotypes using cluster analysis. Int Forum Allergy Rhinol. 2015;5(5):399–407. doi:.https://doi.org/10.1002/alr.21496
  30. Ponikau JU, Sherris DA, Kephart GM, Kern EB, Gaffey TA, Tarara JE, et al. Features of airway remodeling and eosinophilic inflammation in chronic rhinosinusitis: is the histopathology similar to asthma? J Allergy Clin Immunol. 2003;112(5):877–82. doi:.https://doi.org/10.1016/j.jaci.2003.08.009
  31. Tagaya E, Tamaoki J. Mechanisms of airway remodeling in asthma. Allergol Int. 2007;56(4):331–40. doi:.https://doi.org/10.2332/allergolint.R-07-152
  32. Holgate ST. Pathogenesis of asthma. Clin Exp Allergy. 2008;38(6):872–97. doi:.https://doi.org/10.1111/j.1365-2222.2008.02971.x
  33. Sly PD, Kusel M, Holt PG. Do early-life viral infections cause asthma? J Allergy Clin Immunol. 2010;125(6):1202–5. doi:.https://doi.org/10.1016/j.jaci.2010.01.024
  34. Gern JE. The ABCs of rhinoviruses, wheezing, and asthma. J Virol. 2010;84(15):7418–26. doi:.https://doi.org/10.1128/JVI.02290-09
  35. Greve JM, Davis G, Meyer AM, Forte CP, Yost SC, Marlor CW, et al. The major human rhinovirus receptor is ICAM-1. Cell. 1989;56(5):839–47. doi:.https://doi.org/10.1016/0092-8674(89)90688-0
  36. Hofer F, Gruenberger M, Kowalski H, Machat H, Huettinger M, Kuechler E, et al. Members of the low density lipoprotein receptor family mediate cell entry of a minor-group common cold virus. Proc Natl Acad Sci USA. 1994;91(5):1839–42. doi:.https://doi.org/10.1073/pnas.91.5.1839
  37. Bønnelykke K, Sleiman P, Nielsen K, Kreiner-Møller E, Mercader JM, Belgrave D, et al. A genome-wide association study identifies CDHR3 as a susceptibility locus for early childhood asthma with severe exacerbations. Nat Genet. 2014;46(1):51–5. doi:.https://doi.org/10.1038/ng.2830
  38. Bochkov YA, Watters K, Ashraf S, Griggs TF, Devries MK, Jackson DJ, et al. Cadherin-related family member 3, a childhood asthma susceptibility gene product, mediates rhinovirus C binding and replication. Proc Natl Acad Sci USA. 2015;112(17):5485–90. doi:.https://doi.org/10.1073/pnas.1421178112
  39. Foxman EF, Storer JA, Fitzgerald ME, Wasik BR, Hou L, Zhao H, et al. Temperature-dependent innate defense against the common cold virus limits viral replication at warm temperature in mouse airway cells. Proc Natl Acad Sci USA. 2015;112(3):827–32. doi:.https://doi.org/10.1073/pnas.1411030112
  40. Mihaylova VT, Kong Y, Fedorova O, Sharma L, Dela Cruz CS, Pyle AM, et al. Regional differences in airway epithelial cells reveal tradeoff between defense against oxidative stress and defense against Rhinovirus. Cell Rep. 2018;24(11):3000–3007.e3. doi:.https://doi.org/10.1016/j.celrep.2018.08.033
  41. Warner JO, Boner A. Paediatric allergy and asthma. Vol. Chapter 18. 2012: Elsevier Ltd.
  42. Bergeron C, Tulic MK, Hamid Q. Airway remodelling in asthma: from benchside to clinical practice. Can Respir J. 2010;17(4):e85–93. doi:.https://doi.org/10.1155/2010/318029
  43. Jamieson KC, Warner SM, Leigh R, Proud D. Rhinovirus in the Pathogenesis and Clinical Course of Asthma. Chest. 2015;148(6):1508–16. doi:.https://doi.org/10.1378/chest.15-1335
  44. Ordoñez CL, Khashayar R, Wong HH, Ferrando R, Wu R, Hyde DM, et al. Mild and moderate asthma is associated with airway goblet cell hyperplasia and abnormalities in mucin gene expression. Am J Respir Crit Care Med. 2001;163(2):517–23. doi:.https://doi.org/10.1164/ajrccm.163.2.2004039
  45. Van Bruaene N, Bachert C. Tissue remodeling in chronic rhinosinusitis. Curr Opin Allergy Clin Immunol. 2011;11(1):8–11. doi:.https://doi.org/10.1097/ACI.0b013e32834233ef
  46. Cho GS, Moon BJ, Lee BJ, Gong CH, Kim NH, Kim YS, et al. High rates of detection of respiratory viruses in the nasal washes and mucosae of patients with chronic rhinosinusitis. J Clin Microbiol. 2013;51(3):979–84. doi:.https://doi.org/10.1128/JCM.02806-12
  47. Saitoh T, Kusunoli T, Yao T, Kawano K, Kojima Y, Miyahara K, et al. Relationship between epithelial damage or basement membrane thickness and eosinophilic infiltration in nasal polyps with chronic rhinosinusitis. Rhinology. 2009;47(3):275–9. doi:.https://doi.org/10.4193/Rhin08.109
  48. Snidvongs K, Chin D, Sacks R, Earls P, Harvey RJ. Eosinophilic rhinosinusitis is not a disease of ostiomeatal occlusion. Laryngoscope. 2013;123(5):1070–4. doi:.https://doi.org/10.1002/lary.23721
  49. Snidvongs K, Lam M, Sacks R, Earls P, Kalish L, Phillips PS, et al. Structured histopathology profiling of chronic rhinosinusitis in routine practice. Int Forum Allergy Rhinol. 2012;2(5):376–85. doi:.https://doi.org/10.1002/alr.21032
  50. Murdoch JR, Lloyd CM. Chronic inflammation and asthma. Mutat Res. 2010;690(1-2):24–39. doi:.https://doi.org/10.1016/j.mrfmmm.2009.09.005
  51. Holtzman MJ. Asthma as a chronic disease of the innate and adaptive immune systems responding to viruses and allergens. J Clin Invest. 2012;122(8):2741–8. doi:.https://doi.org/10.1172/JCI60325
  52. Medzhitov R, Janeway C, Jr. Innate immunity. N Engl J Med. 2000;343(5):338–44. doi:.https://doi.org/10.1056/NEJM200008033430506
  53. McKenzie EJ, Taylor PR, Stillion RJ, Lucas AD, Harris J, Gordon S, et al. Mannose receptor expression and function define a new population of murine dendritic cells. J Immunol. 2007;178(8):4975–83. doi:.https://doi.org/10.4049/jimmunol.178.8.4975
  54. Fraser IP, Koziel H, Ezekowitz RA. The serum mannose-binding protein and the macrophage mannose receptor are pattern recognition molecules that link innate and adaptive immunity. Semin Immunol. 1998;10(5):363–72. doi:.https://doi.org/10.1006/smim.1998.0141
  55. Takizawa R, Pawankar R, Yamagishi S, Takenaka H, Yagi T. Increased expression of HLA-DR and CD86 in nasal epithelial cells in allergic rhinitics: antigen presentation to T cells and up-regulation by diesel exhaust particles. Clin Exp Allergy. 2007;37(3):420–33. doi:.https://doi.org/10.1111/j.1365-2222.2007.02672.x
  56. Mukhopadhyay S, Malik P, Arora SK, Mukherjee TK. Intercellular adhesion molecule-1 as a drug target in asthma and rhinitis. Respirology. 2014;19(4):508–13. doi:.https://doi.org/10.1111/resp.12285
  57. Slater L, Bartlett NW, Haas JJ, Zhu J, Message SD, Walton RP, et al. Co-ordinated role of TLR3, RIG-I and MDA5 in the innate response to rhinovirus in bronchial epithelium. PLoS Pathog. 2010;6(11):e1001178. doi:.https://doi.org/10.1371/journal.ppat.1001178
  58. Laza-Stanca V, Stanciu LA, Message SD, Edwards MR, Gern JE, Johnston SL. Rhinovirus replication in human macrophages induces NF-kappaB-dependent tumor necrosis factor alpha production. J Virol. 2006;80(16):8248–58. doi:.https://doi.org/10.1128/JVI.00162-06
  59. Chang EH, Willis AL, McCrary HC, Noutsios GT, Le CH, Chiu AG, et al. Association between the CDHR3 rs6967330 risk allele and chronic rhinosinusitis. J Allergy Clin Immunol. 2017;139(6):1990–1992.e2. doi:.https://doi.org/10.1016/j.jaci.2016.10.027
  60. Kurt-Jones EA, Popova L, Kwinn L, Haynes LM, Jones LP, Tripp RA, et al. Pattern recognition receptors TLR4 and CD14 mediate response to respiratory syncytial virus. Nat Immunol. 2000;1(5):398–401. doi:.https://doi.org/10.1038/80833
  61. Johnson SM, McNally BA, Ioannidis I, Flano E, Teng MN, Oomens AG, et al. Respiratory syncytial virus uses CX3CR1 as a receptor on primary human airway epithelial cultures. PLoS Pathog. 2015;11(12):e1005318. doi:.https://doi.org/10.1371/journal.ppat.1005318
  62. Krusat T, Streckert HJ. Heparin-dependent attachment of respiratory syncytial virus (RSV) to host cells. Arch Virol. 1997;142(6):1247–54. doi:.https://doi.org/10.1007/s007050050156
  63. Gonzalez SF, Lukacs-Kornek V, Kuligowski MP, Pitcher LA, Degn SE, Kim YA, et al. Capture of influenza by medullary dendritic cells via SIGN-R1 is essential for humoral immunity in draining lymph nodes. Nat Immunol. 2010;11(5):427–34. doi:.https://doi.org/10.1038/ni.1856
  64. Londrigan SL, Turville SG, Tate MD, Deng YM, Brooks AG, Reading PC. N-linked glycosylation facilitates sialic acid-independent attachment and entry of influenza A viruses into cells expressing DC-SIGN or L-SIGN. J Virol. 2011;85(6):2990–3000. doi:.https://doi.org/10.1128/JVI.01705-10
  65. Wang SF, Huang JC, Lee YM, Liu SJ, Chan YJ, Chau YP, et al. DC-SIGN mediates avian H5N1 influenza virus infection in cis and in trans. Biochem Biophys Res Commun. 2008;373(4):561–6. doi:.https://doi.org/10.1016/j.bbrc.2008.06.078
  66. Upham JP, Pickett D, Irimura T, Anders EM, Reading PC. Macrophage receptors for influenza A virus: role of the macrophage galactose-type lectin and mannose receptor in viral entry. J Virol. 2010;84(8):3730–7. doi:.https://doi.org/10.1128/JVI.02148-09
  67. Eierhoff T, Hrincius ER, Rescher U, Ludwig S, Ehrhardt C. The epidermal growth factor receptor (EGFR) promotes uptake of influenza A viruses (IAV) into host cells. PLoS Pathog. 2010;6(9):e1001099. doi:.https://doi.org/10.1371/journal.ppat.1001099
  68. Ioannidis I, McNally B, Willette M, Peeples ME, Chaussabel D, Durbin JE, et al. Plasticity and virus specificity of the airway epithelial cell immune response during respiratory virus infection. J Virol. 2012;86(10):5422–36. doi:.https://doi.org/10.1128/JVI.06757-11
  69. Wang Q, Tian X, Chen X, Ma J. Structural basis for receptor specificity of influenza B virus hemagglutinin. Proc Natl Acad Sci USA. 2007;104(43):16874–9. doi:.https://doi.org/10.1073/pnas.0708363104
  70. Wang M, Veit M. Hemagglutinin-esterase-fusion (HEF) protein of influenza C virus. Protein Cell. 2016;7(1):28–45. doi:.https://doi.org/10.1007/s13238-015-0193-x
  71. Song H, Qi J, Khedri Z, Diaz S, Yu H, Chen X, et al. An open receptor-binding cavity of hemagglutinin-esterase-fusion glycoprotein from newly-identified influenza D virus: basis for its broad cell tropism. PLoS Pathog. 2016;12(1):e1005411. doi:.https://doi.org/10.1371/journal.ppat.1005411
  72. Takeuchi O, Hoshino K, Kawai T, Sanjo H, Takada H, Ogawa T, et al. Differential roles of TLR2 and TLR4 in recognition of gram-negative and gram-positive bacterial cell wall components. Immunity. 1999;11(4):443–51. doi:.https://doi.org/10.1016/S1074-7613(00)80119-3
  73. Zhang Z, Louboutin JP, Weiner DJ, Goldberg JB, Wilson JM. Human airway epithelial cells sense Pseudomonas aeruginosa infection via recognition of flagellin by Toll-like receptor 5. Infect Immun. 2005;73(11):7151–60. doi:.https://doi.org/10.1128/IAI.73.11.7151-7160.2005
  74. DiMango E, Ratner AJ, Bryan R, Tabibi S, Prince A. Activation of NF-kappaB by adherent Pseudomonas aeruginosa in normal and cystic fibrosis respiratory epithelial cells. J Clin Invest. 1998;101(11):2598–605. doi:.https://doi.org/10.1172/JCI2865
  75. Feldman M, Bryan R, Rajan S, Scheffler L, Brunnert S, Tang H, et al. Role of flagella in pathogenesis of Pseudomonas aeruginosa pulmonary infection. Infect Immun. 1998;66(1):43–51.
  76. Krivan HC, Roberts DD, Ginsburg V. Many pulmonary pathogenic bacteria bind specifically to the carbohydrate sequence GalNAc beta 1-4Gal found in some glycolipids. Proc Natl Acad Sci USA. 1988;85(16):6157–61. doi:.https://doi.org/10.1073/pnas.85.16.6157
  77. Gómez MI, Lee A, Reddy B, Muir A, Soong G, Pitt A, et al. Staphylococcus aureus protein A induces airway epithelial inflammatory responses by activating TNFR1. Nat Med. 2004;10(8):842–8. doi:.https://doi.org/10.1038/nm1079
  78. Gómez MI, Seaghdha MO, Prince AS. Staphylococcus aureus protein A activates TACE through EGFR-dependent signaling. EMBO J. 2007;26(3):701–9. doi:.https://doi.org/10.1038/sj.emboj.7601554
  79. Girardin SE, Boneca IG, Carneiro LA, Antignac A, Jéhanno M, Viala J, et al. Nod1 detects a unique muropeptide from gram-negative bacterial peptidoglycan. Science. 2003;300(5625):1584–7. doi:.https://doi.org/10.1126/science.1084677
  80. Girardin SE, Boneca IG, Viala J, Chamaillard M, Labigne A, Thomas G, et al. Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection. J Biol Chem. 2003;278(11):8869–72. doi:.https://doi.org/10.1074/jbc.C200651200
  81. Arebro J, Tengroth L, Razavi R, Kumlien Georén S, Winqvist O, Cardell LO. Antigen-presenting epithelial cells can play a pivotal role in airway allergy. J Allergy Clin Immunol. 2016;137(3):957–60.e7. doi:.https://doi.org/10.1016/j.jaci.2015.08.053
  82. Kalb TH, Chuang MT, Marom Z, Mayer L. Evidence for accessory cell function by class II MHC antigen-expressing airway epithelial cells. Am J Respir Cell Mol Biol. 1991;4(4):320–9. doi:.https://doi.org/10.1165/ajrcmb/4.4.320
  83. Zhu Z, Tang W, Gwaltney JM, Jr, Wu Y, Elias JA. Rhinovirus stimulation of interleukin-8 in vivo and in vitro: role of NF-kappaB. Am J Physiol. 1997;273(4):L814–24.
  84. Bossios A, Gourgiotis D, Skevaki CL, Saxoni-Papageorgiou P, Lötvall J, Psarras S, et al. Rhinovirus infection and house dust mite exposure synergize in inducing bronchial epithelial cell interleukin-8 release. Clin Exp Allergy. 2008;38(10):1615–26. doi:.https://doi.org/10.1111/j.1365-2222.2008.03058.x
  85. Donninger H, Glashoff R, Haitchi HM, Syce JA, Ghildyal R, van Rensburg E, et al. Rhinovirus induction of the CXC chemokine epithelial-neutrophil activating peptide-78 in bronchial epithelium. J Infect Dis. 2003;187(11):1809–17. doi:.https://doi.org/10.1086/375246
  86. Contoli M, Message SD, Laza-Stanca V, Edwards MR, Wark PA, Bartlett NW, et al. Role of deficient type III interferon-lambda production in asthma exacerbations. Nat Med. 2006;12(9):1023–6. doi:.https://doi.org/10.1038/nm1462
  87. Jackson DJ, Makrinioti H, Rana BM, Shamji BW, Trujillo-Torralbo MB, Footitt J, et al. IL-33-dependent type 2 inflammation during rhinovirus-induced asthma exacerbations in vivo. Am J Respir Crit Care Med. 2014;190(12):1373–82. doi:.https://doi.org/10.1164/rccm.201406-1039OC
  88. Gordon ED, Locksley RM, Fahy JV. Cross-talk between epithelial cells and type 2 immune signaling. The role of IL-25. Am J Respir Crit Care Med. 2016;193(9):935–6. doi:.https://doi.org/10.1164/rccm.201512-2534ED
  89. Iyer AS, Bhatt SP, Garner JJ, Wells JM, Trevor JL, Patel NM, et al. Depression is associated with readmission for acute exacerbation of chronic obstructive pulmonary disease. Ann Am Thorac Soc. 2016;13(2):197–203.
  90. Bedke N, Sammut D, Green B, Kehagia V, Dennison P, Jenkins G, et al. Transforming growth factor-beta promotes rhinovirus replication in bronchial epithelial cells by suppressing the innate immune response. PLoS One. 2012;7(9):e44580. doi:.https://doi.org/10.1371/journal.pone.0044580
  91. Denney L, Byrne AJ, Shea TJ, Buckley JS, Pease JE, Herledan GM, et al. Pulmonary epithelial cell-derived cytokine TGF-β1 is a critical cofactor for enhanced innate lymphoid cell function. Immunity. 2015;43(5):945–58. doi:.https://doi.org/10.1016/j.immuni.2015.10.012
  92. Strieter RM, Belperio JA, Keane MP. Cytokines in innate host defense in the lung. J Clin Invest. 2002;109(6):699–705. doi:.https://doi.org/10.1172/JCI0215277
  93. Coulter KR, Wewers MD, Lowe MP, Knoell DL. Extracellular regulation of interleukin (IL)-1beta through lung epithelial cells and defective IL-1 type II receptor expression. Am J Respir Cell Mol Biol. 1999;20(5):964–75. doi:.https://doi.org/10.1165/ajrcmb.20.5.3458
  94. Saba S, Soong G, Greenberg S, Prince A. Bacterial stimulation of epithelial G-CSF and GM-CSF expression promotes PMN survival in CF airways. Am J Respir Cell Mol Biol. 2002;27(5):561–7. doi:.https://doi.org/10.1165/rcmb.2002-0019OC
  95. Kumar RK, Herbert C, Foster PS. Expression of growth factors by airway epithelial cells in a model of chronic asthma: regulation and relationship to subepithelial fibrosis. Clin Exp Allergy. 2004;34(4):567–75. doi:.https://doi.org/10.1111/j.1365-2222.2004.1917.x
  96. Rao SP, Hayashi T, Catanzaro A. Release of monocyte chemoattractant protein (MCP)-1 by a human alveolar epithelial cell line in response to mycobacterium avium. FEMS Immunol Med Microbiol. 2000;29(1):1–7. doi:.https://doi.org/10.1111/j.1574-695X.2000.tb01497.x
  97. Gómez MI, Sokol SH, Muir AB, Soong G, Bastien J, Prince AS. Bacterial induction of TNF-alpha converting enzyme expression and IL-6 receptor alpha shedding regulates airway inflammatory signaling. J Immunol. 2005;175(3):1930–6. doi:.https://doi.org/10.4049/jimmunol.175.3.1930
  98. Leidal KG, Munson KL, Denning GM. Small molecular weight secretory factors from Pseudomonas aeruginosa have opposite effects on IL-8 and RANTES expression by human airway epithelial cells. Am J Respir Cell Mol Biol. 2001;25(2):186–95. doi:.https://doi.org/10.1165/ajrcmb.25.2.4273
  99. Parker D, Prince A. Type I interferon response to extracellular bacteria in the airway epithelium. Trends Immunol. 2011;32(12):582–8. doi:.https://doi.org/10.1016/j.it.2011.09.003
  100. Sachse F, von Eiff C, Stoll W, Becker K, Rudack C. Induction of CXC chemokines in A549 airway epithelial cells by trypsin and staphylococcal proteases - a possible route for neutrophilic inflammation in chronic rhinosinusitis. Clin Exp Immunol. 2006;144(3):534–42. doi:.https://doi.org/10.1111/j.1365-2249.2006.03089.x
  101. Noutsios GT, Willis AL, Ledford JG, Chang EH. Novel role of surfactant protein A in bacterial sinusitis. Int Forum Allergy Rhinol. 2017;7(9):897–903. doi:.https://doi.org/10.1002/alr.21985
  102. Ferguson JS, Voelker DR, Ufnar JA, Dawson AJ, Schlesinger LS. Surfactant protein D inhibition of human macrophage uptake of Mycobacterium tuberculosis is independent of bacterial agglutination. J Immunol. 2002;168(3):1309–14. doi:.https://doi.org/10.4049/jimmunol.168.3.1309
  103. Sever-Chroneos Z, Krupa A, Davis J, Hasan M, Yang CH, Szeliga J, et al. Surfactant protein A (SP-A)-mediated clearance of Staphylococcus aureus involves binding of SP-A to the staphylococcal adhesin eap and the macrophage receptors SP-A receptor 210 and scavenger receptor class A. J Biol Chem. 2011;286(6):4854–70. doi:.https://doi.org/10.1074/jbc.M110.125567
  104. Bals R, Weiner DJ, Moscioni AD, Meegalla RL, Wilson JM. Augmentation of innate host defense by expression of a cathelicidin antimicrobial peptide. Infect Immun. 1999;67(11):6084–9.
  105. van Wetering S, Sterk PJ, Rabe KF, Hiemstra PS. Defensins: key players or bystanders in infection, injury, and repair in the lung? J Allergy Clin Immunol. 1999;104(6):1131–8. doi:.https://doi.org/10.1016/S0091-6749(99)70004-7
  106. Kim KC. Role of epithelial mucins during airway infection. Pulm Pharmacol Ther. 2012;25(6):415–9. doi:.https://doi.org/10.1016/j.pupt.2011.12.003
  107. Ganz T. Antimicrobial polypeptides in host defense of the respiratory tract. J Clin Invest. 2002;109(6):693–7. doi:.https://doi.org/10.1172/JCI0215218
  108. van der Strate BW, Beljaars L, Molema G, Harmsen MC, Meijer DK. Antiviral activities of lactoferrin. Antiviral Res. 2001;52(3):225–39. doi:.https://doi.org/10.1016/S0166-3542(01)00195-4
  109. Wilson SS, Wiens ME, Smith JG. Antiviral mechanisms of human defensins. J Mol Biol. 2013;425(24):4965–80. doi:.https://doi.org/10.1016/j.jmb.2013.09.038
  110. Wilson SS, Wiens ME, Holly MK, Smith JG. Defensins at the Mucosal Surface: Latest Insights into Defensin-Virus Interactions. J Virol. 2016;90(11):5216–8. doi:.https://doi.org/10.1128/JVI.00904-15
  111. Grandvaux N, tenOever BR, Servant MJ, Hiscott J. The interferon antiviral response: from viral invasion to evasion. Curr Opin Infect Dis. 2002;15(3):259–67. doi:.https://doi.org/10.1097/00001432-200206000-00008
  112. Curran DR, Cohn L. Advances in mucous cell metaplasia: a plug for mucus as a therapeutic focus in chronic airway disease. Am J Respir Cell Mol Biol. 2010;42(3):268–75. doi:.https://doi.org/10.1165/rcmb.2009-0151TR
  113. Kuo C, Lim S, King NJ, Johnston SL, Burgess JK, Black JL, et al. Rhinovirus infection induces extracellular matrix protein deposition in asthmatic and nonasthmatic airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 2011;300(6):L951–7. doi:.https://doi.org/10.1152/ajplung.00411.2010
  114. Ganesan S, Comstock AT, Sajjan US. Barrier function of airway tract epithelium. Tissue Barriers. 2013;1(4):e24997. doi:.https://doi.org/10.4161/tisb.24997
  115. Hogan BL, Barkauskas CE, Chapman HA, Epstein JA, Jain R, Hsia CC, et al. Repair and regeneration of the respiratory system: complexity, plasticity, and mechanisms of lung stem cell function. Cell Stem Cell. 2014;15(2):123–38. doi:.https://doi.org/10.1016/j.stem.2014.07.012
  116. Wilson JW, Li X. The measurement of reticular basement membrane and submucosal collagen in the asthmatic airway. Clin Exp Allergy. 1997;27(4):363–71. doi:.https://doi.org/10.1111/j.1365-2222.1997.tb00720.x
  117. McGrath JJC, Stampfli MR. The immune system as a victim and aggressor in chronic obstructive pulmonary disease. J Thorac Dis. 2018;10(S16, Suppl 17):S2011–7. doi:.https://doi.org/10.21037/jtd.2018.05.63
  118. Drake MG, Bivins-Smith ER, Proskocil BJ, Nie Z, Scott GD, Lee JJ, et al. Human and mouse eosinophils have antiviral activity against parainfluenza virus. Am J Respir Cell Mol Biol. 2016;55(3):387–94. doi:.https://doi.org/10.1165/rcmb.2015-0405OC
  119. Tang FS, Van Ly D, Spann K, Reading PC, Burgess JK, Hartl D, et al. Differential neutrophil activation in viral infections: Enhanced TLR-7/8-mediated CXCL8 release in asthma. Respirology. 2016;21(1):172–9. doi:.https://doi.org/10.1111/resp.12657
  120. De Grove KC, Provoost S, Verhamme FM, Bracke KR, Joos GF, Maes T, et al. Characterization and quantification of innate lymphoid cell subsets in human lung. PLoS One. 2016;11(1):e0145961. doi:.https://doi.org/10.1371/journal.pone.0145961
  121. Jäkel A, Clark H, Reid KB, Sim RB. The human lung surfactant proteins A (SP-A) and D (SP-D) interact with apoptotic target cells by different binding mechanisms. Immunobiology. 2010;215(7):551–8. doi:.https://doi.org/10.1016/j.imbio.2009.09.005
  122. Floros J, Phelps DS. Pulmonary surfactant protein A; structure, expression, and its role in innate host defense, in Surfactant-Update of Intensive Care Medicine, G. Nakos and M.E. Lekka, Editors. 2002, University of Ioannina: Ioannina, Greece. p. 87-102.
  123. Floros J, Phelps DS. Pulmonary surfactant, in Anesthesia: Biologic Foundations, J. Biebuck, et al., Editors. 1997, Lippincott-Raven. p. 1259-1279.
  124. Phelps DS. Surfactant regulation of host defense function in the lung: a question of balance. Pediatr Pathol Mol Med. 2001;20(4):269–92. doi:.https://doi.org/10.1080/15513810109168822
  125. LeVine AM, Gwozdz J, Stark J, Bruno M, Whitsett J, Korfhagen T. Surfactant protein-A enhances respiratory syncytial virus clearance in vivo. J Clin Invest. 1999;103(7):1015–21. doi:.https://doi.org/10.1172/JCI5849
  126. LeVine AM, Whitsett JA, Hartshorn KL, Crouch EC, Korfhagen TR. Surfactant protein D enhances clearance of influenza A virus from the lung in vivo. J Immunol. 2001;167(10):5868–73. doi:.https://doi.org/10.4049/jimmunol.167.10.5868
  127. Woodworth BA, Lathers D, Neal JG, Skinner M, Richardson M, Young MR, et al. Immunolocalization of surfactant protein A and D in sinonasal mucosa. Am J Rhinol. 2006;20(4):461–5. doi:.https://doi.org/10.2500/ajr.2006.20.2892
  128. Lee HM, Kang HJ, Woo JS, Chae SW, Lee SH, Hwang SJ. Upregulation of surfactant protein A in chronic rhinosinusitis. Laryngoscope. 2006;116(2):328–30. doi:.https://doi.org/10.1097/01.mlg.0000194223.22763.5f
  129. Ooi EH, Wormald PJ, Carney AS, James CL, Tan LW. Surfactant protein d expression in chronic rhinosinusitis patients and immune responses in vitro to Aspergillus and alternaria in a nasal explant model. Laryngoscope. 2007;117(1):51–7. doi:.https://doi.org/10.1097/01.mlg.0000243196.75418.6f
  130. Ooi EH, Wormald PJ, Tan LW. Innate immunity in the paranasal sinuses: a review of nasal host defenses. Am J Rhinol. 2008;22(1):13–9. doi:.https://doi.org/10.2500/ajr.2008.22.3127
  131. Madan T, Kishore U, Singh M, Strong P, Clark H, Hussain EM, et al. Surfactant proteins A and D protect mice against pulmonary hypersensitivity induced by Aspergillus fumigatus antigens and allergens. J Clin Invest. 2001;107(4):467–75. doi:.https://doi.org/10.1172/JCI10124
  132. Brinker KG, Garner H, Wright JR. Surfactant protein A modulates the differentiation of murine bone marrow-derived dendritic cells. Am J Physiol Lung Cell Mol Physiol. 2003;284(1):L232–41. doi:.https://doi.org/10.1152/ajplung.00187.2002
  133. Brinker KG, Martin E, Borron P, Mostaghel E, Doyle C, Harding CV, et al. Surfactant protein D enhances bacterial antigen presentation by bone marrow-derived dendritic cells. Am J Physiol Lung Cell Mol Physiol. 2001;281(6):L1453–63. doi:.https://doi.org/10.1152/ajplung.2001.281.6.L1453
  134. Wang JY, Shieh CC, You PF, Lei HY, Reid KB. Inhibitory effect of pulmonary surfactant proteins A and D on allergen-induced lymphocyte proliferation and histamine release in children with asthma. Am J Respir Crit Care Med. 1998;158(2):510–8. doi:.https://doi.org/10.1164/ajrccm.158.2.9709111
  135. Borron PJ, Mostaghel EA, Doyle C, Walsh ES, McHeyzer-Williams MG, Wright JR. Pulmonary surfactant proteins A and D directly suppress CD3+/CD4+ cell function: evidence for two shared mechanisms. J Immunol. 2002;169(10):5844–50. doi:.https://doi.org/10.4049/jimmunol.169.10.5844
  136. Phelps DS, Umstead TM, Quintero OA, Yengo CM, Floros J. In vivo rescue of alveolar macrophages from SP-A knockout mice with exogenous SP-A nearly restores a wild type intracellular proteome; actin involvement. Proteome Sci. 2011;9(1):67. doi:.https://doi.org/10.1186/1477-5956-9-67
  137. Crouch E, Wright JR. Surfactant proteins a and d and pulmonary host defense. Annu Rev Physiol. 2001;63(1):521–54. doi:.https://doi.org/10.1146/annurev.physiol.63.1.521