1932

Abstract

Club cell secretory protein (CCSP), also known as secretoglobin 1A1 (gene name ), is one of the most abundant proteins in the lung, primarily produced by club cells of the distal airway epithelium. At baseline, CCSP is found in large concentrations in lung fluid specimens and can also be detected in the blood and urine. Obstructive lung diseases are generally associated with reduced CCSP levels, thought to be due to decreased CCSP production or club cell depletion. Conversely, several restrictive lung diseases have been found to have increased CCSP levels both in the lung and in the circulation, likely related to club cell dysregulation as well as increasedlung permeability. Recent studies demonstrate multiple mechanisms by which CCSP dampens acute and chronic lung inflammation. Given these anti-inflammatory effects, CCSP represents a novel potential therapeutic modality in lung disease.

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2023-01-27
2024-12-14
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Literature Cited

  1. 1.
    Klug J, Beier HM, Bernard A et al. 2000. Uteroglobin/Clara cell 10-kDa family of proteins: nomenclature committee report. Ann. N. Y. Acad. Sci. 923:348–54
    [Google Scholar]
  2. 2.
    Liu Z, Kim J, Sypek JP et al. 2004. Gene expression profiles in human nasal polyp tissues studied by means of DNA microarray. J. Allergy Clin. Immunol. 114:783–90
    [Google Scholar]
  3. 3.
    Basil MC, Cardenas-Diaz FL, Kathiriya JJ et al. 2022. Human distal airways contain a multipotent secretory cell that can regenerate alveoli. Nature 604:120–26
    [Google Scholar]
  4. 4.
    Montoro DT, Haber AL, Biton M et al. 2018. A revised airway epithelial hierarchy includes CFTR-expressing ionocytes. Nature 560:319–24
    [Google Scholar]
  5. 5.
    Berg T, Cassel TN, Schwarze PE, Nord M. 2002. Glucocorticoids regulate the CCSP and CYP2B1 promoters via C/EBPβ and δ in lung cells. Biochem. Biophys. Res. Commun. 293:907–12
    [Google Scholar]
  6. 6.
    Chen Y, Vasquez MM, Zhu L et al. 2017. Effects of retinoids on augmentation of club cell secretory protein. Am. J. Respir. Crit. Care Med. 196:928–31
    [Google Scholar]
  7. 7.
    Sawaya PL, Stripp BR, Whitsett JA, Luse DS. 1993. The lung-specific CC10 gene is regulated by transcription factors from the AP-1, octamer, and hepatocyte nuclear factor 3 families. Mol. Cell Biol. 13:3860–71
    [Google Scholar]
  8. 8.
    Zhu L, An L, Ran D et al. 2019. The club cell marker SCGB1A1 downstream of FOXA2 is reduced in asthma. Am. J. Respir. Cell Mol. Biol. 60:695–704
    [Google Scholar]
  9. 9.
    Peri A, Cordella-Miele E, Miele L, Mukherjee AB. 1993. Tissue-specific expression of the gene coding for human Clara cell 10-kD protein, a phospholipase A2-inhibitory protein. J. Clin. Investig. 92:2099–109
    [Google Scholar]
  10. 10.
    Jackson PJ, Turner R, Keen JN et al. 1988. Purification and partial amino acid sequence of human urine protein 1. Evidence for homology with rabbit uteroglobin. J. Chromatogr. 452:359–67
    [Google Scholar]
  11. 11.
    Uhlen M, Fagerberg L, Hallstrom BM et al. 2015. Proteomics. Tissue-based map of the human proteome. Science 347:1260419
    [Google Scholar]
  12. 12.
    Bustos ML, Mura M, Hwang D et al. 2015. Depletion of bone marrow CCSP-expressing cells delays airway regeneration. Mol. Ther. 23:561–69
    [Google Scholar]
  13. 13.
    Zissler UM, Jakwerth CA, Guerth F et al. 2021. Allergen-specific immunotherapy induces the suppressive secretoglobin 1A1 in cells of the lower airways. Allergy 76:2461–74
    [Google Scholar]
  14. 14.
    Wang SZ, Rosenberger CL, Bao YX et al. 2003. Clara cell secretory protein modulates lung inflammatory and immune responses to respiratory syncytial virus infection. J. Immunol. 171:1051–60
    [Google Scholar]
  15. 15.
    Harrod KS, Mounday AD, Stripp BR, Whitsett JA. 1998. Clara cell secretory protein decreases lung inflammation after acute virus infection. Am. J. Physiol. 275:L924–30
    [Google Scholar]
  16. 16.
    Xu B, Janicova A, Vollrath JT et al. 2019. Club cell protein 16 in sera from trauma patients modulates neutrophil migration and functionality via CXCR1 and CXCR2. Mol. Med. 25:45
    [Google Scholar]
  17. 17.
    Knabe L, Petit A, Vernisse C et al. 2019. CCSP counterbalances airway epithelial-driven neutrophilic chemotaxis. Eur. Respir. J. 54:1802408
    [Google Scholar]
  18. 18.
    Johnson MDL, Younis US, Menghani SV et al. 2021. CC16 Binding to α4β1 integrin protects against Mycoplasma pneumoniae infection. Am. J. Respir. Crit. Care Med. 203:1410–18
    [Google Scholar]
  19. 19.
    Andersson O, Nordlund-Moller L, Barnes HJ, Lund J. 1994. Heterologous expression of human uteroglobin/polychlorinated biphenyl-binding protein. Determination of ligand binding parameters and mechanism of phospholipase A2 inhibition in vitro. J. Biol. Chem. 269:19081–87
    [Google Scholar]
  20. 20.
    Dudek SM, Munoz NM, Desai A et al. 2011. Group V phospholipase A2 mediates barrier disruption of human pulmonary endothelial cells caused by LPS in vitro. Am. J. Respir. Cell Mol. Biol. 44:361–68
    [Google Scholar]
  21. 21.
    Yoshikawa S, Miyahara T, Reynolds SD et al. 2005. Clara cell secretory protein and phospholipase A2 activity modulate acute ventilator-induced lung injury in mice. J. Appl. Physiol. 1985 98:1264–71
    [Google Scholar]
  22. 22.
    Kropski JA, Fremont RD, Calfee CS, Ware LB. 2009. Clara cell protein (CC16), a marker of lung epithelial injury, is decreased in plasma and pulmonary edema fluid from patients with acute lung injury. Chest 135:1440–47
    [Google Scholar]
  23. 23.
    Nakos G, Kitsiouli E, Hatzidaki E et al. 2005. Phospholipases A2 and platelet-activating-factor acetylhydrolase in patients with acute respiratory distress syndrome. Crit. Care Med. 33:772–79
    [Google Scholar]
  24. 24.
    Liu Y, Lu X, Yu HJ et al. 2010. The expression of osteopontin and its association with Clara cell 10 kDa protein in allergic rhinitis. Clin. Exp. Allergy 40:1632–41
    [Google Scholar]
  25. 25.
    Benson M, Jansson L, Adner M et al. 2005. Gene profiling reveals decreased expression of uteroglobin and other anti-inflammatory genes in nasal fluid cells from patients with intermittent allergic rhinitis. Clin. Exp. Allergy 35:473–78
    [Google Scholar]
  26. 26.
    Wang H, Long XB, Cao PP et al. 2010. Clara cell 10-kD protein suppresses chitinase 3-like 1 expression associated with eosinophilic chronic rhinosinusitis. Am. J. Respir. Crit. Care Med. 181:908–16
    [Google Scholar]
  27. 27.
    Liu Y, Yu HJ, Wang N et al. 2013. Clara cell 10-kDa protein inhibits TH17 responses through modulating dendritic cells in the setting of allergic rhinitis. J. Allergy Clin. Immunol. 131:387–94.e12
    [Google Scholar]
  28. 28.
    Zheng F, Kundu GC, Zhang Z et al. 1999. Uteroglobin is essential in preventing immunoglobulin A nephropathy in mice. Nat. Med. 5:1018–25
    [Google Scholar]
  29. 29.
    Milne S, Li X, Hernandez Cordero AI et al. 2020. Protective effect of club cell secretory protein (CC-16) on COPD risk and progression: a Mendelian randomisation study. Thorax 75:934–43
    [Google Scholar]
  30. 30.
    Kim DK, Cho MH, Hersh CP et al. 2012. Genome-wide association analysis of blood biomarkers in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 186:1238–47
    [Google Scholar]
  31. 31.
    Zhai J, Emond MJ, Spangenberg A et al. 2022. Club cell secretory protein and lung function in children with cystic fibrosis. J. Cyst. Fibros 21:81120
    [Google Scholar]
  32. 32.
    Zhai J, Stern DA, Sherrill DL et al. 2018. Trajectories and early determinants of circulating CC16 from birth to age 32 years. Am. J. Respir. Crit. Care Med. 198:267–70
    [Google Scholar]
  33. 33.
    Hermans C, Dong P, Robin M et al. 2003. Determinants of serum levels of surfactant proteins A and B and Clara cell protein CC16. Biomarkers 8:461–71
    [Google Scholar]
  34. 34.
    Robin M, Dong P, Hermans C et al. 2002. Serum levels of CC16, SP-A and SP-B reflect tobacco-smoke exposure in asymptomatic subjects. Eur. Respir. J. 20:1152–61
    [Google Scholar]
  35. 35.
    Beamer PI, Furlong M, Lothrop N et al. 2019. CC16 Levels into adult life are associated with nitrogen dioxide exposure at birth. Am. J. Respir. Crit. Care Med. 200:600–7
    [Google Scholar]
  36. 36.
    Bernard A, Sardella A, Voisin C, Dumont X. 2017. Nasal epithelium injury by chlorination products and other stressors predicts persistent sensitization to aeroallergens in young schoolchildren. Environ. Res. 158:145–52
    [Google Scholar]
  37. 37.
    Ge XN, Chu HW, Minor MN et al. 2009. Roflumilast increases Clara cell secretory protein in cigarette smoke-exposed mice. COPD 6:185–91
    [Google Scholar]
  38. 38.
    Shiyu S, Zhiyu L, Mao Y et al. 2011. Polydatin up-regulates Clara cell secretory protein to suppress phospholipase A2 of lung induced by LPS in vivo and in vitro. BMC Cell Biol 12:31
    [Google Scholar]
  39. 39.
    Rava M, Tares L, Lavi I et al. 2013. Serum levels of Clara cell secretory protein, asthma, and lung function in the adult general population. J. Allergy Clin. Immunol. 132:230–32
    [Google Scholar]
  40. 40.
    Guerra S, Halonen M, Vasquez MM et al. 2015. Relation between circulating CC16 concentrations, lung function, and development of chronic obstructive pulmonary disease across the lifespan: a prospective study. Lancet Respir. Med. 3:613–20
    [Google Scholar]
  41. 41.
    Zhai J, Insel M, Addison KJ et al. 2019. Club cell secretory protein deficiency leads to altered lung function. Am. J. Respir. Crit. Care Med. 199:302–12
    [Google Scholar]
  42. 42.
    Lomas DA, Silverman EK, Edwards LD et al. 2008. Evaluation of serum CC-16 as a biomarker for COPD in the ECLIPSE cohort. Thorax 63:1058–63
    [Google Scholar]
  43. 43.
    Pilette C, Godding V, Kiss R et al. 2001. Reduced epithelial expression of secretory component in small airways correlates with airflow obstruction in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 163:185–94
    [Google Scholar]
  44. 44.
    Braido F, Riccio AM, Guerra L et al. 2007. Clara cell 16 protein in COPD sputum: a marker of small airways damage?. Respir. Med. 101:2119–24
    [Google Scholar]
  45. 45.
    Laucho-Contreras ME, Polverino F, Gupta K et al. 2015. Protective role for club cell secretory protein-16 (CC16) in the development of COPD. Eur. Respir. J. 45:1544–56
    [Google Scholar]
  46. 46.
    Lange P, Celli B, Agusti A et al. 2015. Lung-function trajectories leading to chronic obstructive pulmonary disease. N. Engl. J. Med. 373:111–22
    [Google Scholar]
  47. 47.
    Vestbo J, Edwards LD, Scanlon PD et al. 2011. Changes in forced expiratory volume in 1 second over time in COPD. N. Engl. J. Med. 365:1184–92
    [Google Scholar]
  48. 48.
    Petersen H, Leng S, Belinsky SA et al. 2015. Low plasma CC16 levels in smokers are associated with a higher risk for chronic bronchitis. Eur. Respir. J. 46:1501–3
    [Google Scholar]
  49. 49.
    Laing IA, Hermans C, Bernard A et al. 2000. Association between plasma CC16 levels, the A38G polymorphism, and asthma. Am. J. Respir. Crit. Care Med. 161:124–27
    [Google Scholar]
  50. 50.
    Shijubo N, Itoh Y, Yamaguchi T et al. 1999. Serum levels of Clara cell 10-kDa protein are decreased in patients with asthma. Lung 177:45–52
    [Google Scholar]
  51. 51.
    Guerra S, Vasquez MM, Spangenberg A et al. 2016. Club cell secretory protein in serum and bronchoalveolar lavage of patients with asthma. J. Allergy Clin. Immunol. 138:932–34.e1
    [Google Scholar]
  52. 52.
    Shijubo N, Itoh Y, Yamaguchi T et al. 1999. Clara cell protein-positive epithelial cells are reduced in small airways of asthmatics. Am. J. Respir. Crit. Care Med. 160:930–33
    [Google Scholar]
  53. 53.
    Gray RD, MacGregor G, Noble D et al. 2008. Sputum proteomics in inflammatory and suppurative respiratory diseases. Am. J. Respir. Crit. Care Med. 178:444–52
    [Google Scholar]
  54. 54.
    Starosta V, Ratjen F, Rietschel E et al. 2006. Anti-inflammatory cytokines in cystic fibrosis lung disease. Eur. Respir. J. 28:581–87
    [Google Scholar]
  55. 55.
    Laguna TA, Williams CB, Brandy KR et al. 2015. Sputum club cell protein concentration is associated with pulmonary exacerbation in cystic fibrosis. J. Cyst. Fibros. 14:334–40
    [Google Scholar]
  56. 56.
    Buendia-Roldan I, Ruiz V, Sierra P et al. 2016. Increased expression of CC16 in patients with idiopathic pulmonary fibrosis. PLOS ONE 11:e0168552
    [Google Scholar]
  57. 57.
    Tian Y, Li H, Gao Y et al. 2019. Quantitative proteomic characterization of lung tissue in idiopathic pulmonary fibrosis. Clin. Proteom. 16:6
    [Google Scholar]
  58. 58.
    Kumar A, Elko E, Bruno SR et al. 2022. Inhibition of PDIA3 in club cells attenuates osteopontin production and lung fibrosis. Thorax 77:669–78
    [Google Scholar]
  59. 59.
    Ye Q, Fujita M, Ouchi H et al. 2004. Serum CC-10 in inflammatory lung diseases. Respir. Int. Rev. Thorac. Dis. 71:505–10
    [Google Scholar]
  60. 60.
    Kokuho N, Ishii T, Kamio K et al. 2015. Diagnostic values for club cell secretory protein (CC16) in serum of patients of combined pulmonary fibrosis and emphysema. COPD 12:347–54
    [Google Scholar]
  61. 61.
    Fukumoto J, Leung J, Cox R et al. 2019. Oxidative stress induces club cell proliferation and pulmonary fibrosis in Atp8b1 mutant mice. Aging 11:209–29
    [Google Scholar]
  62. 62.
    Habermann AC, Gutierrez AJ, Bui LT et al. 2020. Single-cell RNA sequencing reveals profibrotic roles of distinct epithelial and mesenchymal lineages in pulmonary fibrosis. Sci. Adv. 6:eaba1972
    [Google Scholar]
  63. 63.
    Olewicz-Gawlik A, Trzybulska D, Kuznar-Kaminska B et al. 2016. Serum Clara cell 16-kDa protein levels and lung impairment in systemic sclerosis patients. Rev. Bras. Reumatol. (Engl. Ed.) 56:309–13
    [Google Scholar]
  64. 64.
    Riviere S, Hua-Huy T, Tiev KP et al. 2018. High baseline serum Clara cell 16 kDa predicts subsequent lung disease worsening in systemic sclerosis. J. Rheumatol. 45:242–47
    [Google Scholar]
  65. 65.
    Janssen R, Sato H, Grutters JC et al. 2003. Study of Clara cell 16, KL-6, and surfactant protein-D in serum as disease markers in pulmonary sarcoidosis. Chest 124:2119–25
    [Google Scholar]
  66. 66.
    Hermans C, Petrek M, Kolek V et al. 2001. Serum Clara cell protein (CC16), a marker of the integrity of the air-blood barrier in sarcoidosis. Eur. Respir. J. 18:507–14
    [Google Scholar]
  67. 67.
    Zhang S, Jia Q, Song J et al. 2020. Clinical significance of CC16 and IL-12 in bronchoalveolar lavage fluid of various stages of silicosis. Ann. Palliat. Med. 9:3848–56
    [Google Scholar]
  68. 68.
    Thongtip S, Siviroj P, Prapamontol T et al. 2020. A suitable biomarker of effect, club cell protein 16, from crystalline silica exposure among Thai stone-carving workers. Toxicol. Ind. Health 36:287–96
    [Google Scholar]
  69. 69.
    Lesur O, Bernard A, Arsalane K et al. 1995. Clara cell protein (CC-16) induces a phospholipase A2-mediated inhibition of fibroblast migration in vitro. Am. J. Respir. Crit. Care Med. 152:290–97
    [Google Scholar]
  70. 70.
    Lin J, Zhang W, Wang L, Tian F 2018. Diagnostic and prognostic values of Club cell protein 16 (CC16) in critical care patients with acute respiratory distress syndrome. J. Clin. Lab. Anal. 32:e22262
    [Google Scholar]
  71. 71.
    Tiezzi M, Morra S, Seminerio J et al. 2021. SP-D and CC-16 pneumoproteins’ kinetics and their predictive role during SARS-CoV-2 infection. Front. Med. 8:761299
    [Google Scholar]
  72. 72.
    Rallis D, Baltogianni M, Dermitzaki N et al. 2022. Clara cell protein expression amongst infants with respiratory distress syndrome. Pediatr. Pulmonol. 57:1543–46
    [Google Scholar]
  73. 73.
    Verleden GM, Glanville AR, Lease ED et al. 2019. Chronic lung allograft dysfunction: definition, diagnostic criteria, and approaches to treatment—a consensus report from the Pulmonary Council of the ISHLT. J. Heart Lung. Transpl. 38:493–503
    [Google Scholar]
  74. 74.
    Nord M, Schubert K, Cassel TN et al. 2002. Decreased serum and bronchoalveolar lavage levels of Clara cell secretory protein (CC16) is associated with bronchiolitis obliterans syndrome and airway neutrophilia in lung transplant recipients. Transplantation 73:1264–69
    [Google Scholar]
  75. 75.
    Kelly FL, Kennedy VE, Jain R et al. 2012. Epithelial Clara cell injury occurs in bronchiolitis obliterans syndrome after human lung transplantation. Am. J. Transpl. 12:3076–84
    [Google Scholar]
  76. 76.
    Itabashi Y, Ravichandran R, Bansal S et al. 2021. Decline in club cell secretory proteins, exosomes induction and immune responses to lung self-antigens, Kα1 tubulin and collagen V, leading to chronic rejection after human lung transplantation. Transplantation 105:1337–46
    [Google Scholar]
  77. 77.
    Paantjens AW, Otten HG, van Ginkel WG et al. 2010. Clara cell secretory protein and surfactant protein-D do not predict bronchiolitis obliterans syndrome after lung transplantation. Transplantation 90:340–42
    [Google Scholar]
  78. 78.
    Liu Z, Liao F, Scozzi D et al. 2019. An obligatory role for club cells in preventing obliterative bronchiolitis in lung transplants. JCI Insight 5:e124732
    [Google Scholar]
  79. 79.
    Gassas A, Schechter T, Krueger J et al. 2015. Serum Krebs Von Den Lungen-6 as a biomarker for early detection of bronchiolitis obliterans syndrome in children undergoing allogeneic stem cell transplantation. Biol. Blood Marrow. Transpl. 21:1524–28
    [Google Scholar]
  80. 80.
    Wendt C, Tram K, Price A et al. 2013. Club cell secretory protein improves survival in a murine obliterative bronchiolitis model. Am. J. Physiol. 305:L642–50
    [Google Scholar]
  81. 81.
    Levy L, Huszti E, Tigert A et al. 2019. Decreased club cell secretory protein in bronchoalveolar lavage is associated with chronic lung allograft dysfunction (CLAD) but not with CLAD phenotypes. J. Heart Lung. Transpl. 38:S255
    [Google Scholar]
  82. 82.
    Ohchi T, Shijubo N, Kawabata I et al. 2004. Polymorphism of Clara cell 10-kD protein gene of sarcoidosis. Am. J. Respir. Crit. Care Med. 169:180–86
    [Google Scholar]
  83. 83.
    Chen LC, Tseng HM, Wu CJ et al. 2012. Evaluation of a common variant of the gene encoding Clara cell 10 kd protein (CC10) as a candidate determinant for asthma severity and steroid responsiveness among Chinese children. J. Asthma 49:665–72
    [Google Scholar]
  84. 84.
    Candelaria PV, Backer V, Laing IA et al. 2005. Association between asthma-related phenotypes and the CC16 A38G polymorphism in an unselected population of young adult Danes. Immunogenetics 57:25–32
    [Google Scholar]
  85. 85.
    Laing IA, de Klerk NH, Turner SW et al. 2009. Cross-sectional and longitudinal association of the secretoglobin 1A1 gene A38G polymorphism with asthma phenotype in the Perth Infant Asthma Follow-up cohort. Clin. Exp. Allergy 39:62–71
    [Google Scholar]
  86. 86.
    Laing IA, Goldblatt J, Eber E et al. 1998. A polymorphism of the CC16 gene is associated with an increased risk of asthma. J. Med. Genet. 35:463–67
    [Google Scholar]
  87. 87.
    Sengler C, Heinzmann A, Jerkic SP et al. 2003. Clara cell protein 16 (CC16) gene polymorphism influences the degree of airway responsiveness in asthmatic children. J. Allergy Clin. Immunol. 111:515–19
    [Google Scholar]
  88. 88.
    Martin AC, Laing IA, Khoo SK et al. 2006. Acute asthma in children: relationships among CD14 and CC16 genotypes, plasma levels, and severity. Am. J. Respir. Crit. Care Med. 173:617–22
    [Google Scholar]
  89. 89.
    Nie W, Xue C, Chen J, Xiu Q 2013. Secretoglobin 1A member 1 (SCGB1A1) +38A/G polymorphism is associated with asthma risk: a meta-analysis. Gene 528:304–8
    [Google Scholar]
  90. 90.
    Zhao G, Lin X, Zhou M, Zhao J. 2013. Association between CC10 +38A/G polymorphism and asthma risk: a meta-analysis. Pak. J. Med. Sci. 29:1439–43
    [Google Scholar]
  91. 91.
    Kim KW, Ober C. 2019. Lessons learned from GWAS of asthma. Allergy Asthma Immunol. Res. 11:170–87
    [Google Scholar]
  92. 92.
    Rigoli L, Di Bella C, Procopio V et al. 2007. Uteroglobin-related protein 1 gene -112G/a polymorphism and atopic asthma in Sicilian children. Allergy Asthma Proc 28:667–70
    [Google Scholar]
  93. 93.
    Cheng D, Di H, Xue Z, Zhen G. 2015. CC16 gene A38G polymorphism and susceptibility to asthma: an updated meta-analysis. Intern. Med. 54:155–62
    [Google Scholar]
  94. 94.
    Knabe L, Varilh J, Bergougnoux A et al. 2016. CCSP G38A polymorphism environment interactions regulate CCSP levels differentially in COPD. Am. J. Physiol. Lung. Cell. Mol. Physiol. 311:L696–703
    [Google Scholar]
  95. 95.
    Cho MH, McDonald ML, Zhou X et al. 2014. Risk loci for chronic obstructive pulmonary disease: a genome-wide association study and meta-analysis. Lancet Respir. Med. 2:214–25
    [Google Scholar]
  96. 96.
    Liu S, Li B, Zhou Y et al. 2007. Genetic analysis of CC16, OGG1 and GCLC polymorphisms and susceptibility to COPD. Respirology 12:29–33
    [Google Scholar]
  97. 97.
    Park HY, Churg A, Wright JL et al. 2013. Club cell protein 16 and disease progression in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 188:1413–19
    [Google Scholar]
  98. 98.
    Janssen R, Sato H, Grutters JC et al. 2004. The Clara cell10 adenine38guanine polymorphism and sarcoidosis susceptibility in Dutch and Japanese subjects. Am. J. Respir. Crit. Care Med. 170:1185–87
    [Google Scholar]
  99. 99.
    Hin A, Kannengiesser C, Roussel A et al. 2018. Donor club cell secretory protein G38A polymorphism is associated with a decreased risk of primary graft dysfunction in the French Cohort in Lung Transplantation. Transplantation 102:1382–90
    [Google Scholar]
  100. 100.
    Bourdin A, Mifsud NA, Chanez B et al. 2012. Donor Clara cell secretory protein polymorphism is a risk factor for bronchiolitis obliterans syndrome after lung transplantation. Transplantation 94:652–58
    [Google Scholar]
  101. 101.
    Li XX, Peng T, Gao J et al. 2019. Allele-specific expression identified rs2509956 as a novel long-distance cis-regulatory SNP for SCGB1A1, an important gene for multiple pulmonary diseases. Am. J. Physiol. Lung Cell Mol. Physiol. 317:L456–63
    [Google Scholar]
  102. 102.
    Lopez E, Fujiwara O, Nelson C et al. 2020. Club cell protein, CC10, attenuates acute respiratory distress syndrome induced by smoke inhalation. Shock 53:317–26
    [Google Scholar]
  103. 103.
    Chandra S, Davis JM, Drexler S et al. 2003. Safety and efficacy of intratracheal recombinant human Clara cell protein in a newborn piglet model of acute lung injury. Pediatr. Res. 54:509–15
    [Google Scholar]
  104. 104.
    Levine CR, Gewolb IH, Allen K et al. 2005. The safety, pharmacokinetics, and anti-inflammatory effects of intratracheal recombinant human Clara cell protein in premature infants with respiratory distress syndrome. Pediatr. Res. 58:15–21
    [Google Scholar]
  105. 105.
    Davis JM, Pilon AL, Shenberger J et al. 2019. The role of recombinant human CC10 in the prevention of chronic pulmonary insufficiency of prematurity. Pediatr. Res. 86:254–60
    [Google Scholar]
  106. 106.
    Widegren H, Andersson M, Greiff L. 2009. Effects of Clara cell 10 (CC10) protein on symptoms and signs of allergic rhinitis. Ann. Allergy Asthma Immunol. 102:51–56
    [Google Scholar]
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