Severe asthma: Lessons learned from the National Heart, Lung, and Blood Institute Severe Asthma Research Program

American Journal of Respiratory and Critical Care Medicine

Volumn 185, Issue 4, 2012, Pages 356-362

  Jarjour, Nizar N ^a   Erzurum, Serpil C ^b   Bleecker, Eugene R ^c   Calhoun, William J ^d   Castro, Mario ^e   Comhair, Suzy A A ^b   Chung, Kian Fan ^f   Curran Everett, Douglas ^g   Dweik, Raed A ^b   Fain, Sean B ^a   Fitzpatrick, Anne M ^h   Gaston, Benjamin M ⁱ   Israel, Elliot ^j   Hastie, Annette ^c   Hoffman, Eric A ^k   Holguin, Fernando ^l   Levy, Bruce D ^j   Meyers, Deborah A ^c   Moore, Wendy C ^c   Peters, Stephen P ^c   Sorkness, Ronald L ^a   Teague, W Gerald ⁱ   Wenzel, Sally E ^l   Busse, William W ^a   more..

^a UNIVERSITY OF WISCONSIN MADISON   (United States)

^b LERNER RESEARCH INSTITUTE   (United States)

^c WAKE FOREST SCHOOL OF MEDICINE   (United States)

^d UNIVERSITY OF TEXAS MEDICAL BRANCH   (United States)

^e WASHINGTON UNIVERSITY   (United States)

^f IMPERIAL COLLEGE SCHOOL OF MEDICINE   (United Kingdom)

^g UNIVERSITY OF COLORADO   (United States)

^h EMORY UNIVERSITY   (United States)

ⁱ UNIVERSITY OF VIRGINIA   (United States)

^j BRIGHAM AND WOMEN S HOSPITAL   (United States)

^k UNIVERSITY OF IOWA   (United States)

^l UNIVERSITY OF PITTSBURGH   (United States)

more..

Author keywords

Asthma; Bronchoscopy; Imaging; Inflammation; Remodeling

Indexed keywords

AIRWAY REMODELING; ASTHMA; BRONCHOSCOPY; DISEASE PREDISPOSITION; DISEASE SEVERITY; GENETIC VARIABILITY; HUMAN; LUNG FUNCTION; LUNG STRUCTURE; MEDICAL RESEARCH; NATIONAL HEALTH ORGANIZATION; PATHOGENESIS; PRIORITY JOURNAL; RESPIRATORY TRACT INFLAMMATION; REVIEW; RISK FACTOR;

ADOLESCENT; ADULT; AIRWAY REMODELING; ASTHMA; BIOLOGICAL MARKERS; BRONCHOSCOPY; CHILD; CLINICAL PROTOCOLS; COHORT STUDIES; CROSS-SECTIONAL STUDIES; HUMANS; RISK FACTORS; SEVERITY OF ILLNESS INDEX;

EID: 84857410928     PISSN: 1073449X     EISSN: 15354970     Source Type: Journal    
DOI: 10.1164/rccm.201107-1317PP     Document Type: Review

References (65)

1. Busse WW, Banks-Schlegel S, Wenzel SE. Pathophysiology of severe asthma. J Allergy Clin Immunol 2000;106:1033-1042. (Pubitemid 32006254)
2. Proceedings of the ATS workshop on refractory asthma: current understanding, recommendations, and unanswered questions. American Thoracic Society. Am J Respir Crit Care Med 2000;162:2341-2351.
3. The ENFUMOSA cross-sectional European multicentre study of the clinical phenotype of chronic severe asthma. European Network for Understanding Mechanisms of Severe Asthma. Eur Respir J 2003;22:470-477.
4. Guidelines for the diagnosis and management of asthma. National Heart, Lung, and Blood Institute. National Asthma Education Program. Expert Panel Report. J Allergy Clin Immunol 1991;88:425-534.
5. Moore WC, Bleecker ER, Curran-Everett D, Erzurum SC, Ameredes BT, Bacharier L, Calhoun WJ, Castro M, Chung KF, Clark MP, et al. Characterization of the severe asthma phenotype by the National Heart, Lung, and Blood Institute's Severe Asthma Research Program. J Allergy Clin Immunol 2007;119:405-413. (Pubitemid 46210080)
6. Fitzpatrick AM, Gaston BM, Erzurum SC, Teague WG. Features of severe asthma in school-age children: atopy and increased exhaled nitric oxide. J Allergy Clin Immunol 2006;118:1218-1225. (Pubitemid 44854125)
7. Bel EH, Sousa A, Fleming L, Bush A, Chung KF, Versnel J, Wagener AH, Wagers SS, Sterk PJ, Compton CH. Diagnosis and definition of severe refractory asthma: an international consensus statement from the Innovative Medicine Initiative (IMI). Thorax 2011;66:910-917.
8. Farha S, Asosingh K, Laskowski D, Hammel J, Dweik RA, Wiedemann HP, Erzurum SC. Effects of the menstrual cycle on lung function variables in women with asthma. Am J Respir Crit Care Med 2009;180:304-310.
9. Tantisira KG, Colvin R, Tonascia J, Strunk RC, Weiss ST, Fuhlbrigge AL. Airway responsiveness in mild to moderate childhood asthma: sex influences on the natural history. Am J Respir Crit Care Med 2008;178:325-331.
10. Moore WC, Meyers DA, Wenzel SE, Teague WG, Li H, Li X, D'Agostino R Jr, Castro M, Curran-Everett D, Fitzpatrick AM, et al. Identification of asthma phenotypes using cluster analysis in the Severe Asthma Research Program. Am J Respir Crit Care Med 2010;181:315-323.
11. Holguin F, Bleecker ER, Busse WW, Calhoun WJ, Castro M, Erzurum SC, Fitzpatrick AM, Gaston B, Israel E, Jarjour NN, et al. Obesity and asthma: an association modified by age of asthma onset. J Allergy Clin Immunol 2011;127:1486-1493.e2.
12. Holguin F, Fitzpatrick A. Obesity, asthma, and oxidative stress. J Appl Physiol 2010;108:754-759.
13. Gamble C, Talbott E, Youk A, Holguin F, Pitt B, Silveira L, Bleecker E, Busse W, Calhoun W, Castro M, et al. Racial differences in biologic predictors of severe asthma: data from the Severe Asthma Research Program. J Allergy Clin Immunol 2010;126:1149-1156.e1.
14. Comhair SA, Gaston BM, Ricci KS, Hammel J, Dweik RA, Teague WG, Meyers D, Ampleford EJ, Bleecker ER, Busse WW, et al. Detrimental effects of environmental tobacco smoke in relation to asthma severity. PLoS ONE 2011;6:e18574.
15. Sorkness RL, Bleecker ER, Busse WW, Calhoun WJ, Castro M, Chung KF, Curran-Everett D, Erzurum SC, Gaston BM, Israel E, et al. Lung function in adults with stable but severe asthma: air trapping and incomplete reversal of obstruction with bronchodilation. J Appl Physiol 2008;104:394-403. (Pubitemid 351231486)
16. Sorkness RL, Teague WG, Penugonda M, Fitzpatrick AM. Sex dependence of airflow limitation and air trapping in children with severe asthma. J Allergy Clin Immunol 2011;127:1073-1074.
17. Fitzpatrick AM, Teague WG. Progressive airflow limitation is a feature of children with severe asthma. J Allergy Clin Immunol 2011;127:282-284.
18. Busacker A, Newell JD Jr, Keefe T, Hoffman EA, Granroth JC, Castro M, Fain S, Wenzel S. A multivariate analysis of risk factors for the air-trapping asthmatic phenotype as measured by quantitative CT analysis. Chest 2009;135:48-56.
19. Castro M, Fain SB, Hoffman EA, Gierada DS, Erzurum SC, Wenzel S. Lung imaging in asthmatic patients: the picture is clearer. J Allergy Clin Immunol 2011;128:467-478.
20. Jarjour NN, Peters SP, Djukanovic R, Calhoun WJ. Investigative use of bronchoscopy in asthma. Am J Respir Crit Care Med 1998;157:692-697.
21. Investigative use of bronchoscopy, lavage and bronchial biopsies in asthma and other airways diseases. Clin Exp Allergy 1991;21:533-539.
22. Busse WW, Wanner A, Adams K, Reynolds HY, Castro M, Chowdhury B, Kraft M, Levine RJ, Peters SP, Sullivan EJ. Investigative bronchoprovocation and bronchoscopy in airway diseases. Am J Respir Crit Care Med 2005;172:807-816. (Pubitemid 41369062)
23. Summary and recommendations of a workshop on the investigative use of fiberoptic bronchoscopy and bronchoalveolar lavage in asthmatics. Am Rev Respir Dis 1985;132:180-182.
24. Moore WC, Evans MD, Bleecker ER, Busse WW, Calhoun WJ, Castro M, Fan Chung K, Erzurum SC, Curran-Everett D, Dweik RA, et al. Safety of investigative bronchoscopy in the severe asthma research program. J Allergy Clin Immunol 2011;128:328-336.e3.
25. Aysola RS, Hoffman EA, Gierada D, Wenzel S, Cook-Granroth J, Tarsi J, Zheng J, Schechtman KB, Ramkumar TP, Cochran R, et al. Airway remodeling measured by multidetector CT is increased in severe asthma and correlates with pathology. Chest 2008;134:1183-1191.
26. Balzar S, Fajt ML, Comhair SA, Erzurum SC, Bleecker E, Busse WW, Castro M, Gaston B, Israel E, Schwartz LB, et al. Mast cell phenotype, location, and activation in severe asthma: data from the Severe Asthma Research Program. Am J Respir Crit Care Med 2011;183:299-309.
27. Brasier AR, Victor S, Boetticher G, Ju H, Lee C, Bleecker ER, Castro M, Busse WW, Calhoun WJ. Molecular phenotyping of severe asthma using pattern recognition of bronchoalveolar lavage-derived cytokines. J Allergy Clin Immunol 2008;121:30-37.e6.
28. Brasier AR, Victor S, Ju H, Busse WW, Curran-Everett D, Bleecker E, Castro M, Chung KF, Gaston B, Israel E, et al. Predicting intermediate phenotypes in asthma using bronchoalveolar lavage-derived cytokines. Clin Transl Sci 2010;3:147-157.
29. Cohen L, E X, Tarsi J, Ramkumar T, Horiuchi TK, Cochran R, DeMartino S, Schechtman KB, Hussain I, Holtzman MJ, et al. Epithelial cell proliferation contributes to airway remodeling in severe asthma. Am J Respir Crit Care Med 2007;176:138-145.
30. Dweik RA, Sorkness RL, Wenzel S, Hammel J, Curran-Everett D, Comhair SA, Bleecker E, Busse W, Calhoun WJ, Castro M, et al. Use of exhaled nitric oxide measurement to identify a reactive, at-risk phenotype among patients with asthma. Am J Respir Crit Care Med 2011;181:1033-1041.
31. Lara A, Khatri SB, Wang Z, Comhair SA, Xu W, Dweik RA, Bodine M, Levison BS, Hammel J, Bleecker E, et al. Alterations of the arginine metabolome in asthma. Am J Respir Crit Care Med 2008;178:673-681.
32. Miranda C, Busacker A, Balzar S, Trudeau J, Wenzel SE. Distinguishing severe asthma phenotypes: role of age at onset and eosinophilic inflammation. J Allergy Clin Immunol 2004;113:101-108. (Pubitemid 38096168)
33. Planaguma A, Kazani S, Marigowda G, Haworth O, Mariani TJ, Israel E, Bleecker ER, Curran-Everett D, Erzurum SC, Calhoun WJ, et al. Airway lipoxin A4 generation and lipoxin A4 receptor expression are decreased in severe asthma. Am J Respir Crit Care Med 2008;178:574-582.
34. Wenzel SE, Balzar S, Ampleford E, Hawkins GA, Busse WW, Calhoun WJ, Castro M, Chung KF, Erzurum S, Gaston B, et al. IL4R alpha mutations are associated with asthma exacerbations and mast cell /IgE expression. Am J Respir Crit Care Med 2007;175:570-576. (Pubitemid 46438941)
35. Hastie AT, Moore WC, Meyers DA, Vestal PL, Li H, Peters SP, Bleecker ER. Analyses of asthma severity phenotypes and inflammatory proteins in subjects stratified by sputum granulocytes. J Allergy Clin Immunol 2010;125:1028-1036. e13.
36. Kotaru C, Schoonover KJ, Trudeau JB, Huynh ML, Zhou X, Hu H, Wenzel SE. Regional fibroblast heterogeneity in the lung: Implications for remodeling. Am J Respir Crit Care Med 2006;173:1208-1215. (Pubitemid 43848390)
37. Zhou X, Wu W, Hu H, Milosevic J, Konishi K, Kaminski N, Wenzel SE. Genomic differences distinguish the myofibroblast phenotype of distal lung from airway fibroblasts. Am J Respir Cell Mol Biol 2011;45:1256-1262.
38. Shin HW, Shelley DA, Henderson EM, Fitzpatrick A, Gaston B, George SC. Airway nitric oxide release is reduced after PBS inhalation in asthma. J Appl Physiol 2007;102:1028-1033. (Pubitemid 46377028)
39. Comhair SA, Ricci KS, Arroliga M, Lara AR, Dweik RA, Song W, Hazen SL, Bleecker ER, Busse WW, Chung KF, et al. Correlation of systemic superoxide dismutase deficiency to airflow obstruction in asthma. Am J Respir Crit Care Med 2005;172:306-313. (Pubitemid 41026140)
40. Wedes SH, Khatri SB, Zhang R, Wu W, Comhair SA, Wenzel S, Teague WG, Israel E, Erzurum SC, Hazen SL. Noninvasive markers of airway inflammation in asthma. Clin Transl Sci 2009;2:112-117.
41. Wedes SH, Wu W, Comhair SA, McDowell KM, Didonato JA, Erzurum SC, Hazen SL. Urinary bromotyrosine measures asthma control and predicts asthma exacerbations in children. J Pediatr 2011;159:248-255.
42. Fitzpatrick AM, Teague WG, Burwell L, Brown MS, Brown LA. Glutathione oxidation is associated with airway macrophage functional impairment in children with severe asthma. Pediatr Res 2011;69:154-159.
43. Fitzpatrick AM, Teague WG, Holguin F, Yeh M, Brown LA. Airway glutathione homeostasis is altered in children with severe asthma: evidence for oxidant stress. J Allergy Clin Immunol 2009;123:146-152.e8.
44. Fitzpatrick AM, Brown LA, Holguin F, Teague WG. Levels of nitric oxide oxidation products are increased in the epithelial lining fluid of children with persistent asthma. J Allergy Clin Immunol 2009;124:990-996.e1-9.
45. Greenwald R, Fitzpatrick AM, Gaston B, Marozkina NV, Erzurum S, Teague WG. Breath formate is a marker of airway s-nitrosothiol depletion in severe asthma. PLoS ONE 2010;5:e11919.
46. Fitzpatrick AM, Holguin F, Teague WG, Brown LA. Alveolar macrophage phagocytosis is impaired in children with poorly controlled asthma. J Allergy Clin Immunol 2008;121:1372-1378, 1378.e1-3.
47. Fitzpatrick AM, Teague WG, Meyers DA, Peters SP, Li X, Li H, Wenzel SE, Aujla S, Castro M, Bacharier LB, et al. Heterogeneity of severe asthma in childhood: Confirmation by cluster analysis of children in the national institutes of health/national heart, lung, and blood institute severe asthma research program. J Allergy Clin Immunol 2011;127:382-389.e1-13.
48. Levy BD, Bonnans C, Silverman ES, Palmer LJ, Marigowda G, Israel E. Diminished lipoxin biosynthesis in severe asthma. Am J Respir Crit Care Med 2005;172:824-830. (Pubitemid 41369064)
49. Bhavsar PK, Levy BD, Hew MJ, Pfeffer MA, Kazani S, Israel E, Chung KF. Corticosteroid suppression of lipoxin A4 and leukotriene B4 from alveolar macrophages in severe asthma. Respir Res 2010;11:71.
50. Chupp GL, Lee CG, Jarjour N, Shim YM, Holm CT, He S, Dziura JD, Reed J, Coyle AJ, Kiener P, et al. A chitinase-like protein in the lung and circulation of patients with severe asthma. N Engl J Med 2007;357:2016-2027. (Pubitemid 350106709)
51. Gaston B. The biochemistry of asthma. Biochim Biophys Acta 2011;1810:1017-1024.
52. Wenzel SE. Asthma: defining of the persistent adult phenotypes. Lancet 2006;368:804-813. (Pubitemid 44279058)
53. Irusen E, Matthews JG, Takahashi A, Barnes PJ, Chung KF, Adcock IM. P38 mitogen-activated protein kinase-induced glucocorticoid receptor phosphorylation reduces its activity: role in steroid-insensitive asthma. J Allergy Clin Immunol 2002;109:649-657. (Pubitemid 34327193)
54. Bhavsar P, Hew M, Khorasani N, Torrego A, Barnes PJ, Adcock I, Chung KF. Relative corticosteroid insensitivity of alveolar macrophages in severe asthma compared with non-severe asthma. Thorax 2008;63:784-790.
55. Hew M, Bhavsar P, Torrego A, Meah S, Khorasani N, Barnes PJ, Adcock I, Chung KF. Relative corticosteroid insensitivity of peripheral blood mononuclear cells in severe asthma. Am J Respir Crit Care Med 2006;174:134-141. (Pubitemid 44015386)
56. Chaudhuri R, Livingston E, McMahon AD, Thomson L, Borland W, Thomson NC. Cigarette smoking impairs the therapeutic response to oral corticosteroids in chronic asthma. Am J Respir Crit Care Med 2003;168:1308-1311. (Pubitemid 37487324)
57. Ito K, Lim S, Caramori G, Chung KF, Barnes PJ, Adcock IM. Cigarette smoking reduces histone deacetylase 2 expression, enhances cytokine expression, and inhibits glucocorticoid actions in alveolar macrophages. FASEB J 2001;15:1110-1112.
58. Hancock DB, Eijgelsheim M, Wilk JB, Gharib SA, Loehr LR, Marciante KD, Franceschini N, van Durme YM, Chen TH, Barr RG, et al. Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function. Nat Genet 2010;42:45-52.
59. Repapi E, Sayers I, Wain LV, Burton PR, Johnson T, Obeidat M, Zhao JH, Ramasamy A, Zhai G, Vitart V, et al. Genome-wide association study identifies five loci associated with lung function. Nat Genet 2010;42:36-44.
60. Li X, Howard TD, Moore WC, Ampleford EJ, Li H, Busse WW, Calhoun WJ, Castro M, Chung KF, Erzurum SC, et al. Importance of hedgehog interacting protein and other lung function genes in asthma. J Allergy Clin Immunol 2011;127:1457-1465.
61. Torgerson DG, Ampleford EJ, Chiu GY, Gauderman WJ, Gignoux CR, Graves PE, Himes BE, Levin AM, Mathias RA, Hancock DB, et al. Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations. Nat Genet 2011;43:887-892.
62. Moffatt MF, Gut IG, Demenais F, Strachan DP, Bouzigon E, Heath S, von Mutius E, Farrall M, Lathrop M, Cookson WO. A large-scale, consortium-based genomewide association study of asthma. N Engl J Med 2010;363:1211-1221.
63. Slager RELX, Meyers DA, Bleecker ER. Recent developments in the genetics of asthma susceptibility and severity. Eur Respir Mon 2011;51:82-106.
64. Jain S, Kamimoto L, Bramley AM, Schmitz AM, Benoit SR, Louie J, Sugerman DE, Druckenmiller JK, Ritger KA, Chugh R, et al. Hospitalized patients with 2009 H1N1 influenza in the United States, April-June 2009. N Engl J Med 2009;361:1935-1944.
65. Busse WW, Peters SP, Fenton MJ, Mitchell H, Bleecker ER, Castro M, Wenzel S, Erzurum SC, Fitzpatrick AM, Teague WG, et al. Vaccination of patients with mild and severe asthma with a 2009 pandemic H1N1 influenza virus vaccine. J Allergy Clin Immunol 2011;127:130-137, 137.e1-3.