Will the asthma revolution fostered by biologics also benefit adult ICU patients?
Corresponding Author
Arnaud Bourdin
Department of Respiratory Diseases, Univ Montpellier, CHU Montpellier, Montpellier, France
PhyMedExp, Univ Montpellier, CNRS, INSERM, CHU Montpellier, Montpellier, France
Correspondence
Arnaud Bourdin, Département de Pneumologie et Addictologie, PhyMedExp, University of Montpellier, INSERM U1046, CNRS UMR 9214, Hôpital Arnaud de Villeneuve, CHU Montpellier – France.
Email: [email protected]
Search for more papers by this authorJérémy Charriot
Department of Respiratory Diseases, Univ Montpellier, CHU Montpellier, Montpellier, France
PhyMedExp, Univ Montpellier, CNRS, INSERM, CHU Montpellier, Montpellier, France
Search for more papers by this authorClément Boissin
Department of Respiratory Diseases, Univ Montpellier, CHU Montpellier, Montpellier, France
Search for more papers by this authorEngi Ahmed
Department of Respiratory Diseases, Univ Montpellier, CHU Montpellier, Montpellier, France
Search for more papers by this authorCarey Suehs
Department of Respiratory Diseases, Univ Montpellier, CHU Montpellier, Montpellier, France
Department of Medical Information, Univ Montpellier, CHU Montpellier, Montpellier, France
Search for more papers by this authorArthur De Sevin
Department of Respiratory Diseases, Univ Montpellier, CHU Montpellier, Montpellier, France
Search for more papers by this authorMathilde Volpato
Department of Respiratory Diseases, Univ Montpellier, CHU Montpellier, Montpellier, France
Search for more papers by this authorLaurie Pahus
Aix Marseille Univ, APHM, Hôpital NORD, CIC 9502, Clinique des bronches allergies et sommeil, Chemin des Bourrely, 13015, Marseille, France
Aix Marseille Univ, CNRS, EFS, ADES, Marseille, France
Aix Marseille Univ, INSERM U1263, INRA 1260 (C2VN), Marseille, France
Search for more papers by this authorDelphine Gras
Aix Marseille Univ, INSERM U1263, INRA 1260 (C2VN), Marseille, France
Search for more papers by this authorIsabelle Vachier
Department of Respiratory Diseases, Univ Montpellier, CHU Montpellier, Montpellier, France
Search for more papers by this authorLaurence Halimi
Department of Respiratory Diseases, Univ Montpellier, CHU Montpellier, Montpellier, France
Search for more papers by this authorDominic Hamerlijnck
Dutch Lung Foundation, Amersfoort, The Netherlands
Search for more papers by this authorPascal Chanez
Aix Marseille Univ, APHM, Hôpital NORD, CIC 9502, Clinique des bronches allergies et sommeil, Chemin des Bourrely, 13015, Marseille, France
Aix Marseille Univ, INSERM U1263, INRA 1260 (C2VN), Marseille, France
Search for more papers by this authorCorresponding Author
Arnaud Bourdin
Department of Respiratory Diseases, Univ Montpellier, CHU Montpellier, Montpellier, France
PhyMedExp, Univ Montpellier, CNRS, INSERM, CHU Montpellier, Montpellier, France
Correspondence
Arnaud Bourdin, Département de Pneumologie et Addictologie, PhyMedExp, University of Montpellier, INSERM U1046, CNRS UMR 9214, Hôpital Arnaud de Villeneuve, CHU Montpellier – France.
Email: [email protected]
Search for more papers by this authorJérémy Charriot
Department of Respiratory Diseases, Univ Montpellier, CHU Montpellier, Montpellier, France
PhyMedExp, Univ Montpellier, CNRS, INSERM, CHU Montpellier, Montpellier, France
Search for more papers by this authorClément Boissin
Department of Respiratory Diseases, Univ Montpellier, CHU Montpellier, Montpellier, France
Search for more papers by this authorEngi Ahmed
Department of Respiratory Diseases, Univ Montpellier, CHU Montpellier, Montpellier, France
Search for more papers by this authorCarey Suehs
Department of Respiratory Diseases, Univ Montpellier, CHU Montpellier, Montpellier, France
Department of Medical Information, Univ Montpellier, CHU Montpellier, Montpellier, France
Search for more papers by this authorArthur De Sevin
Department of Respiratory Diseases, Univ Montpellier, CHU Montpellier, Montpellier, France
Search for more papers by this authorMathilde Volpato
Department of Respiratory Diseases, Univ Montpellier, CHU Montpellier, Montpellier, France
Search for more papers by this authorLaurie Pahus
Aix Marseille Univ, APHM, Hôpital NORD, CIC 9502, Clinique des bronches allergies et sommeil, Chemin des Bourrely, 13015, Marseille, France
Aix Marseille Univ, CNRS, EFS, ADES, Marseille, France
Aix Marseille Univ, INSERM U1263, INRA 1260 (C2VN), Marseille, France
Search for more papers by this authorDelphine Gras
Aix Marseille Univ, INSERM U1263, INRA 1260 (C2VN), Marseille, France
Search for more papers by this authorIsabelle Vachier
Department of Respiratory Diseases, Univ Montpellier, CHU Montpellier, Montpellier, France
Search for more papers by this authorLaurence Halimi
Department of Respiratory Diseases, Univ Montpellier, CHU Montpellier, Montpellier, France
Search for more papers by this authorDominic Hamerlijnck
Dutch Lung Foundation, Amersfoort, The Netherlands
Search for more papers by this authorPascal Chanez
Aix Marseille Univ, APHM, Hôpital NORD, CIC 9502, Clinique des bronches allergies et sommeil, Chemin des Bourrely, 13015, Marseille, France
Aix Marseille Univ, INSERM U1263, INRA 1260 (C2VN), Marseille, France
Search for more papers by this authorAbstract
Purpose
Asthma exacerbations are inflammatory events that rarely result in full hospitalization following an ER visit. Unfortunately, certain patients require prolonged support, including occasional external lung support through ECMO or ECCOR (with subsequent further exposure to other life-threatening issues), and some die. In parallel, biologics are revolutionizing severe asthma management, mostly in T2 high patients.
Methods
We extensively reviewed the current unmet needs surrounding ICU-admitted asthma exacerbations, with a focus on currently available drugs and the underlying biological processes involved. We explored whether currently available T2-targeting drugs can reasonably be seen as potential players not only for relapse prevention but also as candidate drugs for a faster resolution of such episodes. The patient's perspective was also sought.
Results
About 30% of asthma exacerbations admitted to the ICU do not resolve within five days. Persistent severe airway obstruction despite massive doses of corticosteroids and maximal pharmacologically induced bronchodilation is the main cause of treatment failure. Previous ICU admission is the main risk factor for such episodes and may eventually be considered as a T2 surrogate marker. Fatal asthma cases are hallmarked by poorly steroid-sensitive T2-inflammation associated with severe mucus plugging. New, fast-acting T2-targeting biologics (already used for preventing asthma exacerbations) have the potential to circumvent steroid sensitivity pathways and decrease mucus plugging. This unmet need was confirmed by patients who reported highly negative, traumatizing experiences.
Conclusions
There is room for improvement in the management of ICU-admitted severe asthma episodes. Clinical trials assessing how biologics might improve ICU outcomes are direly needed.
CONFLICT OF INTEREST
None of the authors report interests related to the present work.
Dr Arnaud Bourdin reports industry-sponsored grants from AstraZeneca-MedImmune, Boehringer-Ingelheim, Cephalon/Teva, GlaxoSmithKline, Novartis, Sanofi-Regeneron; consultancies for AstraZeneca-MedImmune, Boehringer-Ingelheim, GlaxoSmithKline, Novartis, Regeneron-Sanofi, Med-in-Cell, Actelion, Merck, Roche, Chiesi; investigator/Co-investigator activities for trials promoted by AstraZeneca-MedImmune, Boehringer-Ingelheim, GlaxoSmithKline, Novartis, Regeneron-Sanofi, Chiesi, Actelion, Merck, Roche, Vertex, Galapagos; no personal financial support from a non-commercial source; no personal relationships with tobacco industry entities; no off-label disclosures. Dr Charriot, Dr Boissin, Dr Ahmed, Mr De Sevin, Dr Volpato, Dr Gras, and Dr Isabelle Vachier have no conflict of interest to declare. Dr Carey Suehs reports one grant from Astra Zeneca. Dr Laurie PAHUS reports consultancies for Astra Zeneca and Chiesi pharmaceuticals. Dr Laurence Halimi reports industry-sponsored grants and lecturer activities for GlaxoSmithKline, Actelion, and Novartis. D. Hamerlijnck is a patient expert for European Federation of Allergy and Airways (EFA) and European Lung Foundation (ELF), a patient independent advisor to Novartis and Chiesi on patient involvement; patient co-chair of the ERS Severe Heterogeneous Asthma Registry, Patient-centred CRC, and a GINA advocate; Dr Pascal Chanez, as an advisory board member, consultant, or lecturer, has previously received honoraria or grants from Boehringer Ingeheim, Almirall, Centocor, GSK, MSD, Astra Zeneca, Novartis, Teva, Chiesi, Shering Plough, and Aix Marseille University.
REFERENCES
- 1Ernst P, Spitzer WO, Suissa S, et al. Risk of fatal and near-fatal asthma in relation to inhaled corticosteroid use. JAMA. 1992; 268: 3462-3464.
- 2Suissa S, Ernst P, Benayoun S, et al. Low-dose inhaled corticosteroids and the prevention of death from asthma. N Engl J Med. 2000; 343: 332-336. https://doi.org/10.1056/NEJM200008033430504
- 3Bourdin A, Bjermer L, Brightling C, et al. ERS/EAACI Statement on severe exacerbations in asthma in adult: facts, priorities and key research questions. Eur Respir J. 2019; 54(3). https://doi.org/10.1183/13993003.00900-2019
- 4Fuhlbrigge A, Peden D, Apter AJ, et al. Asthma outcomes: exacerbations. J Allergy Clin Immunol. 2012; 129: S34-S48. https://doi.org/10.1016/j.jaci.2011.12.983
- 5Reddel HK, FitzGerald JM, Bateman ED, et al. GINA 2019: a fundamental change in asthma management: treatment of asthma with short-acting bronchodilators alone is no longer recommended for adults and adolescents. Eur Respir J. 2019; 53(6): 1901046. https://doi.org/10.1183/13993003.01046-2019
- 6Price DB, Trudo F, Voorham J, et al. Adverse outcomes from initiation of systemic corticosteroids for asthma: long-term observational study. J Asthma Allergy. 2018; 11: 193-204. https://doi.org/10.2147/JAA.S176026
- 7Bourdin A, Molinari N, Vachier I, et al. Mortality: a neglected outcome in OCS-treated severe asthma. Eur Respir J. 2017; 50(5): 1701486. https://doi.org/10.1183/13993003.01486-2017
- 8Sweeney J, Brightling CE, Menzies-Gow A, et al. Clinical management and outcome of refractory asthma in the UK from the British Thoracic Society Difficult Asthma Registry. Thorax. 2012; 67: 754-756. https://doi.org/10.1136/thoraxjnl-2012-201869
- 9Al-Dorzi HM, Al-Shammary HA, Al-Shareef SY, et al. Risk factors, management and outcomes of patients admitted with near fatal asthma to a tertiary care hospital in Riyadh. Ann Thorac Med. 2014; 9: 33-38. https://doi.org/10.4103/1817-1737.124441
- 10Alvarez GG, Schulzer M, Jung D, Fitzgerald JM. A systematic review of risk factors associated with near-fatal and fatal asthma. Can Respir J. 2005; 12: 265-270.
- 11Gelb AF, Schein A, Nussbaum E, et al. Risk factors for near-fatal asthma. Chest. 2004; 126: 1138-1146. https://doi.org/10.1378/chest.126.4.1138
- 12Turner M, Noertjojo K, Vedal S, et al. Risk factors for near-fatal asthma. A case-control study in hospitalized patients with asthma. Am J Respir Crit Care Med. 1998; 157: 1804-1809. https://doi.org/10.1164/ajrccm.157.6.9708092
- 13Abramson M, Bailey M, Couper F, et al. Are asthma medications and management related to deaths from asthma? Am J Respir Crit Care Med. 2001; 163: 12-18. https://doi.org/10.1164/ajrccm.163.1.9910042
- 14Beasley R. A historical perspective of the New Zealand asthma mortality epidemics. J Allergy Clin Immunol. 2006; 117: 225-228. https://doi.org/10.1016/j.jaci.2005.10.029
- 15Pendergraft TB, Stanford RH, Beasley R, et al. Rates and characteristics of intensive care unit admissions and intubations among asthma-related hospitalizations. Ann Allergy Asthma Immunol. 2004; 93: 29-35. https://doi.org/10.1016/S1081-1206(10)61444-5
- 16Doshi V, Shenoy S, Ganesh A, et al. Profile of acute asthma exacerbation in drug users. Am J Ther. 2017; 24: e39-e43. https://doi.org/10.1097/MJT.0000000000000118
- 17Nair P, Wenzel S, Rabe KF, et al. Oral glucocorticoid-sparing effect of benralizumab in severe asthma. N Engl J Med. 2017; 376: 2448-2458. https://doi.org/10.1056/NEJMoa1703501
- 18Bel EH, Wenzel SE, Thompson PJ, et al. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med. 2014; 371: 1189-1197. https://doi.org/10.1056/NEJMoa1403291
- 19Rabe KF, Nair P, Brusselle G, et al. Efficacy and safety of dupilumab in glucocorticoid-dependent severe asthma. N Engl J Med. 2018; 378: 2475-2485. https://doi.org/10.1056/NEJMoa1804093
- 20Wu W, Bang S, Bleecker ER, et al. Multiview cluster analysis identifies variable corticosteroid response phenotypes in severe asthma. Am J Respir Crit Care Med. 2019; 199(11): 1358–1367. https://doi.org/10.1164/rccm.201808-1543OC
- 21 GSK NUCALA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761122s000lbl.pdf. Accessed 2 Apr 2020.
- 22 Astra Zeneca FASENRA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761070s000lbl.pdf. Accessed 2 Apr 2020.
- 23 SANOFI Dupixent. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761055s014lbl.pdf. Accessed 2 Apr 2020.
- 24 Novartis xolair_prescribing.pdf. https://www.gene.com/download/pdf/xolair_prescribing.pdf. Accessed 2 Apr 2020.
- 25 TEVA CINQAERO. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/761033lbl.pdf. Accessed 2 Apr 2020
- 26Castro M, Corren J, Pavord ID, et al. Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma. N Engl J Med. 2018; 378: 2486-2496. https://doi.org/10.1056/NEJMoa1804092
- 27Bleecker ER, FitzGerald JM, Chanez P, et al. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet. 2016; 388: 2115-2127. https://doi.org/10.1016/S0140-6736(16)31324-1
- 28Ortega HG, Liu MC, Pavord ID, et al. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med. 2014; 371: 1198-1207. https://doi.org/10.1056/NEJMoa1403290
- 29Castro M, Zangrilli J, Wechsler ME, et al. Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: results from two multicentre, parallel, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet Respir Med. 2015; 3: 355-366. https://doi.org/10.1016/S2213-2600(15)00042-9
- 30Cabon Y, Molinari N, Marin G, et al. Comparison of anti-interleukin-5 therapies in patients with severe asthma: global and indirect meta-analyses of randomized placebo-controlled trials. Clin Exp Allergy. 2017; 47: 129-138. https://doi.org/10.1111/cea.12853
- 31James AL, Elliot JG, Abramson MJ, Walters EH. Time to death, airway wall inflammation and remodelling in fatal asthma. Eur Respir J. 2005; 26: 429-434. https://doi.org/10.1183/09031936.05.00146404
- 32de Magalhaes Simoes S, dos Santos MA, da Silva Oliveira M, et al. Inflammatory cell mapping of the respiratory tract in fatal asthma. Clin Exp Allergy. 2005; 35: 602-611. https://doi.org/10.1111/j.1365-2222.2005.02235.x
- 33Venegas JG, Winkler T, Musch G, et al. Self-organized patchiness in asthma as a prelude to catastrophic shifts. Nature. 2005; 434: 777-782. https://doi.org/10.1038/nature03490
- 34Wagner EM, Bleecker ER, Permutt S, Liu MC. Direct assessment of small airways reactivity in human subjects. Am J Respir Crit Care Med. 1998; 157: 447-452.
- 35Wagner EM, Liu MC, Weinmann GG, et al. Peripheral lung resistance in normal and asthmatic subjects. Am Rev Respir Dis. 1990; 141: 584-588. https://doi.org/10.1164/ajrccm/141.3.584
- 36King GG, Carroll JD, Müller NL, et al. Heterogeneity of narrowing in normal and asthmatic airways measured by HRCT. Eur Respir J. 2004; 24: 211-218.
- 37Ohrui T, Sekizawa K, Yanai M, et al. Partitioning of pulmonary responses to inhaled methacholine in subjects with asymptomatic asthma. Am Rev Respir Dis. 1992; 146: 1501-1505. https://doi.org/10.1164/ajrccm/146.6.1501
- 38Carroll N, Elliot J, Morton A, James A. The structure of large and small airways in nonfatal and fatal asthma. Am Rev Respir Dis. 1993; 147: 405-410. https://doi.org/10.1164/ajrccm/147.2.405
- 39Green FHY, Williams DJ, James A, et al. Increased myoepithelial cells of bronchial submucosal glands in fatal asthma. Thorax. 2010; 65: 32-38. https://doi.org/10.1136/thx.2008.111435
- 40James AL, Elliot JG, Jones RL, et al. Airway smooth muscle hypertrophy and hyperplasia in asthma. Am J Respir Crit Care Med. 2012; 185: 1058-1064. https://doi.org/10.1164/rccm.201110-1849OC
- 41Gelb AF, Yamamoto A, Mauad T, et al. Unsuspected mild emphysema in nonsmoking patients with chronic asthma with persistent airway obstruction. J Allergy Clin Immunol. 2014; 133: 263-265.e3. https://doi.org/10.1016/j.jaci.2013.09.045
- 42Mauad T, Silva LFF, Santos MA, et al. Abnormal alveolar attachments with decreased elastic fiber content in distal lung in fatal asthma. Am J Respir Crit Care Med. 2004; 170: 857-862. https://doi.org/10.1164/rccm.200403-305OC
- 43James AL, Noble PB, Drew S-A, et al. Airway smooth muscle proliferation and inflammation in asthma. J Appl Physiol. 2018; 125: 1090-1096. https://doi.org/10.1152/japplphysiol.00342.2018
- 44Kan M, Koziol-White C, Shumyatcher M, et al. Airway smooth muscle-specific transcriptomic signatures of glucocorticoid exposure. Am J Respir Cell Mol Biol. 2019; 61: 110-120. https://doi.org/10.1165/rcmb.2018-0385OC
- 45Dolhnikoff M, da Silva LFF, de Araujo BB, et al. The outer wall of small airways is a major site of remodeling in fatal asthma. J Allergy Clin Immunol. 2009; 123(5): 1090-1097.e1. https://doi.org/10.1016/j.jaci.2009.02.032
- 46Serrano-Pariente J, Plaza V. Near-fatal asthma: a heterogeneous clinical entity. Curr Opin Allergy Clin Immunol. 2017; 17: 28-35. https://doi.org/10.1097/ACI.0000000000000333
- 47Hyzy RC, Travis WD, Hanna E, et al. Slow-onset asthma deaths have more eosinophils and health care utilization than rapid-onset deaths. Respir Med. 2008; 102: 1819-1826. https://doi.org/10.1016/j.rmed.2008.06.011
- 48Rosner SR, Pascoe CD, Blankman E, et al. The actin regulator zyxin reinforces airway smooth muscle and accumulates in airways of fatal asthmatics. PLoS One. 2017; 12:e0171728. https://doi.org/10.1371/journal.pone.0171728
- 49de Medeiros Matsushita M, da Silva LFF, dos Santos MA, et al. Airway proteoglycans are differentially altered in fatal asthma. J Pathol. 2005; 207: 102-110. https://doi.org/10.1002/path.1818
- 50Carroll N, Perry S, Karkhanis A, et al. The airway longitudinal elastic fiber network and mucosal folding in patients with asthma. Am J Respir Crit Care Med. 2000; 161: 244-248. https://doi.org/10.1164/ajrccm.161.1.9805005
- 51Milanese M, Crimi E, Scordamaglia A, et al. On the functional consequences of bronchial basement membrane thickening. J Appl Physiol. 2001; 91: 1035-1040. https://doi.org/10.1152/jappl.2001.91.3.1035
- 52McParland BE, Macklem PT, Paré PD. Airway wall remodeling: friend or foe? J Appl Physiol. 2003; 95: 426-434. https://doi.org/10.1152/japplphysiol.00159.2003
- 53Carroll NG, Mutavdzic S, James AL. Increased mast cells and neutrophils in submucosal mucous glands and mucus plugging in patients with asthma. Thorax. 2002; 57: 677-682.
- 54Kuyper LM, Paré PD, Hogg JC, et al. Characterization of airway plugging in fatal asthma. Am J Med. 2003; 115: 6-11. https://doi.org/10.1016/s0002-9343(03)00241-9
- 55Dunican EM, Elicker BM, Gierada DS, et al. Mucus plugs in patients with asthma linked to eosinophilia and airflow obstruction. J Clin Invest. 2018; 128: 997-1009. https://doi.org/10.1172/JCI95693
- 56Chen FH, Samson KT, Miura K, et al. Airway remodeling: a comparison between fatal and nonfatal asthma. J Asthma. 2004; 41: 631-638. https://doi.org/10.1081/jas-200026405
- 57Benatar SR. Fatal asthma. N Engl J Med. 1986; 314: 423-429. https://doi.org/10.1056/NEJM198602133140706
- 58Shijubo N, Itoh Y, Yamaguchi T, et al. Clara cell protein-positive epithelial cells are reduced in small airways of asthmatics. Am J Respir Crit Care Med. 1999; 160: 930-933. https://doi.org/10.1164/ajrccm.160.3.9803113
- 59Ruiz García S, Deprez M, Lebrigand K, et al. Novel dynamics of human mucociliary differentiation revealed by single-cell RNA sequencing of nasal epithelial cultures. Development. 2019; 146(20):dev177428. https://doi.org/10.1242/dev.177428
- 60Rubin BK, Priftis KN, Schmidt HJ, Henke MO. Secretory hyperresponsiveness and pulmonary mucus hypersecretion. Chest 2014; 146: 496-507. https://doi.org/10.1378/chest.13-2609
- 61Rossi RC, Anonni R, Ferreira DS, et al. Structural alterations and markers of endothelial activation in pulmonary and bronchial arteries in fatal asthma. Allergy Asthma Clin Immunol. 2019; 15: 50. https://doi.org/10.1186/s13223-019-0363-0
- 62Mauad T, Nascimento FBPd, Dolhnikoff M, et al. Pulmonary interstitial emphysema in fatal asthma: case report and histopathological review. BMC Pulm Med. 2018; 18: 50. https://doi.org/10.1186/s12890-018-0615-7
- 63Fraenkel DJ, Bardin PG, Sanderson G, et al. Lower airways inflammation during rhinovirus colds in normal and in asthmatic subjects. Am J Respir Crit Care Med. 1995; 151: 879-886. https://doi.org/10.1164/ajrccm/151.3_Pt_1.879
- 64Wang F, He XY, Baines KJ, et al. Different inflammatory phenotypes in adults and children with acute asthma. Eur Respir J. 2011; 38: 567-574. https://doi.org/10.1183/09031936.00170110
- 65Poznanski SM, Mukherjee M, Zhao N, et al. Asthma exacerbations on benralizumab are largely non-eosinophilic. Allergy. 2021; 76(1): 375-379. https://doi.org/10.1111/all.14514
- 66Patel S, Shah NM, Malhotra AM, et al. Inflammatory and microbiological associations with near-fatal asthma requiring extracorporeal membrane oxygenation. ERJ Open Res. 2020; 6(1): 00267-2019. https://doi.org/10.1183/23120541.00267-2019
- 67Corne JM, Marshall C, Smith S, et al. Frequency, severity, and duration of rhinovirus infections in asthmatic and non-asthmatic individuals: a longitudinal cohort study. Lancet. 2002; 359(1): 831-834. https://doi.org/10.1016/S0140-6736(02)07953-9
- 68Lamblin C, Gosset P, Tillie-leblond I, et al. Bronchial neutrophilia in patients with noninfectious status asthmaticus. Am J Respir Crit Care Med. 1998; 157: 394-402. https://doi.org/10.1164/ajrccm.157.2.97-02099
- 69Yii ACA, Tay T-R, Puah SH, et al. Blood eosinophil count correlates with severity of respiratory failure in life-threatening asthma and predicts risk of subsequent exacerbations. Clin Exp Allergy. 2019; 49(12): 1578-1586. https://doi.org/10.1111/cea.13465
- 70Price DB, Rigazio A, Campbell JD, et al. Blood eosinophil count and prospective annual asthma disease burden: a UK cohort study. Lancet Respir Med. 2015; 3: 849-858. https://doi.org/10.1016/S2213-2600(15)00367-7
- 71Westerhof GA, Korevaar DA, Amelink M, et al. Biomarkers to identify sputum eosinophilia in different adult asthma phenotypes. Eur Respir J. 2015; 46: 688-696. https://doi.org/10.1183/09031936.00012415
- 72Mukherjee M, Nair P. Blood or sputum eosinophils to guide asthma therapy? Lancet Respir Med. 2015; 3: 824-825. https://doi.org/10.1016/S2213-2600(15)00419-1
- 73Elliot JG, Noble PB, Mauad T, et al. Inflammation-dependent and independent airway remodelling in asthma. Respirology. 2018; 23: 1138-1145. https://doi.org/10.1111/resp.13360
- 74Elliot JG, Jensen CM, Mutavdzic S, et al. Aggregations of lymphoid cells in the airways of nonsmokers, smokers, and subjects with asthma. Am J Respir Crit Care Med. 2004; 169: 712-718. https://doi.org/10.1164/rccm.200308-1167OC
- 75Cagnoni EF, Ferreira DS, Ferraz da Silva LF, et al. Bronchopulmonary lymph nodes and large airway cell trafficking in patients with fatal asthma. J Allergy Clin Immunol. 2015; 135(5): 1352–1357.e9. https://doi.org/10.1016/j.jaci.2014.08.021
- 76Elliot JG, Abramson MJ, Drummer OH, et al. Time to death and mast cell degranulation in fatal asthma. Respirology. 2009; 14: 808-813. https://doi.org/10.1111/j.1440-1843.2009.01551.x
- 77Berger P, Girodet P-O, Begueret H, et al. Tryptase-stimulated human airway smooth muscle cells induce cytokine synthesis and mast cell chemotaxis. FASEB J. 2003; 17: 2139-2141. https://doi.org/10.1096/fj.03-0041fje
- 78El-Shazly A, Berger P, Girodet P-O, et al. Fraktalkine produced by airway smooth muscle cells contributes to mast cell recruitment in asthma. J Immunol. 2006; 176: 1860-1868. https://doi.org/10.4049/jimmunol.176.3.1860
- 79Girodet P-O, Ozier A, Trian T, et al. Mast cell adhesion to bronchial smooth muscle in asthma specifically depends on CD51 and CD44 variant 6. Allergy. 2010; 65: 1004-1012. https://doi.org/10.1111/j.1398-9995.2009.02308.x
- 80Hollins F, Kaur D, Yang W, et al. Human airway smooth muscle promotes human lung mast cell survival, proliferation, and constitutive activation: cooperative roles for CADM1, stem cell factor, and IL-6. J Immunol. 2008; 181: 2772-2780.
- 81Tunon-de-Lara J-M, Berger P, Bégueret H. Mast cells in airway smooth muscle. N Engl J Med. 2002; 347: 1040-1041; author reply 1040–1041. https://doi.org/10.1056/NEJM200209263471318
- 82Brightling CE, Bradding P, Symon FA, et al. Mast-cell infiltration of airway smooth muscle in asthma. N Engl J Med. 2002; 346: 1699-1705. https://doi.org/10.1056/NEJMoa012705
- 83Fregonese L, Swan FJ, van Schadewijk A, et al. Expression of the anaphylatoxin receptors C3aR and C5aR is increased in fatal asthma. J Allergy Clin Immunol. 2005; 115: 1148-1154. https://doi.org/10.1016/j.jaci.2005.01.068
- 84Sur S, Hunt LW, Crotty TB, Gleich GJ. Sudden-onset fatal asthma. Mayo Clin Proc. 1994; 69: 495-496. https://doi.org/10.1016/s0025-6196(12)61651-6
- 85Burgel P-R, Lazarus SC, Tam D-W, et al. Human eosinophils induce mucin production in airway epithelial cells via epidermal growth factor receptor activation. J Immunol. 2001; 167: 5948-5954. https://doi.org/10.4049/jimmunol.167.10.5948
- 86Persson EK, Verstraete K, Heyndrickx I, et al. Protein crystallization promotes type 2 immunity and is reversible by antibody treatment. Science. 2019; 364(6442): eaaw4295. https://doi.org/10.1126/science.aaw4295
- 87Zhang X, Zhang LI, Wang G, et al. Clinical phenotypes of patients hospitalized for an asthma exacerbation: prognostic implications. J Allergy Clin Immunol Pract. 2020. https://doi.org/10.1016/j.jaip.2020.09.031
- 88Serrano-Pariente J, Rodrigo G, Fiz JA, et al. Identification and characterization of near-fatal asthma phenotypes by cluster analysis. Allergy. 2015; 70: 1139-1147. https://doi.org/10.1111/all.12654
- 89 GBD 2015 Chronic Respiratory Disease Collaborators. Global, regional, and national deaths, prevalence, disability-adjusted life years, and years lived with disability for chronic obstructive pulmonary disease and asthma, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Respir Med. 2017; 5: 691-706. https://doi.org/10.1016/S2213-2600(17)30293-X
- 90Salmeron S, Liard R, Elkharrat D, et al. Asthma severity and adequacy of management in accident and emergency departments in France: a prospective study. Lancet. 2001; 358: 629-635.
- 91Marquette CH, Saulnier F, Leroy O, et al. Long-term prognosis of near-fatal asthma. A 6-year follow-up study of 145 asthmatic patients who underwent mechanical ventilation for a near-fatal attack of asthma. Am Rev Respir Dis. 1992; 146: 76-81. https://doi.org/10.1164/ajrccm/146.1.76
- 92Doshi V, Shenoy S, Ganesh A, et al. Near fatal asthma in an inner city population. Am J Ther. 2016; 23: e1375-e1380. https://doi.org/10.1097/MJT.0000000000000152
- 93Gonzalez Barcala FJ, Aboal Viñas J, Valdes Cuadrado L, et al. Trends in hospital admissions due to asthma in north-west Spain from 1995 to 2007. Allergol Immunopathol (Madr). 2010; 38: 254-258. https://doi.org/10.1016/j.aller.2009.11.008
- 94Ponte EV, Souza-Machado A, Souza-Machado C, et al. Clinical characteristics and prognosis in near-fatal asthma patients in Salvador, Brazil. J Bras Pneumol. 2011; 37: 431-437. https://doi.org/10.1590/s1806-37132011000400004
- 95Tanaka H, Nakatani E, Fukutomi Y, et al. Identification of patterns of factors preceding severe or life-threatening asthma exacerbations in a nationwide study. Allergy. 2018; 73: 1110-1118. https://doi.org/10.1111/all.13374
- 96Aubas C, Bourdin A, Aubas P, et al. Role of comorbid conditions in asthma hospitalizations in the south of France. Allergy. 2013; 68: 637-643. https://doi.org/10.1111/all.12137
- 97Brenner B, Corbridge T, Kazzi A. Intubation and mechanical ventilation of the asthmatic patient in respiratory failure. J Allergy Clin Immunol. 2009; 124: S19-S28. https://doi.org/10.1016/j.jaci.2009.05.008
- 98Bond KR, Horsley CA, Williams AB. Non-invasive ventilation use in status asthmaticus: 16 years of experience in a tertiary intensive care. Emerg Med Australas. 2018; 30: 187-192. https://doi.org/10.1111/1742-6723.12876
- 99Peters JI, Stupka JE, Singh H, et al. Status asthmaticus in the medical intensive care unit: a 30-year experience. Respir Med. 2012; 106: 344-348. https://doi.org/10.1016/j.rmed.2011.11.015
- 100Yamauchi Y, Yasunaga H, Matsui H, et al. Comparison of in-hospital mortality in patients with COPD, asthma and asthma-COPD overlap exacerbations. Respirology. 2015; 20: 940-946. https://doi.org/10.1111/resp.12556
- 101Kaur BP, Lahewala S, Arora S, et al. Asthma: Hospitalization Trends and Predictors of In-Hospital Mortality and Hospitalization Costs in the USA (2001–2010). Int Arch Allergy Immunol. 2015; 168: 71-78. https://doi.org/10.1159/000441687
- 102Nowak RM, Parker JM, Silverman RA, et al. A randomized trial of benralizumab, an antiinterleukin 5 receptor α monoclonal antibody, after acute asthma. Am J Emerg Med. 2015; 33: 14-20. https://doi.org/10.1016/j.ajem.2014.09.036
- 103Tello K, Hoffmann A, Beutel B, et al. Anti-interleukin-5 therapy (mepolizumab) in life-threatening asthma attack: a case-based discussion. Respir Med Case Rep. 2019; 28: 100927. https://doi.org/10.1016/j.rmcr.2019.100927
- 104Shrimanker R, Pavord ID, Yancey S, et al. Exacerbations of severe asthma in patients treated with mepolizumab. Eur Respir J. 2018; 52: https://doi.org/10.1183/13993003.01127-2018
- 105Ramakrishnan S, Camp JR, Vijayakumar B, et al. The use of benralizumab in the treatment of near fatal asthma: a new approach. Am J Respir Crit Care Med. 2020; 201(11): 1441-1443. https://doi.org/10.1164/rccm.202001-0093LE
- 106Pérez de Llano L, Blanco Cid N, Ortiz Piquer M, Dacal Rivas D. Compassionate use of a single dose of benralizumab in a near-fatal asthma exacerbation. J Investig Allergol Clin Immunol. 2020; 31(3). https://doi.org/10.18176/jiaci.0609
- 107Bachert C, Han JK, Desrosiers M, et al. Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials. Lancet. 2019; 394: 1638-1650. https://doi.org/10.1016/S0140-6736(19)31881-1
- 108Ferreira DS, Annoni R, Silva LFF, et al. Toll-like receptors 2, 3 and 4 and thymic stromal lymphopoietin expression in fatal asthma. Clin Exp Allergy. 2012; 42: 1459-1471. https://doi.org/10.1111/j.1365-2222.2012.04047.x
- 109Groneberg DA, Eynott PR, Lim S, et al. Expression of respiratory mucins in fatal status asthmaticus and mild asthma. Histopathology. 2002; 40: 367-373. https://doi.org/10.1046/j.1365-2559.2002.01378.x
- 110Shiang C, Mauad T, Senhorini A, et al. Pulmonary periarterial inflammation in fatal asthma. Clin Exp Allergy. 2009; 39: 1499-1507. https://doi.org/10.1111/j.1365-2222.2009.03281.x
- 111Den Otter I, Silva LFF, Carvalho ALN, et al. High-affinity immunoglobulin E receptor expression is increased in large and small airways in fatal asthma. Clin Exp Allergy. 2010; 40: 1473-1481. https://doi.org/10.1111/j.1365-2222.2010.03576.x
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