Cara J Bossley1, Louise Fleming2, Nicola Ullmann2, Atul Gupta3, Alexandra Adams4, Prasad Nagakumar4, Andrew Bush2, Sejal Saglani5. 1. Respiratory Paediatrics, Royal Brompton Hospital and National Heart & Lung Institute, Imperial College London, London, United Kingdom; Respiratory Paediatrics, Kings College Hospital, London, United Kingdom. 2. Respiratory Paediatrics, Royal Brompton Hospital and National Heart & Lung Institute, Imperial College London, London, United Kingdom; Leukocyte Biology, National Heart & Lung Institute, Imperial College London, London, United Kingdom. 3. Leukocyte Biology, National Heart & Lung Institute, Imperial College London, London, United Kingdom. 4. Respiratory Paediatrics, Royal Brompton Hospital and National Heart & Lung Institute, Imperial College London, London, United Kingdom. 5. Respiratory Paediatrics, Royal Brompton Hospital and National Heart & Lung Institute, Imperial College London, London, United Kingdom; Leukocyte Biology, National Heart & Lung Institute, Imperial College London, London, United Kingdom. Electronic address: s.saglani@imperial.ac.uk.
Abstract
BACKGROUND: There is no agreed upon definition of systemic corticosteroid response in asthmatic children. Moreover, pediatric severe therapy-resistant asthma (STRA) is heterogeneous, and thus response to steroids is unlikely to be uniform in all patients. OBJECTIVE: We sought to evaluate the utility of a multidomain approach incorporating symptoms, lung function, and inflammation to determine steroid responsiveness in pediatric patients with STRA. METHODS: Eighty-two children (median age, 12 years) with STRA received a clinically indicated dose of intramuscular steroid. Changes in 4 separate domains were assessed 4 weeks after intramuscular triamcinolone acetonide: normalization of (1) symptoms (Asthma Control Test score, >19/25 or 50% increase), (2) spirometric results (FEV1 ≥80% of predicted value or ≥15% increase), (3) fraction of exhaled nitric oxide levels (<24 ppb), and (4) sputum eosinophil counts (<2.5%). Fifty-four of 82 children had complete data in all 4 domains. RESULTS: Twenty-three (43%) of 54 children had a symptom response, 29 (54%) of 54 had a lung function response, 28 (52%) of 54 had a fraction of exhaled nitric oxide response, and 29 (54%) of 54 had a sputum eosinophil response. Although a similar proportion of children responded to systemic corticosteroids in each domain, there were no reliable predictors of a response pattern. Seven (13%) of 54 were complete responders (response in all domains), 8 (15%) of 54 were nonresponders (no response in any domain), and 39 (72%) of 54 were partial responders (response in ≥1 domain). CONCLUSIONS: A multidomain evaluation of systemic steroid responsiveness using pragmatic clinical assessments confirms childhood STRA is heterogeneous and that a complete response in symptoms and inflammatory and physiologic parameters is rare. Individual response patterns to systemic steroids might be useful in guiding the choice of add-on therapies in each child as a step toward achieving personalized medicine.
BACKGROUND: There is no agreed upon definition of systemic corticosteroid response in asthmatic children. Moreover, pediatric severe therapy-resistant asthma (STRA) is heterogeneous, and thus response to steroids is unlikely to be uniform in all patients. OBJECTIVE: We sought to evaluate the utility of a multidomain approach incorporating symptoms, lung function, and inflammation to determine steroid responsiveness in pediatric patients with STRA. METHODS: Eighty-two children (median age, 12 years) with STRA received a clinically indicated dose of intramuscular steroid. Changes in 4 separate domains were assessed 4 weeks after intramuscular triamcinolone acetonide: normalization of (1) symptoms (Asthma Control Test score, >19/25 or 50% increase), (2) spirometric results (FEV1 ≥80% of predicted value or ≥15% increase), (3) fraction of exhaled nitric oxide levels (<24 ppb), and (4) sputum eosinophil counts (<2.5%). Fifty-four of 82 children had complete data in all 4 domains. RESULTS: Twenty-three (43%) of 54 children had a symptom response, 29 (54%) of 54 had a lung function response, 28 (52%) of 54 had a fraction of exhaled nitric oxide response, and 29 (54%) of 54 had a sputum eosinophil response. Although a similar proportion of children responded to systemic corticosteroids in each domain, there were no reliable predictors of a response pattern. Seven (13%) of 54 were complete responders (response in all domains), 8 (15%) of 54 were nonresponders (no response in any domain), and 39 (72%) of 54 were partial responders (response in ≥1 domain). CONCLUSIONS: A multidomain evaluation of systemic steroid responsiveness using pragmatic clinical assessments confirms childhood STRA is heterogeneous and that a complete response in symptoms and inflammatory and physiologic parameters is rare. Individual response patterns to systemic steroids might be useful in guiding the choice of add-on therapies in each child as a step toward achieving personalized medicine.
Authors: Adnan Custovic; Danielle Belgrave; Lijing Lin; Eteri Bakhsoliani; Aurica G Telcian; Roberto Solari; Clare S Murray; Ross P Walton; John Curtin; Michael R Edwards; Angela Simpson; Magnus Rattray; Sebastian L Johnston Journal: Am J Respir Crit Care Med Date: 2018-05-15 Impact factor: 21.405
Authors: Elena Goleva; Denise C Babineau; Michelle A Gill; Leisa P Jackson; Baomei Shao; Zheng Hu; Andrew H Liu; Cynthia M Visness; Christine A Sorkness; Donald Y M Leung; Alkis Togias; William W Busse Journal: J Allergy Clin Immunol Date: 2018-07-27 Impact factor: 10.793
Authors: Anne M Fitzpatrick; Susan T Stephenson; Milton R Brown; Khristopher Nguyen; Shaneka Douglas; Lou Ann S Brown Journal: J Allergy Clin Immunol Pract Date: 2016-09-21
Authors: Wanda Phipatanakul; David T Mauger; Ronald L Sorkness; Jonathan M Gaffin; Fernando Holguin; Prescott G Woodruff; Ngoc P Ly; Leonard B Bacharier; Nirav R Bhakta; Wendy C Moore; Eugene R Bleecker; Annette T Hastie; Deborah A Meyers; Mario Castro; John V Fahy; Anne M Fitzpatrick; Benjamin M Gaston; Nizar N Jarjour; Bruce D Levy; Stephen P Peters; W Gerald Teague; Merritt Fajt; Sally E Wenzel; Serpil C Erzurum; Elliot Israel Journal: Am J Respir Crit Care Med Date: 2017-06-01 Impact factor: 21.405
Authors: Andrea M Coverstone; Jonathan S Boomer; Daphne Lew; Leonard B Bacharier; Mario Castro Journal: Ann Allergy Asthma Immunol Date: 2020-12-02 Impact factor: 6.347
Authors: Delaney Griffiths; Lauren M Giancola; Kelly Welsh; Kristen MacGlashing; Christine Thayer; Sigfus Gunnlaugsson; Natalie P Stamatiadis; Gabriella C Sierra; Adam Hammond; Kimberly F Greco; Tregony Simoneau; Sachin N Baxi; Jonathan M Gaffin Journal: Pediatr Pulmonol Date: 2020-10-26