Effects of age and disease severity on systemic corticosteroid responses in asthma

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. PetersW. Gerald Teague, Merritt Fajt, Sally E. Wenzel, Serpil C. Erzurum, Elliot Israel

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Rationale: Phenotypic distinctions between severe asthma (SA) and nonsevere asthma (NONSA) may be confounded by differential adherence or incorrect use of corticosteroids. Objectives: To determine if there are persistent phenotypic distinctions between SA (as defined by 2014 American Thoracic Society/European Respiratory Society guidelines) and NONSA after intramuscular triamcinolone acetonide (TA), and to identify predictors of a corticosteroid response in these populations. Methods: A total of 526 adults age 18 years and older (315 SA) and 188 children age 6 to less than 18 years (107 SA) in the NHLBI Severe Asthma Research Program III were characterized before and 3 weeks after TA. The primary outcome for corticosteroid response was defined as greater than or equal to 10-point improvement in percent predicted FEV1. Measurements and Main Results: Adult asthma groups exhibited a small but significant mean FEV1% predicted improvement after TA (SA group mean difference, 3.4%; 95% confidence interval, 2.2-4.7%; P = 0.001), whereas children did not. Adult SA continued to manifest lower FEV1 and worse asthma control as compared with NONSAafter TA. In children, after TAonly prebronchodilator FEV1 distinguished SA from NONSA. A total of 21% of adults with SA and 20% of children with SA achieved greater than or equal to 10% improvement after TA. Baseline bronchodilator response and fractional exhaled nitric oxide had good sensitivity and specificity for predicting response in all groups except children with NONSA. Conclusions: One in five patients with SA exhibit greater than or equal to 10% improvement in FEV1 with parenteral corticosteroid. Those likely to respond had greater bronchodilator responsiveness and fractional exhaled nitric oxide levels. In adults, differences in airflow obstruction and symptoms between SA and NONSA persist after parenteral corticosteroids, suggesting a component of corticosteroid nonresponsive pathobiology in adults with SA that may differ in children. Clinical trial registered with www.clinicaltrials.gov (NCT 01606826).

Original languageEnglish (US)
Pages (from-to)1439-1448
Number of pages10
JournalAmerican journal of respiratory and critical care medicine
Volume195
Issue number11
DOIs
StatePublished - Jun 1 2017

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Adrenal Cortex Hormones
Asthma
Triamcinolone Acetonide
Bronchodilator Agents
Nitric Oxide
National Heart, Lung, and Blood Institute (U.S.)

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Phipatanakul, Wanda ; Mauger, David T. ; Sorkness, Ronald L. ; Gaffin, Jonathan M. ; Holguin, Fernando ; Woodruff, Prescott G. ; Ly, Ngoc P. ; Bacharier, Leonard B. ; Bhakta, Nirav R. ; Moore, Wendy C. ; Bleecker, Eugene R. ; Hastie, Annette T. ; Meyers, Deborah A. ; Castro, Mario ; Fahy, John V. ; Fitzpatrick, Anne M. ; Gaston, Benjamin M. ; Jarjour, Nizar N. ; Levy, Bruce D. ; Peters, Stephen P. ; Teague, W. Gerald ; Fajt, Merritt ; Wenzel, Sally E. ; Erzurum, Serpil C. ; Israel, Elliot. / Effects of age and disease severity on systemic corticosteroid responses in asthma. In: American journal of respiratory and critical care medicine. 2017 ; Vol. 195, No. 11. pp. 1439-1448.
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abstract = "Rationale: Phenotypic distinctions between severe asthma (SA) and nonsevere asthma (NONSA) may be confounded by differential adherence or incorrect use of corticosteroids. Objectives: To determine if there are persistent phenotypic distinctions between SA (as defined by 2014 American Thoracic Society/European Respiratory Society guidelines) and NONSA after intramuscular triamcinolone acetonide (TA), and to identify predictors of a corticosteroid response in these populations. Methods: A total of 526 adults age 18 years and older (315 SA) and 188 children age 6 to less than 18 years (107 SA) in the NHLBI Severe Asthma Research Program III were characterized before and 3 weeks after TA. The primary outcome for corticosteroid response was defined as greater than or equal to 10-point improvement in percent predicted FEV1. Measurements and Main Results: Adult asthma groups exhibited a small but significant mean FEV1{\%} predicted improvement after TA (SA group mean difference, 3.4{\%}; 95{\%} confidence interval, 2.2-4.7{\%}; P = 0.001), whereas children did not. Adult SA continued to manifest lower FEV1 and worse asthma control as compared with NONSAafter TA. In children, after TAonly prebronchodilator FEV1 distinguished SA from NONSA. A total of 21{\%} of adults with SA and 20{\%} of children with SA achieved greater than or equal to 10{\%} improvement after TA. Baseline bronchodilator response and fractional exhaled nitric oxide had good sensitivity and specificity for predicting response in all groups except children with NONSA. Conclusions: One in five patients with SA exhibit greater than or equal to 10{\%} improvement in FEV1 with parenteral corticosteroid. Those likely to respond had greater bronchodilator responsiveness and fractional exhaled nitric oxide levels. In adults, differences in airflow obstruction and symptoms between SA and NONSA persist after parenteral corticosteroids, suggesting a component of corticosteroid nonresponsive pathobiology in adults with SA that may differ in children. Clinical trial registered with www.clinicaltrials.gov (NCT 01606826).",
author = "Wanda Phipatanakul and Mauger, {David T.} and Sorkness, {Ronald L.} and Gaffin, {Jonathan M.} and Fernando Holguin and Woodruff, {Prescott G.} and Ly, {Ngoc P.} and Bacharier, {Leonard B.} and Bhakta, {Nirav R.} and Moore, {Wendy C.} and Bleecker, {Eugene R.} and Hastie, {Annette T.} and Meyers, {Deborah A.} and Mario Castro and Fahy, {John V.} and Fitzpatrick, {Anne M.} and Gaston, {Benjamin M.} and Jarjour, {Nizar N.} and Levy, {Bruce D.} and Peters, {Stephen P.} and Teague, {W. Gerald} and Merritt Fajt and Wenzel, {Sally E.} and Erzurum, {Serpil C.} and Elliot Israel",
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Phipatanakul, W, Mauger, DT, Sorkness, RL, Gaffin, JM, Holguin, F, Woodruff, PG, Ly, NP, Bacharier, LB, Bhakta, NR, Moore, WC, Bleecker, ER, Hastie, AT, Meyers, DA, Castro, M, Fahy, JV, Fitzpatrick, AM, Gaston, BM, Jarjour, NN, Levy, BD, Peters, SP, Teague, WG, Fajt, M, Wenzel, SE, Erzurum, SC & Israel, E 2017, 'Effects of age and disease severity on systemic corticosteroid responses in asthma', American journal of respiratory and critical care medicine, vol. 195, no. 11, pp. 1439-1448. https://doi.org/10.1164/rccm.201607-1453OC

Effects of age and disease severity on systemic corticosteroid responses in asthma. / Phipatanakul, Wanda; Mauger, David T.; Sorkness, Ronald L.; Gaffin, Jonathan M.; Holguin, Fernando; Woodruff, Prescott G.; Ly, Ngoc P.; Bacharier, Leonard B.; Bhakta, Nirav R.; Moore, Wendy C.; Bleecker, Eugene R.; Hastie, Annette T.; Meyers, Deborah A.; Castro, Mario; Fahy, John V.; Fitzpatrick, Anne M.; Gaston, Benjamin M.; Jarjour, Nizar N.; Levy, Bruce D.; Peters, Stephen P.; Teague, W. Gerald; Fajt, Merritt; Wenzel, Sally E.; Erzurum, Serpil C.; Israel, Elliot.

In: American journal of respiratory and critical care medicine, Vol. 195, No. 11, 01.06.2017, p. 1439-1448.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effects of age and disease severity on systemic corticosteroid responses in asthma

AU - Phipatanakul, Wanda

AU - Mauger, David T.

AU - Sorkness, Ronald L.

AU - Gaffin, Jonathan M.

AU - Holguin, Fernando

AU - Woodruff, Prescott G.

AU - Ly, Ngoc P.

AU - Bacharier, Leonard B.

AU - Bhakta, Nirav R.

AU - Moore, Wendy C.

AU - Bleecker, Eugene R.

AU - Hastie, Annette T.

AU - Meyers, Deborah A.

AU - Castro, Mario

AU - Fahy, John V.

AU - Fitzpatrick, Anne M.

AU - Gaston, Benjamin M.

AU - Jarjour, Nizar N.

AU - Levy, Bruce D.

AU - Peters, Stephen P.

AU - Teague, W. Gerald

AU - Fajt, Merritt

AU - Wenzel, Sally E.

AU - Erzurum, Serpil C.

AU - Israel, Elliot

PY - 2017/6/1

Y1 - 2017/6/1

N2 - Rationale: Phenotypic distinctions between severe asthma (SA) and nonsevere asthma (NONSA) may be confounded by differential adherence or incorrect use of corticosteroids. Objectives: To determine if there are persistent phenotypic distinctions between SA (as defined by 2014 American Thoracic Society/European Respiratory Society guidelines) and NONSA after intramuscular triamcinolone acetonide (TA), and to identify predictors of a corticosteroid response in these populations. Methods: A total of 526 adults age 18 years and older (315 SA) and 188 children age 6 to less than 18 years (107 SA) in the NHLBI Severe Asthma Research Program III were characterized before and 3 weeks after TA. The primary outcome for corticosteroid response was defined as greater than or equal to 10-point improvement in percent predicted FEV1. Measurements and Main Results: Adult asthma groups exhibited a small but significant mean FEV1% predicted improvement after TA (SA group mean difference, 3.4%; 95% confidence interval, 2.2-4.7%; P = 0.001), whereas children did not. Adult SA continued to manifest lower FEV1 and worse asthma control as compared with NONSAafter TA. In children, after TAonly prebronchodilator FEV1 distinguished SA from NONSA. A total of 21% of adults with SA and 20% of children with SA achieved greater than or equal to 10% improvement after TA. Baseline bronchodilator response and fractional exhaled nitric oxide had good sensitivity and specificity for predicting response in all groups except children with NONSA. Conclusions: One in five patients with SA exhibit greater than or equal to 10% improvement in FEV1 with parenteral corticosteroid. Those likely to respond had greater bronchodilator responsiveness and fractional exhaled nitric oxide levels. In adults, differences in airflow obstruction and symptoms between SA and NONSA persist after parenteral corticosteroids, suggesting a component of corticosteroid nonresponsive pathobiology in adults with SA that may differ in children. Clinical trial registered with www.clinicaltrials.gov (NCT 01606826).

AB - Rationale: Phenotypic distinctions between severe asthma (SA) and nonsevere asthma (NONSA) may be confounded by differential adherence or incorrect use of corticosteroids. Objectives: To determine if there are persistent phenotypic distinctions between SA (as defined by 2014 American Thoracic Society/European Respiratory Society guidelines) and NONSA after intramuscular triamcinolone acetonide (TA), and to identify predictors of a corticosteroid response in these populations. Methods: A total of 526 adults age 18 years and older (315 SA) and 188 children age 6 to less than 18 years (107 SA) in the NHLBI Severe Asthma Research Program III were characterized before and 3 weeks after TA. The primary outcome for corticosteroid response was defined as greater than or equal to 10-point improvement in percent predicted FEV1. Measurements and Main Results: Adult asthma groups exhibited a small but significant mean FEV1% predicted improvement after TA (SA group mean difference, 3.4%; 95% confidence interval, 2.2-4.7%; P = 0.001), whereas children did not. Adult SA continued to manifest lower FEV1 and worse asthma control as compared with NONSAafter TA. In children, after TAonly prebronchodilator FEV1 distinguished SA from NONSA. A total of 21% of adults with SA and 20% of children with SA achieved greater than or equal to 10% improvement after TA. Baseline bronchodilator response and fractional exhaled nitric oxide had good sensitivity and specificity for predicting response in all groups except children with NONSA. Conclusions: One in five patients with SA exhibit greater than or equal to 10% improvement in FEV1 with parenteral corticosteroid. Those likely to respond had greater bronchodilator responsiveness and fractional exhaled nitric oxide levels. In adults, differences in airflow obstruction and symptoms between SA and NONSA persist after parenteral corticosteroids, suggesting a component of corticosteroid nonresponsive pathobiology in adults with SA that may differ in children. Clinical trial registered with www.clinicaltrials.gov (NCT 01606826).

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