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Original Research: ASTHMA |

Limited Short-term Steroid Responsiveness Is Associated With Thickening of Bronchial Basement Membrane in Severe AsthmaRemodeling in Severe Asthma

Arnaud Bourdin, MD, PhD; Stephane Kleis, MD; Mohamad Chakra, MD; Isabelle Vachier, PhD; Fabrice Paganin, MD, PhD; Philippe Godard, MD; Pascal Chanez, MD, PhD
Author and Funding Information

Department of Respiratory Diseases, Centre Hospitalier et Universitaire (CHU) Montpellier, and Institut National de la Santé et de la Recherche Médicale (INSERM) U1046, Université Montpellier 1, Université Montpellier 2 (Drs Bourdin, Kleis, Chakra, Vachier, and Godard), Montpellier; Department of Respiratory Diseases, Groupe Hospitalier Sud Réunion (Dr Paganin), Saint Pierre de La Réunion, Réunion; and Département des Maladies Respiratoires (Dr Chanez), Assistance Publique—Hôpitaux de Marseille (AP-HM), Laboratoire d’immunologie, INSERM, Centre National de la Recherche Scientifique (CNRS) U600, Unité Mixte de Recherche (UMR) 6212, Université de la Méditerranée, Marseille, France.

Correspondence to: Arnaud Bourdin, MD, PhD, Department of Respiratory Diseases, Hôpital Arnaud de Villeneuve, CHU Montpellier, 371 Av. Doyen G. Giraud, 34295 Montpellier Cedex 5, France; e-mail: a-bourdin@chu-montpellier.fr


Deceased.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

Funding/Support: This study was supported by Direction de la Recherche Clinique, CHU Montpellier, France.


© 2012 American College of Chest Physicians


Chest. 2012;141(6):1504-1511. doi:10.1378/chest.11-0232
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Background:  The clinical manifestations of bronchial remodeling in asthma and the potential impact of this process on lung function remain unclear. We aimed to determine whether the presence of pathologic features of airway remodeling in patients with asthma was associated with steroid responsiveness in the short term.

Methods:  Sixty-three consecutive patients with severe asthma with chronic airflow impairment (post-bronchodilator FEV1 < 80% predicted values) were recruited, clinically characterized, and had an initial bronchoscopy where endobronchial biopsy and BAL were performed. BAL cellular content was reported and reticular basement membrane (RBM) thickness was measured by validated repeated measures. Patients were then treated with 1 mg/kg/d of methyl prednisone, directly administered IV, for 10 days. A threshold of 15% FEV1 improvement was used to discriminate responsive (group 1) and refractory patients (group 2).

Results:  Thirty-eight patients had a steroid responsiveness > 15% (group 1) and a thinner RBM at the biopsy level (5.78 ± 2.0 μm vs 7.60 ± 2.2 μm; P = .001) compared with nonsteroid responsive group 2 patients as defined. The best predictors for being unresponsive were no long-term treatment with oral steroids and increased RBM thickness. The associated receiver operating characteristic curve indicated that RBM thickness could predict steroid responsiveness below 15% with an area under the curve of 0.747 (P = .0002) at a threshold of 7 μm.

Conclusions:  Features of airway remodeling are associated with limited short-term steroid responsiveness in severe asthma.

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