title: Limited short-term steroid responsiveness is associated with thickening of bronchial basement membrane in severe asthma.
abstract: 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 FEV(1) < 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% FEV(1) 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.
authors.affiliation: 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, Montpellier, France. Electronic address: a-bourdin@chu-montpellier.fr.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Bourdin
authors.affiliation: 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, Montpellier, France.
authors.forename: Stephane
authors.initials: S
authors.lastname: Kleis
authors.affiliation: 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, Montpellier, France.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Chakra
authors.affiliation: 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, Montpellier, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Vachier
authors.affiliation: Department of Respiratory Diseases, Groupe Hospitalier Sud Réunion, Saint Pierre de La Réunion, Réunion, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Paganin
authors.affiliation: 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, Montpellier, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Godard
authors.affiliation: Département des Maladies Respiratoires, 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.
authors.forename: Pascal
authors.initials: P
authors.lastname: Chanez
mesh_terms: D000328:Adult; D000368:Aged; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology*; D001485:Basement Membrane / Q000473:pathology*; D001706:Biopsy; D001999:Bronchoscopy; D015897:Comorbidity; D003937:Diagnosis, Differential; D005260:Female; D005541:Forced Expiratory Volume; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use*; D012372:ROC Curve; D012129:Respiratory Function Tests; D018709:Statistics, Nonparametric; D011795:Surveys and Questionnaires; D014057:Tomography, X-Ray Computed
chemical_list: D018927:Anti-Asthmatic Agents; D005938:Glucocorticoids; D011241:Prednisone