Effectiveness of bronchial thermoplasty in patients with severe refractory asthma: Clinical and histopathologic correlations Marina Pretolani, PharmD,

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Presentation transcript:

Effectiveness of bronchial thermoplasty in patients with severe refractory asthma: Clinical and histopathologic correlations Marina Pretolani, PharmD, PhD, Anders Bergqvist, PhD, Gabriel Thabut, MD, PhD, Marie-Christine Dombret, MD, Dominique Knapp, MS, Fatima Hamidi, MS, Loubna Alavoine, MD, Camille Taillé, MD, PhD, Pascal Chanez, MD, PhD, Jonas S. Erjefält, PhD, Michel Aubier, MD Journal of Allergy and Clinical Immunology Volume 139, Issue 4, Pages 1176-1185 (April 2017) DOI: 10.1016/j.jaci.2016.08.009 Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Histopathologic alterations induced by using BT. Bronchial biopsy specimens were assessed for immunohistochemical and morphometric analyses of ASM area (as a percentage of positive α-actin immunostained area over the submucosal tissue area; A), SBM thickening (in micrometers; B), submucosal blood (C) and lymphatic vessels (D), and submucosal nerve fibers (E) after immunolabeling of CD31, D2-40, and PGP9.5 antigens, respectively (all expressed as ‰ of positive immunostaining over the submucosal tissue area); of PGP9.5+ nerves infiltrating the ASM (in numbers per square millimeter of ASM; F); of mucous glands (as percentage of prevalence; G), eosinophils (H), and neutrophils (I) as proportions of bronchial mucosa with positive immunoreactivity for ECP and MPO, respectively (in percentages); of regenerating epithelium (as percentage prevalence; J); and of stratified columnar epithelium (as percentage prevalence; K), metaplastic epithelium (as percentage prevalence; L), squamous metaplastic epithelium (as percentage prevalence; M), goblet cell hypertrophy/hyperplasia (as percentage prevalence; N), and epithelial neuroendocrine (PGP9.5+) cells (in numbers per square millimeter of intact areas of bronchial epithelium; O). Comparisons were made by using the Student t test for paired values. Journal of Allergy and Clinical Immunology 2017 139, 1176-1185DOI: (10.1016/j.jaci.2016.08.009) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Structural effects of BT in bronchial biopsy specimens from patients with severe asthma. Bright-field micrographs of bronchial biopsy specimens subjected to quadruple immunohistochemical staining for smooth muscle actin (red), the vascular endothelial marker CD31 (green), lymph endothelial marker, podoplanin (D2-40, brown), and the neuronal marker PGP.9.5 (black) are shown. A and B, Biopsy specimens taken before and 3 months after BT, respectively (note that Fig 2, B, rather than representing the average, exemplifies a case in which smooth muscle was virtually absent). C, A neuroendocrine cell (NEC) in the bronchial epithelium detected based on nuclear distribution of PGP (arrowhead). D and E, Subepithelial nerves (arrowheads) in the subepithelial region before (Fig 2, D) and after (Fig 2, E) BT. F, Smooth muscle–associated nerves (arrowhead) exemplified in a biopsy specimen collected before BT treatment. Scale bars = 250 μm (Fig 2, A and B) or 40 μm (Fig 2, C-F). sm, Smooth muscle; bv, blood vessels; lv, lymphatic vessels. Journal of Allergy and Clinical Immunology 2017 139, 1176-1185DOI: (10.1016/j.jaci.2016.08.009) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Differences in histopathologic alterations in patients with BT-responsive and partially responsive severe asthma. ASM area (A), SBM thickening (B), submucosal PGP+ nerves (C), ASM-associated PGP+ nerves (D), and neuroendocrine epithelial PGP+ cells (E) in bronchial biopsy specimens from patients with severe asthma collected before (n = 15) and 3 months after BT are shown. Patients were separated into 2 groups according to their clinical responsiveness (n = 11, ACT score ≥ 15) or partial or no responsiveness (n = 4, ACT score < 15) to BT at 12 months. Overall P values were less than .01 (Fig 3, A), .31 (Fig 3, B), less than .01 (Fig 3, C), .06 (Fig 3, D), and less than .01 (Fig 3, E; Kruskal-Wallis test). *P < .05 compared with values obtained before BT and †P < .05 compared with patients responsive to BT, Student t test for paired values. Journal of Allergy and Clinical Immunology 2017 139, 1176-1185DOI: (10.1016/j.jaci.2016.08.009) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions