Marisa Dolhnikoff, MD, PhD, Luiz F. F. da Silva, MD, Bianca B

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The outer wall of small airways is a major site of remodeling in fatal asthma Marisa Dolhnikoff, MD, PhD, Luiz F.F. da Silva, MD, Bianca B. de Araujo, PhD, Higor A.P. Gomes, MD, Sandra Fernezlian, MSc, Adri Mulder, PhD, Jan H. Lindeman, MD, PhD, Thais Mauad, MD, PhD Journal of Allergy and Clinical Immunology Volume 123, Issue 5, Pages 1090-1097.e1 (May 2009) DOI: 10.1016/j.jaci.2009.02.032 Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Photomicrographs of small airways and PP of asthmatic patients (A, C, E, and G) and control subjects (B, D, F, and H) stained with anti-collagen I (Fig 1, A-D) and anti-collagen III (Fig 1, E-H). L, Lumen; EP, epithelium. Arrows indicate alveolar septa. Scale bars = 50 μm (Fig 1, A-F) and 100 μm (Fig 1, G-H). The graphs show collagen I and III content (in square micrometers per micrometer) in the small airways and PP in asthmatic patients and control subjects. IS, IA of the small airways; OS, OA of the small airways. The median is represented as horizontal bars. Collagen I: ∗P ≤ .001 compared with control subjects. Collagen III: ∗P < .04 compared with control subjects. Journal of Allergy and Clinical Immunology 2009 123, 1090-1097.e1DOI: (10.1016/j.jaci.2009.02.032) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Photomicrographs of small airways and PP of asthmatic patients (A, C, E, and G) and control subjects (B, D, F, and H) stained with anti-fibronectin (Fig 2, A-D) and anti-MMP-9 (Fig 2, E-H). L, Lumen. Scale bars = 50 μm (Fig 2, A, B, E, and F) and 100 μm (Fig 2, C, D, G, and H). The graphs show fibronectin and MMP-9 content (in square micrometers per micrometer) in the small airways and PP in asthmatic patients and control subjects. IS, IA of the small airways; OS, OA of small airways. The median is represented as horizontal bars. Fibronectin: ∗P < .02 compared with control subjects. MMP-9: ∗P < .05 compared with control subjects. Journal of Allergy and Clinical Immunology 2009 123, 1090-1097.e1DOI: (10.1016/j.jaci.2009.02.032) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 The diagram shows a summary of the differences in ECM composition in the small airways between patients with fatal asthma and control subjects observed in the present and previous studies. ↑, Significantly higher compared with that seen in control subjects. ↓, Significantly lower compared with that seen in control subjects. ∗Mauad et al.20∗∗de Medeiros Matsushita.4 #Araujo et al.29 Journal of Allergy and Clinical Immunology 2009 123, 1090-1097.e1DOI: (10.1016/j.jaci.2009.02.032) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions