Presentation is loading. Please wait.

Presentation is loading. Please wait.

Intraepithelial neutrophils in pediatric severe asthma are associated with better lung function  Cecilia K. Andersson, PhD, Alexandra Adams, MBBS, Prasad.

Published byGordon Hudson Modified over 6 years ago

Similar presentations

Presentation on theme: "Intraepithelial neutrophils in pediatric severe asthma are associated with better lung function  Cecilia K. Andersson, PhD, Alexandra Adams, MBBS, Prasad."— Presentation transcript:

1 Intraepithelial neutrophils in pediatric severe asthma are associated with better lung function 
Cecilia K. Andersson, PhD, Alexandra Adams, MBBS, Prasad Nagakumar, MBBS, Cara Bossley, MDRes, Atul Gupta, MDRes, Daphne De Vries, BSc, Afiqah Adnan, BSc, Andrew Bush, MD, Sejal Saglani, MD, Clare M. Lloyd, PhD  Journal of Allergy and Clinical Immunology  Volume 139, Issue 6, Pages e11 (June 2017) DOI: /j.jaci Copyright © 2016 The Authors Terms and Conditions

2 Fig 1 Eosinophils and neutrophils in different lung compartments. Eosinophil percentage in BAL (A) (controls n = 11, STRA n = 31), numbers per area of submucosa (B) (controls without asthma n = 7, STRA n = 20), and intraepithelial eosinophils per length of reticular basement membrane (C) (controls n = 7, STRA n = 20). Representative micrographs of Congo Red stain for eosinophils in controls without asthma (D) and patients with STRA (E). F, High magnification picture of epithelium with no eosinophils in patients with STRA. Neutrophil percentage in BAL (G) (controls without asthma n = 12, STRA n = 52), numbers per area of submucosa (H) (controls without asthma n = 10, STRA n = 28), and proportion of intraepithelial neutrophils (I) (controls without asthma n = 13, STRA n = 37). Representative micrographs of immunohistochemical stain for elastase in controls without asthma (J) and patients with STRA (K). L, High magnification picture of intraepithelial neutrophils in patients with STRA. Scale bar: 200 μm (Fig 1, D and J), 100 μm (Fig 1, E and K), 20 μm (Fig 1, F), and 10 μm (Fig 1, L). Statistical significance between controls without asthma and patients with STRA was tested using Mann-Whitney test. *P < .05, **P < .01, and ***P < .001. Journal of Allergy and Clinical Immunology  , e11DOI: ( /j.jaci ) Copyright © 2016 The Authors Terms and Conditions

3 Fig 2 Sources and expression of IL-17A in children with STRA compared with controls without asthma. Representative micrograph of immunohistochemical stain for IL-17A in children with STRA (A). Scale bar: 100 μm. Quantification of the number of IL-17A–expressing cells per area in submucosa (B) (controls without asthma n = 6, STRA n = 39) and bronchial epithelium (C) (controls without asthma n = 6, STRA n = 32). BAL levels of IL-17A (D) (controls without asthma n = 11, STRA n = 23) and IL-22 (E) (controls without asthma n = 11, STRA n = 23) in controls without asthma and children with STRA. Percentages of IL-17A–expressing TH17 (F) (controls without asthma n = 10, STRA n = 13) and gamma delta (G) (controls without asthma n = 8, STRA n = 11) lymphocytes in children with STRA compared with controls without asthma. Statistical significance between controls without asthma and children with STRA was tested using Mann-Whitney test. NS, Not significant. Journal of Allergy and Clinical Immunology  , e11DOI: ( /j.jaci ) Copyright © 2016 The Authors Terms and Conditions

4 Fig 3 Representative micrographs of immunohistochemical stain for IL-17RA in controls without asthma and patients with STRA (A and B, respectively). Scare bar 100 μm (Fig 3, A) and 50 μm (Fig 3, B). Quantification of the expression (positive pixels per area) of IL-17RA in submucosa (controls without asthma n = 6, STRA n = 31) and epithelium (controls without asthma n = 6, STRA n = 24) (C and D, respectively). mRNA expression of IL-17RA and C in PBECs after stimulation with IL-17A and budesonide (Bud) (controls without asthma n = 3, STRA n = 3) (E and F, respectively). Correlations between ACT score and IL-17RA expression in epithelium (G) (n = 21). Statistical significance between controls without asthma and children with STRA was tested using Mann-Whitney test and correlation analysis was performed using Spearman rank test, where a P value of less than .05 was considered significant. *P < .05, **P < .01, and ***P < .001. Journal of Allergy and Clinical Immunology  , e11DOI: ( /j.jaci ) Copyright © 2016 The Authors Terms and Conditions

5 Fig 4 Levels of IL-8 (A) (controls without asthma n = 9, STRA n = 24) and IL-6 (B) (controls without asthma n = 12, STRA n = 23) in BAL. Levels of IL-8 (C) and IL-6 (D) in culture supernatant from PBECs after stimulation with IL-17A, IL-22, and budesonide (controls n = 4, STRA n = 7). Differences in submucosal eosinophils (E) (Neuhi n = 10, Neulo n = 15), BAL eosinophils (F) (Neuhi n = 12, Neulo n = 20), total IgE (G) (Neuhi n = 10, Neulo n = 21), Feno (H) (Neuhi n = 11, Neulo n = 18), ACT score (I) (Neuhi n = 12, Neulo n = 20), dose of inhaled corticosteroids (J) (Neuhi n = 12, Neulo n = 21), and FEV1 % predicted (K) within the group of children with STRA based on the presence of intraepithelial neutrophils (Neuhi n = 13, Neulo n = 21). Correlations between FEV1 % predicted and proportion of intraepithelial neutrophils (L) (n = 36). Patients from the cohort previously published in Bossley et al5 are shown in gray. Statistical significance between controls and patients with STRA was tested using Mann-Whitney test and correlation analysis was performed using Spearman rank test, where a P value of less than .05 was considered significant. Feno, Fraction of exhaled nitric oxide. *P < .05. Journal of Allergy and Clinical Immunology  , e11DOI: ( /j.jaci ) Copyright © 2016 The Authors Terms and Conditions

6 Fig E1 Measurement of GRO in culture supernatants from PBECs after stimulation with IL-17A, IL-22, and budesonide (Bud) (Fig E1, A) (controls without asthma n = 4, STRA n = 4). Statistical significance between controls without asthma and STRA was tested using Mann-Whitney test, where a *P value of less than .05 was considered significant. Journal of Allergy and Clinical Immunology  , e11DOI: ( /j.jaci ) Copyright © 2016 The Authors Terms and Conditions

7 Fig E2 Tissue density of IL-17A in submucosa (A), IL-17RA in submucosa (B), and IL-17RA in epithelium (C) in bronchial biopsies from children with STRA divided into Neutrophilhigh vs Neutrophillow groups. Statistical significance was tested using Mann-Whitney test, where a P value of less than .05 was considered significant. Neu, Neutrophil. Journal of Allergy and Clinical Immunology  , e11DOI: ( /j.jaci ) Copyright © 2016 The Authors Terms and Conditions

8 Fig E3 Measurement of IL-6 (A), IL-8 (B), IL-13 (C), IP-10 (D), MCP-1 (E), MDC (F), FGF-2 (G), and IFN-γ (H) in culture supernatants from PBECs after stimulation with IL-17A, IL-22, and budesonide (Bud) (controls without asthma n = 4, STRA n = 4) using Milliplex assay. Statistical significance between controls without asthma and STRA was tested using Mann-Whitney test, where a *P value of less than .05 was considered significant. Journal of Allergy and Clinical Immunology  , e11DOI: ( /j.jaci ) Copyright © 2016 The Authors Terms and Conditions

9 Fig E4 Measurement of IL-6 (A) and IL-8 (B) in culture supernatants from 16HBEs after stimulation with IL-17A, IL-22, and budesonide (Bud) using ELISA. Journal of Allergy and Clinical Immunology  , e11DOI: ( /j.jaci ) Copyright © 2016 The Authors Terms and Conditions

10 Fig E5 The effect of IL-17A on airway remodeling parameters. Measurement of VEGF in culture supernatants from PBECs after stimulation with IL-17A, IL-22, and budesonide (A) (controls without asthma n = 4, STRA n = 4). mRNA expression in PBECs after stimulation with IL-17A, IL-22, and budesonide of fibronectin (B) and collagen I (C) (controls without asthma n = 3, STRA n = 3). RBM thickness in controls without asthma compared with STRA (D) (controls without asthma n = 7, STRA n = 21) and RBM thickness within the STRA group when divided into Neutrophilhigh subgroup vs Neutrophillow subgroup (E). Representative micrographs of bronchial biopsies stained with Masson's trichrome staining for collagen (blue) (F control and G STRA). Subepithelial collagen deposition (H) (nonasthmatic controls n = 7, STRA n = 9) in bronchial biopsies from controls without asthma and children with STRA expressed as positive pixels per area. Statistical significance between controls without asthma and STRA was tested using Mann-Whitney test, where a *P value of less than .05 was considered significant. Journal of Allergy and Clinical Immunology  , e11DOI: ( /j.jaci ) Copyright © 2016 The Authors Terms and Conditions

11 Fig E6 Immunohistochemical double staining of bronchial biopsies of IL-17A (red, AlexaF 555) and elastase (A) or CD3 (B) (green, AlexaF 488). Corresponding isotype controls are shown in C and D. Nuclei are stained blue with DAPI. DAPI, 4'-6-Diamidino-2-phenylindole, dihydrochloride; IHC, immunohistochemistry. Scale bar: 100 μm. Journal of Allergy and Clinical Immunology  , e11DOI: ( /j.jaci ) Copyright © 2016 The Authors Terms and Conditions

Download ppt "Intraepithelial neutrophils in pediatric severe asthma are associated with better lung function  Cecilia K. Andersson, PhD, Alexandra Adams, MBBS, Prasad."

Similar presentations

Inhaled corticosteroids decrease subepithelial collagen deposition by modulation of the balance between matrix metalloproteinase-9 and tissue inhibitor.

Inhaled corticosteroids decrease subepithelial collagen deposition by modulation of the balance between matrix metalloproteinase-9 and tissue inhibitor.
Are leukocytes in asthmatic patients aging faster

Are leukocytes in asthmatic patients aging faster
Allergen-induced expression of IL-25 and IL-25 receptor in atopic asthmatic airways and late-phase cutaneous responses  Chris J. Corrigan, MD, PhD, Wei.

Allergen-induced expression of IL-25 and IL-25 receptor in atopic asthmatic airways and late-phase cutaneous responses  Chris J. Corrigan, MD, PhD, Wei.
Simultaneously increased fraction of exhaled nitric oxide levels and blood eosinophil counts relate to increased asthma morbidity  Andrei Malinovschi,

Simultaneously increased fraction of exhaled nitric oxide levels and blood eosinophil counts relate to increased asthma morbidity  Andrei Malinovschi,
Sejal Saglani, MD, Stephen Lui, PhD, Nicola Ullmann, MD, Gaynor A

Sejal Saglani, MD, Stephen Lui, PhD, Nicola Ullmann, MD, Gaynor A
Russell S. Traister, MD, PhD, Crystal E. Uvalle, BS, Gregory A

Russell S. Traister, MD, PhD, Crystal E. Uvalle, BS, Gregory A
Vitamin D enhances production of soluble ST2, inhibiting the action of IL-33  Paul E. Pfeffer, MRCP, Yin-Huai Chen, MSc, Grzegorz Woszczek, PhD, Nick C.

Vitamin D enhances production of soluble ST2, inhibiting the action of IL-33  Paul E. Pfeffer, MRCP, Yin-Huai Chen, MSc, Grzegorz Woszczek, PhD, Nick C.
The antimicrobial protein short palate, lung, and nasal epithelium clone 1 (SPLUNC1) is differentially modulated in eosinophilic and noneosinophilic chronic.

The antimicrobial protein short palate, lung, and nasal epithelium clone 1 (SPLUNC1) is differentially modulated in eosinophilic and noneosinophilic chronic.
IL-13 and TH2 cytokine exposure triggers matrix metalloproteinase 7–mediated Fas ligand cleavage from bronchial epithelial cells  Samuel J. Wadsworth,

IL-13 and TH2 cytokine exposure triggers matrix metalloproteinase 7–mediated Fas ligand cleavage from bronchial epithelial cells  Samuel J. Wadsworth,
IL-25 as a novel therapeutic target in nasal polyps of patients with chronic rhinosinusitis  Hyun-Woo Shin, MD, PhD, Dong-Kyu Kim, MD, Min-Hyun Park, MD,

IL-25 as a novel therapeutic target in nasal polyps of patients with chronic rhinosinusitis  Hyun-Woo Shin, MD, PhD, Dong-Kyu Kim, MD, Min-Hyun Park, MD,
Increased airway smooth muscle in preschool wheezers who have asthma at school age  Ruth O'Reilly, MBChBBAO, Nicola Ullmann, MD, Samantha Irving, BSc,

Increased airway smooth muscle in preschool wheezers who have asthma at school age  Ruth O'Reilly, MBChBBAO, Nicola Ullmann, MD, Samantha Irving, BSc,
Increased TGF-β2 in severe asthma with eosinophilia

Increased TGF-β2 in severe asthma with eosinophilia
Extracellular eosinophilic traps in association with Staphylococcus aureus at the site of epithelial barrier defects in patients with severe airway inflammation 

Extracellular eosinophilic traps in association with Staphylococcus aureus at the site of epithelial barrier defects in patients with severe airway inflammation 
Intraepithelial neutrophils in pediatric severe asthma are associated with better lung function  Cecilia K. Andersson, PhD, Alexandra Adams, MBBS, Prasad.

Intraepithelial neutrophils in pediatric severe asthma are associated with better lung function  Cecilia K. Andersson, PhD, Alexandra Adams, MBBS, Prasad.
Frank Kirstein, PhD, Natalie E

Frank Kirstein, PhD, Natalie E
The airway epithelium nucleotide-binding domain and leucine-rich repeat protein 3 inflammasome is activated by urban particulate matter  Jeremy A. Hirota,

The airway epithelium nucleotide-binding domain and leucine-rich repeat protein 3 inflammasome is activated by urban particulate matter  Jeremy A. Hirota,
Pentraxin 3 deletion aggravates allergic inflammation through a TH17-dominant phenotype and enhanced CD4 T-cell survival  Jyoti Balhara, MSc, Lianyu Shan,

Pentraxin 3 deletion aggravates allergic inflammation through a TH17-dominant phenotype and enhanced CD4 T-cell survival  Jyoti Balhara, MSc, Lianyu Shan,
Type 2 innate lymphoid cells in induced sputum from children with severe asthma  Prasad Nagakumar, MBBS, Laura Denney, PhD, Louise Fleming, MD, Andrew.

Type 2 innate lymphoid cells in induced sputum from children with severe asthma  Prasad Nagakumar, MBBS, Laura Denney, PhD, Louise Fleming, MD, Andrew.
Restoration of T-box–containing protein expressed in T cells protects against allergen- induced asthma  Jung Won Park, MD, Hyun Jung Min, MS, Jung Ho Sohn,

Restoration of T-box–containing protein expressed in T cells protects against allergen- induced asthma  Jung Won Park, MD, Hyun Jung Min, MS, Jung Ho Sohn,
D prostanoid receptor 2 (chemoattractant receptor–homologous molecule expressed on TH2 cells) protein expression in asthmatic patients and its effects.

D prostanoid receptor 2 (chemoattractant receptor–homologous molecule expressed on TH2 cells) protein expression in asthmatic patients and its effects.

Similar presentations

Ads by Google