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Evaluation of airway remode l ling & angiogenesis in C ough V ariant A sthma

Evaluation of airway remode l ling & angiogenesis in C ough V ariant A sthma. İ.Kıvılcım Oğuzülgen , Nalan Akyürek*, Nurdan Köktürk ve Haluk Türktaş Gazi University School of Medicine Dept. Of Pulmonary Medicine and Pathology*, Ankara. Cough Variant Asthma (CVA).

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Evaluation of airway remode l ling & angiogenesis in C ough V ariant A sthma

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  1. Evaluation of airway remodelling & angiogenesis in CoughVariantAsthma İ.Kıvılcım Oğuzülgen,Nalan Akyürek*, Nurdan Köktürk ve Haluk Türktaş Gazi University School of Medicine Dept. Of Pulmonary Medicine and Pathology*, Ankara

  2. Cough Variant Asthma (CVA) • In a subgroup of asthmaticpatients, cough is the predominant or solesymptom. This condition has been termed coughvariant asthma (CVA) in 1979. Dicpinigaitis PV. CHEST 2006; 129:75S–79S. Corrao WM et al. N Engl J Med 1979; 300: 633-7.

  3. Cough Variant Asthma (CVA) • CVA comprise a distinct subgroup of individuals withasthma, rather than simply being asthmatic patientswho cough. Subjects with the typicalform of asthma do not differ from healthy volunteersin terms of experimentally measured cough reflexsensitivity, whereas those with CVA have a significantly more sensitive cough reflex.

  4. Diagnosis of CVA • In a patient suspected of having CVA butin whom physical examination and spirometryfindings are nondiagnostic, MIC testing shouldbe performed to confirm the presence ofasthma. However, a diagnosis of CVA is establishedonly after the resolution of cough with specific antiasthmatic therapy. Dicpinigaitis PV. CHEST 2006; 129:75S–79S.

  5. Airway remodelling in asthma 5 Nature Reviews Immunology 2008; 8:218-230

  6. Airway remodelling in asthma Epithelial desquamation Inflamation Subepithelial fibrosis with tickening of basement membrane Vasodilatation Smooth muscle hypertrophia Mucous gland hyperplasia ... .......... Edema Angiogenesis

  7. Aim: • The aim of this study was to evaluate airway remodeling and bronchial mucosal agiogenesis in CVA patients and compare the findings with classic asthma and control subjects with other causes of cough.

  8. Methods: Patients with cough: • Patients with duration of cough over 8 weeks • Who has never smoked • Who has not experienced any upper or lower airway infection within 3 months • Who do not have any chronic lung disease • With normal oscultation findings, normal PFT, normal chest x-ray

  9. Methods-II: Classic asthmatics: • Steroid naive mild-moderate asthmaics: Classic asthma

  10. Methods-III: Classic asthmatics • Patients with chronic cough (≥ 8 weeks) • (Inclusion /exclusion criteria) • PFT Non-asthmatic cough (-) İnhaled CS • Methacoline challenge test (+) CVA • Fiberoptic bronchoscopy with bronchial biopsies

  11. Methods-IV: • Bronchial biopsy samples were stained with hematoxilen eosin and asseses for the typical morphological cahnges of asthma. • Immunoperoxidase staining was performed to retrieve antigen expression for Collagen type 4 and CD31 antibodies in vessels. By the computerized image analysis system; the total number of vessels was divided by the biopsy area examined to determine the number of vessels per square millimeter of lamina propria to a depth of 150 m below the basement

  12. Non-asthmatic cough patients: • 3 patients: GER • .. patients: Post nasal drip syndrome • .. patents: Cough associated with ACE inhibitors • ... Patients: Miscalenous

  13. Study subjects 13

  14. Patients characteristics

  15. Bronchial biopsy findins Classic asthma Non-asthmatic cough CVA • Hematoxilen eosin (x200)

  16. Bronchial biopsy findins Classic asthma Non-asthmatic cough • Hematoxilen eosin (x400)

  17. Bronchial biopsy findings 17

  18. Presence of airway inflammation

  19. Basal membrane p=0.000 p= 0.000 Basal membrane (µm) p=0.025 Non-asthmatic cough CVA Classic asthma

  20. Bronchial biopsy findings (angiogenesis) Classic asthma (x200) CVA (x200) Non-asthmatic cough(x400) • Anti-human collagen 4

  21. Angiogenesis (Collagen 4) Vessel density / mm2 p= NS p=0.003 p=0.001

  22. Bronchial biopsy findings (angiogenesis) Classic asthma (x200) CVA (x200) Non-asthmatic cough(x400) • Anti-CD 31

  23. Angiogenesis (CD 31) Vessel density / mm2

  24. Discussion • Angiogenesis as a part of airway remodelling in asthma has been accepted in the last 10 years. • Angiogenesis is present even in mild-moderate asthmatics. • The main cause of angiogensis is the secretion of angiogenic growth factors (VEGF) secondary to inflammation. Li X et al. Am J Tespir Crit Care Med 1997; 156:229-33 Doherty T et al Curr Opin Immunol 2007;19:676-680. Walters EH et al. Curr Opin Allergy Immunol 2008;8:39-43.

  25. Inflammation & pathological studies on CVA

  26. Inflammation & pathological studies on CVA

  27. Conclusion • These finding suggest that remodelling and partly angiogenesis is present in CVA but findings are moderate when compared to classic asthma.

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