Corticosteroid Therapy in Asthma

3. Corticosteroid Therapy in Asthma Attaran D, MD,Pulmonologist , Associate professor , Mashhad University of Medical Sciences

4. Definition of Asthma • A chronic inflammatory disorder of the airways • Many cells and cellular elements play a role • Chronic inflammation is associated with airway hyperresponsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing • Widespread, variable, and often reversible airflow limitation

5. Introduction Steroids are the most effective therapy for asthma  Steroids are recommended as the first line therapy for all patients  Inhaled steroids have been a great advance in the management of asthma  Inhaled steroids control inflammation & symptoms without significant side effects

6. Molecular effects of corticosteroids  Anti inflammatory gene activation  Switching off inflammatory genes  Inflammatory cell inhibition ( lymph , Mast cell, Eos , Mac )  Increased B2 receptor effects  Steroids have no distinct effects on airway muscle

7. Asthma Inflammation: Cells and Mediators Source: Peter J. Barnes, MD

9. AsthmaInflammation: Cells and Mediators Source: Peter J. Barnes, MD

11. Clinlcal use  A single dose of steroids has no effect on the early response to allergen But does inhibit the late response  The fraction of steroid that is inhaled acts locally on the airway mucosa  Systemic absorption from airway, alveolar surface & oropharyngeal swallowing  Absorbed fraction metabolized in the liver ( first pass metabolism )  Budesonide & Fluticasone have a greater first pass metabolism

12. Estimate Comparative Daily Dosages for Inhaled Glucocorticosteroids by Age Drug Low Daily Dose (g) Medium Daily Dose (g) High Daily Dose (g) > 5 y Age < 5 y > 5 y Age < 5 y > 5 y Age < 5 y

14.  Use of spacer reduce oropharyngeal deposition and complications  Low dose inhaled steroid up to 400mcg BDP ( 250mcg Fluticasone )  Medium dose inhaled steroid up to 1000mcg BDP ( 500mcg F )  High dose inhaled steroid up to 2000mcg BDP (1000mcg F)

15. In acute severe asthma maximal beneficial effectis usually achieved with 30-40 mg Prednisolone daily •  Usual maintenance dose is 10-15 mg •  Oral steroids are usually given as a single dose in the morning

16. Steroid Complications  Suppression of HPA axis (dose dependent & duration)  Systemic effects  Localized effects

18. Steroid Resistant (SR) Asthma Failure to improve FEV1 > 15 % following 7-14days of 20 mg prednisolone Type1 :Acquired or cytokine induced ,GR normal, GR binding affinity low Steroid side effects yes, reversible and > 95 %SR patients Type 2 :Genetic ,GR low ,GR binding affinity normal ,Steroid side effects no, irreversible and< 5%

19. Steroid Insensitive Asthma  Relative insensitivity to steroids  Response to higher dose and prolonged periods  More common than SR asthma ( 10-30 % patients )

20. Diagnosis  Severe asthma  Persistent respiratory symptoms  Frequent nocturnal symptoms FEV1< 60-70%  Systemic steroid therapy at young age  Higher maintenance dose of oral steroid

21. Management of SR or SI Asthma  Evaluation for comorbid or masquerading conditions  VCD,GERD, ABPA,HP,Upper airway dis  Assessing of persistent tissue inflammation ( e NO , ECP )  Ensure adequate treatment adherence

22.  Possible microbial infection ( MP , CP )  Combination therapy with LABA  Final step is use of alternative anti inflammatory & immunomedulatory ( Omalizomab ,Cyclospurine ,IV Ig )

24. خدايا به من آرامشي عطا فرما • تا بپذيرم آنچه را نمي توانم تغيير دهم • و شهامتي تا تغيير دهم آنچه را مي توانم • و دركي تا بفهم تفاوت اين دو را • خدايا به من آرامشي عطا فرما • تا بپذيرم آنچه را نمي توانم تغيير دهم • و شهامتي تا تغيير دهم آنچه را مي توانم • و دركي تا بفهم تفاوت اين دو را