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Corticosteroid Therapy in Asthma. Attaran D, MD,Pulmonologist , Associate professor , Mashhad University of Medical Sciences. Definition of Asthma. A chronic inflammatory disorder of the airways Many cells and cellular elements play a role

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slide3

Corticosteroid Therapy in Asthma

Attaran D, MD,Pulmonologist , Associate professor ,

Mashhad University of Medical Sciences

slide4

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
slide5

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

slide6

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

slide7

Asthma Inflammation: Cells and Mediators

Source: Peter J. Barnes, MD

slide9

AsthmaInflammation: Cells and Mediators

Source: Peter J. Barnes, MD

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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

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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

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 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)

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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
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Steroid Complications

 Suppression of HPA axis (dose dependent &

duration)

 Systemic effects

 Localized effects

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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%

slide19

Steroid Insensitive Asthma

 Relative insensitivity to steroids

 Response to higher dose and prolonged periods

 More common than SR asthma

( 10-30 % patients )

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Diagnosis

 Severe asthma

 Persistent respiratory symptoms

 Frequent nocturnal symptoms

FEV1< 60-70%

 Systemic steroid therapy at young age

 Higher maintenance dose of oral steroid

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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

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 Possible microbial infection ( MP , CP )

 Combination therapy with LABA

 Final step is use of alternative anti inflammatory & immunomedulatory

( Omalizomab ,Cyclospurine ,IV Ig )

slide24

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