ASTHMA AND STEROIDS

1. Corticosteroids
In Obstructive Airway Disease

2. Outline
Part 1
• Asthma as an inflammatory disease
• Role of steroids in the treatment for asthma
exacerbation
• Steroids vs Steroids
• Management of Asthma Exacerbation
Part 2
• COPD as an inflammatory disease
• Management of COPD exacerbation
• Role of Systemic Corticosteroids in the treatment
of COPD Exacerbation

4. 4
ASTHMA CONTROL = Symptom Control + Future Risk of Adverse Outcomes

5. Pathophysiology
Airway limitation
characterized by:
Bronchoconstriction
Airway
hyperresponsiveness
Airway edema
Influenced by AIRWAY
INFLAMMATION

6. Chronic Inflammation in
Asthma Peter Barnes, 2008

7. Allergic Asthmatic
Inflammation

8. Cellular effect of
corticosteroids
Barnes, P; Adcock, I

9. Asthma Exacerbations
• EXACERBATION is an acute or sub-acute
worsening of symptoms and lung function compared
with the patient’s usual status
• Terminology considerations:
• ‘Flare-up’ is the preferred term for discussion with
patients as ‘Exacerbation’ is a difficult term for patients
• ‘Attack’ has highly variable meanings for patients and
clinicians
• ‘Episode’ does not convey clinical urgency
Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2015. Available from: www.ginasthma.org

10. Complications: Acute
Severe Asthma
• Theophylline Toxicity
• Lactic acidosis
• Electrolyte
disturbances –
hypokalemia,
hypophosphatemia,
hypomagnesemia
• Myopathy
• Anoxic brain injury
Papiris, et al. Clinical Review: Severe Asthma. Crit Care 2002; 6:30-44
• Pneumothorax
• Pneumomediastinum
• Subcutaneous
emphysema
• Tracheoesophageal
fistula (MV pxs)
• Myocardial Ischemia
• Mucus plugging and
Atelectasis

11. Acute Exacerbation
Management Considerations
Early treatment is vital in managing an acute
episode and should be initiated before patient reaches
hospital
The goals of treatment include:
 Arterial oxygenation
 Relief of airway obstruction
 Reduction of inflammation
 Prevention of relapse
Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2015. Available from: www.ginasthma.org

12. Acute Asthma Exacerbations
Role of Corticosteroids
Early use of corticosteroids is associated with:
• Reduced risk of relapse
• Reduction in hospitalization rate
• Reduction in β-agonist use
The main corticosteroids used for asthma include:
• Methylprednisolone
• Prednisolone
• Prednisone
Fiel SB, et al. J Asthma. 2006;43:321-331.

13. Methyl group: increased
glucocorticoid activity and
less mineralocorticoid
property

14. Early Studies on Methylprednisolone
in Acute Asthma

15. Pharmacology of SteroidsRELATIVE POTENCY AND EQUIVALENT DOSES
OF DIFFERENT SYSTEMIC STEROIDS
Brunton LL, Lazo JS, Parker KL, eds. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 11th ed. New York, NY: McGraw-Hill; 2006.

16. Pharmacology of Steroids
COMPARATIVE AFFINITY OF STEROIDS
(TO LUNG RECEPTOR AND CARRIER PROTEINS)

17. 5 10 15
BALFConcentration
(ngGlucocorticoid/µgUrea)
0
25
50
75
Methylprednisolone
r=0.95 (P<0.001)
Prednisolone
r=0.54 (P<0.05)
Plasma Concentration
(ng Glucocorticoid/µgUrea)
Adapted with permission from Vichyanond P et al. J Allergy Clin Immunol. 1989;84;867
Methylprednisolone has higher degree of
BRONCHOALVEOLAR PENETRATION than prednisolone

18. Potential Benefits of Corticosteroids in
the Treatment of Asthma
• Enhancement of B receptor responsiveness by upregulating B
receptors on airway smooth muscle
• Dec in capillary basement membrane permeability; dec vascular leak
from endothelial cells
• Dec leukocyte attachment; dec number of eosinophils, mast cells,
and dendritic cells
• Modulation of calcium migration intracellularly
• Reduction in airway mucus production
• Suppression of IgE receptor binding
• Interruption of arachidonic acid inflammatory pathways
• Decreased airway smooth muscle contraction, mucosal edema, and
airway inflammation
• Airway remodeling
• Decreased cytokine and mediator production from epithelial cells
•

19. Adverse Reactions to
Glucocorticoids
• Ophthalmic – cataracts, inc IOP,
glaucoma
• CV– HTN, CHF, VTE
• GI – PUD, pancreatitis
• Endocrine/Metabolic
• truncal obesity, moon facies, buffalo
hump, lipomatosis, hepatomegaly
• Acne, hirsutism, ED, menstrual
irregularities
• Growth suppression in children
• Hyperglycemia, DKA
• Negative balance of N, K,Ca
• Na retention, hypoK, met alka
• Secondary adrenal insufficiency
• Musculoskeletal– proximal myopathy,
osteoporosis, vertebral compression
fractures, Avascular necrosis of
femoral and humeral heads
• Neuropsychiatric – convulsion,
benign intracranial hypertension,
affective, behavioral, cognitive
defects
• Dermatologic – facial erythema, thin
fragile skin, petechiae and
ecchymoses, violaceous striae,
impaired wound healing
• Immune, infectious – suppression of
delayed hypersensitivity; neutrophilia,
monocytopenia, lymphocytopenia,
dec inflammatory responses;
susceptibility to infection
Jameson L, et. al. ENDOCRINOLOGY Adult and Pediatric
(Chap 100 Glucocorticolid Therapy. Axelrod, L;) 7th edition, Elsevier 2016

20. Corbridge, Thomas. Et al. Severe Asthma Exacerbation
Textbook of Critical Care, Elsevier, 2011

26. Rajaram, S Life Threatening Asthma
Critical Care Medicine 3rd Ed, Elsevier 2008

36. Summary
ON ASTHMA:
Airway inflammation is a KEY feature of asthma
Patients present with variable symptomatology
and asthma severity
Control is a major challenge in asthma
management
Symptom control and reduction of risk are major
goals of therapy

37. Summary
ON CORTICOSTEROIDS:
Corticosteroids play important role in asthma
management:
 acute exacerbations of asthma
 maintenance therapy for severe asthma
 short courses for worsening asthma
In Acute Exacerbations of Asthma, systemic
corticosteroids reduce:
 relapse rate
 B agonist use
 hospital admissions
Basic pharmacologic properties are important
considerations in choosing appropriate systemic steroid
for asthma management