CorticosteroidsIn Obstructive Airway Disease

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

ASTHMA CONTROL = Symptom Control + Future Risk of Adverse Outcomes

Pathophysiology

Airway limitation characterized by:BronchoconstrictionAirway hyperresponsivenessAirway edemaInfluenced by AIRWAY INFLAMMATION

Chronic Inflammation in Asthma Peter Barnes, 2008

Allergic Asthmatic Inflammation

Cellular effect of corticosteroids

Barnes, P; Adcock, I

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

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

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

Acute Asthma ExacerbationsRole of Corticosteroids

Early use of corticosteroids is associated with:• Reduced risk of relapse• Reduction in hospitalization rate• Reduction in β-agonist useThe main corticosteroids used for asthma include:• Methylprednisolone• Prednisolone• Prednisone

Fiel SB, et al. J Asthma. 2006;43:321-331.

Methyl group: increased glucocorticoid activity and less mineralocorticoid property

Early Studies on Methylprednisolone in Acute Asthma

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.

Pharmacology of SteroidsCOMPARATIVE AFFINITY OF STEROIDS (TO LUNG RECEPTOR AND CARRIER PROTEINS)

5 10 15

BA

LF C

once

ntra

tion

(ng

Glu

coco

rtic

oid/

µg U

rea)

0

25

50

75Methylprednisolone 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

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•

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

Corbridge, Thomas. Et al. Severe Asthma ExacerbationTextbook of Critical Care, Elsevier, 2011

Rajaram, S Life Threatening AsthmaCritical Care Medicine 3rd Ed, Elsevier 2008

Summary

ON ASTHMA:Airway inflammation is a KEY feature of

asthmaPatients present with variable

symptomatology and asthma severityControl is a major challenge in asthma

managementSymptom control and reduction of risk are

major goals of therapy

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