Inhaled Corticosteroids: Indications and Uses

• Adrenal cortical hormones are steroid chemicals secreted by the adrenal cortex.
• Endogenous refers to substances produced inside the body.
• Exogenous refers to substances manufactured to be placed inside the body.
• Immunoglobulin E (IgE) is a gamma globulin produced by cells in the respiratory tract.
• Prostaglandins are hormone-type substances circulating throughout the body.
• Steroid diabetes is hyperglycemia resulting from glucocorticoid therapy.
• Steroids, also known as glucocorticoids or corticosteroids, are agents that produce an anti-inflammatory response.

Clinical Indications for Use of Inhaled Corticosteroids

• Inhaled corticosteroids are available in formulations for oral inhalation (lung delivery) and intranasal delivery.
• Orally inhaled agents are for maintenance and control therapy of chronic persistent asthma, identified as requiring step 2 care or greater
• Step 2 asthma has symptoms occurring more than 2 days/week but not daily with night awakenings occurring 3-4 nights/month, having FEV1 or PEF 80% of predicted.
• Inhaled agents can be used with systemic corticosteroids in severe asthma.
• Inhaled corticosteroids in combination with other agents are recommended by the American Thoracic Society (ATS).

Identification of Aerosolized Corticosteroids

• Beclomethasone dipropionate HFA (QVAR)
• Flunisolide hemihydrate HFA (AeroSpan)
• Fluticasone propionate (Flovent HFA, Flovent Diskus)
• Fluticasone furoate (Arnuity Ellipta)

Identification of Aerosolized Corticosteroids (Combinations)

• Fluticasone propionate/salmeterol (Advair Diskus, Advair HFA)
• Budesonide/formoterol fumarate HFA (Symbicort)
• Mometasone furoate/formoterol fumarate HFA (Dulera)
• Fluticasone furoate/vilanterol (Breo Ellipta)

Hypothalamic–Pituitary–Adrenal Axis (HPA Axis)

• The HPA axis is the pathway for release and control of endogenous corticosteroids.
• Stimulation of the hypothalamus causes corticotropin-releasing factor (CRF) to be released.
• CRF goes to the anterior pituitary gland where corticotropin is released into the bloodstream.
• Corticotropin, or adrenocorticotropic hormone (ACTH), stimulates the adrenal cortex to secrete glucocorticoids, such as cortisol.

HPA Suppression with Steroid Use

• The body cannot distinguish between endogenous and exogenous steroids. Glucocorticoid drugs raise the body’s level.
• It inhibits the hypothalamus and pituitary glands, referred to as HPA suppression or adrenal suppression.

Physiology of Aerosolized Corticosteroids

• The production of the body’s own glucocorticoids follows a rhythmic cycle, termed diurnal or circadian rhythm.
• Cortisol levels are highest in the morning at 8 a.m.
• Examples of interference with cycle: Jet lag & night shift work
• Alternate-day steroid therapy mimics the natural diurnal rhythm by giving a steroid drug early in the morning when normal tissue levels are high, allowing regular diurnal secretion in the HPA system to resume on alternate days.
• Corticosteroids treat inflammation in asthmatics and COPD patients to achieve an anti-inflammatory effect.

Nature of the Inflammatory Response

• Inflammation produces redness, swelling, heat, and pain.
• Triple response: redness is the local dilation of blood vessels, occurring in seconds.
• Flare: Reddish color several centimeters from the site, occurring 15 to 30 seconds after injury
• Wheal: Local swelling, occurring in minutes

Nature of Inflammatory Response: Four Categories

• Increased vascular permeability: An exudate is formed in surrounding tissues.
• Leukocytic infiltration: White blood cells (WBC) emigrate through capillary walls in response to attractant chemicals(chemotaxis).
• Phagocytosis: White cells and macrophages (in lungs) ingest and process foreign material such as bacteria.
• Mediator cascade: Histamine and chemoattractant factors are released at the injury site.
• Various inflammatory mediators, such as complement and arachidonic acid products, are generated.

Inflammation of the Airway

• Chronic bronchitis and asthma are most common.
• Treatment with antiinflammatory agents such as glucocorticoids reduces airway inflammation, thereby reducing airway hyperresponsiveness and predisposition to acute episodes of obstruction.
• Asthmatic reactions are biphasic: early phase and late phase.
• The early asthmatic response is caused by immunoglobulin E (IgE).
• Mast Cells and eosinophils trigger an inflammatory response in asthma.
• Mast cell mediators and the release of cytokines recruit other inflammatory cells to cause late-phase reaction.
• The response occurs after ~6–8 hours and can last up to 24 hours.

This lesson covers the clinical indications for inhaled corticosteroids, including their use in maintenance and control therapy for chronic persistent asthma. It also differentiates between orally inhaled and intranasal delivery formulations. Key terms such as endogenous, exogenous, and steroid diabetes are defined.