Inhaled Corticosteroids: Indications & Uses

• Adrenal cortical hormones are chemicals secreted by the adrenal cortex and are referred to as steroids.
• Endogenous means produced inside the body.
• Exogenous means manufactured to be placed inside the body, such as medication.
• 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, which breaks down proteins and fats for gluconeogenesis.
• Steroids, also known as glucocorticoids or corticosteroids, produce an anti-inflammatory response in the body.

Clinical Indications for Use of Inhaled Corticosteroids

• Inhaled corticosteroids are used for oral inhalation (lung delivery) and intranasal delivery, for:
  • Maintenance and control therapy of chronic persistent asthma (step 2 care or greater per guidelines).
  • Step 2 asthma involves symptoms more than 2 days/week, night awakenings 3-4 nights/month, and FEV1 or PEF 80% or greater than predicted.
• Severe asthma, and may allow lessening or stopping systemic corticosteroids for asthma control.
• Use in combination with other agents, as 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)

• Pathway for release and control of endogenous corticosteroids:
  • Hypothalamus stimulation sends impulses to median eminence, releasing corticotropin-releasing factor (CRF).
  • CRF goes to the anterior pituitary gland, releasing corticotropin into the bloodstream.
  • Corticotropin, or adrenocorticotropic hormone (ACTH), stimulates the adrenal cortex to secrete glucocorticoids like cortisol.

HPA Suppression with Steroid Use

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

Physiology of Aerosolized Corticosteroids

• The body's production of glucocorticoids follows a rhythmic cycle, termed diurnal or circadian rhythm.
• Cortisol levels are highest at 8 a.m.
• Interference with this cycle can be caused by jet lag or night shift work.
• Alternate-day steroid therapy mimics the natural diurnal rhythm by administering the steroid drug early in the morning, when normal tissue levels are high.
• On alternate days, regular diurnal secretion in the HPA system can resume.
• Corticosteroids are used to treat inflammation in asthmatics and COPD patients.

Nature of Inflammatory Response

• Inflammation produces redness, swelling, heat, and pain.
• Triple response:
  • Redness: Local dilation of blood vessels, occurring in seconds.
  • Flare: Reddish color several centimeters from the injury 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 forms in surrounding tissues.
• Leukocytic infiltration: White blood cells (WBC) emigrate through capillary walls (diapedesis) 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 with inflammatory mediators, such as complement and arachidonic acid products, are generated.

Nature of Inflammatory Response and Airways

• Chronic bronchitis caused by smoking and asthma with a range of triggers are most common.
• Treatment with anti-inflammatory agents such as glucocorticoids is important. This is to reduce the basal level of airway inflammation, thereby reducing airway hyperresponsiveness and predisposition to acute episodes of obstruction.
• Asthmatic reactions are biphasic with early and late phases.
• The early asthmatic response is caused by immunoglobulin E (IgE).
  • Peaks at about 15 minutes.
• Mast cells and eosinophils are the major cells responsible for an inflammatory response in asthma.
  • Mast cell mediators and release of cytokines recruit other inflammatory cells to cause late-phase reaction.
  • Response occurs after 6–8 hours and can last up to 24 hours.

Overview of adrenal cortical hormones, steroids, and inhaled corticosteroids. Includes clinical indications for use in asthma maintenance and control therapy. Discusses endogenous vs. exogenous sources and the role of IgE and prostaglandins.