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Which of the following describes the primary action of inhaled corticosteroids (ICS) in asthma management?
Which of these mechanisms is NOT associated with glucocorticoids?
What is the expected time frame to realize maximal benefit from inhaled corticosteroid therapy?
Which condition is NOT a valid use for systemic corticosteroids in asthma treatment?
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Among the common adverse effects of inhaled corticosteroids, which is noted most frequently?
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What makes ciclesonide unique among inhaled corticosteroids?
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What is a potential effect of long-term inhaled corticosteroid use in children?
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Which cytokines are primarily reduced by the action of glucocorticoids?
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Which corticosteroid is associated with the highest lipophilicity based on the provided data?
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What common side effect is NOT typically associated with systemic corticosteroids?
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Which inhalation particle size is most likely to be deposited in the alveoli?
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Which corticosteroid has the lowest volume of distribution (Vss) according to the information provided?
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What is the impact of corticosteroids on bone health?
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What is the primary characteristic of asthma as stated in the discussion?
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Which of the following symptoms is NOT typically associated with an acute episode of asthma?
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Which of the following best describes the reversible aspect of bronchodilation in asthma management?
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What differentiates extrinsic asthma from intrinsic asthma?
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What is a significant factor contributing to the global impact of asthma?
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Which mechanism of action is primarily involved in the bronchodilation of asthma medications?
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Which type of asthma is characterized mostly by triggers originating from environmental factors?
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What does GINA guidelines state about the bronchodilator reversibility in asthma?
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What is a key feature that differentiates COPD from asthma in terms of lung function?
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Which of the following components characterizes airway remodeling in both asthma and COPD?
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Which medication class is specifically categorized as controllers to treat inflammation in respiratory conditions?
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What is the main goal of asthma treatment with respect to medication side effects?
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Which of the following drugs is a bronchodilator used as a controller medication?
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What are the characteristics of COPD's pathology?
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In COPD, what role does the loss of elastic recoil play in lung function?
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Which of the following is primarily associated with risk reduction in asthma management?
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What is the main reason GINA no longer recommends SABA-only treatment for Step 1 asthma management?
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Which step in asthma management is defined for patients with mild asthma who experience symptoms less than twice per month?
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What is recommended for adults and adolescents with asthma to reduce the risk of serious exacerbations?
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What defines Step 4 in the new GINA asthma management recommendations?
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What should be done for patients with persistent asthma exacerbations despite adherence and correct inhaler technique?
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Study Notes
Asthma Pathogenesis
- Asthma is a heterogeneous disease characterized by chronic airway inflammation.
- Asthma causes acute bronchoconstriction, resulting in recurrent episodes of shortness of breath, chest tightness, wheezing, rapid respiration, and cough.
- Symptoms are triggered by inhaled irritants or allergens.
- Tracheo-bronchial smooth muscles show increased responsiveness to various stimuli causing widespread narrowing of the airways, with mucosal edema and mucus plugs often present.
- Bronchodilator reversibility is 12% and 200mL of FEV1.
Asthma Global Impact
- Asthma is a common chronic disease, impacting about 339 million people worldwide.
- About 1000 people die from asthma each day.
- Asthma is the 16th leading cause of years lived with disability (YLD).
Asthma Types
- Extrinsic or allergic asthma presents with a history of atopy in childhood, family history of allergies, common triggers (pollen, mold, dust mites, pet dander), positive skin tests, raised IgE levels, and is common below 30 years of age.
- Intrinsic asthma is often caused by long-term exposure to air pollution, secondhand smoke, dust, fumes, and chemicals, and is often work-related.
COPD & Asthma Differentiation
- COPD is most often associated with long-term tobacco smoking.
- COPD is a slow, progressive, and largely irreversible process featuring increased resistance to airflow, loss of elastic recoil, decreased expiratory flow rate, and over-inflation of the lung.
- COPD is clinically defined by a low FEV1 value that fails to respond acutely to bronchodilators, a differentiating characteristic from asthma.
Goals of Asthma Treatment
- Symptom control: few asthma symptoms, no sleep disturbance, no exercise limitation, and normal lung function.
- Risk reduction: decrease airway remodeling, prevent flare-ups (exacerbations), prevent asthma deaths, and avoid medication side-effects.
Airway Remodeling
- Airway remodeling is structural aberrations from a healthy lung.
- Airway remodeling includes hyperplasia of epithelial cells, metaplasia, and hyperplasia of squamous cells, thickening of the reticular basement membrane, deposition of extracellular matrix molecules such as collagen, and angiogenesis.
Asthma Treatment Medications
-
Relievers:
- Short-acting beta-2 agonists (SABAs).
- Anticholinergics.
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Controllers:
- Corticosteroids (inhaled or systemic).
- ICS + LABA combination.
- Leukotriene antagonists.
- Mast cell stabilizers.
- Anti-IgE antibody (omalizumab).
- Biologic therapies (targeting IgE, IL-4, IL-5, IL-13, and TNF-alpha).
Controller Medication Action
- Controllers treat the underlying inflammation to effect prolonged bronchodilation.
- Controllers i.e. mucosal swelling, secretions, and irritability of smooth muscle.
- Controller medication should be taken regularly, even when well, for all asthma except mild intermittent severity.
Systemic Corticosteroids
- Systemic corticosteroids are not bronchodilators, but they reduce airway inflammation and bronchial hyper-reactivity to stimuli.
- Systemic corticosteroids (hydrocortisone and prednisolone) are useful in:
- Acute asthma (status asthmaticus): when bronchodilators and ICS are not effective or worsen the condition.
- Chronic asthma: when the previous regimen fails and there are frequent symptoms of progressive severity.
Inhaled Corticosteroids (ICS)
- Inhaled corticosteroids include beclomethasone dipropionate, budesonide, fluticasone propionate, and triamcinolone acetonide, and ciclesonide. They are often used alone or combined with a long-acting beta-2 agonist (LABA).
- Mechanism of Action (MOA): Long-acting multifactorial actions (reduces initial inflammatory response, decreases the formation of mediators/cytokines, decreases mucosal blood flow, and exudate formation).
- ICSs produce local immunosuppression limiting the lung's hypersensitivity reaction and limit bronchospasm.
- Maximal benefit may be realized 1-2 weeks after initiation of therapy.
-
Adverse effects: common oropharyngeal candidiasis, dysphonia, rare-systemic effects like osteoporosis, cataracts.
- Use ICS with high therapeutic indexes (TIs) at the lowest effective dose in children with persistent asthma.
Glucocorticoids- Mechanism of Action
- Inhibition of phospholipase A2.
- Decrease in prostaglandin/leukotrienes/cytokines production.
- Decrease in infiltration of mast cells/lymphocytes/eosinophils.
- Decreased capillary permeability and mucosal edema.
- Inhibition of antigen-antibody reaction.
- Upregulation of beta-2 receptors (having an additive effect to B2 agonists).
- Potentiating the effects of beta-2 agonists.
Corticosteroid Metabolism
- Ciclesonide is a pro-drug that is enzymatically hydrolysed by bronchial esterases to a pharmacologically active metabolite, des-ciclesonide following inhaled application.
- Des-ciclesonide has anti-inflammatory activity with affinity for the glucocorticoid receptor that is 120 times higher than the parent compound.
- It is associated with less oral candidiasis.
Systemic Corticosteroid Side Effects
- Adrenal suppression.
- Growth retardation in children.
- Osteoporosis.
- Weight gain.
- Fluid retention.
- Hypertension.
- Hyperglycemia.
- Susceptibility to infections.
- Glaucoma.
- Cataract.
- Fat distribution and muscle wasting.
- Psychosis.
Inhalation Delivery
- Aerosols are solid and liquid dispersed particles (1 to 5 mm in size) suspended in a gas.
- They do not coalesce or sink, and the goal is to deliver to the alveoli without settling in larger tubes.
- Particles larger than 10 mm are deposited primarily in the mouth and oropharynx.
- Particles smaller than 0.5 mm are inhaled to the alveoli and exhaled without being deposited in the lungs.
- Starting treatment with SABA trains the patient to regard it as their primary asthma treatment.
- Higher use of SABA is associated with a higher risk of emergency room admissions and death.
GINA 2019 Guidelines: Key Changes in Asthma Management
- GINA no longer recommends SABA-only treatment for Step 1 asthma.
- This decision is based on evidence that SABA-only treatment increases the risk of severe exacerbations, and adding any ICS significantly reduces the risk.
- All adults and adolescents with asthma should receive ICS-containing controller treatment to reduce the risk of serious exacerbations.
- The ICS can be delivered by regular daily treatment or, in mild asthma, by as-needed low-dose ICS-formoterol.
GINA 2019: Steps of Asthma Management
- Step 1: Mild asthma, symptoms less than twice per month, and no risk of exacerbations. No longer SABA use alone.
- Step 2: Preferred controller + as-needed low-dose ICS-formoterol or daily low-dose ICS plus as-needed SABA.
- Step 3: Preferred controller - include a low-dose ICS-long-acting beta-2 agonist (LABA) + as needed SABA, or low-dose ICS-formoterol for both maintenance and reliever therapy.
- Step 4: Preferred controller - low-dose ICS-formoterol as maintenance and reliever therapy, or medium-dose ICS-LABA as maintenance plus as-needed SABA. Note that ICS-formoterol should not be combined with an ICS-LABA containing a different LABA.
- Step 5: Persistent exacerbations or symptom worsening despite adherence and correct inhaler technique - Severe/difficult-to-treat asthma. Refer to a pulmonologist to consider biologic therapy.
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Description
This quiz explores the pathogenesis of asthma, its global impact, and different types of asthma. Learn about the disease's characteristic symptoms, triggers, and the alarming statistics surrounding its prevalence and mortality. Test your knowledge on this significant health issue affecting millions worldwide.
