PRELIM CP2 T2 ASTHMA

______ is defined by the Global Initiative for Asthma (GINA) as a heterogeneous disease usually characterized by chronic airway inflammation.

Asthma

Asthma is defined by the Global Initiative for Asthma (GINA) as a (homogenous/heterogeneous) disease usually characterized by chronic airway inflammation.

heterogeneous

Asthma is defined by the Global Initiative for Asthma (GINA) as a heterogeneous disease usually characterized by acute/chronic airway inflammation.

chronic

Asthma is defined by a history of respiratory symptoms such as _____, __________, __________, and ________ that vary over time and in intensity, together with variable expiratory airflow limitation.

wheezing, shortness of breath, chest tightness, and cough

______-phase allergic inflammation: Inhaled allergens trigger IgE mediated activation of mast cells and macrophages, causing release of leukotrienes, and prostaglandins. These mediators induce bronchoconstriction, mucus secretion, vascular permeability, and airway edema, resulting in acute airway narrowing.

Early-phase allergic inflammation

Early-phase allergic inflammation: Inhaled allergens trigger ____ mediated activation of mast cells and macrophages, causing release of histamines, leukotrienes, and prostaglandins. These mediators induce bronchoconstriction, mucus secretion, vascular permeability, and airway edema, resulting in acute airway narrowing.

IgE

Early-phase allergic inflammation: Inhaled allergens trigger IgE mediated activation of mast cells and macrophages, causing release of ______, ________, and ________. These mediators induce bronchoconstriction, mucus secretion, vascular permeability, and airway edema, resulting in acute airway narrowing.

histamines, leukotrienes, and prostaglandins

_____-phase cellular inflammation: Within hours, eosinophils, lymphocytes, neutrophils, and T macrophages infiltrate the airways. TH2-cell cytokines (IL-4, IL-5, IL-13) sustain eosinophilic inflammation, promote IgE production, and amplify airway hyperresponsiveness.

Late-phase cellular inflammation

Late-phase cellular inflammation: Within hours, ____, _____, _____, and ____ infiltrate the airways. TH2-cell cytokines (IL-4, IL-5, IL-13) sustain eosinophilic inflammation, promote IgE production, and amplify airway hyperresponsiveness.

eosinophils, lymphocytes, neutrophils, and T macrophages

Late-phase cellular inflammation: Within hours, eosinophils, lymphocytes, neutrophils, and T macrophages infiltrate the airways. TH2-cell cytokines (_____, _____, ______) sustain eosinophilic inflammation, promote IgE production, and amplify airway hyperresponsiveness.

IL-4, IL-5, IL-13

____________ and ________: Persistent inflammation damages bronchial epithelium, increases goblet cells and gland size, impairs mucociliary clearance, and heightens neural-mediated bronchoconstriction. These structural and functional changes lead to chronic airway hyperreactivity and variable airflow obstruction characteristic of asthma.

Airway remodeling and hyperresponsiveness

Airway remodeling and hyperresponsiveness: Persistent inflammation damages bronchial epithelium, (increases/decreases) goblet cells and gland size, (impairs/repairs) mucociliary clearance, and heightens neural-mediated bronchoconstriction. These structural and functional changes lead to chronic airway hyperreactivity and variable airflow obstruction characteristic of asthma.

damages bronchial epithelium, increases goblet cells and gland size, impairs mucociliary clearance, and heightens neural-mediated bronchoconstriction

Clinical Presentation

____________________

Symptoms:

• episodes of shortness of breath, chest tightness, coughing (particularly at night), wheezing, or a whistling sound when breathing. These often occur with exercise but may occur spontaneously or in association with known allergens.

Signs:

• expiratory wheezing (rhonchi) on auscultation; dry, hacking cough; and atopy (e.g., allergic rhinitis or atopic dermatitis)

Chronic Asthma

Clinical Presentation

Chronic Asthma

_________:

• episodes of shortness of breath, chest tightness, coughing (particularly at night), wheezing, or a whistling sound when breathing.

• These often occur with exercise but may occur spontaneously or in association with known allergens.

Symptoms

Clinical Presentation

Chronic Asthma

Symptoms:

• episodes of _____, _____, ____ (particularly at night), ______, or ____ sound when breathing. These often occur with exercise but may occur spontaneously or in association with known allergens.

• shortness of breath, chest tightness, coughing (particularly at night), wheezing, or a whistling sound when breathing

Clinical Presentation Chronic Asthma

________:

• expiratory wheezing (rhonchi) on auscultation; dry, hacking cough; and atopy (e.g., allergic rhinitis or atopic dermatitis)

Signs

Clinical Presentation

Chronic Asthma

Signs:

• ________ (rhonchi) on auscultation; ___, ______; and _____ (e.g., allergic rhinitis or atopic dermatitis)

• expiratory wheezing (rhonchi) on auscultation; dry, hacking cough; and atopy

Clinical Presentation

________________

Symptoms:

• Patients may be anxious in acute distress and complain of severe dyspnea, shortness of breath, chest tightness, or burning. They may be able to say only a few words with each breath.

Signs:

• expiratory and inspiratory wheezing on auscultation; dry, hacking cough; tachypnea; tachycardia; pallor or cyanosis; and hyperinflated chest with intercostal and supraclavicular retractions. Breath sounds may be diminished with severe obstruction.

Acute Severe Asthma

Clinical Presentation

Acute Severe Asthma

_______:

• Patients may be anxious in acute distress and complain of severe dyspnea, shortness of breath, chest tightness, or burning. They may be able to say only a few words with each breath.

Symptoms

Clinical Presentation

Acute Severe Asthma

Symptoms:

• Patients may be _____________ and _______, ________, ______ or ______. They may be able to say only a few words with each breath.

• anxious in acute distress and complain of severe dyspnea, shortness of breath, chest tightness, or burning

Clinical Presentation

Acute Severe Asthma

______:

• expiratory and inspiratory wheezing on auscultation; dry, hacking cough; tachypnea; tachycardia; pallor or cyanosis; and hyperinflated chest with intercostal and supraclavicular retractions. Breath sounds may be diminished with severe obstruction

Signs

Clinical Presentation

Acute Severe Asthma

Signs:

• expiratory and inspiratory wheezing on auscultation; (dry/wet), hacking cough; tachypnea; (bradycardia/tachycardia); pallor or cyanosis; and hyperinflated chest with intercostal and supraclavicular retractions. Breath sounds may be diminished with severe obstruction

• dry

• tachycardia

Diagnosis

____________

• recurrent respiratory symptoms (cough, wheeze, chest tightness, dyspnea),

• atopy or allergen/exercise triggers

• spirometry showing reversible airflow obstruction (reduced FEV₁/FVC with ≥12% and ≥200 mL improvement after bronchodilator)

Chronic Asthma

Diagnosis

_____________________

• marked airflow limitation (PEF or FEV₁ <40% predicted)

• hypoxemia on pulse oximetry

• possible metabolic acidosis with low PaO₂ on arterial blood gas

Acute Severe Asthma

_______________________

The GINA long-term goals for asthma management include:

• achieve good control of symptoms and maintain normal activity levels, and

• minimize future risk of exacerbations, fixed airflow limitation, and side effects.

For acute severe asthma, the primary goal is prevention of life-threatening asthma by early recognition of signs of deterioration and early intervention.

Goals of Treatment

Goals of Treatment

The GINA long-term goals for asthma management include:

• achieve good control of symptoms and maintain normal activity levels, and

• minimize future risk of exacerbations, fixed airflow limitation, and side effects.

For ___________, the primary goal is prevention of life-threatening asthma by early recognition of signs of deterioration and early intervention.

acute severe asthma

Nonpharmacologic Therapy

• __________ is mandatory to improve medication adherence, self-management skills, and use of healthcare services.

Patient education

Nonpharmacologic Therapy

• (Long/Short-term) (approximately 2 weeks) home PEF monitoring can be used to assess treatment response.

Short

Nonpharmacologic Therapy

• Avoidance of known __________ triggers can improve symptoms, reduce medication use, and decrease BHR.

allergenic

Non-Pharmacologic Therapy

• In acute asthma exacerbations, initiate (oxygen/water) therapy to achieve an arterial oxygen saturation of 93%–95% in adolescents and adults and 94%–98% in school-aged children and pregnant women or those with cardiac disease.

oxygen therapy

Non-Pharmacologic Therapy

• Correct (dehydration/hydration) if present.

dehydration

Pharmacologic Therapy

______

• SABAs are the most effective bronchodilators.

• In adults, administration as either continuous or intermittent (every 20 minutes for 3 doses) administration over 1-hour results in equivalent improvement.

• Albuterol and other inhaled SABAs are indicated for intermittent episodes of bronchospasm and are the treatment of choice for acute severe asthma and EIB.

• Two long-acting β2-agonists (LABAs), formoterol and salmeterol provide bronchodilation for 12 hours or longer. The LABAs are preferred adjunctive therapy with ICS in adults and children ≥12 years old for step 3 and for children 6–11 years of age for steps 4 and 5.

• Three ultra-LABAs (indacaterol , olodaterol , and vilanterol) have a 24-hour bronchodilator duration of effect.

β2 Agonists

Pharmacologic Therapy

β2 Agonists

• ______ are the most effective bronchodilators.

• In adults, administration as either ______ or _____ (every 20 minutes for 3 doses) administration over 1-hour results in equivalent improvement.

• SABAs

• continuous or intermittent

Pharmacologic Therapy

β2 Agonists

• ______ and other inhaled SABAs are indicated for intermittent episodes of bronchospasm and are the treatment of choice for acute severe asthma and EIB.

Albuterol

Pharmacologic Therapy

β2 Agonists

• Two long-acting β2-agonists (LABAs), _____ and ____ provide bronchodilation for 12 hours or longer. The LABAs are preferred adjunctive therapy with ICS in adults and children ≥12 years old for step 3 and for children 6–11 years of age for steps 4 and 5.

formoterol and salmeterol

Pharmacologic Therapy

β2 Agonists

• Three ultra-LABAs (_____, _____, and ____) have a 24-hour bronchodilator duration of effect.

indacaterol , olodaterol , and vilanterol

Pharmacologic Therapy

__________

• ICS are the preferred maintenance therapy for persistent asthma and the only treatment proven to reduce asthma-related mortality.

• They are dosed once to multiple times daily depending on disease severity, with symptom improvement seen within 1–2 weeks and maximal lung function benefit in 3–8 weeks.

• Low-to-moderate ICS doses have minimal systemic toxicity, while high doses increase risk of growth suppression, osteoporosis, cataracts, and adrenal insufficiency; local effects such as oral candidiasis and dysphonia can be reduced with spacer use.

• Oral or IV corticosteroids are indicated for acute severe asthma unresponsive to initial bronchodilators and are given as short “burst” therapy (3–7 days) to rapidly control inflammation, followed by continued

Corticosteroids

Pharmacologic Therapy

Corticosteroids

• ICS are the preferred maintenance therapy for persistent asthma and the only treatment proven to reduce asthma-related mortality.

ICS

Pharmacologic Therapy

Corticosteroids

• ICS are the preferred maintenance therapy for (persistent/continuous) asthma and the only treatment proven to reduce asthma-related mortality.

• They are dosed once to multiple times daily depending on disease severity, with symptom improvement seen within ___weeks and maximal lung function benefit in ____ weeks.

• persistent

• 1–2

• 3–8

Pharmacologic Therapy

Corticosteroids

• __________ ICS doses have minimal systemic toxicity, while high doses increase risk of growth suppression, osteoporosis, cataracts, and adrenal insufficiency; local effects such as oral candidiasis and dysphonia can be reduced with spacer use.

Low-to-moderate

Pharmacologic Therapy

Corticosteroids

• ____ corticosteroids are indicated for acute severe asthma unresponsive to initial bronchodilators and are given as short “burst” therapy (3–7 days) to rapidly control inflammation, followed by continued

Oral or IV

Pharmacologic Therapy

___________

• are effective bronchodilators but are not as effective as β2-agonists. Ipratropium and tiotropium are commonly used only for COPD, and not for asthma. Both drugs can only be used as an adjunctive therapy whose asthma is not well controlled with first-line treatments.

Anticholinergics

Pharmacologic Therapy

Anticholinergics

• are effective (bronchodilators/bronchodtrictor) but are not as effective as β2-agonists.

• ______ and _____ are commonly used only for COPD, and not for asthma.

• Both drugs can only be used as an adjunctive therapy whose asthma is not well controlled with first-line treatments.

• bronchodilators

• Ipratropium and tiotropium

Pharmacologic Therapy

__________________

• Zafirlukast and montelukast- oral leukotriene receptor antagonists (LTRA) that reduce the proinflammatory and bronchoconstriction effects of leukotriene D4.

• Zileuton- 5-lipoxygenase inhibitor; its use is limited due to potential for elevated hepatic enzymes, especially in the first 3 months of therapy, and CYP3A4 enzyme inhibitor.

Leukotriene Modifiers

Pharmacologic Therapy

Leukotriene Modifiers

• _______ and _____- oral leukotriene receptor antagonists (LTRA) that reduce the proinflammatory and bronchoconstriction effects of leukotriene D4.

• _____- 5-lipoxygenase inhibitor; its use is limited due to potential for elevated hepatic enzymes, especially in the first 3 months of therapy, and CYP3A4 enzyme inhibitor.

• Zafirlukast and montelukast

• Zileuton

Pharmacologic Therapy

Biologic Agents

These agents are indicated for patients with moderate or severe asthma (depending upon the drug) along with other biomarkers or clinical indicators associated with treatment response.

• ________ - an anti-IgE antibody approved for treatment of allergic asthma not well controlled by oral or ICS

• _________________- monoclonal antibodies directed against IL-5 to block activation of the IL-5 receptor on eosinophils.

• __________- binds to the alpha subunit of the IL-5 receptor of eosinophils and prevents binding of IL-5.

Mepolizumab and benralizumab are approved for patients ≥12 years old with severe asthma and are administered SC; reslizumab is approved for severe asthma in patients ≥18 years old and is administered IV.

• ___________ -targets the IL-4α receptor, thus blocking signaling of IL4 and IL 13, which are cytokines that promote IgE synthesis and inflammatory cell recruitment.

• Omalizumab

• Mepolizumab and reslizumab

• Benralizumab

• Dupilumab

Pharmacologic Therapy

______________

These agents are indicated for patients with moderate or severe asthma (depending upon the drug) along with other biomarkers or clinical indicators associated with treatment response.

• Omalizumab - an anti-IgE antibody approved for treatment of allergic asthma not well controlled by oral or ICS

• Mepolizumab and reslizumab- monoclonal antibodies directed against IL-5 to block activation of the IL-5 receptor on eosinophils.

• Benralizumab- binds to the alpha subunit of the IL-5 receptor of eosinophils and prevents binding of IL-5.

Mepolizumab and benralizumab are approved for patients ≥12 years old with severe asthma and are administered SC; reslizumab is approved for severe asthma in patients ≥18 years old and is administered IV.

• Dupilumab -targets the IL-4α receptor, thus blocking signaling of IL4 and IL 13, which are cytokines that promote IgE synthesis and inflammatory cell recruitment.

Biologic Agents

Pharmacologic Therapy

____________

• moderately potent bronchodilator, producing relaxation of smooth muscle by blocking calcium ion influx into smooth muscles; it may also have anti-inflammatory effects.

• may reduce hospital admissions in adults who have an FEV1 <25% 30% predicted upon arrival in the emergency department, children and adults who have persistent hypoxemia after standard treatment, and children whose FEV1 remains <60% predicted after 1 hour of standard treatment.

Magnesium Sulfate

Pharmacologic Therapy

Magnesium Sulfate

• _________________, producing relaxation of smooth muscle by blocking calcium ion influx into smooth muscles; it may also have anti-inflammatory effects.

• may reduce hospital admissions in adults who have an FEV1 <25% 30% predicted upon arrival in the emergency department, children and adults who have persistent hypoxemia after standard treatment, and children whose FEV1 remains <60% predicted after 1 hour of standard treatment.

moderately potent bronchodilator

Pharmacologic Therapy

Methylxanthines

• __________ is a moderately potent bronchodilator with mild anti-inflammatory properties and is available for oral and IV administration.

Theophylline

Pharmacologic Therapy

_________

• Theophylline is a moderately potent bronchodilator with mild anti-inflammatory properties and is available for oral and IV administration.

Methylxanthines

____________________

• Basic education must be implemented, which should include discussion of asthma as a chronic lung disease, the types of medications, and how they are to be used.

• Teach inhaler technique, advise the patient about when to seek medical advice, and provide written action plans.

• The two key components of effective asthma control are “symptom control” and “future risk of adverse outcomes.”

• Ask patients about exercise tolerance because perceived good exercise tolerance may be biased by a sedentary lifestyle adapted to the frequency of bothersome symptoms.

• All patients on inhaled drugs should have their inhalation technique evaluated monthly initially and then every 3–6 months.

• After initiation of anti-inflammatory therapy or increase in dosage, most patients should experience decreased symptoms within 1–2 weeks and achieve maximum improvement within 4–8 weeks.

Evaluation of Therapeutic Outcomes