Asthma is a heterogeneous chronic inflammatory disorder of the airways characterized by recurrent episodes of wheezing, breathlessness, chest tightness, and coughing, particularly at night or in the early morning. These symptoms are associated with variable expiratory airflow limitation that is often reversible either spontaneously or with treatment. For PharmD students, a deep understanding of the complex pathophysiology of asthma—involving intricate interactions between airway inflammation, bronchoconstriction, airway hyperresponsiveness, and structural airway remodeling—is crucial for comprehending its clinical manifestations, diagnostic approaches, and the rationale behind various pharmacological interventions. This MCQ quiz will test your knowledge of the underlying pathophysiological mechanisms of asthma.
1. The hallmark features of asthma pathophysiology include airway inflammation, reversible bronchoconstriction, and which other key characteristic?
- A. Pulmonary fibrosis
- B. Airway hyperresponsiveness (AHR)
- C. Chronic bronchitis
- D. Emphysematous changes
Answer: B. Airway hyperresponsiveness (AHR)
2. In classic allergic asthma, which type of T-helper lymphocyte plays a central role in orchestrating the inflammatory response?
- A. Th1 cells
- B. Th2 cells
- C. Th17 cells
- D. Regulatory T cells (Tregs)
Answer: B. Th2 cells
3. Which inflammatory cell type is characteristically prominent in the airways of many asthmatics, particularly those with allergic asthma, and releases cytotoxic granule proteins?
- A. Neutrophils
- B. Eosinophils
- C. Basophils
- D. Macrophages
Answer: B. Eosinophils
4. Mast cell degranulation in response to allergen exposure in sensitized individuals releases preformed mediators such as:
- A. Interleukin-5 (IL-5) and Interleukin-13 (IL-13)
- B. Histamine, tryptase, and proteoglycans
- C. Leukotriene C4 (LTC4)
- D. Nitric oxide
Answer: B. Histamine, tryptase, and proteoglycans
5. Cysteinyl leukotrienes (LTC4, LTD4, LTE4) are potent mediators in asthma that cause:
- A. Only mucus secretion
- B. Bronchodilation and decreased vascular permeability
- C. Prolonged bronchoconstriction, increased vascular permeability, and mucus secretion
- D. Mast cell stabilization
Answer: C. Prolonged bronchoconstriction, increased vascular permeability, and mucus secretion
6. Immunoglobulin E (IgE) plays a critical role in allergic asthma by binding to high-affinity IgE receptors (FcεRI) on which cells, leading to their activation upon allergen re-exposure?
- A. Neutrophils and eosinophils
- B. Mast cells and basophils
- C. Airway smooth muscle cells
- D. Bronchial epithelial cells
Answer: B. Mast cells and basophils
7. Airway hyperresponsiveness (AHR) in asthma refers to an exaggerated bronchoconstrictor response to:
- A. Only specific allergens
- B. A wide variety of direct and indirect stimuli (e.g., methacholine, histamine, cold air, exercise)
- C. Beta-2 agonists
- D. Inhaled corticosteroids
Answer: B. A wide variety of direct and indirect stimuli (e.g., methacholine, histamine, cold air, exercise)
8. Bronchoconstriction in asthma results from the contraction of airway smooth muscle, which is primarily mediated by:
- A. Increased intracellular cGMP
- B. Increased intracellular cAMP
- C. Increased intracellular calcium (Ca2+) leading to actin-myosin interaction
- D. Activation of potassium channels causing hyperpolarization
Answer: C. Increased intracellular calcium (Ca2+) leading to actin-myosin interaction
9. Which neurotransmitter, acting on M3 muscarinic receptors, is a key mediator of cholinergic bronchoconstriction in the airways?
- A. Norepinephrine
- B. Serotonin
- C. Acetylcholine
- D. Dopamine
Answer: C. Acetylcholine
10. Airway remodeling in chronic asthma involves persistent structural changes. Which of the following is a characteristic feature of airway remodeling?
- A. Thinning of the basement membrane
- B. Decreased airway smooth muscle mass
- C. Subepithelial fibrosis, mucus gland hyperplasia, and increased airway smooth muscle mass
- D. Increased airway elasticity and reduced collagen deposition
Answer: C. Subepithelial fibrosis, mucus gland hyperplasia, and increased airway smooth muscle mass
11. The “early asthmatic response” (EAR) that occurs within minutes of allergen exposure in sensitized individuals is primarily mediated by:
- A. Influx of eosinophils and T-lymphocytes
- B. Release of preformed and newly synthesized mediators from mast cells (e.g., histamine, leukotrienes)
- C. Structural changes of airway remodeling
- D. Neutrophilic inflammation
Answer: B. Release of preformed and newly synthesized mediators from mast cells (e.g., histamine, leukotrienes)
12. The “late asthmatic response” (LAR), occurring 4-12 hours after allergen exposure, is characterized by a more sustained bronchoconstriction and is associated with:
- A. Only mast cell degranulation
- B. The recruitment and activation of inflammatory cells, particularly eosinophils and T-lymphocytes, and release of their mediators
- C. A decrease in airway hyperresponsiveness
- D. Resolution of airway inflammation
Answer: B. The recruitment and activation of inflammatory cells, particularly eosinophils and T-lymphocytes, and release of their mediators
13. Interleukin-5 (IL-5) is a key cytokine in eosinophilic asthma that primarily promotes:
- A. Neutrophil recruitment and activation
- B. Eosinophil differentiation, survival, recruitment, and activation
- C. Mast cell degranulation
- D. IgE production by B cells
Answer: B. Eosinophil differentiation, survival, recruitment, and activation
14. Interleukin-4 (IL-4) and Interleukin-13 (IL-13) are Th2 cytokines that contribute to asthma pathophysiology by promoting:
- A. Suppression of eosinophilic inflammation
- B. IgE production by B cells, mucus hypersecretion, and airway hyperresponsiveness
- C. Bronchodilation
- D. Apoptosis of airway smooth muscle cells
Answer: B. IgE production by B cells, mucus hypersecretion, and airway hyperresponsiveness
15. Goblet cell hyperplasia and mucus hypersecretion in asthmatic airways contribute to:
- A. Improved mucociliary clearance
- B. Airway obstruction by forming mucus plugs and reducing airway lumen diameter
- C. Reduced airway inflammation
- D. Bronchodilation
Answer: B. Airway obstruction by forming mucus plugs and reducing airway lumen diameter
16. What is the role of bronchial epithelial cells in asthma pathophysiology beyond being a physical barrier?
- A. They are passive bystanders in the inflammatory process.
- B. They can be activated by triggers to release pro-inflammatory mediators, cytokines (e.g., TSLP, IL-25, IL-33), and chemokines, contributing to airway inflammation and remodeling.
- C. They primarily secrete bronchodilatory substances.
- D. Their sole function is mucociliary clearance.
Answer: B. They can be activated by triggers to release pro-inflammatory mediators, cytokines (e.g., TSLP, IL-25, IL-33), and chemokines, contributing to airway inflammation and remodeling.
17. Thymic Stromal Lymphopoietin (TSLP), IL-25, and IL-33 are epithelial-derived cytokines considered “alarmins” that can initiate and amplify which type of inflammatory response in asthma?
- A. Predominantly neutrophilic inflammation
- B. Type 2 inflammation (involving Th2 cells, ILC2s, eosinophils, IgE)
- C. Type 1 inflammation (Th1 mediated)
- D. Autoimmune responses
Answer: B. Type 2 inflammation (involving Th2 cells, ILC2s, eosinophils, IgE)
18. Viral respiratory infections are common triggers for asthma exacerbations. They can worsen asthma by:
- A. Decreasing IgE production.
- B. Inducing epithelial damage, augmenting Th2 inflammation, impairing beta-receptor function, and increasing airway hyperresponsiveness.
- C. Promoting bronchodilation.
- D. Suppressing eosinophilic inflammation.
Answer: B. Inducing epithelial damage, augmenting Th2 inflammation, impairing beta-receptor function, and increasing airway hyperresponsiveness.
19. The thickening of the reticular basement membrane seen in asthmatic airways is primarily due to:
- A. Accumulation of edema fluid
- B. Deposition of collagen and other extracellular matrix proteins by myofibroblasts
- C. Infiltration by neutrophils
- D. Hypertrophy of epithelial cells
Answer: B. Deposition of collagen and other extracellular matrix proteins by myofibroblasts
20. Airway smooth muscle (ASM) in asthmatics often exhibits:
- A. Atrophy and reduced contractility
- B. Hypertrophy (increased cell size) and hyperplasia (increased cell number), leading to increased ASM mass and force of contraction
- C. Increased sensitivity to beta-2 agonists
- D. A primary role in initiating inflammation
Answer: B. Hypertrophy (increased cell size) and hyperplasia (increased cell number), leading to increased ASM mass and force of contraction
21. Which of the following best describes the changes in nitric oxide (NO) pathways in asthmatic airways?
- A. Overall decreased NO production leading to bronchoconstriction.
- B. Increased inducible NO synthase (iNOS) activity leading to higher exhaled NO (FeNO), which can be a marker of eosinophilic inflammation, though NO itself can have complex effects.
- C. NO has no role in asthma pathophysiology.
- D. Only neuronal NO synthase (nNOS) is affected.
Answer: B. Increased inducible NO synthase (iNOS) activity leading to higher exhaled NO (FeNO), which can be a marker of eosinophilic inflammation, though NO itself can have complex effects.
22. Aspirin-Exacerbated Respiratory Disease (AERD) involves asthma, chronic rhinosinusitis with nasal polyps, and respiratory reactions upon ingestion of aspirin or other NSAIDs. The pathophysiology is thought to involve dysregulation of which pathway?
- A. Beta-adrenergic pathway
- B. Arachidonic acid metabolism, leading to overproduction of cysteinyl leukotrienes and underproduction of protective prostaglandins (e.g., PGE2)
- C. Cholinergic pathway
- D. IgE-mediated pathway primarily
Answer: B. Arachidonic acid metabolism, leading to overproduction of cysteinyl leukotrienes and underproduction of protective prostaglandins (e.g., PGE2)
23. Genetic predisposition plays a role in asthma development. This means:
- A. Asthma is always caused by a single gene mutation.
- B. Individuals with a family history of asthma or atopy have an increased susceptibility, likely due to multiple interacting genes and environmental factors.
- C. Genetics have no influence on asthma.
- D. Only identical twins will both develop asthma.
Answer: B. Individuals with a family history of asthma or atopy have an increased susceptibility, likely due to multiple interacting genes and environmental factors.
24. How does airway remodeling contribute to the chronicity and severity of asthma?
- A. It makes the airways more responsive to bronchodilators.
- B. It can lead to partially irreversible airflow obstruction and a decline in lung function over time, even with anti-inflammatory treatment.
- C. It primarily involves resolution of airway inflammation.
- D. It reduces airway hyperresponsiveness.
Answer: B. It can lead to partially irreversible airflow obstruction and a decline in lung function over time, even with anti-inflammatory treatment.
25. The “hygiene hypothesis” suggests that reduced exposure to certain microbial agents in early life may:
- A. Protect against asthma development.
- B. Skew the immune system towards Th2 responses, increasing the risk of allergic diseases like asthma.
- C. Increase Th1 responses, reducing asthma risk.
- D. Have no impact on asthma development.
Answer: B. Skew the immune system towards Th2 responses, increasing the risk of allergic diseases like asthma.
26. In severe or refractory asthma, which type of inflammatory cell, other than eosinophils, may play a more prominent role in some patients, often associated with a poorer response to corticosteroids?
- A. Mast cells only
- B. Neutrophils
- C. Basophils
- D. Natural killer (NK) cells
Answer: B. Neutrophils
27. The interaction between IgE and its high-affinity receptor (FcεRI) on mast cells, when cross-linked by an allergen, triggers:
- A. Apoptosis of the mast cell.
- B. Immediate release of preformed mediators (degranulation) and synthesis of newly formed mediators.
- C. Suppression of histamine release.
- D. Phagocytosis of the allergen.
Answer: B. Immediate release of preformed mediators (degranulation) and synthesis of newly formed mediators.
28. Loss of epithelial integrity in asthmatic airways can lead to:
- A. Decreased penetration of allergens and irritants.
- B. Increased exposure of underlying sensory nerves and smooth muscle to irritants and mediators, contributing to AHR.
- C. Enhanced mucociliary clearance.
- D. Reduced inflammation.
Answer: B. Increased exposure of underlying sensory nerves and smooth muscle to irritants and mediators, contributing to AHR.
29. What is the primary role of tachykinins (e.g., substance P, neurokinin A) released from sensory C-fibers in the airways in asthma pathophysiology?
- A. They are potent bronchodilators.
- B. They can cause bronchoconstriction, mucus hypersecretion, and neurogenic inflammation.
- C. They primarily stabilize mast cells.
- D. They inhibit eosinophil recruitment.
Answer: B. They can cause bronchoconstriction, mucus hypersecretion, and neurogenic inflammation.
30. Exercise-induced bronchoconstriction (EIB) is thought to be triggered primarily by:
- A. Direct action of lactic acid on airway smooth muscle.
- B. Respiratory heat and water loss from the airways during hyperventilation, leading to airway cooling and osmolar changes that trigger mediator release.
- C. A decrease in sympathetic tone during exercise.
- D. An increase in IgE levels during exercise.
Answer: B. Respiratory heat and water loss from the airways during hyperventilation, leading to airway cooling and osmolar changes that trigger mediator release.
31. The term “fixed airflow limitation” in some asthma patients refers to:
- A. Airflow limitation that is completely reversible with SABA.
- B. Airflow limitation that is not fully reversible with bronchodilators, often due to significant airway remodeling.
- C. Airflow limitation that only occurs during exercise.
- D. A temporary increase in airway resistance during an infection.
Answer: B. Airflow limitation that is not fully reversible with bronchodilators, often due to significant airway remodeling.
32. Which component of the extracellular matrix is significantly increased in the subepithelial layer of remodeled asthmatic airways?
- A. Elastin
- B. Collagen (types I, III, and V) and fibronectin
- C. Hyaluronic acid
- D. Glycogen
Answer: B. Collagen (types I, III, and V) and fibronectin
33. Angiogenesis (formation of new blood vessels) in the airway wall in chronic asthma can contribute to:
- A. Decreased airway wall thickness.
- B. Increased plasma exudation, edema, and potentially easier recruitment of inflammatory cells.
- C. Improved gas exchange.
- D. Reduced mucus production.
Answer: B. Increased plasma exudation, edema, and potentially easier recruitment of inflammatory cells.
34. The balance between bronchoconstricting (e.g., acetylcholine, leukotrienes) and bronchodilating (e.g., nitric oxide from nNOS, beta-2 agonism) influences is disrupted in asthma, favoring:
- A. Predominant bronchodilation
- B. Predominant bronchoconstriction
- C. No change in airway tone
- C. Only increased mucus production
Answer: B. Predominant bronchoconstriction
35. How does mucus plugging contribute to the pathophysiology of severe asthma exacerbations?
- A. It helps to clear allergens from the airways.
- B. It can cause widespread airway obstruction, ventilation-perfusion mismatch, and respiratory failure.
- C. It primarily leads to bronchodilation.
- D. It reduces airway inflammation.
Answer: B. It can cause widespread airway obstruction, ventilation-perfusion mismatch, and respiratory failure.
36. Non-allergic (intrinsic) asthma often develops later in life and may be associated with:
- A. High serum IgE levels and positive allergen skin tests.
- B. Less prominent eosinophilic inflammation in some cases, and triggers like respiratory infections or irritants, rather than specific allergens.
- C. Complete absence of airway inflammation.
- D. Reversibility only with oral corticosteroids.
Answer: B. Less prominent eosinophilic inflammation in some cases, and triggers like respiratory infections or irritants, rather than specific allergens.
37. Theophylline’s bronchodilator effect, though complex, is partly attributed to non-selective inhibition of phosphodiesterases, leading to increased intracellular levels of:
- A. cGMP only
- B. cAMP and cGMP
- C. Calcium
- D. Histamine
Answer: B. cAMP and cGMP
38. Airway edema, resulting from increased microvascular permeability due to inflammatory mediators, contributes to asthma pathophysiology by:
- A. Increasing airway diameter.
- B. Thickening the airway wall and narrowing the lumen.
- C. Improving mucociliary clearance.
- D. Reducing airway smooth muscle contractility.
Answer: B. Thickening the airway wall and narrowing the lumen.
39. Which structural cell of the airway plays a key role in initiating and perpetuating inflammation by releasing cytokines and chemokines in response to various stimuli?
- A. Airway smooth muscle cell
- B. Goblet cell
- C. Bronchial epithelial cell
- D. Fibroblast
Answer: C. Bronchial epithelial cell
40. The term “atopy” refers to a genetic predisposition to develop allergic diseases, including allergic asthma, often characterized by:
- A. Low levels of total serum IgE.
- B. The production of specific IgE antibodies in response to common environmental allergens.
- C. A deficiency in mast cells.
- D. An overactive Th1 immune response.
Answer: B. The production of specific IgE antibodies in response to common environmental allergens.
41. Impaired function of regulatory T cells (Tregs) has been implicated in asthma pathophysiology, potentially leading to:
- A. Enhanced suppression of Th2-mediated inflammation.
- B. Failure to adequately suppress Th2-mediated allergic and eosinophilic responses.
- C. Increased production of bronchodilating substances.
- D. Promotion of airway remodeling resolution.
Answer: B. Failure to adequately suppress Th2-mediated allergic and eosinophilic responses.
42. How can chronic inflammation lead to airway hyperresponsiveness in asthma?
- A. By making airway smooth muscle less contractile.
- B. By damaging the epithelium, exposing sensory nerve endings, upregulating receptors on smooth muscle, and altering smooth muscle phenotype.
- C. By increasing the production of surfactant.
- D. By promoting permanent bronchodilation.
Answer: B. By damaging the epithelium, exposing sensory nerve endings, upregulating receptors on smooth muscle, and altering smooth muscle phenotype.
43. The cough variant asthma is a phenotype of asthma where:
- A. Wheezing is the only symptom.
- B. Cough is the predominant or sole symptom.
- C. Dyspnea is absent.
- D. Airflow obstruction is irreversible.
Answer: B. Cough is the predominant or sole symptom.
44. The interaction between genetic susceptibility and environmental exposures is crucial in asthma development. This is known as:
- A. Mendelian inheritance only
- B. Gene-environment interaction
- C. Acquired immunity only
- D. Pharmacogenomics
Answer: B. Gene-environment interaction
45. During an asthma exacerbation, ventilation-perfusion (V/Q) mismatch occurs primarily due to:
- A. Uniform constriction of all airways.
- B. Patchy airway obstruction and mucus plugging leading to areas of low V/Q (shunting).
- C. Increased pulmonary blood flow to all lung regions.
- D. Destruction of alveolar walls.
Answer: B. Patchy airway obstruction and mucus plugging leading to areas of low V/Q (shunting).
46. Which of the following is a mechanism by which beta-2 adrenergic agonists cause bronchodilation?
- A. They block muscarinic receptors on airway smooth muscle.
- B. They activate beta-2 receptors on airway smooth muscle, leading to increased cAMP and smooth muscle relaxation.
- C. They inhibit phosphodiesterase-4.
- D. They stabilize mast cell membranes.
Answer: B. They activate beta-2 receptors on airway smooth muscle, leading to increased cAMP and smooth muscle relaxation.
47. The parasympathetic nervous system contributes to bronchoconstriction in asthma through the release of acetylcholine which acts on:
- A. Beta-2 adrenergic receptors
- B. M3 muscarinic receptors on airway smooth muscle
- C. Nicotinic receptors in the airways
- D. Histamine H1 receptors
Answer: B. M3 muscarinic receptors on airway smooth muscle
48. The “epithelial-mesenchymal trophic unit” is a concept in airway remodeling that describes the complex interplay between:
- A. Airway nerves and smooth muscle.
- B. Epithelial cells and underlying mesenchymal cells (like fibroblasts and smooth muscle cells) in driving structural changes.
- C. Mast cells and eosinophils only.
- D. Systemic circulation and pulmonary circulation.
Answer: B. Epithelial cells and underlying mesenchymal cells (like fibroblasts and smooth muscle cells) in driving structural changes.
49. In some severe asthma phenotypes, particularly non-Th2 or neutrophilic asthma, which cytokines may play a more prominent role?
- A. IL-4, IL-5, IL-13
- B. IL-17, IL-8 (CXCL8), TNF-α
- C. Interferon-gamma (IFN-γ)
- D. IL-10
Answer: B. IL-17, IL-8 (CXCL8), TNF-α
50. The ultimate consequence of unchecked airway inflammation, bronchoconstriction, and remodeling in asthma can be:
- A. Spontaneous resolution of the disease.
- B. Development of chronic obstructive pulmonary disease (COPD) in some individuals, or persistent airflow limitation and impaired lung function.
- C. Increased sensitivity to bronchodilators.
- D. A complete cure with inhaled corticosteroids.
Answer: B. Development of chronic obstructive pulmonary disease (COPD) in some individuals, or persistent airflow limitation and impaired lung function.