Asthma is now recognized as a heterogeneous disease with various underlying mechanisms, moving the field of respiratory care away from a “one-size-fits-all” approach. Personalized medicine in asthma aims to tailor treatment and prevention strategies to the individual patient by using specific phenotypes, endotypes, biomarkers, and pharmacogenomic data. This approach allows for more precise and effective therapy, particularly for patients with severe or difficult-to-treat asthma. For PharmD students, understanding these advanced concepts is crucial for navigating the future of asthma management and contributing to optimized, patient-specific care. This MCQ quiz will explore the key principles and applications of personalized medicine in asthma.
1. “Personalized medicine” in the context of asthma refers to tailoring treatment based on:
- A. The cost of the medication only.
- B. An individual patient’s specific disease characteristics, such as inflammatory phenotype, biomarkers, and genetics.
- C. A standardized stepwise approach for all patients regardless of their asthma type.
- D. The patient’s preference for an inhaler device only.
Answer: B. An individual patient’s specific disease characteristics, such as inflammatory phenotype, biomarkers, and genetics.
2. In asthma, a “phenotype” is best described as:
- A. The underlying molecular pathway of the disease.
- B. A set of observable characteristics of a patient’s asthma, such as clinical presentation or triggers (e.g., allergic asthma, exercise-induced asthma).
- C. A specific genetic mutation causing the disease.
- D. The patient’s response to corticosteroid therapy.
Answer: B. A set of observable characteristics of a patient’s asthma, such as clinical presentation or triggers (e.g., allergic asthma, exercise-induced asthma).
3. An “endotype” of asthma refers to:
- A. The severity of asthma symptoms.
- B. The age of asthma onset.
- C. The distinct molecular mechanism or pathway underlying a specific asthma phenotype (e.g., T2-high eosinophilic inflammation).
- D. The patient’s peak expiratory flow rate.
Answer: C. The distinct molecular mechanism or pathway underlying a specific asthma phenotype (e.g., T2-high eosinophilic inflammation).
4. Type 2 (T2)-high asthma is a common endotype characterized by the prominent role of which immune cells and cytokines?
- A. Neutrophils and IL-17
- B. Eosinophils, mast cells, Th2 lymphocytes, and cytokines like IL-4, IL-5, and IL-13
- C. Macrophages and TNF-alpha
- D. B-lymphocytes and IgG
Answer: B. Eosinophils, mast cells, Th2 lymphocytes, and cytokines like IL-4, IL-5, and IL-13
5. Which biomarker is commonly measured in exhaled breath to non-invasively assess eosinophilic airway inflammation (a feature of T2-high asthma)?
- A. Serum IgE
- B. Blood eosinophil count
- C. Fractional Exhaled Nitric Oxide (FeNO)
- D. C-reactive protein (CRP)
Answer: C. Fractional Exhaled Nitric Oxide (FeNO)
6. Omalizumab is a biologic therapy that is personalized for patients with severe allergic asthma. Its use is guided by measuring:
- A. Blood neutrophil count
- B. Serum IgE levels and evidence of sensitization to a perennial aeroallergen
- C. FEV1/FVC ratio only
- D. Blood eosinophil count only
Answer: B. Serum IgE levels and evidence of sensitization to a perennial aeroallergen
7. Mepolizumab, reslizumab, and benralizumab are biologic therapies personalized for patients with severe eosinophilic asthma. They target the pathway of which cytokine?
- A. Interleukin-4 (IL-4)
- B. Interleukin-5 (IL-5) or its receptor
- C. Tumor Necrosis Factor-alpha (TNF-α)
- D. Immunoglobulin E (IgE)
Answer: B. Interleukin-5 (IL-5) or its receptor
8. Dupilumab is a monoclonal antibody that blocks the alpha subunit of the IL-4 receptor. This mechanism allows it to inhibit signaling from which two key T2-cytokines?
- A. IL-5 and IL-6
- B. IL-4 and IL-13
- C. TSLP and IL-33
- D. TNF-α and IL-1β
Answer: B. IL-4 and IL-13
9. Tezepelumab represents a broader approach to treating severe asthma by targeting Thymic Stromal Lymphopoietin (TSLP). TSLP is considered an “alarmin” cytokine released by:
- A. Eosinophils
- B. Mast cells
- C. Bronchial epithelial cells in response to various triggers
- D. B-lymphocytes
Answer: C. Bronchial epithelial cells in response to various triggers
10. Pharmacogenomics studies the influence of genetic variations on drug response. Polymorphisms in the ADRB2 gene, which encodes the beta-2 adrenergic receptor, have been studied for their potential impact on the response to:
- A. Inhaled corticosteroids
- B. Beta-2 agonists (SABAs and LABAs)
- C. Leukotriene modifiers
- D. Anticholinergic agents
Answer: B. Beta-2 agonists (SABAs and LABAs)
11. The Arg16Gly polymorphism in the ADRB2 gene has been associated in some studies with:
- A. Improved response to inhaled corticosteroids.
- B. Potential for tachyphylaxis or reduced bronchodilator response with regular SABA use among individuals homozygous for the Arg16 allele.
- C. Increased risk of oral candidiasis.
- D. Decreased IgE levels.
Answer: B. Potential for tachyphylaxis or reduced bronchodilator response with regular SABA use among individuals homozygous for the Arg16 allele. (This finding is complex and its clinical utility is debated).
12. Personalized management of Aspirin-Exacerbated Respiratory Disease (AERD) primarily involves:
- A. Using aspirin daily to desensitize the patient.
- B. Strict avoidance of aspirin and other COX-1 inhibiting NSAIDs, and often considering leukotriene modifying therapy.
- C. Preferential use of beta-blockers.
- D. Treatment with omalizumab as first-line therapy.
Answer: B. Strict avoidance of aspirin and other COX-1 inhibiting NSAIDs, and often considering leukotriene modifying therapy.
13. A patient with severe asthma has a high blood eosinophil count (>300 cells/µL) and frequent exacerbations despite high-dose ICS/LABA therapy. This biomarker profile suggests they may be a good candidate for which type of biologic?
- A. An anti-IgE agent (omalizumab) only
- B. An anti-IL-5/IL-5Rα agent (e.g., mepolizumab, benralizumab) or an anti-IL4Rα agent (dupilumab)
- C. An anti-TNF-α agent
- D. Tezepelumab only
Answer: B. An anti-IL-5/IL-5Rα agent (e.g., mepolizumab, benralizumab) or an anti-IL4Rα agent (dupilumab) (Tezepelumab could also be an option).
14. What is the primary reason why routine pharmacogenomic testing for ADRB2 is NOT currently standard practice for guiding SABA/LABA therapy in asthma?
- A. The test is prohibitively expensive.
- B. Clinical studies have yielded inconsistent results, and the clinical utility of altering therapy based on the genotype is not clearly established.
- C. There are no known polymorphisms in the ADRB2 gene.
- D. The gene only affects response to oral beta-agonists.
Answer: B. Clinical studies have yielded inconsistent results, and the clinical utility of altering therapy based on the genotype is not clearly established.
15. Bronchial thermoplasty is a non-pharmacological procedure that personalizes treatment for selected severe persistent asthma patients by:
- A. Reducing airway smooth muscle mass through the application of thermal energy.
- B. Delivering targeted corticosteroids directly to the airways.
- C. Altering the patient’s genetic makeup.
- D. Desensitizing the patient to common allergens.
Answer: A. Reducing airway smooth muscle mass through the application of thermal energy.
16. Personalized medicine aims to move beyond a “one-size-fits-all” approach. For asthma, this means selecting controller therapy based on:
- A. A universal algorithm that applies to every patient.
- B. Patient preference for a specific inhaler color alone.
- C. Individual patient characteristics, including asthma severity, control, phenotype, and biomarkers.
- D. The lowest cost medication available, regardless of efficacy.
Answer: C. Individual patient characteristics, including asthma severity, control, phenotype, and biomarkers.
17. T2-low asthma is an endotype that is often characterized by:
- A. High levels of eosinophils and IgE.
- B. Neutrophilic or paucigranulocytic (few inflammatory cells) inflammation and often a poorer response to inhaled corticosteroids.
- C. Excellent response to all current biologic therapies.
- D. A strong association with atopic dermatitis.
Answer: B. Neutrophilic or paucigranulocytic (few inflammatory cells) inflammation and often a poorer response to inhaled corticosteroids.
18. Which of the following best exemplifies a personalized approach to managing exercise-induced bronchoconstriction (EIB)?
- A. Prohibiting all patients with asthma from exercising.
- B. Recommending prophylactic use of a SABA before exercise for patients who specifically experience EIB.
- C. Prescribing daily oral corticosteroids for all athletic individuals.
- D. Using the same controller therapy regimen for all patients regardless of EIB symptoms.
Answer: B. Recommending prophylactic use of a SABA before exercise for patients who specifically experience EIB.
19. Why is identifying a patient’s asthma phenotype important in the era of personalized medicine?
- A. It allows for definitive diagnosis without spirometry.
- B. It helps predict the patient’s likely response to certain targeted therapies, especially biologics.
- C. It is only useful for research purposes.
- D. It guarantees a cure for asthma.
Answer: B. It helps predict the patient’s likely response to certain targeted therapies, especially biologics.
20. A patient has severe asthma with very high serum IgE levels and documented allergies to dust mites. Which biologic agent is specifically designed for this patient profile?
- A. Mepolizumab
- B. Benralizumab
- C. Omalizumab
- D. Dupilumab
Answer: C. Omalizumab
21. A major challenge in implementing personalized medicine for asthma in routine clinical practice is:
- A. The lack of any effective drugs for asthma.
- B. The cost and availability of biomarker tests and biologic therapies, and the need for clinician education on their use.
- C. The fact that all asthma patients have the same underlying pathophysiology.
- D. The simplicity of asthma management not requiring personalization.
Answer: B. The cost and availability of biomarker tests and biologic therapies, and the need for clinician education on their use.
22. Genetic variants in the leukotriene pathway (e.g., ALOX5 promoter) have been studied for their potential to predict response to:
- A. Inhaled corticosteroids
- B. Beta-2 agonists
- C. Leukotriene-modifying drugs (e.g., zileuton, montelukast)
- D. Theophylline
Answer: C. Leukotriene-modifying drugs (e.g., zileuton, montelukast)
23. The “treatable traits” approach to personalized asthma management involves:
- A. Treating only the primary symptom of wheezing.
- B. Identifying and treating specific, individual traits (e.g., eosinophilic inflammation, bronchoconstriction, comorbidities like GERD or obesity) rather than just a general asthma diagnosis.
- C. Focusing only on genetic traits.
- D. Using a single medication to treat all traits.
Answer: B. Identifying and treating specific, individual traits (e.g., eosinophilic inflammation, bronchoconstriction, comorbidities like GERD or obesity) rather than just a general asthma diagnosis.
24. The mechanism of benralizumab is distinct from other anti-IL-5 biologics because it:
- A. Binds directly to circulating IL-5.
- B. Binds to the IL-5 receptor alpha (IL-5Rα) on eosinophils and basophils, leading to their depletion via antibody-dependent cell-mediated cytotoxicity.
- C. Blocks the IL-4 receptor.
- D. Binds to IgE.
Answer: B. Binds to the IL-5 receptor alpha (IL-5Rα) on eosinophils and basophils, leading to their depletion via antibody-dependent cell-mediated cytotoxicity.
25. A personalized approach to selecting an inhaler device for a patient should consider:
- A. Only the cost of the device.
- B. The patient’s age, manual dexterity, inspiratory flow capability, and personal preference.
- C. The color of the device.
- D. Prescribing an MDI for all patients.
Answer: B. The patient’s age, manual dexterity, inspiratory flow capability, and personal preference.
26. The future of personalized asthma care may involve “omics” approaches (genomics, proteomics, metabolomics) to:
- A. Develop a single cure for all asthma.
- B. Create more complex and difficult treatment regimens.
- C. Better define endotypes, discover new therapeutic targets, and predict individual treatment responses.
- D. Eliminate the role of the pharmacist in asthma management.
Answer: C. Better define endotypes, discover new therapeutic targets, and predict individual treatment responses.
27. For a patient with severe asthma and a T2-low (e.g., neutrophilic) endotype, which of the following is likely true regarding their treatment response?
- A. They typically have an excellent response to inhaled corticosteroids.
- B. They are ideal candidates for anti-IgE or anti-IL-5 therapy.
- C. They may have a limited response to corticosteroids and T2-targeted biologics, and other therapies (e.g., macrolides, LAMA) might be considered.
- D. They do not require any controller medication.
Answer: C. They may have a limited response to corticosteroids and T2-targeted biologics, and other therapies (e.g., macrolides, LAMA) might be considered.
28. The role of the pharmacist in personalized asthma medicine is to:
- A. Make all treatment decisions without consulting the patient or prescriber.
- B. Help in selecting appropriate therapy based on patient-specific data (when available), educate patients on complex biologic therapies, and monitor for efficacy and adverse effects.
- C. Only dispense the prescribed medication without review.
- D. Perform genetic testing in the pharmacy.
Answer: B. Help in selecting appropriate therapy based on patient-specific data (when available), educate patients on complex biologic therapies, and monitor for efficacy and adverse effects.
29. Personalized management of comorbidities is crucial in asthma because uncontrolled conditions like _______ can worsen asthma symptoms and control.
- A. Osteoporosis
- B. GERD, obesity, and chronic rhinosinusitis
- C. Hypothyroidism
- D. Peripheral neuropathy
Answer: B. GERD, obesity, and chronic rhinosinusitis
30. The Gln27Glu polymorphism of the ADRB2 gene has been associated with:
- A. Decreased receptor downregulation and potentially better response to beta-agonists.
- B. Increased receptor downregulation and poorer response.
- C. No effect on receptor function.
- D. A direct link to aspirin sensitivity.
Answer: A. Decreased receptor downregulation and potentially better response to beta-agonists. (Again, clinical relevance is debated).
31. The choice of biologic therapy in severe asthma is a key example of personalized medicine. This choice is primarily driven by:
- A. The patient’s preference for the drug name.
- B. The patient’s biomarker profile (e.g., IgE vs. eosinophils) to match the drug’s mechanism of action.
- C. A “trial-and-error” approach starting with the least expensive biologic.
- D. The patient’s age and weight only.
Answer: B. The patient’s biomarker profile (e.g., IgE vs. eosinophils) to match the drug’s mechanism of action.
32. What is a limitation of using blood eosinophil counts to personalize asthma therapy?
- A. They are extremely difficult and expensive to measure.
- B. They can vary over time and be influenced by other factors like infections or oral corticosteroid use.
- C. They do not correlate with airway eosinophilia at all.
- D. They are only useful for guiding anti-IgE therapy.
Answer: B. They can vary over time and be influenced by other factors like infections or oral corticosteroid use.
33. The goal of using pharmacogenomics in asthma treatment is to:
- A. Cure asthma by correcting gene defects.
- B. Predict which patients are most likely to benefit from a specific drug or are at higher risk for adverse effects, thereby optimizing drug selection and dosing.
- C. Replace all other diagnostic tests like spirometry.
- D. Make all asthma medications more expensive.
Answer: B. Predict which patients are most likely to benefit from a specific drug or are at higher risk for adverse effects, thereby optimizing drug selection and dosing.
34. Tezepelumab’s broad mechanism of targeting TSLP makes it a potential personalized option for a wider range of severe asthma patients, including:
- A. Only those with high IgE levels.
- B. Only those with high eosinophil counts.
- C. Patients with both T2-high and some T2-low inflammation, as TSLP is an upstream mediator.
- D. Only patients with exercise-induced asthma.
Answer: C. Patients with both T2-high and some T2-low inflammation, as TSLP is an upstream mediator.
35. A “precision medicine” approach to asthma would involve:
- A. Giving every patient the same high-dose ICS/LABA.
- B. Classifying patients into specific subgroups based on clinical and biological markers to guide therapy.
- C. Relying solely on patient-reported symptoms.
- D. Focusing only on non-pharmacological interventions.
Answer: B. Classifying patients into specific subgroups based on clinical and biological markers to guide therapy.
36. A patient has severe, persistent asthma and frequent exacerbations despite high-dose ICS/LABA. Blood tests show an eosinophil count of 50 cells/µL and a low IgE level. This patient is LEAST likely to benefit from which biologic agent?
- A. Tezepelumab (anti-TSLP)
- B. Dupilumab (anti-IL4Rα)
- C. Mepolizumab (anti-IL5)
- D. An oral corticosteroid burst
Answer: C. Mepolizumab (anti-IL5) (As its primary target population is those with eosinophilic phenotype, though thresholds vary).
37. The concept of “gene-environment interaction” in personalized asthma medicine means that:
- A. A person’s genetic risk for asthma is independent of their environmental exposures.
- B. The effect of a genetic predisposition may be modified or triggered by specific environmental exposures (e.g., tobacco smoke, allergens).
- C. The environment is the sole cause of asthma.
- D. Genes are the sole cause of asthma.
Answer: B. The effect of a genetic predisposition may be modified or triggered by specific environmental exposures (e.g., tobacco smoke, allergens).
38. The use of FeNO to personalize ICS therapy involves:
- A. Increasing the ICS dose if FeNO is very low.
- B. Potentially increasing the ICS dose if FeNO is high (indicating ongoing eosinophilic inflammation) or assessing adherence, and potentially decreasing the dose if FeNO is consistently low in a well-controlled patient.
- C. Measuring FeNO only once at diagnosis.
- D. Using FeNO to guide beta-agonist therapy.
Answer: B. Potentially increasing the ICS dose if FeNO is high (indicating ongoing eosinophilic inflammation) or assessing adherence, and potentially decreasing the dose if FeNO is consistently low in a well-controlled patient.
39. One of the goals of identifying asthma endotypes is to:
- A. Develop new drugs that target the specific molecular pathways driving each endotype.
- B. Stop using inhaled corticosteroids.
- C. Simplify asthma management to a single algorithm.
- D. Prove that all asthma is allergic.
Answer: A. Develop new drugs that target the specific molecular pathways driving each endotype.
40. Why is patient phenotyping more than just “allergic” vs. “non-allergic”?
- A. Because IgE is the only important biomarker.
- B. Because other characteristics like age of onset, presence of obesity, and pattern of inflammation (e.g., neutrophilic) define distinct clinical groups with different prognoses and treatment responses.
- C. Because all asthma is fundamentally the same.
- D. Because phenotyping is not clinically useful.
Answer: B. Because other characteristics like age of onset, presence of obesity, and pattern of inflammation (e.g., neutrophilic) define distinct clinical groups with different prognoses and treatment responses.
41. The development of biologics that target specific cytokines (like IL-5 or IL-4/13) is a prime example of:
- A. A non-personalized, broad-spectrum approach.
- B. A personalized medicine strategy based on targeting specific disease endotypes.
- C. A focus on symptomatic relief only.
- D. A low-cost alternative to inhaled corticosteroids.
Answer: B. A personalized medicine strategy based on targeting specific disease endotypes.
42. A patient with severe asthma is found to have a high blood eosinophil count AND high total IgE with sensitivity to dust mites. This patient may be a candidate for:
- A. Only an anti-IgE biologic.
- B. Only an anti-IL-5 biologic.
- C. Potentially several different biologics (e.g., anti-IgE, anti-IL5/IL5Rα, anti-IL4Rα), and the choice would depend on further clinical details and shared decision making.
- D. No available biologic therapies.
Answer: C. Potentially several different biologics (e.g., anti-IgE, anti-IL5/IL5Rα, anti-IL4Rα), and the choice would depend on further clinical details and shared decision making.
43. A challenge with pharmacogenetic testing for beta-agonist response in asthma is that:
- A. The ADRB2 gene has no known polymorphisms.
- B. The effect of any single polymorphism is often small, and the overall response is polygenic and influenced by many other factors.
- C. The test results are always clear-cut and easy to interpret.
- D. It is a mandatory test before prescribing albuterol.
Answer: B. The effect of any single polymorphism is often small, and the overall response is polygenic and influenced by many other factors.
44. Personalized medicine in asthma also involves personalizing the _________ to ensure the patient can use it correctly and consistently.
- A. Cost of the medication
- B. Inhaler device
- C. Color of the inhaler
- D. Brand name of the medication
Answer: B. Inhaler device
45. For a patient with obesity-associated asthma, a personalized management plan would likely include:
- A. Only high-dose inhaled bronchodilators.
- B. Standard asthma pharmacotherapy along with a strong emphasis on weight management strategies.
- C. A recommendation to gain more weight.
- D. Biologic therapy as a first-line treatment.
Answer: B. Standard asthma pharmacotherapy along with a strong emphasis on weight management strategies.
46. The ultimate goal of personalized asthma therapy is to:
- A. Provide the right treatment to the right patient at the right time.
- B. Use the most expensive medications for every patient.
- C. Treat all patients with the same evidence-based pathway.
- D. Focus only on genetic factors and ignore clinical symptoms.
Answer: A. Provide the right treatment to the right patient at the right time.
47. A key component of personalized medicine is shared decision-making. In asthma, this involves:
- A. The clinician making all decisions for the patient.
- B. A discussion between the clinician and patient about the different treatment options (including their risks, benefits, and costs) in the context of the patient’s phenotype, values, and preferences.
- C. The patient choosing their therapy based on internet searches alone.
- D. Following the “one-size-fits-all” guideline without deviation.
Answer: B. A discussion between the clinician and patient about the different treatment options (including their risks, benefits, and costs) in the context of the patient’s phenotype, values, and preferences.
48. Why might a patient with T2-low, paucigranulocytic asthma not respond well to high-dose inhaled corticosteroids?
- A. Because their asthma is primarily driven by mechanisms other than the T2/eosinophilic inflammation that corticosteroids target most effectively.
- B. Because they have very high IgE levels.
- C. Because they always have better lung function.
- D. Because they are always non-adherent.
Answer: A. Because their asthma is primarily driven by mechanisms other than the T2/eosinophilic inflammation that corticosteroids target most effectively.
49. The use of biomarkers like FeNO and blood eosinophils helps clinicians to:
- A. Diagnose asthma without spirometry.
- B. Objectively assess the type and intensity of underlying airway inflammation to guide therapy.
- C. Measure lung function directly.
- D. Determine the patient’s adherence to beta-agonists.
Answer: B. Objectively assess the type and intensity of underlying airway inflammation to guide therapy.
50. As personalized medicine for asthma evolves, the role of the pharmacist will increasingly involve:
- A. Less patient interaction and more dispensing.
- B. Interpreting biomarker and pharmacogenomic data, counseling on complex biologic therapies, and working within an interprofessional team to tailor regimens.
- C. Only managing inventory of biologic agents.
- D. Focusing solely on non-pharmacological management.
Answer: B. Interpreting biomarker and pharmacogenomic data, counseling on complex biologic therapies, and working within an interprofessional team to tailor regimens.