Posted: June 11th, 2024

ASTHMA Pathophysiology Case Study

Asthma
Asthma is a chronic respiratory condition characterized by airway inflammation, bronchial hyperresponsiveness, and reversible airflow obstruction. It affects individuals of all ages, with a global prevalence of approximately 235 million people (GBD 2019 Diseases and Injuries Collaborators, 2020). Asthma is a complex disease influenced by genetic and environmental factors, and its management requires a multidisciplinary approach.

Pathophysiology
The pathophysiology of asthma involves interactions between various cellular and molecular mechanisms. Airway inflammation plays a central role, with the recruitment of inflammatory cells such as eosinophils, neutrophils, and lymphocytes (Lambrecht & Hammad, 2021). These cells release mediators, including cytokines, chemokines, and growth factors, contributing to airway remodeling and hyperresponsiveness.

Bronchoconstriction, the narrowing of the airways, is a hallmark feature of asthma. This is mediated by the contraction of smooth muscle cells in the bronchial walls, which can be triggered by various stimuli, including allergens, respiratory infections, and environmental irritants (Barnes, 2019). Airway remodeling, characterized by structural changes such as thickening of the airway walls, mucus hypersecretion, and vascular proliferation, further contributes to airflow limitation and symptom exacerbation (Fehrenbach et al., 2017).

Clinical Presentation and Diagnosis
Asthma presents with a variety of symptoms, including wheezing, shortness of breath, chest tightness, and coughing, which can vary in severity and frequency. Diagnosis is based on a comprehensive medical history, physical examination, and objective assessment of lung function through spirometry and bronchial provocation tests (Global Initiative for Asthma, 2022).

Management Strategies
The management of asthma involves a multifaceted approach, including pharmacological and non-pharmacological interventions. Inhaled corticosteroids and bronchodilators, such as β2-agonists and anticholinergics, are the mainstay of pharmacotherapy, aiming to control inflammation and alleviate bronchoconstriction (Sobieraj et al., 2021). Non-pharmacological strategies include environmental control measures, patient education, and lifestyle modifications, such as smoking cessation and physical activity (Lougheed et al., 2022).

Asthma Phenotypes and Endotypes
Recent research has emphasized the heterogeneity of asthma, leading to the identification of different phenotypes and endotypes. Phenotypes are defined by observable characteristics, such as age of onset, triggers, and severity, while endotypes are defined by distinct pathophysiological mechanisms (Wenzel, 2020). This approach aims to personalize treatment strategies based on individual patient characteristics and underlying biological mechanisms.

Emerging Therapies
Advances in the understanding of asthma pathogenesis have paved the way for the development of novel therapeutic options. Biologic therapies, such as monoclonal antibodies targeting specific inflammatory pathways, have shown promising results in the management of severe asthma (Fajt & Wenzel, 2021). Additionally, research is ongoing to explore the potential of small molecule inhibitors, gene therapies, and cell-based therapies for asthma treatment (Carr & Wong, 2019).

Conclusion
Asthma is a complex and heterogeneous respiratory condition with significant global impact. Its management requires a comprehensive approach, integrating pharmacological and non-pharmacological interventions tailored to individual patient needs. Ongoing research efforts are focused on elucidating the underlying pathophysiological mechanisms, identifying asthma endotypes, and developing novel targeted therapies for more effective disease control.

References

Barnes, P. J. (2019). Mechanisms of asthma. Medicine, 47(6), 358-363. https://doi.org/10.1016/j.mpmed.2019.03.006

Carr, T. F., & Wong, G. W. (2019). Emerging therapies for asthma. Current Opinion in Allergy and Clinical Immunology, 19(4), 304-311. https://doi.org/10.1097/ACI.0000000000000545

Fajt, M. L., & Wenzel, S. E. (2021). Biologic therapy for severe asthma: clinical and molecular insights. Seminars in Respiratory and Critical Care Medicine, 42(2), 340-352. https://doi.org/10.1055/s-0041-1726133

Fehrenbach, H., Wagner, C., & Wegmann, M. (2017). Airway remodeling in asthma: From bench to bedside. Cell and Tissue Research, 367(3), 551-569. https://doi.org/10.1007/s00441-016-2566-8

GBD 2019 Diseases and Injuries Collaborators. (2020). Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: A systematic analysis for the Global Burden of Disease Study 2019. The Lancet, 396(10258), 1204-1222. https://doi.org/10.1016/S0140-6736(20)30925-9

Global Initiative for Asthma. (2022). Global strategy for asthma management and prevention. https://ginasthma.org/gina-reports/

Lambrecht, B. N., & Hammad, H. (2021). Asthma: The importance of dysregulated barrier immunity. European Journal of Immunology, 51(3), 542-554. https://doi.org/10.1002/eji.202048847

Lougheed, M. D., Baatjes, A. J., & Canadian Thoracic Society Asthma Assembly. (2022). Non-pharmacological management of asthma in adults. Canadian Respiratory Journal, 2022, 5179203. https://doi.org/10.1155/2022/5179203

Sobieraj, D. M., Weeda, E. R., Nguyen, E., Coleman, C. I., Egginton, J. S., Nguyen, L. H., & Baker, W. L. (2021). Optimal use of inhaled corticosteroids in asthma: Pharmacologic mechanisms and efficacy-to-safety considerations. Pharmacotherapy, 41(6), 508-522. https://doi.org/10.1002/phar.2527

Wenzel, S. E. (2020). Asthma endotypes: Defining a precision medicine approach to asthma. Allergy, 75(2), 283-292. https://doi.org/10.1111/all.14069
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ASTHMA
For the Disease Summary for this case study, see the CD-ROM.

• No siblings
• Paternal grandmother, step-grandfather and maternal grandmother are chain smokers but do not smoke around the patient
Social History
• No alcohol or tobacco use
• Married with two biological children and one stepson
• College graduate with degree in business, currently employed as a business development
consultant with private firm
• There are no pets in the home at this time Review of Systems
• Reports feeling unwell overall, “4/10”
• Denies H/A and sinus facial pain
• Eyes have been watery
• Denies decreased hearing, ear pain, or tinnitus
• Throat has been mildly sore
• () SOB and productive cough with clear, yellow phlegm for 2 days
• Denies diarrhea, N/V, increased frequency of urination, nocturia, dysuria, penile sores or
discharge, dizziness, syncope, confusion, myalgias, and depression
Medications
• Ipratropium bromide MDI 2 inhalations QID
• Triamcinolone MDI 2 inhalations QID
• Albuterol MDI 2 inhalations every 4–6 hours PRN
Allergies
• Grass, ragweed, and cats → sneezing and wheezing
Physical Examination and Laboratory Tests
General
• Agitated, WDWN white man with moderate degree of respiratory distress
• Loud wheezing with cough
• Eyes red and watery
• Prefers sitting to lying down
• SOB with talking
• Speaks only in short phrases as a result of breathlessness
Vital Signs
See Patient Case Table 12.1
Patient Case Table 12.1 Vital Signs
BP 150/80 RR 24 HT 61
P 115 T 100.2°F WT 212 lbs
Pulsus paradoxus 20 Pulse ox 92% (room air)

Patient Case Question 1. Based on the available clinical evidence, is this patient’s asthmatic attack considered mild, moderate, or bordering on respiratory failure?
Patient Case Question 2. What is the most likely trigger of this patient’s asthma attack?
Patient Case Question 3. Identify three major factors that have likely contributed to the development of asthma in this patient.
Skin
• Flushed and diaphoretic
• No rashes or bruises
HEENT
• EOMI
• PERRLA
• Fundi benign, no hemorrhages or exudates
• Conjunctiva erythematous and watery
• Nasal cavity erythematous and edematous with clear, yellow nasal discharge
• Hearing intact bilaterally
• TMs visualized without bulging or perforations
• Auditory canals without inflammation or obstruction
• Pharynx red with post-nasal drainage
• Uvula mid-line
• Good dentition
• Gingiva appear healthy
Neck/Lymph Nodes
• Neck supple
• Trachea mid-line
• No palpable nodes or JVD noted
• Thyroid without masses, diffuse enlargement, or tenderness
Chest/Lungs
• Chest expansion somewhat limited
• Accessory muscle use prominent
• Diffuse wheezes bilaterally on expiration and, occasionally, on inspiration
• Bilaterally decreased breath sounds with tight air movement
Heart
• Tachycardia with regular rhythm
• No murmurs, rubs, or gallops
• S1 and S2 WNL
Abdomen
• Soft, NT/ND
• No bruits or masses
• Bowel sounds present and WNL

Genitalia/Rectum
Deferred
Musculoskeletal/Extremities
• ROM intact in all extremities
• Muscle strength 5/5 throughout with no atrophy
• Pulses 2 bilaterally in all extremities
• Extremities clammy but good capillary refill at 2 seconds with no CCE or lesions
Neurological
• Alert and oriented to place, person, and time
• Thought content: appropriate
• Thought process: appropriate
• Memory: good
• Fund of knowledge: good
• Calculation: good
• Abstraction: intact
• Speech: appropriate in both volume and rate
• CNs II–XII: intact
• Fine touch: intact
• Temperature sensation: intact
• Vibratory sensation: intact
• Pain sensation: intact
• Reflexes 2 in biceps, Achilles, quadriceps, and triceps bilaterally
• No focal defects observed
Laboratory Blood Test Results
See Patient Case Table 12.2
Patient Case Table 12.2 Laboratory Blood Test Results
Na 139 meq/L Hb 13.6 g/dL Monos 6%
K 4.4 meq/L Hct 41% Eos 3%
Cl 105 meq/L Plt 292
103/mm3 Basos 1%
HCO3 26 meq/L WBC 8.9
103/mm3 Ca 8.8 mg/dL
BUN 15 mg/dL Segs 51% Mg 2.5 mg/dL
Cr 0.9 mg/dL Bands 2% Phos 4.1 mg/dL
Glu (non-fasting) 104 mg/dL Lymphs 37%
Peak Flow
175 L/min
Arterial Blood Gases
• pH 7.55
• PaCO2  30 mm Hg
• PaO2  65 mm Hg

Chest X-Ray
Hyperinflated lungs with no infiltrates that suggest inflammation/pneumonia
Patient Case Question 4. Do the patient’s arterial blood gas determinations indicate that the asthmatic attack is mild, moderate or bordering on respiratory failure?
Patient Case Question 5. Identify the metabolic state reflected by the patient’s arterial blood pH.
Patient Case Question 6. What is the cause of this metabolic state?
Clinical Course
The patient is admitted for treatment with oxygen, inhaled bronchodilators, and oral prednisone (60 mg/day initially, followed by a slow taper to discontinuation over 10 days).
However, the patient becomes increasingly dyspneic and more agitated despite treatment.
Heart rate increases to 125 bpm, pulsus paradoxus increases to 30 mm Hg, respiratory rate increases to 35/min, and breathing becomes more labored. Wheezing becomes loud throughout both inspiratory and expiratory phases of the respiratory cycle. Signs of early cyanosis
become evident. The extremities become cold and clammy and the patient no longer is alert and oriented. Repeat ABG are: pH 7.35, PaO2  45 mm Hg, and PaCO2  42 mm Hg (40% oxygen by mask).
Patient Case Question 7. What do this patient’s mental state, heart rate, pulsus paradoxus, respiratory rate, and wheezing suggest?
Patient Case Question 8. Why are the patient’s extremities cold?
Patient Case Question 9. Why is the patient no longer alert and oriented?
Patient Case Question 10. Why is the patient becoming cyanotic?
Patient Case Question 11. Why has the skin become clammy?
Patient Case Question 12. What do the patient’s arterial blood gases indicate now?

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