asthma diagnosis case study

Case Study: Managing Severe Asthma in an Adult

—he follows his treatment plan, but this 40-year-old male athlete has asthma that is not well-controlled. what’s the next step.

By Kirstin Bass, MD, PhD Reviewed by Michael E. Wechsler, MD, MMSc

This case presents a patient with poorly controlled asthma that remains refractory to treatment despite use of standard-of-care therapeutic options. For patients such as this, one needs to embark on an extensive work-up to confirm the diagnosis, assess for comorbidities, and finally, to consider different therapeutic options.

Case presentation and patient history

Mr. T is a 40-year-old recreational athlete with a medical history significant for asthma, for which he has been using an albuterol rescue inhaler approximately 3 times per week for the past year. During this time, he has also been waking up with asthma symptoms approximately twice a month, and has had three unscheduled asthma visits for mild flares. Based on the  National Asthma Education and Prevention Program guidelines , Mr. T has asthma that is not well controlled. 1

As a result of these symptoms, spirometry was performed revealing a forced expiratory volume in the first second (FEV1) of 78% predicted. Mr. T then was prescribed treatment with a low-dose corticosteroid, fluticasone 44 mcg at two puffs twice per day. However, he remained symptomatic and continued to use his rescue inhaler 3 times per week. Therefore, he was switched to a combination inhaled steroid and long-acting beta-agonist (LABA) (fluticasone propionate 250 mcg and salmeterol 50 mcg, one puff twice a day) by his primary care doctor.

Initial pulmonary assessment Even with this step up in his medication, Mr. T continued to be symptomatic and require rescue inhaler use. Therefore, he was referred to a pulmonologist, who performed the initial work-up shown here:

• Spirometry, pre-albuterol: FEV1 79%, post-albuterol: 12% improvement
• Methacholine challenge: PC 20 : 1.0 mg/mL
• Chest X-ray: Within normal limits

Continued pulmonary assessment His dose of inhaled corticosteroid (ICS) and LABA was increased to fluticasone 500 mcg/salmeterol 50 mcg, one puff twice daily. However, he continued to have symptoms and returned to the pulmonologist for further work-up, shown here:

• Chest computed tomography (CT): Normal lung parenchyma with no scarring or bronchiectasis
• Sinus CT: Mild mucosal thickening
• Complete blood count (CBC): Within normal limits, white blood cells (WBC) 10.0 K/mcL, 3% eosinophils
• Immunoglobulin E (IgE): 25 IU/mL
• Allergy-skin test: Positive for dust, trees
• Exhaled NO: Fractional exhaled nitric oxide (FeNO) 53 parts per billion (pbb)

Assessment for comorbidities contributing to asthma symptoms After this work-up, tiotropium was added to his medication regimen. However, he remained symptomatic and had two more flares over the next 3 months. He was assessed for comorbid conditions that might be affecting his symptoms, and results showed:

• Esophagram/barium swallow: Negative
• Esophageal manometry: Negative
• Esophageal impedance: Within normal limits
• ECG: Within normal limits
• Genetic testing: Negative for cystic fibrosis, alpha1 anti-trypsin deficiency

The ear, nose, and throat specialist to whom he was referred recommended only nasal inhaled steroids for his mild sinus disease and noted that he had a normal vocal cord evaluation.

Following this extensive work-up that transpired over the course of a year, Mr. T continued to have symptoms. He returned to the pulmonologist to discuss further treatment options for his refractory asthma.

Diagnosis Mr. T has refractory asthma. Work-up for this condition should include consideration of other causes for the symptoms, including allergies, gastroesophageal reflux disease, cardiac disease, sinus disease, vocal cord dysfunction, or genetic diseases, such as cystic fibrosis or alpha1 antitrypsin deficiency, as was performed for Mr. T by his pulmonary team.

Treatment options When a patient has refractory asthma, treatment options to consider include anticholinergics (tiotropium, aclidinium), leukotriene modifiers (montelukast, zafirlukast), theophylline, anti-immunoglobulin E (IgE) antibody therapy with omalizumab, antibiotics, bronchial thermoplasty, or enrollment in a clinical trial evaluating the use of agents that modulate the cell signaling and immunologic responses seen in asthma.

Treatment outcome Mr. T underwent bronchial thermoplasty for his asthma. One year after the procedure, he reports feeling great. He has not taken systemic steroids for the past year, and his asthma remains controlled on a moderate dose of ICS and a LABA. He has also been able to resume exercising on a regular basis.

Approximately 10% to 15% of asthma patients have severe asthma refractory to the commonly available medications. 2  One key aspect of care for this patient population is a careful workup to exclude other comorbidities that could be contributing to their symptoms. Following this, there are several treatment options to consider, as in recent years there have been several advances in the development of asthma therapeutics. 2

Treatment options for refractory asthma There are a number of currently approved therapies for severe, refractory asthma. In addition to therapy with ICS or combination therapies with ICS and LABAs, leukotriene antagonists have good efficacy in asthma, especially in patients with prominent allergic or exercise symptoms. 2  The anticholinergics, such as tiotropium, which was approved for asthma in 2015, enhance bronchodilation and are useful adjuncts to ICS. 3-5  Omalizumab is a monoclonal antibody against IgE recommended for use in severe treatment-refractory allergic asthma in patients with atopy. 2  A nonmedication therapeutic option to consider is bronchial thermoplasty, a bronchoscopic procedure that uses thermal energy to disrupt bronchial smooth muscle. 6,7

Personalizing treatment for each patient It is important to personalize treatment based on individual characteristics or phenotypes that predict the patient's likely response to treatment, as well as the patient's preferences and practical issues, such as adherence and cost. 8

In this case, tiotropium had already been added to Mr. T's medications and his symptoms continued. Although addition of a leukotriene modifier was an option for him, he did not wish to add another medication to his care regimen. Omalizumab was not added partly for this reason, and also because of his low IgE level. As his bronchoscopy was negative, it was determined that a course of antibiotics would not be an effective treatment option for this patient. While vitamin D insufficiency has been associated with adverse outcomes in asthma, T's vitamin D level was tested and found to be sufficient.

We discussed the possibility of Mr. T's enrollment in a clinical trial. However, because this did not guarantee placement within a treatment arm and thus there was the possibility of receiving placebo, he opted to undergo bronchial thermoplasty.

Bronchial thermoplasty  Bronchial thermoplasty is effective for many patients with severe persistent asthma, such as Mr. T. This procedure may provide additional benefits to, but does not replace, standard asthma medications. During the procedure, thermal energy is delivered to the airways via a bronchoscope to reduce excess airway smooth muscle and limit its ability to constrict the airways. It is an outpatient procedure performed over three sessions by a trained physician. 9

The effects of bronchial thermoplasty have been studied in several trials. The first large-scale multicenter randomized controlled study was  the Asthma Intervention Research (AIR) Trial , which enrolled patients with moderate to severe asthma. 10  In this trial, patients who underwent the procedure had a significant improvement in asthma symptoms as measured by symptom-free days and scores on asthma control and quality of life questionnaires, as well as reductions in mild exacerbations and increases in morning peak expiratory flow. 10  Shortly after the AIR trial, the  Research in Severe Asthma (RISA) trial  was conducted to evaluate bronchial thermoplasty in patients with more severe, symptomatic asthma. 11  In this population, bronchial thermoplasty resulted in a transient worsening of asthma symptoms, with a higher rate of hospitalizations during the treatment period. 11  Hospitalization rate equalized between the treatment and control groups in the posttreatment period, however, and the treatment group showed significant improvements in rescue medication use, prebronchodilator forced expiratory volume in the first second (FEV1) % predicted, and asthma control questionnaire scores. 11

The AIR-2  trial followed, which was a multicenter, randomized, double-blind, sham-controlled study of 288 patients with severe asthma. 6  Similar to the RISA trial, patients in the treatment arm of this trial experienced an increase in adverse respiratory effects during the treatment period, the most common being airway irritation (including wheezing, chest discomfort, cough, and chest pain) and upper respiratory tract infections. 6

The majority of adverse effects occurred within 1 day of the procedure and resolved within 7 days. 6  In this study, bronchial thermoplasty was found to significantly improve quality of life, as well as reduce the rate of severe exacerbations by 32%. 6  Patients who underwent the procedure also reported fewer adverse respiratory effects, fewer days lost from work, school, or other activities due to asthma, and an 84% risk reduction in emergency department visits. 6

Long-term (5-year) follow-up studies have been conducted for patients in both  the AIR  and  the AIR-2  trials. In patients who underwent bronchial thermoplasty in either study, the rate of adverse respiratory effects remained stable in years 2 to 5 following the procedure, with no increase in hospitalizations or emergency department visits. 7,12  Additionally, FEV1 remained stable throughout the 5-year follow-up period. 7,12  This finding was maintained in patients enrolled in the AIR-2 trial despite decreased use of daily ICS. 7

Bronchial thermoplasty is an important addition to the asthma treatment armamentarium. 7  This treatment is currently approved for individuals with severe persistent asthma who remain uncontrolled despite the use of an ICS and LABA. Several clinical trials with long-term follow-up have now demonstrated its safety and ability to improve quality of life in patients with severe asthma, such as Mr. T.

Severe asthma can be a challenge to manage. Patients with this condition require an extensive workup, but there are several treatments currently available to help manage these patients, and new treatments are continuing to emerge. Managing severe asthma thus requires knowledge of the options available as well as consideration of a patient's personal situation-both in terms of disease phenotype and individual preference. In this case, the patient expressed a strong desire to not add any additional medications to his asthma regimen, which explained the rationale for choosing to treat with bronchial thermoplasty. Personalized treatment necessitates exploring which of the available or emerging options is best for each individual patient.

Published: April 16, 2018

• 1. National Asthma Education and Prevention Program: Asthma Care Quick Reference.
• 2. Olin JT, Wechsler ME. Asthma: pathogenesis and novel drugs for treatment. BMJ . 2014;349:g5517.
• 3. Boehringer Ingelheim. Asthma: U.S. FDA approves new indication for SPIRIVA Respimat [press release]. September 16, 2015.
• 4. Peters SP, Kunselman SJ, Icitovic N, et al. Tiotropium bromide step-up therapy for adults with uncontrolled asthma. N Engl J Med . 2010;363:1715-1726.
• 5. Kerstjens HA, Engel M, Dahl R. Tiotropium in asthma poorly controlled with standard combination therapy. N Engl J Med . 2012;367:1198-1207.
• 6. Castro M, Rubin AS, Laviolette M, et al. Effectiveness and safety of bronchial thermoplasty in the treatment of severe asthma: a multicenter, randomized, double-blind, sham-controlled clinical trial. Am J Respir Crit Care Med . 2010;181:116-124.
• 7. Wechsler ME, Laviolette M, Rubin AS, et al. Bronchial thermoplasty: long-term safety and effectiveness in patients with severe persistent asthma. J Allergy Clin Immunol . 2013;132:1295-1302.
• 8. Global Initiative for Asthma: Pocket Guide for Asthma Management and Prevention (for Adults and Children Older than 5 Years).
• 10. Cox G, Thomson NC, Rubin AS, et al. Asthma control during the year after bronchial thermoplasty. N Engl J Med . 2007;356:1327-1337.
• 11. Pavord ID, Cox G, Thomson NC, et al. Safety and efficacy of bronchial thermoplasty in symptomatic, severe asthma. Am J Respir Crit Care Med . 2007;176:1185-1191.
• 12. Thomson NC, Rubin AS, Niven RM, et al. Long-term (5 year) safety of bronchial thermoplasty: Asthma Intervention Research (AIR) trial. BMC Pulm Med . 2011;11:8.

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Patient Diagnosis Case Study Asthma

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Patient Diagnosis Case Study: Asthma Anonymous NRP/511 Advanced Pathophysiology August 8th, 2023 Professor Evette Campos

The scenario: Nancy Smith is a 35-year-old female who presents to the clinic with an asthma exacerbation that began two weeks ago. She was diagnosed with asthma as a child and had several hospitalizations throughout childhood related to asthma. Her asthma was well controlled until the past couple of years when she was treated in urgent care (most recently 4 months ago) and was given a prescription for an inhaled steroid which she did not fill, albuterol inhaler, and oral steroids. She also has a history of eczema as a child and received allergy shots for many years. Her asthma symptoms flared again 2 weeks ago, and she has been using her albuterol 4 to 5 times/day. Nancy’s symptoms include shortness of breath when climbing stairs or walking to the mailbox, night coughing spells, and orthopnea requiring the need to prop herself on pillows to breathe. She indicates that she has had similar previous flares in the past. Medications include: Proair HFA, Claritin, and Flonase PRN. Nancy’s spirometry results are: FEV1: 81% (post-bronchodilator results with 15% increase) FVC: 88% FEV1/FVC Ratio: 82% Pulse Ox: 93% on Room Air Overall Health and Pathophysiology Asthma is an obstructive, chronic inflammatory disorder involving the bronchial mucosa that causes bronchial hypersensitivity, airway constriction, and fluctuating airflow hinderance (McCance & Huether, 2019). Nancy has asthma and when exposed to a triggering substance or antigen, the epithelial cells in her airway initiate an innate and

Darlenski, 2021). Nancy stated she suffered from eczema as a child and received allergy shots for many years. The term “one continuous airway” refers to a hypothesis that upper and lower airway infections and disorders are linked and the pathological process that may affect one may affect the other. This theory is that airway diseases coincide and can be evidenced by research showing a link between viral respiratory tract illness and asthma exacerbation. A study published in 2019 showed Rhinovirus is the most prominent viral agent trigger for asthma exacerbations in children and adults (Adeli et al., 2019). Nancy stated she has experienced nighttime coughing spells each night and must prop herself up on pillows to breathe. Based on the theory of one continuous airway, treating her cough could help treat her asthma, and utilizing this theory could help explain why she received allergy shots as a child. Diagnosis Nancy’s spirometry results are as follows: FEV1: 81% (post-bronchodilator results with 15% increase), FVC: 88%; FEV1/FVC Ratio: 82%. A spirometry test measures pulmonary function by quantifying the volume and flow of air inhaled and exhaled (McCance & Huether, 2019). Forced Vital Capacity (FVC) is the volume exhaled and the normal range is 80-120 percent (Ponce et al., 2022). The Forced Expiratory Volume in One Second (FEV1) measures the volume of air expelled in the first second after a full breath in, with a normal range 80-120 percent (Ponce et al., 2022). The ratio of the two tests is calculated by dividing the FEV1 value by the FVC value and is known as the FEV1/FVC Ratio. Nancy’s spirometry test results show damage or restriction in the airway and confirms her diagnosis.

Based on Nancy’s spirometry results and symptoms and using an Asthma Guide from the National Institute of Health, I would classify her asthma as persistent-severe as evidenced by her dyspnea when doing daily activities, her nighttime coughing spells, daily use of her inhaler, and her uncontrolled asthma symptoms requiring urgent care. Disease Management Nancy’s poor asthma management through the overuse of her rescue medication and unfilled medications is alarming and shows she needs education regarding the pathophysiology of her disease to explain why each prescription medication is crucial for optimal management. The overuse of a rescue medication such as an Albuterol inhaler can have devastating side effects including tremors, nervousness, increased blood pressure, hypokalemia, and bronchospasms which can lead to worsening asthma symptoms (Johnson et al., 2022). Albuterol acts on receptors to relax the bronchial smooth muscles and inhibit the release of hypersensitivity mediators from mast cells (Johnson et al., 2022). Overuse of this rescue medication causes poor asthma control as the body builds a tolerance to the medication leading to increased airway hyperresponsiveness that could be fatal (Azzi et al., 2019). Uncontrolled asthma can lead to airway remodeling or airway tissue damage. Educating Nancy on the course of treatment and how each medication works can help promote medication compliance and disease management for optimal patient outcome.

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