Wheezing and Asthma Case File

Wheezing and Asthma Case File

Eugene C. Toy MD, Donald Briscoe, MD, FA  AFP, Bruce Britton, MD, Joel J. Heidelbaugh, MD, FA  AFP, FACG

Case 56

A 25-year-old man presents to your office complaining of a 3-month history of rhinorrhea, itchy eyes, and exertional cough and wheezing. These symptoms have been progressively worsening over the past few months. His past medical history is significant for seasonal allergies to pollen and ragweed. His family history is significant only for hypertension in both parents. His siblings and children are in good health without allergies or respiratory illness. His social history is negative for smoking. He has worked as an animal laboratory technician for the last 6 months. On questioning, his symptoms were initially more severe toward the end of the work week but are now continuous. He has been taking over-the counter antihistamines, which helped initially but have not relieved his allergic symptoms. On review of systems, he has noted hives that are less prominent now that he has been taking the antihistamines on a regular basis. On examination, his body mass index (BMI) is 23, blood pressure is 120/75 mm Hg, pulse is 72 beats/min, and respiratory rate is 18 breaths/min. His conjunctiva are injected, there is mild clear ocular discharge, and his nasal turbinates are boggy without visible polyps. His lung examination reveals prolonged inspiratory-to-expiratory ratio and end-expiratory wheezing at the bilateral bases. His heart examination is unremarkable and there is no peripheral edema.

⯈ What is the most likely diagnosis?

⯈ What further evaluation should be considered?

⯈ What are the initial steps in therapy?

ANSWER TO CASE 56:

Wheezing and Asthma

Summary: A 25-year-old man presents with classic signs and symptoms of asthma. The constellation of ocular, nasal, and pulmonary symptoms temporally related to work and environmental conditions to a common allergen is suspicious for occupational-related asthma. The physical examination also is consistent with this diagnosis.

• Most likely diagnosis: Occupation-related allergic asthma.
• Further evaluation: Peak flow measurements pre- and post β-agonist treatment. Further workup should include a chest x-ray, pulmonary function testing with bronchodilator challenge, and consideration of allergen testing.
• Initial therapy: Initial treatment is with a short-acting inhaled β-agonist such as albuterol. A short course of oral steroids should be considered if the patient continues to have wheezing, decreased pulse oximetry, and decreased predicted peak flow measurements after β-agonist therapy. This patient should be removed from his current duties of working with laboratory animals.

ANALYSIS

Objectives

1. Recognize the presenting signs and symptoms of the common causes of wheezing.
2. Understand the etiologies and pathogenesis of asthma.
3. Understand the clinical evaluation, diagnosis, and staging of asthma.
4. Implement the treatment and management of asthma in children and adults. 

Approach To:

Wheezing

DEFINITIONS

ASTHMA: A chronic pulmonary disease characterized by inflammation and hyperreactivity of the airways.

REACTIVE AIRWAY DYSFUNCTION S YNDROME: Irritant-induced asthma usually associated with significant environmental exposures to chemical irritants and allergens.

INTERMITTENT ASTHMA: Symptoms of asthma occurring less than two times a week, nocturnal awakening less than two times a month, the need for oral corticosteroid treatment less than two times in a year, and no limitations in normal activities. Spirometry is normal in between exacerbations.

PERSISTENT ASTHMA: Signs and symptoms greater than the above. There are three classifications of persistent asthma: mild, moderate, and severe.

PEAK EXPIRATORY FLOW (PEF): An easily reproduced age- and gendercontrolled measure of pulmonary function that is used as a measure of current levels of pulmonary obstruction that can be used to monitor and manage asthma.

CLINICAL APPROACH

Background

Asthma is one of the most common chronic diseases in the United States, and is accountable for a substantial number of emergency department evaluations and hospitalizations, many of which are preventable with appropriate management. It is diagnosed in approximately 10% of children and 5% of young adults with increasing prevalence in economically developed countries. Genetic and environmental factors play a significant role in the development of asthma. Work-related asthma is implicated in at least 10% of asthma cases in adults. Pathologic changes to the airways reflect inflammatory and remodeling changes including inflammatory cell infiltration, basement membrane thickening, shedding of epithelial cells, proliferation and engorgement of blood vessels, mucus plugging, smooth muscle hypertrophy, and fibrosis.

CLINICAL APPROACH

History

The characteristic history includes dyspnea, wheezing, productive or nonproductive cough, breathlessness, and chest tightness or discomfort. Depending on etiology and patient characteristics, the symptoms can be perennial or seasonal, episodic or continuous, and can have a diurnal pattern. Suggestive symptoms include episodic wheezing and cough with nocturnal, seasonal, or exertional characteristics in the absence of an acute upper respiratory tract illness. Frequent episodes of "bronchitis" are seen in young children who are likely to have asthma. Positive family histories for asthma and patient history of atopy when associated with symptoms are correlated with the diagnosis of asthma. It is important to realize that asthma can occur in all age groups and can present with a varied spectrum of signs and symptoms.

Physical Examination and Classification

The examination may be normal in between symptoms and exacerbations. The variable presentation and often normal examination can account for delays in diagnosis. The eyes and nose should be examined for signs of allergies, including conjunctivitis and nasal polyps. The neck should be evaluated for accessory muscle use in respiratory distress, or lymphadenopathy which may signify an infectious etiology. The chest should be examined for hyperexpansion and hunched shoulders.

Adapted from Sveum R, Keating M, Lowe D, et al. Health Care Guideline: Diagnosis and Management of Asthma.

9th ed. Institute for Clinical Systems Improvement. June 2010.

The skin should be examined for signs of atopy, eczema, or urticaria. The heart examination can reveal tachycardia and pulsus paradoxus during exacerbations. The lung examination may reveal wheezing heard predominantly on end expiration or forced end expiration with prolongation of expiration compared to inspiration. A differential diagnosis for wheezing is included in Table 56-1.

Classification of the severity of asthma is imperative in directing appropriate acute and maintenance care, and to minimize future exacerbations (Tables 56-2 and 56-3).

An acute asthma exacerbation presents with worsening of the classic symptoms and documented decrease from expected peak flow. Emergency treatment should be considered for the following:

• Peak flow less than 40% of predicted normal (based on age, gender, and height)
• Failure to respond to a 􀀌2-agonist
• Severe wheezing or coughing
• Extreme anxiety due to breathlessness
• Gasping for air, sweaty, or cyanotic
• Rapid clinical deterioration over a few hours with hypoxia
• Severe retractions and nasal flaring
• Posture with shoulders hunched forward

Signs and symptoms for patients who are particularly at risk for poor control of the disease and outcomes including death are as follows:

Abbreviations: EIB, exercise-induced bronchoconstriction; FEV,, forced expiratory volume in 1 second; FVC, forced vital capacity.

Source: National Asthma Education and Prevention Program Expert Panel. Guidelines for the Diagnosis and Management of Asthma. Expert Report 3. National Heart Lung and Blood Institute. NIH

Publication number 08-5846. October 2007.

Source: National Asthma Education and Prevention Program Expert Panel. Guidelines for the Diagnosis and Management of Asthma. Expert Report 3. National Heart Lung and Blood Institute. NIH

Publication number 08-5846. October 2007.

At regular ambulatory visits:

• Previous admission for intensive care or intubations
• Three or more emergency department visits for asthma in the last year
• Two or more canisters of short-acting 􀀇-agonists in a month
• Failure to use controllers (inhaled corticosteroids) despite symptoms
• Current or recent cessation of oral corticosteroids
• Large fluctuations in peak flow
• Low socioeconomic status in an urban environment
• Mental disorders or substance abuse

At presentation with symptoms:

• A chest examination with minimal sounds on auscultation
• Distress and difficulty speaking on examination
• Tachycardia
• Extremely low peak flow ( <50% of predicted)
• Elevated carbon dioxide on arterial blood gas with hypoxia. Typically, arterial carbon dioxide is low during an asthmatic attack due to increased respiratory rate. Normalization of carbon dioxide may be a sign of a severe exacerbation indicating CO2 retention and impending respiratory failure.

Diagnostic Studies

Accurate spirometry is recommended in every patient 5 years or older at the time of diagnosis. Additional studies, tailored to the specific patient and symptoms, include the following:

• Bronchial provocation (eg, methacholine challenge) testing is the "gold standard" test for the diagnosis of asthma for patients with normal or near-normal spirometry
• Allergy testing ( eg, skin testing, serum allergen radioallergosorbent test [RAST], in vitro-specific immunoglobulin E [IgE] antibody testing)
• Chest radiography, to exclude alternative diagnosis
• Arterial blood gas measurement
• Plain film radiographs or computed tomography (CT ) scan of sinuses
• Evaluation for gastroesophageal reflux disease (GERD)
• Complete blood count (CBC) with eosinophils, total IgE, sputum culture

TREATMENT

Treatment for asthma always begins with education and counseling, environmental controls, and management of comorbid conditions. Proper use of inhalers is paramount to minimizing morbidity including hospitalization. Reduction in exposure to causative or aggravating environmental exposures including allergens, occupational exposures, smoking, and other irritants and allergens are paramount in limiting the long-term remodeling and damage associated with this chronic disease. The chief cause of poor control in asthma is lack of adherence to environmental controls and prescribed medications. Education in asthma self-management involving selfmonitoring by peak expiratory flow or symptoms, along with regular monitoring and a written plan, improves outcomes for patients.

Pharmacologic measures to treat and manage asthma are instituted in a stepwise fashion based on staging of asthma (Table 56-4). Subcutaneous immunotherapy is an option for any patient with persistent allergic asthma in stages 2 to 4.

Medications-Fast-Acting Agents

Short-acting β2-agonists (SABAs) are the most effective therapy for prompt relief of asthmatic symptoms. Albuterol, levalbuterol, and pirbuterol are the SABAs used in the United States and are generally considered equally effective in onset and duration of action. They have an onset of action of 5 minutes or less, peak in 30 to 60 minutes, and last 4 to 6 hours. They should be used only as needed for relief of symptoms or before anticipated exposure to known asthmatic triggers ( eg, animals, exercise). Metered-dose inhaler (MDI) actuations can be taken in 10- to 15-second intervals, and nebulized treatment doses can be given continuously in severe cases. Increasing use or using them more than 2 days per week for symptom relief (not for prevention) generally indicates inadequate control of asthma or persistent asthma.

Dose-dependent side effects include tremor, anxiety, palpitations, and tachycardia (but not hypertension). B-Blockers may diminish the effectiveness of SABA, but are not contraindicated.

Metered-dose inhalers are the delivery mechanism of choice for all short-acting β2-agonists, and the use of spacers is encouraged. Nebulizer treatments with SABAs are an alternative in those who cannot use an MDI, yet MDIs with spacers work as well as nebulizers when used correctly. If patients are not controlled with MD Is, the clinician should ensure that the medications are being used in the appropriate dosing intervals. In acute care settings, up to 10 puffs from an MDI given sequentially is equivalent to one nebulizer treatment.

Use of oral short-acting β-agonist is discouraged. They are less potent, take longer to act, and have more side effects compared to inhaled SABAs. Anticholinergic bronchodilators, such as ipratropium, combined with SABA are more beneficial in treating severe asthmatic attacks or those induced by β-blockers in the urgent care setting compared to treatment with a SABA alone.

Medications-Long-Acting Agents

The long-term daily use of control medications is indicated for persistent asthma to prevent symptoms, and eventually hospitalizations. These medications are inhaled

aAll patients: short-acting bronchodilator as needed for symptoms.

Data from National Asthma Education and Prevention Program (NAEPP) Expert Panel Report 3. Guidelines for the Diagnosis and Management of Asthma-Summary Report, 2007. Washington,

DC: National Institutes of Health, National Heart, Lung and Blood Institute; October 2007.

corticosteroids (ICSs), leukotriene receptor antagonists (LRAs), and long-acting β2-agonists (LABAs). Other long-acting agents that can be considered are cromolyn, methylxanthines, and immunomodulators, but are rarely used.

When ICSs are used consistently, they improve asthma symptoms more effectively than any other medications in both children and adults. There are no clinically meaningful differences among the various types of inhaled corticosteroids. The use of spacers improves the delivery of inhaled controllers. Except with longterm, high-dose use, systemic side effects of inhaled corticosteroids may occur but are not clinically important. Dysphonia, sore throat, and thrush can occur, but are generally managed well with the use of a spacer and rinsing with water after use.

Due to their delayed onset of action, inhaled steroids are insufficient for moderate-to-severe exacerbations. Instead, oral steroid treatment is recommended: 1 to 2 mg/kg/d for 3 to 10 days in children or 40 to 60 mg/d in one or two divided doses for 5 to 10 days in adults. Tapering steroid doses for short courses is typically not necessary.

The two most widely available LRAs are montelukast and zafirlukast. In patients who are unable or unwilling to use inhaled corticosteroids, montelukast and zafirlukast are appropriate alternative therapies for mild persistent asthma and have the advantages of ease of use. They also play a role in controlling many symptoms of allergic rhinitis. Combining LRAs and ICSs is a viable option for moderate persistent asthma. LRAs are indicated in exercise-induced asthma. They are the treatment of choice for aspirin-sensitive asthma.

The LABAs salmeterol and formoterol are β-agonists with duration of action of more than 12 hours. They have low rates of tremor and palpitations or tachycardia. However, the inhibition of exercise-induced asthma rapidly wanes with regular use. The effectiveness of SABAs is not impaired in regular users of LABAs. There appears to be an increase in severe exacerbations and deaths when LABAs are added to usual asthma therapy. It is recommended that LABAs should never be used as monotherapy for long-term control of persistent asthma, and should only be used in combination therapy. Use of LABAs has been associated with increased mortality. Increasing the dose of an res should be considered before adding a LABA if the initial dosage of the ICS is not effective.

Cromolyn sodium and nedocromil stabilize mast cells and interfere with chloride channel function. They are an alternative, but are not preferred, medication for the treatment of mild persistent asthma. They have few serious side effects including skin pruritis, irritability, and gastrointestinal upset, need to be dosed multiple times per day, and their use has markedly decreased due to the superiority of ICSs and LRAs.

Omalizumab is a monoclonal antibody that should be instituted only in collaboration or consultation with an asthma subspecialist for highest-risk patients 12 years or older, as additive therapy in patients with severe persistent asthma who have demonstrated immediate hypersensitivity to inhaled allergens. Anaphylaxis may occur in patients receiving this medication. It is administered subcutaneously every 2 to 4 weeks.

Sustained-release theophylline is a mild-to-moderate bronchodilator used as an alternative, adjunctive therapy with an ICS. Monitoring of serum theophylline levels is essential to minimize risk of toxicity and common side effects including tachycardia.

Stepped care can be increased or decreased seasonally and with good longterm management with the goal of minimizing medications as environmental and behavioral treatments decrease symptoms and improve PEF measurements. All medication changes should have a follow-up visit in 2 to 4 weeks with an asthma educator to assess effectiveness and frequency of symptoms.

Acute Management of Asthma

In the acute care setting, immediate treatment with a SABA with monitoring of vitals and PEF is indicated. If within 20 minutes, a patient has an incomplete response (PEF 40%-69% predicted), then three more SABA treatments within 1 hour (via MDI or nebulizer) should be given. If there is a poor response (PEF <40% or oxygen saturations <90%), then the addition of oral or intravenous corticosteroids is indicated. If the patient continues to have inadequate or poor response, then in-patient management with continuous oximetry and close monitoring should be considered.

Additional Measures

All asthmatics should have a yearly influenza vaccination, and remain up-to-date with age-appropriate pertussis and pneumococcal immunizations.

CASE CORRELATION

• See Cases 2 (Dyspnea),19 (Upper Respiratory Infections), and 24 (Pneumonia).

COMPREHENSION QUESTIONS

56.1 A 25-year-old white woman who is in training for a competitive marathon complains of " hitting a wall" and "getting short of breath quicker than she should:' She complains of coughing at the end of her training runs, and states that she may be expecting too much of herself. She does not smoke, has no significant family history, and no history of occupational or environmental exposures. Her physical findings including lung examination are unremarkable. Spirometry reveals normal values both pre- and post-albuterol treatment. What would be the most reasonable first step in treatment of this patient?

A. Trial of albuterol MDI before exercise

B. Chest radiograph

C. Chest CT

D. Counseling for athletic burnout or stress

E. An echocardiogram (ECG) to rule out pulmonary hypertension or cardiac disorder

56.2 A 34-year-old man with a past history of asthma presents to an acute care clinic with an asthma exacerbation. Treatment with nebulized albuterol and ipratropium does not offer significant improvement, and he is then admitted to the hospital. He is afebrile, has a respiratory rate of 24 breaths/min, pulse rate is 96 beats/min, and oxygen saturation is 93% on room air. On examination, he has diffuse bilateral inspiratory and expiratory wheezes, mild intercostal retractions, and a clear productive cough. Which one of the following should be the next step in the management of this patient?

A. Chest physical therapy

B. Inhaled corticosteroids

C. Azithromycin orally

D. Theophylline orally

E. Oral corticosteroids

56.3 A 13-year-old adolescent boy has a nonproductive cough and mild shortness of breath on a daily basis. He is awakened by the cough at least five nights per month. Which one of the following would be the most appropriate treatment for this patient?

A. A long-acting β-agonist daily

B. A short-acting β-agonist daily

C. Oral prednisone daily

D. An oral leukotriene inhibitor as needed

E. Inhaled corticosteroids daily

ANSWERS

56.1 A. Exercise-induced asthma or bronchoconstriction is a common, underdiagnosed condition in athletes. Many of the athletes are unaware of the problem. It is defined as a 10% lowering of forced expiratory volume in 1 second (FEV1) when challenged with exercise. It is much more common in high ventilation sports and in cold, dry air. The incidence among cross-country skiers is as high as 50%. A physical examination and spirometry at rest will be normal unless there is underlying asthma. Methacholine challenge testing can be ordered, but if it is not available, a trial with an albuterol inhaler is reasonable. Pulmonary or cardiac dysfunction not found during the physical examination is much less likely and, therefore, an ECG and chest x-ray would not be indicated until common etiologies have been ruled out. Psychological causes are also a less likely etiology.

56.2 E. Hospital management of acute exacerbations of asthma should include inhaled short-acting bronchodilators and systemic corticosteroids. The efficacy of oral versus intravenous corticosteroids has been shown to be equivalent. Antibiotics are not needed in the treatment of asthma exacerbations unless there are signs of infection. Inhaled ipratropium is recommended for treatment in the emergency department, but not in the hospital. Chest physical therapy and theophylline are not recommended for acute asthma exacerbations.

56.3 E. This patient has moderate persistent asthma. The most effective treatment is daily inhaled corticosteroids. A leukotriene inhibitor would be less effective and as a controller should be used daily. Oral prednisone daily is problematic due to the risk of adrenal insufficiency. Short- and long-acting β-agonists are not recommended as daily therapy because they are considered rescue medications rather than asthma controllers.

CLINICAL PEARLS

⯈ Use the rule of twos to differentiate between intermittent and persistent asthma. Two or fewer symptoms or SABA use a week, two or less nocturnal awakenings a month, or two or less episodes needing for oral steroids in a year.

⯈ The chief causes of inadequate control are poor adherence to medication plan, appropriate MDI utilization, and environmental control.

⯈ As with any chronic disease, continuous education and follow-up is essential to optimal management.

⯈ Persistent asthma should have controller therapy. Inhaled corticosteroids are the first-line controller.

⯈ In adults with new-onset asthma, it is important to get a good occupational exposure history.

REFERENCES

Barnes PJ. Asthma. In: Kasper D, Fauci A, Hauser S, et al., eds. Harrison's Principles of Internal Medicine. 19th ed. New York, NY : McGraw-Hill Education; 2015. Available at: http://accessmedicine. mhmedical.com. Accessed May 25, 2015. 

Cowl CT. Occupational asthma: review of assessment, treatment, and compensation. Chest. 2011;139 (3):674-681. 

Elward KS, Pollart SM. Medical therapy for asthma: updates &om the NAEPP guidelines. Am Fam Physician. 2010;82(10):1242-1251. 

Pollart SM, Compton RM, Elward KS. Management of acute asthma exacerbations. Am Fam Physician. 2011;84(1):40-47. 

Sveum R, Keating M, Lowe D, et al. Health Care Guideline: Diagnosis and Management of Asthma. 9th ed. Institute for Clinical Systems Improvement, Bloomington, MN. June 2010. 

Tarlo SM, Lemiere C. Occupational asthma. N Engl] Med. 2014;370(7):640-649. 

Tarlo SM, Liss GM. Prevention of occupational asthma. Curr Allergy Asthma Rep. 2010;10( 4 ):278-286. 

Weiler JM, Anderson SD, Randolph C, et al. Pathogenesis, prevalence, diagnosis, and management of exercise-induced bronchoconstriction: a practice parameter. Ann Allergy Asthma Immunol. 2010;105(suppl 6):Sl-S47.

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