Diagnosis and Management of Asthma
January 2, 2020
Hello, my name is Anna Dolgner, and today, I will be discussing the diagnosis and management of asthma. After this talk, you should be able to identify the signs and symptoms of asthma, understand the underlying pathophysiology, and identify the medications used for asthma maintenance and exacerbations. We will discuss the epidemiology, clinical presentation, pathophysiology, and diagnosis of asthma. We will also discuss maintenance therapy for asthma and how to treat exacerbations. Asthma affects 22 million Americans each year, including 6 million children. No specific genetic predisposition has been identified, but if an individual’s parents have asthma, allergies, or eczema, there are increased risks of developing asthma. There are also hypothesized links to viral and airborne allergen exposure. The hygiene hypothesis has also been proposed. As it has been shown that if children are exposed to typical childhood viral infections as well as other children early in life, that they have a decreased risk of developing asthma. Children who live in non-urban environment also have a decreased risk of developing asthma. Thus, children that live in cities who are not exposed to other children or viral infections early in life are considered to live in hygienic environments and have an increased risk of asthma. Asthma presents with dyspnea, wheezing, and cough. Symptoms are often worse at night and are brought on by certain triggers. These triggers vary by individual and include seasonal allergies, URIs, exercise, weather changes, strong emotions, and exposure to airway irritants such a smoke, airborne chemicals, or pollution. Exam findings can include tachypnea, hypoxia, expiratory wheezing, decreased air movement, a prolonged expiratory phase, accessory muscle use during respiration, tripoding, and pulsus paradoxus. Hypoxia, tripoding, and pulsus paradoxus are only found in severe cases. Laboratory findings can include an uncompensated respiratory acidosis in patients with a severe exacerbation. Eosinophilia can be present in some patients. Typical chest x-ray findings include hyperinflation, peribronchial cuffing, bronchial thickening, and focal atelectasis. The pathophysiology of asthma consists of two main processes– airway inflammation and bronchospasm. Airway inflammation is a chronic process and leads to airway edema and increased mucus secretion which can, in turn, contribute to mucus plugging. Bronchospasm is a more acute event and occurs when airways constrict in response to an irritant or a trigger. Over time, the airways become hyperresponsive to these triggers and lead to worsening of asthma symptoms. This is a schematic of the airway inflammation that occurs in patients with asthma. On the right, you can see the airway swelling that is present due to inflammation as well as the increased mucus secretion that is present. If a diagnosis of asthma is being considered, pulmonary function testing can be performed to help make the diagnosis. Asthma is a disease of intermittent airway obstruction. Thus, spirometry can be normal between exacerbations or if a patient is on appropriate maintenance therapy. If obstruction is present, a decrease in the FEV1 to FVC ratio, and FEF25-75 can be present. The latter of these measures small airway obstruction. Additionally, the reserve volume, functional reserve capacity, and total lung capacity can be increased, although this usually only occurs in patients with severe asthma. During pulmonary function testing in patients with suspected asthma, a bronchodilator is administered to see if any airway obstruction that is present is reversible. it is considered to be reversible if there is a 12% or 200 milliliter improvement in the FEV1 after treatment. Additional testing that can be performed during pulmonary function testing is bronchoprovocation testing, most commonly, a methacholine challenge. Methacholine induces airway obstruction in susceptible patients and, therefore, can also be used to help diagnose asthma. This slide shows several flow volume loops to help demonstrate the differences that are seen in patients with asthma, as compared to patients with normal pulmonary function and patients with another common obstructive lung disease, COPD. As you can see, as compared to the normal control, patients with asthma have both decreased flow and volume over the testing period. Additionally, there is a scooped out or concave appearance to the top of the loop rather than a constant slope that is seen in patients without obstructive lung diseases. You can also see the difference in the shape of the loop in patients with asthma as compared to COPD as the patients with COPD have a more immediate and abrupt drop in flow that, subsequently, becomes more constant. There are multiple classes of medications available to treat asthma, and they target the two main pathophysiologic characteristics of asthma– bronchospasm and airway inflammation. Bronchodilators target bronchospasm. They include a short-acting beta agonists, or SABAs, such as albuterol and levalbuterol, as well as long-acting beta agonists, or LABAs, such as salmeterol and formoterol. SABAs are used for quick relief of asthma symptoms or for pretreatment of exercise-induced bronchospasm. Levalbuterol is the reanimator of albuterol and is hypothesized to have fewer side effects, although this has not been clearly demonstrated. Because of this proposed advantage, however, it is recommended over albuterol in patients with cardiac arrhythmias as tachycardia is one of the main side effects of albuterol. LABAs are not used for quick relief and should only be used as part of a multi-drug treatment regimen. A LABA monotherapy has been associated with an increased risk of asthma related death. The second main category of asthma medications are those to treat airway inflammation. These include inhaled corticosteroids such fluticasone, beclomethasone, mometasone, and budesonide as well as leukotriene modifiers such as montelukast, zafirlukast, and zileuton. Inhaled corticosteroids work by reducing airway hyperresponsiveness and inflammatory cell migration. Oral corticosteroids work in the same way and may be required as part of maintenance therapy in patients with very severe asthma. Leukotriene modifiers interfere with the pathway of inflammatory mediators released from eosinophils, basophils, and mast cells. They can be considered as an alternative to inhaled corticosteroids. There are other medications available to treat asthma such a cromolyn, which is a mast cell stabilizer, and omalizumab, a monoclonal antibody, used to target IgE in patients with severe asthma. These will not be discussed in detail as they are beyond the scope of this talk. One extremely important aspect of asthma therapy is teaching patients how to administer their aerosolized medications. All aerosolized medications should be administered through a spacer device to optimize delivery to the lungs. The medication is delivered into the chamber, and the patient wraps their lips around the mouthpiece and inhales the medication. Children can use this device as well by adding a mask adapter to the mouthpiece. As you can see, there is a removable duck-mask adapter shown in this photograph. This slide depicts the NHLBI guidelines for asthma maintenance therapy. The general idea is that you identify the severity of a patient’s asthma through guidelines that will be presented on the following slides and then pick the appropriate step of therapy. Based on symptomatic control, the medication regimen can be stepped up or stepped down. Generally, the authors recommend stepping up therapy is SABAs are used more than two times per week for symptom relief as this is an indicator of suboptimal control. This table lists the criteria for intermittent and mild-persistent asthma. The main categories used to assess control are frequency of asthma symptoms, the number of nighttime awakenings per week due to asthma symptoms, and the number of times per week a SABA is used to relieve asthma symptoms. Note that pretreatment of exercise-induced bronchospasm does not count towards the number of times a Dolgner is used per week when assessing asthma control. For intermittent asthma, step one therapy, which is the use of a SABA on as needed basis, is recommended. For mild persistent asthma, step two therapy, which is the use of either a low dose inhaled corticosteroid or a leukotriene receptor antagonist in addition to an as needed SABA is recommended. This slide shows the classification of moderate persistent and severe persistent asthma. For moderate persistent asthma, step three is recommended. The options for this include a low dose inhaled corticosteroids plus a LABA, plus a PRN SABA, or a medium dose inhaled corticosteroid, plus a leukotriene receptor antagonist, plus an as needed SABA. For severe persistent asthma, step four of five therapy is recommended. These patients are generally on a high dose inhaled corticosteroid, plus a LABA, and an as needed SABA. The addition of an oral corticosteroid, or omalizumab, is also considered. Mild asthma exacerbations can be treated on an outpatient basis. The treatment of severe exacerbations in patients requiring hospitalization is beyond the scope of this talk. Again, the goal is to treat both the airway inflammation and the bronchospasm. To treat the airway inflammation, an oral corticosteroids, usually prednisone, is considered. To treat the bronchospasm, the use of a SABA up to every four hours is recommended. If a patient is not getting adequate symptom relief from this or if they are using a SABA more frequently than every four hours, they should obtain urgent medical attention. In summary, the main symptoms of asthma are cough, dyspnea, and wheezing. Pathophysiology includes a combination of airway inflammation and bronchospasm. Asthma treatment, both maintenance therapy and management of exacerbations, includes targeting both of these mechanisms. The NHLBI guidelines provide a classification strategy with recommended therapeutic regimens for each level of severity that can be stepped up or stepped down over time based on symptom control. Finally, mild asthma exacerbations are treated with increased frequency of SABA use and consideration of the use of oral corticosteroids. Thank you.