Management of this chronic inflammatory disease requires avoiding triggers and employing several pharmacologic strategies, such as use of rescue agents and long-term control therapy
A chronic disease involving airway inflammation and bronchial hyperreactivity, asthma causes narrowing of the airways. It is now estimated that 15–17 million Americans have asthma.
A better understanding of the pathogenesis of asthma has helped change management strategies. Asthma is now understood to be a chronic inflammatory disease with intermittent exacerbations. Therapy is directed separately at each of these components. Long-term control is best achieved by suppressing the underlying inflammation with corticosteroids. Systemic corticosteroids have undesirable toxicities; these can be minimized or eliminated by using inhaled corticosteroids. Recently, agents that affect the formation or action of leukotrienes have become available for the long-term control of asthma. Beta-agonists, and to a lesser extent anticholinergics, remain the mainstay for the management of acute symptoms.
Asthma is a chronic inflammatory disease of the airways with intermittent periods of acute, reversible airflow obstruction. Clinical manifestations of the chronic process include mucus production, airway edema, and cough. Acute airflow obstruction is associated with bronchial hyperreactivity and typically manifests as wheezing and dyspnea. However, wheezing is not always present in acute asthma.
Infiltration by inflammatory cells (e.g., mast cells, macrophages) results in persistent airway inflammation. Exposure to a trigger (e.g., allergen, cold air) brings on the early stage of asthma, which causes the release of inflammatory mediators from these cells. These mediators, which include histamine and leukotrienes, lead to inflammation, neutrophil recruitment, mucus production, and further airway obstruction. The late phase reaction occurs hours later, despite the removal of the offending trigger. It causes the release of cytokines, which produce further infiltration of inflammatory cells, thus continuing the inflammatory process. The early phase response is best managed with bronchodilators such as inhaled beta-agonists. Bronchial damage that occurs as a result of the late phase response can only be prevented by close attention to the inflammatory process and therapy with anti-inflammatory agents.
Pulmonary Function Tests
Pulmonary function testing (PFT) is an indispensable tool for monitoring and guiding treatment of asthma. PFT allows the clinician to assess the type and degree of impairment, differentiate reversible from irreversible airway disease, and monitor response to therapy.
The standard pulmonary function test is the forced expiratory spirogram, which can generate a variety of different values. The most common measurements are the forced expiratory volume in 1 second (FEV1), the forced vital capacity (FVC), the ratio of FEV1 divided by FVC (FEV1/FVC), and the carbon monoxide diffusing capacity (DLCO). The FEV1 is the volume of air expired in the first second of expiration and is expressed as a volume and as a percentage of predicted. The FVC is the largest air volume measured on complete exhalation after full inspiration. The DLCO is a measure of CO diffusing capacity of the lungs; it is not affected by disease that mostly involves the airways.
Airway obstruction as seen with asthma or chronic obstructive pulmonary disease (COPD) will cause a decrease in the FEV1 with only minimal changes in FVC, reducing the FEV1/FVC ratio. Restrictive lung disease, on the other hand, causes a decrease in both FEV1 and FVC and, therefore, a near normal FEV1/FVC ratio. Once obstructive lung disease is identified (reduced FEV1 and FEV1/FVC ratio), reversible airway disease can be assessed by measuring FEV1 before and after administration of an inhaled bronchodilator (usually albuterol). An improvement in FEV1 of 10% or more is considered a positive response to bronchodilators. The DLCO is considered in patients without reversible airway disease to distinguish between emphysema and chronic bronchitis. The DLCO will be reduced in patients with emphysema and near normal in patients with chronic bronchitis and asthma. A decreased FEV1 and FEV1/FVC ratio, a positive response to bronchodilators, and a near normal DLCO are consistent with asthma. A patient with a history consistent with asthma and normal PFT at the time of testing can be challenged with inhalation of an agent known to induce bronchospasm (histamine or methacholine). A positive response to methacholine challenge confirms the presence of hyperreactive airways.
Another PFT that is especially useful for monitoring therapy is the peak expiratory flow rate (PEFR). The PEFR is measured by the patient via a handheld device called a peak flow meter. The National Asthma Education and Prevention Program (NAEPP) guidelines have recommended measuring the PEFR on a daily basis in patients with persistent asthma. The establishment of a “personal best” PEFR for each patient can assist in the development of an asthma treatment plan. The plan is initiated by the patient if the PEFR decreases to a predetermined percentage of the patient’s personal best. The pharmacist is in a good position to counsel patients on the proper use of these devices. Proper use and prompt initiation of treatment can reduce the severity of an exacerbation and the need for hospitalization. Patients must be properly educated, however, to know when to seek immediate medical attention. The use of peak flow meters and a clearly defined treatment plan can greatly help.