Table 27-1 shows the relative efficacy of various types of respiratory tract drugs, including those used in the treatment of allergic rhinitis and viral rhinitis.

TABLE 27-1

Relative Efficacy of Antiinflammatory Drugs, Bronchodilators, and Miscellaneous Agents in the Management of Respiratory Tract Disorders *

DRUG	ASTHMA	COPD	ALLERGIC RHINITIS	VIRAL RHINITIS
Antiinflammatory Drugs
Corticosteroids	++++	0 to ++	++++	0
Mast cell stabilizers	+++	0 to ++	+++	0
Leukotriene inhibitors	+++	0 to +	Unknown	0
Bronchodilators
Selective β₂-adrenoceptor agonists	++++	++	0	0
Ipratropium	+	+++	++	++
Theophylline	++ to +++	++ to +++	0	0
Miscellaneous Agents
Analgesics	0	0	0	+++
Antihistamines	0 to ++	0	++++	+
Decongestants	0 to ++	0 to ++	+++	+++

COPD, Chronic obstructive pulmonary disease (e.g., emphysema).

^*Ratings range from 0 (not efficacious) to ++++ (highly efficacious).

Chronic Obstructive Pulmonary Diseases

COPD includes chronic bronchitis and emphysema. Chronic bronchitis is characterized by a productive cough associated with inflammation of the bronchioles, whereas emphysema is caused by permanent destruction and enlargement of the airspaces distal to the bronchioles. Both conditions result in airway obstruction, dyspnea (difficult breathing), decreased blood oxygen concentrations, and elevated blood carbon dioxide concentrations. Patients with these conditions have abnormal pulmonary function test values, such as a decreased forced expiratory volume in 1 second (FEV₁). Smoking and advanced age are the primary risk factors for COPD, and smoking cessation can slow disease progression. Although most of the airway obstruction in COPD is irreversible, a portion of the obstruction is caused by smooth muscle spasm and bronchiolar inflammation, and this portion can be reversed by bronchodilator drugs. Patients with COPD often require long-term oxygen therapy, and antibiotics can be used to treat acute exacerbations caused by bacterial infections.

Antiinflammatory Drugs

Corticosteroids

Corticosteroids (glucocorticoids) are effective in the treatment of a wide variety of inflammatory and other diseases. The discussion here focuses on the use corticosteroids for asthma, allergic rhinitis, and COPD. The pharmacologic properties and clinical use of these drugs are described more completely in Chapter 33.

The recognition that asthma is primarily an inflammatory disease has increased the role of corticosteroids in asthma therapy. For persons with moderate to severe asthma, steroids have become the cornerstone of therapy, and some patients with mild asthma may derive significant benefit from their use as well. Although corticosteroids are the most efficacious antiinflammatory drugs available for the treatment of both asthma and allergic rhinitis (see Table 27-1), they have the potential to cause a number of adverse effects if given systemically. The incidence of adverse effects is markedly reduced when these drugs are given by inhalation, so this route of administration is employed whenever possible. Systemic administration is usually reserved for the treatment of severe asthma or for short-term treatment of severe allergic rhinitis.

Among the steroids available as metered-dose inhalers are beclomethasone, budesonide, fluticasone, and triamcinolone. Beclomethasone and triamcinolone are usually administered three or four times a day, whereas fluticasone and budesonide need to be administered only twice a day. The proper use of metered-dose inhalers requires considerable skill and the use of a spacer device between the mouth and the inhaler. The spacer decreases the amount of drug that is deposited in the mouth and upper airway and facilitates the delivery of the drug to the bronchioles.

As with other antiinflammatory drugs, corticosteroids are primarily used on a long-term basis to prevent asthmatic attacks, rather than to treat acute bronchospasm. The maximal response to steroids usually requires treatment for up to 8 weeks. Corticosteroids can reduce the number and severity of symptoms and decrease the need for β₂-adrenoceptor agonists and other bronchodilators.

Adverse effects associated with inhaled corticosteroids are usually mild. Excessive deposition of the drugs in the mouth and upper airway can lead to oral candidiasis (thrush). There has been some concern about the potential for steroids to suppress growth in children. This problem is difficult to evaluate because asthmatic children may have growth disturbances related to their disease. A meta-analysis of 21 studies, however, concluded that inhaled beclomethasone does not cause growth impairment. Another study showed that 95% of children who received inhaled budesonide for an average of 9 years reached their target adult height despite initial growth retardation.

Formulation products combining corticosteroids and long-acting β₂-receptor agonists (see later), including fluticasone and salmeterol (ADVAIR), budesonide and formoterol (SYMBICORT), and mometasone and formoterol (DULERA), are often used for the treatment of asthma.

Mast Cell Stabilizers

Cromolyn Sodium

Chemistry and Mechanisms

Cromolyn sodium and related drugs are nonsteroidal compounds that stabilize the plasma membranes of mast cells and eosinophils and thereby prevent degranulation and release of histamine, leukotrienes, and other substances that cause airway inflammation (see Fig. 27-1). Hence, these drugs are often called mast cell stabilizers. Inhibition of mediator release by cromolyn and related drugs is thought to result from blockade of calcium influx into mast cells. Cromolyn and related drugs do not interfere with the binding of immunoglobulin E (IgE) to mast cells or with the binding of antigen to IgE. Their beneficial effects in asthma and other conditions are largely prophylactic.