How best to diagnose and control asthma in the elderly

Asthma is currently underdiagnosed and undertreated. Its prevalence is increasing in all age groups, including the elderly,^1-3 which is particularly significant given that the population over age 65 in the United States will approach 76 million by 2010.

The prevalence of asthma in persons aged 65 years and older was 5.2% in a National Health Interview Study⁴ and 6% in the Cardiovascular Health Study by Enright and associates.¹ An accurate diagnosis of asthma in the elderly can be difficult to determine, but it is essential for choosing appropriate therapy. In this article, we will discuss the challenges of diagnosing and managing asthma in the elderly population.

PRESENTATION AND DIAGNOSIS

The 3 most common phenotypes of asthma in the elderly are:

• The presence of asthma since early childhood.

• Asthma in childhood that is later "outgrown" and followed by recurrence at middle age.

• Initial onset of asthma after age 45 to 50 years.

In patients of any age, asthma can have an insidious onset or it can follow an acute respiratory infection or a large exposure to an irritant (such as chlorine or ammonia) or an allergen, either seasonal (such as ragweed or oak pollen) or perennial (such as cat or dog dander).

In a study at the Mayo Clinic by Reed and colleagues, 27% of 228 elderly patients with asthma were given allergy skin tests; of these patients, 28% had 1 or more positive results.⁴ The incidence of positive skin test results was associated with the age at asthma onset; positive results were recorded in 56% of patients with asthma onset before age 40 and in 21% of patients with asthma onset after age 40.⁴

Many elderly patients with asthma have elevated IgE levels; of these patients, many have positive results on skin tests or specific IgE tests for allergens.^5,6 In 2 studies of elderly persons, the most frequently reactive allergens were cockroaches (in New York City) and house dust mites (in Clearwater, Florida).^6,7

Allergic or nonallergic rhinitis may accompany asthma, and chronic rhinosinusitis and gastroesophageal reflux disease (GERD) may play an exacerbating role. Comorbidities are more common in elderly patients than in those who are younger, as will be discussed below.

Age-related differences

Somephysiologic changes associated with aging may be factors in the presentation of asthma in elderly patients (Table 1). For example, elderly persons have decreased lung elastic recoil, respiratory muscle strength, chest wall compliance, and mucociliary clearance. They have impaired respiratory reflexes, which may reduce responsiveness to ß-agonists, and impaired perception of respiratory loads.

Older patients with asthma may present with chronic cough or difficulty in walking any distance or performing normal household tasks. Some of these patients may not recognize that they have a breathing problem; the diagnosis may be incidental on auscultation of the lungs for an unrelated presenting complaint, with the finding of decreased air movement or end-expiratory wheeze.

Like younger persons with asthma, elderly patients may have diffuse airway obstruction, airway hyperresponsiveness, wheezing, cough, and dyspnea.The reversibility of airway obstruction that characterizes asthma may be less pronounced in the elderly (Table 2).Although chronic cough may be the presenting symptom of asthma in any age group, it is more likely to be so in the elderly.

Elderly patients are more likely than younger persons to have a significant smoking history and therefore are more likely to have chronic obstructive pulmonary disease (COPD). As a result of this, asthma is more likely to be misdiagnosed as COPD in an elderly person. There is also a greater incidence of congestive heart failure (CHF) in the elderly, and they have more difficulty with chest wall compliance than younger patients. Many patients as well as physicians consider a degree of breathlessness to be part of the aging process, when it may in fact be caused by asthma or another disease.

The physical examination of the elderly patient who presents with cough, dyspnea, or wheezing should include careful auscultation of the lungs. It is important to pay attention to whether wheezes are primarily high-pitched end-expiratory noises (presumably produced by emptying the small bronchioles); rales (fine inspiratory and expiratory sounds associated with pulmonary edema or heart failure); or rhonchi (coarse inspiratory and expiratory sounds heard more often in bronchitis), which can be difficult to differentiate from wheezing. High-pitched inspiratory "squeaks," most readily heard in the upper chest and over the trachea, may indicate laryngeal stridor, which is common in vocal cord dysfunction.

Diagnostic studies

The differential diagnosis of asthma includes other pulmonary diseases, such as COPD and bronchiectasis; cardiovascular diseases, such as CHF; neoplastic diseases, such as lung cancer; and other diagnoses, such as aspiration, GERD, vocal cord dysfunction, and chronic postnasal drip (Table 3). There are key differences between the diagnostic features of asthma and those of COPD. Patients who have asthma typically have reversibil- ity on spirometry and normal carbon monoxide-diffusing capacity (DlCO), whereas patients with COPD have little or no reversibility, a ratio of forced expiratory volume in 1 second (FEV₁) to forced vital capacity of less than 70%, and reduced DlCO (Table 4). Simple spirometry or measurement of peak expiratory flow (PEF) can confirm a decrease in expiratory flow.

The diagnosis of asthma can be further supported by documenting an improvement in bronchial hyperreactivity (reversibility) after the inhalation of a ß₂-agonist, such as albuterol (50 µg, 2 puffs). If the patient is unresponsive to albuterol alone, a combination of albuterol (120 µg) and ipratropium (21 µg, 1 or 2 puffs) can be administered. If the patient's FEV₁ does not improve by at least 12% or 200 mL from baseline, a course of oral prednisone (20 mg, 3 times daily) for up to 2 weeks may improve symptoms; it may also increase the FEV₁, thereby confirming the presence of asthma.⁸ Nonetheless, it is not always possible to differentiate asthma from COPD because many patients have features of both.

CHF can cause breathlessness and wheezing, particularly in the elderly. Serum brain natriuretic peptide (BNP) levels, which can be obtained in most laboratories, are often helpful. A BNP level that is highly elevated can confirm CHF, whereas a normal or minimally elevated BNP level may indicate an exacerbation of asthma or COPD.

Other differences between CHF and asthma can be seen on chest radiographs, which are usually normal in patients with asthma, and in the incidence and severity of orthopnea and ankle edema (Table 5). Compared with patients who have asthma, patients with CHF are more likely to have orthopnea and significant ankle edema.

THERAPY

It is important to ensure the accuracy of the diagnosis of asthma; if in doubt, it should be confirmed by consultation with an asthma specialist, allergist, or pulmonologist. Once confirmed, the first step in improving the patient's quality of life is to consider factors specific to the elderly.

In a study of environmental and social factors associated with hospital admission for asthma in Hillsborough County, Florida, Tamulis⁹ identified the following factors: low income, lack of automobile and telephone, increased number of persons inhabiting 1 room, and lack of a primary care physician. Older nonwhite women were more likely than others to be hospitalized for asthma.

When an elderly patient presents with cough and dyspnea, many physicians may not consider the possibility of asthma. Older patients and their physicians may accept breathlessness as a part of the natural aging process. Polypharmacy can make it difficult to differentiate side effects of medications (such as angiotensin-converting enzyme inhibitors and ß-blockers) from asthma, and some physicians may be reluctant to stop medications that were prescribed by other physicians.

Older patients may not hear the physician's or nurse's directions and may have difficulty in reading the fine print in package inserts. Impaired dexterity can make using complex inhalers challenging. Although drug costs and drug interactions are important considerations for patients of any age, they are particularly so for the elderly.

It is also important that the phy- sician and patient engage in asthma education, agree on realistic goals, and conduct periodic follow-ups. Patients with newly diagnosed asthma should be monitored, first closely and then periodically, using spirometry and PEF measurements to evaluate clinical response as necessary.

Goals

The physician and the patient with asthma should work together to define the goals of therapy. These may include, for example, the ability to get an adequate night's sleep, take longer walks, work around the house, and stay awake to read or watch television. Factors that can influence therapeutic goals for elderly patients include comorbidities, cognitive status, sensory limitations, patient health care values, financial status, and family health and support (Table 6).

Factors central to the patient's quality of life must be considered when setting these goals. Goals such as independent living and participation in leisure activities are usually stronger motivators than objective improvement in lung function. Other therapeutic considerations include the physical properties of medication, such as the capsule or tablet size and the type of delivery device (whether a dry or wet form of metered-dose inhaler [MDI] is used).

Minimizing the side effects of asthma medications is also important, particularly in the elderly.¹⁰ The elderly may require lower doses of medications than younger adults because of decreased metabolism or weight. The presence of dentures may make it more difficult to rinse after use of a dry-powder inhaler. The use of a spacer may help compensate for decreased manual dexterity and deep inspiratory effort. Careful screening for possible drug interactions may help avoid side effects.

Other important considerations include smoking cessation, access to health care, respiratory rehabilitation, environmental control measures (such as avoidance of allergens and secondhand smoke), and influenza and pneumococcal vaccinations. Allergen identification by history, skin testing, or in vitro testing (if the skin is severely photodamaged) can be useful. If clinically significant allergens are identified, allergen avoidance or immunotherapy for select allergens may be helpful.

Treatment guidelines

Current guidelines from neither the National Heart, Lung, and Blood Institute (NHLBI) nor the Global Initiative for Asthma (GINA) provide separate recommendations for treatment of elderly patients with asthma.^8,10-12 Only a few studies have investigated treatment specifically for the elderly. Most studies sponsored by the government or pharmaceutical companies have included patients with "pure asthma"--patients with at least 12% reversibility and no significant history of smoking or comorbidities.

Similarly, there is little information about patients' allergic status; the presence of comorbid conditions, such as chronic rhinosinusitis, GERD, or CHF; and age-specific side effects. The NHLBI guidelines,¹² which group together all patients older than 5 years, were based on studies that usually excluded elderly persons simply on the basis of age. New guidelines based on recent studies of elderly asthmatic patients are needed.

The NIH has updated a set of guidelines for treatment of asthma in children older than 5 years and adults, and in 2005, the NHLBI and World Health Organization updated an abbreviated guide on asthma management and prevention in the same population (Table 7).¹³ The expert panel on asthma in the elderly convened by the NHLBI in 1996 recommended that the guidelines used for children older than 5 years and adults should also be used for the elderly until further research is accomplished¹⁰; however, the group did not define "further research." The complete GINA report, more than 200 pages in length, contains a half page on "Asthma in the Elderly" and has no specific recommendations for further research.⁸

Medications

In treating the elderly patient with asthma, problems with medications can include side effects, drug interactions, difficulty with delivery, and concerns about the effect of metabolic rates on dosing. Likewise, the cost of medications and of other aspects of asthma care can be a significant burden.

Short-acting ß-agonists may cause tachycardia, arrhythmias, and agitation, as well as difficulty in sleeping.¹⁴ Although selective ß-agonists, such as albuterol, are generally preferred, levalbuterol (the l-isomer of albuterol) may be preferred in some patients because it has fewer adverse effects. However, the use of levalbuterol to treat asthma in the elderly population has not been studied.

Both the NHLBI and GINA guidelines indicate that an inhaled corticosteroid (ICS) is the preferred first-line controller drug for persistent asthma. ICSs are available via an MDI with or without a spacer; a dry-powder inhaler; or a nebulizer delivery system. While most elderly patients can use these devices, visual impairment and decreased manual dexterity may make it difficult for some. Before ordering a nebulizer, we recommend a trial of an MDI with a spacer, which may deliver more medication than an MDI without a spacer. Finer particles of 1.2 µm, such as those delivered by a new hydrofluoroalkane-134a-beclomethasone MDI, may reach the smaller airways.

Use of an ICS may lead to thrush, especially if the patient has difficulty with mouth rinsing after use. The use of dentures can cause increased drug deposition and promote the growth of Candida albicans under the dentures. Prolonged use of an ICS has been shown to cause thinning of the mucosa of the pharynx and the larynx, with cough and hoarseness associated with prolonged use in some patients.¹⁵

High doses of an ICS (1.5 mg daily of a lower-potency ICS or 0.75 mg of a higher-potency ICS, such as fluticasone) over a prolonged period may increase the risk of osteoporosis and subcapsular cataracts, both common in the elderly.¹⁶ Therefore, the NHLBI and GINA guidelines recommend that after control is achieved, the ICS should be titrated to the minimum dose that can maintain clinical control.

Long-acting ß-agonists (LABAs) have been recommended for use in combination with ICSs to treat moderate and severe persistent asthma. However, there are concerns about the safety of LABAs, especially in the elderly; these include possible arrhythmias, hypertension, and death. Concerns have also arisen about increased morbidity in African American patients who use LABAs, leading the FDA to issue a black box warning about potential risks associated with these drugs.

In November 2005, the FDA issued a public health advisory stating that LABAs may increase the risk of severe asthma episodes and death.¹⁷ This advisory states that LABAs should not be used as a first-line therapy in the treatment of asthma and should only be added if other medications fail to control asthma. It warns that patients should not stop the use of LABAs without first consulting their physician. It also advises that LABAs do not relieve sudden wheezing and should not be used for wheezing that is worsening.

The multinational "Gaining Optimal Asthma ControL" (GOAL) study included 3241 patients with uncontrolled asthma, aged 9 to 80, who were treated with ICSs and LABAs according to the NHLBI and GINA guidelines.¹⁸ Although most patients attained asthma control, a large number did not meet the study's criteria for "well controlled" or "total control."

Not all patients respond similarly to ICSs and LABAs; some differences in response may be pharmacogenetic. When patients fail to attain control with maximum recommended doses, it may be necessary to add other medications or to substitute other ICSs or LABAs. A different delivery system may be more effective for some patients.

In these circumstances, the NIH and GINA guidelines recommend alternative medications, such as theophylline, leukotriene modifiers, cromolyn or nedocromil, and omalizumab. Theophylline was first recognized as a bronchodilator in 1936, and itwas used extensively in the 1970s and 1980s to treat asthma. However, in the United States, it is not used as a first-line therapy, particularly when recommended doses are exceeded, because of concerns about possible adverse effects, including GI symptoms, arrhythmias, and seizures.

Evans and colleagues¹⁹ have shown that theophylline (at serum levels of 5 to 10 µg/mL) has anti-inflammatory properties. Their findings indicated that adding a low dose of a sustained-release theophylline (200 to 300 mg/d by mouth) is superior to doubling the dose of an ICS.¹⁹ Ito and associates²⁰ showed that ICSs and theophylline acted synergistically to reduce inflammation in a laboratory model of asthma.

Theophylline, when used in proper doses, has been shown to be very safe in a study of more than 6000 elderly patients with either COPD or asthma.²¹ Its generic form is inexpensive, which is of particular advantage to the elderly.

Another recommended alternative medication class is leukotriene modifiers; those available in the United States include montelukast, zafirlukast, and zileuton.In the 1 documented study of asthma in which a significant number of elderly persons were included (321 of the 3759 patients were elderly), zafirlukast was administered. After 4 weeks, the elderly patients demonstrated improvement in morning PEF and a decrease in symptoms.²²

Cromolyn and nedocromil are listed as alternative controllers in the asthma guidelines. These agents are very safe but are not as effective as ICSs. No studies have specifically examined the use of cromolyn or nedocromil in the elderly, but these medications may be useful for some who have mild to moderate persistent asthma.

In addition to the medications recommended by the NHLBI and GINA guidelines, some newer drugs should be considered for treating a patient with moderate to severe asthma who requires systemic corticosteroids or frequent hospitalizations. Omalizumab is an anti-IgE monoclonal antibody that is available in an injectable form. For patients with elevated serum IgE levels who fall within the parameters for weight and IgE level, this drug has shown promise.

Comorbidities

It is important to treat comorbidities that may trigger or exacerbate asthma. Possible comorbidities include allergic rhinitis, acute and chronic rhinosinusitis, GERD, vocal cord dysfunction, and muscular deconditioning.

Allergic rhinitis may be part of a "one airway disease" that includes allergic asthma. Nasal congestion may also lead to mouth breathing and inhalation of colder air, a common trigger of asthma. Treating nasal allergies may help prevent the triggering of asthma. Antihistamines and nasal corticosteroids are first-line therapies for aller- gic rhinitis, and recent interest in leukotriene modifiers has been shown.

Infections, including rhinosinusitis, are often associated with worsening asthma. Treating the rhinosinusitis frequently leads to improvement in asthma. Treatment may include cleansing the nasal passages with saline washes and taking appropriate antibiotics.

Therapy for GERD may help reduce the triggering of asthma by acid reflux. Although there is some controversy as to whether asthma causes GERD or GERD worsens asthma, a trial of GERD therapy may help control asthma.

Vocal cord dysfunction, in which the vocal cords involuntarily close on inspiration, may be treated with instruction on proper speech and breathing techniques. Occasionally, it is treated with biofeedback and with the use of diazepam.

Heart failure may be confused with asthma; both can cause dyspnea and abnormal breath sounds. Patients with asthma may also have heart failure; these patients frequently require both cardiology and pulmonary specialty care. Targeted therapy for the underlying causes of heart failure, and the use of diuretics, can be important.

In elderly persons, the accessory muscles of respiration are often ineffective and the rib cage is not pliable; therefore, diaphragmatic breathing is essential. A goal of pulmonary rehabilitation is to teach abdominal breathing, which can be initiated in the primary care office.

References:

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