ABSTRACT:The diagnosis of asthma in older persons may be complicated by a number of factors, including atypical presentations and comorbid conditions, such as chronic obstructive pulmonary disease and congestive heart failure (CHF). A high index of suspicion for the diagnosis of asthma is warranted in patients with isolated dyspnea or cough. The diagnosis should be based on demonstration of reversible airway obstruction on pulmonary function tests. Additional tests that may be useful in the initial evaluation include chest radiography, arterial blood gas analysis, and standard electrocardiography. CT may help exclude pulmonary embolism and certain neoplasms that can masquerade as asthma. High-resolution CT scans are valuable when pulmonary function test results are consistent with interstitial lung disease. When the diagnosis is uncertain, measurement of brain natriuretic peptide can help distinguish between obstructive lung disease and CHF. (J Respir Dis. 2008;29(10):391-396) With the aging of the US population and the increasing prevalence of asthma, the number of adults older than 65 years who have asthma will increase considerably in future decades.1 These seniors with asthma may present with the typical symptoms of cough, wheeze, and dyspnea or with isolated complaints of fatigue or functional decline (Table 1). Common misdiagnoses include chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), depression, and "aging."2 Available data suggest that asthma is both underdiagnosed and misdiagnosed in seniors.2-4 Failure to pursue the diagnosis of asthma in symptomatic patients may result in lost treatment opportunities that could slow progression of the disease. Underlying medical conditions that mimic asthma or trigger asthma symptoms, such as gastroesophageal reflux and rhinosinusitis, may also go undetected.5 The presence of comorbid conditions, the decreased perception of bronchoconstriction in the elderly, and the propensity of older persons to minimize and adapt to symptoms with lower levels of functioning all contribute to underdiagnosis of asthma.6 These factors may partially explain why the elderly present later after the onset of symptoms and with more advanced airway obstruction than younger asthmatic patients.7,8 Because of these issues, we have developed an algorithmic approach to facilitate the diagnosis of asthma in this vulnerable population. MAKING THE DIAGNOSIS Atypical symptoms Atypical presentations are common in older patients.9 Questioning older patients about shortness of breath, wheezing, chest tightness, and cough may help identify many cases of asthma. However, a high index of suspicion for the diagnosis is warranted in patients with isolated dyspnea, cough, or fatigue. Asthma must be considered if there is a history of allergic disease earlier in life; active atopic diseases, such as rhinosinusitis or eczema; or peripheral blood eosinophilia. Wheeze, cough, and dyspnea may also be present in patients with COPD, CHF, hypersensitivity pneumonitis, sarcoidosis, and other conditions in which endobronchial airflow obstruction is present. Thus, there is a developing consensus that the diagnosis and assessment of the severity of asthma in elderly patients should be based on demonstration and quantification of reversible obstructive airway disease by pulmonary function testing. Pulmonary function testing There are adequate data to establish that most older adults can perform pulmonary function tests well. The Respiratory Health in the Elderly study of 1500 patients found that age and cognitive function were 2 of the most important variables related to poor reproducibility of forced expiratory volume in 1 second. 10 However, the investigators concluded that if rigorous quality-control measures are followed, reliable data can be obtained in most elderly patients.11,12 These findings have been confirmed in 2 smaller studies of patients who were older than 65 years. Even those who had some degree of dementia could adequately perform pulmonary function testing. Using pulmonary function testing as the gold standard, asthma can be diagnosed on the basis of pre-and post-bronchodilator testing that demonstrates 12% or greater reversibility. Some patients with COPD may have episodic reversibility in this range, while some older patients with chronic asthma may have high levels of inflammation leading to fixed obstruction.4 In some cases, repeated pre- and post-bronchodilator testing or treatment with corticosteroids may be necessary to demonstrate adequate reversibility required to meet the diagnostic criteria. Therefore, it is not always possible to differentiate between COPD and asthma based on symptoms or pulmonary function test results. Diagnosis is even more challenging because it is also common for the 2 diseases to coexist, notably in present or former smokers. COPD is very unusual in seniors who have not smoked cigarettes for more than 10 years. Most smokers with COPD have moderate to severe airway obstruction on spirometry with only modest improvement after using an inhaled bronchodilator. They also tend to have a low carbon monoxide–diffusing capacity (DLCO). The DLCO test is quick and easy to perform but is available only from hospital-based pulmonary function laboratories. No data clearly establish the interaction of COPD and asthma with respect to the natural history or treatment of either disease. However, standard asthma treatment should be considered in patients who have both conditions. Other tests In addition to pulmonary function tests, a chest radiograph, a standard ECG, a hemogram, and blood chemistries are useful in the initial evaluation. Arterial blood gas analysis is indicated if pulse oximetry shows low oxygen saturation. Arterial blood gases are important to monitor in those with hypoxemia. In the presence of hypoxemia, normal PCO2 levels are associated with impending respiratory failure. CT may help exclude pulmonary embolism and certain neoplasms that can masquerade as asthma. High-resolution CT can be used when pulmonary function tests reveal patterns such as low total lung capacity and low DLCO, which are consistent with interstitial lung disease. The measurement of fractional expiratory nitric oxide holds promise as a diagnostic aid and is of special interest in this population. It has a high level of sensitivity in children and younger adults with asthma and can be used to monitor the effectiveness of therapy. Other tests are also available to assist in diagnosing asthma in select elderly patients (Table 2). Algorithmic approach An algorithmic approach to diagnosis can be useful in seniors with possible asthma (Figure). When the results of a careful history and physical examination, such as prolonged exhalation time or wheezing on forced exhalation, suggest obstructive airway disease, basic laboratory data (hemogram, blood chemistries) and a chest radiograph are obtained. Pulmonary function tests are then used to pursue the diagnosis and help quantify disease severity. Further workup is determined by the presence or absence of airflow obstruction, reversibility of obstruction, and clinical suspicion for asthma (pretest probability). Lung volume and DLCO studies as well as spirometry may be required in this process. Certain diagnostic tools can be helpful when the diagnosis isuncertain. Measurement of brain natriuretic peptide (BNP) has become a useful laboratory test in the distinction between obstructive lung disease and CHF in patients presenting with a recent onset of severe dyspnea. Values of BNP greater than 700 pg/mL are highly suggestive of CHF in this setting.13 However, the presence of CHF does not exclude the coexistence of asthma. Cough and dyspnea in seniors with CHF may result from nonspecific bronchial hyperreactivity. In this situation, the airways are hyperreactive to methacholine and other acetylcholine congeners that are associated with cough and dyspnea in patients with asthma. One study of 23 patients with left-sided heart failure demonstrated that more than 90% had bronchial hyperresponsiveness to methacholine; 43% of these patients showed improvement in pulmonary function after albuterol inhalation.14 Thus, CHF and asthma, like COPD and asthma, may coexist in the elderly. Although airway hyperresponsiveness to methacholine does not prove the diagnosis of asthma, its absence makes this diagnosis extremely unlikely. For this reason, the greatest value of the methacholine challenge test in older adults is its negative predictive value. However, it should be noted that methacholine challenge is associated with increased risk in elderly patients who have comorbid conditions, such as uncontrolled hypertension and recent myocardial infarction or stroke. AFTER DIAGNOSIS, WHAT NEXT? Potential confounding variables Once the diagnosis is made, what then? There are a number of reasons to be concerned about our present approach to asthma treatment in elderly patients. The natural history of the disease is poorly understood in general and in seniors in particular. Some studies suggest that the course is more persistent and progressive in the elderly and that the mortality rate is higher. The role of allergic triggers appears less important in this population, although the published data are conflicting.7,15 If the natural history of asthma is different in seniors, the interpretation of small clinical trials with patients in this age range could be affected. Therapeutic options The approach to the diagnosis of asthma is evidence-based and a number of promising technologies support the differential diagnosis. Unfortunately, management issues remain less clear. There is a confusing array of therapeutic options for asthma.16 Special concerns have been expressed about adverse-effect profiles of many of the pharmaceutical agents, such as β2-agonists and high-dose inhaled corticosteroids, used routinely to treat asthma in younger populations. The 2007 asthma treatment guidelines listed 8 "special issues" regarding the disease in older adults (Table 3).5 Three of these were related to concerns about adverse effects of β2-agonists, theophylline, and oral corticosteroids. Although these concerns may be valid, none are based on adequate data for evidence-based recommendations. Most treatment recommendations are derived from studies that enrolled patients with a broad range of ages; persons with conditions common to the elderly were excluded from participation. Appropriately controlled studies have never been performed to determine optimal treatment of asthma in patients older than 65 years. Two concerns raised in the 2007 guidelines are the role of drugs used to treat other conditions that may function as triggers for asthma and problems with inhalers and spirometric devices. These are clearly important in asthmatic patients in general, but they have not been demonstrated to be more common in seniors than in older adults. The nonpharmacological management of asthma seems an especially important area for future investigations. For instance, swimming and warm-water exercise seem especially helpful in older patients with asthma. Similarly, weight reduction in obese patients and allergen immunotherapy in those with allergies who have unavoidable ongoing exposure to allergens also seem useful. Clearly, smoking cessation is very important, and avoidance of smoke and pollutants, which sometimes worsen asthma, is also important. Finally, some studies suggest that treatment of coexistent depression and asthma self-management programs may be associated with decreased asthma mortality. CONCLUSION With an increasing population of older Americans with asthma, the time has come to develop an evidence-based approach to asthma management in the elderly. Challenges in meeting this goal include the limited information available about the pathogenesis and natural history of the disease, the difficulty of including this population in clinical trials, and the lack of incentive for pharmaceutical companies to perform clinical trials in this population. This is a special problem, since seniors often use generic drugs preferentially over patent drugs because of cost (although there are no generic inhaled corticosteroids available in the United States). References: REFERENCES 1. NAEPP Working Group Report: considerations for diagnosing and managing asthma in the elderly. 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