Cough, wheezing, and dyspnea are the common symptoms of obstructive lung disease and overlap between asthma and COPD. History can be useful to identify a specific obstructive lung disease, for example, a history of symptoms first appearing in childhood, a persistent cough after an upper respiratory tract infection, and/or a history of atopic disease or occupational exposure favor asthma (10,11). An episodic cough, perhaps brought on by exercise or allergens, also indicates an asthmatic component to obstructive lung disease. In contrast, patients with COPD generally have more constant and progressive symptoms; many patients with longstanding disease may be asymptomatic even in the face of severe disease (12). Age is an indicator of the type of obstructive lung disease. In one study, the mean age of patients with predominantly asthmatic bronchitis was 29.6 years versus 64.6 years for emphysematous COPD (2). Patients with α₁-antitrypsin deficiency develop premature COPD, with a mean age of dyspnea onset at 40 years for smokers and 53 years for nonsmokers. Therefore, patients less than 50 years of age with moderate or severe chronic airflow obstruction, basilar emphysema, and a strong family history of obstructive disease, should be tested for α₁-antitrypsin deficiency (4).

The most useful signs on physical examination of airflow obstruction are objective wheezing, barrel chest deformity, rhonchi, hyperresonance, subxiphoid apical impulses, and an objective measurement of prolonged expiration (11,13,14). Forced expiratory time may be useful to screen for obstructive lung disease; however, physicians are generally poor at estimating the severity of obstruction from physical examination. In one series, only 38% of physicians’ pretreatment estimates were accurate (15). The role of blood studies in the evaluation of obstructive lung disease is limited. An elevated IgE level and increased blood eosinophils may aid in identifying patients with asthmatic airflow obstruction. Patients with any history of asthma have a higher degree of eosinophilia and elevated IgE levels than patients without a history of asthma (3,16). However, patients with newly diagnosed chronic bronchitis may also have elevated IgE and eosinophil levels.

The most useful laboratory studies for the evaluation of airflow obstruction are pulmonary function tests. These tests are necessary for diagnosis, evaluating disease severity, and monitoring response to treatment (4,17). Spirometry is a simple screening test for airflow
obstruction, with spirometers widely available and simple to use. American Thoracic Society guidelines provide normal standards and the framework for the interpretation of results, with values adjusted for age and gender (Table 15.2) (18). The most valuable measurements include the FEV₁, forced vital capacity (FVC), and peak inspiratory/expiratory flows measured from a maximal expiratory maneuver. A decrease in the FEV₁/FVC ratio from the predicted range is diagnostic of airflow obstruction (18,19). A lower initial FEV₁/FVC ratio in COPD may be associated with greater declines in FEV₁ over time (20). Airflow obstruction severity is judged on FEV₁ expressed as a percent of the predicted value (18). A graphic representation of peak expiratory and inspiratory flow versus lung volume, known as the flow-volume loop, should be examined to exclude potential upper airway obstruction (21).

Measurement of spirometric parameters before and after administration of a short-acting β agonist may aid in establishing bronchoreversibility. A rise in FEV₁ of 12% with an absolute rise of at least 200 mL indicates bronchoreversibility (18). Complete reversibility of airflow obstruction makes the diagnosis of asthma likely and strongly argues against COPD (11). However, a subset of patients with asthma develop irreversible airflow obstruction (7,22,23,24). Such patients typically have a longer duration of asthma and more symptomatic disease than asthma patients with reversible obstruction (22). Furthermore, asthma patients with irreversible airflow obstruction may have baseline FEV₁, FVC, and postbronchodilator FEV₁ measurements indistinguishable from COPD patients; therefore, the lack of bronchodilator reversibility cannot be used with sufficient specificity to differentiate COPD from asthma (23). Up to 30% of patients with COPD have bronchoreversibility at spirometric testing (25,26). In a series of patients with asthma (n = 287) or COPD (n = 108), the mean increase in FEV₁ from baseline after inhaled albuterol was higher in asthma patients (16.5% versus 10.6%); however, there was significant overlap (9). The best specificity for the diagnosis of asthma (84%) was defined at a threshold of a 20% or greater increase in FEV₁ from baseline; however, sensitivity was poor. The postbronchodilator FEV₁ has been shown to be the single best predictor of survival in patients with COPD, with a value below 30% of predicted associated with marked reduction in long-term survival (25). As a result, the postbronchodilator FEV₁ has become instrumental in establishing an appropriate time for considering surgical therapy in patients with advanced COPD.

Spirometry can also be performed after the administration of an agent to induce bronchial hyperreactivity, such as methacholine (19,27). Patients with asthma have greater airway hyperresponsiveness than patients with COPD (27,28,29),30), although many patients with COPD also have airway hyperreactivity (27). In the Lung Health Study of almost 6,000 current smokers with borderline to moderate airflow obstruction, nonspecific airway hyperresponsiveness (defined as a drop of at least 20% in FEV₁ after inhalation of no more than 25 mg/mL methacholine) was noted in 85.1% of women and 58.9% of men (31). Baseline airway obstruction, wheeze, cough with or without sputum production, and a past history of asthma or hay fever were associated with hyperresponsiveness.

The measurement of lung diffusing capacity for carbon monoxide (DL_CO) is a routine test in the evaluation of chronic airflow obstruction, particularly for more advanced disease. DL_CO is a sensitive test for emphysema, a disease process associated with loss of alveolar surface area and pulmonary circulation (32). Decreased DL_CO accompanying chronic airflow obstruction suggests at least a component of emphysema (33). The specificity of DL_CO for obstructive lung disease is low, and it should be used together with clinical history and physical examination. In large epidemiologic studies, a normal DL_CO is associated with asthma rather than COPD (34). DL_CO may be also increased in patients with asthma (35,36). However, when asthma manifests with irreversible airway obstruction, DL_CO may be low (23). In patients with emphysema, there is a strong correlation between low DL_CO and greater severity of emphysema on CT (37). A decreased DL_CO is associated with a more rapid decline in pulmonary function over time (20).

Peak expiratory flow is the maximal flow that can be achieved during maximal expiratory effort. This measurement has been widely accepted and advocated for the monitoring of patients with airflow obstruction, particularly asthma (17). Widespread availability of inexpensive, simple, reliable devices has made the routine measurement of peak expiratory flow rate possible (38). There is a close relationship between the FEV₁ and peak expiratory flow rate; however, in general peak expiratory flow rate is consistently higher (38,39). Limitations of using peak expiratory flow rate include a reduction in peak expiratory flow rate both with obstructive lung disease and upper airway obstruction (21) and a lower sensitivity of peak expiratory flow rate than spirometry for detecting reversibility of airflow obstruction after bronchodilators or detecting bronchial response to challenge with occupational sensitizers (40,41).

Posteroanterior and lateral chest radiographs are part of the initial evaluation of dyspnea. Many of the radiographic signs of obstructive lung disease lack specificity, such that chest radiographs are used predominantly to support a diagnosis of obstructive lung disease and not for primary diagnosis. Radiographic signs of obstructive lung disease also lack sensitivity and should not be used to exclude the diagnosis. The radiographic features of asthma, chronic bronchitis, and emphysema often overlap, similar to the overlap in clinical features. Although CT findings in the different forms of obstructive lung disease are well described and CT is the best tool to evaluate the severity of emphysema in vivo, CT has a limited role in the primary diagnosis of obstructive lung disease. In a small subset of dyspnea patients with an isolated reduction in diffusing capacity and otherwise normal pulmonary function tests and a normal chest radiograph, HRCT is useful for establishing the diagnosis of emphysema (42,43). When bronchiectasis is suspected, HRCT is the technique of choice for detecting, localizing, and characterizing bronchiectasis, having replaced bronchography. HRCT examinations can also be performed at end-expiration to add a functional component to the inspiratory HRCT technique. Expiratory CT may demonstrate air trapping in patients with small airway diseases such as asthma and bronchiolitis obliterans, often when inspiratory HRCT images are normal (44).

Chronic bronchitis is diagnosed clinically by the presence of chronic productive cough for 3 months in each of 2 successive years in a patient in whom other causes of chronic cough have been excluded (4). Compared with asthma and emphysema, the radiographic features of chronic bronchitis are poorly described. Findings at chest radiography include pulmonary hyperinflation and thickened bronchial walls, resulting in peribronchial thickening or cuffing, and increased “markings” due to superimposition of the thickened small bronchi and bronchiole walls (70). There is little information on the HRCT findings in chronic bronchitis. The most common HRCT finding is bronchial wall thickening, a nonspecific finding (71). In one series of 45 patients with air trapping on expiratory HRCT, 4 patients with chronic bronchitis were reported (44). All four patients had air trapping on expiratory HRCT, and one patient had a normal inspiratory HRCT. In the remaining three patients, the inspiratory HRCT demonstrated bronchial wall thickening, a tree-in-bud appearance secondary to mucoid impaction, and ground glass opacity presumed to be secondary to concomitant infection.

According to the American Thoracic Society, emphysema is defined as “a condition of the lung characterized by abnormal, permanent enlargement of the air spaces distal to the terminal bronchiole, accompanied by destruction of their walls” and without obvious fibrosis (4). Emphysema occurs due to an imbalance in the proteolytic activity in the lungs, resulting in destruction of alveolar tissue. This may be seen with an overabundance of proteolytic enzymes, a lack of antiproteases, or a combination of both. In smoking-related centrilobular emphysema there is excess protease, whereas in α₁-antitrypsin deficiency there is a deficiency of α₁-antiproteinase.

The pathologic classification of emphysema is based on the secondary pulmonary lobule. The four major categories of emphysema, as listed in Table 15.3, are centrilobular (centriacinar),
panacinar (panlobular), paraseptal, and paracicatricial (Fig. 15.3) (72). Table 15.4 summarizes the differences between centrilobular and panlobular emphysema. Centrilobular emphysema is the most common form of emphysema and is usually secondary to cigarette smoking. The destruction of alveolar walls begins in the central portion of the secondary pulmonary lobule (Fig. 15.4) and is heterogeneous, affecting adjacent lobules with varying degrees of severity; it is usually most severe in the upper lobes (Fig. 15.5). The relatively greater ventilation-perfusion ratio in the upper portion of the lungs compared with the lung bases favors greater deposition of the particulate matter from cigarette smoke in the upper lungs. Activated macrophages release the proteolytic enzyme, elastase; free radicals and oxidants in cigarette smoke inactive normally protective antiproteases, leading to greater destruction of the upper lobes than the lower lobes (72).