3: Evaluation of the patient with pulmonary disease

OUTLINE

Evaluation on a Macroscopic Level, 28

Physical Examination, 28

Chest Radiography, 32

Computed Tomography, 36

Magnetic Resonance Imaging, 38

Radionuclide Lung Scanning, 38

Pulmonary Angiography, 41

Ultrasonography, 41

Bronchoscopy, 41

Evaluation on a Microscopic Level, 43

Obtaining Specimens, 43

Processing Specimens, 45

Assessment on a Functional Level, 46

Pulmonary Function Tests, 46

Arterial Blood Gases, 53

Exercise Testing, 55

In evaluating a patient with pulmonary disease, the physician is concerned with three levels of evaluation: macroscopic, microscopic, and functional. The methods for assessing each of these levels range from simple and readily available studies to highly sophisticated and elaborate techniques requiring state-of- the-art technology.

Each level is considered here, with an emphasis on the basic principles and utility of the studies. Subsequent chapters repeatedly refer to these methods because they form the backbone of the physician’s approach to the patient.

Goals of auscultation:

1.Assessment of intensity and quality of breath sounds

2.Detection of adventitious sounds

When the examiner listens over consolidated lung—that is, lung that is airless and filled with liquid or inflammatory cells—the findings are different. The sound generally is louder and harsher, more tubular in quality, and the most characteristic feature is that expiration is at least as loud and as long as inspiration. Such breath sounds are called bronchial breath sounds, as opposed to the normal or vesicular sounds.

This difference in quality of the sound is due to the ability of consolidated lung to transmit sound better than normally aerated lung. As a result, sounds generated by turbulent airflow in the central airways (trachea and major bronchi) are transmitted to the periphery of the lung and can be heard through the stethoscope. Normally, these sounds are not heard in the lung periphery; they can be reasonably well demonstrated, however, by listening near their site of origin—for example, over the upper part of the sternum or the suprasternal notch. These normal tracheal breath sounds approximate the quality of abnormal bronchial breath sounds heard over consolidated lung. Finally, when the stethoscope is placed over large airways that are not quite as central as the trachea, or over an area of partially consolidated lung, the breath sounds are intermediate in quality between bronchial and normal (vesicular) sounds and therefore are often termed bronchovesicular.

Consolidated lung does not transmit sound in the same way as air-containing lung.

Improved transmission of sound through consolidated rather than normal lung can also be demonstrated when the patient whispers or speaks. The enhanced transmission of whispered sound results in more distinctly heard syllables and is termed whispered pectoriloquy. Spoken words can be heard more distinctly through the stethoscope placed over the involved area, a phenomenon commonly called bronchophony. Because of differences in acoustic filtering between normal and consolidated lung, when the patient says the vowel “E,” the resulting sound through consolidated lung has a nasal “A” quality. This “E-to-A change” is termed egophony. All these findings are variations on the same theme—enhanced transmission of sound through consolidated lung—and basically have the same significance.

Two qualifications are important in interpreting the quality of breath sounds. First, normal transmission of sound depends on patency of the airway. If a relatively large bronchus is occluded, such as by tumor, secretions, or a foreign body, airflow into that region of lung is diminished or absent, and the examiner hears decreased or absent breath sounds over the affected area. A blocked airway proximal to consolidated or airless lung also eliminates the increased transmission of sound described previously. Second, air or fluid in the pleural space acts as a barrier to sound transmission, so a pneumothorax or pleural effusion causes diminution of breath sounds.

The second major feature the examiner listens for is adventitious sounds. Although there is some variation in how different adventitious sounds are described, the most commonly used terms are crackles, wheezes, and friction rubs. Because several additional terms—stridor, rhonchi, and squawks—are also sometimes used, we have described them as well.

Crackles, also called rales, are a series of individual clicking or popping noises heard with the stethoscope over an involved area of lung. Their quality can range from the sound produced by rubbing hairs together to that generated by opening a hook-and-loop (Velcro) fastener or crumpling a piece of cellophane. These sounds are “opening” sounds of small airways or alveoli that have been collapsed or decreased in volume during expiration because of fluid, inflammatory exudate, or poor aeration. On each

TABLE 3.1

Typical Chest Examination Findings in Selected Clinical Conditions

*May be altered by collapse of underlying lung, which will increase transmission of sound.

Although the focus here is the chest examination itself as an indicator of pulmonary disease, other nonthoracic manifestations of primary pulmonary disease may be detected on physical examination. Clubbing (with or without hypertrophic osteoarthropathy) and cyanosis are briefly discussed here.

Clubbing is a change in the normal configuration of the nails and the distal phalanx of the fingers or toes (Fig. 3.1). Several features may be seen: (1) loss of the normal angle between the nail and the skin,

(2) increased curvature of the nail, (3) increased sponginess of the tissue below the proximal part of the nail, and (4) flaring or widening of the terminal phalanx. Although several nonpulmonary disorders can result in clubbing (e.g., congenital heart disease with right-to-left shunting, endocarditis, chronic liver disease, inflammatory bowel disease), the most common causes are clearly pulmonary. Occasionally, clubbing is familial and of no clinical significance. Carcinoma of the lung (or mesothelioma of the pleura) is the single leading etiologic factor. Other pulmonary causes include chronic intrathoracic infection with suppuration (e.g., bronchiectasis, lung abscess, empyema) and some types of diffuse parenchymal lung disease. Uncomplicated chronic obstructive lung disease is not associated with clubbing, so the presence of clubbing in this setting should suggest coexisting malignancy or suppurative disease.

FIGURE 3.1 Clubbing. Curvature of nail and loss of angle between nail and

adjacent skin can be seen.

Respiratory system diseases associated with clubbing:

1.Carcinoma of the lung (or mesothelioma of the pleura)

2.Chronic intrathoracic infection

3.Diffuse parenchymal lung disease

Clubbing may be accompanied by hypertrophic osteoarthropathy, characterized by periosteal new bone formation, particularly in the long bones, and arthralgias and arthritis of any of several joints. With coexistent hypertrophic osteoarthropathy, either pulmonary or pleural tumor is the likely cause of the clubbing, because hypertrophic osteoarthropathy is relatively rare with the other causes of clubbing.

The mechanism of clubbing and hypertrophic osteoarthropathy is not clear. It has been observed that clubbing is associated with an increase in digital blood flow, whereas the osteoarthropathy is characterized by an overgrowth of highly vascular connective tissue. Why these changes occur is a mystery. One interesting theory suggests an important role for stimuli coming through the vagus nerve, because vagotomy frequently ameliorates some of the bone and nail changes. Another theory proposes that megakaryocytes and platelet clumps, bypassing the pulmonary vascular bed and lodging in the peripheral systemic circulation, release growth factors responsible for the soft-tissue changes of clubbing.

Cyanosis, the second extrapulmonary physical finding arising from lung disease, is a bluish discoloration of the skin (particularly under the nails) and mucous membranes. Whereas oxygenated hemoglobin gives mucous membranes and nail beds their usual pink color, a sufficient amount of deoxygenated hemoglobin produces cyanosis. Cyanosis may be either generalized, owing to a low PO2 or low systemic blood flow resulting in increased extraction of oxygen from the blood, or localized, owing to low blood flow and increased O2 extraction within the localized area. In lung disease, the common factor causing cyanosis is a low PO2, and several different types of lung disease may be responsible. The

total amount of hemoglobin affects the likelihood of detecting cyanosis. In an anemic patient, if the total

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quantity of deoxygenated hemoglobin is less than the amount needed to produce the bluish discoloration, even a very low PO2 may not be associated with cyanosis. In a patient with polycythemia, in contrast, much less depression of PO2 is necessary before sufficient deoxygenated hemoglobin exists to produce cyanosis. In patients with darker skin, cyanosis may only be evident in mucous membranes or nail beds, whereas more widespread bluish discoloration of skin may be evident in lighter skinned individuals.

Chest radiography

The chest radiograph is used to evaluate patients with suspected respiratory disease and also sometimes in the routine evaluation of asymptomatic patients. Of all the viscera, the lungs are the best suited for radiographic examination. The reason is straightforward: air in the lungs provides an excellent background against which abnormalities can stand out. In addition, the presence of two lungs allows each to serve as a control for the other so that unilateral abnormalities can be more easily recognized.

A detailed description of interpretation of the chest radiograph is beyond the scope of this text. However, a few principles can aid the reader in viewing films presented in this and subsequent chapters.

First, the appearance of any structure on a radiograph depends on the structure’s density; the denser the structure, the whiter it appears on the film. At one extreme is air, which is radiolucent and appears black on the film. At the other extreme are metallic densities, which appear white. In between is a spectrum of increasing density from fat to water to bone. On a chest radiograph, the viscera and muscles fall within the range of water-density tissues and cannot be distinguished in radiographic density from water or blood.

Second, for a line or an interface to appear between two adjacent structures on a radiograph, the two structures must differ in density. For example, within the cardiac shadow, the heart muscle cannot be distinguished from the blood coursing within the chambers because both are of water density. In contrast, the borders of the heart are visible against the lungs because the water density of the heart contrasts with the density of the lungs, which is closer to that of air. However, if the lung adjacent to a normally denser structure (e.g., heart or diaphragm) is airless, either because of collapse or consolidation, the neighboring structures are now both of the same density, and no visible interface or boundary separates them. This principle is the basis of the useful silhouette sign. If an expected border with an area of lung is not visualized or is not distinct, the adjacent lung is abnormal and lacks full aeration.

Chest radiographs usually are taken in two standard views—posteroanterior (PA) and lateral (Fig. 3.2). For a PA image, the x-ray beam goes from the back to the front of the patient, and the patient’s anterior chest is adjacent to the image receptor (which may be film or a digital device). The lateral view is typically taken with the patient’s left side against the image receptor, and the beam is directed through the patient to the image receptor. If an image cannot be taken with the patient standing and the chest adjacent to the image receptor, as in the case of a bedridden patient, then an anteroposterior (AP) view is taken. For this view, which is generally obtained using a portable chest radiograph machine in the patient’s hospital room, the image receptor is placed behind the patient (generally between the patient’s back and the bed), and the beam is directed through the patient from front to back. Lateral decubitus views, either right or left, are obtained with the patient in a side-lying position, with the beam directed horizontally. Decubitus views are particularly useful for detecting free-flowing fluid within the pleural space and therefore are often used when a pleural effusion is suspected.

FIGURE 3.3 Lobar anatomy as seen from anterior and lateral views. In anterior

views, shaded regions represent lower lobes and are behind upper and middle

lobes. Lingula is part of the left upper lobe; dashed line between the two does not

represent a fissure. LLL, left lower lobe; LUL, left upper lobe; RLL, right lower

lobe; RML, right middle lobe; RUL, right upper lobe.

Both posteroanterior and lateral radiographs are often necessary for localization of an abnormality.

When a lobe becomes filled with fluid or inflammatory exudate, as in pneumonia, it contains water rather than air density and therefore is easily delineated on the chest radiograph. With pure consolidation the lobe does not lose volume, so it occupies its usual position and retains its usual size. An example of lobar consolidation on PA and lateral radiographs is shown in Fig. 3.4.

occlusion of the airway leading to the collapsed region of lung, caused, for example, by a tumor, aspirated foreign body, or mucous plug. All the aforementioned examples reflect either pure consolidation or pure collapse. In practice, however, a combination of these processes often occurs, leading to consolidation accompanied by partial volume loss.

FIGURE 3.5 Posteroanterior (A) and lateral (B) chest radiographs demonstrating

right upper lobe collapse. A, Displaced minor fissure outlines the airless (dense)

right upper lobe. B, Right upper lobe is outlined by an elevated minor fissure

(arrowhead) and an anteriorly displaced major fissure (long arrow).

When the chest radiograph shows a diffuse or widespread pattern of increased density within the lung parenchyma, it is often useful to characterize the process further, depending on the pattern of the radiographic findings. The two primary patterns are interstitial and alveolar. Although the naming of these patterns suggests a correlation with the type of pathologic involvement (i.e., interstitial, affecting the alveolar walls and the interstitial tissue; alveolar, involving filling of the alveolar spaces), such radiographic-pathologic correlations are often lacking. Nevertheless, many diffuse lung diseases are characterized by one of these radiographic patterns, and the particular pattern may provide clues about the underlying type or cause of disease.

Diffuse increase in density on the radiograph can often be categorized as either alveolar or interstitial.

An interstitial pattern is generally described as reticular or reticulonodular, consisting of an interlacing network of linear and small nodular densities. In contrast, an alveolar pattern appears fluffier, and the outlines of air-filled bronchi coursing through the alveolar densities are often seen. This latter finding is called an air bronchogram and is due to air in the bronchi being surrounded and outlined by alveoli that are filled with fluid. This finding does not occur with a purely interstitial pattern. Examples of chest radiographs that show diffuse abnormality as a result of interstitial disease and alveolar filling are shown in Figs. 3.6 and 3.7, respectively.

FIGURE 3.7 Chest radiograph showing a diffuse alveolar filling pattern, most

prominent in middle and lower lung fields.

Two additional terms that describe patterns of increased density are commonly used. A nodular pattern refers to the presence of multiple discrete, typically spherical, nodules. A uniform pattern of relatively small nodules several millimeters or less in diameter is often called a miliary pattern, as can be seen with hematogenous (bloodborne) dissemination of tuberculosis throughout the lungs. Alternatively, the nodules can be larger (e.g., >1 cm in diameter), as seen with hematogenous metastasis of carcinoma to the lungs (Fig. 3.8). Another common term is ground-glass, used to describe a hazy, translucent appearance to the region of increased density. Unlike the more opaque appearance of consolidated lung tissue, which obscures lung (primarily vascular) markings, a ground-glass pattern does not obscure underlying lung markings. Although the term can be used to describe a region or a pattern of hazy increased density on a plain chest radiograph, it is more commonly used when describing abnormalities seen on computed tomography (CT) of the chest (Fig. 3.9).

FIGURE 3.9 High-resolution computed tomography scan of patient with dyspnea

and normal chest radiograph. There are well-demarcated areas of lower density

(either normal lung or areas of air trapping) interspersed between hazy areas of

increased (“ground-glass”) density. Biopsy specimen showed findings of

hypersensitivity pneumonitis.

The preceding focus on some typical abnormalities provides an introduction to pattern recognition on a chest radiograph. However, the careful examiner must also use a systematic approach in analyzing the image. A chest radiograph shows not only the lungs; radiographic examination may also reveal changes in bones, soft tissues, the heart, other mediastinal structures, and the pleural space.

Computed tomography

Compared with the plain chest radiograph, CT of the chest provides greater anatomic detail but is more expensive and exposes patients to a significantly higher dose of radiation. With this technique, a narrow beam of x-rays is passed through the patient and sensed by a rotating detector on the other side of the patient. The beam is partially absorbed within the patient, depending on the density of the intervening tissues. Computerized analysis of the information received by the detector allows a series of crosssectional images to be constructed. Use of different “windows” allows different displays of the collected data, depending on the densities of the structures of interest (Fig. 3.10). With the technique of helical (spiral) CT scanning, the entire chest is scanned continuously (typically during a single breath-hold and using multiple detectors) as the patient’s body is moved through the CT apparatus (the gantry).

FIGURE 3.10 Cross-sectional (axial) images from a computed tomography (CT)

scan showing a solitary pulmonary nodule in the left lung. Images are displayed

using different “windows” at the same cross-sectional level. A, Settings were

chosen to optimize visualization of lung parenchyma. B, Settings were chosen to

distinguish different densities of soft tissues, such as structures within mediastinum.

Iodinated contrast allows vascular structures in the mediastinum to be readily

identified.

CT is particularly useful for detecting subtle differences in tissue density that cannot be distinguished by conventional radiography. In addition, the resolution of the images and the cross-sectional views obtained from the slices provide better definition and more precise three-dimensional spatial location of abnormalities.

CT provides cross-sectional views of the chest and detects subtle differences in tissue density.

Chest CT is used extensively in evaluating pulmonary nodules and the mediastinum. It is also quite valuable in characterizing chest wall and pleural disease. As the technology has advanced, CT has become progressively more useful in the diagnostic evaluation of various diseases affecting the pulmonary parenchyma and the airways. With high-resolution CT, the thickness of individual crosssectional images is reduced to 1 to 2 mm instead of the traditional 5 to 10 mm. As a result, exceptionally fine detail can be seen, allowing earlier recognition of subtle disease and better characterization of specific disease patterns (see Fig. 3.9).

Over a number of years, computed tomographic pulmonary angiography (CTPA) has become the standard imaging test for the diagnosis of pulmonary thromboembolism. This technique, in which the pulmonary arterial system is visualized by helical CT scanning following injection of radiographic contrast into a peripheral vein, has been increasingly used in place of both perfusion lung scanning and traditional pulmonary angiography (see later). Its use is attractive because CTPA is more likely to be diagnostic than perfusion scanning, and it is less invasive than traditional pulmonary angiography. Although CTPA may not be as sensitive as traditional angiography for detecting emboli in relatively small pulmonary arteries, ongoing improvements in CT scanner technology have led to better identification of thromboemboli in progressively smaller pulmonary arteries.

Sophisticated software protocols now allow images obtained by CT scanning to be reconstructed and presented in any plane that best displays the abnormalities of interest. In addition, three-dimensional

images are produced from the data acquired by CT scanning. For example, a three-dimensional view of

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the airways can be displayed in a manner resembling what is seen inside the airway lumen during bronchoscopy (described later in this chapter). This methodology creates an imaging tool that has been dubbed virtual bronchoscopy.

Magnetic resonance imaging

Another technique available for evaluation of intrathoracic disease is magnetic resonance imaging (MRI). The physical principles of MRI are complicated and beyond the training of most physicians and students, but are discussed here briefly. The interested reader is referred to other sources for an in-depth discussion of MRI (see Suggested Readings). In brief, the technique depends on the way nuclei within a stationary magnetic field change their orientation and release energy delivered to them by a radiofrequency pulse. The time required to return to the baseline energy state can be analyzed by a complex computer algorithm, and a visual image created.

MRI has several important features in the evaluation of intrathoracic disease. First, flowing blood produces a “signal void” and appears black, so blood vessels can be readily distinguished from nonvascular structures without the need to use intravenous contrast agents. Second, images can be constructed in any plane so that the information obtained can be displayed as sagittal, coronal, or transverse (cross-sectional) views. Third, differences can be seen between normal and diseased tissues that are adjacent to each other, even when they are of the same density and therefore cannot be distinguished by routine radiography or CT. Some of these features are illustrated in Fig. 3.11.

FIGURE 3.11 Magnetic resonance images of normal chest in cross-sectional (A)

and coronal (B) views. Lumen of structures that contain blood appears black

because flowing blood produces a signal void.

MRI scanning is expensive and time-consuming, so it generally is used when it can provide information not otherwise obtainable by less expensive, equally noninvasive means. MRI does not replace CT; rather, it often provides complementary diagnostic information. It can be a valuable tool in evaluating hilar and mediastinal disease and in defining intrathoracic disease that extends to the neck or the abdomen. On the other hand, it is less useful than CT in evaluating both pulmonary parenchymal disease and pulmonary emboli. However, knowledge about the power and limitations of this technique continues to grow, and applications are likely to expand with further refinements in technology.

out phase). Ventilation scanning shows which regions of the lungs are being ventilated and any significant localized problems with expiratory airflow and “gas trapping” of the radioisotope during the wash-out phase.

Perfusion and ventilation scans are chiefly performed for two reasons: detection of pulmonary emboli and assessment of regional lung function. When a pulmonary embolus occludes a pulmonary artery, blood flow ceases to the lung region normally supplied by that vessel, and a corresponding perfusion defect results. Generally, ventilation is preserved, and a ventilation scan does not show a corresponding ventilation defect. In practice, many pieces of information are considered in the interpretation of the scan, including the appearance of the chest radiograph and the size and distribution of the defects on the perfusion scan. These issues are discussed in greater detail in Chapter 13.

Perfusion and ventilation lung scans are useful for detecting pulmonary emboli and evaluating regional lung function.

Scans to assess regional lung function are sometimes performed before surgery involving resection of a part of the lung, usually one or more lobes. By visualizing which areas of lung receive ventilation and perfusion, the physician can determine how much the area to be resected is contributing to overall lung function. When the scanning techniques are used in conjunction with pulmonary function testing, the physician can approximately predict postoperative pulmonary function, which is a guide to postoperative respiratory problems and impairment.

Positron emission tomography (fluorodeoxyglucose scanning)

Positron emission tomography (PET) scanning detects areas of increased metabolic activity. On the basis of the principle that malignant tumors typically exhibit increased metabolic activity, scanning following injection of the radiolabeled glucose analog 18-fluorodeoxyglucose (FDG) has been used as a way of identifying malignant lesions in the lungs and mediastinum (Fig. 3.13). Malignant cells, as a consequence of their increased uptake and use of glucose, take up the FDG more rapidly than surrounding normal cells. Because the FDG has been chemically modified, it cannot be metabolized beyond the initial phosphorylation step and is trapped within the cell. The radiolabeled FDG emits positrons that are detected by PET using a specialized imaging system, or by adapting a γ camera for imaging of positronemitting radionuclides.

FIGURE 3.14 Normal pulmonary angiogram. Radiopaque dye was injected

directly into the pulmonary artery, and the pulmonary arterial tree is well visualized.

Catheter used for injecting dye is indicated by arrow. Source: (Courtesy Dr. Morris

Simon.)

The pulmonary angiogram has other uses, including investigation of congenital vascular anomalies, chronic thromboembolic disease, and invasion of a vessel by tumor. However, use of the angiogram in these situations is also quite infrequent.

Ultrasonography

The ability of different types of tissue to transmit sound and of tissue interfaces to reflect sound has made ultrasonography useful for evaluating a variety of body structures. A piezoelectric crystal generates sound waves, and the reflected echoes are detected and recorded by the same crystal. Images are displayed on a screen and can be captured for a permanent record.

The heart is the intrathoracic structure most frequently studied by ultrasonography, but the technique is also useful in evaluating pleural disease and can be performed at the patient’s bedside (point-of-care ultrasound, or POCUS). In particular, ultrasonography can detect small amounts of pleural fluid and is often used to guide placement of a needle for sampling the fluid. In addition, it can detect walled-off compartments (loculations) within pleural effusions, distinguish fluid from pleural thickening, identify pleural-based nodules or masses, and detect pneumothorax with high sensitivity.

Ultrasonography can localize the diaphragm and detect disease immediately below the diaphragm, such as a subphrenic abscess. Ultrasonography is not useful for defining structures or lesions within the

bronchoalveolar lavage (BAL).

FIGURE 3.16 Airways as seen through a fiberoptic bronchoscope. At this level,

the carina can be seen separating the right and left mainstem bronchi.

Source: (Courtesy of Dr. George Cheng.)

With the flexible bronchoscope, airways are visualized and laboratory samples are obtained.

A long, flexible wire instrument with a small brush at the tip can be passed through the hollow channel of the bronchoscope. The surface of a lesion within a bronchus can be brushed and the cells collected or smeared onto a slide for cytologic examination. Brushes are frequently passed into diseased areas of the lung parenchyma, and the material collected by the bristles is subjected to cytologic and microbiologic analysis.

A needle at the end of a long catheter passed through the bronchoscope can puncture an airway wall and sample cells from lymph nodes or lesions adjacent to the airway. This technique, called transbronchial needle aspiration, can be used to obtain malignant cells from mediastinal lymph nodes in the staging of known or suspected lung cancer. Using an ultrasound probe within the airway during bronchoscopy (endobronchial ultrasound or EBUS) can help the bronchoscopist localize mediastinal or hilar lymph nodes or solid mass lesions adjacent to the airway and therefore greatly assist with accurate needle placement into the node or the lesion for transbronchial needle aspiration.

With a small biopsy forceps passed through the bronchoscope, the clinician can extract a biopsy specimen from a lesion visualized on the bronchial wall (endobronchial biopsy). The forceps can also be passed through a small bronchus into the lung parenchyma to obtain a small specimen of lung tissue. This procedure, known as transbronchial biopsy, yields specimens that are small but have a sizable number of alveoli. Fluoroscopy can be used during the procedure to better localize the position of the biopsy forceps relative to the desired biopsy site, either a discrete lesion or an area representative of more diffuse disease. EBUS can also be used to help guide placement of the biopsy forceps into relatively peripheral