Results of office spirometry are presented both graphically and numerically, with actual values compared to values predicted by the patient’s age, height, and gender. Figure 18-1 shows the points at which two critical values, forced expiratory volume at 1 second (FEV₁) and forced vital capacity (FVC), are measured on the time-volume curve. Figure 18-2 shows a typical flow-volume loop for patients that compares normal PFTs with obstructive lung disease and restrictive lung disease (Zoorob et al., 2002). Increasingly, the 6-second end point, or FEV₆, is being used as a reliable and reproducible surrogate measure that can replace FVC for patients unable to complete forced expiration beyond 6 seconds.

Figure 18-1 Time-volume spirometry curve showing measurement of FEV₁, FVC, and FEV₆ and curves for obstructive versus restrictive lung disease.

Figure 18-2 Flow-volume loop showing curves for normal (A), obstructive (B), and restrictive (C) lung disease.

The key parameters of office spirometry are the FEV₁, the FVC, and the FEV₁/FVC ratio (percentage of exhaled volume blown out in first second of exhalation). The diagnosis of obstructive lung disease is made by demonstrating an FEV₁/FVC ratio (or FEV₁/FEV₆) of less than 70%. This means that the patient has exhaled less than 70% of FVC (full volume of air exhaled) in the first second of exhalation. Other tests of airway obstruction are the mid-maximal expiratory flow rate (MMEF, or FEF_25-75), which is the average expiratory flow over the middle half of expiration, that is, flow rate during the time when 25% to 75% of the FVC is exhaled. This measure has been described as representing small airway obstruction, but it is less reproducible and has not been included in clinical guidelines for managing patients with obstructive lung disease. However, MMEF can be an early indicator of lung damage caused by smoking or occupational pneumoconioses. The FEF₂₅ and FEF₇₅ are moment-in-time measures of expiratory airflow and are therefore subject to significant patient-to-patient variability unrelated to clinical factors.

One other dimension of office spirometry in diagnosing and managing obstructive lung disease is to measure these parameters before and after a dose of inhaled beta-2 (β₂)–adrenergic agonist is given. Improvement in FEV₁ of at least 12% and at least 200 mL from prebronchodilator to postbronchodilator measurement is considered evidence of reversibility of airway obstruction. Complete reversibility helps establish the diagnosis of asthma, and it is also useful in guiding therapy by establishing the potential efficacy of medications. For example, some patients with chronic obstructive pulmonary disease (COPD) are more responsive to anticholinergic medications such as inhaled ipratropium, whereas others are more responsive to inhaled β₂-agonists such as albuterol.

For restrictive lung disease, the “gold-standard” test is the total lung capacity (TLC), which is a measure of maximal exhaled air (FVC) plus residual capacity (RC). However, this can only be tested in pulmonary function laboratories that can test the patient in a sealed chamber. For practical purposes in the primary care setting, restrictive lung disease can be diagnosed using office spirometry if the FVC is reduced to less than 80% of predicted in the presence of a normal FEV₁/FVC ratio (i.e., no obstruction). One other test that is available in pulmonary function labs but not in office spirometry is the diffusion capacity (DLco), which is a measure of the diffusion of carbon monoxide across the alveolar-capillary membrane. Clinical reductions in DLco can occur with thickening of the alveolocapillary membrane, which can be a sign of interstitial fibrosis.

Chest Radiography and Other Diagnostic Imaging

Despite major advances in imaging technology, the chest x-ray film (CXR) is still an important diagnostic modality that can clearly reveal signs of pneumonia, COPD, heart failure, tuberculosis, lung masses, and pleural effusion. Figure 18-3 shows a chest radiograph with right middle lobe pneumonia. Although the posteroanterior (PA) film shows some consolidation, it is attenuated by the overlying projection of a normal lower lobe. The lateral film, however, shows the classic wedge-shaped profile of a consolidated right middle lobe.

Figure 18-3 Posteroanterior (A) and lateral (B) chest radiographs showing right middle lobe pneumonia.

(From Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock. http://anatomy.uams.edu/anatomyhtml/xrays/xra_atlas39.html and http://anatomy.uams.edu/anatomyhtml/xrays/xra_atlas5.html.)

Chest radiography is also widely used in evaluating patients with suspected exposure to tuberculosis (TB), either because of symptoms, personal contact, or a positive intradermal purified protein derivative (PPD) test. Figure 18-4 shows the patchy infiltrates and hilar adenopathy typical of pulmonary TB, although TB can have a variety of presentations on chest x-ray films, including adenopathy, pleural scarring, infiltrates, cavitary lesions, and miliary TB.

Figure 18-4 Chest radiograph showing tuberculosis, with upper lobe fibrotic patchy infiltrates and hilar adenopathy.

(From Centers for Disease Control and Prevention, Public Health Image Library, Image 2543. http://phil.cdc.gov/phil/home.asp.)

Chest radiography can also be helpful in diagnosing nonpulmonary causes of shortness of breath, as in the case of congestive heart failure, with enlarged heart, bibasilar consolidation, small pleural effusions, and prominent pulmonary vasculature. In other conditions such as asthma, chest x-ray films can be quite normal despite significant respiratory compromise.

Increasingly, chest computed tomography (CT) scan plays an important role in diagnosing lung disease. High-resolution CT (HRCT) can identify pulmonary nodules and hilar lymph nodes at much smaller sizes than can chest radiography, and it is therefore important in diagnosing and staging lung cancers. CT can also detect lung abscess, vascular lesions, and pleural scarring or masses. Whereas early COPD or emphysematous changes can be difficult to detect with even HRCT, additional techniques such as minimum-intensity projection (MIP) can aggregate data from adjacent slices and, by subtracting vascular and other tissue densities not consistent with lung parenchyma and air, demonstrate small air pockets consistent with early emphysema.

Imaging modalities such as spiral CT have been demonstrated to be effective in detecting early lung cancer in patients with high-risk smoking histories, but as yet they have not demonstrated improvements in mortality that would justify this as a universal screening test for smokers in primary care practice. When small, noncalcified pulmonary nodules are detected by CT, the likelihood of malignancy is influenced by nodule size, density, number of nodules, and growth over time, combined with patient factors such as age, smoking history, gender, spirometry, occupational history, and endemic granulomatous disease (Libby et al., 2004).

Positron emission tomography scans using ¹⁸F-fluorodeoxyglucose (FDG-PET) are becoming increasingly useful in evaluating lung cancers and lymphomas. The ability to define anatomy and metabolism, that is, glucose uptake within the tumor, makes the PET scan useful for staging, detecting node involvement, and defining resectability, tumor response to therapy, and tumor recurrence (Avril and Weber, 2005). Diagnosing solitary pulmonary nodules is a common challenge in primary care. A meta-analysis of studies comparing dynamic CT, magnetic resonance imaging (MRI), FDG-PET, and single-photon emission computed tomography (SPECT) scans based on positive and negative likelihood ratios for identifying malignant versus nonmalignant solitary nodules found that all four were similarly accurate (Cronin et al., 2008). Nuclear medicine studies such as gallium scans are also used extensively in evaluating pulmonary symptoms in patients with human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS) and are discussed in the section on HIV-related pulmonary infections in more detail.

Other imaging studies have more specific indications. One nuclear medicine study long used in primary care is the ventilation-perfusion (V/Q) scan. This is specifically performed to rule out pulmonary embolism, revealed by focal perfusion defects in adequately ventilated areas. This V/Q mismatch, in the absence of underlying lung pathology, is consistent with a high probability of pulmonary embolism. Unfortunately, patients can also demonstrate matching V/Q defects, which can occur when blood flow is shunted away from an underventilated area of the lung. Scans with no perfusion defect reflect a low probability for significant pulmonary embolism. Other tests are increasingly taking the place of the V/Q scan (see later discussion).

Bronchoscopy

Fiberoptic bronchoscopy allows direct visualization of the bronchial tree. It is useful for diagnosing conditions that require culture of a lower respiratory tract infection by bronchoalveolar lavage (BAL), or conditions such as bronchogenic carcinoma, that require tissue diagnosis by transbronchial biopsy. Sometimes these techniques are combined, as in the diagnosis of Pneumocystis jiroveci (carinii) pneumonia (PCP), for which the sensitivity of bronchoscopy with BAL is approximately 86% and with transbronchial biopsy is 87% (Broaddus et al., 1985). A comparative assessment of different bronchoscopic techniques in obtaining culture specimens in cases of ventilator-associated pneumonia found no significant difference between blind bronchial brushings and bronchoscope-assisted lavage, bronchoscope-directed brushings, or even blind endotracheal aspirates (Wood et al., 2003). Rates of complications (including hemoptysis and pneumothorax) with traditional bronchoscopy are in the range of 0.5% to 1.0% without biopsy and up to 6.8% with transbronchial biopsy (Pue and Pacht, 1995). In a pulmonary fellowship program, the rate of complications for all bronchoscopies performed (with and without biopsy) was 2.06% (Ouellette, 2006). Therapeutic interventions using bronchoscopy are also increasing, and lesions are treated through the bronchoscope with laser, cryotherapy, electrocautery, and stents (Rafanan and Mehta, 2000).

Newer diagnostic techniques include fluorescent bronchoscopy, which can be more sensitive for detecting early endobronchial tumors (Gilbert et al., 2004; Moghissi et al., 2008), and virtual bronchoscopy, which uses sophisticated software to reconstruct images from HRCT scan, to create three-dimensional imagery without invasive testing. This technique has been found useful in planning partial lung resection surgery, for example, but it cannot provide bronchoscopy’s direct visualization of color, texture, or friability of the bronchial mucosa (Finklestein et al., 2004).

Measurement of Blood Gases

Measurement and monitoring of blood gases can be invasive or noninvasive. Transcutaneous pulse oximetry is the most widely used noninvasive test. It provides a fairly accurate measure of oxygen saturation (So₂) of hemoglobin at values ranging from 70% to 100% by measuring the difference between oxyhemoglobin and reduced hemoglobin in the absorption of light of specific wavelengths. So₂ of 98% corresponds to an arterial oxygen partial pressure (Pao₂) of 100 mm Hg, and 95% to a Pao₂ of 80 mm Hg, demonstrating the challenge of interpreting a test with a 95% confidence interval of ±5%. An oxygen saturation of less than 89% corresponds to a Pao₂ of less than 60 mm Hg. Decreased tissue perfusion or color changes caused by jaundice or intravascular dyes can degrade accuracy. Arterial oxygen levels can also be measured transcutaneously (tcPo₂) with a skin surface oxygen electrode, but its accuracy is also affected by tissue perfusion, skin temperature, and other factors.

Exhaled carbon dioxide can also be measured noninvasively, most often in the ICU for patients on mechanical ventilation or in operating rooms during general anesthesia. Capnography, colorimetric techniques, and CO₂ sensors can detect failure of mechanical ventilation or improper endotracheal tube placement, which generate hypercapnia secondary to hypoventilation.

The invasive technique most often used for measuring oxygen, CO₂, and acid-base blood chemistries is the arterial blood gas (ABG) measurement. Although it requires an arterial needle puncture and several milliliters of blood, it is highly accurate and reproducible. ABG measurement is indicated in any patient with acute respiratory distress or in managing the patient with respiratory failure. In addition to Pao₂ and arterial carbon dioxide partial pressure (Paco₂) measurements, ABG testing also provides a measure of pH, bicarbonate (HCO₃⁻), and the anion gap, which can be used to detect respiratory (rather than metabolic) causes of acidosis and alkalosis. Patients with moderate to severe COPD can have chronic hypoxia plus chronic hypercapnia (decreased Pao₂ and increased Paco₂). They can also show signs of primary respiratory acidosis (reduced pH with elevated CO₂), and a compensatory metabolic alkalosis (partial normalization of the pH despite elevated Paco₂) mediated by renal HCO₃⁻ retention. Nomograms or software used in personal digital assistants (PDAs) allow simultaneous plotting of pH, CO₂, and HCO₃⁻ to facilitate interpretation of mixed respiratory and metabolic acid-base disturbances.

Common Pulmonary Symptoms

Shortness of Breath

A common presenting symptom in pulmonary disease is shortness of breath. The fundamental question in patients presenting with recent-onset or episodic shortness of breath is this: Is it a lung problem, a heart problem, or something else? The most common pulmonary causes of chronic or repeated episodes of shortness of breath include asthma, smoking-related COPD, chronic lung infections (TB and HIV-related infections), and occupational pneumoconiosis. Acute-onset shortness of breath can be caused by acute exacerbations of any of these chronic conditions, by acute infections such as pneumonia or acute bronchitis, or by spontaneous pneumothorax. Among otherwise healthy children, shortness of breath can be related to asthma, bronchiolitis, pneumonia, or upper-airway problems such as croup or epiglottitis. Chronic shortness of breath in children can be related to poorly controlled asthma, bronchopulmonary dysplasia from infancy, or chronic diseases (e.g., cystic fibrosis).

The cardiovascular system is the other organ system most often linked to shortness of breath. In adults, congestive heart failure (CHF) is a leading cause of recent-onset shortness of breath among middle-aged and older adults. In addition to shortness of breath, patients might report symptoms of wheezing from the pulmonary congestion, often referred to as cardiac asthma. Differentiating early CHF from pulmonary causes of dyspnea can be a challenge in middle-aged or older patients who smoke or have other chronic medical conditions. Other cardiac conditions associated with shortness of breath include pericarditis and cardiomyopathy, as well as congenital heart defects in infants presenting with respiratory distress. Vascular conditions include chronic pulmonary hypertension and pulmonary embolism in the setting of acute-onset shortness of breath.

Along with the history and physical examination, testing can help in ruling out pulmonary versus cardiac causes of dyspnea. Physicians often begin diagnostic testing with electrocardiogram (ECG) and even echocardiogram to rule out cardiac causes of shortness of breath, but simple history, auscultation of the heart and lungs, chest radiograph, and office spirometry can also assess for common pulmonary causes of shortness of breath. Improvement on weekends or non-workdays can suggest an occupational exposure, and a prolonged expiratory phase with expiratory wheezing suggests obstructive lung disease. Orthopnea and pedal edema suggest a cardiac cause. Bibasilar rales suggest fluid in the lower lung fields from CHF. ECG can approximate chamber enlargement and identify arrhythmias that might decrease ventricular filling time. Echocardiogram can measure ejection fraction and systolic or diastolic dysfunction indicating heart failure; local wall motion abnormalities suggesting ischemic disease; and valvular abnormalities. Levels of B-natriuretic protein (BNP) have a 90% sensitivity and 76% specificity for CHF; levels less than 100 pg/mL make CHF unlikely as the principal cause of shortness of breath or wheezing (Mueller et al., 2005). Chest radiograph can help rule out pulmonary or other thoracic mass lesions, lung infections, granulomatous or interstitial lung disease, pleural disease, pneumothorax, and cardiomegaly, supplemented with CT as needed. Although young patients with a normal physical examination have a low yield on chest radiography, up to 86% of patients older than 40 years with dyspnea have an abnormal chest x-ray film (Benacerraf et al., 1981). Spirometry showing an FEV₁/FVC ratio less than 70% is diagnostic of obstructive lung disease, and an FVC less than 80% of predicted value in the presence of a normal FEV₁/FVC ratio suggests restrictive lung disease.

Many patients present primarily with dyspnea on exertion. The 6-minute walking exercise test is a valid measure of exercise tolerance (compared with maximal exercise testing) in patients with COPD and other pulmonary conditions, as well as in various stages of CHF. It can be performed in primary care settings to assess functional disability and response to therapy (American Thoracic Society, 2002; Lipkin et al., 1986). In patients with pulmonary hypertension, the distance walked with encouragement in 6 minutes in a controlled environment is also a strong independent predictor of mortality (Miyamoto et al., 2000).

Formal cardiac ECG stress testing by exercise treadmill can quantify the level of exercise tolerance and diagnose cardiac ischemia or angina-equivalent conditions, in which a person has ischemia-induced shortness of breath but no chest pain. However, the test has a sensitivity of only 63% and specificity of 74% (86% specificity in the setting of three-vessel or left main coronary artery disease) (Gibbons et al., 1997). Other types of cardiac stress testing, such as exercise echocardiography or the nuclear medicine thallium treadmill test, can be more specific (see Chapter 27) (Mayo Clinic, 1996). The American College of Cardiology and American Society of Echocardiography published a recent consensus guideline on the appropriate use of stress echocardiography for specific clinical scenarios (Douglas et al., 2008). For patients unable to exercise, increased cardiac work may be induced pharmacologically, but dipyridamole and adenosine can each cause bronchospasm and should be avoided in patients with asthma or any other obstructive lung disease or undiagnosed pulmonary conditions (Tak and Gutierrez, 2004).

The presentation of patients with acute-onset shortness of breath requires more urgent evaluation. In addition to history and physical examination, a peak-flow test, chest x-ray film, ECG, complete blood count, and pulse oximetry or ABG testing may be done in short order. Further testing or treatment is guided by the differential diagnosis generated by this initial evaluation. Cardiac isoenzymes and troponin levels can help rule myocardial infarction in or out. If asthma is suspected, responsiveness to a trial of inhaled bronchodilator is both diagnostic and therapeutic. Antibiotics are initiated in cases of pneumonia or other pulmonary infection, and HIV testing can help in cases of suspected opportunistic infections (e.g., PCP).

Any suspicion of pulmonary embolism (PE) as a cause of acute shortness of breath requires specific diagnostic evaluation to allow quick intervention in this potentially life-threatening condition. Acute-onset shortness of breath coupled with pleuritic chest pain, hemoptysis, wedge-shaped pulmonary infarct lesions on chest radiograph, and an S1Q3 pattern and tachycardia on ECG can all point specifically to a diagnosis of PE, but most patients have a more nonspecific presentation. All patients with acute-onset shortness of breath with no apparent cause should be evaluated for PE. Physical examination for signs of deep venous thrombosis (DVT) (e.g., asymmetry in calf or thigh diameter, calf tenderness, Homans sign) are relatively insensitive and nonspecific, whereas other tests (e.g., D-dimer, CT angiography) can more accurately confirm the presence of significant underlying DVT. Clinical decision rules using objective scoring algorithms help establish pretest probability, which in turn enhances the predictive value of other tests for PE (Wells et al., 2000) (see later discussion).

Cough

Cough is also a common presenting symptom in primary care. Although cough can be part of a constellation of symptoms that leads to a specific diagnosis, it can also be the primary symptom in an undifferentiated patient. In these cases, the diagnosis must be obtained through a combination of careful history, physical examination, limited diagnostic testing, and often a trial of empiric therapy. Several elements of the history guide the initial differential diagnosis, especially a history of smoking, immunocompromise (HIV/AIDS or cancer chemotherapy), chronic pulmonary disease, medication use (ACE inhibitors), specific occupational exposures, or exposure to TB patients or TB-endemic areas.

Acute episodes of cough, defined as less than 3 weeks, are almost always caused by an acute infection (usually viral) or an acute exacerbation of chronic disease such as asthma or COPD, and the first rule should be to “do no harm” (primum non nocere) by treating conservatively and using time as a diagnostic test. Most episodes of acute cough caused by infection are viral in origin, mainly viral upper respiratory tract infections or acute bronchitis. Acute bacterial infections include sinusitis as well as bacterial overgrowth in exacerbations of chronic bronchitis or COPD. Fever, hemoptysis, or significant shortness of breath in association with cough indicates a chest radiograph or other immediate diagnostic evaluation. Frank hemoptysis can require urgent bronchoscopy for diagnosis and potentially for treatment (electrocoagulation of bleeding site). Without evidence of bacterial infection (clear evidence of sinusitis or pneumonia), previously healthy patients should generally be treated symptomatically without antibiotics, unless symptoms persist for more than 3 weeks.

Foreign body aspiration is a diagnostic consideration in children with either acute or chronic cough. Exacerbations of asthma, as well as infections by Bordetella pertussis (whooping cough) or Bordetella parapertussis, can lead to a persistent cough for as long as 3 to 8 weeks. Cough might indeed be the only symptom experienced by some patients with asthma (cough-variant asthma). In patients with underlying chronic bronchitis or COPD, antibiotics may be indicated during episodes of increased shortness of breath, wheezing, hypoxia, or limitations of activity if accompanied by a sudden change in sputum from thin and clear to thick or copious or yellow-green. Other subacute or chronic infections include bronchiectasis, which can manifest with a cough productive of mucopurulent, blood-tinged, or foul-smelling sputum. In children with chronic productive cough or recurrent pulmonary infections, cystic fibrosis must be considered. Survivors of premature birth with mechanical ventilation in neonatal intensive care may have chronic lung disease with acute exacerbations.

In adults, the most common causes of chronic cough in nonsmokers are postnasal drip, asthma, gastroesophageal reflux disease (GERD), and angiotensin-converting enzyme (ACE) inhibitors (Holmes and Fadden, 2004). Among smokers, chronic bronchitis, bronchiectasis, and bronchogenic carcinoma (lung cancer) must also be considered. Additional elements of the history can suggest other diagnoses. For example, occupational exposures can suggest specific diagnoses such as coal miner’s lung or farmer’s lung. Immigration from or travel to TB-endemic areas could suggest tuberculosis.

After the history and physical examination, a chest radiograph is the most valuable diagnostic test in evaluating the patient with chronic cough. Chest x-ray films can reveal infections (atypical pneumonia or TB), mass lesions (carcinoma), granulomatous disease (sarcoidosis), or evidence of occupational lung disease. Radiography can also reveal nonpulmonary causes of chronic cough, such as early CHF or pleural lesions. Office spirometry may also be performed to rule out obstructive lung disease.

In an otherwise healthy nonsmoker with chronic cough and a normal chest x-ray film, a trial of simple measures may be indicated. Persons being treated with an ACE inhibitor should be switched to alternative medication. Patients with occupational exposures should avoid the exposure or use protective equipment and should begin keeping a log to document the association of symptoms with days spent in workplace areas of exposure. Patients with signs of allergic rhinitis or postnasal drip may begin a simple trial of antihistamines. Patients with symptomatic GERD may begin taking a protein pump inhibitor (e.g., omeprazole) or H₂ antagonist. In some cases, chronic cough is the only symptom of GERD, and a successful trial of these agents is diagnostic.

Follow-up is essential, and the primary care practitioner must document instructions to patients that those who do not respond to empiric therapy in 2 to 3 weeks need further diagnostic evaluation. If asthma is suspected and initial office spirometry revealed normal pulmonary function, a simple approach is to ask the patient to keep a log of symptoms and peak flow meter readings, with peak flow tested within 30 minutes of rising each morning. In patients with an abnormal chest radiograph or in smokers with a normal radiograph and a chronic cough that does not respond to empiric therapy, a HRCT scan or even bronchoscopy may be indicated to rule out malignancy. Additional causes of chronic cough that might require further testing include sarcoidosis, TB, and other granulomatous or interstitial lung diseases, as well as pulmonary manifestations of autoimmune disease such as rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE).

Patients with HIV/AIDS or other compromise of the immune system deserve specific evaluation (see Chapter 17). HIV testing may be indicated in patients with any risk factors, because pulmonary symptoms can be the first manifestation of symptomatic HIV disease. In patients known to be HIV positive, tests in addition to chest radiography and HRCT could include gallium scan, PET, bronchoscopy with BAL for stains and cultures, PPD, and sputum testing for PCP.