Current Geriatric Diagnosis & Treatment, 1st Edition
Section III - Common Disorders in the Elderly
22. Respiratory Diseases
Richard W. Rissmiller Jr MD
Norman E. Adair MD
ESSENTIALS OF DIAGNOSIS
- Episodic wheeze, dyspnea, cough, and chest tightness.
- Dyspnea and cough, often worse at night.
- Airflow obstruction by spirometry that is at least partially reversible.
Asthma is a chronic inflammatory disorder of the airways. Airway inflammation in asthma is most closely linked to allergic mechanisms. Infectious agents and air pollution may also contribute to inflammation. A genetic predisposition to asthma is recognized, primarily in the form of atopy. Elderly asthmatics may be less atopic than younger asthmatics, but elderly asthmatics are more atopic than elderly controls without asthma.
The prevalence of asthma peaks in childhood (8–10%) and declines in early adulthood. The prevalence of asthma is 6–8% past 60 years of age. Asthma can present after age 60 (late-onset asthma), but this is less common than long-standing asthma that persists into the later years of life. Asthma mortality is higher in the elderly than in younger asthmatics.
Asthma is underdiagnosed and undertreated in the elderly. Underdiagnosis stems from several factors, including attributing breathlessness to normal aging or to other disorders, primarily cardiovascular disease. In addition, the perception of bronchoconstriction is blunted in the elderly. Elderly asthmatics have less severe asthma symptoms than do younger adult asthmatics with similar degrees of airflow obstruction. Older asthmatics may have adapted to chronic obstruction or are less able to perceive airway narrowing. Thus, they may minimize symptoms and delay investigation for asthma.
Asthmatic airway inflammation, whether allergic or nonallergic, is associated with bronchial hyperreactivity. This results in airway narrowing and increased airflow resistance. Bronchial hyperreactivity can be induced by a variety of stimuli, including cold air, emotions, air pollution, and viral infections. Hyperreactive airways cause recurrent episodes of breathlessness, chest tightness, wheeze, and cough.
Long-standing airway inflammation can lead to structural changes in the airway, characterized by thickening of the airway wall and peribronchial fibrosis. Such changes can produce irreversible airway narrowing. Elderly nonsmokers with long-standing asthma have worse airflow obstruction and less reversibility after bronchodilator inhalation than elderly asthmatics whose disease is of shorter duration.
- SYMPTOMS & SIGNS
Recurrent episodes of wheeze, breathlessness, cough, and chest tightness characterize asthma. Cough can be the only or the predominant symptom. Cough and breathlessness are commonly worse at night or in the early morning. However, if airflow obstruction becomes irreversible, as may occur with chronicity and airway remodeling, symptoms will be unremitting. This situation cannot be differentiated from chronic obstructive pulmonary disease (COPD) except when the patient has no history of tobacco exposure. Chest examination may demonstrate expiratory wheeze, diminished intensity of breath sounds, prolonged expiratory time, hyperinflation, and accessory inspiratory muscle activity. These physical signs are nonspecific and are noted in other obstructive lung diseases.
- LABORATORY FINDINGS
Blood and sputum eosinophilia may occur in asthma but are not useful for diagnosis. The most useful laboratory investigation is spirometry, which measures the forced vital capacity (FVC) and the forced expired volume over 1 s (FEV1). Airflow obstruction may be defined
by an FEV1-FVC ratio of < 0.70. Airflow obstruction that is significantly reversible after inhalation of a bronchodilator is the hallmark of asthma. Significant reversibility is a 12–15% increase in FEV1 that exceeds 200 mL in absolute volume. Spirometry is crucial for diagnosing asthma, assessing severity of airflow obstruction, and evaluating response to therapy. Additional pulmonary function testing can helpful. The diffusion capacity for carbon monoxide, a sensitive test of gas transfer, is typically normal or slightly elevated in asthma, whereas it is low in emphysema. The flow-volume loop is obtained by simultaneously measuring volume and instantaneous flow rate during forceful inspiration and expiration. Upper airway obstruction may mimic asthma and is often first suspected after identifying characteristic changes in the shape of the flow-volume loop.
- OTHER TESTING
Diurnal measurement of peak expiratory flow over 1-2 weeks may be helpful when asthma is suspected but spirometry is normal. Peak expiratory flow is generally lowest in the morning and highest toward the midpoint of the day. Measurements should be taken before inhalation of bronchodilator medication in the morning and after treatment in the afternoon. A 20% difference between these 2 values suggests asthma.
Bronchial hyperreactivity can be assessed by demonstrating enhanced bronchial narrowing after an inhalation challenge with cold air, histamine, or, most commonly, methacholine. Bronchial hyperreactivity is not specific for asthma; it may also be seen in bronchiectasis, COPD, and allergic rhinitis without obvious asthma and after viral respiratory infections. Nevertheless, when bronchial hyperreactivity is present along with characteristic clinical findings, asthma is very likely.
Chest radiography is useful, especially with recent onset of symptoms, to rule out alternative diagnoses. Chest computed tomography (CT) may be of diagnostic value in presumed asthma that is poorly responsive to therapy or in atypical cases; central airway lesions, bronchiectasis, bronchiolar disorders, and parenchymal lung diseases may be identified.
Airflow obstruction and breathlessness, with or without wheeze, are features seen in asthma, COPD, vocal cord dysfunction, anatomic narrowing of the upper airway, endoluminal tumor, airway strictures, aspirated foreign bodies, bronchiectasis, and bronchiolitis and in disorders that are usually classified as interstitial lung diseases, such as sarcoidosis, lymphangioleiomyomatosis, and Langerhan's cell histiocytosis. Chest tightness in asthma is easily confused with angina pectoris. Cough, nocturnal breathlessness, and wheeze may suggest congestive heart failure. Episodic smothering may occur with recurrent pulmonary emboli.
Some circumstances are associated with poor control or worsening asthma. Many elderly patients with asthma also have cardiovascular disease and may be receiving oral β-blocker therapy, which may exacerbate asthma. The use of a cardioselective β-blocker is less likely to precipitate bronchospasm. Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) may produce acute bronchoconstriction in some asthmatics. Chronic sinusitis may make asthma less responsive to therapy, and aggressive medical therapy or surgical intervention may improve asthma control. Gastroesophageal reflux may also foster asthma symptoms. Antireflux therapy has been reported to improve asthma symptoms, but there is debate regarding whether airflow obstruction or medication use is improved.
Asthma causes reduced quality of life, hospitalizations, and increased health care costs. Asthma hospitalization rates are greatest in patients older than 65. Reported mortality rates from asthma are highest in the elderly.
Drug therapy in elderly patients with asthma is the same as in younger asthmatics (Table 22-1). The goals of therapy are to prevent symptoms and exacerbations by attempting to maintain as near normal lung function as possible with minimal side effects and costs.
Avoidance of allergen exposures that induce symptoms is important. Allergen injection therapy has no proven role in older asthmatics, but referral to an allergist may be considered, especially when treatment goals are not achieved with pharmacotherapy. Data from existing studies, which involved few adults, do not indicate that multiple allergen injection immunotherapy has steroid-sparing potential and does not have a major impact on lung function.
Medications to treat asthma are separated into those that provide quick relief of symptoms and those that provide long-term control.
The quick reliever agents are the short-acting β2-agonists, typified by albuterol. Side effects are tremor, palpitations, tachycardia, and, with high doses, hypokalemia. The anticholinergic bronchodilator, ipratropium bromide, has less rapid onset but can be an acceptable bronchodilator if β2-agonists are poorly tolerated because of tremor or cardiac stimulation.
Table 22-1. Commonly used drugs for asthma.
Corticosteroids are the most potent and consistently effective long-term control medications. Inhaled corticosteroids are the principal long-term controllers. The main side effects of inhaled steroids are cough, dysphonia, and oral thrush. High-dose inhaled steroids may induce systemic effects, including rare instances of adrenal suppression, increased intraocular pressure, cataracts, and potential for increased bone loss.
Systemic corticosteroids are prescribed for short-term burst therapy to gain control of worsening symptoms but are discouraged for long-term use except in severe persistent asthma. Short-term therapy should continue until symptoms have improved or the patient achieves 80% of baseline peak expiratory flow. There is no evidence that tapering the dose prevents relapse. The side effects of systemic steroid therapy are well known: osteoporosis, aseptic necrosis of the femur, muscle weakness, immune suppression, cataracts, impaired glucose metabolism, salt retention, hypokalemia, metabolic alkalosis, bruising, and elevated intraocular pressure. If long-term systemic therapy is required, every-other-day dosing is probably preferable, and therapy to prevent osteoporosis is indicated.
Inhaled cromolyn sodium and nedocromil are long-term controllers that seem most effective in younger, atopic asthmatics. These medications are safe. However, their use in older asthmatics has been questioned.
Leukotriene receptor antagonists are long-term controllers that are taken orally once or twice daily. They are not as effective as inhaled steroids for long-term control of asthma. Leukotriene receptor antagonists are useful in aspirin-induced asthma. In persistent asthma they have marginal utility and are inferior to the combination of inhaled fluticasone-salmeterol. There are reports linking leukotriene receptor antagonists with Churg-Strauss vasculitis.
Salmeterol and formoterol are long-acting β-agonists that produce bronchodilation for up to 12 h. They are useful for control of nocturnal asthma. Side effects include tachycardia, tremor, and hypokalemia. Adding a long-acting β-agonist to an inhaled steroid in moderate asthma is more effective than increasing the dose of inhaled steroid.
Sustained-release theophylline is effective in long-term control of symptoms, especially nocturnal asthma. Theophylline toxicity and relatively modest bronchodilator activity limits theophylline use in acute asthma. Serum theophylline concentrations must be monitored to maintain a relatively safe level of 10- 15 µg/mL. Adverse effects at therapeutic doses include insomnia, gastric upset, increased gastroesophageal reflux, and difficulty with urination. Higher blood levels increase the likelihood of serious toxicity, including headache, nervousness, nausea, vomiting, arrhythmias, seizures, and death. Theophylline metabolism may be decreased and blood levels increased by chronic liver disease, congestive heart failure, and many medications such as macrolides, fluoroquinolones, zileuton, cimetidine, and allopurinol.
Impediments to effective control of asthma in older patients should be sought and addressed as best possible. These impediments include inadequate medication usage, which may result from cognitive impairment and poor memory, inability to use inhaler devices correctly, drug interactions, cardiovascular comorbidity, polypharmacy, and depression. In addition, the high cost of some medications can interfere with patient compliance and prevent them from reaching therapeutic goals.
Inhalation drug therapy may be administered by several methods. The pressurized metered-dose inhalers (MDIs) are the most prevalent delivery devices. Drug delivery can usually be enhanced by using a spacer attached to the MDI. A spacer acts as a holding chamber and reduces the need to precisely coordinate inhalation with actuation of the inhaler. Actuation of the MDI requires pressing on the drug canister, which can be difficult if the patient has arthritis of the hand or weakness. An attachment to the MDI is available that reduces the difficulty of actuation. Dry powder inhalers are activated by inspiration, requiring a brisk inspiratory effort but little hand-breath coordination. Nebulizers are another delivery option when MDI or dry powder inhalers are not effective.
Referral to an asthma specialist is indicated if the patient has persistent asthma symptoms or recurrent asthma exacerbations despite recommended treatment.
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
ESSENTIALS OF DIAGNOSIS
- Symptoms: dyspnea, cough, sputum production, and wheeze.
- Risk factors: tobacco smoke, air pollution.
- Spirometry: airflow obstruction that is not fully reversible.
Limitation of expiratory airflow demonstrated by spirometry is the key to diagnosis. Airflow limitation is mostly due to fixed airway obstruction, which is usually progressive.
COPD is an umbrella term that refers to airflow obstruction resulting from airway and lung injury caused by inhalation of toxins and pollutants. Chronic bronchitis and emphysema are included in COPD. Chronic bronchitis is defined by symptoms of cough with sputum production for 3 mo in 2 consecutive years. Chronic bronchitis may be obstructive or nonobstructive. Airflow obstruction in chronic bronchitis is due to airway lumen compromise from thickened and inflamed bronchial walls, hypertrophy of mucus glands, smooth muscle constriction, and excess mucus. Emphysema is an anatomic lesion characterized by dilated airspaces distal to the terminal bronchiole associated with loss of alveolar walls. Airflow obstruction in emphysema results, in part, from loss of support around airways, causing their narrowing during expiration.
The principal risk factor for COPD is tobacco smoking, which accounts for 80–90% of cases. Airflow obstruction and dyspnea typically develop after age 45. Symptomatic COPD usually occurs after 35-40 pack-years of exposure. The prevalence of COPD increases in the sixth decade, affecting equal numbers of women and men. COPD is a major cause of disability and death in most countries and contributes significantly to escalating health care costs.
Heavy exposures to occupational dusts, chemicals, and air pollution (such as biomass fuels) are additional risk factors for COPD. Low socioeconomic status, maternal smoking, subnormal lung growth, childhood respiratory illness, and airway hyperreactivity are also linked to the occurrence. The only known genetic risk factor, α1-antiprotease deficiency, is a rare cause of emphysema.
- SYMPTOMS & SIGNS
Chronic cough with sputum production is usually the first symptom and often precedes airflow obstruction. Physical examination may be unremarkable early in the disease. Dyspnea on exertion is typically evident when the FEV1 is reduced to 50–60% of the predicted level. Patients with predominant emphysema are notably tachypneic, display pursed-lip breathing, and tend to prefer to lean forward and support themselves using the elbows. In more advanced disease, one may observe wheezes, prolonged expiratory time, diminished breath sounds, and hyperresonance with chest percussion. Clinical signs in severe COPD include central cyanosis, ankle edema, and increased jugular venous pressure, indicating cor pulmonale and right-sided heart failure.
Exacerbations in COPD are common. An exacerbation is often caused by infection; however, in some instances, a cause cannot be identified. The symptoms of an exacerbation are worsening dyspnea (often with increased wheezing), tachypnea, and tachycardia. There may be increased cough with sputum production. The sputum may be purulent or described as tenacious and difficult to expectorate. Decreased alertness may signal hypoxemia and hypercapnia.
- LABORATORY FINDINGS
Patients with chronic cough, sputum production, and significant exposure to risk factors should be screened with spirometry, even if they are free of dyspnea. The diagnosis of COPD is confirmed by spirometry. The FEV1- FVC ratio is used to measure airflow obstruction. An FEV1-FVC ratio < 70% and a postbronchodilator
FEV1 < 80% predicted indicate airflow obstruction. Additional lung function testing may include lung volumes that often display hyperinflation with increased total lung capacity and residual volume. The diffusion capacity for carbon monoxide may be reduced, and the degree of reduction correlates roughly with the severity of emphysema. Gas exchange abnormalities are more likely when FEV1 < 40% predicted and arterial blood gas analysis is indicated. Secondary polycythemia may accompany chronic hypoxemia.
- IMAGING STUDIES
Chest x-ray film is often unremarkable in early and moderate COPD. Advanced disease may be associated with hyperlucent lung fields, flattening of the diaphragms, increased retrosternal airspace, or thickened bronchial walls. Bullous lung disease is sometimes seen in COPD. High-resolution computed tomography (HRCT) of the chest is more sensitive than plain radiography for detecting emphysema. The routine use of computed tomography in COPD is not indicated, however. HRCT is used to examine the severity and distribution of emphysema when lung volume reduction surgery is contemplated.
It is often difficult to distinguish an exacerbation of COPD from acute pulmonary embolism (PE). Helical CT angiography can be useful when ventilation-perfusion lung scanning is not helpful.
- SPECIAL TESTS
Screening for α1-antitrypsin deficiency is indicated in patients who experience COPD at a young age (< 45 years) or have a strong family history of obstructive lung disease. Liver dysfunction may also be seen in this condition, especially in younger patients.
The differential diagnosis of obstructive lung disease includes asthma, bronchiectasis, bronchiolitis, upper airway obstruction, tracheo- or bronchomalacia, airway strictures, and endoluminal masses (tumors, amyloid, foreign bodies).
COPD is usually a progressive disease and a leading cause of death in older adults. The FEV1 is a strong correlate with mortality in COPD. Age, hypoxemia, pulmonary hypertension, hypercapnia, low body weight, persistent smoking, and reduced functional capacity are additional predictors of increased mortality in COPD.
Exacerbation in COPD requiring hospitalization is associated with ~11% mortality. If the exacerbation requires intensive care, the mortality ranges from 10–50%. Mechanical ventilation for acute respiratory failure in COPD is associated with mortality ranging from 10–40%. One-year mortality after exacerbation for patients older than 65 has been reported to be > 50%.
The goals of treatment in COPD are to prevent symptoms, prevent exacerbations, preserve lung function, and enhance quality of life.
The management of COPD is primarily symptom driven. Pharmacological therapy does not alter the progressive decline in lung function nor does it appear to affect mortality. One exception is continuous oxygen therapy in hypoxemic patients with COPD, in whom mortality is significantly improved by oxygen therapy. Smoking cessation is known to slow the rate of decline in lung function and is a key treatment goal.
The current medications used in COPD are similar to those used in asthma, but the latter usually displays a relatively large treatment effect whereas COPD does not. Bronchodilator drugs are the cornerstones of symptom control (Table 22-2).
β-Agonist bronchodilators have been the mainstays of drug therapy in COPD, and inhaled therapy is preferred. The short-acting β-agonists are primarily used as needed for symptom relief. The long-acting inhaled β-agonists are given as a scheduled dose and provide significant symptom relief in COPD, including improving exercise tolerance and possibly reducing exacerbations.
The anticholinergic bronchodilator ipratropium bromide is usually the initial drug for scheduled bronchodilator
therapy in COPD. There are few side effects and bronchodilation lasts 4-6 h. Compared with the β-agonist albuterol, ipratropium has similar improvement in FEV1 but a slower onset to peak effect. Combining an anticholinergic with a β-agonist provides effective symptom control while minimizing the side effects associated with maximal doses of either single agent. A long-acting anticholinergic bronchodilator is undergoing review for use in COPD.
Table 22-2. Commonly used drugs for COPD.
Theophylline has modest bronchodilator activity in COPD. Some patients prefer theophylline preparations both for convenience of oral administration and for symptom relief. Exercise performance may be improved with theophylline. Because of the narrow therapeutic window of theophylline, the need for drug level monitoring, and the potential for drug interactions, theophylline is a second-line medication in COPD.
The use of inhaled corticosteroids in COPD has been the focus of investigation. It has been shown that inhaled steroids do not improve the rate of decline in lung function. There may be an initial slight improvement in FEV1, which may not be sustained. A reduction in the frequency of exacerbations has been noted, and symptoms may also be reduced. The current international guidelines suggest that inhaled steroids for COPD are indicated when a 4- to 6-week trial produces documented spirometric improvement and when moderate to severe COPD is associated with frequent exacerbations. Complications of therapy are uncommon, but loss of bone density has been reported. The cost-benefit ratio of inhaled steroids in COPD is unknown.
Chronic treatment with oral corticosteroids is discouraged because of the unfavorable risk-benefit ratio. No adequate trials show long-term benefits. The long-term side effects are well known.
Continuous oxygen therapy is safe and improves survival and quality of life in hypoxemic patients with COPD (Table 22-3).
Exercise training and pulmonary rehabilitation may improve shortness of breath, functional capacity, quality of life measures, and psychosocial function in COPD. Rehabilitation programs often involve multiple health care professionals with the goals of reducing symptoms and improving quality of life through exercise reconditioning, nutritional repletion, patient education, and smoking cessation. Pneumococcal vaccination and annual influenza vaccination are recommended.
Table 22-3. Usual indications for home oxygen therapy.
Treatment algorithms in COPD involve progressive addition of medications in an effort to achieve maximum possible symptom control. A typical approach is as follows:
- Mild and intermittent symptoms: as-needed β-agonist every 2-6 h.
- Regular/daily symptoms: scheduled ipratropium bromide plus as-needed β-agonist.
- If unsatisfactory response: trial of scheduled ipratropium-β-agonist combination.
- If unsatisfactory response: addition or substitution using long-acting β-agonist.
- If unsatisfactory response: addition or substitution using slow-release theophylline.
- If unsatisfactory response: addition of inhaled steroid for 4-6 weeks, to be continued only if significant spirometric improvement is documented.
- All patients must be helped with smoking cessation.
- Hypoxemic patients should be encouraged to use continuous oxygen therapy (> 15 h/day).
- Advise pulmonary rehabilitation for persistently symptomatic patients.
Treatment of acute exacerbations involves oxygen therapy to correct hypoxemia (increasing the dose or frequency of bronchodilators), antibiotics if infection is likely, systemic corticosteroids, and avoidance of complications. Short-acting β-agonists are preferred in the acute setting, often with the addition of an anticholinergic bronchodilator. Theophylline and methylxanthines are generally avoided in the acute setting. Systemic glucocorticoids are indicated in the management of an exacerbation. This is usually given over 10-14 days, starting with a relatively high dose (40-60 mg/day). Antibiotic therapy is indicated in exacerbations when there is increased sputum volume or purulence. Common pathogens associated with exacerbations are Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis.
Noninvasive intermittent positive-pressure ventilation (NIPPV) to treat respiratory failure is effective in selected patients. NIPPV reduces the need for endotracheal intubation and can shorten hospital stay. Contraindications to NIPPV include excessive secretions, impaired mentation, inability to protect the airway, and cardiovascular instability. NIPPV may also be used as a bridge between endotracheal intubation and liberation
from ventilation. Currently, no evidence supports NIPPV for chronic respiratory failure resulting from COPD.
Advanced COPD, especially in the setting of comorbid conditions, should raise concern over ethical issues. It is important to address the patient's wishes regarding end-of-life care.
Lung transplantation and lung volume reduction surgery are options in highly selected patients with COPD. Optimal candidates for lung transplantation should be ≤ 65 years. Lung volume reduction surgery may be considered in selected emphysema patients up to age 75 years.
SLEEP-RELATED BREATHING DISORDERS
ESSENTIALS OF DIAGNOSIS
- Excessive daytime sleepiness.
- Risk factors: obesity or anatomic narrowing of upper airway.
- Overnight sleep study with abnormal breathing events.
Sleep-related breathing disorders (SRBDs) encompass a spectrum of respiratory events during sleep wherein ventilation deviates from the normal rhythmic tidal breathing. An apneic breathing event is defined as absence of airflow for at least 10 s. A central apnea manifests no respiratory effort, whereas an obstructive apnea is characterized by continued effort to breathe against the occluded upper airway. Hypopnea refers to reduced breathing during sleep resulting from partial occlusion of the upper airway. It is often defined as a ≥ 50% reduction in airflow for at least 10 s with an associated decline in oxygen saturation of 3%. Within the spectrum of obstructive SRBD is the upper airway resistance syndrome (UARS), in which sleep is associated with narrowing of the upper airway that is insufficient to lead to apnea or hypopnea but is capable of causing increased respiratory effort. The increased respiratory effort produces arousal from sleep, which can cause excessive daytime sleepiness. Central apnea (cessation of airflow for 10 s with absent effort to breathe) in the elderly usually takes the form of periodic breathing or Cheyne-Stokes respiration.
Obstructive sleep apnea is common in the general population, affecting ~2–4%. Epidemiological studies indicate that 20–30% of men and women older than 65 have > 5 apneic events/h of sleep. More than 50% of older adults have an apnea-hypopnea index (AHI) exceeding 5 events/h.
Obstructive sleep apnea-hypopnea syndrome (OSAHS) is defined as excessive daytime sleepiness that cannot be explained by other factors plus 2 or more additional symptoms (choking or gasping during sleep, recurrent awakenings, unrefreshing sleep, daytime fatigue, impaired concentration) and a sleep monitoring study that demonstrates ≥ 5 obstructed breathing events/h of sleep. Especially in middle age, OSAHS has been linked to increased risk for hypertension, stroke, motor vehicle accidents, neurocognitive deficits, and, possibly, death.
Many older people display an increased AHI (> 5/h) and yet seem to have relatively few OSAHS symptoms. Reasonably strong evidence links OSAHS with morbidity and excess mortality in middle age but not in old age. Despite an increased frequency of abnormal breathing events during sleep, there is less compelling evidence of associated morbidity or mortality in older patients.
Central sleep apnea is less common than obstructive sleep apnea in the general population. Advanced age is associated with an increased frequency of central apneas per hour of sleep, usually in the form of periodic breathing or Cheyne-Stokes respiration. Periodic breathing is closely associated with congestive heart failure and cerebrovascular disease. In some studies of sleep-disordered breathing in patients older than 65, 33–50% of the disordered breathing events were central apneas.
- SYMPTOMS & SIGNS
Snoring is a prominent symptom in OSAHS. The snoring is interrupted by quiet pauses that typically terminate with an increasing struggle to breathe, followed by a loud snort reflecting arousal and opening of the collapsed upper airway. Sleep may also be characterized by body jerks and kicking as well as sleep verbalizations. Sufferers awaken feeling tired (nonrestorative sleep) and have excessive daytime sleepiness, which is the cardinal symptom. The individual may be unaware of the sleepiness. Some may have periods of microsleep during which they are unaware of surroundings but will display automatic behavior, such as driving an automobile. During wakefulness there may be cognitive dysfunction such as poor attention, forgetfulness, and irritability.
Many people with Cheyne-Stokes breathing will also complain of nonrestorative sleep and excessive daytime sleepiness.
Physical examination in OSAHS commonly reveals obesity, and there may be redundant soft tissue in the pharynx, enlarged tonsils, retrognathia, or tongue enlargement. A neck circumference > 43 cm in men or ≥ 41 cm in women increases the risk for OSAHS. The most severe cases, often with morbid obesity or concurrent COPD, will have a plethoric appearance and signs of right-sided heart failure.
- LABORATORY FINDINGS
There are no characteristic laboratory findings. Thyroid function should be assessed if clinical findings suggest hypothyroidism. Secondary polycythemia may occur in severe cases.
- IMAGING STUDIES
CT and magnetic resonance (MR) imaging have been used to assess upper airway size and surrounding anatomic structures but are clinically indicated in only exceptional cases. Lateral radiographs of the head and neck (cephalometry) are helpful when skeletal anomalies are present.
- SPECIAL TESTS
A number of methods exist for monitoring breathing during sleep, ranging from overnight oximetry to technician-dependent multiple-channel recordings of electromyography, cardiac rhythm, electroencephalography, oxygen saturation, and respiratory effort and airflow (polysomnography). Polysomnography is the standard for diagnosis of SRBDs. If the criteria for OSAHS are met, a second night in the sleep laboratory is needed for a trial of continuous positive airway pressure (CPAP) to titrate the pressure until upper airway obstruction is reduced or eliminated.
Home testing and screening with overnight pulse oximetry may become acceptable tools for diagnosis. Currently, however, they are not validated to the extent that insurers will accept them as diagnostic.
Defining excessive daytime sleepiness is problematic with advanced age because napping becomes increasingly more frequent. Arousals from sleep and disturbed sleep are also common with age. Elders often seem to have shifted the circadian rhythm of the sleep-wake cycle forward, retiring earlier and arising earlier.
Difficulty initiating or maintaining sleep may be due to an SRBD but may also be a result of musculoskeletal discomfort, nocturia, congestive heart failure, depression, gastroesophageal reflux, and drugs or drug interactions.
Possible causes of excessive daytime sleepiness include medications, obstructive sleep apnea syndrome (and upper airway resistance syndrome), periodic limb movements in sleep (PLMSs), periodic (Cheyne-Stokes) breathing, depression, central nervous system (CNS) disease, narcolepsy, and hypothyroidism.
Medications that may cause excessive daytime sleepiness include hypnotics, antidepressants, anticonvulsants, α-agonists and α-blockers, antihistamines, and antipsychotics.
PLMSs are uncontrollable sudden, forceful, and repetitive movements, usually of the legs, that can cause arousal from light stages of sleep. Thus, similar to OSAHS, PLMSs produce poor sleep quality and lead to daytime sleepiness. This disorder is more common in the elderly. Polysomnography can determine the presence and suggest the significance of PLMSs in producing daytime sleepiness.
Obstructive sleep apnea may, in some cases, increase mortality risk. Hypertension is common in OSAHS, and the latter appears to worsen the former. Social interactions (marital and occupational) in OSAHS can be impaired by poor concentration, lagging memory, irritability, and lack of attentiveness. Motor vehicle and work accidents may be increased. When OSAHS occurs in association with COPD or marked obesity (often referred to as the overlap syndromes), abnormalities in pulmonary gas exchange are common, producing hypoxemia and hypercapnia. Pulmonary hypertension evolves and leads to right-sided heart failure.
The possible association of sleep-disordered breathing with declining cognition has been investigated in older adults. Sleep-disordered breathing is frequent in dementia, but a causal association has not been proved.
Periodic breathing (Cheyne-Stokes respiration) produces somnolence and daytime sleepiness similar to OSAHS. These patients demonstrate reduced life expectancy, presumably resulting from systolic heart dysfunction.
Treatment options for OSAHS include general measures for sleep, CPAP provided via nose or face mask, oral appliances that enlarge the pharyngeal airway, and surgical procedures. Pharmacological therapy is not used in OSAHS but may have a role in periodic breathing or central apneas.
Sleep-related breathing events are common in the elderly, many of whom lack any symptoms. Clinical
judgment is important when deciding to initiate treatment for obstructive SRBD. Symptoms, especially excessive sleepiness, in association with an abnormal number of apneic-hypopneic events or respiratory effort-related arousals are needed to consider therapy potentially worthwhile.
General measures to promote better sleep and minimize upper airway narrowing are the first consideration. Weight loss can have a substantial impact on OSAHS. Alcohol and sedating medications are to be avoided. Smoking should be eliminated. Sleeping on the side can be helpful. Nasal obstruction should be managed with antihistamines (preferably minimally sedating) and intranasal steroids. Hypothyroidism is treated with thyroid hormone.
CPAP is the principal treatment for OSAHS. Effective CPAP is associated with restoration of sleep, reduction in daytime sleepiness, and improved quality of life. Subjective improvements typically manifest within a few nights use. Hypertension may moderate, but continued antihypertensive medication will likely be needed. Compliance with CPAP is 60–70% and is improved by attention to patient education and by CPAP-induced improvement in symptoms. Complications of CPAP include nasal congestion and dryness, skin irritation from the mask, poor mask fit, noise, insufflation of the stomach, and sense of impaired breathing against the external pressure.
Several types of oral appliances are used in OSAHS, the most promising of which are mandibular advancement devices that fit over the teeth and pull the jaw forward. Snoring, sleep quality, indexes of upper airway occlusion, and symptoms have been shown to improve to varying degrees. Mandibular advancement devices are typically considered when CPAP fails or is not tolerated. These devices require at least some teeth for anchoring, which is often a problem. Acceptability of these devices in elderly patients has not been studied.
A variety of surgical procedures have been used in OSAHS. Tracheotomy is useful and reserved for life-threatening and refractory cases. Palatal surgery is useful for snoring but is inconsistently effective in OSAHS, especially the more severe cases. Tonsillectomy and adenoidectomy can be helpful in appropriate patients. Craniofacial surgery is a consideration in carefully selected older patients.
Periodic breathing/Cheyne-Stokes respiration is managed primarily by optimizing cardiac performance in those patients with congestive heart failure. Respiratory stimulants (eg, medroxyprogesterone, acetazolamide, and theophylline) have been used with variable effects and in small numbers of patients and are not currently recommended. Nocturnal oxygen by nasal cannula has been reported to reduce central apneic events and decrease nocturnal oxygen desaturation but may not improve daytime symptoms. Nasal CPAP, which carries the theoretical advantage of reducing left ventricular afterload and improving cardiac function, has shown inconsistent benefit in Cheyne-Stokes respiration.
ESSENTIALS OF DIAGNOSIS
- Pathological or cytological confirmation of neoplasia.
At least 50% of all lung cancers occur in people older than 65. Lung cancer is the most common cause of cancer mortality in the 60- to 80-year age group in both sexes. Twenty percent of all lung cancers are small cell lung carcinoma (SCLC). Adenocarcinoma is the most frequent histological subtype (30%) of non-SCLC (NSCLC), followed by squamous cell carcinoma (25%). Large cell carcinoma comprise most of the remaining NSCLCs. Only 20% of NSCLCs are resectable at diagnosis. SCLC is not surgically curable because of almost invariable dissemination at diagnosis.
The overall 5-year survival for lung cancer is 10–15%. Younger patients have a slightly better prognosis than older patients. Elimination of tobacco smoke exposure could prevent the majority of lung cancers. Chemoprevention (eg, antioxidants and retinoids) has not been shown to be useful.
- SYMPTOMS & SIGNS
The cardinal symptoms of lung cancer are cough, dyspnea, weight loss, chest pain, and hemoptysis. Radiographs obtained for evaluation of these symptoms often are the first indication of lung cancer. At presentation, most patients with lung cancer have symptoms from either the primary tumor or metastases.
Signs of lung cancer are usually nonspecific. Localized wheeze may be produced by endobronchial tumor. Superior vena cava obstruction, supraclavicular or axillary lymphadenopathy, Horner's syndrome (unilateral exophthalmos, ptosis, miosis, and ipsilateral anhidrosis), vocal cord paralysis, and ipsilateral diaphragm paralysis are important findings that imply unresectable disease. Pleural effusion in lung cancer is usually malignant
and also indicates unresectable disease. The liver may be enlarged from metastatic spread of tumor. Clubbing of the digits is occasionally seen.
Bone pain and CNS symptoms, such as headache, focal weakness, clumsiness, and uncoordination, are important to elicit, indicating the need to pursue investigation for metastatic disease with appropriate imaging studies.
Paraneoplastic syndromes are rare. They do not necessarily imply unresectability. These syndromes result from immunological epiphenomena or from hormones and cytokines produced by cancer cells.
- LABORATORY FINDINGS
Hyponatremia resulting from syndrome of inappropriate antidiuretic hormone production is seen in both SCLC and NSCLC. Hypercalcemia is seen in squamous cell carcinoma and may be the result of osseous metastasis or hormonally mediated by tumor secretion of parathormone-related peptides or other mediators. Elevated liver enzymes should prompt imaging studies to identify hepatic metastases. Anemia and thrombocytosis may be seen in advanced lung cancer. Bone marrow involvement by tumor can produce a leukoerythroblastic picture in the peripheral blood consisting of nucleated red cell precursors and immature myeloid cells.
- IMAGING STUDIES
Screening chest radiography for lung cancer in high-risk smokers has not been shown to improve survival and is not currently recommended by the American Cancer Society. Low-dose helical CT is a more powerful imaging method that is currently being investigated for early detection of lung cancer.
The chest radiograph is usually the first indicator that lung cancer is likely. SCLC often presents a radiographic picture with large mediastinal and hilar nodes plus a contiguous lung mass. Adenocarcinomas are typically peripheral lung masses. In comparison, squamous cell carcinomas are often centrally located masses and may be cavitary. Bronchoalveolar carcinoma, a subtype of adenocarcinoma, may display single or multiple lung masses; a nonresolving consolidative density with air bronchograms, resembling pneumonia, can be seen with bronchoalveolar cell carcinoma.
CT scanning with its enhanced resolution is helpful in further defining lung and hilar opacities, identifying mediastinal or hilar lymph node enlargement, and imaging the liver and adrenal glands.
Positron emission tomography (PET) after intravenous injection of radioactive fluorodeoxyglucose, which can differentiate normal from neoplastic cells as a result of differences in glucose metabolism, has shown value in identifying malignant lung opacities > 1 cm. PET appears more accurate than CT for identifying mediastinal lymph node metastases and can be used to direct biopsy for confirmation of nodal involvement. Whole-body PET scanning and imaging with radioisotope-labeled somatostatin analogues are promising imaging techniques for determining metastatic spread of lung cancer.
Metastases in lung cancer are commonly seen in the brain, bone, lymph nodes, liver, and adrenal glands. Any symptoms or signs referable to these areas warrant imaging studies. Surgical or needle biopsy of abnormal sites is often undertaken to confirm metastatic spread.
Treatment & Prognosis
- NON-SMALL CELL LUNG CANCER
Surgery is the preferred treatment for completely resectable NSCLC in selected patients who are deemed suitable for thoracotomy. Surgery is potentially curative in Stage I (clinical T1N0 and T2N0) and Stage II (clinical T1N1, T2N0, and T2N1) NSCLC. Operative mortality and survival rates are acceptable in patients ≥ 70 years; most recent series of lung cancer surgery in the elderly indicate that age should not be a contraindication for lung cancer surgery. However, age is definitely a high-risk factor for complications and death when pneumonectomy is performed. The 30-day operative mortality for thoracotomy averages 5–8% in patients older than 70. Lobectomy is associated with mortality of ~7%. Pneumonectomy is associated with mortality of 12–15%; right pneumonectomy is least well tolerated. Some patients may be considered candidates for lesser resections or lung-sparing operations (wedge resection and segmentectomy), but cancer recurrence is higher after these lesser procedures (compared with lobectomy), and perioperative risks are not clearly reduced with lesser resections.
Operability (patient's tolerance for surgery) is assessed by history, physical examination, cardiac risk profiling, and pulmonary function testing. Unstable coronary syndromes, congestive heart failure, and myocardial infarction within 3 mo would indicate current inoperability, but effective treatment may allow subsequent reassessment. An FEV1 < 1 L, maximal oxygen uptake < 10 mL/kg/min, and carbon monoxide diffusion test < 40% of predicted indicate inoperability.
If preoperative spirometry is normal, further pulmonary function testing is not needed. If spirometry is abnormal, full pulmonary function testing, including arterial blood gas analysis and carbon monoxide diffusion test, is advised. An FEV1 > 1.5 L is considered sufficient to perform lobectomy and an FEV1 > 2.0 L to perform pneumonectomy.
Poor surgical candidates with potentially resectable lung cancer (T1) can achieve 5-year survival of 20–25% with radiation therapy.
Most patients with NSCLC will have unresectable disease at presentation (75–80%). Carefully selected patients with Stage IIIA (N2) disease can benefit from extended resections; 5-year survival ranges from 20–30%. Patients with N2 disease manifested by bulky ipsilateral or subcarinal lymph node enlargement do not benefit from surgery and should be referred to radiation and medical oncology.
Stages IIIB and IV NSCLC should be referred to medical oncology. Studies have shown that patients with advanced disease who have some capacity for independent function (fair to good performance status) can benefit from chemotherapy with modest improvements in survival and better overall function and well-being compared with supportive care.
- SMALL CELL LUNG CANCER
Combination chemotherapy is the cornerstone of treatment for SCLC. Median survival for SCLC with limited-stage disease (confined to 1 hemithorax) ranges from 15-20 mo. Median survival for extensive-stage SCLC (any extension beyond limited disease) is < 1 year.
VENOUS THROMBOEMBOLIC DISEASE
ESSENTIALS OF DIAGNOSIS
- Advanced age is a significant risk factor for venous thromboembolic disease.
- A high level of suspicion and pursuit of objective testing are necessary for diagnosis.
- Consider pulmonary embolism when patients manifest dyspnea, tachypnea, pleuritic chest pain, tachycardia, anxiety, or hemoptysis.
- Pulmonary embolism is diagnosed by characteristic defects on ventilation-perfusion lung scan, helical computed tomography scan, or pulmonary angiogram.
Venous thrombosis and subsequent PE (venous thromboembolic disease; VTE) are common events in hospitalized patients. Risk factors for VTE include age, prior VTE, malignancy, major surgery, hip or leg fracture, congestive heart failure, myocardial infarction, paralytic stroke, estrogen therapy (eg, prostate cancer, hormone replacement), and immobilization. Age increases the risk for VTE in an exponential manner; the risk approximately doubles for every decade beyond age 40. Knowledge of risk factors is essential for suspecting VTE in a particular patient and for selecting appropriate prophylactic measures.
Prophylaxis for VTE is effective and should be a key consideration in all hospitalized patients. Thromboprophylaxis should also be considered in the skilled nursing facility and other chronic care settings (Table 22-4).
- SYMPTOMS & SIGNS
The symptoms in leg deep vein thrombosis (DVT) include swelling, increased skin temperature, and thigh or calf pain. VTE is often asymptomatic. The common symptoms in PE are dyspnea (especially if acute), pleuritic chest pain, hemoptysis, and anxiety. Syncope suggests extensive occlusion of the pulmonary vascular bed or an arrhythmia with low cardiac output. Prior cardiopulmonary disease will amplify the adverse effects and symptoms of PE. The most common signs in PE are tachypnea and tachycardia. The combination of dyspnea, pleuritic chest pain, and tachypnea are very suggestive of PE. Cyanosis may be seen in 20% of patients at presentation. Fever may be present. Hypotension is the hallmark of massive PE.
- LABORATORY FINDINGS
Electrocardiography often shows nonspecific abnormalities in PE. Signs of acute right-sided heart strain may be seen with massive emboli. Arterial blood gas analysis often displays a reduced carbon dioxide tension (PCO2) with respiratory alkalosis and reduced oxygen tension. However, normal values can occur and should not deter pursuit of further testing when clinical suspicion of PE exists. Absence of D-dimer in the blood measured by a validated assay argues against VTE.
- LUNG IMAGING
The chest radiograph may be normal or have nonspecific findings in PE. Its primary utility is for excluding an alternative diagnosis such as tumor, heart failure, pneumonia, and pneumothorax. Common radiographic findings in PE are pleural effusion, segmental collapse, elevated hemidiaphragm, and focal infiltrate. A wedge-shaped lung opacity with its base toward the pleural surface (Hampton's hump) can be seen in PE. Areas of oligemia or hypovascularity of the lung (Westermark sign) are occasional findings. PE is suspected in an acutely dyspneic patient with a normal radiograph.
Table 22-4. Prevention of venous thromboembolism.
Ventilation-perfusion radionuclide lung scanning has been extensively studied in the investigation of pulmonary embolus. It has advantages of being noninvasive and generally available. Ventilation-perfusion scan is rarely diagnostic and must be combined with an estimate of clinical suspicion. A high-probability scan combined with a high clinical suspicion of PE leads to a likelihood of 96%. The majority (> 80%) of the ventilation-perfusion scans for suspected PE are neither normal nor highly probable for PE (ie, a nondiagnostic study). (See Figure 22-1 for a diagnostic algorithm for acute PE.)
Pulmonary angiography (PAG) is currently the reference standard for diagnosis of PE. It is invasive, requires special equipment and expertise, and is not readily
available in most facilities. PAG is generally well tolerated in all age groups. It is most clearly indicated with hypotension or cardiovascular instability or when the ventilation-perfusion scan is indeterminate and clinical suspicion for PE is uncertain or high.
Figure 22-1. Diagnostic algorithm for acute pulmonary embolism. VP, ventilation-perfusion; CUS, compression ultrasonogram; IPG, impedance plethysmography; CV, contrast venography; MRI, magnetic resonance imaging; CT, computed tomography; MR, magnetic resonance.
Helical (spiral) CT scanning with intravenous contrast enhancement is accurate for identifying PE in the main, lobar, and segmental pulmonary arteries. CT is not reliable for imaging emboli in subsegmental arteries (PAG has a similar limitation). Motion artifacts causing poor contrast enhancement of the vessels and other technical factors produce nondiagnostic studies in 5–10%. Helical CT scanning has the advantageous capability of potentially identifying a nonembolic cause of the patient's symptoms, which is often very useful in clinical decision making.
MR angiography is being developed as a non-contrast-requiring, noninvasive method for vascular imaging.
Echocardiography is readily available and has been used as the initial test when massive PE is suspected in a hypotensive or unstable patient.
- VENOUS IMAGING
Proximal DVT produces the majority of PE and is itself an indication for treatment. Contrast venography is the gold standard for diagnosis of DVT but is seldom used because of the accuracy of noninvasive compression ultrasonography. Compression ultrasonography is the most common method for identifying DVT. A negative ultrasound examination cannot exclude DVT.
Compression ultrasonography is insensitive for identifying calf vein or iliac vein thrombosis, and chronic DVT will cause errors. When DVT is suspected and the initial compression ultrasonogram is negative, serial ultrasound examination every 5-7 days while withholding anticoagulation has been shown to not harm patients. Ultrasonography should not be used to screen asymptomatic high-risk patients (eg, after orthopedic surgery) for DVT because of its low sensitivity.
Pelvic vein DVT can be diagnosed with contrast venography, CT scanning, and MR imaging. MR holds considerable promise for diagnosing DVT.
PE that is promptly diagnosed and properly treated with anticoagulation results in death in < 4%. Untreated, the case-fatality rate is considerably higher. It is estimated that 50,000-200,000 people die from PE annually in the United States.
Chronic thromboembolic pulmonary hypertension is a rare complication, occurring in < 1% of PE. Surgical removal of occluding clot and fibrous tissue (pulmonary thromboendarterectomy) has been shown to help some patients with this condition.
Lower extremity DVT can produce venous valve damage and chronic venous insufficiency, causing postphlebitic syndrome characterized by swelling, pain, poor mobility, stasis dermatitis, and poorly healing ulcers.
Unfractionated heparin has a long history as an effective treatment for VTE (Tables 22-5 and 22-6). It is usually administered as a continuous intravenous infusion, although intermittent subcutaneous injection is an option. Inadequate anticoagulation is associated with increased incidence of recurrent thrombosis. Weight-based dosing is advised.
Table 22-5. Anticoagulation with unfractionated heparin.
Low-molecular-weight heparins (LMWHs) appear to be as effective as unfractionated heparin with the advantages of subcutaneous administration and no laboratory monitoring of activated partial thromboplastin time (APTT; Table 22-7). LMWHs appear to have a reduced risk of heparin-induced thrombocytopenia and may have a reduced risk of bleeding complications. Some studies have indicated that outpatient therapy with LMWH for selected cases of VTE is safe and effective. Complications of heparin therapy include bleeding, which correlates poorly with dose or APTT (with unfractionated heparin). Age increases the risk for bleeding complications. Another complication, heparin-induced thrombocytopenia, occurs in < 1% of patients, usually within the first 2 weeks of therapy. This syndrome may occur sooner if there has been prior exposure to heparin. Heparin-induced thrombocytopenia is associated with arterial thromboembolism and recurrent VTE; the syndrome can lead to limb loss and death. Platelet count should be checked between days 3 and 5 of therapy; if heparin is continued for a longer period the platelet count should be monitored regularly.
Warfarin is administered for 3-6 mo after an initial VTE event that is associated with a reversible or time-limited risk factor (eg, surgery or immobilization). A first-event VTE without an identifiable risk factor is treated with warfarin for ≥ 6 mo because of an expected high incidence of recurrent VTE. Ongoing risk factors such as cancer and hypercoagulability may require indefinite warfarin therapy.
Bleeding is the main complication of warfarin therapy, and the risk correlates with elevation of the international normalized ratio. Aspirin and other platelet-inhibiting drugs increase this risk. Warfarin is subject to numerous drug interactions that may either potentiate or inhibit anticoagulation. The patient's medication list should be carefully reviewed before initiating warfarin and, during maintenance therapy, the INR monitored more closely when adding or removing a drug. Another complication of coumarin drugs is skin necrosis. This uncommon condition manifests as purpuric skin lesions, which may cause extensive dermal loss, and has been associated with protein C deficiency and malignancy.
Thrombolytic agents approved for clot lysis in VTE are streptokinase, urokinase, and alteplase (recombinant tissue plasminogen activator). The principle indication for thrombolysis in VTE is hemodynamically unstable PE. Thrombolysis in PE has not improved mortality
compared with heparin anticoagulation. Severe DVT, especially when leg viability is compromised, has been treated with thrombolytic agents.
Table 22-6. Body weight-based dosing: continuous intravenous unfractionated heparin.
Contraindications to thrombolytic agents include previous hemorrhagic stroke, recent bleeding, intracranial neoplasm, and recent intracranial surgery. Uncontrolled severe hypertension, surgery within 10 days, recent cardiopulmonary resuscitation, and bleeding disorders are relative contraindications. The risk of intracranial bleeding after thrombolysis in VTE is 1–2% and increases with age.
Table 22-7. Anticoagulation with low-molecular-weight heparin.
Interruption of the inferior vena cava with intracaval filter devices is designed to prevent recurrence of embolization to the pulmonary circulation. Indications for placement of filters are contraindication to or complication of anticoagulation, recurrent PE despite adequate anticoagulation, chronic thromboembolic pulmonary hypertension, and massive PE. Complications include recurrent venous thrombosis, chronic lower extremity edema, and filter migration.
Surgical embolectomy and catheter-directed clot extraction or clot fragmentation are potential therapeutic options in massive PE.
INTERSTITIAL LUNG DISEASE
ESSENTIALS OF DIAGNOSIS
- Nonproductive cough.
- Lung crackles and clubbing on physical exam.
Interstitial lung disease is a general term used to describe a large number of unrelated diffuse parenchymal pulmonary disorders. Interstitial lung diseases of known cause include those resulting from inhalation injury (inorganic dust or fumes, pneumoconioses, and organic dusts), drugs, infections, radiation, lymphangitic carcinoma, and lung disorders associated with organ transplant rejection, heart failure, and liver and renal disease.
Those of unknown cause include the idiopathic interstitial pneumonias, sarcoidosis, vasculitides, collagen vascular disorders with interstitial lung disease, hereditable disorders, and Langerhan's cell histiocytosis.
Idiopathic Pulmonary Fibrosis
Idiopathic pulmonary fibrosis (IPF) is one of the more common idiopathic interstitial pneumonias but is nevertheless a rare condition. The prevalence of IPF increases with age, and it has its peak prevalence at or near age 70. Approximately 66% of patients with IPF are older than 65 at presentation. There is a slight male predominance. Patients usually present with exertional dyspnea and nonproductive cough. Systemic symptoms are not characteristic. Symptoms usually evolve over several months to several years, and the disease usually progressively worsens. The relatively slow evolution of dyspnea and cough may delay diagnosis. Confusion with smoking-related lung disease or heart failure can contribute to diagnostic delay. The median survival is ~3 years.
Physical examination reveals dry, bilateral inspiratory crackles, predominately at the lung bases. Clubbing of the fingers is noted in ~50% of patients. End-stage disease will display signs of pulmonary hypertension and cor pulmonale.
The working definition of IPF by international consensus is a fibrotic lung disease with a surgical lung biopsy showing usual interstitial pneumonia plus the following:
- No known causes for interstitial lung disease.
- Restricted lung volumes on pulmonary function testing and abnormal gas exchange.
- Characteristic abnormalities on chest radiograph or high-resolution chest CT.
Confirmation of a diagnosis of IPF requires surgical lung biopsy. A diagnosis of IPF in the absence of a surgical biopsy is likely if all of the following major criteria and 3 of 4 minor criteria are met.
- 1. Major criteria
- Exclusion of known cause of interstitial lung disease.
- Lung volume restriction on pulmonary function testing.
- Bibasilar reticular opacities with minimal ground-glass attenuation on HRCT.
- Transbronchial biopsy showing no features of alternative diagnosis.
- Minor criteria
- Age > 50 years.
- Insidious onset of otherwise unexplained dyspnea.
- Duration of illness > 3 mo.
- Bibasilar inspiratory crackles of the “dry” or “Velcro” type.
The differential diagnosis of IPF is broad. Crackles, dyspnea, and cough are easily confused with left-sided heart failure. Collagen vascular disorders, especially systemic sclerosis and rheumatoid arthritis, and asbestosis can have features that are identical to those of IPF.
- LABORATORY FINDINGS
Low-titer elevations in rheumatoid factor assays and antinuclear antibodies are present in up to 30% of patients, even when no underlying connective tissue disease can be identified.
Pulmonary function testing typically reveals restrictive lung disease. The vital capacity and total lung capacity will be reduced. Reduced carbon monoxide diffusing capacity and hypoxemia, initially seen with exertion and later at rest, reflect impaired gas exchange.
- IMAGING STUDIES
Chest radiographic abnormalities in IPF include bilateral irregular nodular or reticulonodular opacities that are most visible in the lower lung and subpleural areas.
HRCT is extremely useful in evaluating ILD. The HRCT findings in IPF are relatively specific.
- SPECIAL TESTS
Surgical lung biopsy is needed for an accurate diagnosis. Lung tissue in IPF reveals the pathological pattern of usual interstitial pneumonia. The fibrosis is patchy with interspersed normal lung. Honeycombing (cystic dilatation of distal airspaces) is common. Biopsies performed via bronchoscopy can be useful for identifying other disorders that can mimic IPF (such as sarcoidosis, infections, or cancer) but are not suitable to accurately diagnose IPF.
The course of IPF is variable. Occasionally, the functional and radiographic abnormalities may stabilize. However, most cases will progress and the median survival is ~3 years. Progressive respiratory failure, right-sided heart failure, coronary artery disease, pulmonary embolus, or infection may cause death. There seems to be an increased incidence of bronchogenic carcinoma in IPF. Geriatric patients with IPF, especially if they
have had recent acute decline in pulmonary function or advanced fibrosis, have a poor prognosis. Indicators of longer survival include younger age at onset, female sex, and a beneficial response to corticosteroid therapy.
There is limited evidence that any current therapy is effective. Supportive therapy with oxygen and diuretics and symptom palliation may be best for some patients. Treatment in advanced age, obesity, diabetes mellitus, severe lung impairment, advanced cardiac disease, and general debility should be carefully considered in the context of the patient's wishes for end-of-life care. If treatment is pursued, the following has been suggested:
- Prednisone 0.5 mg/kg lean body weight daily for 8 weeks, then reduced to 0.125 mg/kg daily or 0.25 mg/kg every other day; plus either
- Azathioprine starting with 25-50 mg daily and increasing by 25 mg every 2-3 weeks to the maximum dose (2-3 mg/kg lean body weight); or
- Cyclophosphamide starting with 25-50 mg/day, increasing every 1-2 weeks by 25 mg to maximum dose of 2 mg/kg lean body weight (not to exceed 150 mg daily).
Therapy should be continued, if tolerated, for at least 6 mo. If the condition worsens, treatment should be stopped. Failure of treatment is indicated by worsening symptoms, declining oxygenation, worsening opacities on radiographs or CT, or ≥ 10% decline in vital capacity or total lung capacity. If treatment fails, consultation may be undertaken to review possible alternatives. If the condition stabilizes, combination therapy should be continued. Prevention of steroid-induced osteoporosis with bisphosphonates in conjunction with calcium and vitamin D is recommended. Bone mineral density measurements at baseline and serially are advised.
Pulmonary rehabilitation may be a useful adjunct. Oxygen supplementation should be provided for patients who exhibit oxygen desaturation with exercise or at rest.
Lung transplantation is an option in IPF. However, higher posttransplant mortality with age and the limited availability of lungs for transplantation usually limit this option to patients younger than 60-65.
Other Interstitial Lung Disorders
Sarcoidosis is the most common interstitial lung disease and typically presents before age 40. Onset of sarcoidosis past age 65 is unusual.
Hypersensitivity pneumonitis (HP), also called extrinsic allergic alveolitis, has been diagnosed in all age groups. A history of exposure to an organic antigen is key to suspecting this disorder. Diagnosis requires integration of a combination of features. Management emphasizes elimination of exposure to the inciting antigen. Corticosteroids may hasten resolution in the acute or subacute presentations but is not likely to benefit chronic HP.
Drug-induced lung disease is an important cause of diffuse infiltrative lung disease and is easily overlooked. The radiographic and clinical findings in drug-induced lung diseases are varied. Presentations include acute interstitial pneumonitis, acute eosinophilic lung disease, patchy areas of organizing pneumonia (bronchiolitis obliterans organizing pneumonia, or BOOP, pattern on histology), noncardiogenic pulmonary edema, alveolar hemorrhage, and subacute and chronic lung fibrosis. A classic example of subacute lung injury and fibrosis with dyspnea and dry cough is seen in the elderly woman receiving nitrofurantoin for managing recurrent cystitis. Another classic drug-induced diffuse lung disorder in the elderly is salicylate intoxication with pulmonary edema.
Other drugs with recognized associations with 1 or more of these patterns of diffuse lung disease include NSAIDs, phenytoin, amiodarone, hydrochlorothiazide, hydralazine, propylthiouracil, busulfan, bleomycin, methotrexate, penicillamine, gold, and ergot compounds.
Chan ED, Welsh CH: Geriatric respiratory medicine. Chest 1998;114:1704. (A broad review of respiratory disorders in the elderly, including asthma.)
National Asthma Education and Prevention Program: Expert Panel Report 2: Guidelines for the diagnosis and management of asthma (NIH publication no. 97-4051). Bethesda, MD: National Institutes of Health, 1997. (Basic information on diagnosis and therapy of asthma).
Weiner P et al: Characteristics of asthma in the elderly. Eur Respir J 1998;12:564. (More severe airway obstruction in elderly patients with long-standing asthma compared with those with recent-onset disease.)
Chronic Obstructive Pulmonary Disease
McEvoy CE, Niewoehner DE: Corticosteroids in chronic obstructive pulmonary disease. Clin Chest Med 2000;21:739. (Review of systemic and inhaled steroids in COPD.)
Pauwels RA et al: Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop Summary. Am J Respir Crit Care Med 2001;163:1256. (Evidence-based review by international committee of clinical issues in COPD.)
Stoller JK: Clinical practice: acute exacerbations of chronic obstructive pulmonary disease. N Engl J Med 2002;346:988. (Concise review of management issues in COPD exacerbations.)
Sleep-Related Breathing Disorders
American Academy of Sleep Medicine: Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. Sleep 1999;22:667.
Leung RST, Bradley TD: State of the art: sleep apnea and cardiovascular disease. Am J Respir Crit Care Med 2001; 164:2147. (Pathophysiology and epidemiology of obstructive apnea and periodic breathing in relation to cardiovascular disease.)
British Thoracic Society: Guidelines on the selection of patients with lung cancer for surgery. Thorax 2001;56:89. (Evidence-based guidelines for assessing resectability and operability in lung cancer.)
Jaklitsch MT et al: New surgical options for elderly lung cancer patients. Chest 1999;116:480S. (Brief overview of lung cancer surgery in the elderly.)
Reif MS et al: Evidence-based medicine in the treatment of non-small cell lung cancer. Clin Chest Med 2000;21:107. (Review of the studies supporting surgical and nonsurgical therapy in NSCLC.)
Venous Thromboembolic Disease
American College of Chest Physicians: Sixth ACCP Consensus Conference on Antithrombotic Therapy. Chest 2001;119:1S. (Extensive review of the evidence for antithrombotic therapy in multiple clinical settings.)
American Thoracic Society: Clinical practice guideline. The diagnostic approach to acute venous thromboembolism. 1999; 160:1043. (Review of the evidence basis and recommendations for diagnosis of acute VTE.)
Hyers TH: State of the art: venous thromboembolism. Am J Respir Crit Care Med 1999;159:1. (Review of diagnosis and treatment of PE and DVT.)
Interstitial Lung Disease
American Thoracic Society: Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. Am J Respir Crit Care Med 2000;161:646.
American Thoracic Society/European Respiratory Society: International multidisciplinary consensus classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med 2002;165:277.
Gross TJ, Hunninghake GW: Idiopathic pulmonary fibrosis. N Engl J Med 2001;114:1704. (Review of current thinking on the pathogenesis, diagnosis, and management of IPF.)