Patients sometimes have more than one cardiopulmonary disorder, which can result in a clinical picture consistent with both restric- tive and obstructive abnormalities (e.g., a patient with emphysema and CHF, a smoker with interstitial lung disease, or an obese patient with asthma). In addition, some pulmonary disorders can produce combined defects, as in pulmonary edema and some inter- stitial and occupational lung diseases.
Pulmonary Edema
Pathological accumulation of extravascular fluid in the interstitial and alveolar spaces in the lungs is known as pulmonary edema. There are two types:
• Increased pressure, hydrostatic, or cardiogenic pulmonary edema (elevated left heart pressures reflected back to the pulmonary microvasculature leads to flooding of the pulmonary interstitial space and alveoli with low-protein transudative fluid); the most
common causes are coronary artery disease, hypertensive heart disease, aortic or mitral valve disease, and cardiomyopathy. • Increased permeability, or noncardiogenic, pulmonary edema
(acute lung injury causing inflammation-induced damage to the alveolar epithelium and endothelium causes fluid and pro- tein leakage into the alveoli, as described in the preceding sec- tion on ARDS).
Pathophysiology
Increased permeability pulmonary edema (ARDS) has already been described, so only cardiogenic pulmonary edema is presented here. The consequences of pulmonary edema depend on how much fluid accumulates.
• Elevated left atrial (LA) and left ventricular (LV) pressures are reflected back to the lungs, which impedes blood flow through the pulmonary vasculature, leading to increased intrapulmon- ary blood volume (i.e., pulmonary congestion) and pulmonary capillary hydrostatic pressure. Mild elevation of LA pressure (i.e., 18 to 25 mm Hg) produces edema in the peribronchovascular interstitial spaces, whereas LA pressure exceeding 25 mm Hg leads to flooding of the alveoli and often the pleural space (producing pleural effusion).230
4 Interstitial edema can increase airway resistance, raising closing volume and reducing expiratory flow rates. With alveolar flood- ing air trapping can develop as airway closure occurs earlier. 4 Interstitial edema usually diminishes lung compliance,
impeding lung expansion; in addition, chronic interstitial edema can provoke fibrotic changes in the lungs, which fur- ther reduce lung compliance. If alveolar flooding occurs, lung compliance is markedly decreased with resultant reduc- tions in many lung volumes, particularly inspiratory capacity and vital capacity.
4 Impaired alveolar ventilation induces _V/ _Q mismatching and impaired gas exchange, and increases the work of breathing, and so on, as depicted in Figures 4-6 and 4-1. With more severe pulmonary edema and alveolar flooding, gas exchange is seriously impaired, provoking possible respira- tory distress and failure requiring ventilatory assistance. • When cardiac output is significantly reduced, the resultant dec-
rement in peripheral tissue perfusion produces significant tis- sue hypoxia and lactic acidosis.
Clinical Manifestations
The clinical features of cardiogenic and noncardiogenic pulmonary edema are similar:
• Dyspnea, respiratory distress
• Orthopnea (dyspnea when lying flat), paroxysmal nocturnal dyspnea (awakening at night with acute shortness of breath) • Pallor or cyanosis
• Diaphoresis
• Tachycardia, possible arrhythmias • Anxiety, agitation
• Bibasilar or diffuse crackles, possible wheezes (see Table 6-15, page 247)
• Abnormal chest x-ray with pulmonary congestion or central infiltrates
• Third heart sound (S3) (see page 44)
Specific Treatment
Prompt diagnosis of the cause of pulmonary edema is critical to appropriate treatment. The treatment of increased perfusion pul- monary edema is described on the preceding page; the treatment of cardiogenic pulmonary edema consists of:
• Supplemental oxygen, possible assisted ventilation • Morphine
• Diuretics
• Nitroglycerin and other afterload reducers Occupational and Environmental Lung Diseases
A variety of lung diseases, including occupational asthma, hyper- sensitivity pneumonitis, and pneumoconiosis, can be caused by the inhalation of many dusts, fibers, particles, microbes, and fumes. More than 300 causative agents have been identified, some of which are listed in Table 4-5. With the implementation of gov- ernmentally regulated protective measures, there has been a sub- stantial decrease in the frequency of occupational lung disease; however, individual cases of lung disease resulting from exposures to ordinary antigens in the home environment (e.g., molds) are
being recognized with greater frequency, and sometimes a specific causative antigen is never identified.
The development of occupational or environmental lung dis- ease depends on the toxicity of the inhaled substance, the intensity and duration of exposure, and the individual’s physiological and biological susceptibility. Early intervention with remediation of the causative environment and lifestyle modifications to prevent reexpo- sure are crucial to preventing disability and premature death.
Pathophysiology
Exposure to the agents listed in Table 4-5 can cause obstructive disease (e.g., occupational asthma), restrictive disease (e.g., pneumoconiosis or hypersensitivity pneumonitis), or mixed disease (e.g., exposure to coal dust, silica, or beryllium).
• The most common reaction to toxic exposure is occupational asthma, which is characterized by coughing, wheezing, chest tightness, and shortness of breath that occur and often progress during the work week or while at home if that is the locus of expo- sure; improve during the weekend or while on vacation; and recur on returning to work or home. It can be precipitated by direct air- way irritation by substances that trigger preexisting asthma, aller- gic sensitization by repeated exposure to specific substances, or intrinsic reactions caused by excess release of naturally occurring chemicals in the body, such as histamine and acetylcholine. • Hypersensitivity pneumonitis (HP), also called extrinsic allergic
alveolitis, is an immune-mediated interstitial lung diseases pro- duced by repeated inhalation of and sensitization to antigenic organic particles or chemicals.136Chronic inflammation gives rise to multiple nonnecrotizing granulomas, which may prog- ress to severe pulmonary fibrosis. Restrictive changes with impaired diffusion are seen on PFTs.
4 HP accounts for 12% to 19% of incident cases of ILD (see page 86).3
4 HP can present in three overlapping clinical forms: as an acute disease, with sudden onset of fever, chills, myalgia, dyspnea, and nonproductive cough occurring 2 to 9 hours after a high-level exposure and followed by resolution, usu- ally within 12 to 24 hours after cessation of exposure; as a subacute disease with gradual development of productive cough, dyspnea, fatigue, anorexia, and weight loss, which occur after repeated low-level exposures and often improve rapidly with avoidance of exposure; or a chronic disease with insidious onset of cough, progressive dyspnea, fatigue, and weight loss that is caused by prolonged and continuous exposure to low levels of antigens and shows only partial improvement on removal of exposure.
4 In subacute/chronic HP, elevated risk of idiopathic pulmo- nary fibrosis has been noted in workers exposed to metal or wood dusts and in beauticians.91
• Inhalation of mineral particles and dusts (e.g., asbestos, coal, and silica) and sensitizing metals (e.g., beryllium and cobalt) causes pneumoconiosis, a form of interstitial lung disease in which the prevalence and severity of the disease are related to the intensity and duration of the exposure. Although the impo- sition of government regulations has decreased exposure to many materials, the mortality rates of some of the pneumoco- nioses continue to rise because of the long latency periods TABLE 4-5: Occupational Lung Diseases and Causative Agents
Occupational
Lung Disease Causative Agents Occupational
asthma Animal proteins (e.g., hair, dander, andurine of animals, insects, birds, fish) Enzymes (e.g., detergents, spices,
pharmaceutical manufacturing) Plant proteins (e.g., grain dusts, flour,
coffee, tea, soybeans, castor bean, latex, wood dusts, flax, cotton, guar gum)
Metals (e.g., platinum salts, nickel, cadmium, vanadium, tungsten) Chemicals and plastics
(e.g., isocyanates, formaldehyde, formalin, Freon, piperazine, anhydrides, dyes, henna, psyllium, some antibiotics and other drugs)
Pneumoconiosis Inorganic dusts (e.g., asbestos, coal, silica), other minerals and metals (e.g., talc, kaolinite, mica, vermiculite, beryllium, barium, tin, cobalt)
Hypersensitivity
pneumonitis Bird and animal proteins, microbialcontaminants of moist areas, such as heating, ventilating, and air-conditioning systems (e.g., fungi and fungal spores, bacteria) and low molecular weight chemicals (e.g., isocyanates, anhydrides, pyrethrum insecticide)
Inhalation
injuries Noxious gases and fumes(e.g., ammonia, hydrochloric acid, chlorine, cadmium, zinc chloride, osmium tetroxide, vanadium)
between exposure and disease manifestation. In addition, expo- sure to these agents is associated with increased risks for lung cancer, particularly in smokers, and malignant mesothelioma.60 4 Asbestosis appears 15 to 40 years after asbestos exposure (e.g., construction trades, building maintenance, production of acoustic ceiling tiles or insulation, and ship building and repair) and features diffuse inflammatory and fibrotic lesions of the small airways, areas of pleural thickening that may cal- cify into plaques, and benign pleural effusions. Progression of disease with more extensive fibrosis occurs in 20% to 40% of patients.91
4 Inhalation of coal mining dust results in coal workers’ pneumo- coniosis, which is characterized by inflammatory lesions con- sisting of focal collections of coal mine dust–laden macrophages, which surround the respiratory bronchioles and may extend to the alveoli. More advanced disease is marked by larger lesions, progressive massive fibrosis, and/or emphysema.
4 Silicosis follows the inhalation of crystalline silica or silica dusts (e.g., hard rock mining, tunnel drilling, stone quarrying or crushing, granite/stone work, stone carving and sculp- ture; silica flour production; manufacture of plastics and resin, paint, glass, and ceramics; road construction and repair; and concrete construction and demolition) and can present as acute, accelerated, or chronic disease, depending on the clinical picture and time course in relation to exposure.
8 Chronic or classic silicosis is distinguished by silicotic nodules, consisting of a collagen core surrounded by a cap- sule of macrophages, lymphocytes, and fibroblasts, that develop 10 to 40 years after exposure; some patients develop progressive massive fibrosis and hilar adenopathy with possi- ble calcification.
8 Accelerated disease develops more quickly and progresses more rapidly to progressive massive fibrosis.
8 Acute silicosis involves alveolar filling with proteinaceous material with few or no nodules.
8 Patients with silicosis are particularly susceptible to a chronic indolent form of pulmonary tuberculosis.
4 Exposure to certain metals (e.g., cobalt and beryllium) causes lung disease due to sensitization or toxicity rather than cumulative dust exposure, affects only a minority of exposed workers on the basis of individual susceptibility, and manifests itself clinically soon after a relatively brief exposure.61 Once an individual is sensitized, low levels of exposure can trigger disease, and removal from exposure usually stops or reduces the severity of disease; however, sometimes there is continued progression.
8 Chronic beryllium disease (CBD), or berylliosis, is a granulomatous disease similar to sarcoidosis that develops in 2% to 10% of persons exposed to beryllium dust and fumes (e.g., nuclear weapons, electronics, aerospace, cera- mics, metal recycling, and the defense industry).61 CBD is characterized by nodular infiltrates in the middle and upper lung zones, with the gradual onset of dyspnea on exertion and dry cough. Later, easy fatigability, weakness, anorexia, and weight loss may develop; and with severe disease, there
will be dyspnea at rest, hypoxemia, cor pulmonale, and peripheral edema. PFTs show restrictive impairment and diffusion defects, and often evidence of airflow limitation. In addition, other organ systems, including the skin, liver, spleen, lymph nodes, and bone marrow, are occasionally affected.
8 Cobalt exposure can lead to occupational asthma and pneumoconiosis, known as “hard metal disease,” which can occur in a subacute form with rapidly progressive cough, fever, and dyspnea, as well as a more chronic form with grad- ually progressive pulmonary impairment.
4 Other agents that can give rise to pneumoconioses are talc, kaolinite, mica, and vermiculite, as well as metal dusts such as barium and tin.
• Prolonged or severe exposure to any of the agents listed in Table 4-5 can result in progressive _V/ _Q mismatching and increasing work of breathing, as per Figure 4-1, with significant disability.
Specific Treatment
• Avoidance of exposure to causative agent • Corticosteroids
• Supplemental oxygen if hypoxemia is present • Treatment of intercurrent infections