. \212 \212 \212 e n i c i d e m y r a n o m u P Blood tests: CBC, electrolytes, CRP, ABG Radiology: CXR Microbiology: Sputum and blood cult ures (if febrile) Spirometry (COPD, neuromuscular disease, Guillain \200\223Barr syndrom e). l Treat underlying cause. Controlled oxygen therapy: Start at 24% O 2 . Recheck ABG after 20 min. If P a CO 2 is steady or lower, ^ O 2 concen- tration to 28%, If P a CO 2 has risen >1 2 mm Hg and the patient is still hypoxic, consider assisted ventilation (i.e., noninvasive positive pressure ventilation). If type II respiratory failure progresses, consider intubat ion and ventilation. \212 187 Table 6.10 When to consider arterial blood gas (ABG) measurement In these clinical scenarios: Any unexpected deterioration in an ill patient Anyone with an acute exacerbation of a chronic chest condition Anyone with impaired level of consciousness Anyone with impaired respiratory effort Or if any of these signs or symptoms are present: Bounding pulse, drowsiness, tremor (flapping), headache, pink palms, papilledema Cyanosis, confusion, visual hallucinations (signs of hypoxia) Or to monitor the progress of a critica lly ill patient: Monitoring the treatment of known respiratory failure Anyone ventilated in the ICU After major surgery After major trauma To validate measurements from pulse oximetr y: Pulse oximetry (p. 154) effective for monitoring oxygen saturation; accu- rate readings are dependent on appropriate placement of monitor, on normal arterial perfusion, and on cor relation with arterial pO 2 . Pulmonary embolism PE and venous thromboembolism are the most common and preventable causes of death, especially in hospitalized patients. In addition to myocardial infarctions (MIs) and cerebral vascular accidents, venous thromboembolism is a major cause of death in nonho spitalized individuals. See Table 6.11. Causes PE usually arise from a venous thrombosis in the pelvis or legs. Thrombus may dislodge and pass through the venous system to the right side of the heart before occluding an artery in the pulmonary circulation. Rare causes incl ude right ventricular thrombus (post-MI); septic emboli (right-sided endocarditis); fat, ai r, or amniotic fluid embolism; neoplastic cells; parasites. Risk factors: Any cause of immo bility or hypercoagulability: \212 Prolonged travel in automobiles or planes without leg e xercise and stretching. \212 Recent surgery \212 Thrombophilia/antiphospholipid syndrome (p. 590) Prolonged bed rest Pregnancy; postpartum; oral contraceptives/hormone replace- ment therapy \212 \212 Recent stroke or MI Disseminated malignancy \212 \212 Clinical features depend on the number, size, and distribution of the emboli; small emboli may be asymptomatic whereas large, saddle emboli are critical/fatal. Symptoms: Acute breath lessness, pleuritic chest pain, hemop- tysis; dizziness; syncope. Review risk factors (abov e), past history or family history of thromboembolism. Signs: Pyrexia; cyanosis; tachypnea; tachycar- dia; hypotension; \206\221 JVP, pleural rub; pleural effusion. Examine for sign s of a cause; e.g., deep vein thrombosis (DVT); scar from recent surgery. Prognosis of PE i s related to comorbidities and to the presence or absence of hypotension and to the functio n of the right ventricle. PE in normoten- sive patients has an encouraging prognosis and us ually requires anticoagu- lation only. In PE patients with hypotension or with normal BP, y et with evidence of right ventricular dysfunction, the prognosis is guarded; these PE patie nts may need thrombolysis and/or embolectomy in addition to anticoagulation. Tests \212CXR may be normal or may show dilated pulmonary artery, linear atelectasis, small pleural effu sion, wedge-shaped opacities; cavitations may occur with pulmonary infarction. 188 \212ECG may be normal or show tachycardia, right bundle branch block, right ventricular st rain (inverted T in V 1 to V 4 ). The classical S i Q iii T iii pattern is rare. \212Echocardiogram assessment of right ventricular function is important for prognosis; ri ght ventricular heart failure is the cause of death in most patients with PE; evidence of r ight ventricular enlargement or dysfunction suggests significant physiologic impairment and thus a poor prognosis. \212ABG may show a low P a O 2 and a low P a CO 2 . \212Radiographic studies Ultrasonogra phy is crucial in evaluation of the lower extremities for thrombosis; pelvic US is difficul t to assess for venous thrombosis. CT of the chest (spiral CT with contrast) is the radiogr aphic study of choice for detecting PE; also may be useful in assessment of the right ven- tricle; right ventricular enlargement is associated with a poor prognosis. Treatment (p. 71 0) Initiate anticoagulation with low-molecular-weight heparin (e.g., enoxaparin 1 mg/kg/12 h SC); start oral warfarin 10 mg \212 (p. 574). Stop heparin when International Normalized Ratio (INR) is >2 and continue warfari n for a minimum of 3 months; aim for an INR of 2 \200\2233. Consider placement of a vena ca va filter in patients who develop emboli despite adequate anticoagulation, or in critically ill patients in whom another PE might be fatal. (NB \206\221 risk of recurrence if placed without concomitant anticoagulation). Prevention Give heparin (7,500 U/12 h or 5,000 U/8 h ) to all immobile patients. Prescribe TED stockings and encourage early mobilization. Women should stop hormone replacement therapy (HRT) and oral contraceptives preoperatively. Pati ents with a past or family history of thromboembolism should be investigated for coagulatio n disorders associated with enhanced thrombus formation. e n i c i d e m y r a n o m u P l Pneumothorax Management on p. 706 and X-RAY PLATE 6 Causes A pneumothorax is the presence o f air/gas within the pleural space. Spontaneous pneumatothoraces occur (especially in young thin men) due to rupture of a subpleural bulla. Other causes : Asthma, COPD, TB, pneumonia , lung abscess, carcinoma, CF, lung fibrosis, sarcoidosis, connective tissue disorders (Mar fan \200\231s syndrome, Ehlers \200\223Danlos syndrome), trauma, iatrogenic (subclavian cen tral venous pressure [CVP] line insertion, pleural aspiration or biopsy, percutaneous liver biopsy, positive pressure ventilation). Table 6.11 Investigation of suspected PE 189 \212 \212 \212 First assess the likely probability of a PE. Numerous scoring systems are available. One si mple system is the presence of clinical features of a PE (short- ness of breath (SOB) and t achypnea, with or without pleuritic chest pain and hemoptysis) and either (a) the absence o f another reasonable explanation or (b) the presence of a major risk factor. If a and b coe x- ist, the probability is high; if only one exists, intermediate; if neither exist, the pr obability for PE is low. \212D-dimer: This study is useful as a screening test, especially in those patients withou t a high probability of a PE. A negative D-dimer test excludes a PE in patients with a low clinical probability, and imaging may not be required. A positive D-dimer test does not pro ve a diagno- sis of a PE, and follow-up radiographic studies are crucial. \212Imaging: The recommended first-line imaging modality is a spiral CT scan, which show c lots down to fifth-order pulmonary arteries. This may be useful in subjects with indetermin ate isotope scans. Bilateral leg US (or rarely venograms) may confirm a DVT in patients wit h a coexisting clinical PE. Ventilation-perfusion nuclear lung scans are a secondary choice for diagnosing PE; may be useful in patients who have an allergy to radiographic dye. Major risk factors for PE Surgery \212 \212 \212 \212 \212 \212 \212 \212 \212 \212 Lower limb problems Fracture Varicose veins Malignancy Reduced mobility Previous PE Estroge n therapy Major abdominal/pelvic Hip/knee replacement Obstetrics \212 \212 Late pregnancy; postpartum Cesarean section Clinical features Symptoms: Asymptomatic in well-conditioned younger individuals; pneumotho rax may present as a sudden onset of dyspnea and/ or pleuritic chest pain. Patients with as thma or COPD may present with emergent respiratory deterioration. Mechanically ventilated p atients may develop hypoxia or an increase in ventilation pressures. Signs: Reduced expansi on, hyperresonance to percussion, and diminished breath sounds on the affected side. With a tension pneumothorax, the trachea will be devi- ated away from the affected side . Managem ent of tension pneumothorax See p. 706, and placing a chest drain (p. 662). Pleural effusion Definitions A pleural effusion is excessive fluid in the pleural space. Ef fusions can be divided, by their protein and LDH concentrations, into transudates and exuda tes (see pleural fluid analysis, Table 6.12). Blood in the pleural space is a hemothorax, p us in the pleural space is an empyema , and chyle in the pleural space (lymph with fat) is a chylothorax . Both blood and air in the pleural space is termed a hemopneumothorax . Caus es Transudates may be due to increased venous pressure (cardiac fail- ure, constrictive per icarditis, fluid overload) or hypoproteinemia (cirrhosis, nephrotic syndrome, malabsorption ). Transudative pleural fluid occurs in hypothyroidism and Meigs \200\231 syndrome (right p leural effusion and ovarian fibroma). Exudates are mostly due to increased permeability of pleural capillaries secondary to infection, inflammation, or malignancy. Causes : Pneumonia , TB, pulmonary infarction, rheumatoid arthritis, SLE, bronchogenic car- cinoma, malignant metastases, lymphoma, mesothelioma, lymphangitic carcinomatosis. Symptoms Asymptomatic or s ymptoms of dyspnea, pleuritic chest pain, shortness of breath. Signs Decreased chest expans ion with inspiration; dull percussion noted; diminished breath sounds occur on the affected side. Tactile vocal fremitus and vocal resonance are \206\223 (inconstant and unreliable) . Above the effusion, where lung is compressed, there may be bronchial breathing and egopho ny (vocal resonance). With large effusions, there may be tracheal deviation away from the e ffusion. Look for aspiration marks and signs of associated disease: Malignancy (cachexia, c lubbing, lymphadenopathy, radiation marks, and mastectomy scar), stigmata of chronic liver disease, cardiac failure, hypothyroidism, rheumatoid arthritis, butterfly rash of SLE. Test s CXR Small effusions blunt the costophrenic angles, larger ones are seen as water-dense sh adows with concave upper borders. A completely horizontal upper border implies that there i s also a pneumothorax; an effusion-side-down chest radiograph may be helpful in detecting a n effusion and determining whether it is free flowing or loculated. US is useful in identif ying the presence of pleural fluid and in guiding diag- nostic or therapeutic aspiration. D iagnostic aspiration Percuss the upper border of the pleural effusion and choose a site 1 \200\2232 intercostal spaces below it. Infiltrate down to the pleura with 5 \200\22310 mL o f 1% lidocaine. Attach a 21 French (F) needle to a syringe and insert it just above the upp er border of an appropriate rib (avoids neurovascular bundle). Draw off 10 \200\22330 mL of pleural fluid and send it to the lab for clinical chemistry (protein, glucose, pH, LDH, am ylase), bacteriology (Gram and AFB staining, bacterial and TB culture), and cytology . 190 Pleural biopsy If pleural fluid analysis is inconclusive, consider parietal pleu- ral biops y. Video-assisted thoracoscopy or CT-guided pleural biopsy will increase diagnostic yield ( by enabling direct visualization of the pleural cav- ity and biopsy of suspicious areas). M anagement is of the underlying cause. \212Drainage: If the effusion is symptomatic, drain it, repeatedly if necessary. Fluid is best removed slowly ( \211 2 L/24 h). It may be asp irated in the same way as a diagnostic tap or using an intercostal drain (p. 661). e n i c i d e m y r a n o m u P \212Pleurodesis with tetracycline, bleomycin, or talc may be helpful for recur- rent effus ions. Thoracoscopic talc pleurodesis is most effective for malig- nant effusions. Empyemas (p. 161) are best drained using a chest tube drain, inserted under US or CT guidance. \212 Intrapleural streptokinase: Doubtful benefit. \212Surgery: Persistent collections and incr eased pleural thickening may require l video-assisted thoracoscopy or open thoracotomy. Table 6.12 Pleural fluid analysis Gross appearance Clear, straw-colored Turbid, yellow Cause Transudate, exudate Empyema, parapneumonic effusion Hemorrhagic Trauma, malignancy, pulmo- nary infarction Cytology Neutrophils ++ Lymphocytes ++ Parapneumonic effusion, PE Malignancy, TB, rheuma- 191 toid arthritis (RA), SLE, sarcoidosis Mesothelial cells ++ Abnormal mesothelial cells Multinucleated giant cells Lupus erythemato sus cells Clinical chemistry Pleural fluid/serum protein <0.5 and Pleural fluid/serum LDH < 0.6 and Pleural fluid LDH <2/3 top normal Pulmonary infarction Mesothelioma RA SLE If all 3 criteria are met, effusion is a transudate. Otherwise, it is an exudate serum LDH Glucose <60 mg/dL Empyema, malignancy, TB, RA, SLE pH <7.2 Empyema, malignancy, TB, RA, SLE LDH ^ (pleural: Serum >0.6) Empyema, malignancy, TB, RA, SLE Amylase ^ Pancreatitis, carcinoma, bacte- rial pneumonia, esophageal rupture Sarcoidosis Sarcoidosis is a multisystem noncaseating granulomatous disorder of unknown cau se. Prevalence in the United States is 5/10 5 of the population among Caucasians, 40/10 5 a mong African Americans. It commonly affects adults aged 20 \200\22340 yrs. African American s are affected more severely than Caucasians, particularly by extrathoracic disease. Clinic al features Asymptomatic: In 20 \200\22340%, the disease is discovered inci- dentally, afte r a routine CXR. Acute sarcoidosis often presents with ery- thema nodosum (PLATE 18) pol yarthralgia; acute sarcoidosis usually resolves spontaneously. Pulmonary disease: 90% have abnormal CXRs with bilateral, symmetrical, hilar lymphadenopathy (BHL) pulmonary infiltr ates or fibrosis. Symptoms: Dry cough, progressive dyspnea, exercise intolerance and chest pain. In 10 \200\22320%, symptoms progress, with concurrent deterioration in lung function. Nonpulmonary manifestations : Lymphadenopathy, hepatomegaly, splenom- egaly, uveitis, conj unctivitis, keratoconjunctivitis, glaucoma, terminal pha- langeal bone cysts, enlargement o f lacrimal and parotid glands, Bell \200\231s palsy, neuropathy, meningitis, brainstem and spinal syndromes, space-occupying lesion, erythema nodosum (PLATE 18), lupus pernio, subcut aneous nod- ules, cardiomyopathy, arrhythmias, hypercalcemia, hypercalciuria, renal stones, pituitary dysfunction. Investigations Blood tests: \206\221 ESR, lymphopenia, abnormal LF TS, \206\221 serum angiotensin-converting enzyme \206\221 immunoglobulins. 24 h urine: Ca 2+ \206\221 ; hyper- calciuria. Tuberculin skin test is \200\223ve in two-thirds. CXR is abnormal 90%. Stage 0: Normal. Stage 1: BHL. Stage 2: BHL + peripheral pulmonary infiltrat es. Stage 3: Peripheral pulmonary infiltrates alone. Stage 4: Progressive pulmonary fibrosi s; bulla formation (honeycombing); pleural involvement. See Table 6.13. ECG may show arrhyt hmias or bundle branch block. Lung function tests may be normal or show reduced lung volume s, impaired gas transfer, and a restrictive lung disorder. Tissue biopsy (lung, liver, lymp h nodes, skin nodules. or lacrimal glands) is diagnostic and shows noncaseating granulomata . BAL shows \206\221 lymphocytes in active disease; \206\221 neutrophils with pulmonary f ibrosis. US may show nephrocalcinosis or hepatosplenomegaly. Bone x-rays show \200\234punc hed out \200\235 lesions in terminal phalanges. CT/MRI may be useful in assessing severity of pulmonary disease or diagnos- ing neuro-sarcoidosis. Ophthalmology assessment (slit lamp examination, fluo- rescein angiography) is indicated in ocular disease. Kveim tests are ob solete. Management Patients with BHL alone do not require treatment since the majority reso lve spontaneously. Acute sarcoidosis: Bed rest, NSAIDs. Indications for corticosteroid ther apy: \212 \212 \212 \212 Prednisone (40 mg/24 h) PO for 4 \200\2236 wks, then reduce do se over 1 yr according to clinical status. A few patients relapse and may need a further co urse or long-term therapy. In severe illness, IV methylprednisolone or immunosuppressants ( methotrexate, cyclosporin, azathioprine, cyclophos- phamide) may be needed. Prognosis 60% o f patients with thoracic sarcoidosis show spontaneous resolution within 2 yrs. 20% of patie nts respond to steroid therapy. In the remainder, improvement is unlikely despite therapy. For differential diagno- ses, see Table 6.14. 192 Parenchymal lung disease (symptomatic, static, or progressive) Uveitis Hypercalcemia Neurol ogical or cardiac involvement. e n i c i d e m y r a n o m u P Table 6.13 Causes of bilateral hilar lymphadenopathy (BHL) Infection TB Mycoplasma Lymphoma Carcinoma Mediastinal tumors Silicosis Berylliosis Malignancy Industrial dust disease l Extrinsic allergic alveolitis Table 6.14 Differential diagnosis of granulomatous diseases Infections Bacteria TB Leprosy Syphilis Cat scratch fever Cryptococcus Fungi neoformans Histoplasma capsu- latumCoccidioides immitis Schistosomiasis 193 Protozoa Primary biliary cirrhosis Granulomatous orchitis Giant cell arteritis Polyarteriti s nodosa Takayasu \200\231s arteritis Wegener \200\231s granulomatosis Silicosis Berylliosi s Crohn \200\231s disease de Quervain \200\231s thyroiditis Sarcoidosis Autoimmune Vasculitis Industrial dust disease Idiopathic Extrinsic allergic alveolitis Histiocytosis X Hypersensitivity pneumonitis/Extrinsic allergic alveolitis (EAA) In sensitized individuals, inhalation of allergens, fungal spores, or proteins provoke a hypersensitivity reaction. I n the acute phase, the alveoli are infiltrated with acute inflammatory cells. With chronic exposure, granu- lomatous formation and obliterative bronchiolitis occur. Eosinophilia is s pecifically absent. Causes (representative examples) \212Bird fancier \200\231s and pigeon fancier \200\231s lung : Proteins in bird droppings of pigeon, chicken, parakeet, turkey \212Farmer \200\231s lung : Thermophilic actinomycetes \212Malt worker \200\231s lung : A spergillus fumigates or A. clavatus \212Bagassosis : Thermophilic actinomyces \212Cheese washer \200\231s lung : Penicillium casei \212Familial hypersensitivity pneumonia : Bacill us subtilis \212Furrier \200\231s lung : Animal fur particles \212Mushroom worker \200 \231s lung : Thermophilic actinomycetes \212Suberosis : Cork dust, Penicillium glabrum \212Wood worker \200\231s lung : Oak, cedar, pine, mahogany dusts Clinical features 4 \200 \2236 h postexposure, Acute: Fever, rigors, myalgias, dry cough, dyspnea, crackles (no whee ze). Subacute : Usually occurs over a 2-wk interval with cough and shortness of breath. Chr onic: \206\221 Dyspnea, weight \206\223 , exertional dyspnea, progressive hypoxemia. Test s Acute: Blood: CBC (neutrophilia); ESR \206\221 ; ABGs; eosinophilia is not present; posi tive serum precipitins (indicate exposure only). CXR: Mid-zone mottling/consolidation; hila r lymphadenopathy (rare). HRCT yields greater definition of lung parenchymal changes, speci fically, ground-glass infiltrates, reticulonodular or alveolar consolidation patterns. Lung function tests: Restrictive pulmonary disease findings; reduced diffusion capacity during acute attacks. Chronic: Blood: Positive serum precipitins. CXR: Upper-zone fibrosis; hon- e ycomb lung. Lung function tests: Persistent changes (see above). BAL fluid shows \206\221 lymphocytes and mast cells. Management Acute attack: Remove allergen and give O 2 (35 \200 \22360%), then: \212 \212 Chronic: Avoid exposure to allergens or wear a face masks. Long -term ste- roids often achieve radiographic and physiological improvement. 194 Hydrocortisone 200 mg IV Prednisone (40 mg/24 h PO), followed by reducing dose Hypersensitivity pneumonitis with eosinophilia In contrast to hypersensitivity pneumonitis related to fungi, proteins, aller- gens, and the lack of eosinophilia, this group of disord er is associated with serum and pulmonary eosinophilia. The original description by Loeffle r was a presentation of a benign migratory pneumonitis associated with eosinophilia; the cl inical course was usually self-limiting, and most cases were subsequently attributed to a p arasitic infection or to an adverse reaction to medications. The latter includes the classi c culprits, nitrofurantoin, sulfonamides, penicil- lin, thiazide diuretics, gold salts, hyd ralazine, isoniazid, and chlorpropamide. Other pulmonary syndromes with eosinophilia are al lergic bronchopulmo- nary aspergillosis, acute eosinophilic pneumonia, allergic granulomato sis of Churg-Strauss, and chronic eosinophilic pneumonia. In most instances, the clinical presentation is one of a mild pneumonia with peripheral eosinophilia and with tran sient, peripheral infiltrates on CXR. BAL in these patients will usually yield a high perce ntage of eosinophils (>25%). However, in chronic eosinophilic pneumonia and in the hypereos inophilia syndrome, systemic symptoms of fever with constitutional symptoms exist; multiorg an involve- ment, especially cardiac involvement, is discovered in hypereosinophilia syndro me. In hypersensitivity pneumonitis with eosinophilia, treatment with glucocorti- costeroid s most often produces immediate resolution of clinical symptoms and radiographic findings. Nonetheless, in chronic eosinophilic pneumonia, recurrence is common; in the hypereosinophi lia syndrome, because of the cardiac complications, and in contrast to the benignity of oth er eosinophilic syndromes, a high morbidity and mortality occurs. e n i c i d e m y r a n o m u P l Pulmonary hypertension Pulmonary hypertension is defined by an increase in pulmonary artery pressure and secondary changes of the right ventricular anatomy or func- tion. A normal me an arterial pulmonary artery pressure is 8 \200\22320 mm Hg; determined by cardiac catheter ization or by echocardiography, pulmonary artery hypertension is present when the mean pulm onary artery pressure is >25 mm Hg, with a pulmonary capillary wedge pressure of <15 mm Hg. Furthermore, if, during exercise, the mean pulmonary artery pressure is >30 mm Hg, then pu lmonary artery hypertension is present. Pulmonary hypertension should be considered as prim ary or secondary and is best categorized in five groups: \212Idiopathic pulmonary hyperten sion is a rare group, 20% of which may be familial; may be related to medications/drug use and to collagen vas- cular diseases. Usually more common in women; pulmonary capillary wedg e pressure is normal. Histological findings include vasoconstriction, inflammatory changes, and vascular proliferation in small pulmonary arterioles. 195 \212Pulmonary hypertension with left-heart disease: Valvular heart disease or left ventric ular failure; increases in mean pulmonary capillary wedge pressure \212 Pulmonary hypertension associated with primary lung disease and/or hypoxemia: Associa ted with copd, interstitial fibrosis, restrictive lung diseases \212Pulmonary hypertension caused by chronic thromboembolism disease/ PE \212 Miscellaneous causes of pulmonary hypertension: Sarcoidosis, chronic anemia The most important component of treatment of pulmonary hyperten- sion is the establishment of the diagnosis and the inclusion or exclusion of causative disease; e.g., anticoagulation in recurrent PE or modification of chronic hypoxemia from COPD or interstitial lung diseas e with supple- mental oxygen. Other forms of therapy include calcium-channel blockers causi ng vasodi- latation and decrease in pulmonary artery pressure; endothelial receptor antagon ists, which may improve exercise tolerance; phosphodiesterase inhibitors, which modify micr ovascular growth and enhance vasodilatation; and prostacyclins, which inhibit vascular smoo th muscle growth, dilate the microvasculature, and result in platelet inhibition. Once pulm onary hypertension is physiologically entrenched, the mean sur- vival is 2 \200\2233 yrs; i f patients have a functional cardiac classification of VI, then their mean survival is <6 m onths; death is usually secondary to right-heart failure, progressive hypoxemia, and hypote nsion. Industrial dust diseases Coal worker \200\231s pneumoconiosis (CWP) results from inhalation of coal dust particles (1 \200\2233 mcm in diameter) over 15 \200\22320 yrs; these micropa rticles are ingested by macrophages that degenerate, release their enzymes and cause an inf lammatory reaction resulting in fibrosis. Clinical features: Asymptomatic, but coexisting c hronic bronchitis is com- mon. A high incidence of cigarette smoking is common in coal work ers. CXR : Many round opacities (1 \200\22310 mm), especially upper zone. Management: Avoid exposure to coal dust; treat coexisting chronic bronchitis. Progressive massive fibrosis ( PMF) is due to progression of CWP, which causes progressive dyspnea, fibrosis, and eventual ly, cor pulmonale. CXR : Upper-zone fibrotic masses (1 \200\22310 cm). Management: Avoid ex posure to coal dust. Caplan \200\231s syndrome is the association between rheumatoid arthri tis, pneumoconiosis, and pulmonary rheumatoid nodules. Silicosis is caused by inhalation of silica particles, which cause an intense fibrotic reaction. A number of jobs may be associ ated with exposure, e.g., metal mining, stone quarry exposure, sandblasting, and pottery/ce ramic manufacture. Clinical features : Progressive dyspnea, \206\221 incidence of TB, CXR shows diffuse miliary or nodular pattern in upper and mid-zones and egg-shell calcifi- cati on of hilar nodes. PMF may occur. Spirometry : Restrictive ventilatory defect. Management : Avoid exposure to silica. Asbestosis is caused by inhalation of asbestos fibers. Chrysotil e (white asbestos) is the least fibrogenic; crocidolite (blue asbestos) is the most fibroge nic. Amosite (brown asbestos) is the least common and has inter- mediate fibrogenicity. Asb estos was commonly used in the construction industry for fire-proofing, pipe wrapping, elec trical wire insulation, and roofing tile. Clinical features: Similar to other fibrotic lung diseases with progressive dyspnea, clubbing, and fine end-inspiratory crackles. Also cause s pleural plaques, \206\221 risk of bronchial adenocarcinoma and mesothelioma. Management: Symptomatic. Patients are often eligible for workers compensation. Byssinosis is an asthma tic, obstructive airways-type pulmonary-occupational disorder characterized by chest tightn ess and a decreased FEV 1 when exposed to cotton dust, flax, and hemp in the production of yarns and textiles. Classically, employees describe symptoms on the first day of work, with lessening of their frequency and intensity throughout the work week. A chronic form of bys sinosis may evolve over a period of years, resulting in COPD; especially found in cotton wo rker who are cigarette smokers. Current environmental control measures have reduced cotton dust exposure and thus reduced the incidence of byssinosis; the Occupational and Safety and Health Administration has specific cotton dust exposure guidelines and requires pulmonary function surveillance in cotton/textile workers. Beryllium is a lightweight, high-tensile-s trength metal with solid electri- cal conduction, commonly used in manufacturing of alloys, ceramics, and high-technology electronics. The importance of beryllium exposure is primari ly in the chronic form and in the patient \200\231s genetic makeup, which predisposes to a hypersensitive response to beryllium exposure. 196 Patient \200\231s sensitivity is associated with a genetic risk factor \200\224the presence of HLA-DPB 1 alleles that are positive for glutamate at position 69. Although beryllium ex posure has an acute form, chronic beryllium disease is similar to sarcoidosis and other gra nulomatous diseases. Clinical presentation and radiographic findings resemble sarcoidosis; pulmonary function studies are a mix of restrictive and obstructive patterns. Toxic occupat ional exposure Exposure to toxic substances usually causes tracheobronchitis, a noxious air way reaction or, in severe instances, may cause destructive alveolar injury. Toxic chemical s affecting the lung include acid fumes, ammonia, formaldehyde, hydrogen sulfide, isocyanid es, ozone and sulfur dioxide, and nitrogen dioxide. The severity of toxic exposure may vary from a mixing of volatile clean- ing agents in a closed bathroom to a massive chemical spi ll involving large populations. Ozone exposure results in a sterile inflammatory reac- tion associated with pulmonary macrophages releasing cytokines and pro-inflammatory mediators. Paraquat, a herbicide, induces acute lung injury; chlorine gas initiates an inflammatory re action in the airways and alveoli and is associated with an oxidative lung injury secondary to reactive chlorinated by-products; nickel fumes cause a diffuse alveolitis/pneumonitis; sulfur mustard may cause an acute respiratory distress syndrome, acute bronchitis, bronchio litis obliterans, or chronically evolving tracheobron- chial stenosis. Smoke inhalation is commonly encountered in fire-fighters; smoke inhala- tion and direct thermal injury to the airways are responsible for more deaths in fire victims and fire-fighters than are burn inj uries. The toxicity of smoke inhalation to the lungs is related to the materials combusted in a fire; e.g., burning plastics may produce cyanide and hydrochloric acid. The World Trad e Center attack and the collapse of the buildings produced pulverized cement with a high al kalinity, resulting in acute respiratory symp- toms and chronic lung disease. Follow-up stu dies of fire-fighters and victims with concentrated exposure from the New York catastrophe have defined a significant percentage of lung disease associated with long-term reduction i n lung function. For more causes of interstitial lung disease, see Table 6.15. Malignant me sothelioma is a neoplasm from mesothelial cells that usu- ally occurs in the pleura and rar ely in the peritoneum or other organs. Mesothelioma are associated with occupational exposu re to asbestos; asbestos exists as fibers, either amphiboles or chrysotile. Because the ris k of mesothelioma is more likely with amphibole exposure, the risk of meso- thelioma is rel ated to accumulative or total dose of exposure. >80% of patients report previous exposure t o asbestos; only 20% of patients have pulmonary asbestosis. The latent period between expos ure and develop- ment of a mesothelioma is 30 \200\22340 yrs, with rare occurrences at <20 years from exposure. Cigarette smoking does not affect the risk of developing mesothelioma. Incidence in the United States 3 \200\2237 cases/million; with 2,200 new cases per year. C linical features include chest pain, dyspnea, weight loss, finger clubbing, recurrent pleur al effusions. If the tumor has metastasized, there may be lymphadenopathy, hepatomegaly, bo ne pain/tenderness, abdominal pain/ obstruction (peritoneal malignant mesothelioma). 50% of malignant meso- thelioma metastases are usually local within the thorax or to the mediasti - num or pericardium. Tests: CXR/CT: Pleural thickening/effusion, decreased size of the hem ith- orax, bloody pleural fluid. Calcified pleural plaques are characteristic of asbestos e xposure, especially when calcified pleural plaques are along the diaphragms. e n i c i d e m y r a n o m u P l 197 Table 6.15 Causes of interstitial lung disease Granulomatous diseases Tuberculosis Sarcoidosis Amiodarone Bleomycin Busulfan Nitrofurantoin Sulfasalazine Ankylos ing spondylitis Rheumatoid arthritis SLE Systemic sclerosis Bird fancier \200\231s lung Drugs Connective tissue diseases Extrinsic allergic alveolitis/Hyper- Sensitivity pneumonia (EAA) (p. 184) Farmer \200\231s lung Malt worker \200\231s lung Mushroom picker \200\231s lung Pigeon fanc ier \200\231s lung Asbestosis Berylliosis Pneumoconiosis Silicosis Industrial dust diseases 198 Radiation Chronic pulmonary edema (mitral stenosis) Bronchiolitis obliterans/ organizing pn eumonia Idiopathic pulmonary fibrosis Individuals without evidence of mesothelioma yet with a history of asbestos exposure, with calcified or noncalcified pleural plaques, should be followed regularly; a routine asbestos evaluation includes a history and physical exam and pulmonary function studies, along with CXR and, if necessary, chest CT for detection of pleural or lung parenchyma neoplastic typ e changes and for detection of functional lung changes. Diagnosis: Histology of tissue, fol lowing a pleural biopsy, video-assisted thoracic surgery, or limited thoracotomy. Often the diagnosis is made postmortem. Management/Treatment: Symptomatic care; no effective radiati on therapy or chemotherapy. Prognosis is very poor (<2 yrs, produces 2,400 deaths/yr in the United States). Cor pulmonale Cor pulmonale is defined as secondary right-sided cardiac modifications and r ight ventricular dilation and/or hypertrophy in response to primary lung disease, either pu lmonary vascular or lung parenchymal disorders. Causes include COPD, interstitial fibrosis, pulmonary vascular disorders, and neuromuscular and skeletal diseases (see Table 6.16). Al though cor pulmonale or right-heart failure results from primary lung conditions, the most common caus e of cor pulmonale is left-heart failure. Clinical features Symptoms include dyspnea, fatig ue, or syncope. Signs : Cyanosis, tachycardia, raised JVP with prominent a and v waves, rig ht ven- tricular heave, loud P 2 , pan-systolic murmur (tricuspid regurgitation), early dia stolic Graham Steell murmur, hepatomegaly and edema. Investigations CBC: Hemoglobin and hem atocrit \206\221 (secondary poly- cythemia). ABG: Hypoxia, with or without hypercapnia and /or presence of respiratory acidosis. CXR: Enlarged right atrium and ventricle, prominent p ulmonary arteries. ECG: Right axis deviation; right ventricular hypertro- phy/strain; enlar gement of P waves, P pulmonale. Pulmonary function studies assist in differentiating betwee n obstructive airways disease and restrictive pulmonary disease and in defining severity. E chocardiography reveals pulmonary hypertension, right ventricular func- tion, right ventric ular size, thickness, and paradoxical intraventricular sep- tum motion and gives an assessm ent of left ventricular function and mitral/ aortic valve functions. Management \212Treat underlying cause (e.g., COPD, pulmonary infections, or treatment of e n i c i d e m y r a n o m u P l left ventricular failure). \212Treat respiratory failure : In the acute situation, give 24% oxygen if P a O 2 <60 mm Hg. Monitor ABG and gradually increase oxygen concentration if P a CO 2 is stable. In COPD patients, LTOT for 18 h/d improves survival. Patients with chronic hypoxia, when clinically stable, should be assessed for LTOT. \212Treat cardiac failure with diuretics such as furosemide (e.g., 40 \200\223160 mg/24 h PO). Monitor electrolytes; treat with potassium supplements if neces- sary. Alternative : S pironolactone. 199 Table 6.16 Causes of cor pulmonale \212Lung disease Asthma (severe, chronic) COPD Bronchiectasis Pulmonary fibrosis Lung resection \212Pulmonary vascular disease PE Pulmonary vasculitis Primary pulmonary hypertension Pulmonary hypertension secondary to left-heart failure Sickle-cell disease Parasite infestation \212Thoracic cage abnormality Kyphosis Scoliosis Thoracoplasty \212Neuromuscular disease Myasthenia gravis Poliomyelitis Motor neuron disease \212Hypoventilation Sleep apnea/hypopnea syndrome Obesity Cerebral vascular disease \212 \212 Prognosis Poor; once symptoms and signs of cor pulmonale develop, 50% of patien ts die within 5 yrs. Consider Consider phlebotomy if the hematocrit is >55%. heart \200\223lung transplantation in young patients. Obstructive sleep apnea/hypopnea syndrome Obstructive sleep apnea/hypopnea syndrome is defi ned as daytime sleepi- ness associated with a minimum of five obstructive-type breathing ev ents per hour of sleep; the events are apnea, defined as pauses of breathing last- ing >10 sec, and hypopnea, defined as reduced ventilation by at least 50% for >10 sec during contin uous breathing. The cause of sleep apnea/hypopnea syndrome is related to relaxation of uppe r airway musculature and resultant inward movement of the upper airway soft tissue in inspi ration during sleep. Predisposing factors include excessive weight, BMI of >30; male sex; s hortened jaw and/or mandible; and age 40 \200\22365 yrs. The syndrome may occur in children with enlarged tonsils and adenoids. Clinical points important in completion of the diagnos is include daytime sleepiness, reduced cognitive performance, depression, disturbed sleep, hypertension, morning headaches, decreased libido, increased incidence of auto accidents. C linical factors related to the sleep apnea/hypopnea syndrome are a greater risk of cardiova scular and cerebral vascular events; an association with DM related to increased insulin re sistance; an elevation of liver function stud- ies, unrelated to obesity; and, last, a high er risk of anesthesia and surgical procedures. Diagnosis \212 \212 \212 Investigations S imple studies (pulse oximetry, video recordings) may be all that are required for diagnosis . Polysomnography (which monitors oxy- gen saturation, airflow at the nose and mouth, ecg, and electromyogram [emg] of chest and abdominal wall movement during sleep) is diagnostic. The occurrence of \211 15 episodes of apnea or hypopnea during 1 h of sleep indicates sig nificant sleep apnea. The comparison of home- versus hospital-/ office-based sleep studies reveals the home studies (especially in screening scenarios) are more cost effective, with similar clinical outcomes. Management \212 \212 \212 \212 200 Detailed history from patient and patient \200\231s partner Sleep questionnaire Physical ex amination; BP readings; jaw and oral pharynx exams Weight reduction Avoidance of tobacco and alcohol CPAP Continuous positive airway pressure during sleep is effective. Surgical procedures to relieve pharyngeal obstruction (tonsillec tomy, uvulopalatopharyngoplasty, or tracheostomy) are occasionally necessary. Treatment/Outcomes \212 \212 \212 \212 \212 Without daytime sleepiness and other dayti me performance aberrations, patients with obstructive sleep apnea/hypopnea syndrome have do ubtful clinical outcomes. Reduces sleepiness and improves quality of life Improves cognition Diminishes driving risk Hypertension resolves or is more easily controlled Betterment of work performance Lung transplantation Lung transplantation is performed at a frequency of approximately 2,20 0 cases per year. The underlying pulmonary diseases for which lung trans- plantation is a t reatment option are COPD,30%; interstitial lung disease, 30%; CF, 15%; 1 -antitrypsin de ficiency, 3%; and primary pulmonary artery hypertension, 2%. Recipients of donor lungs basi cally do not have therapeutic options; their predictive transplant survival should be subst antially greater than their native lung disease prognosis. Additionally, the recipient \200 \231s quality of life should be predictably better with lung transplantation than with thei