164 polymerase chain reaction (PCR) and culture. Treatment : Erythromycin, azithromycin, tetrac ycline, clarithromycin, fluoroquinolones. Chlamydia psittaci causes psittacosis, an ornitho sis acquired from infected birds, parrots, parakeets, turkeys, and ducks; greatest exposure to bird owners and poultry workers. Symptoms include headache, fever, dry cough, lethargy, arthralgia, anorexia, and diarrhea. CXR shows patchy consolida- tion. Diagnosis: Chlamydia serology. Treatment : Tetracycline 250 mg qid for at least 3 wks to avoid relapse; also er ythromycin 500 mg qid. Viral pneumonia: The development of viral diagnostic studies, PCR, t issue cultures, and immunofluorescence, have improved the detection of viruses; viral analy zes have discovered viruses as a more frequent causative agent in both CAP and in HAP, with an incidence of 15 \200\22318%. In CAP, the most common viruses are influenza A/B and resp iratory syncytial virus, as well as adenovirus, parainfluenza virus, rhinovirus, coronaviru s, and the SARS virus; in HAP, the causative viruses are herpes simplex and cytomegalovirus . Pneumocystis pneumonia : Pneumocystis is a world -wide distributed fungus that commonly c olonizes immunosuppressed patients and persons with COPD. This opportunistic organism is a frequent cause of pneumonia in immunocompromised patients. Combination of cellular and humo ral deficiencies predispose to Pneumocystis infection. Clinical presentation is relatively nonspecific; CXR may be normal or show bilateral perihilar interstitial infiltrates. Diagno sis: Visualization of the organism in induced sputum, BAL, or in lung biopsy specimens. Tre atment : First choice is trimethoprim-sulfamethoxazole, 14 d treatment for non-HIV; 21 d th erapy for HIV patients. Alternative treatments include trimethoprim with dapsone, clindamyc in plus primaquine, pentamidine. Prophylaxis for Pneumocystis: First choice is trimethoprim -sulfamethoxazole, in patients with and without HIV, recovering from Pneumocystis pneumonia . e n i c i d e m y r a n o m u P l 165 Complications of pneumonia Respiratory failure (p. 176): Hypoxemia, respiratory failure ( P a O 2 <60 mm Hg) is relatively common. Treatment is with high-flow (60%) oxygen. Transfer the patient to icu if hypoxia does not improve with O 2 therapy or P a CO 2 rises to >45 mm Hg. Careful O 2 administration is required in COPD patients; check ABG frequently and cons ider elective mechanical ventilation if rising P a CO 2 or worsening acidosis and hypoxemia . Hypotension may be due to a combination of dehydration and vasodilata- tion due to bacter emia/ sepsis. If systolic blood pressure (BP) is <90 mm Hg, give an IV fluid challenge of 2 50 mL colloid/crystalloid over 15 min. If BP does not rise, insert a central line and infus e IV fluids to maintain the systolic BP >90 mm Hg. If systolic BP remains <90 mm Hg despite fluid therapy, asses for vasopressive support. Atrial fibrillation (p. 120) is a quite com mon arrhythmia, particularly in the elderly; usually resolves with treatment of the pneumon ia. Digoxin, calcium-channel blockers, or \222 -blockers may be required to slow the ven- tricular response rate. Pleural effusion Inflammation of the pleura by adjacent pneumonia m ay cause fluid exudation into the pleural space. If fluid accumulates in the pleu- ral spac e faster than reabsorption, a pleural effusion develops. If the effusion is small, <10% of the hemithorax area, then it may be of little consequence. If it becomes larger and symptom atic, or infected (empyema), drainage is required (pp. 180, 661). Empyema is pus within the pleural space; clinically suspected if a patient with pneumonia and a pleural effusion doe s not respond to antibiotic therapy or if a patient with a resolving pneumonia develops a r ecurrent fever. Diagnosed by clinical features and a CXR indicating a pleural effu- sion. The aspira ted pleural fluid is typically yellow and turbid, or with frank pus, with a pH <7.1, glucos e \206\223 , and lactate dehydrogenase(LDH) \206\221 . The empyema should be drained usin g a chest drain, preferably inserted under sonographic guidance. Lung abscess is a cavitati ng area of localized, suppurative infection within the lung. Causes: \212 \212 \212 \212 \212 \212 Clinical features: Cyclical fever; cough; purulent, foul-smelling sputum; pleu- ritic chest pain; hemoptysis; malaise; weight loss. Look for finger clubbing, anemia. Empyema develops in 20 \200\22330% of lung abscesses. Tests: Blood: CBC (anemia, neutrophi lia), erythrocyte sedimentation rate (ESR), CRP, blood cultures. Sputum: Microscopy, cultur e, and cytology. CXR : Walled cavity, often with a fluid level. Consider CT scan to exclude obstruction, and bronchoscopy to obtain diagnostic specimens. Treatment: Antibiotics as in dicated by sensitivities; continue until healed (4 \200\2236 wks). Postural drainage. Repea ted aspiration, antibiotic instillation, or surgical excision may be required. Septicemia m ay occur as a result of bacterial spread from the lung paren- chyma into the bloodstream. B acteremia may cause physiologic changes of hypotension, tachycardia, renal insufficiency, a nd metastatic infection (e.g., infective endocarditis, meningitis). Treatment is with IV an tibiotic according to sensitivities. Pericarditis and myocarditis may also complicate pneum onia. Jaundice This is usually cholestatic, and may be due to sepsis or secondary to antibi otic therapy (particularly penicillin or erythromycin derivatives). Inadequately treated pneumonia Aspiration (e.g., alcoholism, esophageal obstruction, bulbar palsy) Bronchial obstruction (tumor, foreign body) Pulmonary infarction Septic emboli (sep ticemia, right-heart endocarditis, IV drug use) Subphrenic or hepatic abscess. 166 Cystic fibrosis Cystic fibrosis (CF) is an autosomal recessive disease that is classically detected in childhood, yet 5% of patients are diagnosed with CF as adults. The primary muta tions occur in CFTR gene found on chromosome 7; at least, 1,400 mutations have been documen ted. CF manifests ethnic variabil- ity with 1 in 3,000 Caucasian births 1 in 17,000 births in African Americans and 1 in 90,000 in Asian populations. Although in previous decades the life expectancy of a CF patient was short, today \200\231s median survival is >40 yrs. The genetic defect in the CFTR gene causes abnormalities in sodium absorp- tion and in chlorid e secretion; this dysfunction of electrolyte movement affects normal hydration of the pulmo nary airways, pancreatic ducts, sweat glands, and sex glands. This genetically induced dehy dration within the air- ways impairs ciliary movement and airway clearance, both primary de fense mechanisms, thus leading to susceptibility to infections. See Table 6.3. Clinical man ifestations Neonates and early childhood: Common presentation in neonates; one-fifth of neo nates present within 24 hours of birth with GI obstruction, meco- nium ileus, emesis, inabi lity to pass stool; within the first 2 yrs of life, respi- ratory tract infections are prom inent, along with recurrent sinusitis. Children and young adults: As with early childhood, respiratory manifestation are major; however, with older ages the evolution of pancreatic i nsufficiency and insulin deficiency are common. Respiratory: Cough, wheeze, recurrent infections, bronch iectasis, pneumothorax, common in 10% of CF patients, hemoptysis, respiratory failure, cor pulmonale. Gastrointestinal: Pancreatic insufficiency (DM, steatorrhea), distal intestinal obstruction syndrome ( \200\234meconium ileus equivalent \200\235), gallstones, cirrhosis. Other: Male infertility, osteoporosis, arthritis, vasculitis, nasal polyps, sinusitis, and hypertrophic pulmonary osteoarthropathy (HPOA). Signs: Cyanosis, finger clubbing, bilateral coarse crackles. Diagnosis The diagnosis of CF is usually apparent especially at younger a ges; nonetheless, the combination of clinical presentation and an abnormal sweat chloride o r an abnormal nasal potential differential (PD) measure- ment complete the diagnosis: An el evated sweat chloride is pathognomonic for CF. Furthermore, CFTR analysis is available. In the 5% of the adult popu- lation who have CF, the diagnosis may be more insidious; 1 \200 \2232% of CF patients have a normal sweat chloride study yet their nasal PD measure- ments are abnormal . Sweat test: Sweat sodium and chloride >60 mmol/L; chloride usually > sodium. Genetics: cftr mutation analysis; DNA testing identifies CF mutations in over 90% of patie nts with CF. Tests Blood: CBC, electrolytes, LFTs; clotting; vitamin A, D, E levels; annual glucose tolerance test. Bacteriology: Cough swab, sputum culture. Radiology: CXR : Hyperin flation, bronchiectasis. Abdominal US: Fatty liver, cirrhosis; chronic pancreatitis. Spirom etry: Obstructive defect. Aspergillus serology/skin test (20% develop allergic bronchopulmo nary aspergillosis [ABPA; p. 164]). Biochemistry: Fecal fat analysis. e n i c i d e m y r a n o m u P l Table 6.3 Management of cystic fibrosis 167 The cornerstones of treatment are the control of infections with anti- biotics, the movemen t of secretions with inhalational treatments and mucous-modifying agents, the use of chest physiotherapy, and the cre- ation of a multidisciplinary plan involving parents, nurses, re spiratory therapists, dieticians, and psychologists. Although 95% of CF patients expire as a consequence of pulmonary infections, the use of antibiotics in acute events, as well as t heir use in preventative therapy, have dramati- cally improved survival. The most common or ganisms are Pseudomonas , and S. aureus , H. influenza. Antibiotics in acute circumstances are admin- istered IV; in subacute or chronic situations, antibiotics may be given orally a nd in inhalational solutions/therapy. With mild exacerbations, oral penicillin, cephalospor in, or ciprofloxacin, along with inhaled tobramycin or Colistin and chest physiotherapy are effective. In moderately severe or severe infections, antibiotic coverage is broadened to include cepha- losporins and aminoglycosides IV, along with hospitalization and aggres- siv e chest physiotherapy and antibiotic inhalational treatment. Therapies to diminish the visc osity of the chronically infected sputum are mucolytic agents, hypertonic saline, and recom binant DNA. Breathing exercises, chest percussion, postural drainage, and mechanisms to imp rove mucociliary clearance are instrumental along with antibiotics in preserving lung funct ion and modifying the progression of CF. Gastrointestinal : Pancreatic enzyme replacement; fat soluble vitamin sup- plements (A, D, E, K); ursodeoxycholic acid for impaired liver fun ction. Other : Treatment of CF-related DM; screening for and treatment of osteoporosis; tre atment of arthritis, sinusitis, and vasculitis; fertility and genetic counseling. Advanced lung disease : Oxygen, diuretics (cor pulmonale); noninvasive ventilation; lung or heart/lu ng transplantation. Prognosis : Median survival is >37.4 yrs. Bronchiectasis Bronchiectasis is a chronic infection of primarily the medium-sized airways, which results in irreversible dilation and destruction of the normal airway architecture. Bronchiectasis may be localized to one lobe or may be dif- fuse, involving all lobes of the lung; the extent of disease has a significant impact on clinical outcome. Classically, inf ections with Bordetella pertussis (whooping cough) in childhood have been associated with t he development of bronchiectasis. Pulmonary infections with Staph, Klebsiella, Pseudomonas , Haemophilus, and anaerobes, as well as with adenovirus and influenza virus may be respons ible for the evolution of bronchiectasis. Tuberculosis is the major cause of bronchiectasis worldwide; atypical Mycobacterium infections may be a primary causative bacterium or more usually is a secondary infection. CF, with its thickened secretions and poor mucociliary cl earance, is notoriously associated with bronchiectasis. Other predisposing causes of bronch iectasis include primary ciliary dyskinesis, hypogammaglobulinemia, HIV infections, endobro nchial obstruction by a foreign body, and 1 -antitrypsin deficiency, as well as allergic bronchopul- monary aspergillosis, rheumatic diseases, and inhalation of toxic fumes. Clini cal features Symptoms: Constant or recurrent coughing of purulent sputum associated with re current respiratory tract infection is common in bronchiectasis; hemoptysis is common, occu rring in 50 \200\22370% of patients. Historically, patients may recall an episode of pneumo nia after which their symptoms of chronic cough started. On physical exam, auscultation of the chest may disclose a variety of sounds (crackles, rhonchi, wheezes), along with clubbin g of digits, peripheral cyanosis, and signs of cor pulmonale. Complications: Pneumonia, ple ural effusion; pneumothorax; hemoptysis; cerebral abscess. Investigations Sputum culture . CXR: Cystic shadows, thickened bronchial walls (streetcar-tracking and ring shadows) Routin e CXRs are the usual ini- tial study, yet the most definitive radiographic study is CT and, especially, HRCT of the chest ; it assesses the extent and distribution of disease. The fi ndings are specific to the airways, with dilated thickened airways, cystic changes within t he lung parenchyma with or without fluid levels, and sac- cular and peribronchial inflammat ory changes of the airways. Spirometry often shows an obstructive airway pattern; reversibi lity with bronchodila- tors should be assessed. Bronchoscopy: Used to locate site of hemopt ysis or exclude obstruction. Other tests: Serum immunoglobulins, CF sweat chlo- ride test, Aspergillus precipitins. Management/Treatment Treatment is fourfold: Treat infection, impro ve tracheobronchial clearance, diminish airway inflammation, and diagnose and/or reverse pr edisposing factors. Antibiotic selection is based on the clinical findings of acuity and on Gram stain and cultures; most commonly Pseudomonas and other gram-negative organisms, as w ell as Staph, are the offending bacteria; treatment with aminoglycosides and third-generati on cephalosporins (e.g., carbapenem) is based on antibiotic sensitivity; in gen- eral, bron chiectasis requires a longer duration of treatment than other pul- monary infections, usual ly 14 \200\22321 d. Medicated aerosol therapy with bronchodilators and normal saline dimini sh bronchial obstruction and promote bronchial dilation and thus airway clear- ance, especi ally in individuals with bronchiectasis with airway hyperactivity. Mucolytic agents and hyd ration of airways with IV fluid replacement or oral intake may thin secretions. Chest percu ssion and postural drainage may also facilitate secretion removal/expectoration. Fiberoptic bronchoscopy may be beneficial in instances of mucous plugging and airway obstruction. Dec reasing generalized inflammation in airways is addressed with antibiotic treatment and puru lent secretion removal; anti-inflammatory agents, such 168 as leukotriene receptor antagonists and inhaled glucocorticosteroids, may be additive in re ducing airway inflammation. In instances of localized bron- chiectasis, surgery in the form of lobectomy is a reasonable approach to eliminating recurrent infections or hemoptysis; i n cases of massive hemop- tysis emanating from a specific lobe, surgical resection is relev ant. A new approach in massive hemoptysis is bronchial artery embolization, most effectivel y used in cases of diffuse bronchiectasis where a single lobectomy is not indicated. e n i c i d e m y r a n o m u P Lung abscess Lung abscess is defined as an infectious process associated with necrosis of t he lung parenchyma. Lung abscess are categorized as acute and chronic, and primary versus s econdary. Acute lung abscesses occur with an immedi- ate illness, whereas chronic lung absc esses are detected symptomatically or radiographically over 4 \200\2236 wks. Secondary lung abscesses occur with CF or in HIV infection, with lung neoplasms, in contrast to a primary lung abscess that develops in the absence of underlying pulmonary disorders (e.g., alcohol ic-related aspiration). Common symptoms are fever, cough, fatigue, weight loss; lung absces ses are usually found in individuals with poor dental hygiene, pyorrhea, or gingivitis. Phy sical examination is typically unrevealing; chest radiographs and chest CT are the primary methods for detecting and defining a lung abscess. Routine sputum analysis is usually unrel iable due to contamination of the specimen by upper airway organisms. Bronchoscopy with bro nchial lavage should be helpful in establishing a diagnosis; CT-guided percutaneous drain- age of a lung abscess may provide more specific identification of the cause and thus may fa cilitate more accurate antibiotic treatment. Anaerobic bacteria are the most common finding in a primary lung abscess; other causes may include Mycobacterium tuberculosis, Blastomyco sis, Histoplasmosis , Coccidioidomycosis, and atypical mycobacterium. In immu- nocompromise d patients, causes of lung abscess are aspergillosis, Nocardia, Legionella, and Klebsiella pneumonia , in addition to the more common causes. In previously healthy individuals, S . a ureus, Streptococcus , and Klebsiella and Actinomyces are causative considerations. Treatme nt is based on identification of the causative organism; if an empy- ema is present, then p leural drainage is important; surgical resection is a consideration in cases of nonresponsi veness to antibiotics, yet lung resec- tion is utilized in <10% of patients with lung absce ss. l 169 Fungal infection of the lung Aspergillus This group of fungi affects the lung in five ways: 1 Asthma: This group includes those patients with severe asthma who may not meet clinical criteria of allergic bronchopulmonary aspergillosis, yet have considerable reactivity to th e fungus; Aspergillus fumigates is a com- mon fungus, thus commonly may be associated with asthma. 2 Allergic bronchopulmonary aspergillosis: The syndrome of ABPA consists of active asthma, whole blood eosinophilia, increased IgE level, pulmo- nary infiltrates and bronchial obstru ction, bronchiectasis, and skin tests sensitivity to A. fumigatus . ABPA represent a hypers ensitivity reaction to the fungus and is found in 1% of asthmatics and in up to 15% of CF p atients. Symptoms: Wheeze, cough, sputum (plugs of mucus containing fungal hyphae), dyspnea , and \200\234recurrent pneumonia. \200\235 Investigations: CXR; transient segmental colla pse or consolidation, central bronchiectasis, fleeting infiltrates; Aspergillus in sputum; positive Aspergillus skin test and/ or Aspergillus -specific IgE RAST; positive serum precipitins; eosinophilia; raised serum I gE. Treatment: Corticosteroids/Itraconazole. 3 Aspergilloma: A \200\234fungus ball \200\235 within a pre-existing pulmonary cavity >2.5 cm in dimension; cavity often caused by TB, sarcoidosis; usually asymp- tomatic yet may ca use cough, hemoptysis, lethargy weight loss (see Figure 6.5). Most common complication i s life-threatening hemoptysis; may spontaneously resolve; however, the cavity is persistent ly infected. Investigations: CXR: Round opacity within a cavity, usually apical; sputum cul ture; strongly positive serum precipitins; Aspergillus skin test (30% +ve). Treatment : Sur gery. 4 Invasive aspergillosis is a true opportunistic organism in that primary risk factors for infection with this fungus are neutropenia and glucocorticoster- oid use; other risk factor s : HIV, leukemia, underlying pulmonary disease, Wegener \200\231s granulomatosis, and syst emic lupus erythematosus (SLE); treatment with antitumor necrosis factor may predispose to Aspergillus infection. Opportunistic infections are predominantly pulmonary and/or sinuses. Investigations: Sputum culture; serum precipitins; antigen detec- tion; CXR findings inclu de infiltrates, consolidation, or abscess; serum measurements of galactomannan ( Aspergillu s antigen) may be helpful. Diagnosis: Positive culture and confirmatory histology in affect ed tissue/ organ. In less than half of patients with invasive aspergillosis, the diagnosis is made postmortem. Treatment: IV itraconazole, caspofungin, micafungin, voriconazole, and Amphotericin B; voriconazole is preferred in invasive aspergillosis. 5 Hypersensitivity pneumonitis: Hypersensitivity to A. clavatus/fumigatus results in inters titial pneumonitis, eosinophilia associated with frequent expose to the fungus ( \200\234ma lt worker \200\231s lung \200\235). Clinical features and treat- ment are as for other caus es of EAA (p. 184). Diagnosis is based on a history of exposure and the presence of serum p recipitins to A. Clavatus/ fumigatus . Pulmonary fibrosis may occur if untreated. 170 Histoplasmosis Infection with Histoplasmosis capsulatum is by inhalation of the microconidi a; infections may vary from an asymptomatic presenta- tion to a life-threatening illness; s everity of illness depends on the extent of exposure, the health status of lungs, and cellu lar and humoral competence. In normal individuals residing in endemic areas, 50 \200\22380% may have chest radiograph or skin test evidence of prior exposure. In the United States, m ost common endemic areas are the Mississippi and Ohio River valleys. Most common presentati ons are in patients who seek medical attention with flu-like illnesses with chest radiograp hic changes of infiltrates associ- ated with mediastinum lymphadenopathy and with a course of spontaneous resolution. The enlargement and subsequent calcification of chest lymph node s is the most common finding in endemic areas, representing prior infection and usually req uiring minimal evaluation or medical follow-up care. In contrast, a most severe form of his toplasmosis is a progressive dissemi- nated form that is most often found in immunocompromi sed individuals with HIV having a low T-cell count and in patients on immunosuppressive med ications, such as prednisone and anti-tumor necrosis factor (TNF). A chronic form of histop lasmosis is found in patients with emphysema and persistent smokers; usually associated wit h progressive chest radiographic changes of advancing infiltrates with or without cavitatio ns. Treatment is recommended in the chronic progressive form and in progressive disseminate d histoplasmosis; preferred medications are lipid-formulations of Amphotericin B or Itracon azole; because acute his- toplasmosis is self-limiting and is without clinical injury, trea tment is not recommended. Coccidioidomycosis is a fungal infection endemic to south-central Arizona, the southwestern United States, and the southern portion of the San Joaquin Valley of California, commonly described as \200\234Valley Fever. \200\235 The fungus exists in the soil as a filament ye t subunits, arthroconidia , become airborne and cause disease through inhalation, predomina tely involving the lungs. Similar to histoplasmosis, coccidioidomycosis may be an asymptom- atic subclinical infection, may present as a CAP, or rarely may present in a disseminated form. Along with the pulmonary infection, several skin mani- festations of coccidioidomycos is occur and include erythema nodosum, erythema multiforme, and toxic erythema. Usually, ac ute coccidioidomycosis infections resolve within weeks and do not require treatment; howeve r, postinfection pulmonary nodules and cavi- ties are notable. In immunosuppressed patients , the fungal pneumonia may progress to a diffuse pneumonia and rarely progress to a dissemi nated dis- ease, not uncommonly including meningitis. The diagnosis is usually based on tra vel and/or living within the endemic areas, presenting as a CAP. Diagnostic findings : Pulm onary infiltrates and positive serologic studies, including tube precipitin, complement fix ation assays, immunodiffusion, and enzyme immunoassays to detect IgM and IgG antibodies. Co ccidioidomycosis may be easily grown on culture and thus direct cultures are useful. Treatm ent : Most cases of coccidioidomycosis do not need treatment; therapy is indicated in patie nts with a prolonged clinical course or who have extensive disease or in patients who are i mmunocompromised. Use fluconazole and itraconazole; Amphotericin in disseminated and mening itis cases. Blastomycosis is primarily a pulmonary infection, yet skin manifestations of ul ceration and verrucous lesions, as well as osteomyelitis, are common extrapulmonary conditi ons. Blastomycosis is found in the southeastern and south-central United States, and, simil ar to histoplasmosis, along the Ohio and Mississippi River basins. Acute blastomycosis pres ents with symptoms and signs of a community-acquired infection; it is frequently associated with epidemiological outbreaks. However, although spontaneous resolu- tion is reported, pr ogression is more usual. Most blastomycosis patients have a chronic pneumonia associated wi th fever, weight loss, and systemic symptoms. Blastomycosis has a high mortality rate in im munosuppressed patients. Diagnosis depends on the growth of the organism and Blastomyces an tigen detection in serum and in urinary assays. Treatment : Because prediction of those pat ients who may spontaneously resolve versus those patients who may progress/disseminate is i mpossible, almost all patients with blastomycosis require treatment with itraconazole, Amph otericin, or voriconazole. Cryptococcosis is a rare fungal infection in individuals with no rmal humeral and cellular immune systems; infections commonly occur in patients with hemato logic malignancies, HIV, with organ transplants, and in patients with high-dose glucocortic osteroids use. Cryptococcus infections are usually present as pneumonia or meningitis. Cryp tococcus is usually inhaled as aero- solized particulate matter, and, depending on the immu nologic status of the host, the organism is eliminated from the body or assumes a latent ph ase. A common presentation is chronic meningoencephalitis associated with head- ache, fever , and neurologic symptoms usually of several weeks duration. Pulmonary manifestations are l ess obvious with cough and possible fever, as numerous cases are discovered during an evalu ation of an abnormal chest radiograph in an immunosuppressed patient. With India ink prepar a- tion, Cryptococcus may be found in the cerebrospinal fluid (CSF), along with positive cu ltures in the CSF and blood; diagnosis is also made with e n i c i d e m y r a n o m u P l 171 the Cryptococcus antigen in CSF/blood. Treatment is with fluconazole for pulmonary Cryptoco ccus in an immunocompetent individual; for extrapul- monary manifestations, Amphotericin B; for immunosuppressed patients, combination therapy with fluconazole, Amphotericin B, and f lucytosine. Morbidity and mortality with and without treatment is high. Figure 6.5 172 After Kumar PJ, Clark ML. Clinical Medicine 2nd ed. London: Bailli re Tindall, 1990:686. Neoplasms of the lung Lung cancer is the leading cause of death in men and women; more pati ents die yearly from lung cancer than from breast, prostate, and colon cancers combined. Br onchogenic carcinoma accounts for about 30% of all cancer deaths/year. More women expire fr om lung neoplasm than from breast carcinoma; the 5-yr survival rate is now 15%; this surviv al improvement from previous decades is related to early detection and treatment regimens o f surgery, radiation therapy, and chemotherapy. 85% of lung neoplasms are caused by cigaret te smoking, found in both current smokers and former smokers. Conversely, 10 \200\22315% of lung neoplasms are discovered in indi- viduals who have never smoked; a majority of these non-cigarette related tumors are found in women. The major cell types are squamous cell car cinoma, adenocarcinoma, large cell carcinoma, and bronchoalveolar cell carcinoma. Although the distinc- tion of cell types is important due to the differing cell type responses to tr eatment and clinical courses, the categorization into small cell carcinoma and non-small ce ll carcinoma is ultimately beneficial in consideration of treatment and outcomes. See Table 6.4. Carcinoma of the bronchus Incidence is increasing in women. Risk fac- tors: Cigarette smoking is the major risk factor. Others : Asbestos, chro- mium, arsenic, iron oxides, and radiation (radon gas). Histology: Squamous (30%), adenocarcinoma (30%), small cell (25%), large cell (15%), alveolar cell carcinoma (<1%). Symptoms: Cough (80%), hemoptysis (70%), d yspnea (60%), chest pain (40%), recurrent or slowly resolving pneumonia, anorexia, weight l oss. Signs: Cachexia, anemia, clubbing, hypertrophic pulmonary osteoarthropa- thy causing j oint pain; supraclavicular or axillary lymphadenopathy. Chest signs : Chest exam may be nor mal yet may have auscultation/percussion findings of consolidation, collapse, pleural effus ion. Metastases : Bone ten- derness, hepatomegaly, confusion, seizures, myopathy, periphera l neuropa- thy. Lung neoplasms are uniquely associated with specific syndromes. Pancoast sy ndrome Neoplastic growth from the apex of the lung into the eighth cervical and first/secon d thoracic nerves resulting in pain radiat- ing into the arm and shoulder; often involving the first and second ribs. Horner \200\231s syndrome Enophthalmos (an eye recessed into the orbit); pto- sis (failure of eyelid opening); miosis (pupillary constriction), and, on the same side of the body, loss of sweating; the latter is related to sympathetic nerve invasi on by tumor. Superior vena cava syndrome Engorgement of the veins of the head, arms, and ne ck with facial edema associated with the obstruction of the superior vena cava by lung neop lasm; most instances of superior vena cava syndrome are medical emergencies. Treatment is a imed at alleviating ele- vated central venous pressure; usually represents a poor prognosis . Endocrine syndromes Hypercalcemia and hypophosphatemia associated with the production of PTH by a squamous cell carcinoma. Antidiuretic hormone (adh) secretion by a small cell carc inoma results in inappropriately low serum sodium levels. Adrenocorticotropic hormone(acth) : Ectopic secretion by a tumor causing clinical findings of cortisone excess. Eaton Lamber t syndrome is usually associated with a small cell carcinoma of the lung; presentation of m yasthenia gravis-like symptoms with proximal muscle and trunk weakness, with sparing of ocu lar dysfunction. Usually associated with increased muscle strength with repetitive contract ions, in e n i c i d e m y r a n o m u P l 173 contrast to myasthenia gravis, in which muscle strength decreases with repetitive contracti ons; minimal response to edrophonium. Trousseau \200\231s syndrome presents with migratory venous thrombophlebitis, especially with thrombosis in unusual areas of body. Tests Cytolog y : Sputum and pleural fluid. CXR : Peripheral abnormality or opacity; hilar enlargement; c onsolidation; lung collapse (X-RAY PLATE 4); pleural effusion; bony metastases. Peripheral lesions and superficial lymph nodes may be amenable to percutaneous fine-needle aspiration/ biopsy . Bronchoscopy : To yield a histological diagnosis and to begin staging. CT: To stag e the tumor. Radionuclide bone scan : For suspected metastases. Lung function tests : To as ses physiologic staging. Staging of a lung neoplasm requires a tissue diagnosis with lung o r bronchial biopsies or biopsies of areas of obvious neoplastic disease. Once the diag- nos is is established, then staging should be undertaken in two paths-one is anatomic staging a nd the other is physiologic staging. Anatomic staging utilizes CT scans of the chest, brain , and abdomen; PET scans to search for yet-undetected metastatic disease; bone scans to sea rch for osseous lesions. Refer to the anatomic staging Table 6.5 (p. 167). Physiologic stag ing is aimed at assessing the overall ability of a patient to withstand surgery, radiation therapy, or chemotherapy; this staging includes laboratory studies, pulmonary function stud ies, cardiovascular assessment, and psychological appraisal. Treatment: Non-small cell tumo rs: Excision is the treatment of choice for peripheral tumors, with no metastatic spread ( 25%). Curative radiotherapy is an alternative in patients with inadequate respiratory reser ve. Small cell tumors are almost always disseminated at presentation. They may respond to c hemotherapy . Palliation: Radiotherapy is used for bronchial obstruction, superior vena cav a obstruction, hemoptysis, bone pain, and cerebral metas- tases. Endobronchial therapy incl udes tracheal stenting, cryotherapy, laser therapy, and brachytherapy (a radioactive source is placed close to the tumor). Pleural drainage/pleurodesis for symptomatic pleural effusi ons. Drug therapy : Analgesia, corticosteroids, antiemetic, codeine, bronchodilators, antid epressants. Prognosis: Non-small cell: 50% 2-yr survival without spread; 10% with spread. S mall cell: Median survival is 3 months if untreated; 1 \200\2231.5 yrs if treated. Preventi on: Actively discourage smoking. Prevent occupational exposure to carcinogens. Other lung t umors Bronchial adenoma: Rare, slow-growing tumor. 90% are carcinoid tumors; 10% are cylind romas. Treatment : Surgery. Hamartoma: Rare, benign tumor. ct scan : Lobulated mass with fl ecks of calcification. Often excised to exclude malignancy. Mesothelioma (p. 186). 174 Table 6.4 Coin lesions of the lung \212 \212 Malignancy (1 or 2 ) Abscess \212 \212 Arteriovenous malformation Encysted effusion (fluid, blood, pus) Cyst Foreign body Lung par enchyma scar \212 \212 \212 Granulomata Carcinoid tumor Pulmonary hamartoma \212 \212 \212 e n i c i d e m y r a n o m u P Table 6.5 TNM Staging for lung neoplasms Primary tumor (T) TX Malignant cells in bronchial secre- tions, no other evidence of tumor Carcinoma in situ Non e evident \211 3 cm, in lobar or more distal Tis T0 T1 airway T2 >3 cm and >2 cm distal to carina or any size if pleural involvement or obstructive pneumoni tis extend- ingto hilum, but not all the lung Involves the chest wall, diaphragm, mediastin al pleura, pericardium, or <2 cm from, but not at, carina l T3 T4 Involves the mediastinum, heart, great vessels, trachea, esophagus, vertebral body, carina, or a malig- nant effusion is pre sent Regional nodes (N) N0 None involved (after mediastinoscopy) N1 N2 N3 Peribronchial and/or ipsilateral hilum Ipsilateral mediastinum or subcarinal Contralateral mediastinum or hilum, scalene, or supraclavicular 175 Distant metastasis M0 None (M) M1 Tumor TX Tis, T1, or T2 Distant metastases present Lymph nodes N0 N0 Stage Occult I Metastasis M0 M0 II T1 or T2 N1 N0 T3 N1 T3 N2 T1 \200\223T3 N3 T1 \200\223T4 N0 \200\223N2 T4 N0 \200\223N3 T1 \200\223T4 M0 M0 M0 M0 M0 M0 M1 III a III b IV Asthma Asthma affects 10 \200\22312% of adults and 15% of children. Asthma is a syndrome co mplex characterized by variable airflow obstruction. Three factors are involved in airway o bstruction: bronchial muscle hyperreactivity, inflamma- tion in the airways, and bronchial mucous production. Factors contributing to the evolution and persistence of asthma are atop y (allergic rhinitis and atopic dermatitis, eczema), nonallergic influences, respiratory in fections, genetic predisposition, and environmental elements including allergens, air pollu tion, and occupational exposure. Symptoms Intermittent dyspnea, wheezing, cough (often noct urnal) and sputum production. \212Precipitants: Cold air, exercise, emotion, allergens (ho use dust, mites, pol- len, animal fur), infection, drugs (e.g., aspirin, NSAIDs, \222 -blockers). \212Diurnal variation in symptoms or peak flow. Marked morning dipping of peak flow is com mon and can tip the patient over into a serious attack, despite having normal peak flow at other times. \212Exercise: Quantify the exercise tolerance. \212Disturbed sleep: Quantify as nights pe r week (a sign of serious asthma). \212Acid reflux: Individuals with asthma have an increa sed prevalence of gas- troesophageal reflux disease; esophageal reflux of acid or acidic fu mes may stimulate bronchospasm/laryngospasm. \212Other atopic disease: Eczema, hay fever, allergy, or family history? \212The home (es pecially the bedroom): Pets? Carpet? Feather pillows? Floor cushions and other \200\234soft furnishings \200\235? \212Occupation: If symptoms remit at weekends or holidays, something at work may be a trig ger. Ask the patient to measure his or her peak flow at work and at home (at the same time of day) to confirm this. 176 \212Days per week off work or school. Signs Tachypnea, audible wheeze, hyperinflated chest , hyperresonant per- cussion, diminished air entry, widespread, polyphonic wheeze. Severe a ttack : Inability to complete sentences; pulse >110 bpm; respiratory rate >25/min; PEF 33 \200\22350% of predicted. Life-threatening attack: Silent chest, cyanosis, bra- dycardia, e xhaustion, PEF <33% of predicted, confusion, feeble respiratory effort. Tests Peak expirato ry flow: PEF monitoring (p. 154): A diurnal variation of >20% on \211 3 d a week for 2 wk s. Spirometry: Obstructive defect ( \206\223 FEV 1 / FVC, \206\221 RV); usually \211 15 % improvement in FEV 1 following \222 2 agonists or steroid trial. CXR: Hyperinflation. Sk in-prick tests may help to identify allergens. Histamine or methacholine challenge. Aspergi llus serology. Acute attack: PEF, sputum culture, CBC, electrolytes, CRP, blood cultures. A BG analysis usually shows a normal or slightly reduced P a O 2 and low P a CO 2 (hyperventi lation). If P a O 2 is normal but the patient is hyperventilating, watch carefully and repe at the ABG a little later. If P a CO 2 is raised, transfer to a step-down unit or icu for m echanical ventilation . CXR (to exclude infec- tion or pneumothorax). Treatment Refractory asthma, asthmatic bronchitis (p. 170). Emergency treatment (p. 702). Differential diagnosis Pulmonary edema ( \200\234cardiac asthma \200\235), COPD (often coexists), large airway ob struction (e.g., foreign body, tumor), supe- rior vena cava (SVC) obstruction (wheeze/dyspn ea not episodic), pneu- mothorax, PE, bronchiectasis, obliterative bronchiolitis (suspect i n elderly). Exercise-induced asthma Commonly misdiagnosed as wheezing during exercise; more accurately, exercise-induced asthma occurs after exertion has ended. It is usually self-li miting; may be pretreated with pre-exercise \222 2 -agonist and antileukotriene. Associated diseases Acid reflux; polyarteritis nodosa (PAN); Churg \200\223 Strauss syndrom e; ABPA. Natural history Most childhood asthmatics either grow out of asthma in adolescence or suffer much less as adults. A significant number of peo- ple develop chronic asthma lat e in life, adult-onset asthma, or asthmatic bronchitis. e n i c i d e m y r a n o m u P