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 Asthmatic bronchitis/Refractory asthma Lifestyle education Stop smoking; avoid precipitants . Check inhaler tech- nique. Teach patients to use a peak flow meter to monitor PEF twice a day. Educate patients to manage their disease by altering their medication in response to changes in symptoms or PEF. Give specific advice about what to do in an emergency; provide a written action plan. National Asthma Education and Prevention Program (NAEPP) Guidelines Start treatment at the step most appropriate to severity. Review treatment every 1 \200\223 6 months. A gradual stepwise reduction in treat- ment may be possible; alternatively, consi der step-up if control is not main- tained. A short course of prednisone may be used to gai n control as quickly as possible. Step 1 Mild intermittent asthma : Occasional short-acting inhaled \222 2 -agonist as required for symptom relief. If daytime symptoms occur >2 days per week (but not every day), or if nocturnal symptoms occur >2 nights per month, go to St ep 2. Step 2 Mild persistent asthma: Add low-dose inhaled steroid: beclometha- sone 40 \200 \223120 mcg/12 h, budesonide 100 \200\223200 mcg/12 h, or fluticasone 44 \200\223132 mcg/12 h. If symptoms occur daily or >1 night per week, go to Step 3. Step 3 Moderate persistent asthma : Add long-acting \222 2 -agonist (e.g., salmeterol 50 mcg/12 h or formoterol 12 mc g/12 h). If benefit \200\224but still inadequate control \200\224continue and increase dose of inhaled steroid to medium-dose (beclomethasone 120 \200\223240 mcg/12 h, budesonide 200 \200\223600 mcg/12 h, or fluticasone 132 \200\223330 mcg/12 h). If symptoms are continual or occur frequently at night, go to Step 4. Step 4 Severe persistent asthma : Continue long -acting \222 2 -agonist and increase dose of inhaled steroid to high-dose (beclomethasone up to 320 mcg/12 h, budesonide up to 800 mcg/12 h, or fluticasone up to 440 mcg/12 h). Drug s \222 2 -adrenoreceptor agonists relax bronchial smooth muscle, acting within minutes. Al buterol is best given by inhalation (aerosol, powder, nebulizer), but may also be given PO (see Table 6.6). Side effects ( SE) : Tachyarrhythmia, \206\223 K + , tremor, anxiety. Lon g-acting inhaled \222 2 -agonist (e.g., salmeterol, formoterol) can help nocturnal symptom s and reduce morn- ing symptoms. They should never be used as mono-therapy for asthma, and should only be added when symptoms are inadequately controlled on inhaled corticosteroids. SE : Same as albuterol: Tolerance, arrhythmias, paradoxical bronchospasm (salmeterol),? \206\221 risk of death. Corticosteroids are best inhaled (e.g., beclomethasone via spacer [ or pow- der]), but may be given PO or IV. They act over days to reduce bronchial mucosal in flammation. Rinse mouth after inhaled steroids to prevent oral candidiasis. Oral steroids a re used acutely (high-dose, short courses; e.g., prednisone 30 \200\22340 mg/24 h PO for 7 d) and longer term in lower dose (e.g., 5 \200\22310 mg/24 h) if control is not optimal on inhalers. Warn about SE. Aminophylline (metabolized to theophylline) may act by inhibiting phospho-diesterase, thus reducing bronchoconstriction by increasing cyclic adenosine monoph osphate (cAMP) levels. Stick with one brand name (bio- availability is variable). It may be useful as \200\234add-on \200\235 treatment if inhaled therapy is inadequate. In acute se vere asthma, it may be given IVI. It has a l 177 narrow therapeutic ratio, causing arrhythmias, GI upset, and seizures in the toxic range. C heck theophylline levels, then do electrocardiogram (ECG) monitoring and check plasma level s after 24 h if IV therapy is used. Anticholinergics (e.g., ipratropium) may reduce muscle spasm synergistically with \222 2 -agonists. They may be of more benefit in COPD than in a sthma. Try each alone and then together; assess with spirometry. Cromolyn May be used as pr ophylaxis in mild and exercise-induced asthma (always inhaled), especially in children. As an adverse effect, cromolyn may precipitate asthma. Leukotriene receptor antagonists (e.g., montelukast, zafirlukast) block the effects of cysteinyl leukotrienes in the airways. May be used as \200\234add-on \200\235 therapy to recommended inhaler regimens. Table 6.6 Doses of inhaled medications used in asthma Inhaled aerosol Inhaled powder Nebulized ( supervised ) Albuterol Dose example: 90 \200\223180 mcg/ 4 \200\2236 h 2.5 \200\2235 mg/6 h (The same for cfc and cfc -free devices; Proventil HFA is an example of a cfc -free inhaler) Salmeterol Dose/puff Recommended regimen \200\224 \200\224 50 mcg 50 mcg/12 h \200\224 \200\224 178 Ipratropium bromide Dose/puff 17 mcg \200\224 500 mcg/ mL Recommended regimen Steroids Fluticasone (Flovent HFA ) Doses available/puff (CFC-free) Re commended regimen 20 \200\22380 mcg/6 h \200\224 500 mcg/6 h 44, 110, & 220 \200\224 \200\224 mcg 88 \200\223440 mcg/12 h \200\224 \200\224 Beclomethasone (Qvar ) Doses available/puff (CFC-free) Recommended regimen 40 & 80 mcg \200\224 \200\224 40 \200\223320 mcg/12 h Budesonide (Pulmicort ) \200\224 Doses available/puff (CFC-free) Recommended regimen 200 mcg \200\224 \200\224 200 \200\223800 \200\224 mcg/12 h Any puff/dose \211 250 mcg produces significant steroid absorption. Complications: Catara cts, easy bruisability, osteoporosis. Chronic obstructive pulmonary disease Definitions COPD is defined as a progressive disorder of airway obstruc- tion ( FEV 1 , FEV 1 /FVC) with little or no reversibility. COPD includes chronic bronchitis (chronic cough with sputum production), emphysema (destruction and expansion of alveolar air spaces), and small airways disease (narrowing of the small br onchioles). Although airway hyperresponsiveness is characteristic of asthma, a percentage o f individuals with COPD have airway hyperresponsiveness to external stimuli, infections, an d, in some cases, to allergens. COPD is favored by: \212 \212 \212 \212 \212 e n i c i d e m y r a n o m u P Age of onset >35 yrs Smoking Chronic dyspnea Sputum production 1 variation. Chronic bronchi tis is No marked diurnal or day-to-day FEV defined clinically as cough and sputum productio n on most days for 3 months in 2 successive years. There is no increase in mortality if lun g function is normal. Symptoms improve in 90% of patients if they stop smoking. Emphysema i s defined histologically as enlargement of the air spaces distal to the terminal bronchiole s, with destruction of the alveolar walls. l Prevalence 14 million in the United States. COPD mortality: 126,000 deaths/yr in the Unite d States. Pink puffers and blue bloaters Pink puffers have increased alveolar ven- tilation , a near normal P a O 2 , and a normal or low P a CO 2 . Patients have shortness of breath, yet maintain adequate ventilation without cyanosis. Blue bloaters have decreased alveolar ventilation, with a low P a O 2 and a high P a CO 2 . They can be cyanotic but usually are not breathless; may go on to develop cor pulmonale. Their respiratory centers are relativel y insensitive to CO 2 , and they rely on their hypoxic drive to maintain respiratory effort \200\224 - supplemental oxygen should be given with care . Although the traditional dif- f erentiation of pink puffers versus blue bloaters suggests that pink puffers have emphysema and blue bloaters have chronic bronchitis, more recent clinical studies show elements of bo th are present in COPD, and physi- ological/physical differentiation is no longer relevant. Clinical features Symptoms: Cough, sputum, dyspnea, and wheeze. Signs: Tachypnea, use of a ccessory muscles of respiration, hyperinflation, cricos- ternal distance (<3 cm), exp ansion, resonant or hyperresonant percussion, quiet breath sounds (e.g., over bullae), whee ze, cyanosis, cor pulmonale. Complications: Acute exacerbations infection, polycythemia, respiratory failure, cor pulmonale (edema, JVP ^ ), pneumothorax (ruptured bullae), lung c ancer. Tests CBC: PCV ^ . CXR: Hyperinflation (>6 anterior ribs seen above diaphragm in mid -clavicular line), flat hemidiaphragms, large central pulmonary arteries, peripheral vas cular markings, bullae. ECG: Right atrial and ventricular hypertrophy (cor pulmonale). ABG: P a O 2 hypercapnia. Lung function (p. 154): Obstructive + air trapping (FEV 1 <80% of predicted \200\224 see below, FEV 1 /FVC ratio <70%, TLC ^ , RV ^ , DLCO in emphysema ). Treatment Chronic stable: See Table 6.7. Emergency treatment (p. 704). Smoking cessation advice. Body mass index (BMI) is often low: Diet advice dietary supplements may help. M ucolytic agents may help chronic produc- tive cough. Disabilities may cause serious, treata ble depression. Respiratory failure (p. 176). Preventative treatment : Flu and pneumococcal vaccinations. 179 Long-term O 2 therapy (ltot): An MRC trial showed that if P a O 2 was main- tained \211 6 0 mm Hg for 15 h a day, 3-yr survival improved by 50%. LTOT should be given for (1) clinica lly stable nonsmokers with P a O 2 <55 mm Hg despite maximal treatment. These values should be stable on two occasions >3 wks apart; and (2) if P a O 2 55 \200\22360 and pulmonary hy pertension (e.g., right ventricular hypertrophy [RVH]; loud S 2 ) + cor pulmonale. O 2 can also be prescribed for terminally ill patients. For additional treatment guidelines, see Ta ble 6.8. 180 Table 6.7 Predicted FEV 1 Caucasian males; in liters, level in other races a 175 155 Hei ght (cm ) 3.7 2.8 Age(yr) 10 4.2 3.2 25 4.1 3.1 30 3.8 2.8 40 3.5 2.5 50 3.3 2.2 60 3.0 2.0 70 2.7 1.7 80 Caucasian females 145 2.1 2.6 2.5 2.3 2.1 1.7 1.6 1.4 150 2.5 2.9 2.8 2.5 2.2 2.0 1.7 1.4 160 3.0 3.4 3.3 3.0 2.8 2.5 2.2 2.0 165 3.2 3.7 3.6 3.3 3.0 2.8 2.5 2.2 170 3.5 4.0 3.8 3.6 3.3 3.0 2.7 2.5 180 3.9 4.3 4.3 4.1 3.8 3.5 3.3 3.0 185 4.1 4.7 4.6 4.3 4.0 3.8 3.5 3.3 190 4.4 5.0 4.9 4.6 4.3 4.0 3.8 3.5 195 4.6 5.3 5.1 4.9 4.6 4.3 4.0 3.8 150 2.2 2.7 2.6 2.4 2.2 2.0 1.8 1.6 155 2.3 2.9 2.8 2.5 2.3 2.1 1.9 1.7 160 2.5 3.0 2.9 2.7 2.5 2.3 2.1 1.9 165 2.6 3.1 3.0 2.8 2.6 2.4 2.2 2.0 170 2.7 3.3 3.2 3.0 2.7 2.5 2.3 2.1 175 2.9 3.4 3.3 3.0 2.9 2.7 2.5 2.2 180 3.0 3.5 3.4 3.2 3.0 2.8 2.6 2.4 185 3.1 3.7 3.6 3.3 3.1 2.9 2.7 2.5 190 3.3 3.8 3.7 3.5 3.3 3.1 2.9 2.7 www.nationalasthma.org.au/publications/spiro/appc.html#Mean a African FEV 1 is 10 \200\22315% lower; Chinese: 20% lower; Indian: 10% lower. PEF varies little between groups. 1 8 1 Pulmonary medicine Table 6.8 Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2003 Guidelines Spirometry (FEV 1 /FVC <70%) Bronchodilator response Trial of oral steroids is a poor predi ctor of response to inhaled steroids. CXR?Bullae?Other pathology ABG?Hypoxia?Hypercapnia At risk (0) Assessment of COPD Severity of COPD Normal spirometry (Stage) FEV 1 \211 80% predicted FEV 1 50 \200\22379% predicted FEV 1 30 \200\22349% predicted FE V 1 <30% predicted Mild (I) Moderate (II) Severe (III) Very-severe (IV) Treating stable COPD NB : Patients who fly should be able to maintain an in-flight P a O 2 of \211 50 mm Hg. Nonpharmacological Stop smoking, encourage exercise, treat poor nutrition or obesity, influenza and pneumo- co ccal vaccination, pulmonary rehabilitation/ palliative care 182 Pharmacological: Mild Add PRN short-acting bronchodilator (inhaled ipratropium, albuterol, or combination of two) Moderate Add long-acting inhaled \222 2 agonist (salmeterol or formoterol) or inhaled anticholinerg ic (tiotropium) Severe Add inhaled steroids if repeated exacerba- tions (Advair combines salmeterol and fluticas one.) More advanced COPD \212 \212 Pulmonary rehabilitation in patients with moderate or worse COPD Long-term oxygen therapy i f P a O 2 <55 mm Hg and/or oxygen satura- tion \211 85%. Indications for surgery: Recurre nt pneumothoraces; isolated bullous disease; lung volume reduction surgery or lung transpla ntation in selected patients. In select COPD patients, lung volume reduction sur- gery impr oves lung function exercise tolerance, improves survival, and results in a better quality o f life. Assess home set-up and support needed. Treat depression. \212 \212 (Continued) e n i c i d e m y r a n o m u P Table 6.8 (Continued) Indications for specialist referral \212 \212 \212 \212 \212 \212 Uncertain diagnosis Suspected severe COPD or a rapid decline in FEV 1 Onset of cor pulmonal e Assessment for oral corticosteroids, nebulizer therapy, or LTOT Bullous lung disease (to assess for surgery) <10 pack-years smoking (PYS; equals the number of packs/day times the n umber of years of smoking). Smokers have an excess loss of FEV 1 of 7.4 \200\22312.6 mL per pack year for men and 4.4 \200\2237.2 mL per pack year for women. Symptoms disproportionat e to pulmonary function tests Frequent infections (to exclude bronchiectasis) COPD in patie nt <40 yrs (exclude l \212 \212 \212 1 -antitrypsin deficiency?) Interstitial lung diseases Interstitial lung disease is group of disorders that, in contras t to COPD, do not involve the airways but involve the interstitial region of lung paren- ch yma. The anatomy of the lung parenchyma primarily affected by these disorders are the alveo li, alveolar epithelium, the capillary endothelium, and the interstitial space surrounding those structures. Interstitial lung disease is characterized by progressive shortness of br eath usually associated with a chronic nonproductive cough. Within this group of interstiti al lung diseases, historical presentation, physical examination, and radiographic appearanc e do not help in differentiating among the various types of lung parenchyma diseases. Histo pathology may demonstrate alveolitis, fibrosis, and interstitial inflam- matory changes or may indicate a granulomatous interstitial process. A major portion of interstitial lung dis ease, 40%, is idiopathic, without a known cause, and with the histopathology revealing fibr osis, bronchi- olitis, and/or pneumonia. A second common presentation of interstitial lung disease is related to inhalational exposures, such as in hypersensitivity pneumonitides, as bestosis, or fumes or gas exposure. Sarcoidosis, a granu- lomatous process of unknown cause , may present as interstitial lung disease, with histologic findings of granulomata present within the spaces between alveoli and pulmonary capillaries. Connective tissue diseases, s uch as SLE, rheumatoid arthritis, and systemic sclerosis, may be associated with inter- sti tial fibrosis and inflammatory changes. Last, medications may initiate an inflammatory inte rstitial process and result in fibrosis; these drugs include amiodarone, gold, radiation th erapy, and chemotherapy medications. Dyspnea is the most common symptom; interstitial lung disease charac- teristics are a chronic presentation of illness, shortness of breath, and a nonproductive cough, especially prevalent in persons >60 yrs, with a family history of int erstitial lung disease, a history of smoking, and a history of occupational or environmenta l exposures. Physical exam, especially early in the disease process, is nonspecific, yet cr ackles heard bilaterally in the lung bases are a common finding. Laboratory studies are als o nonspecific; however, excluding underlying connective tis- sue diseases with antibasement membrane antibodies, rheumatoid factor, and antinuclear antibody titer is important; serum precipitins aid in rul- ing out hypersensitivity pneumonitis; an elevation in angiotensin- converting enzyme may be present in sarcoidosis; an elevation in LDH is common yet also non specific. Depending on the phase of interstitial lung disease, an 183 echocardiogram is helpful in excluding or including pulmonary hyperten- sion with right ven tricular hypertrophy or dilation. Chest radiographs show a reticular, possibly nodular, pat tern in both lung bases, usually in a clinical setting without associated symptoms/signs of an acute infection. HRCT is the best radiographic study, with clearer defini- tion of an i nterstitial process and with the exclusion of other mediastinal or parenchyma disorders. Pu lmonary function studies classically identify restrictive lung disease, demonstrating decre ased total lung volumes, with decreased diffusion capacity and some reduction of expiratory flow; how- ever, the ratio of FEV 1 /FVC is usually normal or, in fact, increased due to t he loss of lung compliance and increased elasticity secondary to fibrosis. The most effecti ve method of diagnosis is lung biopsy; fiberoptic bron- choscopy with BAL and with multiple lung biopsies may be useful, but a generous tissue biopsy is more helpful in defining the overall histology of an interstitial process and thus may necessitate surgical lung biopsy with video-assisted thoracic surgery or open surgical lung biopsy. Treatment of interstitia l lung disease is not effective; most cases have a progressive, advancing fibrosis terminat ing in hypoxemia, cor pulmonale, and respiratory failure. Glucocorticosteroids therapy may counteract the inflammatory phase (e.g., in alveolitis); however, with fibrosis, corticoste r- oids are not beneficial; in fact, although glucocorticosteroids may transiently improve symptoms, these drugs do not have an impact on morbidity and mortality. Other medications f or interstitial lung disease are cyclophosph- amide, azathioprine, colchicine, methotrexate , and penicillamine; all may have some positive effect in the short term, yet their long-te rm benefit is doubtful. Idiopathic pulmonary fibrosis Most common; usual interstitial pneu- monitis has a mixture of inflammation, fibroblasts interspersed between normal lung tissue , and dense fibrosis and honeycomb changes on hrct. Nonspecific seen with clinical-serologi cal evidence of connective tissue disease; more common in younger patients, especially wome n; uniform histologic involvement with fibrosis and cellular alterations. Hamman-Rich syndr ome High mortality; sudden onset, rapidly pro- gressive (as in acute respiratory distress s yndrome [ARDS]); deteriorating hypoxemia associated with histologic evidence of extreme alv eolar damage. Most deaths occur within 6 months. Interstitial lung disease associated with connective tissue diseases Typical interstitial lung disease presentation within clinical c ircumstances of SLE, rheumatoid arthritis, Sj gren \200\231s syndrome, dermatomyositis-p olymyositis, progressive systemic sclerosis. Pulmonary involvement in these disorders porte nd a poor prognosis. associated with medications Interstitial Chemotherapeutic agents, amio darone, gold, antibiotics (nitrofuran- toin); inflammatory lung changes usually resolve wit h discontinuation of medication. Pulmonary alveolar proteinosis Presentation is similar to interstitial lung disease; lung biopsy reveals an abundance of lipoprotein in distal air- s paces; common in men; elevated titer of anti-granulocyte-macrophage colony stimulating fact or. Treatment consists of whole lung lavage. Pulmonary in premenopausal lymphangioleiomyoma tosis Rare; women; emphysema, recurrent pneumothorax and chylous pleural effu- sions; pulmo nary function studies are mixed, with restrictive and obstruc- tive patterns; survival of 8 \200\22310 yrs from time of diagnosis. No effective treatment. 184 interstitial pneumonia is usually lung disease Diffuse alveolar hemorrhage Primary example is Goodpasture \200\231s syn- drome; alveolar h emorrhage with hypoxemia characterized by autoantibod- ies to renal glomerular and lung bas ement membranes; histologic finding of damage to the pulmonary capillary basement membrane. Treatment, especially when associated with connective tissue disease, is glucocorticos- te roids; plasmapheresis is additive therapy. Interstitial lung disease associated with cigare tte smoking Diagnoses include desquamative interstitial pneumonia, respiratory bron- chioli tis, pulmonary histiocytosis, all in smokers, mostly males; progressive hypoxemia; restrict ive pulmonary function patterns with decrease diffusion capacity. Clinical improvement with smoking cessation. e n i c i d e m y r a n o m u P l Acute respiratory distress syndrome The acute lung injury of ARDS may be caused by direct l ung injury or occur secondary to severe systemic illness. Lung damage and release of inflam ma- tory mediators cause increased capillary permeability and noncardiogenic pulmonary edem a, often accompanied by failure in other organs systems. Causes Pulmonary : Pneumonia, gast ric aspiration, inhalation, injury, vasculi- tis, contusion. Other causes: Shock, septicemi a, hemorrhage, multiple trans- fusions, disseminated intravascular coagulation (DIC; p. 577 ), pancreatitis, acute liver failure, trauma, head injury, fat embolism, burns, obstetric e vents (eclampsia, amniotic fluid embolus), drugs/toxins (aspirin overdose, heroin, paraquat ). See Table 6.9. Clinical features Cyanosis, tachypnea, tachycardia, peripheral vasodilata - tion, bilateral fine inspiratory crackles on lung auscultation. Investigations CBC, elect rolytes, LFT, amylase, clotting, CRP, blood cul- tures, ABG. CXR shows bilateral pulmonary infiltrates. Pulmonary artery catheter to measure pulmonary capillary wedge pressure (PCWP) . Diagnostic criteria One consensus requires these four to exist: (1) Acute onset. (2) CXR: Bilateral infiltrates. (3) PCWP <19 mm Hg or a lack of clinical congestive heart failure. (4) Refractory hypoxemia. Management Admit to ICU, provide supportive therapy, and treat th e under-lying cause; artificial ventilator support is common. \212Respiratory support: In early ARDS, continuous positive airway pressure (CPAP) with 40 \200\22360% oxygen may be ad equate to maintain oxygenation; most patients need mechanical ventilation. Indications for ventilation: P a O 2 : <60 mm Hg despite 60% O 2 ; P a CO 2 : >45 mm Hg. The large tidal vo l- umes (10 \200\22315 mL/kg) produced by conventional ventilation plus reduced lung compli ance in ARDS may lead to high peak airway pressures pneu- mothorax. Positive end-expirat ory pressure (PEEP) may improve oxygen- ation, but may reduce venous return, cardiac output , and perfusion of the kidneys and liver. Other approaches include inverse ratio ventilatio n (inspiration > expiration), permissive hypercapnia, high-frequency jet ven- tilation, and other low-tidal-volume techniques. 185 \212Circulatory support: Invasive hemodynamic monitoring with an arterial line and Swan \200\223Ganz catheter aids the diagnosis and may be helpful in moni- toring PCWP and cardia c output. Maintain cardiac output and O 2 deliv- ery with inotropes (e.g., dobutamine 2.5 \200\22310 mcg/kg/min IV), vasodilators, and blood transfusion. Consider treating pulmonary hypertension with low-dose (20 \200\223120 parts per million) nitric oxide, a selective pu lmonary vasodilator. Hemodialysis may be needed in renal failure and to achieve a negative fluid balance. \212Sepsis: Identify organism(s) and treat accordingly. If clinically septic, but no organ isms cultured, use empirical broad-spectrum antibiotics (p. 159). Avoid nephrotoxic antibio tics. \212Other: Nutritional support: Enteral nutrition is best. Steroids do not decrease mortal ity in the acute phase, but may help later on (>7 d), particularly if eosinophilia in blood or in fluid from BAL. Prognosis Overall mortality is 50 \200\22375%. Prognosis varies with age of patient, cause of ARDS (pneumonia 86%, trauma 38%), and number of organs involved (three organs involved f or >1 wk is invariably fatal). Table 6.9 Risk factors for ARDS \212 \212 \212 \212 \212 \212 \212 \212 \212 \212 \212 \212 Sepsis Hypovolemic shock Trauma Pneumonia Diabetic ketoacidosis Gastric aspiration Pregnanc y Eclampsia Amniotic fluid embolus Drugs/toxins Paraquat, heroin, aspirin overdose Pulmonar y contusion \212 \212 \212 \212 \212 DIC \212 \212 \212 \212 \212 \212 \212 Massive transfusion Burns Smoke inhalation Near drowning Acute pancreatitis Head injury Intracranial pressure Fat embolus Heart/lung bypass Tumor lysis syndrome Malari a \206\221 Respiratory failure Respiratory failure occurs when gas exchange is impaired, resulting in hypoxemia and/or impairment in CO 2 elimination. See Table 6.10. Type I respiratory failure is defined as hypoxia ( P a O 2 <60 mm Hg) with a normal or low P a CO 2 . Type I respirat ory failure is caused primarily by . /Q . ) mismatch. Causes include: ventilation/perfusion (V \212 \212 \212 \212 \212 \212 \212 Type II respiratory failure is defined as hyp oxia ( P a O 2 <60 mm Hg) with hypercapnia ( P a CO 2 is >45 mm Hg). Respiratory failure ty pe II is caused . /Q . ) abnormalities. Causes by alveolar hypoventilation, with or without (V include: \212Pulmonary disease : Asthma, COPD, pneumonia, pulmonary fibrosis, 186 Pneumonia Pulmonary edema PE Asthma Emphysema Pulmonary fibrosis ARDS (P. 174) obstructive sleep apnea (OSA; p. 189) \212Reduced respiratory drive : Sedative drugs, CNS tumor, or trauma \212Neuromuscular di sease : Cervical cord lesion, diaphragmatic paralysis, poliomyelitis, myasthenia gravis, Guillain \200\223Barr syndrome \212Thoracic wall disease : Flail chest, kyphoscoliosis Clinical features are those of the underlying cause, together with symp- toms and signs of hypoxia, with or without hypercapn ia. Hypoxia: Dyspnea, restlessness, agitation, confusion, central cyanosis. If long- standi ng hypoxia : Polycythemia, pulmonary hypertension, cor pulmonale. Hypercapnia: Headache, peripheral vasodilatation, tachycardia, bounding pulse, tremor/flap, papilledema, confusion, drowsiness, coma. Investigations are aimed at determining the unde rlying cause: \212 \212 \212 \212 Management depends on the cause: Type I respiratory f ailure: \212 Treat underlying cause. Give oxygen (35 \200\22360%) by face mask to correct hypoxia. \212 P a O 2 <60 mm Hg despite 60% O 2 . \212 Assisted ventilation if Type II re spiratory failure: In type II respiratory failure, the respiratory center within the brains tem is relatively insensitive to CO 2 ; breathing may be driven by hypoxia. Oxygen therapy should be administered with caution and with gradual increases in O 2 . Treatment of hypoxe mia is crucial in prevention and modification of pulmonary hypertension caused by hypoxemia . \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.