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Pulmonary and Critical Care Medicine Asthma Diagnosis Common symptoms of asthma are cough, wheezing, chest tightness, and shortness of breath that are intermittent. The cardinal features of asthma are reversible airway obstruction, inflammation, and airway hlperreactivi[2. I'iesting Diagnostic studies include spirometry before and after bronchodilator administration. Must meet both criteria: . FEVr 'l >12?, . FEVr 1)200 mL In patients with atypical features, perform PFTs. The presence ofairflow irreversibility, restrictive patterns, and significantly reduced vital capacity suggest other diseases. Bronchial challenge testing is indicated for patients with a suggestive clinical history for asthma but normal spirometry. Bronchial challenge testing with exercise is indicated to diagnose exercise-induced asthma in patients who have dyspnea fol lowing exercise but normal spirometry. DOil'T BE TRICKED . Normal spirometry does not rule out asthma. . A normal bronchoprovocation test rules out asthma; a positive test confirms airway hyperresponsiveness, of which asthma is but one cause; clinical correlation of this finding with symptoms and other testing is needed. . Wheezing does not equal asthma; consider HF, COPD, vocal cord dysfunction, and upper airway obstruction. STUDY TAELE: Differential Diagnosis of Asthma Disease Characteristics Chronic eosinophilic Chest x-ray shows "photographic-negative" pulmonary edema (peripheral pulmonary edema) pneumonia Clinical findings: striking peripheral blood eosinophilia, fever, and weight loss in a long-term smoker Diagnose by bronchoscopy with biopsy or bronchoalveolar Iavage showing a high eosinophil count Allergic bronchopulmonary Manifests as asthma with eosinophilia, markedly high serum lgE levels, and intermittent pulmonary aspergillosis nfi ltrates i

DOil'T BE TRICKED . Normal spirometry does not rule out asthma. . A normal bronchoprovocation test rules out asthma; a positive test confirms airway hyperresponsiveness, of which asthma is but one cause; clinical correlation of this finding with symptoms and other testing is needed. . Wheezing does not equal asthma; consider HF, COPD, vocal cord dysfunction, and upper airway obstruction. STUDY TAELE: Differential Diagnosis of Asthma Disease Characteristics Chronic eosinophilic Chest x-ray shows "photographic-negative" pulmonary edema (peripheral pulmonary edema) pneumonia Clinical findings: striking peripheral blood eosinophilia, fever, and weight loss in a long-term smoker Diagnose by bronchoscopy with biopsy or bronchoalveolar Iavage showing a high eosinophil count Allergic bronchopulmonary Manifests as asthma with eosinophilia, markedly high serum lgE levels, and intermittent pulmonary aspergillosis nfi ltrates i Diagnose with positive skin test for Aspergi//us and lgG and lgE antibodies to Aspergillus, characteristic radiographic opacities in the upper lobes This is often overlooked until onset of more advanced disease, including fixed obstruction and bronchiectasis Eosinophilic granulomatosis Upper airway and sinus disease precedes difficult-to-treat asthma; look for flares associated with use with polyangiitis of leukotriene inhibitors and glucocorticoid tapers Serum p-ANCA may be elevated Hallmark diagnostic finding is eosinophilic tissue infiltrates Consider alternative diagnoses when asthma is difficult to control. Additional studies in these cases may include chest x-ray and echocardiography. Obtaining flow-volume loops and direct visualization of the larynx during an acute episode may be helpful in diagnosing tracheal obstruction and vocal cord dysfunction. Asthma may be an extraesophageal manifestation ofGERD. 338

Pulmonary and Critical Care Medicine STUDY TABLEI Asthma Syndromes Syndrome Features Allergic asthma Seasonal exacerbations; hay fever and allergen sensitization Cough-variant asthma Cough without other symptoms. Normal baseline spirometry, (+) bronchoprovocation testing. Rule out other causes of cough (GERD, ACE inhibitor, smoking, UACS) Exercise-ind uced Airway obstruction only with exercise or can trigger symptoms in patients with asthma (common) bronchoconstrictio n Vocal cord dysfunction Paradoxical adduction of the vocal cords during inspiration, causing functional upper airway obstruction Throat tightness, voice dysfunction. Laryngoscopy may demonstrate paradoxical vocal cord adduction during a symptomatic episode Occupational Symptoms improve during weekends and time away from work. Spirometry before and after workplace exposures, abnormal bronchoprovocation testing, or serial peak flow measurements can help diagnose Reactive airways Follows single high-level exposure to fumes, gases, vapors; persistent asthma >3 mo; (+) spirometry or dysfunction syndrome bronchoprovocation testing Asthma and rhinosinusitis precipitated by aspirin or NSA|Ds. Adult onset, airway and blood eosinophilia, sinusitis + nasal polyps Treatment Assess asthma control with standardized instruments (Asthma Control Test, Asthma Control Questionnaire) Institute therapy: l. All patients require a rescue medication (usually a SABA). 2. All patients with persistent asthma require a controller medication (tG or IG plus LABA). 3. Assess proper inhaler technique. Review response and adjust therapy by stepping controller medications up or down.

Treatment Assess asthma control with standardized instruments (Asthma Control Test, Asthma Control Questionnaire) Institute therapy: l. All patients require a rescue medication (usually a SABA). 2. All patients with persistent asthma require a controller medication (tG or IG plus LABA). 3. Assess proper inhaler technique. Review response and adjust therapy by stepping controller medications up or down. DO]II,T BE TRICKED All patients should receive one of these three combination treatments: . For mild asthma, an inhaled glucocorticoid-formoterol combination as needed or low-dose inhaled glucocorticoid whenever a SABA is taken. . Regular inhaled glucocorticoid or inhaled glucocorticoid + LABA daily plus SABA when needed. . Maintenance and rescue treatment with inhaled glucocorticoid-formoterol. Treat severe asthma associated with type 2 inflammation (1 IgE or 1 sputum/blood eosinophils often associated with atopy). Elevated lgE: Omalizumab is a monoclonal antibody directed at lgE for patients with moderate to severe persistent asthma with t he followi ng characteristics: o inadequate control of symptoms with inhaled glucocorticoids . evidence ofallergies to perennial aeroallergen . elevated lgE levels Elevated eosinophils: Anti interleukin monoclonal antibodies (mepolizumab, reslizumab, benralizumab, dupilumab). Treatment is reserved fbr patients with an absolute eosinophil count >150 cells/pl and severe asthma not controlled with standard therapy' Treatment of asthma syndromes: . Allergic asthma: treat as asthma; may require monoclonal antibody treatment if severe and associated with type 2 asthma phenotype 339

Pulmonary and Critical Care Medicine St p6 Step 3 Stop tl Stcp 5 Traatnent $cp f Stcp 2 SABA Daily Daily and Daily and Daily medium- Daily highdose as needed' lowdose ICS as-needed as-needed to highdose |C9IABA+ OR and SABA combination combination ICS-IABA+ LAMA oral ICS and SABAb as needed low"dose mediumdose and SABA glucocorticoid + as needed OR lC$formoterol lC$formoterol as needed SABA as needed Concomitant ICS and SABA Consider as needed add-on anti-l9E anti-lL-5, ami-lL-5& antiJL4/lL-13

SABA Daily Daily and Daily and Daily medium- Daily highdose as needed' lowdose ICS as-needed as-needed to highdose |C9IABA+ OR and SABA combination combination ICS-IABA+ LAMA oral ICS and SABAb as needed low"dose mediumdose and SABA glucocorticoid + as needed OR lC$formoterol lC$formoterol as needed SABA as needed Concomitant ICS and SABA Consider as needed add-on anti-l9E anti-lL-5, ami-lL-5& antiJL4/lL-13 Daily LTRA Daily Daily Daily + SABA as mediumdose medium-dose medium-to needed ICS + SABA rcs-r-ABA highdose as needed or ICS-LABA OR IC$I.AMA, and SABA Daily low-dose and SABA as needed ICS-LABA as needed or ICS-IAMA, Consider and SABA add-on anti-lgE, as needed anti-lL-5, anti-lL-5R, antilL4/lL-13

Daily LTRA Daily Daily Daily + SABA as mediumdose medium-dose medium-to needed ICS + SABA rcs-r-ABA highdose as needed or ICS-LABA OR IC$I.AMA, and SABA Daily low-dose and SABA as needed ICS-LABA as needed or ICS-IAMA, Consider and SABA add-on anti-lgE, as needed anti-lL-5, anti-lL-5R, antilL4/lL-13 $ep up if needed (first check adherence, inhaler technique. environmental factorc, and comorbidities) $tap down if possible (and asthma is well controlled x 3 months) . At each stap, include patient education, environmental control, and management of comorbidhies. . For steps 24: Consider subcutaneous allergen immunotherapy for patients whose asthma is controlled at initiation, buildup, and maintenance phases. . lf step 4 care or higher is needed, consuh with an ssthma speciali3t.

$ep up if needed (first check adherence, inhaler technique. environmental factorc, and comorbidities) $tap down if possible (and asthma is well controlled x 3 months) . At each stap, include patient education, environmental control, and management of comorbidhies. . For steps 24: Consider subcutaneous allergen immunotherapy for patients whose asthma is controlled at initiation, buildup, and maintenance phases. . lf step 4 care or higher is needed, consuh with an ssthma speciali3t. Ouick relief for all patients: . SABA as needed for symptoms: up to 3 treatments at 2Gminute intervals as needed . ln steps 3 and 4, ICS-formoterol 1-2 puft as needed up to a maximum total daily dosage of I 2 puft (54 pg) . Use of SABA >2 days a week (not prevention of EIB) indic.t$ inadequate control and the need to step up therapy SteFdlG Apptoach to Asdrma lhct'py: EIB = exercise-induced bronchospasm; ICS = inhaled corticosteroid; ITRA= leukotriene recepto] anlagonist. aNational Asthma Education and Prsention Program (NAEPP) re(ommendation. bGlobal lnitiative for Anhma recommendation. o Aspirin-exacerbated respiratory disease: aspirin and NSAID avoidance; stepped asthma care, including leukotriene- receptor antagonist o Cough-variant: treat as asthma if reversible bronchoconstriction demonstrated o Exercise-induced bronchospasm: SABA or low-dose budesonide-formoterol 15 minutes before exercise 340

Pulmonary and Critical Care Medicine Diagnosis COPD is a heterogeneous disorder that includes emphysema, chronic bronchitis, obliterative bronchiolitis, and asthmatic bron chitis. Patients typically present with cough, sputum production, dyspnea, and decreased exercise tolerance and energr level. The features most predictive of COPD in a symptomatic patient are the combination of: . smoking history . wheezing on auscultation o self reported wheezing Diagnose COPD when postbronchodilator spirometry shows an FEV'/FVC ratio <0.7 (or below LLN) associated with symptoms of chronic bronchitis, emphysema, or both. Measure AAT level in all patients with COPD. STUDY TABLE: Mimics of COPD Disease Characteristics Bronchiectasis Often secondary to an inciting event, such as childhood pneumonia orTB; may be associated with foreign body, CF, immotile ciliary syndrome, nontuberculous mycobacteria, and allergic bronchopulmonary aspergillosis Large-volume sputum production with purulent exacerbations; hemoptysis Chest x-ray showing "tram lines"; diagnose with HRCT, which will show airway diameter greater than that of its accompanying vessel and lack of distal airway tapering Cystic fibrosis Obstructive pulmonary disease (ultimately with bronchiectasis) or Gl symptoms are the most common presentation in adult patients; other symptoms may include recurrent respiratory infections and infertility Positive sweat chloride test result Adult Found in current orformer smokers; may be idiopathic or associated with other diseases such as RA bronchiolitis Poorly responsive to bronchodilators; may respond to smoking cessation and glucocorticoids Treatment Smoking cessation is essential in the management of all patients with COPD to reduce the rate of decline in lung function Many classification schemes help guide pharmacologic therapy of COPD, based on symptoms, number of exacerbations, and spirometry results. Strong evidence-based recommendations:

Large-volume sputum production with purulent exacerbations; hemoptysis Chest x-ray showing "tram lines"; diagnose with HRCT, which will show airway diameter greater than that of its accompanying vessel and lack of distal airway tapering Cystic fibrosis Obstructive pulmonary disease (ultimately with bronchiectasis) or Gl symptoms are the most common presentation in adult patients; other symptoms may include recurrent respiratory infections and infertility Positive sweat chloride test result Adult Found in current orformer smokers; may be idiopathic or associated with other diseases such as RA bronchiolitis Poorly responsive to bronchodilators; may respond to smoking cessation and glucocorticoids Treatment Smoking cessation is essential in the management of all patients with COPD to reduce the rate of decline in lung function Many classification schemes help guide pharmacologic therapy of COPD, based on symptoms, number of exacerbations, and spirometry results. Strong evidence-based recommendations: . For symptomatic patients with COPD and FEV, <60% of predicted, monotherapy using long-acting anticholinergic agents (LAMAs or LABAs) is recommended. . For symptomatic patients with an FEV, <50'1, of predicted, pulmonary rehabilitation is recommended. o Pulmonary rehabilitation is recommended following hospitalization for a COPD exacerbation. . For patients with COPD who have severe resting hypoxemia (arterial Po2 <5S mm Hg or O, saturation <BB%), continuous oxygen therapy is recommended. Weaker evidence based recommendations: o For stable patients with COPD with respiratory symptoms and FEV, between 60% and 80% of predicted, inhaled broncho dilators may be used. . For symptomatic patients with stable COPD and FEV, <60'L of predicted, combination inhaled therapies (LAMAs, LABAs, or inhaled glucocorticoids) may be considered. o For symptomatic or exercise limited patients with an FEV, >S0,/. of predicted, pulmonary rehabilitation may be considered. 342

Pulmonary and Critical Care Medicine An additional indication for which long term oxygen therapy should be considered is an arterial blood Po, <59 mm Hg with signs of tissue hypoxia (polycythemia, PH, right sided HF) Other therapies for stable COPD: . PDE 4 inhibitor (roflumilast) as add on therapy for severe COPD (bronchitis variant) to prevent recurrent exacerbations o long term macrolide therapy (bronchitis variant) to prevent recurrent exacerbations o nocturnal noninvasive mechanical ventilation to improve oxygenation, improve sleep, and decrease daytime somnolence in patients with chronic hypercapnia o palliative use of oral or parenteral opioids in patients with severe COPD and unremitting dyspnea at end of life . pneumococcal and COVID 19 vaccinations and annual influenza immunizations . consideration of lung volume reduction surgery for patients with upper lobe emphysema (heterogeneous disease) and low baseline exercise capacity to improve mortality, exercise capacity, and quality of life o lung transplantation (can increase quality of life and functional capacity in select patients) . augmentation therapy with IV human AAT for patients with severe AAT deficiency, AAT activity level <11 pm, and FEV, <65"/,, Antibiotics, glucocorticoids, oxygen supplementation, and noninvasive ventilation are indicated for exacerbations of COPD defined by increased sputum production, purulent sputum, and worsening dyspnea. Consider: . antibiotics: macrolide, tetracycline, B-lactam/B lactamase inhibitor . prednisone, 40 mg for 5 7 days o increased dose/frequency ofbronchodilators; combined SABA and short-acting muscarinic antagonist o noninvasive ventilation for acute hypercapnic respiratory failure with acidosis (unless patient is obtunded, vomiting, or has excessive secretions) . invasive mechanical ventilation if not responding or is not a candidate for noninvasive ventilation (see Invasive Mechanical Ventilation) r pulmonary rehabilitation following hospital discharge TESTYOURSELF A 55 year old man is evaluated for progressive dyspnea. He has a 40 pack-year cigarette smoking history. On spirometry his FEV, is 54% of predicted. He is using an albuterol inhaler with increasing frequency. Therapy is prescribed. ANSWER: For management, choose a LAMA or LABA.

. antibiotics: macrolide, tetracycline, B-lactam/B lactamase inhibitor . prednisone, 40 mg for 5 7 days o increased dose/frequency ofbronchodilators; combined SABA and short-acting muscarinic antagonist o noninvasive ventilation for acute hypercapnic respiratory failure with acidosis (unless patient is obtunded, vomiting, or has excessive secretions) . invasive mechanical ventilation if not responding or is not a candidate for noninvasive ventilation (see Invasive Mechanical Ventilation) r pulmonary rehabilitation following hospital discharge TESTYOURSELF A 55 year old man is evaluated for progressive dyspnea. He has a 40 pack-year cigarette smoking history. On spirometry his FEV, is 54% of predicted. He is using an albuterol inhaler with increasing frequency. Therapy is prescribed. ANSWER: For management, choose a LAMA or LABA. DOil'T BE TRICKED r Do not use short-acting and long-acting anticholinergic agents together. . Do not use theophylline. . PDE-4 inhibitors are not indicated for acute bronchospasm. . Lung volume reduction therapy is not indicated for patients with an FEVI <20% of predicted or a Dlco <20% of predicted. Cystic Fibrosis Diagnosis Chronic airway inflammation and bacterial infection characterize CF related pulmonary disease. Most adults with CF present with pulmonary disease. Characteristic findings are recurrent or persistent respiratory infections with Pseudomonas 343

Pulmonary and Critical Care Medicine aeruginosa, Staphylococcus anreus, Haemophilus influenzcre, ot Burkholderia cepacia; bronchiectasis; or hyperinflation' Other findings may include: . chronic sinusitis and nasal polyps . chronic or recurrent pancreatitis . clubbing . diabetes o infertility . malabsorption and steatorrhea The diagnosis is confirmed by a sweat chloride test followed by genetic testing. Treatment All patients should receive pneumococcal conjugate and polysaccharide vaccines, COMD 19 vaccine, and annual influenza vaccine. Select: . antipseudomonal antibiotics for acute pulmonary exacerbations . aerosolized tobramycin for suppression of chronic pulmonary infections . aerosolized recombinant human DNase (dornase alfa) or hypertonic saline for persistent airway secretions . inhaled bronchodilators and glucocorticoids for airway obstruction r nighttime noninvasive mechanical ventilation for nocturnal hypoxemia or hypercapnia . chestphysiotherapy o pancreatic enzyme replacement and fat-soluble vitamin supplementation if indicated Choose evaluation for transplantation for patients with advanced lung or liver disease. TESTYOURSELF A 34 year old woman has had frequent episodes of bronchitis and three episodes of pneumonia in the past 5 years. Between epi sodes, she has a persistent cough producing yellow sputum. She also has been treated for multiple episodes of sinusitis. The patient is a lifelong nonsmoker. BMI is 18. The thorax is hyperresonant to percussion and has diminished air movement bilaterally. Digital clubbing is present. ANSWER: For diagnosis, choose CF, For management, select sweat chloride testing followed by genetic testing. Diffuse Parenchymal Lung Disease Diagnosis DPLD most commonly presents with dyspnea and cough, and imaging abnormalities are most often diffuse rather than focal. Consider DPLD as a cause ofsubacute or chronic progressive dyspnea after infection and HF have been excluded. Lung examination findings can range from normal to inspiratory Velcro like crackles, or inspiratory squawks suggestive of fibrosis. The diagnosis and differential of DPLD is aided by paying particular attention to the following:

Diffuse Parenchymal Lung Disease Diagnosis DPLD most commonly presents with dyspnea and cough, and imaging abnormalities are most often diffuse rather than focal. Consider DPLD as a cause ofsubacute or chronic progressive dyspnea after infection and HF have been excluded. Lung examination findings can range from normal to inspiratory Velcro like crackles, or inspiratory squawks suggestive of fibrosis. The diagnosis and differential of DPLD is aided by paying particular attention to the following: o time course (typically months or years) . active smoking history (suggests respiratory bronchiolitis-associated interstitial lung disease, desquamative interstitial pneumonia, pulmonary Langerhans cell histocytosis, smoking-related interstitial fibrosis) 344

Pulmonary and Critical Care Medicine ldiopathic PulmonarY Fibrosis Diagnosis IPF, the most common of the idiopathic interstitial pneumonias, is a fibrosing interstitial pneumonia' C)nset occurs befvveen 50 over several months in and 70 years of age. Characteristic findings are the gradual onset of a nonproductive cough and dyspnea older adults. Physical examination findings include: . normal temperature . bibasilar crackles ("dry" end inspiratory and "Velcro-1ike" in quality) . late-phase cor pulmonale . clubbing (50'2, of patients) Testing Chest x ray shows peripheral reticular opacities and honeycomb changes at the lung bases. HRCT scan reveals subpleural cystic changes and traction bronchiectasis. A restrictive pattern with decreased Dt.co is lound on PFTs. Diagnosis is based on clinical and radiographic findings, absence of exposure to substances or drugs that can cause interstitial lung disease, and negative evaluation for rheumatologic disease. Treatment Lung transplantation may improve survival and quality of life. Pirfenidone and nintedanib have demonstrated benefit in slowing disease progression for select persons. Oxygen therapy is indi cated {br patients with hypoxemia. DOil'T BE TRICKED . Do not intubate and mechanically ventilate patients with respiratory failure caused by IpF. ldiopathic Pulmonary Fibrosis: High-resolution, thin-section chest CI scan . Glucocorticoids are ineffective in IpF. showing extensive parenchymal involvement with Iibrotic and honeycomb changes compatible with lPF. Sarcoidosis Diagnosis Sarcoidosis is a multisystem granulomatous inflammatory disease of unknown cause. Ninety percent of patients with sarcoido sis have pulmonary involvement, which may include a clinical presentation consistent with DpLD. Possible fi ndings include: . fever, weight loss, and night sweats . dry cough and dyspnea 346

Pulmonary and Critical Care Medicine . eye pain or burning and photosensitivity OEN o violaceous or erythematous indurated papules, plaques, or nodules of the central face (lupus pernio); often associated with pulmonary disease . a variety of papular, nodular, and plaque like cutaneous lesions . lymphadenopathy and hepatosplenomegaly o asymmetric joint swelling o Lofgren syndrome (fever, bilateral hilar lymphadenopathy, EN, and often ankle arthritis) . uveoparotid fever (Heerfordt syndrome, featuring anterior uveitis, parotid gland enlargement, lacial palsy, and fever) Testing A detinite diagnosis requires a compatible clinical picture, pathologic demonstration of noncaseating granulomas, and the exclusion of alternative explanations for the abnormalities (known causes of granulomatous inflammation such as infection). A diagnosis can be made without histologic studies in a patient with all f'eatures of Lofgren syndrome (95'1, diagnostic specific ity) or in patients with asymptomatic hilar lymphadenopathy (stage I pulmonary sarcoidosis). Diagnostic studies include: . chest x ray (bilateral hilar lymphadenopathy + parenchymal lung disease, or lung parenchymal disease) . HRCT (nodules along bronchovascular bundles) . PFT (sarcoidosis may cause obstruction, restriction, or both) . fiberoptic bronchoscopy with transbronchial biopsy and bronchoalveolar lavage for interstitial lung disease or nodu lar lung involvement . serum calcium level (kidney stones and hypercalcemia) . serum PTH level (low) for patients with hypercalcemia/ hypercalciuria . l,2s-dihydroxy vitamin D, level (high) in patients with kid Waxy Papular Lesions: Waxy papular lesions on the nose consistent with sar' ney stones and hypercalcemia coid osis. . biopsy of suspicious skin lesions o slit lamp examination fbr all patients r ECG to rule out heart block or other cardiac abnormalities in all patients DON'T BE TRICKED . Always rule out TB and fungal infections by ordering appropriate stains and culture on tissue biopsy. . Exposure to beryllium (often found in workers in tight bulb or semiconductor factories) may cause a sarcoidosis-like clinical syndrome. . Don't select a serum ACE level. It won't conflrm the diagnosis or help in managing sarcoidosis.

DON'T BE TRICKED . Always rule out TB and fungal infections by ordering appropriate stains and culture on tissue biopsy. . Exposure to beryllium (often found in workers in tight bulb or semiconductor factories) may cause a sarcoidosis-like clinical syndrome. . Don't select a serum ACE level. It won't conflrm the diagnosis or help in managing sarcoidosis. Treatment Topical glucocorticoids are prescribed for skin lesions or anterior uveitis, and inhaled glucocorticoids are used for nasal polyps or airway disease. Oral glucocorticoids are indicated for progressive or symptomatic pulmonary sarcoidosis; hypercaicemia; or cardiac, ophthalmologic, or neurologic sarcoidosis. Patients with glucocorticoid refractory disease are treated with immuno suppressive, cytotoxic, and antimalarial agents. Ldfgren syndrome has a very high rate (80'2,) of spontaneous remission and resolution. 347

Pulmonary and Critical Care Medicine DON'T BE TRICKED . Do not treat asymptomatic pulmonary sarcoidosis. TEST YOURSELF A 66 yelr old man is hospitrrlizecl because ol:tzotemia lnd hyper calcenrirr. Labor-ator.r studies shorv a norntal serum P'['H lere] and an elcvated 1.25 dihydrory vitanrir.t D, level. A chest x nty shorts an illterstitial inflltrate irnd an enlrrged lelt parirtracheal lynrph node. ANSWER: For diagnosis, choose sarcoidosis. For mirnagement, select trlnsbronchial lung biopsli Occupational Lung Disease DiagnOSiS Sarcoidosis: X'ray shows bilateral hilar lymphadenopathy characteristic of sar coidosis sarcoidosis can be associated with interstitial lung disease clinical manifestirtions may ir.rclude asthma, copD. constrictive bronchiolitis. rhinitis, and DPl.D. Symptom onset following exp<r sllre ciln be acutc (reactive airways diseaseismall airways dysfunction as occLlrs in acutc chiorine gas exposure) as rtell as prolonged or subacute with a sigr.rificant lirtent period (as u,ith asbestosis). STUDY TABLE: Clues to Occupational Lung Disease Relationship to clinical symptoms and work is temporal: Symptoms worsen during or after work Symptoms abate or improve with time off or away from the workplace Work-related changes in FEVI or PEF Coworkers are affected with similar symptoms Workplace has known respiratory hazards (these can be identified by Material Safety Data Sheets from the workplace) Symptoms fail to respond to initial therapy or are further exacerbated upon returning to work Onset of a respiratory disorder without typical risk factors Clustering of disease in one geographic area A positive response to a specific inhalation challenge test is the "gold stand:rrd" lbr diaplnosis but not always necess:rry. Treatment The overriding principle is cliscontinuing the exposure. Occupational asthma irnd reactive air-ways dysfunction syndrome :rre treated u,ith inhaled glucocorticoids. DON'T BE TRICKED . The incidence of TB is increased in those with silicosis and should be evaluated in patients with silicosis. fever. and cough

Treatment The overriding principle is cliscontinuing the exposure. Occupational asthma irnd reactive air-ways dysfunction syndrome :rre treated u,ith inhaled glucocorticoids. DON'T BE TRICKED . The incidence of TB is increased in those with silicosis and should be evaluated in patients with silicosis. fever. and cough IEST YOURSEtF A previously healthy ,15 lear old man has a cough of 6 months' duration. He is a lifelong nonsmoker and n,orks as an automotrilc spray painter. Physical examinirtion discloses a fert, expiratory r,a,rheezes. FEV, is 0.65 and FEV,rf!6 ratio is 6511, of predicted. r,r,ith a 22'){, improvement after bronchodilator administration. ANSWER: For cliagnosis, choose occupational asthma. For managentent, select spirometry or PEF measurement before and atter r,r,ork (or during vacation). 348

1 l i r Pulmonary and Critical Care Medicine I I Pulmonary Hypertension 1 I '1 I Diagnosis \ I pressure s15 mm Hg' PH is defined by a resting mean pulmonary arterial pressure of >20 mm Hg and a pulmonary capillary wedge The current classification system subdivides PH into five groups' I

I Diagnosis \ I pressure s15 mm Hg' PH is defined by a resting mean pulmonary arterial pressure of >20 mm Hg and a pulmonary capillary wedge The current classification system subdivides PH into five groups' I o Group 1is distinguished by disease localized to small pulmonary arterioles resulting in high pulmonary vascular resistance I and is referred to as PAH. I o Groups 2 through 5 refer to important secondary causes of PH and include left-sided heart disease, respiratory disorders (COPD, interstitial lung disease, and sleep-disordered breathing), and chronic venous thromboembolic disease' I Characteristic symptoms of PH include: I . unexplaineddyspnea I . decreased exercise tolerance : I . syncope and near syncope i o chest pain o lower extremity edema Physical examination findings indicating RV failure may include an RV heave, right-sided Sr, widely split Sr, increased Pr, increased jugular venous distention with a large o wave, and a murmur of TR. Look for use of fenfluramine, amphetamines, and cocaine, as well as the presence of Raynaud phenomenon (suggesting SLE and SSc) and history ofVTE. Testing Typical evaluation of Group 1 PH (PAH) includes:

Physical examination findings indicating RV failure may include an RV heave, right-sided Sr, widely split Sr, increased Pr, increased jugular venous distention with a large o wave, and a murmur of TR. Look for use of fenfluramine, amphetamines, and cocaine, as well as the presence of Raynaud phenomenon (suggesting SLE and SSc) and history ofVTE. Testing Typical evaluation of Group 1 PH (PAH) includes: o echocardiography as the initial study . right heart catheterization to confirm the diagnosis and quantiff the degree of PH o left heart catheterization and coronary angiography exclude LV dysfunction as a cause of PH If the diagnosis of PAH is confirmed, the next step is a vasoreactivity test using vasodilating agents to measure changes in pul- monary artery pressure with a right heart catheter in place. Additional recommended tests to rule out other causes of PH include PFTs, HRCT (if considering interstitial lung disease), liver function tests, polysomnography if clinically indicated, and serologic tests for HIV infection or connective tissue disease. In some patients (<5%,) after an acute PE, thromboemboli within the pulmonary arteries become remodeled into large occlusive scars, causing CTEPH and leading to right-sided HF. Two diagnostic criteria for CTEPH: o pulmonary artery pressure >20 mm Hg in the absence of left-sided HF o compatible imaging evidence of chronic thromboembolism by V/Q scanning DO]I'T BE TRICKED o Most cases ofPH are attributed to left sided heart disease and hypoxic respiratory disorders. . Do not select CTA to diagnose CTEPH. A Vi e scan is superior. 352

Pulmonary and Critical Care Medicine Treatment Therapy fbr PH groups 2 through 5 is typically directed at the underlying condition. For Group I PH (PAH), vascular targeted treatments provide symptomatic relief but are not curative. o Calcium channel blockers are used for patients demonstrating a vasodilator response on right heart catheterization. I o Combination therapy with ambrisentan (prostacyclin analogue) and tadalafil (pDE S inhibitor) is the recommended first line therapy if the patient is willing and able to tolerate it. Lung or heart lung transplantation should be considered for patients in whom drug treatment is unsuccessful. i I . Oxygen therapy is indicated for O, saturation <90,/u. i I Life long anticoagulant therapy is indicated in all patients with CTEpH. pulmonary thromboendarterectomy is the only defini I I tive therapy for CTEPH. s I DOil'T BE TRICKED o Do not select calcium channel blockers ifpulmonary artery pressure is not decreased with a vasoreactivity test Lung Cancer Screening ln high risk populations, lung cancer screening results in a 20% lung cancer mortality reduction. Screen patients between the ages of 50 and 80 years (guidelines vary) who have a 20 pack year history of smoking and who are currently smoking or have quit within the last 15 years. Continue annual low dose CT imaging until comorbidity limits survival or the patient reaches the age of80 years. Stop screening in patients who have stopped smoking lbr 15 years. DOil'T BE TRICKED r The risks ofscreening outweigh the beneflt in patients at low risk for lung cancer Hemoptysis Diagnosis Bronchitis, bronchogenic carcinoma, and bronchiectasis are the most common causes of hemoptysis.

Lung Cancer Screening ln high risk populations, lung cancer screening results in a 20% lung cancer mortality reduction. Screen patients between the ages of 50 and 80 years (guidelines vary) who have a 20 pack year history of smoking and who are currently smoking or have quit within the last 15 years. Continue annual low dose CT imaging until comorbidity limits survival or the patient reaches the age of80 years. Stop screening in patients who have stopped smoking lbr 15 years. DOil'T BE TRICKED r The risks ofscreening outweigh the beneflt in patients at low risk for lung cancer Hemoptysis Diagnosis Bronchitis, bronchogenic carcinoma, and bronchiectasis are the most common causes of hemoptysis. DOil'T BE TRIGKED . Confirm that a patient has hemoptysis rather than epistaxis or GI bleeding; then check the platelet count and coagulation parameters. gTUDY TABLE: Diagnostic Tests for Hemoptysis Test Considerations Chest x-ray Crucial initial study, but normal findings do not exclude lung cancer Fi beroptic bronchoscopy For patients at high risk for lung cancer even if chest x-ray is normal Chest CT Alternative test when fiberoptic bronchoscopy is contraindicated or when bleeding persists despite normal bronchoscopic findings Treatment Treatment is cause specific. The cause of death fiom massive hemoplysis is asphyxiation from airway obstruction' If the bleed ing site can be localized to one lung, position the patient with the bleeding lung in the dependent position' Intubation and mechanical ventilation are required when adequate gas exchange is threatened. Angiography can localize and treat bronchial artery lesions. 353

Pulmonary and Critical Care Medicine l may first be mani Dillicult ventilation or complications of mechanical ventilation resulting from changes in airway resistance f'ested by an increase in the peak inspiratory pressure alone, resulting from: i j . bronchospasm l . secretions in airways, endotracheal tube, or ventilator tubing I . obstructing mucus plug '1 l . agitation with dyssynchrony with the ventilator II When a patient can maintain an arterial O, saturation >90'1, breathing Fto, <0'5, PEEP <5 cm HrO, and pH >7'30' it is reasonable 1 to consider extubation. Paired daily spontaneous awakening trials (withdrawal of sedatives) with daily spontaneous breathing I trials result in a reduction in mechanical ventilation time, ICU and hospital length of stay, and 1 year mortality rates' l t DOil'T BETRICKED r Do not select synchronized intermittent mandatory ventilation as a weaning mode, because studies have demonstrated it actually takes longer to liberate patients from the ventilator.

trials result in a reduction in mechanical ventilation time, ICU and hospital length of stay, and 1 year mortality rates' l t DOil'T BETRICKED r Do not select synchronized intermittent mandatory ventilation as a weaning mode, because studies have demonstrated it actually takes longer to liberate patients from the ventilator. TESTYOURSETF A 73-year-old woman who weighs 56 kg (123 lb) is admitted to the ICU with an exacerbation of severe COPD. lntubation and mechanical ventilation are required: FIo, of 0.4, tidal volume of 450 mL, and respiration rate of l6lmin. Thirfy minutes later, her BP has dropped to 82/60 mm Hg. She is restless and has diffuse wheezing with prolonged expiration' ANSWER: For diagnosis, choose auto PEEP. For management, select treatment of airway obstruction' Sepsis Diagnosis Operationally, sepsis can be identified whenever infection is known or suspected and clinical criteria defining organ dysfunc- tion are met. Know the differential diagnosis of shock syndromes and their associated hemodynamic parameters STU3Y TAEL*: Shock Syndromes Condition Characteristics Cardiogenic shock Low cardiac output, elevated PCWB and high SVR Elevated CVe 53, pulmonary crackles, edema, and CVD risk factors Hypovolemic shock Low cardiac output, low PCWP, and high SVR Obvious source of volume loss (hemorrhage, dehydration, diarrhea, nausea/vomiting) Obstructive shock Low cardiac output, variable PCWB and high SVR Consider cardiac tamponade, PE, and tension pneumothorax Anaphylactic shock High cardiac output, normal PCWP, and low SVR Rash, urticaria, angioedema, and wheezing/stridor Septic shock High cardiac output (early)that can become depressed (late) and low SVR Known or suspected infection SVR = systemic vascular resistance. 360

Pulmonary and Critical Care Medicine Treatment Treatment is supportive and includes early mobility and ongoing physical and occupational therapy. TEST YOURSEIF A 65 year old woman with ffpe 2 diabetes cannot be weaned from mechanical ventilation' She has required prolonged respiratory support because of ARDS secondary to septic shock and bacterial pneumonia. Her course was complicated by an episode of AKI. During spontaneous weaning trials, her tidal volume is low and respiratory rate is elevated. She has weakness of her extremities and hyporeflexia. ANSWER: For diagnosis, choose ICU acquired weakness. For management, select treatment with physical and occupational therapy. Hyperthermic Emergencies Severe hyperthermia is temperature >40.0'C (104.0'F) resulting from a failure of normal thermoregulation. Findings include loss of consciousness, muscle rigidity, seizures, and rhabdomyo$sis with kidney failure, DlC, and ARDS.

TEST YOURSEIF A 65 year old woman with ffpe 2 diabetes cannot be weaned from mechanical ventilation' She has required prolonged respiratory support because of ARDS secondary to septic shock and bacterial pneumonia. Her course was complicated by an episode of AKI. During spontaneous weaning trials, her tidal volume is low and respiratory rate is elevated. She has weakness of her extremities and hyporeflexia. ANSWER: For diagnosis, choose ICU acquired weakness. For management, select treatment with physical and occupational therapy. Hyperthermic Emergencies Severe hyperthermia is temperature >40.0'C (104.0'F) resulting from a failure of normal thermoregulation. Findings include loss of consciousness, muscle rigidity, seizures, and rhabdomyo$sis with kidney failure, DlC, and ARDS. STUDY TABLE: Severe Hyperthermia Causes and Therapy Diagnosis Suggestive History Key Examination Treatment Notes Findings Heat stroke (exertional) Young athlete or soldier Encephalopathy and lce water immersion Rapid response with environmental fever supports diagnosis exposure Nonexertional heat Age >70 years Encephalopathy and Evaporative, external Avoid ice water stroke fever cooling immersion Use of anticholinergic, sympathomimetic, and diuretic drugs Malignant hyperthermia Exposure to volatile Masseter muscle Stop the inciting drug Monitor and treat; t K* anesthetics ( halothane, rigidity; t arterial Pco, and l arterial Pco2 isoflurane), Dantrolene succinylcholine, or decamethonium Neuroleptic malignant Haloperidol, olanzapine, Altered mentation, Stop the inciting drug Resolves over days to syndrome quetiapine, and severe rigidity, t HR, weeks Dantrolene risperidone or lBP withdrawal from r-dopa; Bromocriptine onset over days to No myoclonus, J reflexes weeks Severe serotonin Onset within 24 h of Agitation, rigidity, Stop the inciting drug Resolves in 24 hours syndrome' initiation or increasing myoclonus, l reflexes dose Benzodiazepines Cyproheptadine a cause o{ severe hyperthermia but commonly con{used with neuroleptic malignant syndrome.

STUDY TABLE: Severe Hyperthermia Causes and Therapy Diagnosis Suggestive History Key Examination Treatment Notes Findings Heat stroke (exertional) Young athlete or soldier Encephalopathy and lce water immersion Rapid response with environmental fever supports diagnosis exposure Nonexertional heat Age >70 years Encephalopathy and Evaporative, external Avoid ice water stroke fever cooling immersion Use of anticholinergic, sympathomimetic, and diuretic drugs Malignant hyperthermia Exposure to volatile Masseter muscle Stop the inciting drug Monitor and treat; t K* anesthetics ( halothane, rigidity; t arterial Pco, and l arterial Pco2 isoflurane), Dantrolene succinylcholine, or decamethonium Neuroleptic malignant Haloperidol, olanzapine, Altered mentation, Stop the inciting drug Resolves over days to syndrome quetiapine, and severe rigidity, t HR, weeks Dantrolene risperidone or lBP withdrawal from r-dopa; Bromocriptine onset over days to No myoclonus, J reflexes weeks Severe serotonin Onset within 24 h of Agitation, rigidity, Stop the inciting drug Resolves in 24 hours syndrome' initiation or increasing myoclonus, l reflexes dose Benzodiazepines Cyproheptadine a cause o{ severe hyperthermia but commonly con{used with neuroleptic malignant syndrome. DOil'T BE TRICKED . Neuroleptic malignant syndrome may occur in patients who have abruptly discontinued I dopa for parkinson disease. o The serotonin syndrome is often caused by the use ofSSRIs and the addition ofa second drug that increases serotonin release or blocks its uptake or metabolism.

STUDY TABLE: Severe Hyperthermia Causes and Therapy Diagnosis Suggestive History Key Examination Treatment Notes Findings Heat stroke (exertional) Young athlete or soldier Encephalopathy and lce water immersion Rapid response with environmental fever supports diagnosis exposure Nonexertional heat Age >70 years Encephalopathy and Evaporative, external Avoid ice water stroke fever cooling immersion Use of anticholinergic, sympathomimetic, and diuretic drugs Malignant hyperthermia Exposure to volatile Masseter muscle Stop the inciting drug Monitor and treat; t K* anesthetics ( halothane, rigidity; t arterial Pco, and l arterial Pco2 isoflurane), Dantrolene succinylcholine, or decamethonium Neuroleptic malignant Haloperidol, olanzapine, Altered mentation, Stop the inciting drug Resolves over days to syndrome quetiapine, and severe rigidity, t HR, weeks Dantrolene risperidone or lBP withdrawal from r-dopa; Bromocriptine onset over days to No myoclonus, J reflexes weeks Severe serotonin Onset within 24 h of Agitation, rigidity, Stop the inciting drug Resolves in 24 hours syndrome' initiation or increasing myoclonus, l reflexes dose Benzodiazepines Cyproheptadine a cause o{ severe hyperthermia but commonly con{used with neuroleptic malignant syndrome. DOil'T BE TRICKED . Neuroleptic malignant syndrome may occur in patients who have abruptly discontinued I dopa for parkinson disease. o The serotonin syndrome is often caused by the use ofSSRIs and the addition ofa second drug that increases serotonin release or blocks its uptake or metabolism. 362

Pulmonary and Critical Care Medicine TESTYOURSETF A 45 year old woman undergoes open cholecystectomy. At the conclusion of the operative procedure, her temperature has abruptly increased to39.2 "C (102.5'F). ANSWER: For diagnosis, choose malignant hyperthermia caused by anesthesia. For management, select dantrolene initiation. Anaphylaxis Diagnosis Anaphylaxis is a life-threatening syndrome caused by the release of mediators from mast cells and basophils triggered by an IgE allergen interaction (anaphylactic reqction) or by a non-antibody-antigen mechanism (anaphylactoid reaction). The most common causes are nut ingestion, insect stings, latex, and medications (penicillin, NSAIDs, aspirin). Flushing, urticaria, conjunctival pruritus, bronchospasm, nausea, and vomiting usually develop within minutes to t hour if the antigen was injected or up to 2 hours if ingested. Anaphylactic shock is caused by severe hypovolemia (fluid shifts owing to increased vascular permeability) and vasodilatation. The diagnosis of anaphylaxis is made clinically. Death occurs from refractory bronchospasm, respiratory failure with upper airway obstruction, and cardiovascular collapse. DON'T BE TRICKED . Consider latex allergy as the cause of anaphylaxis during surgery or anaphylaxis in a woman during coitus. Treatment IM or IV epinephrine is first line therapy even if the only presenting signs are hives or pruritus. Repeated doses are often neces sary. Adjuvantly use inhaled bronchodilators for bronchospasm and IV saline for shock or hypotension. B-Blockers may blunt the effect of epinephrine, but epinephrine remains the drug of flrst choice. Patients with diffuse rash or anaphylaxis from hymenoptera sting (bee, yellow jacket, and wasp) should undergo venom skin testing and immunotherapy. DO]I'T BE TRICKED o Glucoeorticoids are not flrst line therapy for anaphylaxis; evidence for an adjunctive role is weak. IEST YOURSETF A 2S-year-old woman has shortness of breath and wheezing after a bee sting t hour ago. Her BP is 80/50 mm Hg and HR is 110/min. ANSWER: For diagnosis, choose anaphylaxis. For management, select epinephrine and IV fluids, observation for at least 12 hours, and self-administered epinephrine at discharge. Angioedema Diagnosis Angioedema is characterized by a sudden, temporary edema, usually of the lips, face, hands, feet, penis, or scrotum. Abdominal pain may be present owing to bowel wall edema.

IEST YOURSETF A 2S-year-old woman has shortness of breath and wheezing after a bee sting t hour ago. Her BP is 80/50 mm Hg and HR is 110/min. ANSWER: For diagnosis, choose anaphylaxis. For management, select epinephrine and IV fluids, observation for at least 12 hours, and self-administered epinephrine at discharge. Angioedema Diagnosis Angioedema is characterized by a sudden, temporary edema, usually of the lips, face, hands, feet, penis, or scrotum. Abdominal pain may be present owing to bowel wall edema. 353

Pulmonary and Critical Care Medicine Mast cell -mediated angioedema is often associated with urticaria, bronchospasm, or hypotension. This can be the result of an allergic reaction (peanuts, shrimp, latex, insect stings) or to direct mast cell stimulation (NSAIDs, radiocontrast media, opioids). Bradykinin mediated angioedema is NOT associated with urticaria. In the setting of angioedema without urticaria, the differen- tial is very limited. Diagnose by testing for quantitative and functional levels of Cl esterase inhibitor and C4 complement levels. Sf USY TA*t"E: Differential Diagnosis of Bradykinin-Mediated Angioedema Condition Historical Clues/Disease Associations Hereditary angioedema Family history of angioedema Acquired C1 inhibitor deficiency Lymphoma, MGUS, or SLE ACE inhibitor effect Medication history DOil'T BE TRICKED . In patients with urticaria and angioedema, do not diagnose hereditary angioedema. Treatment Select epinephrine for acute episodes of mast cell mediated (allergic) angioedema with airway compromise or hypotension. TESTYOURSEIF A 40-year old man has a 1 year history of cramping abdominal pain and 2- to 3 day episodes offace and hand swelling that have not responded completely to epinephrine and antihistamines. His mother died suddenly of "suffocation." ANSWER: For diagnosis, choose hereditary angioedema. For management, select serum C4 and Cl inhibitor levels (functional and antigenic) and treatment of severe acute episodes of swelling with C1 inhibitor concentrate. Angioedema: Angioedema differs from urticaria in that it covers a larger surface area and involves the dermis and subcutaneous tissues. Smoke lnhalation Ensuring upper airway patency is the priority. . Patients with a visibly damaged airway or stridor require immediate intubation. o Assess carbon monoxide level. Cyanide exposure is common in house fires where cyanide is produced and aerosolizedwhen vinyl burns. Cyanide is a common coexposure with carbon monoxide. A normal LDH level excludes cyanide poisoning. Treat cyanide poisoning with hydroxocobalamin.

. Patients with a visibly damaged airway or stridor require immediate intubation. o Assess carbon monoxide level. Cyanide exposure is common in house fires where cyanide is produced and aerosolizedwhen vinyl burns. Cyanide is a common coexposure with carbon monoxide. A normal LDH level excludes cyanide poisoning. Treat cyanide poisoning with hydroxocobalamin. DON'T BE TRICKED o Patients with inhalational injury involving the lower airways typically present with a clear chest x_ray; wheezing, cough, and dyspnea manifest 12 to 86 hours after exposure. . Normal oxygen saturation does not exclude either carbon monoxide or cyanide poisoning. 364

Pulmonary and Critical Care Medicine STUSY TAELE: Toxic Syndrome Manifestations and Treatments (Continued) Syndrome Manifestations Representative Drugs Treatment Anticholinergic Hyperthermia Antihistamines Physostigmine forthose with peripheral and CNS symptoms Dry skin and mucous Tricyclic antidepressants membranes Benzodiazepines for agitation Antiparkinson agents Agitation, delirium May require ventilatory support Atropine Tachyca rdia, tachypnea Scopolamine Hypertension Mydriasis Opioids Miosis Morphine and related drugs Naloxone Respiratory depression Heroin Lethargy, confusion Hypothermia Bradycardia Hypotension SLUDGE = Salivation, Lacrimation, increased Urination and Defecation, Gastrointestinal upset, and Emesis. : : : I ) 1 \ : 366

F Rheumatology Approach to the Patient Analyze joint disease using three parameters: acuit! (acute or chronic), inflammation (inflammatory or noninflammatory), and number of joints involved (monoarticular, oligoarticular, or polyarticular). STUDY TABI-E: Features of lnflammatory vs. Noninflammatory Pain Feature lnflammatory Pain Noninflammatory Pain Physical examination findings Erythema; warmth; soft-tissue swelling No soft-tissue swelling; minimal or no warmth; bony enlargement and joint effusions may occur in OA Morning stiffness >60 min <30 min Constitutional symptoms Fever; fatigue; malaise Generally absent Synovialfluid Leukocyte count >2000/pL, neutrophils in Leukocyte count between 200/pLand 2000/1tL, acute inflammation, monocytes in chronic predominantly monocytes inflammation Other laboratory findings Elevated ESR, CRP; anemia o{ inflammation lnflammatory markers usually normal or minimally elevated

STUDY TABI-E: Features of lnflammatory vs. Noninflammatory Pain Feature lnflammatory Pain Noninflammatory Pain Physical examination findings Erythema; warmth; soft-tissue swelling No soft-tissue swelling; minimal or no warmth; bony enlargement and joint effusions may occur in OA Morning stiffness >60 min <30 min Constitutional symptoms Fever; fatigue; malaise Generally absent Synovialfluid Leukocyte count >2000/pL, neutrophils in Leukocyte count between 200/pLand 2000/1tL, acute inflammation, monocytes in chronic predominantly monocytes inflammation Other laboratory findings Elevated ESR, CRP; anemia o{ inflammation lnflammatory markers usually normal or minimally elevated STUDY TAELET Synovial Fluid Analysis Normal Noninflammatory lnflammatory Crystal lnduced lnfectious Hemorrhagic Appearance Clear/yellow/ Clear/yellow/ Yellow/white/ Yellow/white/ Yellow/white/ Red/opaque tra nsparent transparent translucenV translucenV opaque opaque opague Leukocyte <200/ytL 200-2000/1tL 2000-20,000/pL 1 0,000-50,000/pL >50,000/pL count (may be higher) (may be higher) (may be lower) Other studies Negative Gram Negative Gram Negative Gram Negative Gram Positive Gram Negative Gram stain; negative stain; negative stain; negative stain; positive stainb; positive stain; negative culture culture culture crystalsa culture' culture

STUDY TAELET Synovial Fluid Analysis Normal Noninflammatory lnflammatory Crystal lnduced lnfectious Hemorrhagic Appearance Clear/yellow/ Clear/yellow/ Yellow/white/ Yellow/white/ Yellow/white/ Red/opaque tra nsparent transparent translucenV translucenV opaque opaque opague Leukocyte <200/ytL 200-2000/1tL 2000-20,000/pL 1 0,000-50,000/pL >50,000/pL count (may be higher) (may be higher) (may be lower) Other studies Negative Gram Negative Gram Negative Gram Negative Gram Positive Gram Negative Gram stain; negative stain; negative stain; negative stain; positive stainb; positive stain; negative culture culture culture crystalsa culture' culture blue when parallel to the axis and yellow when perpendicular. bGram stain sensitivity for infection is approximately 30% to 50%. 'Nearly all cultures are positive except for infection caused by Neisseria gonorhoeae, which may be positive in 50olo or fewer cases. Categorization of arthritis by number and distribution of involved joints narrows the differential diagnosis.

blue when parallel to the axis and yellow when perpendicular. bGram stain sensitivity for infection is approximately 30% to 50%. 'Nearly all cultures are positive except for infection caused by Neisseria gonorhoeae, which may be positive in 50olo or fewer cases. Categorization of arthritis by number and distribution of involved joints narrows the differential diagnosis. STUDY IABlE: Categories of Common Joint Disease Acuity and lnflammation Monoafticular Oligoarticular (2-4 Joints) Polyarticular (25 Joints) Acute inflammationu Bacterial infection Disseminated gonococcal Viral infeaions: hepatitis A infection and B, parvovirus, rubella, Crystal induced HIV RF Lyme disease Chronic inflammation lnfections related to fungi, Spondyloarthropathies RA, SLE, psoriatic arthritis, mycobacteria, spirochetes crystalline arthritis (syphilis and Lyme disease) Chronic without inflammation OA OA OA "Acute is usually defined as symptoms for less than 6 weeks; chronic is symptoms lasting >6 weeks. 367