Pulmonary and Critical Care Medicine

Pulmonary and Critical Care Medicine
Pulmonary Function Tests

Indications
The four pulmonary function tests commonly used to measure static lung function are spirometry, flow-volume loops, lung
volumes, and Dlco.
Key Tests and Patterns

Spirometry is used to diagnose airflow obstruction such as asthma, COPD, and bronchiectasis.
• FEV1/FVC <0.7 indicates airflow obstruction.

• A ≥12% increase in either FEV1 or FVC and an increase ≥200 mL from baseline in either parameter with bronchodilator
therapy indicates reversible airway obstruction.
• Equal reductions in FEV1 and FVC suggest restrictive lung disease.
Flow-volume loops can help localize anatomic sites of airway obstruction. Refer to the “Flow-Volume Loops” figures and consider
the following factors:
• a “scooped-out” pattern with a decreased slope on the expiratory curve that does not improve with bronchodilation
indicates COPD
• a “scooped-out” pattern with a decreased slope on the expiratory curve that improves with bronchodilation indicates
reversible obstructive airway disease (asthma)
• “flattening” in both inspiratory and expiratory curves and decreased airflow indicates fixed obstruction (e.g., tracheal
stenosis)
• following attainment of peak flow, the flow rate declines linearly and proportionally to volume, producing a relatively
straight slope characteristic of a normal flow-volume loop
Lung volumes aid in confirming findings on spirometry:
• TLC <80% indicates restrictive lung disease (fibrosis, neuromuscular disease, skeletal abnormalities)
• decreased vital capacity with increased residual volume indicates airflow obstruction
Dlco evaluates gas transport across the alveolar-capillary membrane.
STUDY TABLE: Interpreting Dlco

Finding Interpretation
↓ Dlco and reduced lung volumes Pulmonary fibrosis

↓ Dlco and normal lung volumes Pulmonary vascular disease, anemia
↓ Dlco and airflow obstruction COPD, bronchiectasis
↑ or normal Dlco and airflow obstruction Asthma
↑ Dlco Pulmonary hemorrhage, left-to-right shunt, polycythemia
DON’T BE TRICKED
• In patients with low lung volumes, a normal Dlco suggests an extrapulmonary cause (e.g., obesity).
344
.
STUDY TABLE: Understanding Important Pulmonary Tests

Tests Considerations
Pulse oximetry Measures percentage of oxyhemoglobin; performed at rest or during exercise

Use co-oximetry when carboxyhemoglobin is suspected (e.g., smoke inhalation, carbon monoxide poisoning)
Bronchial challenge Challenges include cold air, exercise, histamine, and methacholine
testing
Airflow is measured before and after challenge
Methacholine is commonly used for patients with a history suggestive of bronchospastic disease but normal
spirometry
Cardiopulmonary Performed for unexplained dyspnea, symptoms disproportionate to the measured pulmonary function
exercise testing abnormality, and other exercise-related symptoms
6-Minute walk test Useful to assess disability, need for supplemental oxygen, and prognosis in chronic lung conditions
Simple oximetry and desaturation studies are performed at rest and with exertion
Exhaled nitric oxide test Exhaled nitric oxide is increased in patients with airway inflammation, including asthma
DON’T BE TRICKED
• Pulse oximetry is normal in patients with carbon monoxide and cyanide poisoning.
• Pulse oximetry may be falsely low in patients with shock.
Flow-Volume Loops: Flow-volume loops plot flow (L/sec) as a function of volume.
345
.
Asthma
Diagnosis
The cardinal features of asthma are reversible airway obstruction, inflammation, and airway hyperresponsiveness.
Characteristic findings are wheezing and dyspnea; consider any cough that is nocturnal, seasonal, or related to a workplace
or activity as possible asthma. Look for nasal polyps and aspirin sensitivity.
Testing
Diagnostic studies include spirometry before and after bronchodilator administration. In patients with atypical features, per-
form PFTs. The presence of airflow irreversibility, restrictive patterns, and significantly reduced vital capacity suggest other
diseases.
Bronchoprovocation testing is indicated for patients with a suggestive clinical history for asthma but normal spirometry.
Bronchoprovocation testing with exercise is indicated to diagnose exercise-induced asthma in patients who have dyspnea fol-
lowing exercise but normal spirometry.
DON’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 one cause.
• Wheezing does not equal asthma; consider HF, COPD, vocal cord dysfunction, and upper airway obstruction.
STUDY TABLE: Differential Diagnosis of Asthma

Disease Characteristics
Chronic Chest x-ray shows “photographic-negative” pulmonary edema (peripheral pulmonary edema)
eosinophilic
Clinical findings: striking peripheral blood eosinophilia, fever, and weight loss in a long-term smoker
pneumonia
Diagnose by bronchoscopy with biopsy or bronchoalveolar lavage showing a high eosinophil count
Allergic Asthma manifests with eosinophilia, markedly high serum IgE levels, and intermittent pulmonary infiltrates
bronchopulmonary
Diagnose with positive skin test for Aspergillus and IgG and IgE antibodies to Aspergillus, characteristic
aspergillosis
radiographic opacities in the upper lobes
This is often overlooked until onset of more advanced disease, including fixed obstruction and bronchiectasis
Eosinophilic Upper airway and sinus disease precedes difficult-to-treat asthma; look for flares associated with use of
granulomatosis leukotriene inhibitors and glucocorticoid tapers
with polyangiitis
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 visual-
ization of the larynx during an acute episode may be helpful in diagnosing tracheal obstruction
and vocal cord dysfunction. Asthma may be an extraesophageal manifestation of GERD.
TEST YOURSELF
A 17-year-old man has difficult-to-control asthma associated with inspiratory tracheal sounds
and minor wheezing. A flow-volume loop is shown.
ANSWER: For diagnosis, choose vocal cord dysfunction characterized by flattening of the
inspiratory portion of the flow-volume loop.
346
.
Treatment
Asthma must be classified correctly to select proper therapy. Severity is based on the worst feature present.
STUDY TABLE: Step Classification of Asthma

Step Classification Symptoms Nocturnal Symptoms
Step 1: Intermittent Symptoms ≤2 per week ≤2 per month

Asymptomatic and normal PEF between
exacerbations
Step 2: Mild persistent Symptoms >2 per week but <1 per day >2 per month
Step 3: Moderate persistent Need for daily use of short-acting β-agonist ≥1 per week
Acute exacerbations ≥2 per week
Step 4: Severe persistent Continual symptoms that limit physical activity Frequent
STUDY TABLE: Asthma Treatment

Step Classification Treatment
Step 1: Intermittent Select a short-acting β-agonist as needed

Step 2: Mild persistent Add a low-dose inhaled glucocorticoid
Step 3: Moderate persistent Add one of the following:
1. Low to medium doses of an inhaled glucocorticoid and a LABA (preferred)
2. Medium doses of an inhaled glucocorticoid
3. Low to medium doses of an inhaled glucocorticoid and a single long-term controller medication
(leukotriene modifier or theophylline)
Step 4: Severe persistent Add high doses of an inhaled glucocorticoid plus a LABA or LAMA and possibly oral glucocorticoids
If asthma is difficult to control, discontinue β-blockers (including ophthalmologic agents). If β-blockers must be continued, use
selective β-blockers (metoprolol, atenolol). Also stop aspirin and NSAIDs if the patient is sensitive to these drugs.
Omalizumab is a monoclonal antibody directed at IgE for patients with moderate to severe persistent asthma with the following
characteristics:
• inadequate control of symptoms with inhaled glucocorticoids

• evidence of allergies to perennial aeroallergen
• IgE levels between 30 and 700 kU/L
Anti–interleukin-5 monoclonal antibodies (mepolizumab, reslizumab) reduce symptoms, asthma exacerbations, and the need
for oral glucocorticoids. Treatment is reserved for patients with an absolute eosinophil count >150 cells/µL and severe asthma
not controlled with standard therapy.
Peak flow meters can be used at home for serial measurement of lung function and to assess the relationship of lung function
to symptoms.
For all patients:
• annual influenza vaccination and pneumococcal vaccination for adults requiring controller medications
• instruction about proper inhaler technique
• evaluation for thrush, hoarseness, and osteopenia caused by inhaled glucocorticoids
• calcium and vitamin D supplements for patients taking chronic glucocorticoid treatment; early screening for osteoporo-
sis with DEXA
DON’T BE TRICKED
• Do not administer theophylline with fluoroquinolones or macrolides (may result in theophylline toxicity).
• Do not use LABAs as single agents in asthma (increased mortality rate).
347
.
Treatment of exercise-induced asthma:
• For infrequent symptoms, treat with a SABA 15 to 30 minutes before exercise.

• For symptoms more than twice weekly, follow the Step Classification of Asthma Study Table (shown earlier).
Treatment of asthma in pregnancy:
• Control GERD.
• Step-care therapy for chronic asthma is the same for pregnant and nonpregnant patients.
• Early addition of glucocorticoids is indicated for rapid reversal of airway obstruction during an exacerbation.
Treatment of severe asthma exacerbation in the emergency department:
• Administer repeated doses of albuterol by continuous flow nebulizer or metered-dose inhaler with a spacer.
• Give early IV glucocorticoids when inhaled albuterol is ineffective.
• Inhaled ipratropium may be helpful.
• IV magnesium sulfate may be helpful for patients who have life-threatening exacerbations.
• Hospitalize patients who do not respond well after 4 to 6 hours.
• Intubate and mechanically ventilate patients with respiratory failure (see Invasive Mechanical Ventilation).
• Give oral glucocorticoids, inhaled glucocorticoids, an asthma action plan, and follow-up instructions to patients dis-
charged home.
DON’T BE TRICKED
• A normal arterial Pco2 in a patient with severe symptomatic asthma indicates impending respiratory failure.
• Consider vocal cord dysfunction for patients with “asthma” that improves immediately with intubation.
TEST YOURSELF
A 35-year-old woman with asthma has daily coughing and shortness of breath. She uses triamcinolone, 4 puffs twice daily, and
albuterol, 2 puffs twice daily as needed. Her sleep is disturbed nightly by coughing. The chest examination shows soft bilateral
expiratory wheezing. PEF is 60% of predicted.
ANSWER: For diagnosis, choose severe persistent asthma. For management, select adding a long-acting bronchodilator. The short-
term addition of an oral glucocorticoid to the inhaled glucocorticoid and a long-acting bronchodilator would also be correct.
Chronic Obstructive Pulmonary Disease

Screening
Screening asymptomatic patients for COPD is not recommended.
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 energy level.
The features most predictive of COPD in a symptomatic patient are the combination of:
• smoking history
• wheezing on auscultation
• self-reported wheezing
Diagnose COPD when postbronchodilator spirometry shows an FEV1/FVC ratio <0.70 associated with symptoms of chronic
bronchitis, emphysema, or both.
348
.
Measure AAT level in patients with COPD <45 years who have a strong family history of COPD or without identifiable COPD risk
factors (some guidelines recommend testing all patients).
STUDY TABLE: Mimics of COPD

Bronchiectasis Often secondary to an inciting event, such as childhood pneumonia or TB; may be associated with foreign body,
CF, immotile ciliary syndrome, nontuberculous mycobacteria, and aspergillus colonization
Large-volume sputum production with purulent exacerbations; hemoptysis
Chest x-ray showing “tram lines”; diagnose with HRCT
Cystic fibrosis Obstructive pulmonary disease is most common presentation in adult patients; other symptoms may include
recurrent respiratory infections, infertility
Positive sweat chloride test result
Adult bronchiolitis Found in current or former smokers; may be idiopathic or associated with other diseases such as RA
Poorly responsive to bronchodilators; responds to smoking cessation and glucocorticoids
Bronchiolitis Presents with dyspnea without improvement following bronchodilators, normal or hyperinflated lungs on chest
obliterans x-ray; associated with injury to small airways; consider in patients after lung or stem cell transplantation
Upper airway Stridor, which may be both inspiratory and expiratory
obstruction
Flow-volume loop shows expiratory or inspiratory flattening, or both
Treatment
Smoking cessation is essential in the management of all patients with COPD to reduce the rate of decline in lung function.
Treatment is determined by the frequency and severity of clinical symptoms and the exacerbation risk.
Strong evidence-based recommendations:
• For symptomatic patients with COPD and FEV1 <60% of predicted, monotherapy using either long-acting anticholinergic
agents (LAMAs or LABAs) is recommended.
• For symptomatic patients with an FEV1 <50% of predicted, pulmonary rehabilitation is recommended.
• For patients with COPD who have severe resting hypoxemia (arterial Po2 <55 mm Hg or O2 saturation <88%), continuous
oxygen therapy is recommended.
Weaker evidence-based recommendations:
• For stable patients with COPD with respiratory symptoms and FEV1 between 60% and 80% of predicted, inhaled broncho-
dilators may be used.
• For symptomatic patients with stable COPD and FEV1 <60% of predicted, combination inhaled therapies (LAMAs, LABAs,
or inhaled glucocorticoids) may be considered.
• For symptomatic or exercise-limited patients with an FEV1 >50% of predicted, pulmonary rehabilitation may be
considered.
Additional indications for which long-term oxygen therapy should be considered:
• arterial blood Po2 is 55 to 60 mm Hg with signs of tissue hypoxia (polycythemia, PH, right-sided HF)
• exercise arterial blood Po2 is ≤55 mm Hg or O2 saturation ≤88%
Other therapies for stable COPD:
• PDE-4 inhibitor (roflumilast) as add-on therapy for severe COPD

• long-term macrolide therapy (may reduce frequency of exacerbations when prescribed to patients with severe COPD and
a history of frequent exacerbations)
• nocturnal noninvasive mechanical ventilation to improve oxygenation, improve sleep, and decrease daytime
somnolence
349
.
• palliative use of oral or parenteral opioids in patients with severe COPD and unremitting dyspnea at end of life
• annual influenza and pneumococcal vaccination according to current guidelines
• 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
• 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 µm, and FEV1
<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:
• tetracycline or trimethoprim-sulfamethoxazole for mild exacerbations

• β-lactam/β-lactamase inhibitor, extended-spectrum macrolides, second- or third-generation cephalosporins, or a
fluoroquinolone for moderate or severe exacerbations
• IV or oral glucocorticoids
• short-acting bronchodilators (albuterol, ipratropium, or both)
• noninvasive ventilation (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)
• pulmonary rehabilitation following hospital discharge
TEST YOURSELF
A 55-year-old man is evaluated for progressive dyspnea. He has a 40-pack-year cigarette smoking history. On spirometry, his FEV1
is 54% of predicted. He is using an albuterol inhaler with increasing frequency. Therapy is prescribed.
ANSWER: For management, choose a LAMA or LABA.
DON’T BE TRICKED
• Do not use short-acting and long-acting anticholinergic agents together.
• Short-term glucocorticoid use (<7 days) is as good as longer-term use.
• PDE-4 inhibitors are not indicated for acute bronchospasm.
• Clubbing is not a feature of COPD and suggests bronchiectasis, right-to-left cardiac shunts, or malignancy.
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 aerugi-
nosa, Staphylococcus aureus, Haemophilus influenzae, or Burkholderia cepacia; bronchiectasis or hyperinflation; chronic
sinusitis and nasal polyps; chronic or recurrent pancreatitis; clubbing; diabetes; inability to gain weight; infertility; and steator-
rhea. The diagnosis is confirmed by a sweat chloride test followed by genetic testing.
DON’T BE TRICKED
• In patients with CF and acute abdominal pain, consider intestinal intussusception.
350
.
Treatment
All patients should receive pneumococcal conjugate and polysaccharide vaccines and 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
• nighttime noninvasive mechanical ventilation for nocturnal hypoxemia or hypercarbia
• chest physiotherapy
• pancreatic enzyme replacement and fat soluble vitamin supplementation if indicated
Choose evaluation for transplantation for patients with advanced lung or liver disease.
TEST YOURSELF
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 of subacute or chronic progressive dyspnea after infection and HF have been excluded.
The diagnosis and differential of DPLD is aided by paying particular attention to the following:
• time course (typically months or years)

• active smoking history (suggests respiratory bronchiolitis–associated interstitial lung disease)
• occupation and environmental exposure history (e.g., automobile mechanics, ship builders, and asbestos exposure)
• rheumatologic disease review of symptoms
• exposure to drugs and/or radiation
Testing
Look for interstitial reticular or nodular infiltrates on chest x-ray; the type and pattern of the infiltrate correlate well with under-
lying pathology on lung biopsy.
Look for restrictive or combined restrictive/obstructive findings on pulmonary function tests.
Obtain chest HRCT, even if chest x-ray is normal, if clinical suspicion is high. Look for presence of hilar lymphadenopathy
(sarcoidosis), pleural effusion (connective tissue–related DPLD), and pleural plaques (asbestosis).
351
.
STUDY TABLE: Distinguishing Features of Select Forms of DPLD

Known Causes
Drug induced Examples: amiodarone, methotrexate, nitrofurantoin, chemotherapeutic agents

Smoking related “Smokers” respiratory bronchiolitis characterized by gradual onset of persistent cough and dyspnea
X-ray shows ground-glass opacities and thickened interstitium
Radiation May occur 6 weeks to months after radiation therapy
Chronic aspiration Aspiration is often subclinical
Pneumoconiosis Asbestosis, silicosis, berylliosis
Connective tissue diseases
Rheumatoid arthritis May affect the pleura (pleuritis and pleural effusion), parenchyma, airways (bronchitis, bronchiectasis),
and vasculature
The parenchymal disease can range from nodules to organizing pneumonia to usual interstitial
pneumonitis
Progressive SSc Antibody to Scl-70 or PH portends a poor prognosis
Polymyositis/ Many different types of histology; poor prognosis
dermatomyositis
Hypersensitivity pneumonitis Immune reaction to an inhaled low-molecular-weight antigen; may be acute, subacute, or chronic;
ground-glass opacities on high resolution CT scan
Unknown Causes
Idiopathic interstitial
pneumonias
Idiopathic pulmonary Chronic, insidious onset of cough and dyspnea, usually in a patient age >50 y; chest x-ray shows
fibrosis honeycombing, bibasilar infiltrates with fibrosis
Diagnosis of exclusion (see Idiopathic Pulmonary Fibrosis)
Acute interstitial Dense bilateral acute lung injury similar to ARDS; 50% mortality rate
pneumonia
Cryptogenic organizing May be preceded by flulike illness; x-ray shows focal areas of consolidation that may migrate from one
pneumonia location to another
Sarcoidosis Variable clinical presentation (see Sarcoidosis)
Rare DPLD with Well-Defined Features
LAM Affects women in their 30s and 40s; associated with spontaneous pneumothorax and chylous effusions
Chest CT shows cystic disease
Chronic eosinophilic Chest x-ray shows “photographic negative” of HF, with peripheral alveolar infiltrates predominating
pneumonia
Other findings may include peripheral blood eosinophilia and eosinophilia on bronchoalveolar lavage
Pulmonary alveolar Median age of 40 years, and males predominate among smokers but not in nonsmokers
proteinosis
Diagnosed via bronchoalveolar lavage, which shows abundant protein in the airspaces; chest CT shows
“crazy paving” pattern
DON’T BE TRICKED
• Patients with dyspnea for days or weeks (vs months) are more likely to have pneumonia or HF than DPLD.
• Plain radiography may be normal in 20% of patients with early DPLD; continue evaluation if suspicion remains high.
• Consider DPLD in patients with dyspnea and pulmonary crackles but no other findings of HF.
Treatment
When possible, treatment is directed toward the underlying cause (connective tissue disease), limiting exposure (drug discon-
tinuation), and smoking cessation (respiratory bronchiolitis–associated interstitial lung disease). The evidence for glucocorti-
coid efficacy is weak.
352
.
Idiopathic Pulmonary Fibrosis

Diagnosis
IPF, the most common of the idiopathic interstitial pneumonias, is a fibrosing interstitial pneumonia. Characteristic findings
are the gradual onset of a nonproductive cough and dyspnea over approximately 3 months in older adults. Physical examination
findings include:
• normal temperature
• bibasilar crackles (“dry,” end-inspiratory, and “Velcro-like” in quality)
• late-phase cor pulmonale
• clubbing (25% 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 is
found on pulmonary function tests.
Serum ANA, rheumatoid factor, c-ANCA, and p-ANCA levels are

negative or low. Video-assisted thoracoscopic lung biopsy is
indicated for patients with atypical presentations.
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 slow-
ing disease progression for select persons. Oxygen therapy is
indicated for patients with hypoxemia.
Idiopathic Pulmonary Fibrosis: High-resolution, thin-section chest CT scan

DON’T BE TRICKED showing extensive parenchymal involvement with fibrotic and honeycomb changes
• Do not intubate and mechanically ventilate patients compatible with IPF.
with respiratory failure caused by IPF.
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.
Characteristic findings include:
• fever, weight loss, and night sweats

• dry cough and dyspnea
• eye pain or burning and photosensitivity
353
.
• erythema nodosum
• 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
• asymmetric joint swelling
• Löfgren syndrome (fever, bilateral hilar lymphadenopathy, EN, and often ankle arthritis)
• uveoparotid fever (Heerfordt syndrome, featuring anterior uveitis, parotid gland enlargement, facial palsy, and fever)
• hypercalcemia (extrarenal production of calcitriol by granuloma cells) and kidney stones
• bilateral hilar lymphadenopathy, often with other enlarged mediastinal lymph nodes
• lymphadenopathy and lung parenchymal disease on chest x-ray
Testing
A definite 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 features of Löfgren syndrome (95% diagnostic
specificity).
Diagnostic studies include:
• PFT (sarcoidosis may cause obstruction, restriction, or both)

• fiberoptic bronchoscopy with transbronchial biopsy and
bronchoalveolar lavage for interstitial lung disease or nod-
ular lung involvement
• serum PTH level (low) for patients with hypercalcemia/
hypercalciuria
• 1,25-dihydroxy vitamin D3 level (high) in patients with
kidney stones and hypercalcemia
• biopsy of suspicious skin lesions
• slit-lamp examination for all patients
• ECG to rule out heart block or other cardiac abnormali-
Waxy Papular Lesions: Waxy papular lesions on the nose consistent with sar-
ties in all patients coidosis.
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 light bulb or semiconductor factories) may cause a sarcoidosis-like
clinical syndrome.
• Don’t select a serum ACE level. It won’t confirm 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; hypercalcemia; or
cardiac, ophthalmologic, or neurologic sarcoidosis. Patients with glucocorticoid-refractory disease are treated with immuno-
suppressive, cytotoxic, and antimalarial agents. Löfgren syndrome has a very high rate (80%) of spontaneous remission and
resolution.
354
.
DON’T BE TRICKED
• Do not treat asymptomatic sarcoidosis.
TEST YOURSELF
A 66-year-old man is hospitalized because of azotemia and
hypercalcemia. Laboratory studies show a normal serum PTH
level and an elevated 1,25-dihydroxy vitamin D3 level. A chest
x-ray shows an interstitial infiltrate and an enlarged left para-
tracheal lymph node.
ANSWER: For diagnosis, choose sarcoidosis. For management,
select transbronchial lung biopsy.
Occupational Lung
Disease
Sarcoidosis: X-ray shows bilateral hilar lymphadenopathy characteristic of sar-
coidosis. Sarcoidosis can be associated with interstitial lung disease.
Diagnosis
Clinical manifestations may include asthma, COPD, constrictive bronchiolitis, rhinitis, and restrictive diseases. Symptom onset
following exposure can be acute (reactive airways disease/small airways dysfunction as occurs in acute chlorine gas exposure)
as well as prolonged or subacute with a significant latent period (as with 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 FEV1 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 standard” for diagnosis, but not always necessary.
Treatment
The overriding principle is discontinuing the exposure. Occupational asthma and reactive airways dysfunction syndrome are
treated with 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.
TEST YOURSELF
A previously healthy 45-year-old man has a cough of 6 months’ duration. He is a lifelong nonsmoker and works as an automobile
spray painter. Physical examination discloses a few expiratory wheezes. FEV1 is 0.65 and FEV1/FVC ratio is 65% of predicted, and a
22% improvement occurs after bronchodilator administration.
ANSWER: For diagnosis, choose occupational asthma. For management, select spirometry or PEF measurement before and after
work (or during vacation).
355
.
Asbestos-Associated Lung Diseases

Diagnosis
The most important risk factor for developing asbestos-related lung diseases is the cumulative exposure to the asbestos fiber.
Occupations with the greatest exposure include those in the construction industry, the automotive servicing industry, and the
shipbuilding and repair industry. The latent period for development of asbestosis and mesothelioma is 10 to 15 years. Exposure
to asbestos increases the risk of lung cancer in cigarette smokers.
STUDY TABLE: Asbestos-Related Lung Syndromes

Condition Characteristics
Pleural plaques (localized, Often an incidental finding; usually bilateral; most common manifestation of asbestos exposure
often partially calcified)
Monitor patients for development of intrathoracic disease
Diffuse pleural thickening Extensive pleural thickening extends into the visceral pleura and obliterates the costophrenic angles
May cause hypercapnic respiratory failure secondary to impairment of ventilation
Rounded atelectasis Presents as single or multiple masses caused by infolding of thickened visceral pleura with collapse of
the adjacent peripheral lung
The classic radiographic finding is a “comet tail” on chest CT scan extending from the hilum toward
the base of the lung and then sweeping into the inferior pole of the lesion
Can cause ventilatory failure
Benign pleural effusion Exudative hemorrhagic or eosinophilic effusion; may be painful
Mesothelioma Suggested by weight loss, fever, cough, dyspnea, chest pain, unilateral pleural abnormalities, and
pleural effusion
Tissue diagnosis required; cytologic diagnosis can be established by thoracentesis or closed pleural
biopsy
Asbestosis Manifests with bilateral interstitial fibrosis of the lung parenchyma, bibasilar inspiratory crackles,
clubbing, restrictive physiology, and low Dlco
Lung cancer Most asbestos-related cases occur in patients with asbestosis, but a diagnosis of asbestosis is not
necessary to attribute lung cancer to asbestos exposure
Treatment
In patients with a history of asbestos exposure or asbestosis,
the risk of lung cancer mortality can be decreased at any time
with smoking cessation. Surgery is indicated for patients with
localized mesothelioma, and radiation and chemotherapy are
used to prevent recurrences. Most patients with mesothelioma
have advanced disease and are treated symptomatically by con-
trolling pleural effusions with thoracentesis.
Mesothelioma: Frontal chest x-ray showing multiple pleural-based nodular infil-

trates at the right chest wall and pleural thickening consistent with mesothelioma.
356
.
Pleural Effusion
Diagnosis
Most pleural effusions in the United States are the result of HF, pneumonia, or malignancy. A thoracentesis is indicated for any
new unexplained effusion; however, observation and therapy without thoracentesis is reasonable in the setting of known HF,
small parapneumonic effusions, or following CABG surgery.
Testing
Pleural fluid is characterized as transudative or exudative.
STUDY TABLE: Laboratory Tests for Identifying a Pleural Effusion as an Exudate

Test Interpretation
Pleural fluid protein–serum protein ratio >0.5

Pleural fluid LDH >200 U/L (or >2/3 the upper limit of normal)
Pleural fluid LDH–serum LDH ratio >0.6
An effusion is considered an exudate if any one of the above criteria are met. However, treatment (diuretics for HF), a dual
diagnosis (HF and a concomitant parapneumonic effusion), or some specific diagnoses (e.g., chylothorax) can result in discord-
ant exudates (an exudate by either the protein or LDH criterion but a transudate by the other criteria). A common cause of
discordant findings is diuretic use. In the setting of ongoing diuresis, if the serum to pleural fluid albumin gradient is >1.2 g/dL,
the fluid is most likely a transudate.
STUDY TABLE: Common Causes of Transudative and Exudative Pleural Effusions

Transudative Pleural Effusions Exudative Pleural Effusions
Increased hydrostatic pressure (HF, constrictive pericarditis, SVC Infection

obstruction)
Decreased oncotic pressure (hypoalbuminemia, nephrotic Neoplasm
syndrome, cirrhosis, malnutrition)
Autoimmune diseases
Pulmonary infarction
Hemothorax
Benign asbestos effusion
Post-coronary bypass
Pancreatitis
Yellow-nail syndrome (lymphatic disorders)
Pleural fluid cell counts and chemistries can further narrow the differential diagnosis.
STUDY TABLE: Pleural Fluid Cell Counts and Chemistries

If you see this… Think this…
Bloody pleural fluid (RBC count 5000-10,000/µL) Malignancy, pulmonary infarction, asbestos related
Nucleated cells >50,000/µL Complicated parapneumonic effusions and empyema
Lymphocytosis >80% TB, lymphoma, chronic rheumatoid pleuritis, sarcoidosis
pH <7.0 Complicated parapneumonic effusion, TB, rheumatoid and lupus pleuritis,
esophageal rupture
Pleural fluid amylase to serum amylase ratio >1 Pancreatic disease, esophageal rupture, cancer
Glucose <60 mg/dL Complicated parapneumonic effusion or empyema, cancer, TB, rheumatoid and
lupus pleuritis, esophageal rupture
357
.
Other key points:
• Pleural fluid adenosine deaminase is elevated in most TB effusions.

• Pleural biopsy is most likely to yield a positive TB culture.
• The yield for positive malignant cytology is maximized after two samples.
• Thoracoscopy should be performed for an undiagnosed exudative effusion (two negative cytology examinations) when
malignancy is suspected.
Treatment
Parapneumonic pleural effusion requires chest tube drainage when the pH is <7.2 or the pleural fluid glucose level is <60 mg/dL.
Anaerobes are cultured in up to 72% of empyemas; empiric antibiotic therapy should include anaerobic coverage.
For patients with malignant effusions, indwelling pleural catheters provide symptom relief, and up to 70% of patients achieve
spontaneous obliteration of the pleural space (pleurodesis) after 6 weeks. Chemical pleurodesis with talc has a 90% success rate.
Pleural Effusion: Chest x-ray showing a right-sided pleural effusion (left panel) that layers out along the right thorax in the right lateral decubitus view (right panel).
DON’T BE TRICKED
• Always obtain thoracentesis for moderate to large effusions associated with pneumonia.
• Pleural effusions associated with nephrotic syndrome are common, but PE should be excluded in such patients
because PE and renal vein thrombosis often occur in patients with nephrotic syndrome.
• Consider pulmonary LAM when chylothorax is diagnosed in a premenopausal woman.
TEST YOURSELF
A 65-year-old woman has a 2-week history of shortness of breath. A chest x-ray shows a large right-sided pleural effusion. Serum
LDH is 190 U/L and total protein is 6.0 g/dL. On thoracentesis, pleural fluid protein is 2.8 g/dL and pleural fluid LDH is 110 U/L.
ANSWER: For diagnosis, choose a transudative pleural effusion.
358
.
Pneumothorax
Diagnosis
Characteristic symptoms are chest pain and dyspnea. Spontaneous pneumothorax is considered to be primary when the lung
is overtly normal. Tall men who smoke are at risk. Other risk factors include cocaine use and Marfan syndrome. Subpleural blebs
and bullae are commonly detected on CT scan and predispose to primary pneumothorax.
Secondary pneumothorax is associated with lung disease. Consider
• emphysema as the most common cause of secondary pneumothorax.

• pulmonary LAM in a premenopausal woman presenting with a spontaneous pneumothorax and lung disease.
• secondary pneumothorax in patients with HIV and Pneumocystis jirovecii pneumonia.
• tension pneumothorax with falling BP and oxygen saturation, tracheal deviation, and absence of breath sounds in one
hemithorax.
Obtain an upright chest x-ray in patients with dyspnea, pleurisy, or both, even if the physical examination is normal.
Treatment
Treatment depends on the type of pneumothorax:
• observation and oxygen in asymptomatic patients with a small pneumothorax (rim of air <2 cm on chest x-ray)
• simple aspiration for symptomatic primary spontaneous pneumothorax of any size
• release of pressure with a large needle for tension pneumothorax followed by chest tube placement
• chest tube if a secondary pneumothorax measures >2 cm
• pleurodesis for a second primary spontaneous pneumothorax and after a first occurrence in secondary spontaneous
pneumothorax
DON’T BE TRICKED
• Do not wait for chest x-ray results before treating suspected tension pneumothorax with needle decompression.
Pulmonary Hypertension
Screening
Patients with SSc (scleroderma) should be screened with TTE. Also screen the following patients: liver transplantation candi-
dates with portal hypertension, first-degree relatives of patients with familial PAH, and patients with congenital heart disease
with systemic-to-pulmonary shunts.
Diagnosis
PH is defined by a resting mean pulmonary arterial pressure of ≥25 mm Hg. The current classification system subdivides PH
into five groups.
• Group 1 is distinguished by disease localized to small pulmonary arterioles resulting in high pulmonary vascular resistance
and is referred to as PAH.
• 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.
359
.
Characteristic symptoms of PH include:
• unexplained dyspnea
• decreased exercise tolerance
• syncope and near-syncope
• chest pain
• lower extremity swelling
Physical examination findings indicating RV failure may include an RV heave, right-sided S3, widely split S2, increased P2,
increased jugular venous distention with a large a 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 of VTE.
Testing
Typical evaluation of Group 1 pulmonary hypertension (PAH) includes:
• echocardiography as the initial study; a systolic pulmonary artery pressure >40 mm Hg is suggestive of PH
• bubble contrast echocardiography or TEE is indicated to evaluate for intracardiac shunts (e.g., ASD)
• right heart catheterization to confirm the diagnosis and quantify the degree of PH
• 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 pulmonary function tests, liver function tests, polysom-
nography 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:
• pulmonary arterial pressure ≥25 mm Hg in the absence of left-sided HF

• compatible imaging evidence of chronic thromboembolism by V/Q scanning
DON’T BE TRICKED
• Most cases of PH are attributed to left-sided heart disease and hypoxic respiratory disorders.
• Do not select an HRCT scan to diagnose CTEPH. A V/Q scan is superior.
Treatment
Therapy for PH groups 2 through 5 is typically directed at the underlying condition.
For Group 1 PH (PAH), vascular-targeted treatments provide symptomatic relief but are not curative.
• Calcium channel blockers are used for patients demonstrating a vasodilator response on right heart catheterization.
• Lung or heart-lung transplantation should be considered for patients in whom drug treatment is unsuccessful.
• Oxygen therapy is indicated for O2 saturation ≤90%.
Life-long anticoagulant therapy is indicated in all patients with CTEPH. Pulmonary thromboendarterectomy is the only defini-
tive therapy for CTEPH.
DON’T BE TRICKED
• Do not select calcium channel blockers if pulmonary artery pressure is not decreased with a vasoreactivity test.
360
.
Pulmonary Arteriovenous Malformation

Diagnosis and Testing
Pulmonary AVMs consist of abnormal communications between pulmonary arteries and veins. They are included in the dif-
ferential diagnosis of hypoxemia, pulmonary nodules, and hemoptysis. The following suggest a pulmonary AVM:
• hemoptysis
• mucocutaneous telangiectasias
• evidence of right-to-left pulmonary shunts (hypoxemia, polycythemia, clubbing, cyanosis, stroke, brain abscess)
Chest CT is the initial diagnostic test.
Treatment
Symptomatic or large pulmonary AVMs (>2 cm) are treated with either embolotherapy
or surgery.
TEST YOURSELF
A 46-year-old man is evaluated for a TIA. Telangiectasias are present on the lips. The
lungs are clear, and cardiovascular and neurovascular examinations are normal.
Laboratory evaluation reveals polycythemia and an arterial Po2 of 68 mm Hg. Chest
x-ray shows a 2-cm solitary pulmonary nodule.
ANSWER: For diagnosis, choose pulmonary AVM.
Telangiectasia: Telangiectasias on the tongue in a

patient with hereditary hemorrhagic telangiectasia.
Lung Cancer Screening
In high-risk populations, lung cancer screening results in a 20% lung cancer mortality reduction. Screen patients between the
ages of 55 and 74 to 79 years (guidelines vary) who have a 30-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 of 75 to 80 years. Stop screening in patients who have stopped smoking for 15 years.
DON’T BE TRICKED
• The risks of screening outweigh the benefit in patients at low risk for lung cancer.
Hemoptysis
Diagnosis
Bronchitis, bronchogenic carcinoma, and bronchiectasis are the most common causes of hemoptysis.
DON’T BE TRICKED
• Confirm that a patient has hemoptysis rather than epistaxis or GI bleeding; then check the platelet count and
coagulation parameters.
STUDY TABLE: Diagnostic Tests for Hemoptysis

Test Considerations
Chest x-ray Crucial initial study, but normal findings do not exclude lung cancer
Fiberoptic 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
361
.
Treatment
Treatment is cause specific. The cause of death from massive hemoptysis is asphyxiation from airway obstruction. If the bleed-
ing site can be localized to one lung, position the patient with the bleeding lung dependent. Intubation and mechanical venti-
lation are required when adequate gas exchange is threatened. Angiography can localize and treat bronchial artery lesions.
Solitary Pulmonary Nodule

Diagnosis
An SPN is a lesion of the lung parenchyma measuring ≤3 cm in diameter that is not associated with other lesions or lymphad-
enopathy and is not invading other structures. Approximately 35% of SPNs are bronchogenic carcinomas.
STUDY TABLE: Diagnostic Tests for a Pulmonary Nodule

Test Considerations
Comparison with previous chest x-ray Stability over time helps rule out malignancy
Contrast-enhanced CT Most useful imaging method
Fiberoptic bronchoscopy with biopsy Provides sufficient information in only 30% of lesions
Percutaneous transthoracic needle aspiration biopsy Has a higher yield for malignant lesions but is not always diagnostic
PET scan Positive in >90% of malignant solitary nodules >1 cm in diameter. Can
demonstrate unsuspected mediastinal and/or distant disease.
The management of SPNs depends on the size and risk of malignancy. Solid SPNs <8 mm are managed differently than larger
nodules and subsolid nodules. A subsolid nodule is less dense than a solid nodule, and normal lung structures such as blood
vessels can be seen through the nodule. Subsolid nodules, either pure ground glass or with a solid component, often represent
premalignant disease such as adenocarcinoma in situ.
STUDY TABLE: Fleischner Society Recommendations for Single Pulmonary Nodule Follow-Up
Risk Factors for Lung Cancer? Size Recommended Follow-Up
No (low-risk patient) <6 mm No follow-up

6-8 mm CT at 6-12 months, then consider CT at 18-24 months
>8 mm Consider CT at 3 months, PET/CT, or tissue sampling
Yes (high-risk patient) <6 mm Optional CT at 12 months
6-8 mm CT at 6-12 months, then CT at 18-24 months
>8 mm Consider CT at 3 months, PET/CT, or tissue sampling
Data from MacMahon H, Naidich DP, Goo JM, Lee KS, Leung ANC, Mayo JR, et al. Guidelines for management of incidental pulmonary nodules detected on CT images: from the
Fleischner Society 2017. Radiology. 2017;284:228-243. [PMID: 28240562] doi:10.1148/radiol.2017161659.
STUDY TABLE: Fleischner Society Recommendations for Follow-Up of Solitary Subsolid Lung Nodule
Imaging Findings Size Recommended Follow-Up
Pure ground glass <6 mm No follow-up

≥6 mm CT at 6-12 months to confirm persistence, then CT every 2 years until 5 years
Part solid nodule <6 mm No follow-up
≥6 mm CT at 3-6 months to confirm persistence. If unchanged and solid component
remains <6 mm, annual CT should be performed for 5 years
362
.
TEST YOURSELF
A 65-year-old man is incidentally found to have a 7 mm pulmonary nodule on chest x-ray obtained before an elective cholecystec-
tomy. On chest CT, the nodule is subsolid, and no other nodules or lymphadenopathy is evident. He has a 50-pack year history of
cigarette smoking.
ANSWER: For management, choose follow-up chest CT in 1 year.
Pulmonary mass, defined as >3 cm in diameter, is highly suspicious for malignancy in a patient with risk factors. Either a biopsy
for tissue diagnosis (in the absence of suspected metastases) or surgical resection (if no evidence of metastatic disease) is typi-
cally the first step in the evaluation.
DON’T BE TRICKED
• Before ordering contrast CT, bronchoscopy, or PET scan, compare current image with previous image to determine
stability over time.
• PET scans may be falsely negative in alveolar cell carcinoma or lesions <1 cm in diameter and falsely positive in
various inflammatory lesions.
• A nonspecific negative result from fiberoptic bronchoscopy or transthoracic needle aspiration biopsy does not
reliably exclude the presence of a malignant growth.
Mediastinal Masses
Diagnosis
The mediastinum can be divided into three separate compartments, which can help narrow the differential diagnosis of a medi-
astinal mass.
STUDY TABLE: Mediastinal Masses

Origin of Mass Important Associations
Anterior Mediastinum
Thymus Most common tumor of anterior

mediastinum; 40% have MG
Other syndromes include pure red cell
aplasia and acquired
hypogammaglobulinemia
Teratoma/germ Teratomas may contain fat, fluid, and
cell bone discernable on CT imaging
Lymphoma Second most common anterior
mediastinal tumor; Hodgkin disease is the
most common lymphoma
Thyroid Often causes compressive symptoms
(dyspnea, dysphagia)
Middle Mediastinum
Lymph nodes Lymphadenopathy is the most common
cause of middle mediastinal masses
Cysts Includes benign pericardial,
bronchogenic, and esophageal cysts
Posterior Mediastinum
Neurogenic Schwannomas are most common in
tumors adults Mediastinum: A lateral chest x-ray demonstrates the anterior (red), middle
(yellow), and posterior (blue) mediastinal compartments.
363
.
Obstructive Sleep Apnea

Diagnosis
OSAs are typically accompanied by oxyhemoglobin desaturations and are terminated by an awakening from sleep. The severity
of OSA can be classified based on the number of apneas plus hypopneas per hour of sleep (apnea-hypopnea index [AHI]).
Characteristic findings of OSA include snoring, apnea, excessive daytime sleepiness, and obesity (determined by either BMI >30
or neck circumference >17 in) and an enlarged and elongated soft palate (crowded pharynx).
Occasionally, OSA first presents following a surgical procedure involving general anesthesia and/or narcotic analgesia, where
repeated apneas, acute respiratory failure, and even death occur. Screening questionnaires (STOP-Bang) are available to identify
OSA during preanesthesia evaluation.
Patients with untreated OSA have a greater likelihood of developing CAD, acute MI during sleep, systemic and PAH, HF, recur-
rent AF, stroke, insulin resistance, mood disorders, and parasomnias.
Diagnose OSA in patients with an AHI of >5/h during a sleep study. Other options include out-of-center sleep testing.
DON’T BE TRICKED
• Do not confuse obesity-hypoventilation syndrome with OSA. Obesity-hypoventilation syndrome is usually
associated with COPD and always with elevated arterial Pco2 levels when awake.
• Obesity-hypoventilation syndrome may coexist with OSA.
• Overnight oximetry has not been validated as a screening tool for OSA.
Treatment
Lifestyle changes, including weight loss, avoiding alcohol and sedatives before bedtime, and sleeping in the lateral position are
always indicated. CPAP is the initial treatment of choice for OSA and has been shown to improve quality of life, cognitive func-
tion, and symptoms of daytime sleepiness.
BPAP therapy, in which inspiratory and expiratory pressures can be adjusted separately, may be useful in patients who have
coexisting OSA and obesity-hypoventilation syndrome, who do not tolerate CPAP, have concurrent central sleep apneas, or have
persistent oxygen desaturation because of hypoventilation despite CPAP therapy. Therapy may be required for up to 4 weeks
before ABGs improve.
Oral appliances are an alternative to CPAP therapy for mild to moderate OSA. Oral appliances are not as effective as CPAP in
reducing AHI.
DON’T BE TRICKED
• Supplemental oxygen is not recommended as a primary therapy for OSA.
• Upper airway surgery is not recommended as initial therapy for OSA.
High-Altitude−Related Illness
Diagnosis
HAI encompasses a number of disorders that can occur when a person residing at low altitude ascends to higher elevation. HAI
is more common at elevations ≥2500 meters (approximately 8200 feet).
364
.
STUDY TABLE: High-Altitude Illnesses

Disorder Pathophysiology Clinical Findings
High-altitude periodic breathing (HAPB) Hypoxia-induced hyperventilation lowers Repetitive arousals from sleep, often with
Pco2 toward the apneic threshold, paroxysms of dyspnea
decreasing respiratory rate, which raises
Pco2 and results in recurrent
hyperventilation
Acute mountain sickness (AMS) Hypoxia and hypocarbia-induced Headache, fatigue, nausea, and vomiting,
alterations in cerebral blood flow in addition to disturbed sleep related to
HAPB
High-altitude cerebral edema (HACE) Brain edema at altitudes typically above Confusion, irritability, ataxia, coma, and
10,000-13,000 feet death
High-altitude pulmonary edema (HAPE) PH and pulmonary edema Cough, dyspnea at rest, pink frothy
sputum, hemoptysis, and pulmonary
crackles
Prevention and Treatment

HAI can be prevented by gradually ascending. Acetazolamide accelerates the acclimatization. Acetazolamide, dexamethasone, and
supplemental oxygen are used to treat AMS. Definitive treatment for HACE is immediate descent from altitude; dexamethasone,
supplemental oxygen, and hyperbaric therapy may also be used. The HAPE treatment of choice is supplemental oxygen and rest.
DON’T BE TRICKED
• Do not treat HAPE with diuretics and nitrates.
Hypercapnic Respiratory (Ventilatory) Failure

Diagnosis
Hypercapnic respiratory (ventilatory) failure occurs when alveolar ventilation is inadequate and the level of CO2 increases in the
blood. Because oxygenation also depends on ventilation, patients are often hypoxic as well. However, hypoxia will often improve
with supplemental oxygen. Chronic hypercapnic respiratory failure occurs most often in patients with:
• COPD
• neuromuscular disease (MG, ALS, MS)
• restrictive lung diseases (parenchymal lung disease, chest wall skeletal disorders, obesity)
• depressed respiratory drive (opioids and sedatives)
Testing
In patients with neuromuscular disease, pulmonary function tests show restriction on spirometry and lung volume measure-
ment but normal diffusing capacity.
Patients with respiratory muscle weakness, obesity-hypoventilation syndrome, and disorders of ventilatory control first
hypoventilate during REM sleep. Order polysomnography if nocturnal hypoventilation is suspected (daytime sleepiness, noc-
turnal awakenings, morning headaches).
TEST YOURSELF
A 36-year-old man with myotonic dystrophy awakens at night gasping for air and experiences increasing fatigue. Cardiopulmonary
examination is normal. Neurologic examination shows 4+/5 strength in all muscle groups.
ANSWER: For diagnosis, choose nocturnal hypercapnic respiratory failure. For management, elect polysomnography.
365
.
Hypoxic Respiratory Failure

Hypoxic respiratory failure is caused by inadequate oxygenation of hemoglobin. The most common causes of hypoxic respira-
tory failure in the ICU are V/Q mismatch and shunt, which occurs when perfused areas of the lung are not ventilated.
Acute Respiratory Distress Syndrome

ARDS is a syndrome of hypoxemic respiratory failure presenting as noncardiogenic pulmonary edema. Precipitating causes of
ARDS include pulmonary infection, hemorrhagic shock, pancreatitis, trauma, transfusions, and sepsis.
STUDY TABLE: Diagnosing and Classifying ARDS

Features Acute onset (<1 week), known clinical insults (ARDS risk factors)
common to all
Bilateral lung opacities on imaging not fully explained by effusions, lobar/lung collapse or nodules
cases of ARDS
Respiratory failure not explained by HF or volume overload (although ARDS can coexist with HF or fluid overload states)
Mild ARDS Arterial Po2/Fio2 ratio of 201-300 mm Hg, measured with PEEP ≥5 cm H2O
Moderate ARDS Arterial Po2/Fio2 ratio of 101-200 mm Hg, measured with PEEP ≥5 cm H2O
Severe ARDS Arterial Po2/Fio2 ratio of ≤100 mm Hg, measured with PEEP ≥5 cm H2O
STUDY TABLE: Mimics of ARDS

Cardiogenic pulmonary History of cardiac disease, enlarged heart, S3, chest x-ray showing an enlarged cardiac silhouette, pleural
edema effusions, and Kerley B lines
Rapid improvement with diuresis or afterload reduction
Diffuse alveolar Acute kidney injury with microscopic or gross hematuria or other evidence of vasculitis present
hemorrhage
Associated with stem cell transplantation
Hemosiderin-laden macrophages in bronchoalveolar lavage fluid
Acute eosinophilic Cough, fever, pleuritic chest pain, and myalgia; may be precipitated by initiation of smoking
pneumonia
>15% eosinophils in bronchoalveolar lavage fluid
Hypersensitivity Typically slower onset than ARDS (over weeks) with progressive course; however, may present in an
pneumonitis advanced stage, mimicking ARDS
Positive exposure history (farmers, bird fanciers, hot tub exposure)
Cryptogenic organizing May be precipitated by viral syndrome
pneumonia
Slower onset than ARDS (>2 weeks) with progressive course; however, may present in an advanced stage,
mimicking ARDS
Acute interstitial May be impossible to distinguish from ARDS
pneumonia
Absence of typical inciting factors for ARDS
May respond to glucocorticoid administration
Treatment
Optimal mechanical ventilation associated with the prevention of ventilator-associated lung injury includes:
• lung-protective ventilation using volume-controlled ventilation with a tidal volume of ≤6 mL/kg of ideal body weight (low
tidal volume)
• plateau (end-inspiratory) pressure <30 cm H2O (even if this results in “permissive” hypercapnia and acidosis)
• PEEP
Limiting IV fluids and using diuretics to keep CVP at lower targets has been associated with a more rapid improvement in lung
function, shorter duration of mechanical ventilation, and shorter ICU length of stay but no effect on mortality.
Use of prone positioning in severe ARDS has a mortality benefit.
366
.
DON’T BE TRICKED
• Glucocorticoids are not indicated for the acute treatment of ARDS.
TEST YOURSELF
A 55-year-old woman with acute pancreatitis has increasingly severe shortness of breath for 12 hours. She has no history of cardiac
disease. Pulse rate is 116/min, respiration rate is 40/min, and arterial O2 saturation is 86% (on supplemental oxygen). Diffuse bilat-
eral crackles are heard. Chest x-ray shows diffuse airspace disease. She is intubated and mechanically ventilated. With an Fio2 of
1.0, her arterial Po2 is 150 mm Hg.
ANSWER: For diagnosis, choose moderate ARDS. For management, select a tidal volume of 6 mL/kg of ideal body weight.
Noninvasive Positive-Pressure Ventilation

Indications in Critically Ill Patients
NPPV is the use of positive-pressure ventilation without the need for an invasive airway. NPPV may be used as the ventilatory
mode of first choice in four conditions:
• COPD exacerbations (not stable COPD)

• cardiogenic pulmonary edema
• neuromuscular disease
• prevention of recurrent respiratory failure in recently extubated high-risk patients
The most common contraindications to NPPV include:
• respiratory arrest
• medical instability
• inability to protect airway and/or excessive nausea or vomiting
• uncooperative or agitated patient
Improvements in blood gas values and clinical condition should occur within 2 hours of starting NPPV. If not, intubation should
be considered to avoid undue delay and prevent respiratory arrest.
Invasive Mechanical Ventilation

Indications
Patients may require invasive mechanical ventilatory support for hypoxic respiratory failure (low arterial Po2) or impaired alveo-
lar ventilation (increased arterial Pco2). In general, if a patient cannot maintain an arterial Po2 >60 mm Hg or an O2 saturation
>90% despite supplemental oxygen of 60% or higher, initiating mechanical ventilation is usually appropriate, regardless of the
arterial Pco2.
Management
In volume-targeted ventilation, set tidal volume first:
• the recommended range is 6 to 8 mL/kg of ideal body weight (≤6 mL/kg for ARDS)
• tidal volumes that are too high can result in barotrauma, respiratory alkalosis, and decreased cardiac output
• tidal volumes that are too low can result in atelectasis, hypoxemia, and hypoventilation
367
.
Set respiratory rate:
• the respiration rate is usually started at 8 to 14/min if the patient is otherwise clinically stable
• a respiratory rate that is too high can result in respiratory alkalosis and air trapping (auto-PEEP)
• a respiratory rate that is too low can result in hypoventilation, acidosis, hypoxemia, and patient discomfort
Set oxygen flow and PEEP to maintain arterial Po2 >60 mm Hg.
Be alert for auto-PEEP.
• In the presence of increased airway resistance, a high demand for ventilation, or a short expiratory time, air flow may still
occur at end exhalation, resulting in positive pressure in the alveoli at end exhalation.
• Suspect auto-PEEP if the flow tracing on the ventilator shows continuous expiratory flow until the start of inspiratory flow.
Common causes of auto-PEEP include COPD or acute asthma, ARDS (increased flow resistance), and a high minute ventilation
(>12-15 L/min). Characteristic findings are wheezing and marked expiratory prolongation, drop in BP, and patient restlessness.
Strategies to minimize auto-PEEP:
• treat airway obstruction (e.g., bronchodilators in COPD or asthma)

• decrease the respiratory rate or tidal volume
• increase the inspiratory flow rate (shorten inspiratory time)
• prolong the expiratory time
• allow permissive hypercapnia
• sedate and/or paralyze the patient
STUDY TABLE: Ventilator Management

If you would like … the … make the ventilator do this by: Notes:
to … intermediate
step is …
Improve respiratory ↓ Arterial Pco2 Increasing respiratory rate Watch for auto-PEEP at high respiratory
acidosis rates, which can cause hypotension by
Increasing tidal volume: in volume control reducing preload
mode, directly choose the tidal volume; in
pressure control mode, increase the Don’t be tricked: If the patient has ARDS,
inspiratory support pressure to increase respiratory acidosis (pH ~7.2) should
tidal volume generally be tolerated rather than raising
the tidal volume >6 mL/kg
Improve respiratory ↑ Arterial Pco2 Decreasing respiratory rate If the patient is breathing faster than the set
alkalosis ventilator rate, this strategy won’t work
Decreasing tidal volume
Determine why respiratory alkalosis is
present (sepsis, PE, liver disease, pain)
Improve tissue ↑ O2 saturation, Increasing Fio2 Occasionally, increasing PEEP will lower
oxygenation arterial Po2 cardiac output by reducing preload; this
Increasing PEEP can worsen oxygen delivery to tissues
If no contraindications, attempt to increase
preload with IV fluids
Difficult ventilation or complications of mechanical ventilation resulting from changes in airway resistance may first be mani-
fested by an increase in the peak inspiratory pressure alone, resulting from:
• bronchospasm
• secretions in airways, endotracheal tube, or ventilator tubing
• obstructing mucus plug
• agitation with dyssynchrony with the ventilator
368
.
Difficult ventilation resulting from a change in lung compliance will be manifested by an increase in both peak inspiratory
pressure and plateau pressure, resulting from:
• right mainstem intubation

• pneumothorax
• worsening airspace disease (ARDS, pneumonia, pulmonary edema)
Placing intubated patients in a semirecumbent position and using selective decontamination of the oropharynx (using topical
gentamicin, colistin, or vancomycin) reduces the risk of VAP.
When a patient can maintain an arterial O2 saturation >90% breathing Fio2 ≤0.5, PEEP <5 cm H2O, and pH >7.30, it is reasonable
to consider extubation. Paired daily spontaneous awakening trials (withdrawal of sedatives) with daily spontaneous breathing
trials result in a reduction in mechanical ventilation time, ICU and hospital length of stay, and 1-year mortality rates.
DON’T BE TRICKED
• 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.
TEST YOURSELF
A 73-year-old woman who weighs 56 kg (123 lb) is admitted to the ICU with an exacerbation of severe COPD. Intubation and
mechanical ventilation are required: Fio2 of 0.4, tidal volume of 450 mL, and respiration rate of 16/min. Thirty 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
Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock is defined as a
subset of sepsis in which profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortal-
ity than with sepsis alone.
Know the differential diagnosis of shock syndromes and their associated hemodynamic parameters.
STUDY TABLE: Shock Syndromes

Condition Characteristics
Cardiogenic shock Low cardiac output, elevated PCWP, and high SVR
Hypovolemic shock Low cardiac output, low PCWP, and high SVR
Obstructive shock Low cardiac output, variable PCWP, 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
Fever and leukocytosis
SVR = systemic vascular resistance.
369
.
Treatment
STUDY TABLE: Treatment of Sepsis and Septic Shock
Treatment Application
Fluid resuscitation Balanced crystalloids

500-1000 mL boluses
2-4 L (30 mL/kg) in the first 6 h
Vasopressors Norepinephrine, vasopressin (norepinephrine sparing agent)
Indicated for persistent hypotension unresponsive to fluids
Target MAP ≥65 mm Hg
Target lactic acid ↓ by 10%-20% in first 6 h
Source identification and control Blood cultures, cultures of potential sites of infection, chest x-ray, urinalysis
Antibiotic therapy Initiate within 1 h of diagnosis
Narrow coverage based on culture and sensitivity findings
Reasonable choice for sepsis of unclear cause and low Pseudomonas risk: vancomycin plus one
of the following: ceftriaxone or cefotaxime, piperacillin-tazobactam, or imipenem
If high Pseudomonas risk: vancomycin plus two antipseudomonal agents (e.g., ceftazidime,
cefepime, imipenem, piperacillin-tazobactam)
Hydrocortisone 200 mg/d IV for persistent hypotension despite fluids and vasopressors
Glucose control Insulin therapy to maintain glucose between 140- 200 mg/dL
Mechanical ventilation Tidal volume ≤6 mg/kg of ideal body weight if ARDS present
DON’T BE TRICKED
• Do not perform cortisol stimulation testing.
• Do not use noninvasive ventilation.
Nutritional Support During Critical Illness

Diagnosis
Nutrition is an essential part of management for patients in the ICU and can be given enterally or parenterally, with the enteral
route preferred. Total parenteral nutrition is associated with GI mucosal atrophy and translocation of gut bacteria into the
bloodstream, which predisposes patients to infection.
Treatment
Initiation of enteral nutrition is recommended at 24 to 48 hours following admission. Critically ill patients who cannot maintain
volitional nutritional intake may be fed using a gastric tube, large-bore tube, small-bore tube, or postpyloric tube. The formula
of 25 to 35 kcal/kg/d can be used to estimate caloric need in patients in the ICU. For patients who cannot tolerate enteral feeding,
total parenteral nutrition should not be started before day 7 of an acute illness. However, parenteral nutrition should be started
as soon as possible for severely malnourished patients and those at high risk of malnutrition when enteral nutrition is not
possible.
370
.
ICU-Acquired Weakness
Diagnosis
ICU-acquired weakness includes critical illness polyneuropathy (with axonal nerve degeneration) and critical illness myopathy
(with muscle myosin loss), resulting in profound weakness. ICU-acquired weakness may be first recognized when a patient is
unable to be weaned from mechanical ventilation. Risk factors include hyperglycemia, sepsis, multiple organ dysfunction, and
SIRS.
Therapy
Treatment is supportive and includes early mobility and ongoing physical and occupational therapy.
TEST YOURSELF
A 65-year-old woman with type 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 rhabdomyolysis with kidney failure, DIC, 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 Ice 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; ↑ K+
anesthetic (halothane rigidity; ↑ arterial Pco2 and ↑ 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, ↑ HR, ↑ weeks
Dantrolene
risperidone or BP, no clonus, ↓ reflexes
withdrawal from L-dopa; Bromocriptine
onset over days to
weeks
Severe serotonin Onset within 24 h of Agitation, rigidity, Stop the inciting drug Resolves in 24 hours
syndromea initiation or increasing clonus, ↑ reflexes
Benzodiazepines
dose
Cyproheptadine
aNot
routinely considered a cause of severe hyperthermia but commonly confused with neuroleptic malignant syndrome
371
.
DON’T BE TRICKED
• Neuroleptic malignant syndrome may occur in patients who have abruptly discontinued l-dopa for Parkinson
disease.
• The serotonin syndrome is often caused by the use of SSRIs and the addition of a second drug that increases serotonin
release or blocks its uptake or metabolism.
TEST YOURSELF
A 45-year-old woman undergoes open cholecystectomy. At the conclusion of the operative procedure, her temperature has abruptly
increased to 39.2 °C (102.5 °F).
ANSWER: For diagnosis, choose malignant hyperthermia caused by anesthesia. For management, select dantrolene initiation.
Hypertensive Emergency
Hospitalize a patient with hypertensive emergency (BP ≥180/120 mm Hg and symptoms or evidence of end-organ damage).
For a compelling condition (such as aortic dissection, severe preeclampsia or eclampsia, or pheochromocytoma crisis), SBP
should be reduced to <140 mm Hg during the first hour and to <120 mm Hg in aortic dissection.
Without a compelling condition, SBP should be reduced by no more than 25% within the first hour; then, if stable, reduce to
160/100 mm Hg within the next 2 to 6 hours; finally, cautiously reduce to normal during the following 24 to 48 hours. See
Neurology for treatment of hypertension associated with ischemic stroke and intracerebral hemorrhage.
For patients without a compelling indication, treatment consists of short-acting IV drugs administered in the ICU (e.g., nitro-
glycerin, nitroprusside, labetalol, nicardipine).
STUDY TABLE: IV Antihypertensive Drugs for Treatment of Hypertensive Emergencies in Patients with a Compelling Comorbidity
Comorbidity Preferred Drugs
Acute aortic dissection Esmolol, labetalol

Acute pulmonary edema Nitroglycerin, nitroprusside
β-Blockers contraindicated
ACS Esmolol, nitroglycerin
AKI Nicardipine
Eclampsia or preeclampsia Hydralazine, labetalol, nicardipine
ACE inhibitors, ARBs, renin inhibitors, nitroprusside contraindicated
DON’T BE TRICKED
• Do not select sublingual nifedipine for either hypertensive urgency or emergency.
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 reaction) 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 1 hour if the
antigen was injected or up to 2 hours if ingested.
372
.
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 cause of anaphylaxis during surgery or anaphylaxis in a woman during coitus.
Treatment
Epinephrine is first-line therapy even if the only presenting signs are hives or pruritus. Use inhaled bronchodilators for bron-
chospasm and IV saline for shock or hypotension.
β-Blockers may blunt the effect of epinephrine, but epinephrine remains the drug of first choice; reserve glucagon for
epinephrine-refractory anaphylaxis.
Patients with diffuse rash or anaphylaxis from hymenoptera sting (bee, yellow jacket, and wasp) should undergo venom skin
testing and immunotherapy.
DON’T BE TRICKED
• IM or subcutaneous epinephrine (0.3-0.5 mg of 1:1000) is first-line treatment for classic anaphylaxis. IV epinephrine
(1:10,000) is reserved for anaphylactic shock or refractory symptoms.
• Red man syndrome seen with IV vancomycin infusion is not an allergic reaction.
TEST YOURSELF
A 25-year-old woman has shortness of breath and wheezing after a bee sting 1 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.
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,
opiates).
Bradykinin-mediated angioedema is NOT associated with urticaria. In the setting of angioedema without urticaria, the differ-
ential is very limited.
STUDY TABLE: Differential Diagnosis of Bradykinin-Mediated Angioedema

Condition Historical Clues/Disease Associations Laboratory Studies
Hereditary angioedema Family history of angioedema Low C1 inhibitor and C4 levels

Acquired C1 inhibitor deficiency Lymphoma, MGUS, or SLE Low C1q levels (in addition to low C4 and
C1 inhibitor levels)
ACE inhibitor effect Medication history Low C1 inhibitor and C4 levels
373
.
DON’T BE TRICKED
• In patients with urticaria and angioedema, do not diagnose hereditary angioedema.
Treatment
Select epinephrine, antihistamines, and glucocorticoids for
acute episodes of mast cell–mediated (allergic) angioedema with
airway compromise or hypotension. Patients should carry an
epinephrine autoinjector. Use antihistamines alone in cases of
allergic angioedema that is not part of an anaphylaxis syndrome
(absent airway compromise or hemodynamic instability).
Select C1 inhibitor concentrate for acute episodes of bradykinin-

mediated angioedema (hereditary or acquired angioedema); use
FFP in an emergency. For long-term management of hereditary
angioedema, select danazol and stanozolol to elevate hepatic
synthesis of C1 esterase inhibitor protein.
Angioedema: Angioedema differs from urticaria in that it covers a larger surface

DON’T BE TRICKED area and involves the dermis and subcutaneous tissues.
• Epinephrine is not effective for hereditary angioedema.
TEST YOURSELF
A 40-year-old man has a 1-year history of cramping abdominal pain and 2- to 3-day episodes of face 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 C1 inhibitor levels (functional and
antigenic) and treatment of severe acute episodes of swelling with C1 inhibitor concentrate.
Smoke Inhalation
Ensuring upper airway patency is the priority.
• Patients with a visibly damaged airway or stridor require immediate intubation.

• Assess carbon monoxide level.
• Cyanide exposure is common in house fires where cyanide is produced and aerosolized when 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
• Patients with inhalational injury involving the lower airways typically present with a clear chest x-ray; wheezing,
cough, and dyspnea manifest 12 to 36 hours after exposure.
• Normal oxygen saturation does not exclude either carbon monoxide or cyanide poisoning.
374
.
Poisoning with Therapeutic Agents

Key Considerations
STUDY TABLE: Poisoning with Common Therapeutic Agents
Toxin Clinical Syndrome Antidote/Intervention
Acetaminophen Hepatotoxicity N-acetylcysteine

Benzodiazepines Sedative/hypnotic Observation; flumazenil
β-Adrenergic blockers Bradycardia, hypotension Glucagon, calcium chloride, pacing
Calcium channel blockers Bradycardia, hypotension Atropine, calcium, glucagon, pacing
Digoxin Dysrhythmias Digoxin-immune fab
Heparin Bleeding diathesis Protamine sulfate
Narcotics Narcotic effects Naloxone
Salicylates Metabolic acidosis/respiratory alkalosis Urine alkalinization, hemodialysis
Tricyclic antidepressants Anticholinergic effects Blood alkalinization, α-agonist
Carbon Monoxide Poisoning

Diagnosis and Testing
Characteristic findings are unexplained flulike symptoms, frontal headache, lightheadedness, difficulty concentrating, confu-
sion, delirium, coma, dyspnea, nausea, and chest pain that are often associated with use of a grill or burning heat source
indoors. Order ABG studies and serum carboxyhemoglobin measurement for all patients with neurologic changes, dyspnea,
chest pain, or smoke exposure. A carboxyhemoglobin level >25% in any patient is diagnostic of severe acute carbon monoxide
poisoning.
DON’T BE TRICKED
• Pulse oximetry data are unreliable because the oximeter is unable to differentiate carboxyhemoglobin from
oxyhemoglobin.
Treatment
Normobaric oxygen therapy is the treatment of choice. Hyperbaric oxygen therapy is indicated for patients with severe carbon
monoxide poisoning (characterized by loss of consciousness and persistent neurologic deficits), pregnant patients, or patients
with evidence of cardiac ischemia.
TEST YOURSELF
A 39-year-old man is found unconscious by his family. He had not been seen since late the previous evening. The outside tem-
perature was below freezing overnight. He is unresponsive and deeply cyanotic. The patient is intubated and ventilated with 100%
oxygen. Although the O2 saturation is 100%, he remains comatose.
ANSWER: For diagnosis, choose carbon monoxide poisoning. For management, select carboxyhemoglobin level measurement.
375
.
Alcohol Poisoning
See the Nephrology chapter for discussion of alcohol poisoning.
Toxidromes
STUDY TABLE: Toxic Syndromes Manifestations and Treatments
Syndrome Manifestations Representative Drugs Treatment
Sympathomimetic Tachycardia Cocaine Benzodiazepines for agitation

Hypertension Amphetamines Avoid β-blockers for hypertension
Diaphoresis Ephedrine Haloperidol may worsen
hyperthermia
Agitation Caffeine
Seizures
Mydriasis
Cholinergic “SLUDGE” Organophosphates Organophosphates poisoning
(insecticides, sarin) requires external decontamination
Confusion
Carbamates Atropine
Bronchorrhea
Physostigmine May require ventilatory support
Bradycardia
Edrophonium Add pralidoxime for CNS toxicity
Miosis
Nicotine Benzodiazepines for convulsions
Anticholinergic Hyperthermia Antihistamines Physostigmine for those with
peripheral and CNS symptoms
Dry skin and mucous membranes Tricyclic antidepressants
Benzodiazepines for agitation
Agitation, delirium Antiparkinson agents
May require ventilatory support
Tachycardia, tachypnea Atropine
Hypertension Scopolamine
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.
376
.

Pulmonary and Critical Care Medicine

Uploaded by

Copyright:

Available Formats

Pulmonary and Critical Care Medicine

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Pulmonary and Critical Care Medicine

Uploaded by

Copyright:

Available Formats

Pulmonary and Critical Care Medicine

Pulmonary Function Tests

Key Tests and Patterns

• FEV1/FVC <0.7 indicates airflow obstruction.

Lung volumes aid in confirming findings on spirometry:

Dlco evaluates gas transport across the alveolar-capillary membrane.

STUDY TABLE: Interpreting Dlco

↓ Dlco and reduced lung volumes Pulmonary fibrosis

STUDY TABLE: Understanding Important Pulmonary Tests

Pulse oximetry Measures percentage of oxyhemoglobin; performed at rest or during exercise

Flow-Volume Loops: Flow-volume loops plot flow (L/sec) as a function of volume.

STUDY TABLE: Differential Diagnosis of Asthma

STUDY TABLE: Step Classification of Asthma

Step 1: Intermittent Symptoms ≤2 per week ≤2 per month

STUDY TABLE: Asthma Treatment

Step 1: Intermittent Select a short-acting β-agonist as needed

• inadequate control of symptoms with inhaled glucocorticoids

For all patients:

Treatment of exercise-induced asthma:

• For infrequent symptoms, treat with a SABA 15 to 30 minutes before exercise.

Treatment of asthma in pregnancy:

Treatment of severe asthma exacerbation in the emergency department:

Chronic Obstructive Pulmonary Disease

STUDY TABLE: Mimics of COPD

Strong evidence-based recommendations:

Weaker evidence-based recommendations:

Additional indications for which long-term oxygen therapy should be considered:

Other therapies for stable COPD:

• PDE-4 inhibitor (roflumilast) as add-on therapy for severe COPD

• tetracycline or trimethoprim-sulfamethoxazole for mild exacerbations

• antipseudomonal antibiotics for acute pulmonary exacerbations

Diffuse Parenchymal Lung Disease

• time course (typically months or years)

Look for restrictive or combined restrictive/obstructive findings on pulmonary function tests.

STUDY TABLE: Distinguishing Features of Select Forms of DPLD

Drug induced Examples: amiodarone, methotrexate, nitrofurantoin, chemotherapeutic agents

Rare DPLD with Well-Defined Features

Idiopathic Pulmonary Fibrosis

Serum ANA, rheumatoid factor, c-ANCA, and p-ANCA levels are

Diagnosis is based on clinical and radiographic findings, absence

Idiopathic Pulmonary Fibrosis: High-resolution, thin-section chest CT scan

Characteristic findings include:

• fever, weight loss, and night sweats

Diagnostic studies include:

• PFT (sarcoidosis may cause obstruction, restriction, or both)

STUDY TABLE: Clues to Occupational Lung Disease

Asbestos-Associated Lung Diseases

STUDY TABLE: Asbestos-Related Lung Syndromes

Mesothelioma: Frontal chest x-ray showing multiple pleural-based nodular infil-

STUDY TABLE: Laboratory Tests for Identifying a Pleural Effusion as an Exudate

Pleural fluid protein–serum protein ratio >0.5

STUDY TABLE: Common Causes of Transudative and Exudative Pleural Effusions

Increased hydrostatic pressure (HF, constrictive pericarditis, SVC Infection

STUDY TABLE: Pleural Fluid Cell Counts and Chemistries

Other key points:

• Pleural fluid adenosine deaminase is elevated in most TB effusions.

Secondary pneumothorax is associated with lung disease. Consider

• emphysema as the most common cause of secondary pneumothorax.

Characteristic symptoms of PH include: