Perelman School of Medicine at the University of Pennsylvania

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Pulmonology Pearls


How do you diagnose ARDS?

  • Diagnosis: New bilateral infiltrates that are non-cardiogenic w/ a P/F ratio < 300
    • Mild < 300
    • Moderate < 200
    • Severe < 100

How do you manage mechanical ventilation of ARDS patients?

  • Lung Protective Ventilation (ARMA study demonstrated 31% mortality compared to 40% with 6 cc/kg IBW:
    • 4-6 cc/kg IBW, targeting plateau pressure < 30
    • Permissive hypercapnia to pH ~ 7.20
    • Can increase RR to max of 35 to maintain minute ventilation

How do you manage refractory hypoxemia in ARDS?

  • Recruitment maneuvers: (40 mmHg for 40 seconds of positive airway pressure) may recruit alveoli and increase PaO2
    • Usually followed by higher PEEP e.g. 15
  • Inhaled NO and prostacyclins (flolan) improve oxygenation but not mortality
  • Paralytics (cisatracurium) may benefit severe ARDS (P/F < 120)
  • Proning




Describe the step-wise therapy for chronic asthma management.

  • Intermittent (daytime symptoms < 2/week, nocturnal symptoms < 2/month): SABA
  • Mild persistent (daytime > 2/week, nocturnal 3-4/month): low ICS
  • Mod persistent (daily symptoms, nocturnal > 1/week): low ICS + LABA OR medium ICS
  • Severe persistent (symptoms throughout day): medium/high ICS + LABA

What is the role of anti-IgE therapy in asthma?

  • Omalizumab (Xolair) is anti-IgE antibody
  • Efficacy: 2014 systematic review of 25 randomized trials of moderate-severe asthma demonstrated reduction in exacerbations and risk of hospitalization:
  • Indications (requires all):
    • Moderate/Severe Persistent Asthma
    • Symptoms inadequately controlled by ICS
    • Total serum IgE 30-700
    • Positive skin or in vitro testing for allergen-specific IgE present year round

What are common mimickers of asthma?

  • Vocal cord dysfunction most common
    • Dyspnea, wheezing, stridor (usually inspiratory, louder over anterior neck), dysphonia, cough, inability to get air out
    • Diagnosis: direct laryngoscopy gold standard and easiest to obtain in emergency setting
    • Treatment:
      • Acute: CPAP, supportive care
      • Chronic: Speech therapy, psychotherapy

How is Allergic Bronchopulmonary Apergillosis (ABPA) diagnosed?

  • Diagnosis:
    • Predisposing condition (Asthma or CF)
    • Obligatory criteria (Positive Aspergillus skin test/anti-Aspergillus IgE PLUS total serum IgE > 1000)
    • Other criteria (2 of the following: serum antibodies to Aspergillus, radiographic opacities, total eosinophils > 500)
      • Imaging findings include central bronchiectasis, mucus plugging
  • Evaluation: skin test usually first test if suspected




What are the triggers for COPD exacerbations?

  • Bacterial pathogens: Haemophilus influenzae, Moraxella catarrhalis, Streptococcus Pneumoniae, Pseudomonas aeruginosa
  • Pulmonary embolism: 2008 systematic review in NEJM demonstrated 20% prevalence of PE in COPD exacerbations:

When should you give supplemental O2 in the management of a COPD exacerbation?

  • Target O2 sat of 88-92% or PaO2 of 60-70
  • Evidence: small randomized trial demonstrated mortality benefit with titrated oxygen compared to high flow oxygen:
  • Logic: the main thought behind lower O2 goals is to allow the natural mechanism of hypoxic vasoconstriction to compensate for areas of “bad” lung during a COPD flare and NOT reducing the drive for respiration (probably only plays a small role)

When do you use antibiotics in management of COPD exacerbations?

  • Change in sputum amount or character OR moderate-severe COPD exacerbation
    • Moderate-Severe defined as 2/3 cardinal symptoms PLUS 1 or more of following risk factors (2015 GOLD guidelines):
      • Age > 65
      • FEV1 < 50% predicted
      • ≥ 3 exacerbations per year
      • Cardiac disease

What is the role of steroids in the management of COPD exacerbations

  • Steroids reduce treatment failure and hospital length of stay
  • PO and IV formulations have equal efficacy in hospitalized patients (demonstrated by randomized trial that compared 5 days of PO to IV prednisolone in 210 hospitalized patients:
    • Can use IV when unable to tolerate PO or severe exacerbation
  • Duration:

What are the only interventions that have mortality benefit in COPD management?

How is chronic management of COPD determined?

  • Assessment of severity as combination of symptoms and risk:
    • Less Symptomatic (during exercise) vs. More Symptomatic (SOB on level ground)
    • Low Risk (FEV1 > 50% and < 2 exacerbations/year) vs. High Risk (FEV1 < 50% and ≥ 2 exacerbations/year)
    • Less Symptomatic plus Low Risk: SABA prn
    • More Symptomatic plus Low Risk: LABA
    • Less Symptomatic plus High Risk: LABA plus ICS or tiotropium
    • More Symptomatic plus High Risk: LABA plus ICS plus tiotropium

Your COPD patient is on triple inhaler therapy (tiotropium + LABA + ICS), but continues to have frequent flares. What other medications can be beneficial?



Cystic Fibrosis

Describe the microbiology of cystic fibrosis flares.

  • Staph aureus most common during childhood
  • Haemophilus influenzae also common in children, but less common among adults
  • Pseudomonas most common in adults
    • Conversion to mucoid phenotype associated with worse prognosis
  • Burkholderia cepacia complex: chronic infection associated with progressive decline

Describe the antibiotic management of cystic fibrosis flares.

  • Tailor antibiotics towards previous and current culture data
    • One antibiotic for each isolate, except pseudomonas which requires two antibiotics e.g. pip-tazo PLUS tobramycin
  • Continue any chronic antibiotics e.g. azithromycin
  • Airway clearance in CF flares
    • Beta-agonists
    • Inhaled hypertonic saline (give beta-agonists first)
    • Pulmozyme
    • Chest physical therapy
    • Generous IV fluids

What are some disease-modifying drugs in CF?

Describe the role of chronic antibiotic therapy in cystic fibrosis.

  • Generally harms outweigh benefits with two exceptions:
    • Azithromycin if chronic cough or reduced FEV1
    • Inhaled tobramycin if chronic Pseudomonas infection




What is the role of NIPPV (non-invasive positive pressure ventilation) in the management of acute respiratory distress?

  • High quality evidence supports the use of NIPPV in the management of COPD exacerbations and cardiogenic pulmonary edema
    • COPD: meta-analyses demonstrate mortality benefit (e.g. 11% vs. 21%) in COPD flare with PaCO2 > 45:
    • Cardiogenic pulmonary edema: multiple meta-analyses and randomized trials demonstrate reduced intubation and improved respiratory parameters, but data on mortality is mixed

What is the role of High-Flow Nasal Cannula in the management of acute hypoxemic respiratory failure?

  • Appears to be a good option in acute hypoxemic respiratory failure without hypercapnia
    • Multicenter trial had improved mortality and fewer days of mechanical ventilation compared to standard O2 or NIPPV:
    • The poor outcomes in the NIPPV warrant further confirmation given the possibility of more severe lung injury in this treatment group



Lung Cancer

What is the most common type of lung cancer?

  • Adenocarcinoma is most common at 38%, followed by squamous cell carcinoma at 20%

What is the Pancoast syndrome?

  • Lung cancers, usually squamous cell carcinoma, in the superior sulcus causing the following constellation of findings: pain, Horner’s syndrome (ptosis, anhidrosis, miosis), and atrophy of the hand muscles

What are examples of paraneoplastic effects from lung cancers?

  • Hypercalcemia due to PTHrP secretion (most commonly SCC), SIADH (most commonly SCLC), and Lambert-Eaton syndrome (most commonly SCLC)

What is the Lambert-Eaton syndrome?

  • Paraneoplastic syndrome characterized by autoantibodies against voltage-gated calcium channels resulting in slowly progressive symmetric proximal muscle weakness and autonomic dysfunction (e.g. dry mouth, blurry vision, impotence). On exam, maximal isometric contraction can lead to temporary improvement of muscle weakness

What is the role of palliative care in the management of advanced NSCLC?

  • 2010 NEJM study randomly assigned 150 patients with newly diagnosed metastatic NSCLC to standard care plus palliative care vs. standard care alone. Palliative care group had significantly improved quality of life and mood. Perhaps most note-worthy, the palliative care group also had reduced mortality (median survival 11.6 months vs. 8.9 months) despite receiving less aggressive care:



Obesity Hypoventilation Syndrome

How do you diagnose Obesity Hypoventilation Syndrome?

  • Obesity (BMI > 30) with awake alveolar hypoventilation (PaCO2 > 45), which cannot be attributed to other disease e.g. pulmonary disease, neuromuscular weakness etc.

How do you evaluate for Obesity Hypoventilation Syndrome?

  • Once you demonstrate awake hypoventilation via ABG in an obese individual, you must rule out other causes of hypoventilation
    • PFTs to evaluate for COPD or restrictive lung disease
    • CXR to evaluate for parenchymal lung disease
    • TSH and serum electrolytes
    • Polysomnography not required for diagnosis, but can help guide therapy

What is the pathogenesis of Obesity Hypoventilation Syndrome?

  • Complex interaction of several physiologic abnormalities
    • Upper airway obstruction from OSA
    • V/Q mismatch from obesity
    • Altered ventilatory control (e.g. potential inhibition from leptin)



Pleural Effusion

What are the Light’s Criteria for characterizing pleural effusions?

  • Any one of the following 3 criteria is supportive of an exudative effusion
    • Pleural fluid to serum protein ratio > 0.5
    • Pleural fluid to serum LDH ratio > 0.6
    • Pleural fluid LDH > 2/3 the upper limit of normal

What are the sensitivity and specificity of Light’s Criteria for exudative pleural effusions?

  • 97.5% sensitivity and 80% specificity for detecting exudative pleural effusions according to 2006 retrospective study:
  • One key take home point is that due to the relatively low specificity, 1 in 5 effusions characterized as exudative by Light’s Criteria may actually be transudative.

What can you do if the effusion is exudative by Light’s Criteria, but the patient is suspected clinically to have a transudative effusion?

  • You can measure the serum to pleural fluid protein gradient. If the gradient is > 3.1, the exudative criteria can be ignored, as nearly all of these patients will actually have a transudative effusion

What is the role of triglyceride testing in pleural fluid analysis?

  • Triglycerides > 110 mg/dL support a diagnosis of chylothorax, while triglycerides < 50 reasonably exclude the possibility of chylothorax

What is the role of pleural fluid NT-proBNP in pleural fluid analysis?

  • A pleural fluid NT-proBNP > 1500 is virtually diagnostic that the effusion is due to congestive heart failure

What is the role of adenosine deaminase testing in pleural fluid analysis?

  • May be helpful in distinguishing malignant effusions from tuberculous effusions. ADA levels typically > 35-50 in tuberculous effusions, but false positives and negatives occur, so results should be considered in context of the patient’s presentation.

What are the 3 types of effusions you can see with pneumonia?

  • Uncomplicated parapneumonic effusion – simple exudative effusion in the context of a pneumonia
  • Complicated parapneumonic effusion – persistent bacterial invasion of the pleural space
  • Empyema – characterized by bacterial organisms on gram stain and/or aspiration of pus during thoracentesis

When is tube thoracostomy drainage needed in the management of parapneumonic effusions?

  • Positive culture or gram stain
  • Gross pus on aspiration during thoracentesis
  • Pleural fluid pH < 7.20
  • Loculated effusions or effusion with thickened parietal pleura on CT (suggestive of empyema)




What are the types of pneumonia?

  • Viral pneumonia
  • Bacterial pneumonia
    • Community-acquired pneumonia
    • Hospital-acquired pneumonia
    • Healthcare-associated pneumonia
    • Ventilator-associated pneumonia
    • Aspiration pneumonia
  • Fungal pneumonia
  • Idiopathic interstitial pneumonia (non-infectious)
  • JAMA Rational Clinical Examination on Does this Patient have Ventilator-Associated Pneumonia?

What physical exam findings suggest pneumonia?

What are physical exam findings that you can use to distinguish pneumonia from pleural effusion?

  • Tactile fremitus will be increased in consolidation and decreased with effusion
  • Consolidation should also produce egophony (E to A change)

What does CURB-65 stand for and how does it affect pneumonia treatment?

  • CURB-65 score used to determine if a patient should be hospitalized
  • C=confusion, U=Urea > 20, R=Respiratory rate>30, B=BP <90/60, 65=Age >=65 (1 pt each)
  • Score 0-1 = likely can be managed at home
  • Score 2 = close followup or short hospitalization
  • Score 3-5 = hospitalization recommended
  • Original 2003 Thorax paper introducing the CURB-65 score:

What organisms generally cause community acquired pneumonia?

  • Strep pneumoniae (most common), Staph aureus, Haemophilus influenzae, Legionella, Pseudomonas, viruses

What are the criteria for healthcare-associated pneumonia?

  • Recent hospitalization in the last 90 days for at least 48 hours
  • Resident in a nursing home or long-term care facility
  • All dialysis patients
  • Anyone who has received IV antibiotics or chemotherapy in the last 30 days

What are the criteria for hospital-acquired pneumonia?

  • Pneumonia that occurs 48 hours or more after admission and was unlikely to be present on admission

How do we empirically cover for bacterial pneumonia?

  • Community-acquired pneumonia: ceftriaxone/azithromycin or levofloxacin alone
  • Healthcare-associated pneumonia/ventilator-associated pneumonia: cefepime/vancomycin

How do you switch from IV antibiotics to PO antibiotics in CAP treatment?

  • Switch to IV can happen early
  • No need to observe patients in the hospital after switching

What is the duration of antibiotics for pneumonia treatment?

What is the role of the MRSA swab in treatment of patients hospitalized for pneumonia?

  • MRSA swab has excellent negative predictive value (99%) for MRSA pneumonia in populations with low MRSA pneumonia incidence

What is the role of follow-up chest X-ray after resolution of pneumonia?

  • Not routinely indicated, but can be considered in patients over the age of 50, especially male smokers, to rule out underlying lung cancer
  • Should be obtained 7-12 weeks after treatment

What are the concerns about daptomycin in pneumonia?

  • If you are trying to cover MRSA pneumonia and either cannot use vancomycin or the pathogen is resistant to vancomycin, you cannot use daptomycin
  • Daptomycin is inactivated by the surfactant in the lungs



Pulmonary Embolism

What is the Wells criteria assessment for pulmonary embolism?

  • Clinical symptoms of DVT (3), Other diagnoses less likely than PE (3), Heart rate > 100 (1.5), Immobilization or surgery in past 4 weeks (1.5), Previous DVT/PE (1.5), Hemoptysis (1), Malignancy (1)
  • Low probability (< 2), Moderate probability (2-6), High probability (>6)

What is the role of D-dimer in evaluation for pulmonary embolism?

  • In patients whom pulmonary embolism is felt to be unlikely (e.g. low probability Wells score), a normal D-dimer effectively excludes PE

What are the EKG findings for pulmonary embolism?

  • Sinus tachycardia and non-specific ST-segment and T-wave changes most common
  • S1Q3T3 (large downward S wave in I, deep Q wave in III, downward T wave in III) and other signs of right heart strain are historically associated with PE, but are neither sensitive nor specific for PE

What are the chest x-ray findings associated with pulmonary embolism?

  •  Primary role is to exclude other pulmonary causes of dyspnea/chest pain
  • Atelectasis (18-69%) and pleural effusions (47%) most common
  • Hampton’s hump (wedge-shaped opacity at periphery) and Westermark’s sign (sharp cut-off of pulmonary vessels with distal hypoperfusion) are rare

When are thrombolytics indicated in the treatment of pulmonary embolism?

  • Only indicated in hemodynamically unstable PE
  • Absolute contraindications include intracranial neoplasm, recent (< 2 months) intracranial/spinal surgery or trauma, history of hemorrhagic stroke, or active bleeding
  • Relative contraindications include severe uncontrolled hypertension, nonhemorrhagic stroke within past 3 months, surgery within previous 10 days, or pregnancy

What are the indications for an IVC filter?

  • DVT or PE with contraindication or s/p complication of anticoagulation
  • Failure of anticoagulation therapy (new embolic event while on anticoagulation)
  • Free-floating iliofemoral or IVC thrombus

What are the complications of an IVC filter?

  • From jugular access: pneumothorax, access site thrombosis, bleeding
  • From filter itself: IVC trauma/penetration, filter fracture/migration/infection, IVC thrombus, death

When should you evaluate for hypercoagulability in unprovoked DVT/PE?

  • Varies according to practice pattern, but the key variable is whether or not it will change management in regards to long-term anticoagulation
  • As an example, the largest risk factor for subsequent DVT/PE is the occurrence of the initial unprovoked DVT/PE

Which thrombophilic defects can be evaluated for in setting of acute PE and anticoagulation?

  • Factor V Leiden and Prothrombin gene mutations are not affected by acute thrombosis or anticoagulation
  • Anticardiolipin antibodies and anti-beta2-glycoprotein can also be sent
  • All others must wait for 2 weeks after discontinuation of anticoagulation

Should you evaluate for occult malignancy in patients with unprovoked DVT/PE?

  • Yes, but evaluation should be limited to H&P, basic labs, and routine age-appropriate cancer screening
    • Prospective study of over 600 patients with unprovoked DVT/PE compared limited screening to extensive screening (additional CT A/P and mammography) found slightly more cancers (3.5% vs. 2.4%), but no difference in mortality (



Pulmonary Hypertension

What are the Pulmonary Hypertension WHO Groups?

  • WHO Group 1: pulmonary arterial hypertension (e.g. idiopathic, HIV, CTD, congenital heart disease, porto-pulmonary HTN)
  • WHO Group 2: pulmonary hypertension due to left heart disease
  • WHO Group 3: pulmonary hypertension due to lung disease (COPD, ILD, OHS)
  • WHO Group 4: pulmonary hypertension due to chronic thromboembolic disease
  • WHO Group 5: pulmonary hypertension from other causes (important ones to remember are sarcoidosis and sickle cell disease)

How does treatment vary by WHO Group?

  • Diuretics indicated if volume overload in any Group
  • Anticoagulation indicated in Group 1 and 4
  • Mechanical thrombectomy potentially curable for Group 4
  • Advanced therapies for Group 1 and potentially Groups 3-5 if evidence of vasodilator response
    • Prostacyclins (Epoprostenol aka Flolan)
    • Endothelin Receptor Antagonists (Bosentan)
    • PDE-5 Inhibitors (Sildenafil)