Endobronchial Tuberculosis 11/5/2018

Sarasa presented a case of a young woman with recently diagnosed pulmonary TB on HREZ presenting with worsening dyspnea and voice changes. Her fiberoptic endoscopy of the upper airway was normal. She was found on CT to have tissue thickening and stranding in the mid/lower trachea as well as a small tracheal diverticula, very suspicious for endobronchial TB!


Endobronchial tuberculosis

Definition: TB that involves the tracheobronchial tree


  • More common among patients with extensive pulmonary TB, especially with cavitary lesions, can occur in 10-40% of patients but less common now with anti-TB therapy.
  • For some reason more likely to occur in women in second to third decades of life.
  • Usually seen in main and upper bronchi, but in 5 % of cases: involves the lower trachea


  • Unclear but thought to be by either direct extension of pulmonary disease into the bronchi, spread via infected sputum, or hematogenous/lymphatic spread.


  • Cough, CP, hemoptysis, wheezing (low pitch), fatigue, fever, dyspnea. Can mimic foreign body aspiration, non-resolving pneumonia, or malignancy.
  • Can have significant sputum production, leading to bronchorrhea (> 500mL/day of sputum)
  • Complications: Atelectasis, obstruction, bronchiectasis, tracheal stenosis, fistula, hilar lymph node rupture

Diagnosis: CT and bronchoscopy are methods of choice for dx, with bronch being the most validated for confirming the diagnosis.

  • XR: Can be normal in 10-20% of cases
  • CT: Can demonstrate endobronchial lesions, stenosis (up to 2/3 of patients), or fistulas.
  • Bronchoscopy: able to visualize stenosis and biopsy. Can interview if severe symptomatic stenosis.


  • Same as for other forms of TB but also prevent tracheobronchial stenosis
  • Medical Therapy
    • Intensive Phase: HREZ (aka RIPE) x 2 months
      • R: Rifampin
      • I: Isoniazid
      • P: Pyrazinamide
      • E: Ethambutol
    • Continuation Phase
    • Ex: 2HREZ/4HR = standard regimen, 2 months of HREZ (RIPE), followed by 4 months of isoniazid and Rifampin
  • Specific for endobronchial TB
    • Corticosteroids: Controversial.
      • Shown improvement in outcome (prevention of bronchial compression) in children.
      • Some data on shortening healing time and decrease severity of bronchial stenosis
    • Nebulized INH or streptomycin, mixed data
    • Surgery: Usually indicated for stenosis or stricture. Balloon dilatation, stenting, ablation, resection, cryosurgery.
    • Severe tracheobronchial stenosis sometimes requires pneumonectomy or lobectomy

Laryngeal TB:

Distinctive entity, also more prevalence in younger patients, most commonly presents with dysphonia (96%), odynophagia (25%), and stridor (9%). True vocal cords, epiglottis, and false vocal cords are most commonly involved.

Drug Resistance and TB


  • Drug-resistance TB: resistant to one or more anti-TB drugs
  • Mono-resistant: single agent
  • Poly-resistant: resistant to multiple drugs, but susceptible to either INH or rifampin but not both
  • MDR: R to INH and rifampin + others.
  • XDR-TB: Extensively drug resistant TB: resistant to INH, rifampin, fluoroquinolones + either aminoglycosides or capreomycin or both.

1st Line Agents

  • Rifampin
  • Isoniazid
  • Pyrazinamide
  • Ethambutol
  • Streptomycin

2nd Line Agents

  • Fluoroquinolones (Levofloxacin, Moxifloxacin)
  • Injectable: Amikacin, Capromycin, Kanamycin
  • Other: Cycloserine, Linezolid, Ethionamide

Addon Agents/Tertiary

Bedaquiline, Para-aminosalicyclic acid, imipenem, meropenem + Augmentin, thioacetazone.

If suspecting resistant, strategy usually is to add at least 2 additional drugs. Adding single drug inc risk for resistance.

Management of drug-resistant TB:

Tx of MTB PCR will be based on susceptibility data

  • Conventional: 20-26 months treatment, with an intensive phase with at least 5 effective drugs for at least 6 months after negative sputum, followed by a continuation phase of at least 4 drugs for 18-24 months
  • Shorten version for 9-12 months if no extra-pulmonary manifestation and susceptible to quinolones.

Please refer to this informative article on a review of endobronchial TB.

All about PE – 11/1/18

Thanks to Barnie for presenting the case of a middle-aged woman who was admitted with acute onset of SOB, found to have submassive PE.

Clinical Pearls:

  • Risk stratification tools are helpful in estimating the pre-test probability of PE.  The best and most validated is Wells criteria.
    • YEARS items is a newer tool that was studied in an RCT in the Netherlands and found to lower the number of CTPA scans ordered by 14% without a significant impact on rates of missed PE diagnoses.
  • For patients at low risk of PE according to Wells, PERC is useful in ED or outpatient setting to rule out PE without ordering a d-dimer (see graphic below).
  • Age-adjusted d-dimer is age x 10 for patients older than 50 years.  This accounts for the increase in d-dimer baseline related to aging.  ADJUST-PE trial showed that age-adjusted d-dimer leads to higher specificity without subsequent VTE.
    • Studies have shown an 11.6% reduction in CTPA scans with the use of this correction factor without an appreciable increase in missed diagnoses of PE.
  • Think of PE in three broad categories:
    • Massive PE = hemodynamically unstable ⇒ anticoagulation + thrombolysis
    • Submassive PE = hemodynamically stable + RV strain ⇒ anticoagulation + thrombolysis
    • Low risk PE = hemodynamically stable, no RV strain ⇒ anticoagulation.  Use the PESI score to determine if your patient can be treated outpatient.
  • Remember that the most common EKG finding in PE is normal sinus rhythm!  The most common abnormal  EKG finding is sinus tachycardia.  S1Q3T3 pattern is only seen in 10% of patients with PE.


Suggested algorithm for diagnostic work up of suspected PE:

PE diagnostics

Remember that the scoring tools above are only there to add to your clinical judgment, not replace it!

Recent study in the Lancet looked at the utility of a different diagnostic algorithm, using the three most predictive items on Wells together with d-dimer.  Compared to Wells, this diagnostic tool led to a 14% reduction in unnecessary CTPA!

PE diagnostics 2


PE treatment.PNG

  • Remember that clot burden does not factor into the treatment categories of PE.  Low clot burden in a patient with baseline cardiopulmonary disease can still lead to hemodynamic compromise and would be considered massive PE.
  • Submassive PE treatment is an area of much debate.  A famous trial (PEITHO trial) in 2014 randomized 1006 patients to receive heparin + placebo vs heparin + tenecteplase (European version), and found a >50% reduction in combined death and cardiovascular collapse at 7 days but a > four-fold increase in risk of major bleed including intracranial hemorrhage.  Subsequent meta-analyses (and this one) found that the risk of major bleeding was highest in people >65 years of age.  So treatment decisions here are tricky and require consulting multiple services!

Signs of RV strain: 

  • EKG findings:
    • S1Q3T3: this is a sign of cor pulmonale and can be seen in a number of conditions in addition to PE
      • Bronchospasm (really bad asthma)
      • ARDS
      • Pneumothorax
  • Echo findings:
    • Elevated RVSP
    • Septal bowing
    • McConnell’s sign (regional wall motion abnormality sparing the RV apex)
      • Not sensitive but helpful in distinguishing RV strain due to chronic pulmonary HTN from RV strain due to acute PE
    • Increased RV size
    • Decreased RV function
    • Tricuspid regurgitation
  • Labs
    • Elevated troponin
    • Elevated BNP

Diffused Alveolar Hemorrhage (DAH) AND Hemophagocytic Lymphohistiocytosis (HLH) 10/22/2018

Thank you Charles for presenting this really interesting case. A 18 year old woman with a history of asymptomatic thrombocytopenia who presents with several days of non-specific fever, chills, malaise, mild shortness of breath and she was found to have acute anemia, thrombocytopenia, elevated transaminitis, and patchy bilateral pulmonary infiltrates on CXR during initial presentation. She became acutely ill with submassive hemoptysis and went into respiratory failure in 24-48 hours. She was found to have DAH on BAL. Her autoimmune and infectious work up came back negative, but her ferritin  came back at 75776. Base on this and her constellation of symptoms, further work up revealed a 6/8 criteria for diagnosis of hemophagocytic lymphohistiocytosis!



  • Dyspnea, cough fever, respiratory failure, acute anemia
  • Hemoptysis only in 2/3 of cases
  • Definition: Hemoptysis, diffuse alveolar infiltrates, acute anemia, and hypoxemic respiratory failure


  • Widespread damage to pulmonary small vessels, leading to blood within the alveoli eventually causing impaired gas exchange.
  • Causes: Autoimmune/connective tissue disease leading to pulmonary vasculitis (ANCA, anti-GBM), certain pulmonary infections, toxins, drug reactions, mitral stenosis in some cases
  • 3 distinct histologic subtypes that can give hints to underlying pathology
    • Most common: Pulmonary capillaritis: ANCA vasculitis, GPA, EPGA, pauci-immune, Goodpasture, HSP, SLE, RA, APLS, MCTD, Behcet, drug-induced, lung transplant rejection, etc.
      • Systemic vasculitis manifestation
    • Bland pulmonary hemorrhage: Coagulopathy, mitral stenosis, toxin/inhalation, SLE, drugs, Goodpasture
      • Anti-GBM, SLE, no inflammation or destruction of capillaries but RBC leakage
    • Diffuse alveolar damage: BM transplantation, radiation, ARDS, cytotoxic drugs, other causes


  • CXR: Diffuse bilateral alveolar infiltrates, no pathognomonic findings
  • BAL: serial bloody aspirate with sequential sampling
  • DAH
  • CT: Non-specific GGO
  • Biopsy: Tissue biopsy of the lung is definitive in confirmation of DAH but underlying cause might not be revealed.


  • Treat underlying cause
  • Respiratory support, most patients die from respiratory failure
  • High dose corticosteroids, i.e. methylprednisolone up to 500mg Q6H (up to 2g daily)
  • Other agents: Cyclophosphamide, azathioprine, MTX, mycophenolate, etanercept.
  • Plasmapheresis for Goodpasture or vasculitidies.
  • Key: Early identification and treatment



  • Worldwide incidence is unknown, not enough data available, thought to be rare AND underrecognized but growing recognitive leads to higher incidence.
  • Familial types: more common to occur in pts < 18yo
  • Secondary HLH: any age


  • Uncontrolled hyperinflammatory response with dysregulated macrophage activity leading to excessive cytokine production
  • Primary: HLH due to an underlying genetic abnormality or without clear cause
    • Autosomal recessive familial HLH
    • Idiopathic
  • Secondary: Due to something else
    • Retrospective study at Mayo in 2014:
      • Infection (34%), most commonly EBV
      • Autoimmune (8%), Macrophage activation syndrome (MAS), most often associated with AOSD, systemic juvenile idiopathic arthritis, or SLE.
      • Malignancy (52%) NHL, HL, acute leukemia
      • Idiopathic/Immune deficiency/other (6%)


  • Fever, splenomegaly, cytopenias are most common
  • + manifestation of the trigger
  • Complications: Infection, DIC, bleeding complications (reports of intracranial hemorrhage, GIB, DAH), end organ damage.

Diagnosis: Per the Histiocyte Society: 5/8 criteria for diagnosis. In case you cannot remember all 8, please refer here for the famous HLH Song by Dr. Eric Lau:

    1. Fever
    2. Splenomegaly
    3. Peripheral cytopenia (> 2 cell lines)
    4. Hypertriglyceridemia or Hypofibrinogenemia
    5. Elevated ferritin > 500 (> 10000 = 90% sensitive and 96% specific for HLH)
    6. Low NK cell activity
    7. Elevated soluble CD25 (soluble IL2-R)
    8. Hemophagocytosis in BM, spleen, or LN: Only seen in later course of the diseases and not required for the diagnosis, neither sensitive nor specific, can be seen in severe sepsis/critical illness)


  • Like all things in medicine, treat the underlying cause
  • Current treatment is based on the HLH-94 study on pediatric population
    • Induction: 8 weeks dexamethasone and etoposide.
    • Maintenance: Cyclosporine, tacrolimus, dex pulses
    • If MAS: Steroids alone, usually responsive.
    • Hematopoietic stem cell transplant is refractory/relapsing.

For more information on HLH, please refer to this article by Dr. Schram and Dr. Berliner published in Blood (as in the journal) in 2015.

Parapneumonic effusions

Thanks to Julie for presenting the case of a middle-aged man with recent CAP who presented with progressive SOB, pleuritic chest pain, weight loss, and anorexia, found to be septic with a large empyema, eventually requiring open decortication!

Clinical Pearls

  • Think of parapneumonic effusions in two broad categories: infected (complicated and empyema) and sterile (uncomplicated).
    • Infected (complicated and empyema) require chest tube placement and can be complicated by loculated effusions.
    • Uncomplicated resolve with the treatment of underlying pneumonia
  • Anaerobic organisms are a common cause of infected parapneumonic effusions.  Malodorous fluid at the time of thoracentesis is diagnostic!  But make sure to send anaerobic cultures to the lab to help with speciation.
  • pH of pleural fluid can be falsely elevated if not immediately stored on ice upon collection and processed in a blood gas analyzer.
  • Differential for pleural fluid that has low glucose/low pH is short: infection, TB, malignancy, rheumatoid pleurisy, and lupus pleuritis.
  • Remember that while ADA has high sensitivity (86%) and high specificity (87%) for TB, the study on which it is based was done in a high risk population so its utility in screening low risk patients is limited.

Parapneumonic effusions:

  • Form in 40% of bacterial pneumonia:
      • Uncomplicated: negative GS and Cx, pH>7.2, glucose >60, no loculations
      • Complicated: positive GS or Cx or pH <7.2, or glucose <60. LDH >1000 makes it more likely
      • Empyema: frank pus aspirated during thora, cell count with >50k WBCs

The latter two categories require chest tube placement to prevent formation of pleural “peels” that can lead to trapped lung and loss of lung function.

  • Imaging
    • Lateral decub or ultrasound, latter is more sensitive than CXR for diagnosing complicated parapneumonic effusions.
    • CT with contrast is the optimal imaging for empyema or loculated effusion
      • Look for the “split pleura sign”
  • Labs:
    • Serum procalcitonin >0.18 ng/mL is 83% sensitive and 81% specific for effusion having a bacterial infectious etiology
    • Bacteriology:
      • Anaerobic bugs are often the culprit!  So it is important to send pleural fluid for both aerobic and anaerobic cultures
      • Other bacteria: CAP organisms such as strep and staph as well as klebsiella in diabetic patients
      • Fungi
      • TB
  • Treatment:
    • Tube thoracostomy (chest tube): first intervention
      • CT within 24 hours to ensure correct positioning and adequate drainage, left in place until drainage is <50 cc/day
    • Fibrinolytic agents
      • DNA is a main contributor to viscosity of empyema fluid.  However, based on this trial published in NEJM in 2011, tPA and DNAase combined is associated with significant radiographic improvement of empyema, reduction in hospital stay, and lower number of surgical referrals.
    • VATS
    • Decortication
      • To remove the thickened fibrin layer covering the pleura.
    • Open thoracostomy
      • Rib resection and opening the chest wall at the inferior border of empyema to allow for ongoing drainage.  High risk of infection and complications.

Hepatopulmonary Syndrome 10/10/2018

A 67 year old man with history of cirrhosis secondary to Hepatitis C and alcohol, hepatocellular carcinoma with recent TACE, presented with worsening dyspnea on exertion and positional shortness of breath. His breathing was worse when he sat upright, and better when he was supine. What’s going on?

Just to go over some terms:

  • Orthodoxia: Drop in PaO2 by 5mmHg or O2sat by 5% when moving from supine to upright.
  • Platypnea: Dyspnea that is induced by moving to an upright position, relieves when supine.

Hepatopulmonary syndrome


  • Chronic liver disease or portal hypertension
  • Intrapulmonary vascular dilations (IPVD)
  • Impaired oxygenation


Up to 25% of patients with chronic liver disease will have some degree of shunting, can occur at any stage (mild or severe)


  • Not well understood but the theory is due to increased nitric oxide production and reduced NO clearance, resulting in pulmonary vasodilation (IPVDs) mostly concentrated at the lung bases.
  • When upright, blood preferentially perfuse the lower lung  zones due to gravity.
  • Vasodilation leads to poor gas exchange.


  • This leads to a VQ mismatch


  • CXR: Not helpful, might show e/o interstitial lung markings.
  • CT: Can reveal IPVDs
    • Dilated peripheral pulmonary vessels
    • Inc pulmonary artery to bronchus ratios
  • PFT: Not helpful
  • Transthoracic contrast echo (TTCE): Can be used to demonstrate presence of intrapulmonary shunts supportive of presences of IPVDs
    • Concept of bubble study: Shooting agitated saline (with bubbles into the vasculature
    • Bubbles visible in the R heart chambers, should not be visible in the left heart chambers.
    • If presence of bubbles in the left: This is indicative of a shunt:
      • Intracardiac shunt: bubbles seen within 1 beat
      • Intrapulmonary shunts: bubbles seen after 3-8 beats.


Normal Echo: Notice how the agitated saline bubbles remain on the right side of circulation and do not cross over. The bubbles were filtered out by the pulmonary vasculature.

Normal Echo


Echo demonstrating intrapulmonary shunting (see bubbles crossing over from the right to the left)




  • Supplemental O2 indicated if O2 sats < 88%, PaO2 < 55mmHg
  • Mild to moderate: Monitor Q6-12 months
  • Severe to very severe: Referral for liver transplant
  • Insufficient data on other treatment options (garlic, pentoxifylline, NO synthase inhibitors, IPVD embolization, plasma exchange, oxtreotide).


Image adapted from Uptodate

Check out this article if you’re interested in the data behind pentoxifylline!