1/31 PPMC Report: Aspiration and PJP Pneumonia

Thank you to Dr. Palevsky and Dr. Gluckman for helping us discuss a really interesting case of an 82 year old gentleman with persistent hypoxia who was ultimately found to have a new diagnosis of HIV presenting with PJP pneumonia.

We discussed techniques for performing a thorough pulmonary exam: (images: https://meded.ucsd.edu/clinicalmed/lung.htm)pcp1

Many of these exam maneuvers use principles of physics to help us determine if the lung tissue is aerated normally, or if there is a process compromising aeration and anatomy. Since sound waves are vibrations, they are transmitted differently through air and solid/liquid media. Thus processes causing consolidation of lung tissue, alveolar filling, or other anatomic/functional pathology will transmit sound waves differently – leading to different findings on egophony, whispered pectoriloquy, tactile fremitus, and percussion.

Our patient experienced respiratory distress and decompensation following an upper endoscopy procedure. We discussed that his clinical circumstances were concerning for aspiration – which can cause either a pneumonitis (transient inflammation without leading to infection) or a pneumonia (infection). Dr. Palevsky taught us that due to anatomy of the airways branching, aspiration does not always go to the lung bases, and it is important to listen in the central lung fields too.

After a course of treatment for aspiration pneumonia, our patient continued to be hypoxic and tachypneic, so additional workup was pursued and ultimately he was diagnosed with HIV/AIDS and PJP pneumonia. We learned from Dr. Gluckman that 6% of new HIV diagnoses are made in patients older than 80 years, so always think about sending an HIV test on all of your patients, regardless of their age!

PJP is currently classified as a fungus, which is normally cleared by host macrophages and CD4 cells coordinating an immune response – which is why patients with CD 4 < 200 (and other immunocompromised states) are at risk of this infection. Typical symptoms include progressive shortness of breath especially with exertion, fever, and tachypnea, although patients can be asymptomatic. Classic imaging shows bilateral diffuse patchy pulmonary infiltrates. A very elevated beta-D-glucan is supportive of this diagnosis, but the definitive diagnosis requires confirming the presence of PJP in the respiratory secretions or sputum. PJP does not grow in cultures, and obtaining samples can sometimes be difficult and require invasive techniques.

Treatment recommendations depend on severity of disease. Our patient progressed to respiratory failure requiring mechanical ventilation, so he definitely had severe disease! The recommended regimen in that case is high dose trimethoprim-sulfamethoxazole (weight-based) for 21 days, given IV until patient stabilizes. Patients with severe disease should also be treated with steroids. Finally, studies support early initiation of ART in patients presenting with PJP pneumonia.



1/3 PPMC Report: New Insights on Treatment of NSCLC

Thank you to Dr. Ciunci for joining us to discuss the case of a 44 year old female smoker who presented with subacute cough and scant hemoptysis, found to have a new diagnosis of stage IV NSCLC adenocarcinoma.

We discussed that when lung malignancy is suspected, initial staging usually involves a PET scan as well as a brain MRI as patients often have intracranial metastases at the time of diagnosis. If imaging is suspicious for malignancy, then tissue biopsy is indicated to confirm the diagnosis. Tissue can be obtained via several routes, from endoscopic bronchoscopy biopsy to a more surgical approach with mediastinoscopy, or biopsy of other organs as indicated. If there is suspicion of metastases to distant organs, it is usually preferable to attempt to biopsy these lesions — if they are positive for metastatic lung cancer, that helps with staging and is important to ensure that there is not a separate process occurring in the organ with mets. The only exception may be with bony metastases — bone biopsies are not amenable to molecular testing, which is important to guide treatment.

Lung cancers are broadly divided into small cell (approximately 15%) and non-small cell (85%); NSCLC is subdivided based on histology. Regarding NSCLC, the traditional treatment for stage IV disease had been a combination chemotherapy regimen using a platinum-based compound. Recently, certain targetable mutations have been discovered in a minority of tumors, so it is important to always test all non-squamous NSCLC (and some squamous, like nonsmokers and young patients) for these mutations, including EGFR, ALK, and ROS1. If a mutation is detected, then the patient can be treated with a specifically-targeted chemotherapy and expect an increased progression-free survival.

More recently, immunotherapy has also entered the mix and has been amazingly effective in the right circumstances. It is now suggested that squamous NSCLC or other NSCLC that does not have a targetable mutation get tested for PDL1 levels, and if >50% then pembrolizumab can be considered as a first line agent! Here are some figures from a recent NEJM article about this topic.



Our patient had some palliative radiation and since she did not have a targetable mutation was started on a standard chemotherapy regimen — but had progression of disease. She had high PDL1 expression and was started on pembrolizumab with an excellent response, and has continued to do well for over a year!

Also for lung cancer, always remember to consider early involvement of palliative care — this has been associated with better outcomes for patients (see first reference below for more information).


Temel et al. Early Palliative Care for Patients with Metastatic Non–Small-Cell Lung Cancer. N Engl J Med 2010; 363:733-742August 19, 2010DOI: 10.1056/NEJMoa1000678

Reck, M and Rabe, KF. Precision Diagnosis and Treatment for Advanced Non-Small-Cell Lung Cancer. N Engl J Med 2017; 377:849-861August 31, 2017DOI: 10.1056/NEJMra1703413



HUP Report 12/19: UC-assosciated ILD after colectomy

At this conference, we reviewed the case of a 45 year old man who presented to pulmonary clinic for 2 years of productive cough and SOB.  His symptoms were progressive, and for the last few months he had been unable to walk a block or up a flight of stairs, which was a change from his baseline of being very fit.  His only medical history was having ulcerative colitis that was “cured” by colectomy many years prior.  His initial work-up was notable for PFTs with mixed lung disease (FEV1 40% => obstruction, FVC 65% => restriction), and a CT-scan of the chest showing diffuse bronchiectasis.  The salient learning points from the case were:

  1. Chronic cough is defined as lasting longer than 8 weeks.  If a patient is a non-smoker, and has a negative CXR, then the most common culprits are Meds (ACE), Upper-airway cough syndrome (aka post-nasal drip), cough-variant asthma, and GERD.  These can be diagnosed individually, or by medication trials.  This is an important differential for primary care, but our patient is already beyond this differential due to severe progressive functional restriction.
  2. Bronchiectasis is a radiographic diagnosis defined by bronchial wall thickening and dilation.  It is caused by a number of disorders that ultimately fall into one of the 4 categories in the vicious cycle shown below.  For all-comers, the most likely diagnosis is aspiration, but other common players are MAI, Immunodeficiency, ABPA, IBD, CTD, CF, and airway obstruction (ex. COPD or peanut aspiration).Capture
  3. Our patient was diagnosed (by exclusion) with IBD-associated bronchiectasis.  This is a rare phenomenon, but has been described since the 1970’s in various case series, and is often found after colectomy; in fact, bronchiectasis is one of the most common pulmonary manifestations of IBD (although the boards answer for most common is “necrobiotic lung nodules”).

The patient was treated with steroids and improved, although has not been able to be fully weaned.  If he cannot get off of steroids, there is a plan to treat with IBD medications even though he has no intestinal symptoms.  This would be an interesting and novel approach to care.

11/28 HUP Report: Hemoptysis due to ABPA

Thank you Dr. Dine for coming to report to discuss a case of Allergic BronchoPulmonary Aspergillosis (ABPA for short!). The patient we talked about today was a young female who had a history of asthma diagnosed in childhood who presented with a subacute history of cough and subjective fevers, with recent recurrent non-massive hemoptysis.

We discussed important characteristics of hemoptysis to gather information about during a history, including volume, appearance, color, rate and any associated symptoms or triggers. The lungs receive a dual blood supply – the bronchial artery usually arises from the aorta and has a relatively small circulating blood volume at high pressure, while the pulmonary circulation is at lower pressure and involves almost the entire blood volume. Usually, massive hemoptysis arises from bronchial arteries due to their higher pressure and the fact that they supply the airways and airway lesions. It is important to remember that in a minority of patients a spinal artery can originate from the bronchial artery, so a potential rare but serious complication of embolizing the bronchial artery can be paralysis in these patients. Diagram below is from Netter’s Anatomy.

ABPA1.pngThis patient’s imaging was notable for bronchiectasis and mucus plugging, and her workup showed elevated total IgE, eosinophilia, and positive aspergillus skin test. She was diagnosed with ABPA. In this disease, the airways are colonized with aspergillus and a hypersensitivity reaction causes inflammation –it is important to realize that the pathology here is not due to fungal infection, but rather an inflammatory response to fungal colonization. There are differing guidelines for diagnostic criteria; below is the set proposed by the International Society for Human and Animal Mycology (patient must have predisposing condition and both obligatory criteria plus two other criteria; non-CF bronchiectasis patients can also get ABPA).

ABPA2Glucocorticoids are the cornerstone of therapy for ABPA. There are differing perspectives on antifungal therapy – some physicians use antifungal therapy only if patients fail glucocorticoid therapy, and some physicians use antifungal therapy in all patients with this diagnosis. There are studies looking into use of monoclonal antibodies for treatment (omalizumab) – stay tuned for more data!



11/21 Presby report: pulmonary complications of cocaine, cavitary lung lesions

Thanks to Robin Mansour for presenting a great case of a middle aged woman who presented with a cough, chest pain and a 90 lb (!) weight loss, who was found to have several cavitary chest masses

We talked about some of the pulmonary complications of cocaine use:

Screen Shot 2017-11-21 at 10.19.35 AM.png

Restrepo et al. RSNA Radiographics 2007


Crack lung is a specific term for an acute hemorrhagic alveolitis after crack inhalation, characterized by cough, SOB, hypoxia, fever, bronchospasm and even hemoptysis and focal infiltrates (and diffuse alveolar damage, microscopically)

Remember that cocaine can be adulterated with substances that can cause a variety of toxic effects in and of themselves:

  • Levamisole (a veterinary antihelminthic): can cause P- and C-ANCA+ leukocytoclastic vasculitis
  • Clenbuterol (beta agonist) that can cause hyperglycemia, hypokalemia, tachycardia (which cocaine can also cause)
  • Other ‘cutting’ agents like talc or baking soda can lodge in the pulmonary microcirculation and cause a local granulomatous reaction

What’s the difference between a cavity and a cyst?

  • Cavities tend to be thicker walled: generally we call something with a wall >5mm a cavity, while <5mm is called a cyst
  • Cavity wall thickness can help with figuring out etiology
    • in one study, cavities w/ max wall thickness >15mm were 90% malignant while those <4mm were 95% nonmalignant

Here’s a framework for thinking about cavitary lung lesions:

Screen Shot 2017-11-21 at 11.32.10 AM.png

Derived from Gadkowski et al, Clin Microbio Rev 2008

Lastly, a differential for skin lesions involving tattoos:

  • Sarcoidosis
  • Nontuberculous mycobacteria
  • Discoid lupus
  • Local foreign-body granulomatous skin reaction


  1. Restrepo et al. Pulmonary Complications from Cocaine and Cocaine-based Substances: Imaging Manifestations. RSNA 2007.
  2. Gadkowski et al. Cavitary Pulmonary Disease. Clin Microbio Rev 2008.

11/9 Presby report: a moste curious case of metformin-associated lactic acidosis

Late post because I’m on service (sorry!).

A huge thanks to recent Penn IM alum Geoff Bass for giving a great talk on a middle-aged diabetic man who came in with abdominal pain and was found to have metformin-associated lactic acidosis (MALA).

Screen Shot 2017-11-13 at 2.18.09 PM.png

Lactate metabolism is intertwined with that of glucose and pyruvate

Hyperlactatemia occurs via one of four mechanisms:

  • Tissue hypoxia
  • Aerobic glycosis (aka glycolysis that depends on factors other than tissue hypoxia (think high-epinephrine states)
    • Sepsis
    • Severe asthma + beta-agonist use
    • Cardiogenic or hemorrhagic shock
    • Pheochromocytoma, cocaine
  • Impaired oxidative phosphorylation
    • Drugs: ARVs, propofol (PRIS), metformin, toxic alcohols, salicylates, cyanide
  • Liver dysfunction
    • the liver normally clears ~70% of whole body lactate, so acute liver dysfunction can lead to elevated serum lactate; but chronic liver disease (ie cirrhosis) usually doesn’t (in the absence of sepsis or some other driver)

Metformin toxicity is generally rare, and usually only occurs in the context of other predisposing conditions: AKI/CKD, liver disease, alcohol use, concurrent critical illness, heart failure

It is a clinical diagnosis, as there is no one test that confirms the diagnosis; you can send off a metformin level, but it takes a while to come back and is generally unhelpful unless it’s totally negative (in which case you should look for other causes)

MALA is mostly treated with conservative measures:

  • Gastric decontamination
  • Supportive care
  • Hemodialysis
    • Consider if lactate >15-20, pH <7.1, or other conditions such as shock, renal failure, etc


  1. DeFonzo R, Fleming GA, Chen K, et al. Metformin-associated lactic acidosis: Current perspectives on causes and risk. Metabolism, 2016 Feb; 65(2): 20-29.

  2. Kraut JA, Madias NE. Lactic Acidosis. NEJM,  2014 Dec 11;371(24):2309-19.

10/23 VA Report: Pleural Effusions with Lymphocytosis

Today’s report focused in on a patient with a history of adenocarcinoma of the lung s/p Chemo/XRT/surgical resection and who lived in South East Asia for 10 years who presented with hemoptysis, chronic cough and a new pleural effusion.

We re-reviewed Light’s Criteria — acknowledging that we sacrifice specificity for sensitivity by pooling the three criteria — with a reported ~97% sensitivity and ~80% specificity.

Our patient had an effusion demonstrating >95% lymphs on diff — creating a nice tidy differential to work with — TB, malignancy, sarcoidosis, chronic rheumatoid pleurisy, yellow nail syndrome or chylothorax. We followed his work up narrowing the differential down to TB vs. malignancy.

In doing so we discussed the use of ADA and the proper time to send it — distinguishing between malignant and TB pleurisy with an exudative effusion that is lymphocytic AND has initial cytology and smear and culture negative for TB. We discussed that in patients with a lymphocytic:neutrophil radio >0.75 and ADA >40 empiric treatment for TB is reasonable — with pleural biopsy as a confirmatory test if either of those two criteria are not met. We discussed the diagnostic accuracy of the ADA in reviewing this paper. 

In the end our patient had an ADA <1.6 and is awaiting biopsy for continued malignancy work up.


  1. Liang QL, Shi HZ, Wang K, Qin SM, Qin XJ. Diagnositc Accuracy of adenosine deaminase in tuberculous pleurisy: a meta-analysis. Respir Med. 2008 May; 102(5): 744-54. PMID: 18222681