Pulmonary Hypertension (Wang - 8/2/23)

 A recording of this presentation can be viewed HERE.

***

Dr. Helena Wang gave an excellent Grand Rounds this week on Pulmonary Hypertension. It is worth watching!

We currently have at least three patients on our adult medicine service that we are evaluating for this condition after getting a TTE to look at their heart failure status. Pulmonary hypertension is such an interesting intersection between the lungs and the heart and a good opportunity to review basic physiology too! Dr. Wang gave an earlier version of this presentation 2 1/2 years ago, and I felt then, as I did this week, that I could watch it over and over. You can! 

But for those who prefer the written word:

The definition of pulmonary hypertension (pHtn) is simple enough: a mean PAP of > 20mmHg at rest.

Dr. Wang likens the pulmonary artery to something like a six lane highway (think of the 101 going north from Novato into Petaluma). When the lanes decrease from six to two in northern Novato, there is suddenly a lot of congestion, and all the cardiac output has to move through that smaller space at higher pressures. Voila! Elevated PAP.

Pulmonary arterial hypertension is rare, but not that rare, 15-50 cases/million, and more common in people with HIV (regardless of CD4 count or duration), connective tissue disease, and portal hypertension. For patients with any of these diagnoses, should be screened annually for pHtn with an echocardiogram (TTE).

Symptoms of pHtn include dyspnea on exertion, fatigue, edema, bloating, and syncope (obviously pretty non-specific). 

On exam, you can see elevated JVP (check the neck veins!), hear a split S2, and see peripheral edema.

Chest imaging reveals often a dilated R pulmonary artery on CXR, and even sometimes a prominent L pulmonary artery. Also, look for the "banana and egg sign" on CT, in which the aortic arch and the pulmonary artery are a little too close in size for comfort. The aortic arch is the banana; the pulmnoary artery is the egg.

Banana and egg sign (photo credit: CHEST Journal)

Okay, what about the TTE??

Oh, reminds the pulmonologist and the family physician, don't forget to pay attention to the right side of the heart in the echocardiogram! Dr. Wang urged us to scroll down, skip the conclusion,  and look at the text (often the third paragraph). Is the RV big? What is the velocity of the regurgitant jet? What is the TAPSE?

A first hint of pulmonary hypertension on a TTE comes on apical 4 chamber view where the R ventricle shows turbulent flow back into the R atrium

RVSP (right ventricular systolic pressure) is an estimate reported on most echo reports and can be very challenging for the Echo tech to calculate. However, a calculated RVSP>25 is considered HIGH right sided pressure and increases your suspicion for pHtn.

The R ventricle is often very plump and dilated under high pressure (so. . .a big chubby RV on echo is another clue that you might have pulmonary hypertension)

Tricuspid Annular Plane Systolic Excursion (TAPSE): RV contracts in a twisting motion with each contraction as RV shortens. Normal excursion is 1.5cm. If RV is volume overloaded and dilated, cannot squeeze as well, not shortening, TAPSE drops <1.5cm on echo

And finally, right heart catheterization is still gold standard for measuring R sided pressures, but really this should be done after you have done a full evaluation (see below) once you are pretty certain you have primary pulmonary hypertension (WHO Group 1). And, due to changes in insurance, it is no longer required always for diagnosis.

WHO Classification of Pulmonary Hypertension

• WHO Class 1: Pulmonary ARTERIAL Hypertension (pressure goes up, fluid backs up)
• WHO Class 1 has the worst outcome: 5 year survival 61%
• only diagnosed once other causes of pulmonary hypertension are identified and treated
• Seen in patients with HIV (regardless of viral load, duration), connective tissue disease (e.g. scleroderma), and portal hypertension
• All other WHO classes are actually pulmonary VENOUS hypertension (something downstream to the lungs causing poor forward flow, back up of blood, then high pressure on R side of heart). These include
• WHO 2: L heart disease (LV systolic or diastolic dysfunction, valvular disease, s/p TAVR, myxomatous disease)
• WHO 3: bad lung disease or hypoxia (COPD, inadequately treated asthma, ILD, sleep disordered breathing (OSA), OHS, chronic exposure to high altitute, developmental lung disease. Consider high resolution CT (with very thin cuts with and without contrast), home sleep test, pulmonary function tests.
• WHO 4: chronic thromboembolic pulmonary hypertension (small, little tiny chronic). You cannot see this on typical PE protocol CT scan. You need a VQ scan to evaluate chronic thromboembolic disease.
• WHO 5: potpourri

Once Pulmonary Hypertension is identified, the next question is DOES the patient have pulmonary hypertension that is primary or secondary

Ddx pulmonary arterial hypertension (WHO Group 1)

• idiopathic
• heritable (no current gene therapies)
• drug and toxin induced (fen fen, methamphetamines including stimulant medications prescribed)
• connective tissue disease (scleroderma)
• HIV
• portal hypertension
• congenital heart disease
• Schistosomiasis (#1 cause of pulmonary hypertension outside the US)

A quick interruption to review the three types of CT chest you might consider to evaluate the lungs:

• CT angiogram (aka CTA) is a very quick scan from feet to head chasing the dye, itskips very low bases and apices of lungs and should never be used to assess for interstitial lung disease. Great for acute PE asessment.
• A High Resolution CT Chest: much thinner cuts (2mm) than a CTA starting at apices and going all the way to the bases. 
• Very high detail of parenchyma
• Ground glass opacities can be atelectasis vs. ILD--> flip when prone to see if atelectasis resolves while doing high res scan
• CT w/wo contrast (e.g. nodule) 
• can see 4 generations of branches of bronchial tree, but keep in mind that there are 17, so you cannot see filling defects in the small peripheral vessels

Treatment of Pulmonary Arterial Hypertension (PAP)

1. First identify if the patient has any WHO 2-5 diagnoses that may be influencing their pHtn and treat them maximally, then repeat TTE to check for PAP
2. If they still display pHtn on TTE, they now meet criteria for pulmonary arterial hypertension (PAP).
3. Consider pulmonary vasodilator therapy (obviously in conjunction with pulmonologist). These, while still very expensive, are coming down in price. The meds range currently between $40,000 to $100,000 per year.

When to treat Pulmonary Arterial Hypertension?

There is NO specific number for pressure goals. Look at patients functional class, 6 minute walk, and Echo

Treatment goals:

• Functional class: symptoms at rest (class IV), normal (class I): goal is 2 or less
• 6 minute walk test: goal is 400mg in 6 minutes ("please walk as far as you can in 6 minutes", not "as fast as you can walk")
• BNP: can be elevated in R heart strain, goal is normal
• Echo: goal is RV not fat and chubby, decompressed and slender, TAPSE moving nicely

Pulmonary Hypertension Therapy

• Endothelin pathway: block (bosentan (black box liver toxicity, no longer used), ambrisentan, macicentan: side effects: edema, check LFTs, watch for rare malignant facial edema
• Nitric oxide pathway: enhance (sildenafil TID, tadalafil QD, no lab monitoring, can get blue green colorblindness, rare complication anterior ischemic optic neuropathy (sudden blindness one eye, reversible when stop), riociguat (TID, more systemic hypotension)
• Prostacyclin pathway: enhance (potent, short half life and unstable)
• epoprostenol: IV infusion, tubing connected to a pump, best mortality data, very labor intensive
• treprostinil: IV vs. sq (like insulin pump) and inhaled QID (takes a lot of time, breathing treatment like nebulizer, 20-30 minutes per treatment
• iloprost: inhaled 6-9 times/day
• selexipag: oral BID, no labs but unrealistic uptitration protocol

Guidelines for treatment are based on functional class. The ultimate goal is minimal symptoms with regular activity

If functional class IV-->  needs prostacyclins right away

If functional class III-->  can start with orals (e.g. tadalafil and macicentan)

Any questions? Email or staff message Dr. Helena Wang at: helena.wang@sutterhealth.org

Elimination of TB in the US: 2021 Updates (Toub, 8/4//2021)

Many thanks to Dr. Danny Toub, a family physician, teacher, and public health professional-- who so often bridges the impossible gaps that exist between individual patient care conundrums and public health. While this bridge may seem intuitive, it is often rickety and not always clear how to begin to build it-- look to Dr. Toub, though, he always shows us the way. 

A recording of his presentation is available HERE. 

This week's topic was Tuberculosis (TB), a global behemoth; the original and ever-present airborne illness that still kills 1.4 million people worldwide per year, more than HIV/AIDS While we sit in the middle of a harrowing COVID-19 Pandemic and the words N-95 have become every day jargon, TB is still global problem. And while we have made great progress in the US with TB eradication, TB still unnecessarily killed 542 Americans in 2018, 200 of which were right here in California.

TB, much like COVID, disproportionately affects people who are living in poverty, people of color, and those who have less access to stable housing and health care services.

What is our responsibility as primary care providers?

• Screen ALL patients for TB Risk
• Screen HIGH RISK patients with a Tuberculin Skin test (TST) or interferon gamma release assay (IGRA)
• Treat Latent TB infections (LTBI)
• Report to Public Health any active TB cases and/or any LTBI in children or recent converters (<2 years)
• Oh, and don't forget to have TB on your ddx for other acute/subacute illness presentations!

If we break that down,

1) Screen ALL patients for TB Risk using the California TB Risk Assessment Tool which can be found HERE and is pictured below as well. 

Remember to AVOID testing low risk folks for LTBI (this form alone counts as a screen!) and if you have limited resources, prioritize those who are most likely to convert from LTBI to active TB. Key risk factors include being foreign born/immigrant from certain regions, immunosuppression, and those who have been in close contact with someone with TB. 

Important additional risk factors include, recent conversion, substance use disorder, patients with DM, patients with CKD, those with autoimmune conditions, people who smoke, people with cancer, and more. 

The point of screening is to prevent a future conversion to active TB by treating people before they get sick. Low risk patients have ~10% lifetime risk of converting. Higher risk (e.g. people with diabetes) have ~ 30% lifetime risk, and highest risk folks (e.g. HIV + LTBI) have a 7-10% per year risk of converting. 

2) Screen HIGH risk patients with TST or IGRA. The best TB test depends on your pretest probability. Here is a good cheat sheet.

• Low risk patient--> do not screen
• Asymptomatic child--> use the California Pediatric TB Risk Assessment
• Asymptomatic adult--> use the CA Adult TB Risk assessment
• Volunteer for school without risk factors--> use the CA Schools TB Risk Tool
• College or University student--> use the CA College tool
• Health care worker--> use CDC guidelines#
• Pregnant woman--> pregnancy itself is not a risk factor
• 2 year old foreign-born patient--> TST*
• Foreign born >2 year old, hx BCG--> IGRA**
• Patient experiencing homelessness--> IGRA
• Patient to start TNF alpha blocker--> IGRA
• Patients with >4 weeks cough, 5 pound weight loss--> Chest Xray
• SE Asian smoker with RUL cavity, and a1c>9%--> sputum (x-pert MTB)+

#Note that the CDC no longer recommends annual TB testing for healthcare workers!! Official recommendations released in 2019 are available here and recommend a risk based technique. Maybe that means YOU don't need that annual TST!

*TST: tuberculin skin test, **IGRA: interferon gamma release assay (often referred to as quantiferon gold). There is limited data in IGRA in children <5. IGRA are more specific than TST in pts with a history of a BCG vaccine.

+Remember, a negative IGRA or TST does NOT rule out active TB (you need sputum!)

3) Treat LTBI infection. Treatment for LTBI has been shortened and simplified over the last decade. It does not involve routine lab work (except in high risk folks) or directly observed therapy (DOT). 

Dr. Toub recommends this handy LTBI pocket card to help simplify your decision-making and treatment regimen planning. The image below to too small to actually read, but follow the link for specifics on indications, completion criteria, considerations, etc. 

Briefly, prior to initiating LTBI treatment, you want to be sure to r/o pregnancy, check for pre-existing peripheral neuropathy (which can be a side effect of tx), screen for liver disease risk factors (e.g. alcohol use disorder, NASH, HCV). 

Baseline LFTs are only indicated for patients with HIV, known liver disease, regular alcohol use, pregnancy or < 3 months postpartum, and other risks for liver disease.

And, Dr. Toub reminded us to remind your patients that EVERYthing will be orange (sweat, tears, and urine). Also be sure to check for drug drug interactions on any tool that you use for this purpose, as there are many. 

4) Report to SoCo Public Health any active TB cases and/or any LTBI in children or recent converters (<2 years). 

5) Oh, and don't forget to have TB on your ddx for other acute/subacute illness presentations! Remember TB can show up just about anywhere. 

For local assistance, you can utilize the Sonoma County TB Control Guidelines, which you can find at the bottom of this webpage. And if you ever have any TB questions, reach out to our local TB Control program at 707-565-4567.

And, finally, a list of trusted resources from Dr. Toub:

Non-TB Mycobacterial Infections of the Lung (Miniae, 7/21/2021)

Thanks to our new(ish) SMGR Pulmonologist, Dr. Mike Minaie, we all know a LOT more about Non-TB Mycobacterial Infections of the lung (NTM) after the excellent Grand Rounds he gave this week on the topic. 

First a random literary malady allusion: NTM is sometimes called "Lady Windemere Syndrome" in reference to a Victorian era character from an Oscar Wilde play (see above) who suffers a chronic cough and malady and is unable to cough and spit (because she has to be 'ladylike' in Victorian times). Historically it was believed that NTM (often presenting in thin post/perimenopausal women) was made pathogenic by the act of suppressing one's cough. Not sure the premise is quite correct. . . 

For those of you who would like to see the entire presentation, it can be found HERE.

For those of you who prefer my Cliff's notes, here goes:

• NTM is generally a subacute infection (symptoms occur over weeks, even months)
• NTM is NOT contagious
• NTM is often recurrent 
• Symptoms of NTM include non-specific complaints, e.g. night sweats, weight loss,  shortness of breath, low grade fever, hemoptysis as well as chronic cough (often with thick sputum) x months

Many NTM-- e.g. mycobacterium avium complex (MAC), are readily present in soil, air, and water. People with intact immune systems may be exposed to these mycobacterium (and even incidentally or transiently acquire them in their respiratory tract) but a the healthy immune system is generally able to clear the NTM without disease.

In contrast, patients who are immunocompromised (e.g. chronic steroid use, HIV) may be less successful in clearing the NTM from their airway, and then the mycobacterium can become pathogenic.

There are a variety of NTM, including those more commonly found (MAC/MAI, M Kansasli) and less common (M maxium, M. xenopi, M simiae). They are also often classified as slow growing (2-4 weeks) vs. rapid growing (4-8 weeks). Different varieties tend to be  regional (e.g. M Abscessus is more frequently encountered in these parts). 

CT findings in NTM are various:

• ground glass lesions
• evidence of bronchiectasis (straw-like lesions on CT)
• solid nodules
• cystic changes
• fibrosis

Diagnosis of NTM is accomplished via BOTH clinical and microbiological assessments:

1. clinical: pulmonary symptoms AND appropriate exclusion of other diseases (e.g. bacterial pneumonia, cancer, COPD)
2. microbiologic (+ culture from at least TWO expectorated sputum spaced out by ONE MONTH, or +culture from a single bronchoscopy sample, or transbronchial or other biopsy with mycobacterial features)

Does NTM always need to be treated?

The answer is NO, if the patient is asymptomatic and/or if symptoms resolve spontaneously (which is often seen in immunocompetent hosts). If you get a single +NTM in sputum but then does not recur, assume the immune system cleared the NTM itself. 

Indications for therapy:

• respiratory or constitutional symptoms with radiographic abnormalities
• recurrent/consistent isolation of NTM in  moderate to high numbers (i.e. not trace amounts on a single sample)
• histologic evidence of pulmonary parenchymal involvement

Treatment:

usually starts IV, then transitions to PO

often lasts >1 year (time starts at first CLEAR sputum)

3 drug abx regimen for MAC (e.g.) is typically: 

• Clarithromycin (1000mg three times per week) OR azithromycin (500mg three times/week) AND
• Rifampin (600mg thrice weekly) AND
• Ethambutol (25mg/kg thrice weekly)

Surgery can be considered in certain circumstances: if disease is isolated to a particular part of the lung, or there is a very large cavity (>8cm, risk of rupture and bleed is high: 50% in 2 years). Surgery may also be indicated if cultures don't clear after 6 months of active treatment. If patient cannot tolerate oral treatment. If they have macrolide resistance

Side effects of the 3 drug cocktail are many: GI intolerance, low WBC, impaired visual acuity and color vision, decreased auditory function, decreased renal function, peripheral neuropathy

NOTE: If patients are on the three drug regimen, be sure to monitor them for vision changes (risk of optic neuritis) is moderate, and meds may need to be stopped (particularly ethambutol, rifampin). Also tinnitus is a sign of macrolide toxicity, which must be stopped immediately in the setting of tinnitus

Also remember there is radiologic lag, so radiographic findings should not be used to guide treatment duration; but rather, clinical improvement and clearing of cultures.

And lastly, don't suppress that cough!

Pulmonary Hypertension (Wang, 1/13/2021)

Dr. Helena Wang gave an excellent Grand Rounds this week on Pulmonary Hypertension. 

You know when you have read about a particular topic a hundred times and you still don't quite grasp even the most basic of concepts? Well, that is pretty much how I have felt about pulmonary hypertension for the last decade. I get all tangled up in the RVSP and the strange WHO Classifications and have never quite been able to solidify my illness script for pulmonary hypertension. 

Well, Dr. Wang, thank you. I feel like I am finally here. Pulmonary hypertension is such an interesting intersection between the lungs and the heart and a good opportunity to review basic physiology too! As one of our residents said to me yesterday after the talk, " I feel like hers is a presentation I want to watch again and again." Me too (and I did!). For those of you who want the written summary, here goes:

First a refresher on Pulmonary Function Tests (PFTs):

• The FEV1/FVC Ratio should be used to determine if a patient has an OBSTRUCTIVE lung disease. 
• Remember that an FEV1/FVC <70% is consistent with an obstructive disorder (e.g. asthma, COPD, etc)
• Total Lung Capacity (TLC) is used to decide if a patient has a RESTRICTIVE lung disease
• 80-120% is considered normal 
• Patients with restrictive lung disease will have a TLC <80%
• Diffusion capacity for carbon monoxide (DLCO) provides information on the efficiency of gas transfer from alveolar air into the bloodstream
• for these defects in gas exchange, ddx includes pulmonary hypertension and liver disease

Second, reminds the pulmonologist, don't forget to pay attention to the right side of the heart in the echocardiogram!!  Dr. Wang urged us to scroll down and look at the text. Is the RV big? What is the velocity of the regurgitant jet? What is the TAPSE?

• A first hint of pulmonary hypertension on a TTE comes on apical 4 chamber view where the R ventricle shows turbulent flow back into the R atrium
• RVSP (right ventricular systolic pressure) is an estimate reported on most echo reports and can be very challenging for the Echo tech to calculate
• First they measure the velocity of tricuspid regurgitant jet (velocity >3 is a clue that there may be pulmonary hypertension present)
• then they guestimate of CVP (0, 5, 10) based on compressibility of IVC
• NOTE: a calculated RVSP>25 is considered HIGH right sided pressure
• The R ventricle is often very plump and dilated under high pressure (so. . .a big chubby RV on echo is another clue that you might have pulmonary hypertension)
• Tricuspid Annular Plane Systolic Excursion (TAPSE): RV contracts in a twisting motion with each contraction as RV shortens. Normal excursion is 1.5cm. 
• If RV is volume overloaded and dilated, cannot squeeze as well, not shortening, TAPSE drops <1.5cm on echo

And finally, right heart catheterization is gold standard for measuring R sided pressures, but really this should be done after you have done a full evaluation (see below) once you are pretty certain you have primary pulmonary hypertension (WHO Group 1)

WHO Classification of Pulmonary Hypertension

• WHO Class 1: Pulmonary ARTERIAL Hypertension (it's like going from a 6 lane highway down to a 2 lane highway--> pressure goes up, fluid backs up)
• WHO Class 1 has the worst outcome: 5 year survival 61%
• only once other causes of pulmonary hypertension are identified and treated
• Seen in HIV (regardless of viral load, duration), Connective tissue disease (e.g. scleroderma), portal hypertension
• All other WHO classes are actually pulmonary VENOUS hypertension (something downstream to the lungs causing poor forward flow, back up of blood, then high pressure on R side of heart). These include
• WHO 2: L heart disease
• WHO 3: bad lung disease or hypoxia
• WHO 4: chronic thromboembolic pulmonary hypertension (small, little tiny chronic)
• WHO 5: potpourri

Once Pulmonary Hypertension is identified, the next question is DOES the patient have pulmonary hypertension that is primary or secondary

Ddx pulmonary arterial hypertension (WHO Group 1)

• idiopathic
• heritable (no current gene therapies)
• drug and toxin induced (fen fen, methamphetamines including stimulant medications prescribed)
• connective tissue disease (scleroderma)
• HIV
• portal hypertension
• congenital heart disease
• Schistosomiasis (#1 cause of pulmonary hypertension outside the US)

Ddx WHO Group 2: a bad heart

• left heart disease: LV dysfunction (systolic and diastolic), valvular dz, outflow obstruction

Ddx WHO group 3: bad lungs

• asthma and COPD (need PFT: spirometry, lung volumes, diffusion capacity)
• ILD (need HIGH resolution CT chest)
• sleep disordered breathing (episodic hypoxia at night causes vasospasm), need sleep study
• chronic high altitude
• developmental lung dz

A quick interruption to review the three types of CT chest you might consider to evaluate the lungs:

• CT angiogram (aka CTA) is a very quick scan from feet to head chasing the dye, itskips very low bases and apices of lungs and should never be used to assess for interstitial lung disease
• A High Resolution CT Chest: much thinner cuts (2mm) than a CTA starting at apices and going all the way to the bases. 
• Very high detail of parenchyma
• Ground glass opacities can be atelectasis vs. ILD--> flip when prone to see if atelectasis resolves while doing high res scan
• CT w/wo contrast (e.g. nodule) 
• can see 4 generations of branches of bronchial tree, but keep in mind that there are 17, so you cannot see filling defects in the small peripheral vessels

Ddx WHO group 4: chronic thromboembolic pulmonary hypertension (itty bitty clots on VQ scan)

• need VQ scan to get the level of detail in microvasculature

Ddx WHO group 5: potpourri

• hematological disorder (myeloproliferative)
• systemic disorders (sarcoid, LAM--> chylothorax)
• glycogen storage disorder
• thyroid disorders
• chronic renal failure
• mechanical (fibrosing mediastinitis, tumoral obstruction)

Right heart catheterization

Once you have maximally treated all WHO 2-5 diagnoses, treat as aggressively as possible (e.g. diastolic dysfunction, COPD/asthma, chronic clots, sleep apnea, etc), then you repeat ECHO and see if there is still elevated pressure on R side of heart--> NOW, patient should get a right heart cath to confirm exactly what the pressure is.

• On A R heart cath, PA pressure normal <25/15
• Mean PA pressure normal is <25
• Pulmonary hypertension = mean pressure >25

• Gold standard is also to do a vasodilator challenge during R heart cath to see if there is reversible spasm in the pulmonary arteries? (inhaled nitrous oxide, epoprostenol, or adenosine--> look for decreased pressure)
• if PA pressure decreases by 10 mmg HG, ending pressure <40, no drop in cardiac output
• less than 10% of patients have + response to vasodilator
• calcium channel blockers are treatment of choice for those who do have vasospasm

When to treat Pulmonary Arterial Hypertension?

There is NO number for pressure goals. Look at patients functional class, 6 minute walk, and Echo

Treatment goals:

• Functional class: symptoms at rest (class IV), normal (class I): goal is 2 or less
• 6 minute walk test: goal is 400mg in 6 minutes ("please walk as far as you can in 6 minutes")
• BNP: can be elevated in R heart strain, goal is normal
• Echo: goal is RV not fat and chubby, decompressed and slender, TAPSE moving nicely

Pulmonary Hypertension Therapy

• Endothelin pathway: block (bosentan (black box liver toxicity, no longer used), ambrisentan, macicentan: side effects: edema, check LFTs, watch for rare malignant facial edema
• Nitric oxide pathway: enhance (sildenafil TID, tadalafil QD, no lab monitoring, can get blue green colorblindness, rare complication nonarterici anterior ischemic optic neuropathy (sudden blindness one eye, reversible when stop), riociguat (TID, more systemic hypotension)
• Prostacyclin pathway: enhance (potent, short half life and unstable)
• epoprostenol: IV infusion, tubing connected to a pump, best mortality data, very labor intensive
• treprostinil: IV vs. sq (like insulin pump) and inhaled QID (takes a lot of time, breathing treatment like nebulizer, 20-30 minutes per treatment
• iloprost: inhaled 6-9 times/day
• selexipag: oral BID, no labs but unrealistic uptitration protocol

Guidelines for treatment are based on functional class. The ultimate goal is minimal symptoms with regular activity

If functional class IV-->  needs prostacyclins right away

If functional class III-->  can start with orals (e.g. tadalafil and macicentan)

Any questions? Email or staff message Dr. Helena Wang at: wanghl@sutterhealth.org

Pediatric Asthma: 2020 Global Initiative for Asthma (Prystowsky, 10/2020)

Many thanks to Sutter Medical Group of the Redwoods Pediatrician, Dr. Brian Prystowsky, for an amazing (and quite unique) Grand Rounds presentation this week on the "New" Global Initiative for Asthma (GINA) 2020 guidelines. 

Dr. Prystowsky took us to The Land of Make Believe and introduced us to:

• The 2020 Global Initiative for Asthma (aka GINA, the elephant in the room)
• Simba (Symbicort=formoterol/budesonide)
• Bert and Ernie (SABA=Albuterol)
• Jose Canseco (inhaled corticosteroids), and
• "The Purple One" (Advair) 

Stick with me here, and the teaching will stick with you. The 46-page GINA Pocket Guide is available for your here for your bedtime reading enjoyment. 

Asthma management has been upended this year by the 2020 GINA Guidelines.  Here's why.

Traditional management of mild asthma, mild/moderate intermittent asthma, persistent asthma, and exercise-induced asthma has been based on a few standard assumptions that may need some re-evaluation

•  First, that bronchoconstriction is the fundamental pathophysiological problem in asthma
• Second, that intermittent symptoms only need intermittent treatment, a short-acting beta agonist (SABA, e.g. albuterol). 
• Third, that inhaled corticosteroids (ICS) work for patients with persistent symptoms if prescribed chronically but are not indicated for intermittent symptoms. 
• Standard management of asthma involved prn SABA for patients with intermittent/exercise-induced asthma and addition of daily maintenance ICS with SABA as rescue for those with persistent symptoms.

ALL this is changing! A batch of studies suggest that asthma is likely more of an inflammatory condition that we might've previously thought-- or at least that inhaled corticosteroids (ICS) used in combination with a Rescue beta agonist is associated with better outcomes. 

The big practice change from GINA is moving away from use of SABA (albuterol) PRN to use of Symbicort PRN for asthmatics over 12. Symbicort, by the way, is a combination inhaler, which includes Budesonide (ICS) and Formoterol (LABA).

Studies in favor of  SYMBICORT PRN for the treatment of asthma: 

NEJM 2018 study (patients >12 with mild asthma x 52 weeks) found that patients treated with Symbicort PRN (compared with SABA prn in one arm and ICS maintenance with SABA prn) had higher percentage of weeks well controlled, LOWEST rate of severe exacerbation and lower median daily steroid dose (57mcg vs. 340mcg in ICS maintenance).

A NEJM 5/2019 study (patients >18 with mild asthma x 52 weeks) had similar findings: lower exacerbation rate, lowest number of severe exacerbations, and lower mean steroid dose.

A study from Thorax 2/2014 study (of patients >12 with exercise induced asthma, x6 weeks) found use of Symbicort PRN had best symptomatic control (compared to SABA prn and ICS maintenance/SABA prn) with much less steroid exposure.

Btw, Steroid exposure in an older study from Lancet 2011 (children 5-18 years old with mild persistent asthma) was associated with 1.1 cm growth restriction. Unclear how clinically significant this is, but as Dr. Brian said, parents don't want their children to be growth restricted..

What about "The Purple One"?

It seems that "the purple one" (aka ADVAIR; fluticasone/salmeterol) is not as effective as Symbicort in the care of asthma. 

Lancet 2011 study (5-18 years, 44 weeks) found that compared to PRN SABA, a QVAR+SABA prn vs. QVAR maintenance + SABA prn did not improve outcomes.

A 1/2020 study from Journal of Allergy and Clinical Immunology (mild asthma, ages 6-17 years) found that the use of QVAR+ SABA prn vs. QVAR maintenance + SABA prn had basically equal outcomes, except children had higher rates of steroid exposure in the maintenance group

And a study from Journal of Allergy and Clinical Immunology 12/2014 (ages 12-64) found Symbicort (vs. ADVAIR) had less exacerbations, lower oral steroid rates,  and less ER visits (though same hospitalization rates).

Can formoterol be an effective rescue?  Yes And is it safe in young children? Yes.

Compared to salmeterol, formoterol has a more rapid onset of action (at 3 minutes) at all doses

A study of 300 children in Pediatric Allergy and Immunology (3/2019) ages 8 months to 4 years found no safety concerns with the use of formoterol in children.

What are Dr. Brian's take home points for GINA?

• For children over age 12, Symbicort should be used both as rescue and maintenance as a PRN. Children will get at least as good control (maybe better) and will get less steroid.
• For children under age 12, the evidence is still not clear enough to change the historical practice. Continue to use albuterol PRN with ICS prn vs. ICS daily.

Thanks neighbors! And thanks Dr. Brian!

COVID-19 in Pregnancy (Mason, 8/18/2020)

Many thanks to Dr. Antoinette Mason for her excellent review of the emerging literature on COVID-19 in Pregnancy. As Dr. Mason explained at the start of her presentation, much of the information regarding COVID in pregnancy is based on observational data with recommendations that are expert opinion at best. But as we continue to increase our understanding of this disease, we are gaining a better understanding of its impact on pregnant women and infants. I consider Dr. Mason one of our local experts-- herself having cared for several of our first OB patients with COVID locally this past month. With that, I will do my best to summarize Dr. Mason's key learning points.

Epidemiology

• In the US to date, there have been 16,798 documented cases of COVID-19 in pregnancy, 4,262 hospitalizations, and 37 deaths
• As is true across our country, OB patients of color are disproportionately affected by COVID (Reference: https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/special-populations/pregnancy-data-on-covid-19.html)
• Here at SSRRH, we have had 9 total OB patients with COVID ( some only triaged, others admitted). In these patients:
• Gestational age ranged from 22-39 weeks
• 5 have delivered (2 returned later with PROM)
• 2 were picked up by admission screening (asymptomatic)

Is pregnancy a risk factor for COVID-19? Answer: We don't really know. 

The incidence of COVID-19 in pregnancy is similar to that of the general population. Several studies suggest that pregnancy and childbirth do not increase the risk of acquiring COVID-19. There is mixed data on whether or not pregnancy worsens the course of the disease. An MMWR from the CDC June 2020 showed the following: pregnant women were 5.4 times more likely to be hospitalized, 1.5 times more likely to be admitted to the ICU, 1.7 times more likely to receive mechanical ventilation, but no increased risk of death. (Reference: https://www.cdc.gov/mmwr/volumes/69/wr/mm6925a1.htm). Some of these stats are likely impacted by providers being more likely to admit and act more conservatively with sick pregnant women, but it is hard to see that in this data.

What is the clinical presentation of COVID-19 in pregnancy? Answer: The same as the general population

1/3-1/2 of OB patients with COVID-19 are asymptomatic

How to assess severity of disease in pregnant women? Answer: Oxygen saturation, consideration of comorbidities and close follow-up are key

• Oxygen saturation should be >95% on RA for pregnant women. This is a different standard than for non pregnant COVID patients (>92%). Also consider tachypnea (RR>30bpm).  
• Outpatient management is appropriate for pregnant women with COVID-19 with mild symptoms, but women should be monitored  (at least once within 1-2 weeks of diagnosis)
• should have home pulse oximeter if possible
• should have easy access to care if needed
• antenatal testing should be done as per standard recommendations
• Inpatient management: pregnant patients with moderate or severe disease (O2 sat <95% on room air, refractory T>39 despite antipyretics) and/or significant comorbidity (e.g. DM, CKD, immunosuppresion) should be managed in the hospital
• See diagrams below from ACOG and SMFM. Top diagram is indications for testing, bottom diagram is for triage in known COVID disease.

What are the maternal and fetal outcomes in COVID-19?    Answer: we don't really know.

From case reports, observational studies, and some reviews, there is concern that COVID may be associated with an increase in preterm birth, PPROM, cesarean delivery, and stillbirths. We do know that severe viral illnesses (e.g. influenza) have been associated with these outcomes.

One systematic review found aere possible increase in preterm delivery, including spontaneously and medically indicated preterm birth and c-section in pregnant women with confirmed COVID-19 infections. (Reference: https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(20)30190-5/fulltext). A UK study looking at outcomes pre and post pandemic preterm found a higher rates of still births-- the authors speculated that outcomes had more to do with access to care and comorbidities directly related to the virus rather than the virus itself.

Is there vertical transmission of COVID-19? Answer: Probably not.

While there is a theoretical risk of vertical transmission, most studies with significant number of cases have demonstrated no evidence of vertical transmission: looking at placenta, cord blood, amniotic fluid, and NP samples. There are a couple of case reports that call question to this, but the data is very limited. In addition, we have little to no data on the effect of COVID-19 infection on the first and second trimesters of pregnancy.

What is appropriate management of COVID-19 pregnant patients? Answer: Treatment for COVID-19 in pregnant women mirrors treatment of COVID-19 in non-pregnant women with slight modifications

• Remdesivir is considered safe in pregnancy (no known fetal toxicity, recommended by SMFM when indicated)
• Convalescent plasma is considered safe (currently under investigation for benefit)
• Steroids if indicated (NIH recommends for "patients needing oxygen")
• SMFM says maternal mortality benefit likely outweighs risk to fetus.
• Can do dexamethasone 10mg IV/PO as per the RECOVERY trial OR
• Some expert opinion recommending methylprednisolone  (see paper for details)(Reference: https://journals.lww.com/greenjournal/Abstract/9000/Corticosteroids_in_the_Management_of_Pregnant.97288.aspx)
• COVID-19 infection is NOT an indication for delivery;  mechanical ventilation is NOT an indication for delivery
• For severe disease, risks/benefits should be weighed
• Caution with magnesium sulfate because can increase risks of respiratory compromise (weigh risks/benefits depending on comorbidities)
• Most standard obstetrical management is safe: internal monitors, amniotomy, forceps/vacuum
• Might consider early epidural if symptomatic patient to mitigate risks of gen anesthesia for emergent c-section
• Nitrous oxide: not recommended for PUI/COVID+ patients (because of risk of aerosolization) but nitrous is okay to use in women who test COVID negative.

Does COVID-19 in combination with pregnancy increase risk of VTE? Answer: Yes, probably.

While there are only a few case reports of VTE in COVID in pregnancy, both COVID and pregnancy are hypercoagulable states and separately increase risk of VTE. Thus current recommendations for VTE prophylaxis: 

• All pregnant women admitted with COVID-19 should receive enoxaparin unless delivery is anticipated in <12 hours. 
• Also all hospitalized pregnant women should be 10 days of VTE prophylaxis after hospital discharge.

How should COVID-19 couplets be managed postpartum? 

• Moms with COVID-19 are prone to hypervolemia (keep strict Ins/Outs, watch respiratory status)
• Infants of COVID moms should be bathed after birth
• Breastfeeding should be encouraged!! 
• Separation of mother and infant is NOT recommended (likelihood of testing positive is the same if separated or kept together, if precautions maintained)
• infant should be tested once at 24 hours of life (no retest indicated)
• mom should use mask/hand hygiene
• baby should be in isolette when not breastfeeding

What about mental health in COVID in pregnancy? Answer: Ah, so much to say. . .

• Social isolation is associated with increased risk of depression and anxiety. Screen and ask!
• PTSD  has been recognized for those who are isolated/quarantined--> be sure to check in with new moms about the impact this may have on their postpartum period