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Chronic PPI Use and Asthma

Chronic PPI Use and Asthma

New research shows that prolonged use of proton pump inhibitors (PPI’s) can increase the risk for developing asthma.  PPI’s are the “drugs of choice” for esophageal reflux, gastritis and gastric ulcers.  But their long-term use impacts the gut microbiome which in turn can cause immune dysregulation.  It is this “tilting” of immune function that increases the risk for asthma.  Prolonged use of PPI’s by women during pregnancy also increases the risk for their child to develop asthma. 

One strategy to lessen this risk is to use the PPI to gain control of the problem and then segue to an H2 antihistamine such as Pepcid (famotidine). 

Cross Reactive Epitopes & Food Allergy

Cross Reactive Epitopes & Food Allergy

A recent article in the Journal of Allergy and Clinical Immunology provided an update on our understanding of cross reactivity. 

First by way of definition an epitope is a discreet (usually small) portion of a molecule that is the binding target of an antibody.  In the case of allergic problems, the antibody is IgE.  By way of example think of distinguishing features that help you identify a car:  the Mercedes Star and the Dodge Ram. 

Allergy is directed at this epitope, not at the very large complete molecule.  As it turns out certain epitopes are found on both foods and airborne allergens.  The most common examples are crustaceans and dust mites, tree nuts and birch pollen, wheat and grass pollen.  The cross reactivity can be a two-way street where exposure to a food worsens an airborne allergy or vice versa.  Also, allergy shots for the airborne allergen can actually reduce the food allergy by desensitization reactivity to the shared epitope.  What will be very interesting to find out is whether desensitization to foods will help airborne allergy.  Food desensitization is still in its infancy with peanut desensitization being the main inroad in this regard.  But many academic centers have ongoing research to develop therapies for other common food allergens; milk, egg, wheat, soy and corn.  Stay tuned. 

Dear Dr. K;

Dear Dr. K;

I’ve seen you and multiple other doctors for what has been called unexplained chronic cough.  Now I’ve read about the new drug Gefapixant.  Do you think I’m a candidate?

My answer is a qualified yes. But before I continue my answer let me first give a summary of your own situation that might be of help to other kindred spirits.  Your cough is called “unexplained” because despite our best efforts the medical specialists you’ve seen have failed to find a cause.  Your primary doctor listened to your lungs (normal) and ordered a chest x-ray (normal) and a CT scan (normal).  Your ENT did nasal endoscopy and a sinus CT, both of which were normal.  Your allergist (me) did allergy tests that were negative.  Your pulmonary doctor did a series of breathing tests and even a methacholine challenge test, all of which were normal.  He did have you try some inhalers which did not stop your chronic cough.  Your gastroenterologist did an upper GI x-ray and then an endoscopy both of which were normal.  Your speech pathologist examined your larynx and vocal cords and found no abnormality.  And yet, you continue to cough. 

Gefapixant is an antagonist (blocker) of the P2RX3 receptor.  This receptor functions as a ligand-gated ion channel for nociceptor activation.  I’m sorry for all the big words, but basically a nociceptor is a sensor that tells a nerve that it is being stimulated.  This sensor is activated through an entrance doorway called an ion channel. 

As it turns out this particular receptor plays a role in sensing pain, sensing the need to empty our bladder and sensing the need to cough.  And you might correctly guess the medication is being studied for these applications as well. 

Compared to placebo Gefapixant 45mg twice a day reduced cough frequency and cough severity and improved cough-specific quality of life.  Its main side effect was causing taste perversion.

Dear Dr. K;  I read something that indicated chronic sinusitis can predispose to stroke.  It scared me.  Is it true? 

Dear Dr. K;  I read something that indicated chronic sinusitis can predispose to stroke.  It scared me.  Is it true? 

The short answer to your question is yes. But, the best answer to your question is maybe.  First of all, it is important to know that vascular problems in general whether due to blockage from plaque or due to a clot have inflammation as a common denominator.  Whether you’re talking about a coronary artery or a carotid artery or an intracranial artery its arterial inflammation that sets the stage for the problem.  By way of example, its arterial inflammation that acts as the “Velcro effect” enabling cholesterol plaque to build up.  As it turns out any repository of inflammation in the body can contribute to this “Velcro effect”.  Thus, chronic sinusitis has this potential.  But what is important to understand is that its untreated, smoldering chronic sinusitis that has this potential. 

There is some evidence that the proximity of the sinus inflammation to the carotid arteries and the intracranial arteries gives this a more potent negative effect in terms of stroke initiation. 

In your particular case you treat the chronic inflammation with your allergy shots, your Singular (a non-steroid respiratory anti-inflammatory) and your topical nasal steroid spray.  However, some people choose not to treat a chronic sinusitis and therein lies the potential mischief. 

The worst case I have personally seen was a patient of mine who had chronic infected sinuses producing yellow and green mucus who declined therapy from me, her PCP and an ENT.  She suffered both a stroke and a brain abscess from the condition.

Another way that chronic sinusitis might lead to stroke is due to self-medication with either topical or oral decongestants.  Both have the potential to raise blood pressure and pulse and

if used as a chronic therapy (as opposed to brief and occasional use) they can add to the hazard of stroke.  

Bones and Alzheimer’s

Bones and Alzheimer’s

Whoever would have thought that bone health could impact the development of dementia?  Until I learned about new research in this regard, I wouldn’t have connected the two.  The operant word here is “health” and that is a function of exercise.  Now, if you’ve read these newsletters in the past you’re probably thinking; Oh boy, here comes another sermon on the value of exercise.  And guess what?  You’re right!

The research connecting the two is from the fields of neuroscience and endocrinology.  It turns out that our bones are an endocrine organ that produces a hormone called osteocalcin.  Osteocalcin acts on many organs in the body including the brain but also on gene expression (the functionality of genes).  Regular exercise promotes bone mass (helping prevent fracture) and the increased mass leads to higher output of osteocalcin. 

At a brain level osteocalcin improves the production of serotonin, dopamine, GABA and other neurotransmitters.  These chemicals are vital to establishing new memories and maintaining previous memories. 

At a genetic level osteocalcin ramps up gene expression (function) of RbAp48.  This gene is critical for protein formation that allows the brain to convert short term memory to long term memory. Research in mice demonstrated that a normal part of aging is reduced osteocalcin production which is also true in humans hence the usual “benign senescent forgetfulness” which is not dementia.  But in mice, experiments knocking out the RbAp48 gene led to very early and rapid onset of dementia.  Injecting RbAp48 into these young, demented mice allowed recovery of memory function.  The next step will be to extend these findings to humans

The T(r)OOTH of the Matter

The T(r)OOTH of the Matter

By:  Sasha Klemawesch, MD

During residency, we had a DDS come do a grand rounds lecture. During it, he advised not rinsing after brushing. I paid no heed to his recommendation at the time since the idea of not rinsing your mouth out after you brush your teeth seemed so bizarre and gross (also probably I was too busy passing notes w my coresident to listen all that closely to a dental lecture – snore!).

The American zeitgeist writ large tends to reinforce the “normality” of swishing and spitting after brushing; picture every couple in every movie you have ever seen standing at the vanity together getting ready for bed; all of them brush, rinse, spit and then smile lovingly at one another (or glare daggers depending on the film).

However, apparently Hollywood and I have gotten it all wrong for decades. My personal dentist recently prescribed fluoride toothpaste and told me to not rinse, eat or drink for at least 15 min after brushing with it, preferrable 30, explaining that were I to do so, I would be giving the fluoride a few mere seconds to try and act before washing it away. You wouldn’t shell out 20 bucks for topical steroids or pain relievers to just immediately scrub them off post-application, would you? When he put it that way it made sense, but I was still Super averse to the notion of not rinsing after brushing; it just seemed so sticky and foreign! However, I assure you, in less than a week, not only did I get over the lack of rinse, but my mouth actually came to feel good and fresh by doing so, and now it’s second nature.

Two other tidbits related to teeth-brushing but non-dental in nature:

(1) Try using your non-dominant hand when brushing next time. Doing so will force your brain to work to establish novel neural pathways which can be especially helpful in delaying cognitive decline as you age.

Second, while the hand swap will benefit brain health, standing on one leg will help your physical health. While seemingly insignificant, if you really force yourself to balance on one leg at a time even for the minute you are brushing your teeth, you are working on balance, core, and leg strength, and those daily minutes will add up. 

I confess, the latter two are coming much more slowly and with greater difficulty than the no-rinsing thing, but I keep trying.

Finally, last teeth-related item; when you finish reading this article, look up and whoever the first person you see is, flash them a big toothy grin. I guarantee both you and they will immediately feel happier by doing so!

TEWL

TEWL

TEWL stands for trans epidermal water loss.  It is the “unperceived” loss of water through our skin, in distinction to the “perceived” loss of water when we sweat.  It is also sometimes called insensible water loss.  It has been known for quite some time that children and adults with eczema have a greater TEWL than normal, but the difference has never been carefully measured.  The Allergy and Asthma Proceedings recently published new research doing just that. 

The measurements were adjusted for body surface area and were 2 ½ times greater in people with eczema than those without.  This water loss leads to excess dryness of the skin which disrupts the barrier function of the skin.  Think of the cracks in the bottom of a dry lake bed.  These micro-cracks in the skin allow ingress of both allergens (such as pollen, dust mites, animal dander) and irritants (such as soap, preservatives in personal care products including their fumes) to get “under the skin” and therefore potentiate the eczema. Two simple strategies work: maintain good hydration and always apply a moisturizer after bathing.

PLE

PLE

PLE stands for protein losing enteropathy and was the subject of a review article in a recent issue of The New England Journal of Medicine. PLE is a syndrome not a specific disease and can occur for a wide variety of reasons.  The problem is caused by the loss of plasma proteins through the intestines (they “leak” out).  In general terms it is caused by illnesses that damage the intestinal lining or that block the intestinal lymphatic drainage.

The resultant loss of proteins causes a drop in oncotic pressure which lead to edema. The loss of immune proteins causes a greater predilection to infections.  The most common cause for PLE is inflammatory bowel disease such as regional enteritis or Crohn’s disease.  But for our purposes, food allergy, eosinophilic enteritis, and gluten sensitivity are all potential causes.  All three of these conditions can cause inflammation in the GI tract and if its is severe enough to cause disruption of the GI tract mucosa and PLE.  Clues to this possibility include “GI tumult”, edema in the ankles/legs, and a low albumin and/or globulin on blood work.  Correcting the cause of inflammation fixes the PLE.

Zorro Returns

Zorro Returns

A recent issue of the New England Journal of Medicine had an editorial (not a research paper) titled “Strategic Masking to Protect Patients from all Respiratory Viral Infections”.   It was written by four Harvard physicians whose specialty is epidemiology and public health. 

The authors preamble alludes to the understandable mask wearing pushback/mask use fatigue in both the general population and in healthcare workers.  That’s very understandable.  We are all sick of constraints.  But the focus of the article is with the first word: “strategic”.  They make a rational argument for what they call strategic masking.  Myriads of studies during the Covid 19 pandemic came to diverse findings on mask benefit.  From “doesn’t seem to do much” to “has a major impact on transmission”.  The authors point out that the naysay findings are probably due to inappropriate mask type or improper use.  How many times have you seen people wearing a mask covering their mouth but not their nose.  Duh!  Collating all the data it seems that there is up to a 60 to 70% effectiveness of preventing viral transmission with masking.  This includes the SARS-COV-2 virus along with other pesky viruses: influenza, RSV, human metapneumovirus, parainfluenza and rhinovirus.  One fifth of patients hospitalized for pneumonia have a viral pathogen not a bacterial one.  Influenza alone accounts for 50 to 60 thousand deaths a year in the US.

The strategies they offer are several.  One is to consider mask use in public places and health care facilities during months of the year with high viral illness.  Another is to consider universal masking in health care settings when patients being attended to are at a higher risk due to age or underlying premorbid conditions.

My own personal experience does not constitute science.  But prior to Covid-19 and mask use this aging physician was catching two to three viral respiratory infections a year.  Since my mask use over the past 4 years, I have not been sick. 

Ice Cream Therapy

Ice Cream Therapy

Finally, a medical therapy I can relate to.  I love ice cream.  Actually, it’s not a medical therapy, but a safe mechanism to “test the waters” in alpha-gal syndrome.  This newsletter has previously discussed this uncommon condition that unfortunately is becoming more common.  By way of reminder the syndrome is the new onset of anaphylaxis due to eating meat.  It is a strange condition in that the allergic symptoms occur suddenly (hives, swelling, throat constriction) but are delayed 3 to 6 hours from the meat ingestion.  It’s kind of similar to touching a hot stove and then feeling the sudden pain hours later.  The reason it develops is due to allergic sensitization from a tick bite.  The other peculiar aspect of the syndrome is that the allergic issue usually doesn’t develop for several months after the tick bite.  Thus, people often don’t associate the two.  The tick saliva contains a molecule called alpha-gal which is also found in meat, especially beef and pork.  The diagnostic test is to draw blood and see if there are antibodies to alpha-gal.  An antibody level greater than .10 IU/L makes the diagnosis “possible” and a level greater than 2 IU/L is definitive. 

If a patient avoids further tick bites this antibody level can decrease over time.  Once it has decreased enough then the likelihood for reaction goes away.  So it is in this setting that the ice cream test comes in to play.  High fat ice cream has a very small amount of alpha-gal, so if ingesting it turns out to be safe, then the patient can feel greater comfort returning to meat. 

I guess I can justify my nightly ice cream dessert as a proof that I’m not developing alpha-gal.