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Dear Dr. K- 

Dear Dr. K- 

I recently read that monkey pox vaccine can be given ID.  Is that true?

Yes, it is true.  In fact, early research indicates that it is the preferred route of administration in terms of getting the best immunologic protection. 

At this point the only other vaccines approved for ID (intradermal) dosing are the flu vaccines and the polio vaccine.  The advantages of ID vaccination are several.  It can generate an immune response as good or better than an intramuscular vaccine but with as little as one fifth the dose.  Owing to its superficial administration it avoids the rare risk of nerve, blood vessel or muscle injury that can occur with IM dosing.  The Gates Foundation has spent 5 billion dollars to help eradicate global polio and have used the dosing efficiency to great advantage.

A Shift in Asthma Strategy

A Shift in Asthma Strategy

They say “nothing stays the same” and as I keep aging, I couldn’t agree more! Change is always occurring in medical guidelines as well.  What I’d like to address here is how this applies to asthma therapy. 

For quite some time now, the standard of care for asthmatics has been to have both a rescue inhaler and a maintenance inhaler.  The majority of rescue inhalers use albuterol, a bronchodilator, which relaxes airway smooth muscles that are constricted.  The benefit is brief, lasting 3 to 6 hours, and the medication does not address the underlying inflammation which is the cause of the muscle constriction, that’s where a maintenance inhaler comes in.  Most maintenance inhalers are either single entity topical steroid or a combination steroid and long-acting bronchodilator. 

Overuse of albuterol is associated with excess risk for severe asthma exacerbations and even death.  Globally the majority of asthma related deaths are due to this scenario.  And a contributing cause is the cost of different inhalers: albuterol being relatively inexpensive while maintenance inhalers being expensive. 

This has led the Global Initiative for Asthma (GINA) to a new guideline that adds a topical steroid to all albuterol inhalers.  So far, the United States has not adopted this strategy.  Multiple international studies have documented a major improvement in patient outcomes with this approach:  marked reduction in the need for systemic steroids (oral or injected), reduced visits to emergency departments, reduced hospitalizations and reduced death. 

Tardigrade Research

Tardigrade Research

Tardigrades are microscopic organisms about the size of a dust mite but are really cute as they look like a baby manatee.  For being so tiny they have some really special properties that scientists hope to adapt to human health. 

Tardigrades are incredibly tough.  They can survive being frozen down to minus 272° Celsius, being exposed to a vacuum in outer space, being completely dried out and being exposed to 500 times the dose of x-rays that would kill a human. 

Tardigrade indestructibility stems from its ability to adapt.  Cold, dryness, vacuum, and x-radiation all cause damage to cell walls and to DNA within cells.  A tardigrade can abrogate these damages by synthesizing special “repair proteins”.  These special proteins support the cell’s membranes, essential proteins, and DNA.  One of these “repair proteins” Dsup has only been found in tardigrades and no other living organism.  Dsup binds to DNA and physically shields it from oxidative damage. 

In human cells our DNA has built in spare repair parts called telomeres.  As we live and are exposed to oxidative/inflammatory stresses our cells use the telomeres to repair damage.  But once the telomere resource is used up the cell will misfunction and even potentially become cancerous. 

And so, there is very active research into finding a way to protect human cells with Dsup.  Already scientists have inserted the gene to produce Dsup in experimental animals and it is working beautifully.  As a side-bar NASA scientists are looking at the possibilities of using Dsup to help long term space flight (with its attendant exposure to ionizing radiation for astronauts). 

Bronchiectasis

Bronchiectasis

Bronchiectasis is a lung condition characterized by cough and sputum production in the presence of abnormal thickening and pocket formation of bronchial walls which is visible on special lung imaging.  The little pockets are similar in their mischief to the pockets that can occur in the wall of the colon:  diverticula.  In both scenarios the pockets can sometimes accrete enough bacteria that it leads to acute bronchitis in the lung and diverticulitis in the colon.   

In the bronchial tubes the pockets can sometimes provide a haven for a smoldering presence of what are referred to as atypical bacteria.  Most common in this regard is MAC, mycobacterium avium intracellular (a cousin of the TB germ).  Also seen are Nocardia, Aspergillus and Pseudomonas.  The presence of these “smolderers” leads to chronic inflammation which in turn leads to bronchial wall thickening.  The condition is best diagnosed by high resolution CT scanning.  The “high resolution” format allows sufficient magnification of the bronchi to see the changes. 

There are a variety of treatment options.  However, key to all of these is what is referred to as “good pulmonary toilet”, that is, taking measures to keep the bronchi open and pockets empty.  Using a nebulizer daily with either saline or a bronchodilator is very helpful.  Some patients benefit from an external device called the VEST which through vibrations to the chest wall helps clearance of sputum. Antibodies can be used either for acute exacerbations or on a regular on/off schedule each month. Identifying “atypicals” either through expectorated sputum cultures or via bronchoscopy is also of value. 

In the US 1.5% of women and 1.1% of men have bronchiectasis.  So, if an individual is experiencing a chronic cough, it is a diagnosis to consider. 

Hydrogels

Hydrogels

Hydrogels are cross linked networks of biocompatible polymers that can swell or shrink in a controlled and reversible manner that can be tuned to specific physiologic conditions.  Wow!  That was a mouthful.  But if you re-read that sentence carefully you will find the description of an almost perfect delivery system (think UPS/Fedex) for intact proteins via the GI tract. 

Since the development of recombinant human insulin in the 1970’s a new class of medications called protein therapeutics has changed the practice of medicine.  Protein therapeutics are used to treat a broad array of illnesses including allergic conditions, rheumatologic disease, inflammatory bowel diseases, cancer, and endocrine disorders.  But these medicines can only work if the intact protein enters the blood stream.  Therefore, to date, the only delivery that works is to inject or infuse the protein.  Unprotected, the protein medication if taken by mouth, would be broken down into inactive digested molecules by the intestinal tract. 

Hydrogels are proving to be the perfect delivery system especially when engineered as nanogels.  This technology has already been applied to the administration of clotting factor IX (whose absence causes hemophilia B).  The potential exists for oral administration of a multitude of drugs such as; Humira, Rituxin, Xolair, Herceptin, Enbrel and many more.  The benefits would include home administration, removing the pain of being poked and cost reduction. 

Dear Dr. K;

Dear Dr. K;

I recently read something about micro needles and vaccines.  Is that anything similar to my getting my flu shot intradermally?

Actually yes, it is.  As you know, the traditional and standard way to administer most vaccines (including Covid) is intramuscular; that is, injecting the vaccine fluid into a muscle.  The vaccine is then processed by migratory immune cells in the blood vessels and lymph system.  Obviously, this method works well. 

But the dermis of our skin actually contains 1,000 times the density of immune cells than our muscle.  This leads to a much more efficient response by our immune system.  An individual gets an as good or better antibody response by “skin vaccination” and it requires a smaller volume of the vaccine material. 

Until the advent of micro needle research, the only other way to do this was by a single needle intradermally: aka your flu shot.  3D printing has allowed the production of micro-needles.  The chip itself is about the size of a small fingernail and contains 60 tiny needles on one side.  The vaccine material is applied to these tiny pain-free needles and dried.  So, all that needs to be done is to press the small chip against the skin for a minute and then remove it.  Current research using this technique has led to a 50-fold increase in antibodies compared to intramuscular dosing. 

Since the vaccine is dry and “pre-loaded” it could be mailed to our homes and self-administered.

Constrictive Bronchiolitis

Constrictive Bronchiolitis

Many smokers consider electronic cigarettes (vaping) to be a safer alternative to traditional cigarettes.  In some respect they are correct.  However, a newly described condition: constrictive bronchiolitis is appearing in some people who vape. 

Bronchioles are the smaller arborations in the “bronchial tree”.  The trachea branches into bronchi which in turn branch into bronchioles.  The people who develop this condition have significant narrowing of these smaller airways that is caused by tissue thickening called fibrosis. 

The pathophysiology of this condition is different than asthma or COPD.  Basically, the scarred and narrowed airways restrict adequate air flow to the alveoli (air sacs) where oxygen exchange occurs.  This causes the resultant symptoms of dry cough, shortness of breath, and chest pain.  The condition has been seen as quickly as after two to three years of electronic cigarette use and unfortunately there is no known treatment. 

Long Haulers

Long Haulers

The plodding nature of scientific research is a source of frustration to many of us, especially with reference to this Covid pandemic and the long haulers.  But recent research at Stanford University seems to provide new insight.  In their studies of long haulers, they discovered that the majority of them continue to shed live virus in their stool.  Moreover, some of the long haulers who were “stool negative” did show live virus in biopsies of the intestinal lining.  And yet these patients were not shedding virus in their respiratory membranes (nasal swab negative). 

These findings have led the Stanford group to posit that sequestered but active infection in the GI tract elicits an ongoing immune inflammation that can affect the entire body but most specifically the areas that were most severely impacted with the early infection be it lungs, heart, brain, or other organ systems.  If this turns out to be true then eradicating the GI infection should provide a cure for the long haulers. 

Dear Dr. K –

Dear Dr. K –

My husband has intrinsic asthma and I have extrinsic asthma.  Despite having our COVID vaccines he caught COVID and I didn’t.  What’s up?

Well, first of all I’m impressed that you know the difference between intrinsic and extrinsic asthma phenotypes.  To try and simplify what is a complex science most asthma can be categorized as high TH2 (extrinsic) or low TH2 (intrinsic).  TH2 is a type of lymphocyte that can cause inflammation.  In high TH2 asthma the main mediators of inflammation are IL4, IL5, and IL13.  IL means “interleukin” a chemical that communicates to cells (cytokine).  In low TH2 the main cytokines are IL-1B, IL17, IL8, and IL6.  The inflammatory cells that cause the mischief are eosinophils (in high TH2) and neutrophils (in low TH2). 

OK, I know that was a lot to throw at you but it is extremely relevant.  It’s not just you and your husband that have had different outcomes but asthmatics worldwide.  As it turns out extrinsic (allergic) asthma (high TH2) causes high levels of IL13.  IL13 seems to have three protective effects for corona virus infection.  First of all, IL-13 increases the density of the cilia lining our airway cells.  These microscopic hairs are a natural clearance mechanism to sweep microbes out of our bodies.  IL-13 also dials back production of a surface protein ACE2 which is the portal of entry for corona virus to cause infection.  Finally, IL-13 ramps up production of a protective carbohydrate called keratin sulfate.  Think “Teflon coating”.  The keratin provides a physical barrier to the corona virus.  You produce extra IL-13 and your husband doesn’t.  Hence the different outcome. 

RSV Vaccine

RSV Vaccine

Many Americans “have reached their limit” with vaccines due to the ongoing Covid pandemic.  But sadly, Covid isn’t the only game in town.  RSV (Respiratory Syncytial Virus) hasn’t gone away and continues to cause illness, hospitalization and death.  It is a single stranded RNA virus that can infect people at all ages.  It is the leading cause of respiratory hospitalizations in infants.  It is also problematic for people over 65, also causing hospitalization and death. 

RSV vaccine research has been ongoing for the past 30 years.  Just recently Pfizer has conducted trials in senior adults where a single dose of vaccine was 100% effective in preventing RSV and was fairly free of side effects.  Research is still ongoing for a vaccine applicable to the infant/child population.