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Author: Stephen J. Klemawesch, MD

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. 

Ticks Bite!

Ticks Bite!

By:  Sasha Klemawesch, MD

It used to be that you only had to worry about ticks in certain parts of the country and during certain times of the year. However (at the risk of mentioning any potentially “politically charged” content), climate change has not only prolonged tick season, but has also changed the geographic distribution of various bites.

Depending where you live in the country, a variety of ticks abound, leading to various infections endemic to each area. For the most part, as long as you remove the tick promptly, there is little chance of incurring any diseases from it. In fact, EM doctors are taught that if the tick is removed within 72 hours of the bite (or before it becomes engorged w blood), then there is no need for antibiotics.

We are seeing more and more ticks in Florida. If you are planning to go hiking or otherwise be tromping through preserves and grassy areas, one of the easiest ways to avoid getting bitten is to wear long sleeves and pants. When you come in from your day in nature, check all over your body to make sure there are no ticks on you. If you find one, use tweezers to grasp it as close to the skin as possible. Gently pull, straight up, perpendicular away from the skin, with slow steady traction, until it comes off. Do not smash it. Do not burn it. Do not smother it in petroleum jelly.

If you want to save it, you could, so that in the unlikely event that you were to go on to develop any rashes or symptoms, then it could be used to facilitate ID, but it really is not necessary in Florida. The ticks we have here almost never carry the more dangerous diseases that do occur elsewhere in the US such as Babesiosis or Powassan virus.

Even if you get bitten when you are out West, up in the Great Lakes, or New England, as long as you remove it right away, you are still almost certain to be just fine. The one exception to that rule is Rocky Mountain Spotted Fever. This would be the one time I would suggest possibly going to an urgent care if you were bitten. While the name makes you think you’d get it in Colorado, the 6 most common states to see it are actually Arizona, Arkansas, Missouri, North Carolina, Oklahoma, and Tennessee. If you got bit by a tick in any of those areas, it would be prudent to get checked and possibly start prophylactic antibiotics. Rocky Mountain Spotted Fever can be fatal if untreated, and it is the one tick-borne illness that the tick can transmit in a few hours and before it becomes engorged by blood. Since Doxycycline came on the market, the fatality rates have plummeted, and nowadays if you start treatment early it is still a very curable disease.  The CDC is a great resource if you are interested in reading more about Tick Borne Illnesses.

Bacteriophages

Bacteriophages

Bacteriophages are viruses that infect bacteria.  Phage is a Greek word meaning “to eat”.  Bacteriophages invade bacteria, replicate themselves and then destroy the host cell.  There are many types of viruses in the world.  Some infect only certain animals.  Some infect only humans.  But bacteriophages are by far and away the most numerous viruses.  They number 10 to the 31st power on the planet and this number is greater than all of the other organisms on earth added together (including bacteria).  Despite being earths most populous organism science is just starting to understand their niche. 

In a previous newsletter we alluded to bacteriophages when discussing the immune mechanisms that bacteria have adapted to fight these viruses.  Now two new areas of research have looked at bacteriophages.  One has to do with gut bacteria, the phages they support, and cognitive health.  It seems that people whose gut microbiome supports the bacteriophages Caudovirales have better executive function and memory than people whose microbiome supports Microviridae.  When feces from humans with Caudovirales was transplanted into mice their performance on cognitive tests improved.  Examination of their brains revealed an up-regulation of the genes known to be associated with superior cognitive skills.  The potential application of this knowledge to humans with dementia is compelling.

The other area of research is harnessing bacteriophages to treat human bacterial infections.  The idea is to select phages whose prime host is the bacteria causing a certain illness.  Early efforts in this regard have been safe and effective.  If this continues to be the case, it may provide a safe answer to the rising problem of multidrug resistant infections.

Dear Dr. K;

Dear Dr. K;

Any new information on peanut vaccines?

Actually yes; and it seems to be very promising news.  As you may recall from previous articles in this newsletter, the one FDA approved oral peanut vaccine is less than ideal:  it causes a lot of side effects including occasional anaphylaxis and it confers very modest protection.  But, a breath of fresh air came to peanut vaccine research based on astute observation by immunologists at Boston Children’s Hospital.  They discovered a major difference in the stool microbiome of children with food allergies versus those without. 

The non-allergic children had two “protective” bacteria Subdoligranulum variable and Clostridia species.  Based on this discovery they did experiments in mice who were peanut allergic.  Transferring these bacteria to the mice stopped the anaphylaxis they would otherwise have if given peanut.  As it turns out the healthy bacteria stimulated a subset of immune cells called regulatory T cells (Treg’s).  The Treg’s protect against allergic reactions. 

With this exciting result they have moved forward to small clinical trials in children.  (“small” in terms of number of participants, not because of the size of the patients).  By adding the bacteria to the peanut protein in the oral peanut vaccine the patients did not experience allergic reactions from the vaccine and they developed good protective response. 

In a second phase of the study, they gave a brief course of oral antibiotics targeted to killing bad colon bacteria and then the oral vaccine.  This group had an even better protective response.  The only bad news in all of this is that the Boston researchers couldn’t refrain from referring to their new vaccine as “Poop Pills”.