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Author: Stephen J. Klemawesch, MD

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”.   

New Treatment for HAE (HANE)

New Treatment for HAE (HANE)

The New England Journal of Medicine recently published research done at the University of California on a new treatment for hereditary angioneurotic edema (HANE) also called hereditary angioedema (HAE). 

HANE or HAE is a rare genetic disorder that leads to unpredictable, disabling and occasionally fatal episodes of swelling.  The swelling can occur in any part(s) of the body.  It is caused by uncontrolled activity of the contact system components factor X11a and plasma Kallikrein which leads to excessive release of a bradykinin which in turn causes leaky blood vessels (vascular permeability) with the resultant swelling from the fluid that leaks out of the blood vessels. 

The most common form is due to reduced production or reduced functionality of a controller protein called C-1-esterase inhibitor.  But there are other forms including ones with normal C-1-inhibitor.

This latter group has been difficult to treat with most current therapies because they work by increasing production of function of C-1-inhibitor replace it directly or inhibit Kallikrein or block the bradykinin receptor.  The currently available therapies can be used either to treat/stop acute attacks or prophylactically.  In general, they work quite well but not 100%.  That is why improved therapies are being researched. 

The new drug being researched is donidalorsen which is an antisense oligonucleotide that selectively inhibits plasma prekallikrein production.  (Say what?)   Donidalorsen inhibits the production of plasma prekallikrein by means of ribonuclease (RNase) enzyme that degrades messenger RNA that would otherwise lead to prekallikrein production.  The idea is by moving a step earlier in the domino-like chain of events by reducing prekallikrein this will prevent kallikrein and eventually bradykinin. 

The UC researchers have conducted a small trial in 32 patients with a 90% reduction in attacks.  Moreover, the medication was not prone to causing side effects.  Larger trials are underway. 

EILO not EIEIO

EILO not EIEIO

EILO stands for exercise induced laryngeal obstruction and it is a newly understood reason for DOE (dyspnea on exertion) especially in children and adolescents.

Dyspnea (breathlessness) on exertion can occur for very diverse reasons including anemia, cardiovascular problems, neuro muscular problems and respiratory issues.  The most common respiratory cause for DOE is exercise induced bronchospasm (EIB) due to underlying asthma.  But asthma is an exhalation disease; that is, the main issue is getting air back out of the lungs.  EILO is an inhalation disease.  The larynx narrows with breathing in and causes stridor.  The narrowing doesn’t occur when the individual is at rest.  To complicate matters EILO can occur in asthmatics, so it’s important to understand the distinction. 

The University of Cincinnati Children’s Hospital has contributed significant understanding to EILO.  They feel it’s part of the spectrum of other laryngeal problems including irritable larynx syndrome and paradoxical laryngeal motion (also known as vocal cord dysfunction). 

Interestingly, using an asthma rescue inhaler prior to exercise does not prevent EILO (but it works like a charm for EIB).  What helps these patients most is retraining their laryngeal muscles via exercises prescribed by a speech pathologist.

Global Warming

Global Warming

The Journal of Allergy and Clinical Immunology had a recent article on global warming and the allergy epidemic.  Allergic diseases have reached epidemic proportions globally affecting 30% of the people on earth.  Just 20 years ago statistics in the US showed allergy affecting roughly 15 to 18% of Americans.  Despite new therapies allergic conditions are increasing in spectrum, frequency and severity. 

Since 1970 average temperatures have increased by 2 degrees Fahrenheit and green house gases have increased dramatically (primarily carbon dioxide and methane).  Thus, climate change has invoked allergic disease by a variety of mechanisms.  The changes in rainfall patterns, storms and winds affect pollination including the length and severity of pollen seasons.   Plants produce more pollen with higher levels of carbon dioxide.  Pollens are not only allergenic but carry lipid mediators that are proinflammatory. 

Flooding increases ambient mold levels.  More severe thunderstorms fractionate (split) pollens and make them more allergenic.  Wildfires and dust storms have both local and remote impacts.