My sister is on a JACK medicine for her ulcerative colitis but she said it may soon be used for allergies. Is that true?
Well, kind of. First of all, not to be too picky but there is a whole family of JAK drugs and the “JAK” refers to Janus kinase which is a pathway that transmits signals across cell membranes. The JAK system plays important roles in embryonic development, stem cell development, blood cell production and inflammation signaling.
This last role is why it can be targeted to prevent inflammation, because left to its own devices it transduces signals from cytokines (chemical messengers) into cells leading to inflammation. I’m pretty sure your sister is taking tofacitinib which is also being used to treat rheumatoid arthritis and most recently Covid-19.
You might have heard about a phenomenon in severely ill Covid patients called cytokine storm. Basically, these particular individuals have an unbridled inflammatory response to Covid which causes the severe lung inflammation. Tofacitinib has saved the lives of thousands of ICU hospitalized Covid patients by abrogating this “over the top” inflammation.
But to get to the point of your question, the JAK system has great potential to help a myriad of allergic conditions. Just as Covid related cytokine storm, and autoimmune diseases such as your sister’s rheumatoid arthritis are due to failure to properly regulate the immune system, so too is allergy.
The currently available JAK drugs are taken orally and therefore work systemically. Because of their systemic nature there is some potential for untoward side effects such as immune suppression. The research on JAK’s for
allergy has focused on site delivery either by inhalation to treat asthma or by skin application to treat eczema. Research on both of these applications is very promising. In fact, the FDA just approved the first topical JAK for treating eczema: Opzelura (ruxolitinib cream). For both asthma and eczema, the JAK drugs will provide an alternative to steroids to treat the inflammation that causes both conditions.
Patients who come to this office know well the exercise sermon both doctors preach. Exercise is one of the key foundational elements of general health and also allergic/immunologic health. New research is adding cognitive health to the list of benefits.
Recent journal articles in the Journal of Cellular Physiology and in Journal of Nature Metabolism contain new data on the fact that exercise leads to the production of a hormone irisin. It has been known for some time that irisin transforms white fat cells (which store fat) into brown fat cells (which burn fat) and also improves insulin resistance (the cause of Type II diabetes).
Now it seems that irisin enhances cognition in humans and in experimental mice. Several experiments in mice were very compelling. In one experiment either injecting irisin into mouse brains or increasing irisin production via gene therapy led to marked improvement in cognitive function in otherwise normal mice. Then in two established mouse models of Alzheimer’s disease increasing irisin restored lost cognition. It did so by reducing neuro inflammation which is the cause of Alzheimer’s disease.
It has been known for quite a while that certain viruses such as respiratory syncytial virus (RSV) and rhinovirus (the common cold) have been associated with the development and/or worsening of asthma. Both of these viruses are RNA viruses. This fact led researchers to wonder about certain DNA viruses. The one most recently studied is polyomavirus. This virus is widespread and consists of 117 species. Once thought to be totally innocuous, it is now understood that these viruses can cause clinical illness in people with compromised immune systems. But people with normal immune systems don’t have a clinical illness. However, now it seems that some of these asymptomatic infections can be either helpful or hurtful. Two of the viruses: KIPyV and HPyV6 have been shown to confer protection from children developing eczema; whereas, a different virus WUPyV is associated with a strong proclivity for children to develop asthma.
What is really weird is where these viruses infect a child. The KIPyV and HPyV6 infect the skin while the WUPyV infects the lungs. It seems that this is what makes the difference. The immune response to the virus can either help or hurt. So, even though healthy children exhibit absolutely no symptoms from these infections, their immune response to the viruses can have either a protective or harmful effect in terms of allergy. Researchers want to extend these findings especially in terms of finding the “friendly and protective” viruses.
Previous issues of the Allergic Reaction have had several articles about the human microbiome and its impact on health including its effects on the immune system and other systems. Now, add an additional new finding to this list. This research was recently published in Nature and it studied interactions of gut bacteria with oral drugs.
Among people who have the same disease a particular medicine can vary greatly in its effectiveness and side effects. Much of this variability has been attributed to genetic differences. This new research indicates that some of the variability is also due to the patients’ gut flora.
Scientists studied the effects of 15 drugs on 25 strains of human gut bacteria and found a remarkable variability in drug-bacteria interactions. For a given medicine some bacteria stored it without modifying it; whereas, other bacteria modified it either to make it more or less bioactive. Either way, the bacteria can lead to the patient receiving a bigger dose or a lower dose of the medicine than was intended. Getting a bigger dose than intended has potential to lead to greater incidence of side effects.
The other side of the research coin showed that some of the drugs altered the growth rate and metabolism of the bacteria. This in turn led to an increase or decrease in the molecules secreted by the gut bacteria including: hormones, neurotransmitters and inflammatory molecules.
At first blush many people are going to feel frustrated by this new level of complexity in how medicines affect us, but scientists have known for a long time this variability in patient response and it was dealt with via “trial and error”. Hopefully, this new research will lead to a scientific algorhythm for proper dosing based on individual microbiome.
-Nuts (especially walnuts & chestnuts), chocolate, cinnamon and “re-gifted” fruit cake can be non-allergic irritants to the mouth and tongue even to the point of causing canker sores, so tread lightly
-Mistletoe can be a contact irritant similar to poison ivy so when kissing stand beneath it but don’t hold it
-“Fresh” Christmas trees are often not so fresh but are often harvested weeks beforehand and kept damp. This in turn can lead to mold contamination which can be both an allergen and a respiratory irritant.
-Sleepiness after eating turkey is caused by its high content of the amino acid L-tryptophan which is readily converted to the neurotransmitter serotonin.
My husband and I are pre-planning for our first pregnancy. I’ve had asthma since I was 11years old, can I stay on my asthma medications while pregnant?
The short answer is yes. The emphatic answer is yes, its vital. The long answer comes next.
Asthma affects 5 to 8% of women of childbearing age and is one of the most common underlying health conditions that can complicate pregnancy. Poorly controlled asthma is associated with increased risk of maternal morbidity, spontaneous miscarriage, gestational diabetes, hypertension of pregnancy, pre-term delivery, fetal growth retardation, and congenital abnormalities.
Therefore, the basic take home message is “control your asthma as well as you can during pregnancy”. In 2019 the NIH (National Institute of Health) hosted a scientific workshop to better define the safety of asthma medications during pregnancy. Based on their findings they recommended a six-step approach to treating pregnant asthmatics based on the severity of their condition.
Step 1 for very mild intermittent asthma was to use a rescue inhaler as needed but no daily “controller” medicine.
Step 2 for mild persistent asthma was to start a controller medication. The preferred controller was low dose inhaled steroid but alternative controllers were theophylline, cromolyn, or a leukotriene antagonist (LTRA) such as Singular or Accolate.
When intestinal bacteria that are part of the microbiome were first linked to obesity it seemed to be a scientific curiosity. That was in 2007. Now fast forward 14 years and the microbiome has become the subject of hundreds of thousands of research projects around the globe. This research has led to the understanding of how our gut bacteria can influence the development of many human diseases including asthma and allergy. Not to over simplify all this research but it comes down to the fact that our gut bacteria effectively give us a second genome (genetic makeup) and an additional endocrine organ.
Now, the current focus of research is shifting to the viruses that infect bacteria (aka bacteriophages). Yes Virginia, there is a Santa Claus and believe it or not viruses infect bacteria. This fact has actually been known for quite some time. What wasn’t known until just recently is what, if any, impact those bacteriophages might have on human health.
The National Academy of Science recently published novel research in this area. The scientists found over 2000 specific bacteriophages that were strongly associated with human diseases. Two of the diseases most correlated with the viruses were obesity and Parkinson’s disease. What was especially shocking was the finding that many of the viral genetic sequences were integrated into the human chromosomal DNA. This viral research is too new to lead to any practical recommendations but hopefully that will be forthcoming.
Acute liver injury caused by accidental or intentional acetaminophen overdose is well known. If ingested all at once, 30 acetaminophens are lethal by causing acute liver failure.
One of the metabolites of acetaminophen is N-acctyl-p-benzoquinone imine (NAPQI) which is produced by the liver enzyme system P-450. Glutathione stores in the liver detoxify this otherwise harmful metabolite. Acute overdose can deplete the glutathione stores in the liver and this will cause the liver cells to die.
New research published in the journal Hepatology indicates that acute liver injury can occur from “normal” doses of acetaminophen in the right (wrong) setting. Eighty-nine hospital cases of acute liver injury in an academic medical center were caused by doses of acetaminophen of 3,000 to 4,000 mg a day (4,000 mg is the largest recommended dose) when combined with either fasting for 24 hours or excess alcohol intake or both. The authors of the article suggested people who fast periodically or who use alcohol liberally be aware of this potential pitfall. Fasting depletes the liver of resources as the liver is a source for energy supplies when no calories are consumed. Excess alcohol monopolizes the liver’s metabolism and makes it difficult to handle the breakdown of medicines.
-Social isolation is still a good strategy and it works.
-Early Covid infection can be successfully treated with monoclonal antibodies casirivimab and imdevimab given as a one-time injection or IV infusion.
-Post-exposure prophylaxis can also be given to high-risk individuals who have been exposed to someone with active Covid 19 infection before they develop the infection themselves. The same monoclonal antibodies are used.