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.
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 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 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.
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.