Cause of asthma symptoms and conditions

Why does Singulair cause these symptoms? I am going to give my explanation which is only a HYPOTHESIS. This should not be categorized as any thing but an educated guess. This is not backed by scientific research because nobody will do any research that would appear to anger
Merck even if people are suffering in the thousands.

1. The original research that preceded the development of Singulair (montelukast) seemed to focus on the theory that asthma was caused by an unusual immune response to certain pathological stimulus. There are many references to the observation that a high percentage of asthma sufferers are people whose asthma is caused by fungus. Many people suffer from asthma and are told that they are allergic to dust mites. Dust mites can live only because the fungus aspergillus pre-digests the
food source that dust mites can then absorb. Other sources of fungus occur in the home due to dampness or problems with wood rot.

2. The body's immune system fights certain categories of pathogens such as bacteria and fungus by creating nitric oxide which kills them at the site where they try to enter the body. The mast cell is the immune cell that is responsible for the production of nitric oxide. Mast cells are found in the skin, airways, intestines etc. The mast cell is capable of many different types of biochemical functions that are designed to signal other cells or other chemical responses. When the mast cell knows that pathogens
are present and nitric oxide is NOT produced, then it signals other immune cells to be sent to the site of the infection. Thus in the case of asthma, it is known that excessive numbers of eosinophils appear in the airways and these cells create inflammation.

3. Singulair was developed for asthma and later allowed to be prescribed for other reasons. I believe that montelukast probably creates a source of nitric oxide that prevents the mast cell from signalling for other immune cells to arrive at the source of infection. I arrived at that conclusion from studying the chemical structure of montelukast, the chemical structure of the gene cysLT1 receptor, and the chemical structure of the cell wall of fungus which would be what the mast cell uses to determine "what to do in order to kill the fungus."

The researchers who invented montelukast first had to clone the gene-cysLT1 receptor meaning that they had to be able to identify the gene and replicate it. Then by trial and error they had a find a "chemical"
that would bind (connect chemically) to the cysLT1 receptor. The theory would be that montelukast would take the place of the fungus or other pathogen and thus prevent the gene from reacting to produce the
responses that the sick patient with asthma produced. Merck says in the literature that montelukast binds with the cysLT1 receptor in order to prevent the mast cell from signalling the eosinophils to arrive in excessive
numbers that cause inflammation. I believe that montelukast is also causing the production of an amount of nitric oxide that is actually killing the pathogens that are present. For one thing, I would think that it
would be dangerous to incapacitate the immune system in that way without providing a way to kill the pathogens. I don't believe that the asthma response is just allergies to something like dust. Pollen from trees and flowers is loaded with fungus spores.

4. IF, IF, IF, montelukast does actually produce nitric oxide, then it does so by binding with the gene. Any place in the body where a molecule of montelukast encounters the cysLT1 receptor (a gene) then the corresponding molecules of nitric oxide are produced before the liver enzymes break the montelukast molecules up. Nitric oxide is TOXIC and
INFLAMMATORY. So let's look at the symptoms in regard to the location of the cysLT1 receptors. The location of these symptoms would not be places in the body where the mast cells normally encounter fungus or bacteria. The cysLT1 also has other functions in that it communicates with the cysLT2 receptors. Obviously, nitric oxide
should not be produced in these locations because of the signalling effect of nitric oxide on other physiological functions.

a. intestinal pain - the cysLT1 receptors are located in the small intestines
b. leg pain actually caused by vasculitis - cysLT1 receptors are found inside blood vessels- consistent with the fact that montelukast causes
Churg-Strauss
c. some people who didn't have asthma develop asthma - the cysLT1 receptors are in the airways
d. nightmares, depression, neurological damage - when montelukast penetrates the blood brain barrier probably due to unusual conditions of blood pH or electrolyte imbalance then nitric oxide in the brain causes neuron damage and excitoxicity

5. Why do some patients not experience side effects? Probably because genetically they are completely compatible with the model that researchers created when they cloned the cysLT1 receptor gene. I didn't not find any information about whether researchers knew that there are many different variations of this gene.

6. IF, my theory is even close to being correct, then why doesn't Merck do anything about researching these side effects. Maybe because nobody in the company knows how this drug works but the researchers who created it. All of the Merck literature is very vague about any biochemical information.

Again, this is just speculation and hypothesis. I have made an attempt to put this in simplistic language and therefore sacrifice scientific accuracy. But, I think that you will get the point.

SINGULAIR IS VERY DANGEROUS TO PATIENTS WHO EXPERIENCE NEGATIVE SIDE EFFECTS. DOCTORS SHOULD JUST REALIZE THAT
THOSE PATIENTS ARE NOT COMPATIBLE WITH THE MODEL FOR THE DRUG.

I am a 57 year old man, who has been suffering from asthma several years. This spring my doctor put me on Singulair as an additional medicine to my cortisone-inhalator. after one month I feel symptoms of depression an mood-changing, severe ups and downs.
AND - as an additional symptom i have partially lost my feeling in some fingertips, and now parts of my left thumb and even a feeling of "cold2, mostly in my left hand.
anyone who share that symptom?
M.

One of the most important questions we should be asking as parents is:

How does Singulair - a leukotriene receptor antagonist (blocks the receptors) affect the normal function of the mast cell?

The mast cell is the FRONT LINE DEFENSE against invading micro-organisms. When Singulair was invented, there was limited knowledge regarding the mechanisms by which the mast cell performed it's function. In my opinion, the focus was very narrow - those interested zeroed in on how the leukotriene receptor performed a role in the cause of asthma attacks and how ashma attacks could be prevented. Well, that's good preventing asthma attacks. But what happens to the mast cell if that receptor is blocked on a long term basis. I am not suggesting that blocking the receptor is bad but what if the long term effect is different than what we are are lead to believe-which is this is a safe medication with no known long term effects. What if the leukotriene receptor was just blocked short term a week or two to allow the body to clean up the mess from the last attack?

I seriously question what is going on with all of these infections. Are they related to crippling the mast cell? Parents should be allowed to question. If Merck doesn't want to answer questions regarding what happens to the mast cell (including are the numbers of mast cell decreased on Singulair), then something really BIG is missing. If by any chance (unknown at the moment) that the mast cell is significantly changed and therapy by montelukast is proper on a short but not long term basis, so freakin' what if Singulair is not a huge money maker any more.

Parents deserve every answer possible when decisions regarding their child's growth and development is on the line. I hope that we get some answers.

Of course, what was there in 2002 were new questions-not necessarily answers about the mast cell. Did anybody apply this to Singulair studies?
May 2002

From Journal of Clinical Investigation

Pattern recognition receptors on mast cells
The Toll-like receptors (TLRs) fit the definition of pattern-recognition molecules, which were originally postulated to allow the innate immune system to detect the 'molecular signatures' of various infectious agents. Although the innate immune system has no memory, it shows a degree of specificity, in part because the various TLRs recognize different sets of pathogen-associated molecules. Dermal mast cells are usually associated, not with the innate immune system, but with atopic dermatitis, but Supajatura et al. have found that these cells also express TLRs. They report here that TLR4, which binds the gram-negative product lipopolysaccharide (LPS), and TLR2, which binds peptidoglycan (PGN) from gram-positive organisms like Staphylococcus aureus, induce distinct mast cell responses. Staphylococcus is known to exacerbate allergic dermatitis, but it has generally been thought to act by inducing antibacterial IgE's, which trigger mast cell degranulation by stimulating the IgE receptor. Interestingly, the authors show that the interaction between PGN and TLR2 can provoke mast cell degranulation directly, sidestepping the need for IgE receptor engagement.

I had been taking Advair 500/50 for several years, however, most of that time I only took it once a day (not the recommended 2X). My diagnosis is near fatal asthma/COPD. About a year and a half ago I began taking Spiriva in addition. I am stable, but with a low pulmonary function for the past year (peak flow remains around 200). I see an acupuncturist/herbalist and an currently trying Wei Labs products: Soup A and LC Balancer, that are supposed to reverse lung damage. I recently visited a new, conventional, pulmonary specialist who wanted me to retry Advair at its recommended dosage, which I did. I noticed a nagging headache (at my forehead), a tendency to be agitated very easily, and a diminished peak flow. His response was to continue and add another medication (Singulair, which I have tried years ago with no good result). I stopped the Advair (though I am continuing on the Spiriva, until I see more results from the herbs). Also, I am a thin person who exercises all the time, and I had noticed that my weight was about 10 lbs more than I would like it to be (this had been the case for a couple of years). I have yet to see if that will drop, I have only been off for a couple of days. Additionally, I have had the experience with conventional steroid sinus meds over the years; the meds would stop working after a month or two and I would end up with worse congestion. I ultimately had a surgery to clear polyps and extra tissue, and have been breathing well through my nose since 2004 without meds. I feel I need to get off the conventional meds for the asthma too, on them I appear to be in a slow decline.