From: Al Grimes on

"Peter B." <.@.> wrote in message news:4c1d7b2a$1(a)
> It appears someone is blowing smoke here

That someone would be you.
From: pautrey on

Fungal Sinusitis

W. S. Tichenor, M. D.
New York, New York

An article published in the Mayo Clinic Proceedings in September, 1999
by the Mayo Clinic suggests that fungal sinusitis may be much more
common than previously thought. The disease is now know as EFRS
(eosinophilic fungal rhinosinusitis) or EMRS (eosinophilic mucinous

Fungal growth was found in washings from the sinuses in 96% of
patients with chronic sinusitis. Normal controls had almost as much
growth, the difference being that those patients with chronic
sinusitis had eosinophiles ( a type of white blood cell involved in
allergic and other reactions) which had become activated. As a result
of the activation, the eosinophiles released a product called MBP
(Major Basic Protein) into the mucus which attacks and kills the
fungus but is very irritating to the lining of the sinuses. We believe
that MBP injures the lining of the sinuses and allows the bacteria to

The injury to the lining of the sinuses by the fungus and mucus led to
the belief that treatment of chronic sinusitis should be directed at
the fungus rather than the bacteria. Obviously the optimal treatment
would address the reason the eosinophiles attack the fungus, however,
at the present time, we do not know the reason.

There has been much speculation about why people develop the
sensitivity to fungi. Some people believe that it is as a result of
extensive use of antibiotics causing overgrowth of fungi. Others
believe that it is the result of extensive exposure to mold and fungi
in the environment, both due to water leaks from roofs and plumbing as
well as more efficient homes with less air exchange. Needless to say
it is important to fix leaks and repair damage immediately so that
this exposure doesn't occur. None of these fully explain the problem,

Unfortunately the discussion above was not included in the original
article by the Mayo clinic. As a result, the article was not well
received initially. There was also no information about the success of
treatment in the original article, and there was very little discussed
about mechanisms. As more data has accumulated, there is more evidence
that the problem may be as important as the Mayo Clinic suggests and
the significance is starting to be accepted.

Prior to the Mayo group's work on fungal sinusitis, it was recognized
that there were several types of fungal sinusitis, which we will
discuss later in this webpage.

Whenever a new finding is discovered in medicine, it is often met with
resistance. It becomes important for that finding to be confirmed by
an independent group. This has now been accomplished by a well
respected group from Graz, Austria, They were able to show positive
fungal cultures in 92 % of their patients. Almost as many of the
controls also had fungi. Clusters of eosinophiles were found around
fungi in 94 % of patients. This is important because we believe that
this shows that the eosinophiles are involved in attacking and killing
the fungi.

The Mayo Clinic researchers have done elegant work on the interaction
of eosinophils and fungi in patients with chronic sinusitis. They have
been able to film videos of eosinophils from patients with chronic
sinusitis in which the eosinophils are shown attacking and killing the
fungi, as contrasted to patients without sinusitis in whom the
eosinophils will "sniff" the fungus (as Dr. Ponikau suggests) and then
ignore it. Current techniques make it difficult for doctors who are
not in research institutions to clearly determine that it is the
fungus which is causing the problem. For example, it is possible to
tell by electron microscopy that the degranulation of the eosinophile
is in response to fungus. Unfortunately, however, there is not a good
way to tell that the eosinophile is degranulating in response to the
fungus by methods that most physicians can use. Those techniques are
under investigation.

At the present time, patients are being treated with irrigation with
topical antifungals such as Amphotericin B. The Mayo clinic has found
that 75 % have an improvement. A paper was presented at the American
Academy of Allergy, Asthma and Immunology meeting in 2004 which
compared 6 months of irrigation with Amphotericin (250 micrograms/ml)
vs. a placebo. There was a statisticly significant difference in the
amount of mucosal thickening on the CT scan as well as endoscopic
scores. In addition there were changes in levels of interleukin-5 and
eosinophil-derived neurotoxin. There has long been a concern that
there were no double blind studies done on use of antifungal agents.
This should help in that regard. The Mayo clinic is now recommending a
concentration of 100 micrograms/ml, however.

A study has begun which will hopefully lead to the approval by the FDA
of the first treatment for chronic sinusitis. This involves a new
formulation of Amphotericin B. For more information on the study,
please contact Accentia Pharmeuticals. If you are in the New York
area, you can contact our office (212-517-6611).

Itraconazole (Sporanox) can also be used topically, but it is very
difficult to make up since most mixtures cause the itraconazole to be
inactivated immediately. Although many pharmacies claim to be able to
make up the itraconazole, almost all pharmacies are unable to make it
up correctly and be able to ensure that there is active drug in the
mixture. It must be made up by Anazao pharmaceuticals, Sinucare or JCB
labs. (The Mayo clinic is no longer making up itraconazole.) (If your
local pharmacy thinks that they are able to make it up, I would
suggest that you insist that they provide you with an outside analysis
that shows that there is active drug in the formulation.) Many
patients require other agents such as nasal or systemic steroids,
however many patients in the Mayo clinic trial were able to stop
treatment with oral steroids .

Although when given intravenously there are serious side effects with
Amphotericin B, topically it causes minimal problems. These can
include burning due to the fact that it must be mixed with sterile
water. It cannot be mixed with saline, and must be protected from
light and refrigerated. It is therefore very inconvenient to use. More
acceptable formulations are being evaluated. We anticipate that
patients will need to be treated indefinitely, or at least until we
understand better why these problems are occuring.

Some patients seem to respond to treatment with oral antifungals,
including Sporanox, Diflucan, and possibly Nizoral or Lamisil. We are
working on other treatments which we hope will be able to be used in
the near future.

Because irrigation must get into the sinuses in order to be effective,
it is often necessary for patients to have endoscopic sinus surgery
before irrigation can be effective. It is possible that by using an
irrigation device such as the Grossan irrigator, it will be possible
to irrigate effectively without surgery.

Some doctors have added antifungals ( or antibiotics ) to the Grossan
irrigator. One method is to add 1 tsp of salt ( or Breathease, or salt-
baking soda solution ) to 500 cc of water in the Hydropulse and
irrigate. When the solution is almost gone, it is possible to add the
antifungal to the irrigation fluid and continue irrigating. The
antifungal solution should not be added at the beginning because it
may become too diluted.

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