
Scientists discover asthma's potential root cause and a novel treatment - denzil_correa
http://www.cardiff.ac.uk/news/view/96649-researchers-hugely-exciting-asthma-discovery
======
long
Link to the paper, "Calcium-sensing receptor antagonists abrogate airway
hyperresponsiveness and inflammation in allergic asthma":
[http://stm.sciencemag.org/content/7/284/284ra60](http://stm.sciencemag.org/content/7/284/284ra60)

Abstract:

 _Airway hyperresponsiveness and inflammation are fundamental hallmarks of
allergic asthma that are accompanied by increases in certain polycations, such
as eosinophil cationic protein. Levels of these cations in body fluids
correlate with asthma severity. We show that polycations and elevated
extracellular calcium activate the human recombinant and native calcium-
sensing receptor (CaSR), leading to intracellular calcium mobilization, cyclic
adenosine monophosphate breakdown, and p38 mitogen-activated protein kinase
phosphorylation in airway smooth muscle (ASM) cells. These effects can be
prevented by CaSR antagonists, termed calcilytics. Moreover, asthmatic
patients and allergen-sensitized mice expressed more CaSR in ASMs than did
their healthy counterparts. Indeed, polycations induced hyperreactivity in
mouse bronchi, and this effect was prevented by calcilytics and absent in mice
with CaSR ablation from ASM. Calcilytics also reduced airway
hyperresponsiveness and inflammation in allergen-sensitized mice in vivo.
These data show that a functional CaSR is up-regulated in asthmatic ASM and
targeted by locally produced polycations to induce hyperresponsiveness and
inflammation. Thus, calcilytics may represent effective asthma therapeutics._

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lifeisstillgood
Tl;Dr - calcium receptors in the lungs are linked to allergic asthma - and a
class of drugs developed for osteoporosis appears effective in preventing the
allergic reaction from being triggered. (Edit : in in vitro tests, and models)

Which given the shit I have poured into my lungs for twenty years is probably
a nice thing to hear.

What is not a nice thing to hear is how a small but plucky university (ranked
fifth in UK) is struggling so much for cash they have to put out press
releases mentioning lack of funding - twice. That's not something I notice
when MIT announces a breakthrough. We could double our science budget (5bn)
and not really notice it among the debt repayments and welfare bills and
wasted infrastructure projects.

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phkahler
Cured mine. I've told this before, but I take Magnesium (250mg) and Iodine
(1-2mg) every day. This has "cured" my asthma. I put that in quotes because as
someone pointed out there is no recognized cure, and I have not stopped, so I
don't know if the condition would return. But it beats the heck out of inhaled
steroids. Going on 1 year with no meds and no problems - PFT says lungs
function above average. Of course YMMV, but why not try it?

~~~
silencio
Because maybe you're personally just lucky and not having any symptoms for
whatever reason? And because "just try it" can do real harm?

My anecdote for you: both of those are in the prenatal vitamins I take and
have been taking for a while.... along with singulair, dulera, and my rescue
inhaler. No positive change here.

~~~
phkahler
Because my PFT showed the lungs of an 84 year old (twice my age) prior to
treatment. Then after giving up treatment for self treatment for a while I had
it done again and have lung function above average. Also, my decision was not
on a whim, it was based on research. And finally, your prenatal vitamins do
not contain much iodine - it should be milligrams, not micrograms (yep, I know
about how much you're getting).

In this case, just try it should not do any harm. 250mg of magnesium is not a
big deal. My doctor said iodine can screw up your thyroid - that's an old
medical myth, but I've had mine checked a few times and the levels are very
much in range.

So I stand by "just try it" along with YMMV because not everyones condition is
the same.

~~~
DrJosiah
That "old medical myth" has studies as recent as 2011/2012 showing that
consumption of over 400 micrograms/daily of Iodine can cause subclinical
hypothroidism [1]. That study needs to be confirmed, but given current
recommended consumption in the 150-300 micrograms/daily range, recommending
the consumption of 4x recommended levels or more as "should not do any harm"
is strictly bad advice.

I'm stoked for you that you seem to have managed to treat your asthma problems
with two mineral supplements, but please try to cite your research before
trying to give medical advice.

[1]
[http://ajcn.nutrition.org/content/early/2011/12/26/ajcn.111....](http://ajcn.nutrition.org/content/early/2011/12/26/ajcn.111.028001.abstract)

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tokenadult
This is news about a preliminary animal model and in vitro tissue study, not
news about a clinical trial with human patients. From the Cardiff University
press release (not usually a good source for a medical story):

"The team used mouse models of asthma and human airway tissue from asthmatic
and non-asthmatic people to reach their findings."

"If we can prove that calcilytics are safe when administered directly to the
lung in people, then in five years we could be in a position to treat patients
and potentially stop asthma from happening in the first place," added
Professor Riccardi." Do I need to add emphasis to the words "if" and "safe"
and "could be" and "potentially" here, or is that already apparent to
everyone?

I care about finding effective asthma prevention and treatment, as I have
close relatives who have asthma, but this isn't the news I have been waiting
for, not yet. It will be wonderful if other researchers are able to replicate
these preliminary findings and if findings about this receptor in human
tissues helps lead to development of an effective asthma treatment, but that
is not a sure outcome from this news, alas.

~~~
robbiep
It sounds like they want to give everyone that thinks they could get asthma
this drug on a regular basis, and then claim the non-asthmatics as successes.

------
walterbell
Do calcilytics increase or decrease calcium in the patient?
[http://www.wikinvest.com/stock/NPS_Pharmaceuticals_%28NPSP%2...](http://www.wikinvest.com/stock/NPS_Pharmaceuticals_%28NPSP%29/Calcilytics)
says:

 _" Calcilytics are small, orally active molecules licensed to GlaxoSmithKline
(GSK) for development and eventual sale. They act on calcium receptors to
cause brief increases in plasma levels of parathyroid hormone in order to
stimulate the growth of bone, which might be beneficial in the treatment of
osteoporosis. "_

~~~
trhway
>They act on calcium receptors to cause brief increases in plasma levels of
parathyroid hormone in order to stimulate the growth of bone, which might be
beneficial in the treatment of osteoporosis.

From what i read here
[http://en.wikipedia.org/wiki/Parathyroid_hormone](http://en.wikipedia.org/wiki/Parathyroid_hormone)
the release of PTH causes release of calcium from bones into blood, it also
causes increased absorption of calcium from intestine. So one can see how
osteoporosis situation may become better or worse depending on a lot of other
factors.

Anyway googling "asthma and calcium" brings articles as old as '83, so there
seems to be long established connection as Ca ions regulate muscle
contractions.

------
ajuc
Great, I wonder if this is also cause of related Cron's disease and Colitis
ulcerosa.

------
mrbill
_" a class of drugs developed for osteoporosis appears effective in preventing
the allergic reaction from being triggered."_

... am I the only one who thought "surely someone taking this drug for
osteoporosis also has asthma? See if it's helped."

~~~
robbiep
You develop asthma as a child. Old people have osteoperosis. It sounds like
this drug is meant to prevent it developing so the patient populations don't
really fit

~~~
Mifuyuu
I beg to differ; you don't have to be old to get osteoporosis. Likewise, you
can develop asthma at a later age. IANAMD but I work at a medical centre, deal
directly with patients and medical staff and have come across a few such
instances.

------
refurb
From the abstract: _Thus, calcilytics may represent effective asthma
therapeutics_

That's the real story.

Keep in mind this mechanism is for _allergic_ asthma, that's about ~1/2 (?) of
all asthma patients?

~~~
dogma1138
No, non-allergic (intrinsic) Asthma is a fancy name for a "panic attack"
besides that the other causes of non-allergic asthma are commonly various
infections, in any case non-allergic is not a chronic condition.

Chronic Asthma or "Allergic" Asthma an auto immune disease in which the immune
system triggers a violent response which causes the airways to pretty much
close up, which is the actual Asthma you hear about when people say "I got
Asthma".

While the symptoms of both Asthmas are quiet similar, the treatment is very
different. Yes if you go to the hospital due to a very bad panic attack or
have a bad respiratory infection they might put you on a vapaorator which is
also used to treat actual severe Asthma attacks but besides that there's
nothing much in common in form of treatment, nor should there be because the
causes of that Asthma are either psychological or environmental which are
quite easy to fix.

~~~
philjohn
There's another cause of asthma, apart from allergic and intrinsic, I know,
because a lot of my early asthma attacks were caused by it.

I had acid reflux, which was tracked down as one of the causes - once I
started taking a drug (Prepulsid/Cisapride) to strengthen the muscles by the
stomach, a lot of my attacks subsided.

I still suffer from allergies, and get the occasional attack, so it wasn't the
only cause.

Professor Casimir in Belgium is probably the reason I'm still alive - and has
done a lot of amazing research into Asthma and Allergies. Need to look him up
and see if he's still practising actually.

------
minthd
A detailed criticsm/explanation of this is here:

"Not OP's fault, but the headline and the story itself are extremely
inaccurate. This post should be labelled "misleading."

The story's deck says: "Scientists at Cardiff University and Kings College
London have found out what causes asthma and how to switch it off "

This is not true. The researchers found a pathway that can trigger some parts
of asthma, but the researchers do not claim that this is the cause of asthma.
Most asthma researchers now believe that the disease has probably many
different causes, all leading to a similar set of symptoms.

In the story itself, the reporter writes "...researchers at Cardiff University
and Kings College London identified which cells cause the airways to narrow
when triggered by irritants like pollution."

This as well is not true. The researchers looked at airway smooth muscle
cells, but it was already known that these cells are responsible for the
constriction seen in asthma. What this team did discover is a type of receptor
in these cells that can trigger this constriction.

"Crucially, drugs already exist which can deactivate the cells. They are known
as calcilytics and are used to treat people with osteoporosis. "

These aren't drugs, because none of them have been approved by any government
agency. And they definitely haven't been prescribed by any doctor to treat
osteoporosis. In fact, many have been abandoned as possible treatments for
osteoporosis. Also they don't deactivate the smooth muscle cells. They
deactivate the receptors in those cells.

Finally, the claim that asthma could be cured in five years is extremely
problematic. First, even if these molecules get approved as asthma drugs, they
would not cure the disease. People would still have asthma. They'd just have a
new medication they'd take to prevent symptoms such as wheezing and breathing
problems. And, going back to what I wrote above, this is probably not going to
treat all asthmatics because there isn't a singular root cause of the disease.

And the biggest issue here, and what the story leaves out, is that study, in
part, involved studies of a mouse model of allergic asthma--one type of the
disease. Mouse models are great for pointing in a direction, but they are not
people. And for asthma, mouse models don't have the greatest success rate in
finding drug leads. So until there are clinical data on these compounds, it is
way too early to call these treatments for asthma. And definitely not cures.

Again, this isn't OP's fault, but this story is extremely misleading. "

[http://www.reddit.com/r/science/comments/33kucg/asthma_drug_...](http://www.reddit.com/r/science/comments/33kucg/asthma_drug_that_can_prevent_patients_from_ever/cqm1jcg)

------
Kluny
This article is weak. Here is more information:
[http://www.cardiff.ac.uk/news/view/96649-researchers-
hugely-...](http://www.cardiff.ac.uk/news/view/96649-researchers-hugely-
exciting-asthma-discovery)

~~~
denzil_correa
Thanks. I would request the mods to edit the link submitted.

~~~
dang
Ok, url changed from [http://www.bbc.com/news/uk-wales-south-east-
wales-32418080](http://www.bbc.com/news/uk-wales-south-east-wales-32418080).

