Asthma in children: Guidelines for primary care management
21
August

By Adem Lewis / in , , , , , , , , , , , , , /


– Well, good morning everyone. Thank you very much for the opportunity to give you this talk. And I also wanna start off by saying that it’s a real pleasure
to work with you all around this state and to receive referrals and to have some bilateral
exchanges of ideas on how we can manage patients. So thank you for the
referrals and I really enjoyed the collaboration that we’ve
had over the last few years. So before I begin, I wanna share that the most common medication
we use in pulmonary medicine is albuterol and so albuterol is known as a short-acting beta agonist, so a SABA, short-acting beta agonist and
so people ask me all the time, “Hey, Dr. Saba, did you
go into pulmonary medicine “because of SABA?” And I say, “That’s totally ridiculous. “Of course, that’s why I went
it’s a pulmonary medicine.” So I do participate in a
clinical trial for patients with PCD but the medications
used in that trial will not be talked about in this talk. So there are many guidelines for pediatric asthma out there. There are American Thoracic
Society guidelines. There are European guidelines. There are the NHLBI guidelines,
which probably most of us have been using over the
last few years for management of chronic asthma and acute
asthma flare-ups in children but these are getting
a little bit old now. They were published in 2007 and these were American guidelines. So today I’m gonna talk to you
about a new set of guidelines from the Global Initiative for Asthma and so the purpose of this
talk is to give you updates on asthma so this is the
most up-to-date guideline. And this is gonna be kind
of the structure of the most of the recommendations I’m
gonna share with you today. So these were published in 2018. Now certainly, you can
use any guideline you want and in fact, the NHLBI will probably be releasing new guidelines very shortly but I’m gonna share with you
what the GINA organization is recommending. So some key features
of asthma; number one, it’s an inflammatory condition. There is inflammation of the airways. Number two, symptoms are
episodic and the symptoms can be pretty much a
number of different things. It could be cough, it
could be exclusively cough. It can be wheezing, it
can be shortness of breath or any combination thereof
and a key component of asthma is that there’s variable or reversible expiratory
airflow limitation. In other words, there’s
obstruction to the airflow and it’s reversible. There are some exceptions
there in patients with long standing asthma for many years who have had some
remodeling of their airways. It might not demonstrate reversibility but the strict diagnosis of
asthma is episodic symptoms and reversible airways obstruction. So over the years, the
prevalence of asthma has been going up and
I have a few theories that I’m gonna share with
you as to why that might be but it’s estimated that the
prevalence of asthma today in the United States is
approximately 10% of the population. So going back to Michigan
Stadium here, 1,000 of those people are gonna
have congenital heart disease. 10,000 people in Michigan Stadium on a given day have asthma. See, it’s a serious condition. 25 of those people have Kawasaki disease. (members of the audience laughing) So there’s a big discrepancy
in who has asthma in different demographics
in a given population. Overall, children are
more affected than adults. females more than males,
black non-Hispanics, Puerto Ricans and those
living below the poverty line. (coughs) Pardon me, are at
highest risk for having asthma. So what makes a patient develop asthma? There’s a few risk factors;
number one is atopy, any allergic or eczema type of history, any type of inflammatory condition that is an allergic type of inflammation will help drive asthma. So there’s something called
the hygiene hypothesis that states that: in the
past, when people lived more in rural communities on farms,
the prevalence of asthma was much lower and it could be, because that environment
skewed your immune system in favor of a Th1 phenotype
which is the allergic phenotype that mounts responses to bacteria
and those types of things. Nowadays, kids are a little bit cleaner. They’re not around germs and bacteria so their immune system
is skewed more in favor of a Th2 phenotype and
that’s the phenotype that elaborates inflammatory cytokines of the allergic immune
system, IL 4, IL 13, mast cells, basophils, eosinophils. And those are the inflammatory components that drive asthma. So some people hypothesize
that the prevalence of asthma is going up because our
kids are just too clean. So genetics obviously play a major role. If there’s a family history of asthma, a child is at risk for having asthma. The environment plays a major role. Another environmental
factor that I consider would be prematurity, chronic
lung disease from prematurity. Even if the child is a late preterm baby, that puts you at risk for having asthma. Viral infections, we know for certain that early life exposure
to RSV and Rhinovirus in the first six months of
life are a major risk factor for the eventual pathogenesis of asthma. The human microbiome is
probably a contributing factor. We don’t know too much about
exactly how that contributes but the human microbiome,
meaning all the bacteria we normally have, not just bad bacteria, the bacteria we normally
have and the contribution of one group of bacteria
to another bacteria, that’s the microbiome, that
contributes the pathogenesis of asthma somehow. So what’s the inflammation in asthma? Well, there are many different
types of inflammation you can have in asthma. There’s neutrophilic asthma,
there’s eosinophilic asthma. Today I’m gonna focus on allergic asthma. It’s probably the most
common type you’re gonna see. So in allergic asthma, you’ve got most of the problems start at
the airway epithelium here. Your airway epithelium
elaborates some cytokines IL 25, IL 33 which then leads to
the further proliferation of key cytokines here, IL 13 and IL 5 and these go back to the airway epithelium and the airway epithelium
then elaborates chemokines which attract cells and
which cells are attracted? Your big-time allergic cells:
CD4+ Th2 cells, basophils, mast cells, eosinophils
and these are the cells that produce histamine,
leukotrienes, prostaglandins. Those are the things that
cause your bronchoconstriction and goblet cell hyperplasia
and mucus accumulation and those types of things. So this is the basic concept
of allergic inflammation of the airways causing asthma. Now what happens to the airways over time? So on the left here, is a normal
airway, a nice open lumen. There’s not really any fibrosis, a normal amount of smooth muscle. In a patient with asthma,
the lumen is much smaller and that’s because there’s
massive proliferation of goblet cells around the epithelium. There’s lots of smooth muscle here. This is airway remodeling
and you also have a significant amount of
collagen and fibrosis. So there is airway fibrosis, there’s smooth muscle
hypertrophy and proliferation and there’s goblet cell hyperplasia. This is airway remodeling. Now this is reversible except in a patient who’s been living with this inflammation for a really long time, at which point, this might become irreversible. How does one make the diagnosis of asthma? Well, as I said before, there
are key clinical features. There should be episodic
symptoms of shortness of breath, chest tightness, wheezing, coughing. In addition to that,
there should be evidence of reversible airways obstruction. So one way to test for
that is to simply get that on history, does your
child respond to albuterol? Does the wheezing go away with albuterol? In a patient who’s old enough to perform pulmonary function tests, that’s a really key part
of your diagnostic workup. Here we have a flow volume
loop as a result of spirometry. This is a normal flow volume loop. This is a flow volume loop of a patient who has airway obstruction,
this characteristic scooping of the expiratory portion
of the loop suggests that there’s obstruction of the airflow. This is a volume-time
curve so the patient blows into the spirometer and
the amount of volume they can blow out is called
the vital capacity here. Now the volume blown out
is what in one second is called the FEV1 and so
if the volume blown out in one second is much less
than the total amount of volume they can blow out, it means
that there’s some obstruction to that air flow. So the FEV1 FVC ratio is
an important predictor of airways obstruction. Now, if you give your patient
albuterol in the clinic, four puffs of albuterol or so
and there’s a 12% improvement in FEV1, that’s diagnostic
of airways obstruction with reversibility. Now, you can determine the
severity of the obstruction based on the FEV1. This is not the severity of asthma. The severity of asthma is
based on different criteria. This is the severity of the
obstruction that contributes to your determination of asthma severity but this is simply severity
of the obstruction. So you make a diagnosis
of asthma in your patient then you try to determine
how severe is this asthma and then what am I gonna do about it? So to make a determination
of asthma severity, it’s based on the amount of
asthma medications needed to control the asthma. So it’s actually a diagnosis
provided retrospectively. If you determine in-clinic,
a few months later that on this level of asthma
control I’ve achieved, on this level of asthma therapy, I’ve achieved control, then
it’s this degree of severity. For example, if your patient’s
controlled on step one or step twp of therapy and I’ll show you what those steps are in a
minute, you say it’s mild. If they’re controlled on
step three, it’s moderate. If they’re controlled
on steps four or five or not controlled at all on
steps four or steps five, you call it severe. So I’m gonna talk mostly
about children older than the age of five
and kids less than five, the management is a little bit different and I’ll tell you why that
is but in children older than the age of five and
adolescents and adults, you initiate inhaled
corticosteroids if your patient has asthma symptoms
more than twice a week. I’m sorry, month is incorrect. It’s more than twice per week. If they’re waking due to
asthma more than twice a month, so that should be month
and if they’re having any asthma symptoms plus any risk factors for exacerbations, I’ll show
you what those are in a minute. So if you have any of those things, you should start your patient
on an inhaled corticosteroid. Many people request referrals
to pediatric pulmonary at this step and that’s
entirely appropriate and I’m thrilled to get involved
at this step of therapy. The GINA guidelines suggest
referrals at a little bit of a later step in
management but you refer whenever you want to and I’m
more than happy to see patients at this step to help
determine what controller to start them on. And you can consider
starting at a higher step like step three or four of therapy if the patient’s got
troublesome asthma symptoms on most days or if they’re
waking from asthma more than once a week, especially
if there’s risk factors for bad exacerbations. So this is what the GINA guidelines have for asthma management at this point. This is a busy slide but
I’m gonna walk through it. So obviously the steps mean if the patient is not well controlled, you step up. If the patient is well
controlled, you can step down. So step one is where you
might just start some short-acting beta agonists
and see how things go. Step two is when you start
your inhaled steroids and there are some additional medications they’re recommending like
leukotriene receptor antagonists. Theophylline is not one
that it really has any level of popularity after the 1980s really, so I wouldn’t use theophylline and most pulmonary specialists
do not use theophylline but it’s on this grid here. So step three is when you start
using your inhaled steroids with long-acting beta agonists. In kids less than 12, they’re saying, “Well, hold off a little bit “on the long-acting beta agonists “and just use medium-dose
inhaled corticosteroids.” You go up and up from that point. So another thing I wanna
point out on this table is reliever medications
are medications patients should take whenever
they feel symptomatic. So short-acting beta
agonists are the mainstay of reliever medications here. They are suggesting the
use of inhaled steroids with long-acting beta agonists,
for example, Symbicort as reliever medications. Now in our practice, we have
not adopted this practice yet. There is some data to show that in adults, it might be beneficial
to do so but those data have not held up in kids. So I still recommend using
albuterol exclusively or an anticholinergic in some cases as your rescue medications and not using your long-acting beta agonists
with inhaled corticosteroids as a reliever medications. If you care for adults
as well, then you might also consider that but in
kids, that has not really been part of our practice in our division. So you start your
patient on asthma therapy then you see them back in
clinic a few months later, you review the response,
you assess their symptoms, you assess their exacerbation risk, you assess for side effects,
you determine if the patient is satisfied and you
determine lung function. Based on this, you make an assessment of whether or not their
asthma is controlled and if their asthma is not well controlled then you make an assessment
for why that might be. You confirm that you’re dealing with the right diagnosis first, you talk about symptom
control and risk factors. Maybe there’s a major comorbid
condition I’m missing here. You assess inhaler technique and adherence and you talk about patient preference then you adjust treatment, that might be adjusting asthma medications but most of the time, it’s gonna be
non-pharmacological strategies, which I’ll tell you about in a minute and you treat your
modifiable risk factors. So this is the overall approach to outpatient asthma management
from the GINA guidelines in kids older than the age of five. So you start an inhaled corticosteroid. Problem is, which one do you use? There are many inhaled corticosteroids that are delivered in many
different delivery devices and I’ll be quite honest;
I know about all these but I’ve probably only
used about half of them. I have mine that work really well for me and I’m really used to
and and I know really well how to educate families on them so you kinda wanna
probably pick two or three. You certainly don’t have to
be an expert in all of these. There are some that come in the form of a powered metered dose inhaler. And most of these are patient actuated. The only ones that are
not patient actuated that just kind of blow
into the patient’s mouth are the dose inhalers, the
Respimat and the nebulization. All the rest of these
require a significant amount of inhalation on the part of the patient. Some of them are dry powder inhaler. Some of them are HFA devices. So like I said, you don’t
have to know about all of them because there are many
of them on the market. Maybe I’d recommend getting
comfortable with two or three. I have this in my office
because oftentimes, patients get referred to me and tell me that they’re on a medication
but don’t know the name of it and I don’t get a whole
lot of notes so it’s nice that these all come in different colors so they can point out on
your poster what they’re on. So the basic concepts of
inhaled corticosteroid therapy is you should treat with
a minimum effective dose that treats symptoms. As soon as my patient’s well-controlled, I start stepping down
inhaled steroid therapy. In kids less than five,
I would recommend using a metered dose inhaler or a nebulizer. I wouldn’t recommend
the dry powder inhalers or the patient actuated
devices in kids less than five because I don’t think they’re generating enough inspiratory force to get
it down to the lower airways which is really where
you want for it to go. Metered dose inhaler should always be used with a valved holding
chamber and as I said before, breath actuated devices like
the RespiClick, Redihaler, Handihalers, these should
always be used in kids just older than the age of six
who can do it appropriately. So when you see your
patient, a few more details about how to assess asthma control. So what are the questions
you wanna ask them? These again are the GINA guidelines, the questions are a little bit different in the NHLBI guidelines. So if they say yes to
three out of these four: are you having daytime symptoms
more than twice a week? Are you having nighttime
symptoms more than twice a month? Are you needing your
reliever medications more than twice a week and do you
have any exercise limitations? If they say yes to three
out of these four questions, your asthma is poorly controlled. You wanna assess for risks as well. So you wanna get lung function, if you have that capability in your office and that would be a FEV1. I’m not talking about peak flow meters. I’m talking about FEV1
which has to be done with a spirometry machine. Most people don’t have those capabilities so you wanna assess risks in other ways. Exacerbation risk, what’s
the risk this patient’s gonna have a bad exacerbation
in the next six months? Basically if they have
uncontrolled symptoms, if they’re using a lot of albuterol, if they’re having more than
one exacerbation a year, if they’re not adherent,
if they’re smoking around in the home, if they have
lots of comorbidities, if they have elevated
FeNO which is a measure of lower airway nitric
oxide which is a marker of eosinophilic inflammation, we do that in our pulmonary clinic and
if they’ve ever been intubated for asthma, these are risk
factors for bad asthma outcomes. And that’s certainly something you should assess periodically. So what are the non
pharmacological interventions? And I would say these
occupy most of my time when I visit with patients. Choosing an inhaled steroid
is actually pretty easy. Adjusting doses, I mean,
there’s a protocol for that. I don’t really need to be involved for adjusting medication doses. This is probably the main area where we can be mostly helpful. So every patient needs an
asthma action plan to tell them what medications to use
when they’re feeling well, what medications to use when
they’re not feeling well and when to call the office. Every patient should
have lots of education at every single clinic visit. We have a designated nurse
educator that does this with all of our patients who have asthma. Talk about adherence and technique. It’s estimated that 50%
of patients both in kids and adults and this is well
supported in the literature are not adherent to their medications the way it’s prescribed. Now what percentage of patients
have inadequate technique? In my experience I would
say close to 80% of patients have poor technique until I see them at least three times in clinic. Environmental exposures are
also a major risk factor. If I have a patient
with dust mite allergies and they’re not appropriately
avoiding those dust mites, their asthma is not
gonna be well controlled, addressing comorbidities as well, obesity acid reflux, rhinosinusitis,
obstructive sleep apnea and immunotherapy, which is considered a non-pharmacological approach. So just a few words about
asthma in preschool children. So why are we talking about
this as a separate group? So this study was done,
probably many of you are familiar with it, it’s a
famous study done in Arizona about 30 years ago and
they looked at all kids entering school and they said, “How many of these kids
have ever wheezed?” And among all, they’re six-year-olds, about 50% of them had
a history of wheezing and among those that wheezed,
a third of those kids wheezed early in life
and then grew out of it. They called them transient wheezers. Most of those kids had
maternal smoke exposure. A third of them only started
wheezing later in life like after the age of
three and a third of them started wheezing early
and continued to wheeze at the age of six, they called
those persistent wheezers, which many of us would call asthmatics. Those who have asthma really had a strong atopic family
history or personal history. So the reason this study
is important is to say that most little kids who
wheeze, don’t have asthma and they’ll probably grow out of it and it’s really hard to determine
if a two-year-old coming to clinic with wheezing truly has asthma or whether they just have
viral transient wheezing that they’ll grow out of. Once the patient ends up in my clinic, usually you have all done
a really good job making that assessment and my
job is easy at that point but I do wanna give you a few extra tools to help make that
distinction of determining whether a young child truly has asthma or whether it’s just viral wheezing that they’ll grow out of. So kids with just viral wheezing
usually you have illnesses that last for a shorter period of time, less than 10 days. They have few episodes,
two to three times a year, which actually, I would say
that’s very conservative. I’d give them at least
five or six episodes of wheezing per year
before I get concerned and no symptoms between episodes. Those who you’d worry more
that they probably have asthma are those who have illnesses
lasting more than 10 days, more than three episodes a year and again, I’d say probably more
like five episodes a year would be appropriate
and they have symptoms between illnesses of coughing and wheezing and those types of things and lastly, a strong personal or family
history of atopic disease. Those are the kids that I would say, “Well, you know what,
you’re wheezing with colds “but you might very well be wheezing “because you have asthma and
I’m more likely to treat you “as though you have asthma here.” I think all of these kids probably need a short-acting beta agonist at home because the response to that
short-acting beta agonist is another really good predictive
factor of whether or not this is truly asthma and it’s
just another piece of history that’s gonna help you
determine whether or not this child needs to be on an
inhaled corticosteroid or not. So why do we have to go
through this process, why not just say, “Well, it’s asthma, “you might grow out of
it, I don’t really care “if it’s asthma or not, we’re
gonna treat it the same?” Well there are many other
things that could be. It’s important to go through
a thorough evaluation and if you have any concerns
that you’re dealing with any of these conditions,
we’re more than happy to see them in clinic to
provide further consultation and workup if needed, with
bronchoscopy and sweat test and you know CAT scans and
whatever needs to be done to look through all these potential things that might be playing a
role in why this young child might be wheezing if it’s not asthma. So the GINA guidelines
have a different table for how to manage children
less than the age of five once the diagnosis of
asthma has been established and that is, as I said before,
frequent illnesses lasting for a longer period of time. Once you’ve made that diagnosis
of asthma, you start them on a daily low-dose
inhaled corticosteroid. Now there are tables
through the GINA guidelines to tell you what low dose,
medium dose and high dose inhaled corticosteroids actually are. For example, fluticasone
dosing is gonna to be different than beclomethasone dosing
even if there’s still low dose and I would recommend
that, you have them in here but it’s just numbers
and you can certainly go look at those tables
if you’re interested in knowing what low,
medium, high dose truly are. So they are saying, obviously
it’s the same approach. You step up if they’re not controlled, you step down when they’re
not well controlled and they are saying to refer
when you get to step four but I’m saying, and usually
what we do once you get to this point is we
would consider starting on a long-acting beta agonist, getting further diagnostic
tests and those types of things but I don’t think you have
to wait till step four, we’re more than happy to see
patients even at step two, if you have a question
of whether this is asthma or whether there’s
something different going on that I should work up
before starting this patient on long term asthma therapy. So you can refer to any step. So a few words about
allergy immunotherapy. If you’ve really confirmed
that your patient has atopic asthma and they
are around perennial allergen, sometimes you just can’t do anything. You can’t avoid perennial allergens 100%. Immunotherapy might be a good option. This is not something we
provide in pulmonary clinic. It would be an allergy clinic
but I wanna share with you how it actually works. So when somebody is exposed
to a low-dose allergen every day, their immune
system is ramping up the Th2 limb, in other words
the limb of the immune system that elaborates histamine,
leukotrienes and prostaglandins and the mediators that
drive the constriction of the airways. When you’re giving the patient a high dose of allergens through immunotherapy, the immune system
behaves much differently. It goes towards the Th1
branch of the immune system and you elaborate totally
different cytokines like IL 10, which suppresses the Th2 limb
and you produce plasma cells which elaborate IgG4 which
also suppresses the Th2 limb of the immune system. So allergy shots actually
make the immune system work differently to block
the allergic component of the immune system and drive
down that atopic inflammation that’s contributing to the asthma. So the GINA guidelines are
saying that they recommend it for adults with dust
mite sensitive patients who have bad asthma. I would say this also
should definitely be a part of management for children
with atopic asthma. So these are a couple of new
things on the market here. Omalizumab is a monoclonal
antibody against IgE and as you know, IgE binds to
mast cells and it degranulates and releases histamine
and things like that. Well, if you can kind of
get rid of some of that IgE a little bit and bind it
up with this medication, then there will be less IgE
binding to your mast cells and less degranulation
of those mast cells. So this is a medication for kids, it’s FDA approved for children
older than the age of six, in those who have poorly
controlled moderate to severe allergic asthma
with high levels of serum IgE and you have to document that they also have cutaneous allergic reactions. And it’s been shown in
this Cochrane review that it limits the amount of exacerbations and hospitalizations
so it definitely works but it only works for the
right type of patient. There are other medications
like Mepolizumab and Reslizumab. Mepolizumab is for those
older than the age of 12. Reslizumab is for those over 18 and these are monthly subcutaneous
injections for people who have allergic asthma
but their allergic asthma is driven mostly by eosinophils. So you need to also have
poorly controlled atopic asthma and two or more exacerbations per year with eosinophils over 300 or
three exacerbations per year with eosinophils over 150. So if you have a patient with bad asthma and you know that they
also have eosinophils, lots of eosinophils in their blood, this might be the right
medication for him. It’s a little bit newer on the market so it hasn’t necessarily, we
haven’t had as much experience with it as we have had with
Xolair but it certainly has been proven to improve
the quality of life and reduce exacerbation rates. So an asthma flare-up, just
a couple key concepts here. The GINA guidelines are suggesting the use of the term flare-up instead
of attack or exacerbation. Oral steroids are gonna be key. Recommended that you
taper those steroids down if the patient’s been on
it for at least two weeks and close follow-up. Now there is some data
that came out this year in the New England
Journal with a few studies that looked at whether you
should increase the dose of the inhaled steroid
during an exacerbation and these data are from an adult study which showed that in adults
that quadrupled their dose of inhaled corticosteroids
during exacerbations, there were fewer bad exacerbations. In other words, they were able to get over those exacerbations without
needing oral steroids. So this is the group that
quadrupled their inhaled steroid. This is the group that did not quadruple their inhaled steroid and
the bad exacerbation rate was better in those that did quadruple their inhaled steroid rate. Similar study was done in
kids and it did not hold up. Kids that quintupled
their inhaled steroid rate during exacerbations still
needed those oral steroids. So in the end you just
had kids on oral steroids and quintupled doses of inhaled steroids and they ended up with growth problems. So just increasing the
dose of inhaled steroids during exacerbations doesn’t
really work very well in kids. It’s gonna be oral steroids in kids. In adults that might work. So growth concerns are a real… It’s reality and kids that are
on inhaled corticosteroids. This study came out in the
New England Journal in 2012 that showed that in kids
on relatively high doses of budesonide, they had a decrease in their mean adult height
by about 1.2 centimeters. It happened early like
in the first few years then it didn’t get any worse after that. So it happened early and remained stable. This was a meta-analysis in 2015 that kind of show the
same data that the kids on long-term inhaled steroids might be about a centimeter shorter
than they otherwise could be, potentially, certainly doesn’t
happen in every patient but that’s a serious risk. Now what do I tell families? Your child has a very
serious chronic condition that has a high rate of
morbidity and mortality and if they’re a centimeter shorter than they otherwise could
be, that might just be a risk you’re gonna have to accept
in order to get their asthma under good control and
I’ve almost never had a family refuse because of that reason. I have families who want the
data so I give it to them but it’s a bad disease,
you need to treat it. So a couple words about peak flow meters. I really don’t use them in my practice. There’s a lot of variability. It depends on the patient effort. The numbers depend on the device
that the reference ranges, depend on the device you’re using. It might be valuable for teenage patients that have been living
with it for a long time and don’t recognize
their symptoms so well. So it might be good for
poor perceivers of symptoms and poor perception of
symptoms is a major risk factor for mortality. So in those that perceive
their symptoms poorly, might be good way to just
kind of trend over time how things are going but self monitoring is the most valuable way to
determine whether a patient needs to be treated
for an asthma flare up. So thank you for your time. I welcome any questions and
I welcome your referrals and I’m happy to even talk
about patients on email. It’s a pleasure for me,
thank you for your time. (audience applause)


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