Dr. Qaadri

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Medical Post Asthma Interview

By Dr. Shafiq Qaadri, MD

Is asthma only wheezing?
No. Patients with asthma have a range of symptoms of which wheeze is a common one, as is chest tightness and breathlessness. One symptom that is frequently overlooked in primary care is chronic cough.

What is asthma control?
Complete asthma control is where patients have no symptoms and—this is key--are able to undertake full normal activity. If you don’t ever exercise or if you avoid activities, you won’t have symptoms. So control means the absence of any symptoms, WHILE undertaking full normal daily activity, including exercise.

How well do we control asthma in Canada, especially compared to other jurisdictions?
You do as well in Canada as in the United States and many countries in Europe, perhaps better than some.
But even so, the Asthma Control in Canada Survey shows that a very substantial proportion of patients have continuing problems--they may have emergency asthma attacks, or they have symptoms that stop them from participating in the activities that they wish to do.
A large percentage of patients in Canada fall into those categories. Therefore, although you do as well as in many countries, you don’t have perfect control.

You spoke about a “disconnect” between patient perception and physician prescribing found in the Asthma in Canada Survey. Could you elaborate?
Prescribing does not mean that patients take therapy. In Canada, there is fairly good use of inhaled steroids amongst patients who have regular symptoms. It’s not perfect: there’s still a significant proportion of patients who do not get adequate controller therapy, one of the prime determinants of whether they have their asthma well-controlled. The survey showed what symptoms patients complained of and how frequent they were.

Is there an under-utilization of appropriate therapy?
Certainly. The survey shows there are many patients out there who have continued symptoms and limitations of daily activities. So there is clearly under-utilizaition, part of which is physician-driven, because the physician may not be prescribing the appropriate therapy, or they may not be prescribing it through a device that the patient can use. It may be patient-driven--the patient elects not to use their therapy on a regular basis.

Is asthma on the increase?
There’s no doubt in my lifetime I have seen a substantial increase. There are many factors that might influence that. Certainly the environment is critical-- domestic allergens, city dwelling and pollution have effects…

One factor is maternal smoking: there are good data to show that women who smoke during pregnancy have children who have a much higher incidence of wheezing and allergic disease. It’s multifactorial, but it’s definitely increasing.

What is GINA?
GINA is the Global Initiative in Asthma Management. It is an attempt for the whole world to come to a unified agreement about what control of asthma requires and what therapies should be offered to achieve that control.

I enthuse over people getting together rather than individuals following parochial guidelines. However, I do see the importance of individual countries being able to fine tune guidelines to suit particular requirements.
Some countries, including Canada, have been very efficient in producing guidelines and have led the way.

How has the thinking for first choice for controller therapy evolved?
As a medical student, the idea of asthma was that it was a disease of the smooth muscle, of bronchoconstriction, and control of asthma would be achieved with the use of regular bronchodilator therapy. Such thinking continued well into the 1980s.

In the mid-80s, when people biopsied airways to look in greater detail at the underlying pathologic mechanisms, we realized that inflammation was very important.

Perhaps the pendulum swung too far by 1990, when we were saying that inflammation was absolutely everything; hence corticosteroids rose rapidly to the top of the controller heap because they are good at controlling inflammation.

Now, people are recognizing that there are more components than JUST inflammation, or JUST bronchoconstriction. That’s why we’re seeing good studies with combination therapy--with inhaled steroids and long-acting beta-2 agonists together--which are providing even better control of asthma than the anti-inflammatory therapy alone.

Is there a move towards early combination therapy?
In the mid to late 1990s, studies that compared combination therapy with inhaled steroid therapy alone have tended to look at patients who were already taking moderate doses of inhaled steroids. We’re now seeing in the past three years a number of studies genuinely addressing the question as to whether combination therapy is as good, or better than, low doses of inhaled steroids.

The first studies strongly support the conclusion that combination therapy is better…
And we are going to see the Canadian and other guidelines change in the next few years to recommend combination therapy earlier--at a lower dosage of inhaled steroids.

What conclusions or clinical pearls should doctors draw from recent trials such as FACET, MIASMA and SIESTA?
All studies tend to give you a range of messages.

The FACET Study was extremely good—the size of the study, the duration, design, and outcomes--and it was the first study that looked specifically at exacerbations of asthma as the primary outcome, rather than just lung function or symptom control.

It was unequivocal in showing two things. In terms of asthma exacerbations, you do better with a higher dose of inhaled steroid than with a lower dose.

But it also shows that if you add a long-acting beta agonist to either low or higher dose inhaled steroid, control of asthma exacerbations improves further.

The drugs do seem to work together in an enhanced fashion. FACET isn’t the only study that has shown that. MIASMA, which is a meta-analysis of several studies, showed that the combination of salmeterol with inhaled steroid [ADVAIR], like the combination of formoterol with an inhaled steroid [SYMBICORT], reduces exacerbation rates.

Those studies enhance our view of what the best long term therapy for asthma might be. SIESTA, which isn’t yet published, is one of the first studies to carefully look at an even milder end of the asthma spectrum--patients not on any steroids, who were simply on short-acting beta agonists as required.
We have shown unequivocally that the combination of low dose fluticasone plus salmeterol gave better outcomes in terms of lung function, exacerbations of asthma, symptom control, and days of very good asthma control—even in this group of mild asthmatics.

I think SIESTA is an early example of a new generation of studies saying combination therapy truly has a role in milder asthma.

In your presentation, you urged physicians to be mindful of patients’ individual response—cluster analysis and asthma subtypes. Could you elaborate?
Yes, of scientific necessity, clinical trials are presented showing the group mean data, with standard deviation of responses around those mean data.

What those studies fail to address is the true range of individual responses to various treatment modalities. To do that, you have to analyze the data in a different fashion. One way might be to look at centiles of response—to divide the patient groups into 10% bands and see what the distribution of response for each treatment modality. That I think is helpful because it will show you that there is a small percentage of patients who don’t do particularly well with inhaled steroids, and certainly who don’t respond once the dose of fluticasone has gone beyond 200 micrograms per day.

The same applies to the whole range of asthma drugs—the long-acting bronchodilators, LTRAs [leukotriene receptor antagonists], as well as steroids. While the majority respond, some may not have such a good response.

When we are sitting in our offices with one asthma patient in consultation with us, we don’t actually know that they’re going to follow the group mean result of the 1000 patients in the last study.
It is very important that we recognize that you can have individual responses, greater or lesser benefits to different treatments; therefore, the key message that I hope I was conveying, was that when you as a clinician institute one therapy for one patient, it is important that you look at the outcome of that therapeutic change, to make sure that the patient has responded.

The benefit of the large trials is that it tells you statistically what is your best bet for a good response.

What changes to the Canadian Consensus Guidelines have you observed and do you anticipate?
The great strength of the initial guidelines was to remind the non-expert that inhaled steroids are very effective in asthma management. In the UK we have seen a substantial reduction in asthma mortality over the 1990s, which reflects more widespread use of inhaled corticosteroid therapy.

So I think the initial guidelines served a very good purpose.

As they are refined, as we get more information, as we look at our evidence base more critically, we can make more comments. So the next big step of the guidelines, in the mid 1990s, recognized that adding a long-acting beta-2 agonist with an inhaled steroid, gave you something extra, and perhaps was a better option than pushing the dose of inhaled steroid to very high levels. So that’s the evolution of the guidelines.

I would predict that the next guidelines will push the dose of inhaled steroid at which you can consider adding a long-acting beta-2 agonist to much lower levels.

In specific Canadian terms, Consensus suggests that if you have regular symptoms, your first choice is an inhaled steroid, and that once that inhaled steroid—beclomethasone or budesonide--has gone to 500 micrograms per day, then maybe you need more than one controller agent.

I’m quite certain that over the next few years, we will see the guidelines move that marker from 500 micrograms of inhaled steroid down to 200 micrograms, perhaps even a bit further.

What’s your final advice to physicians treating asthma?
Look at a patient as a whole, and not simply as an airway that has abnormal function. You cannot separate the patient and their environment from their asthma, and the patient’s perception of symptoms.

Make sure that they can use the therapy that you offer; that is, give them an inhaler device that the patient can use; make it simple, so that the patient is encouraged to take it. Use good therapy, as you’re likely to have a quick positive outcome, so that the patient gets positive reinforcement.

Follow the patient up to make sure that they have responded to treatment, and have further feedback so that you can modify your choices to achieve the best asthma control possible.

Dr. Shafiq Qaadri is a Toronto family physician and Continuing Medical Education lecturer. www.doctorQ.ca

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