Knowledge
When spirometry alone does not settle the question, the airways can be challenged gently and under control, so a tendency to react can be measured. The clinic offers mannitol, methacholine, EVH and a standardised exercise challenge on a cycle ergometer in one place. What each test measures. What the answer means. What it does not mean.
Every work-up starts with spirometry with a reversibility test: you blow into a device before and after airway-opening medication. A clear improvement can settle the diagnosis on the spot. The criterion is an increase in FEV1 or FVC of at least 12 per cent and at least 200 ml.
A normal spirometry does not rule asthma out. Lung function is often entirely normal between symptom periods, and in a Canadian study of 500 adults who reported having been given an asthma diagnosis by a doctor and who had a negative reversibility test, 43 per cent nevertheless had a positive methacholine challenge. That is precisely who a provocation test is for: the answer is not no, it is not yet settled.
If the result is to support an exemption application with Anti Doping Danmark, it is the increase in FEV1 of at least 12 per cent and at least 200 ml (or a positive provocation test) that counts.
Direct provocation
Methacholine acts directly on the smooth muscle in the airway wall and makes it tighten. Everyone's airways react if the amount is large enough; what the test measures is how little it takes before yours do. That sensitivity is one of the core features of asthma.
You inhale methacholine in gradually increasing amounts, and lung function is measured after each step. The methacholine test stops as soon as FEV1 has fallen by 20 per cent from the starting value, or when the last step has been given without a fall. You then get airway-opening medication, and the measurement is repeated, so your breathing is back to normal before you leave.
A negative answer (no fall through the whole protocol) speaks strongly against current asthma, and that is the test's most important property. Two conditions must hold for it: you must have had the symptoms in the days around the test, and the medication pause (the one the clinic has agreed with you) must have been kept. A positive answer shows that the airways are hyperreactive, but that is not in itself an asthma diagnosis: hyperreactivity is also seen with hay fever, after an airway infection, in COPD and in smokers. There is a grey zone, where a fall appears only at the highest doses; that result is assessed together with your symptoms, while a fall at low doses carries a great deal of weight.
Methacholine is one of the most sensitive provocation tests in a general asthma work-up. That does not hold for athletes: in athletes the test performs markedly less well, and some with a positive hyperpnoea test have a negative methacholine test. For exercise-related symptoms, one of the indirect tests below is the right choice.
Indirect provocation
The indirect tests work through the same mechanism as exercise itself: the lining of the airways loses water and heat, and that sets off the reaction. Exactly how is not settled; the drying of the lining and the rapid rewarming afterwards are the two prevailing explanations, and they are not mutually exclusive. The tests therefore say something closer to what happens in real life, and a positive answer is more specific for asthma than a positive direct test.
You inhale a dry powder in increasing amounts, and lung function is measured along the way. It requires no special equipment beyond the inhaler and is practical in an outpatient setting. Most people cough during the test, and it passes quickly.
Eucapnic voluntary hyperpnoea. You breathe rapidly and deeply for six minutes from a dry gas mixture, so the airways lose water the way they do during hard exercise, without the body doing physical work. The breathing itself is demanding while it lasts. It is one of the indirect tests the IOC recommends for athletes.
A standardised exercise test on a cycle ergometer, where lung function is measured repeatedly afterwards. It reproduces your own trigger, which is its strength. Its weakness is that the ventilation reached in a laboratory is often lower than the one you reach in your own sport.
There is no established reference test for exercise-induced bronchoconstriction in athletes. The IOC recommends indirect provocation over direct, and in the systematic review behind the IOC consensus, EVH and the sport-specific exercise challenge were assessed as comparable, with moderate sensitivity and specificity. Mannitol was not included in that review. Where EVH is not an option, the sport-specific exercise challenge is the alternative. Two indirect challenges are not done on the same day.
A negative laboratory test in someone with convincing symptoms should therefore not stand alone. The symptoms may have a cause outside the lower airways altogether.
Choosing a test
Is the question whether there is asthma at all, and is the aim to be able to rule it out? Then methacholine is the strongest tool, because a negative answer in someone with current symptoms carries real weight.
Is the question whether exercise sets off a narrowing (in an athlete, or in anyone whose symptoms come with exertion)? Then it is an indirect test: EVH or a standardised exercise challenge. Mannitol is the practical alternative and is well suited to an outpatient setting.
For referring doctors: it helps to state in the referral whether the question is obstruction here and now or a tendency to react, and to enclose earlier lung-function measurements, so the variation over time can be assessed. You are welcome to call during phone hours if you are in doubt about which test to ask for.
The most common reason for an unusable result is that airway-opening medication has not been paused as agreed. The medicine has then already opened the airways before the test begins. Only pause if the clinic has asked you to. The pause times are listed on the lung function page.
Before an indirect test (mannitol, EVH or an exercise challenge) you should also avoid caffeine (coffee, tea, cola, energy drinks) on the day itself and hard exercise for the last four hours. Neither applies before a methacholine test. Both can dampen the reaction and give a falsely negative answer.
Set aside time. A provocation test takes considerably longer than an ordinary lung function measurement, because the measurement is repeated after every step and again after the airway-opening medication at the end. Expect up to two hours at the clinic. The time covers preparation, the test itself and the period afterwards, and it cannot be squeezed in on the way to something else.
Tell us in advance if any of this applies to you. It is easier to move an appointment than to repeat a test that could not be interpreted.
FAQ
The test is carried out under the supervision of staff who can manage a strong reaction in the airways, and with emergency equipment in the room. The narrowing that is provoked is intended and comes step by step, and it is reversed with airway-opening medication before you leave. Some notice chest tightness, cough or mild breathlessness along the way, and it passes with the medication. The test is stopped as soon as the measurement shows what it needs to show.
Then that is important information, not a dead end. Breathlessness during exertion has several possible causes, and two of the most common (exercise-induced laryngeal obstruction and dysfunctional breathing) do not show up on an asthma test at all. A negative answer moves the question on rather than closing it.
Only what the clinic has told you to continue. Airway-opening medication that has not been paused is the single most common reason a test cannot be interpreted, and it means the appointment has to be repeated. If you are in doubt, call rather than guess.
That is decided from your history and from what the question actually is, and it is settled at the consultation. You do not need to choose in advance.
Selected references behind this page.
The clinic offers all four tests and chooses the one that fits your situation and your question. A referral from your GP is normally required; you can also be seen as a private or insurance patient. This page is general information and does not replace a medical assessment.