By Jeffrey M. Haynes RRT RPFT FAARC
Diagnostic tests are performed to identify or rule out the presence of disease.
An ideal test would provide clinicians with a “yes or no” answer with 100% certainty.
However, bronchial challenge tests are not capable of giving a “yes or no” answer with 100% certainty.
The catch phrase I like to use when discussing bronchial challenge testing is “there is no pregnancy test for asthma”.
Pregnancy tests are 99.99% sensitive (pregnant, + test) and 99.99% specific (not pregnant, – test).
Bronchial challenge tests (e.g. methacholine, mannitol, exercise) don’t even come close to that.
In one study the sensitivity (asthmatic, + test) of methacholine was 66% and the specificity (no asthma, – test) was 63%. [1]
Bronchial challenge test are not really testing for asthma, they are looking for the presence of airway hyper-responsiveness (AHR).
AHR means that the airway smooth muscle constricts too much and too easily.
AHR is a feature of asthma; however, AHR is not exclusive to asthma.
Allergic rhinitis, sarcoidosis, CF, acute bronchitis and COPD are just a few disorders that may also result in AHR.
There is also a phenomenon called asymptomatic AHR in which subjects demonstrate AHR without any clinical signs or symptoms of lung disease. [2]
Because we don’t have a pregnancy test for asthma, the process of making an asthma diagnosis is similar to obtaining a conviction in a circumstantial criminal case: there is no smoking gun, but the preponderance of the evidence points to the diagnosis/conviction beyond a reasonable doubt.
In short we must weigh all of the evidence not just one piece of evidence (e.g. methacholine challenge) to determine the likelihood that the patient does or does not have asthma.
Suggestive symptoms, atopy, family history, positive response to empiric therapy, and AHR increase the likelihood of asthma.
None of these are reliable on their own, but together gain weight.
So if you believe that the pre-challenge test probability of asthma is intermediate (50/50), a positive challenge test increases the post-test probability of asthma.
A negative challenge test in a similar patient decreases the post-test probability of asthma.
That’s all a challenge test really tells you.
Those who believe that every patient with a positive test has asthma will make a lot of false positive mistakes, and those who believe that every patient with a negative test does not have asthma will make a lot of false negative mistakes.
It is not wise to challenge patients with a very low pre-test probability of asthma because even a positive test probably doesn’t push the post-test probability of asthma above 50% [depending on the provocative dose resulting in a 20% reduction in FEV1 (PD20)].
It is not necessary to challenge patients with a very high pre-test probability of asthma (e.g. 20-year-old atopic non-smoker with a family history of asthma who presents to the emergency department with wheezing, coughing, and dyspnea which is relieved by bronchodilator and steroids) because the probability of asthma won’t change much even with a positive test.
In other words, if the pre-test probability of asthma is 90%, a post-test probability of 99% will not change the diagnosis or treatment plan.
Sometimes challenge tests are ordered in these types of patients to “confirm” the diagnosis, that is confirmation to me that the ordering provider doesn’t understand how challenge tests should be used.
Until someone comes up with a perfect test, we’ll remain engaged in a game of probability with not much certainty.
[1] Anderson SD, Charlton B, Weiler JM, Nichols S, Pearlman DS, A305 Study Group. Comparison of mannitol and methacholine to predict exercise-induced bronchoconstriction and a clinical diagnosis of asthma. Respir Res. 2009;10(1):4.
[2] Boulet LP. Asymptomatic airway hyperresponsiveness, a curiosity or an opportunity to prevent asthma? Am J Respir Crit Care Med 2003;167(3):371-378.