Some patients have post infection bronchial hyperreactive airways which resolves with time and/or treatment. Retesting in these patients will result in a negative metacholine challenge test. In this case the test was initially not indicative for asthma but rather a consequence of  a previously undiscovered or undisclosed transient condition.

Hi Mace

Thank you for your kind reply.

Am I safe to conclude that

1. Metacholine challenge test is not the gold standard to determine asthma no matter how transient it is?

2. What is the actual gold standard to determine asthma in a patient, if any?

Warmest Regards and Merry Christmas.

Mariam

Always remember that MCh challenge indicates hyper-reactivity which may not be synonymous with asthma. There are many confounding factors that can increase airway hyper-reactivity (some were mentioned above).

Adenosine (AMP) challenge has been shown to have excellent sensitivity AND specificity. Mannitol may be as good

MCT IS INDEED THE GOLD STANDARD FOR RULING OUT HYPER REACTIVE AIRWAYS. ITS NEGATIVE PREDICTIVE NEARLY EQUAL TO 100% WHEN DONE RESPECTING ALL THE PREREQUISITES IS DEFINITELY THE MOST INTERESTING PART OF THIS TEST. WHEREAS WHEN POSITIVE IT NEEDS TO BE CORRELATED WITH CLINICAL SIGNS AND INTERPRETED WITH DIFFERENTIAL DIAGNOSIS IN MIND OF OTHER DISEASE THAN ASTHMA THAT RESULT IN HRB. IN THIS CASE COUPLING IT WITH OTHER TESTS LIKE PRICKS TEST GIVES IT THE BEST YIELD.

The gold standard for the diagnosis of asthma is spirometry as it shows FEV1 reductions which must be reversible of at least 12% after beta-2 short acting  inhalation. Even if FEV1 values are normal asthmatic patients present airway inflammation which causes  the reduction of the small airways parameters. For allergic asthma  Nitric Oxide determination could be useful for monitoring treatment efficacy. 

the diagnosis of asthma is a clinical diagnosis supported by spirometry and reversibility tests on FEV1 after bronchodilator or MCT

Please remember that symptoms together with tests (supported by reversibility test FEV1 after bronchodilator and   Methacholine challenge indicates hyper-reactivity which may not be asthma. Other test as Adenosine or Mannitol may be a good test to support the initial symptoms.

The metacholine challenge test is one of the diagnostic tools, which is useful as a method of exclusion of bronchial hiperreactivity rather than confirmation of bronchial asthma. Hyperreactivity is not characteristic just for asthmatic patients, but it is also observed in other patients eg. some patients with COPD, sarcoidosis, allergic alveolitis, in patients after respiratory system infection mainly viral or atypical etiology, as well as in patients with heart failure and pulmonary congestion.

On the other hand, a bronchodilation test, previously recognized as pivotal for asthma diagnosis, currently is not the key point. According to current guidelines (GINA 2014, GOLD 2014) positive bronchodilator reversibility test (increase FEV1 of 12% and 200 mL) supports asthma diagnosis. Nevertheless the presence of the post-bronchodilator FEV1%FVC < LLN (lower limit of normal) does not allow to differentiate between bronchial asthma and COPD.

Thus the clinical respiratory symptoms, a detailed history and examination are crucial, and results of the diagnostic measurements should be interpreted in relation to that.

Absolutely agree with Monika Franczuk.

Happy New Year

Mariam, do not forget that MCT is highly sensitive and not so specific. It is a tool used to discriminate between patients with and without BHR. That syndrome is typical for asthma - so a negative test rules out the condition. A positive test on the other hand can be found in patients with other respiratory conditions with BHR. BHR level can change in the course of asthma controller treatment so do MCT results. As far as the gold standard for asthma diagnosis is concerned it is well known that all tests that can prove variable airflow limitation are of great use. BDT with SABA resulting in FEO1 increase with >12% or >200 ml is the cornerstone but far from being the only one. Since asthma is a complex multifactorial condition one should use an array of tests and approaches in order to confirm or rule it out.

I totally agree with the above voted answers from me.

I must emphasize on what is the most important nowadays: good history, godd clinical exam ; unfortunately we are losing this 

I totally agree with you Mirna and thank you for your upvote. Happy New Year to all of you!

Thanks all, I do agree with all of you on the adoption of AMP and Mannitol to rule out asthma. Unfortunately both are not readily available in Singapore public or restructured hospitals

Bronchospasm exists on a continuum.  Asymptomatic patients (on days of testing) may pass an MCT on one occasion and fail on another (20% decline in FEV-1).  Some patients who test + on MCT will decline asthma medications stating (to the effect) that their breathing does not improve, and their breathing is fine as is.  Patients on the lower end of normal for FVC will be affected clinically far more by any given degree of bronchospasm than those at the high end (the variability in my experience is that FVC varies from 70 - 169% of predicted, in the absence of any detectable pulmonary pathology (~10,000 patients).  A patient whose FVC was 140% of predicted, & an FEV-1 decline of 35% during MCT, had notable expiratory wheezing, and declared that he felt fine, and had routinely run up many flights of stairs feeling exactly this way in his capacity as a firefighter.  He reacted as expected to albuterol.   I'd expect that had his FVC been 80% of predicted, his clinical appearance and subjective experience during MCT would have been more severe.  Physical exhaustion as the MCT proceeds can bias the test, while remaining repeatable.  Some patients show a sharp decline in FEV-1 on the first FVC, & a considerable increase on trials 2 and 3.  If trials 2 & 3 are used, being repeatable, and trial 1 is discarded, it may miss those patients who rapidly improve post methacholine exposure.  Never under estimate biochemical diversity.  Clinically, choosing whether to treat using only MCT results, may not be optimal for all patients.  

Dear Michael,

Thank you for your kind feedback.

It is true indeed, the accuracy of such test is highly dependent on the condition the patients are at that period of time. Unless the patients adhere to the instructions given  by abstaining any physical activities, refrain from taking inhalers xx hours preceding the tests and so forth, the result could always be misconstrued.

Above all, this does not take into account the technicians know-how, apparatus reliability and the physicians (mis)interpretation.

Removing all the biases would ensure patients test being accurate but as Prof Mirna spelt out - good history and good clinical exam rules. Sadly, this is indeed lacking too.

Best regards.

Mariam