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Mannitol Challenge Test for Asthma Needs to Be Interpreted Differently as Screen Versus Diagnostic

NEW YORK (360Dx) – Clinicians using the mannitol challenge test to screen for asthma need to be cautious in interpreting its findings, according to a recent study.

The test, which measures bronchoconstriction upon exposure to increasing amounts of mannitol, was designed to diagnose asthma among patients suspected of having the condition because of wheezing, a cough, or other symptoms. But it is increasingly being used to screen the general public for asthma, such as firefighter and military recruits, elite athletes, and young children participating in sports.

In a recent paper appearing in Respirology, Graham Hall from the Telethon Kids Institute and Curtin University in Perth, Australia, and his colleagues examined the diagnostic utility of the mannitol challenge test in a population of people with asthma-like symptoms as well as in the general population. Among symptomatic people, they found that the test could identify people with asthma, but among the general population, they found it is better at identifying people who don't have asthma.

"The mannitol challenge test is still a very useful test," Hall told 360Dx. "It is very good at [diagnosing] people with asthma if they come in with symptoms that suggest that they do have asthma. It can be very good at excluding asthma if you are using it as a screening test.

"People using the test and the test results just need to be aware of that subtle difference in how they use the test results depending on the person that they have in front of them," he added.

How the test should be interpreted comes down to a person's pre-test probability of having asthma and why the test was conducted. Hall noted that people who go to their doctor because they experienced wheezing or have a cough — people for whom the mannitol challenge test was designed — are more likely to have asthma than people randomly plucked off the street.

To examine the diagnostic utility of the mannitol challenge test in these two populations — people suspected of having asthma and the general public — Hall and his colleagues turned to the Western Australian Pregnancy (Raine) birth cohort.  

The participants filled out a questionnaire asking about their respiratory health and underwent skin prick, spirometry, and mannitol challenge testing.  Of the 2,086 members of the 22-year Raine follow-up cohort, 772 participants completed all testing and 33 participants had a positive mannitol challenge test.

Some 148 people from the Raine cohort reported wheezing or other asthma symptoms. Of these, half met the strict criteria Hall and his colleagues set for having current asthma: physician-diagnosed asthma accompanied by wheezing and the use of asthma medications in the previous year.

Twenty percent of those in this group who had asthma had a positive mannitol challenge test, while 6 percent of those who did not have asthma had a positive mannitol challenge test. The researchers further calculated that the test had a positive predictive value of 79 percent — meaning that a positive test accurately identified someone with asthma about 8 out of 10 times — and a negative predictive value of 52 percent.

These results, Hall said, reflects what previous clinical trials had shown.

In the more general population of 772 participants, 10 percent had current asthma, which is in line with the incidence of the condition in the public, the researchers noted.

In this cohort, 15 participants with current asthma had a positive mannitol challenge test, indicating that the test has a sensitivity of 19 percent. In addition, as 18 participants without asthma also had a positive mannitol challenge test, that suggests the test has a specificity of 97 percent.

The researchers calculated that the mannitol challenge test has a positive predictive value of 45 percent and a negative predictive value of 92 percent in this general population cohort.

This, Hall told 360Dx, indicates that in the general population a positive mannitol challenge test could identify people who do not have asthma. However, in that same population, a negative test result "was very, very good at excluding asthma," he said, noting that it is more than 90 percent accurate.

This means that the test might need to be interpreted differently for clinical and non-clinical populations, he and his colleagues cautioned. As an example, Hall said that a professional football player who doesn't respond to the test might be barred from taking albuterol or another asthma medication, but a football player who did respond to the test might have to answer a physician's follow-up questions before being added to the list of players allowed such medications.

"The test is still very useful, it's still very accurate, but you have to make sure that you are asking the right question," Hall said.