Multiple Breath Washout Test May Outdo X-rays at Early Detection

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

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Multiple breath washout testing is superior to chest X-rays at detecting early signs of cystic fibrosis (CF) in infants and preschoolers, a study shows.

The data also suggest that combining information from both techniques provides a considerable degree of assurance regarding the absence or potential presence of early lung structural changes detected through  computerized tomography (CT) chest scans.

As such, a combination of multiple breath washout (MBW) tests and chest X-rays may be used instead of CT scans until clear signs suggestive of disease are detected. This may help reduce the frequency of CT scans, which involve greater exposure to radiation than X-rays, the researchers noted.

The study, “Chest X-rays are less sensitive than multiple breath washout examinations when it comes to detecting early cystic fibrosis lung disease,” was published in the journal Acta Paediatrica.

“The onset and progression of clinical manifestations of lung disease in children with cystic fibrosis (CF) starts early in life and often progresses without respiratory symptoms,” the researchers wrote.

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As such, objective lung tests, such as chest X-rays, chest CT scans, and/or MBW examinations, are conducted on a regular basis to detect and prevent CF progression.

While chest X-rays and CT scans examine lung structure, CT scans are far more sensitive “when it comes to detecting early lung disease and it is regarded as the gold standard to assess structural changes of the airway,” the researchers wrote.

However, chest CT scans require additional specialized training and is more burdensome to young children — who typically need general anesthesia to allow proper testing — besides involving greater exposure to radiation.

MBW is a non-invasive test that typically measures lung function through the lung clearance index (LCI) and that is considered complementary to chest scans.

LCI is assessed by having a person inhale a “tracer gas,” and then seeing how long it takes for that person to “clear” the tracer gas from their lungs. Longer times are typically associated with structural changes in the lungs.

Notably, “whether annual MBW and CXR [chest X-ray] examinations, separately or a combination of both methods, can add clinical information about early CF lung disease progression on an individual level” remains unclear.

To address this, a team of researchers in Sweden retrospectively analyzed data from 75 children (24 girls and 51 boys) with CF who underwent chest X-rays, MBW, and chest CT examinations from 1996 to 2016 at a single pediatric CF center.

At the center, chest X-rays were carried out since 1996 as part of an annual review in clinically stable condition, MBW tests were implemented in 1999 and collected annually or twice a year, and chest CTs were available from 2003 onward, starting at age 6 and then every three years.

A total of 941 X-rays and 186 CT scans (with a matching X-ray or MBW examination within one month) were included in the analysis and interpreted with a respective tool, and results were compared with LCI from 777 MBW examinations.

Children were followed for a median of 11.9 years (range, three to 18 years), and each underwent a median of 13 chest X-rays, 11 MBW tests, and two chest CT scans. None had been diagnosed with CF through newborn screening, since this type of testing is not performed routinely in Sweden.

Results showed that the annual worsening in lung structural damage based on chest X-rays was slow in these children and that there was high variability in terms of chest X-rays scoring when done by different radiologists and in scans re-analyzed by the same radiologist.

Notably, 40% of the X-rays originally classified as normal were scored by radiologists in this study as abnormal.

Also, a significantly lower proportion of children showed abnormal chest X-ray scores relative to abnormal LCI values up to age 4. After that age, there were no significant differences between the two methods.

These results suggest “chest X-rays were less sensitive than multiple breath washout examinations to detect early CF lung disease,” in preschoolers, the researchers wrote.

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In addition, abnormal chest X-ray scores and abnormal LCI values were independently and significantly associated with a greater extent of structural lung damage detected by chest CT scans. Similar results were obtained after adjusting for potential influencing factors, including sex, age at diagnosis, and simultaneous and chronic airway infections.

When both X-rays and LCI were within normal at age 6 (the time of first CT scan), the extent of CT-assessed structural lung damage was low. Similar associations were found at age 9.

These findings suggest that chest X-ray alone is “not an optimal marker of early structural lung disease,” and highlight “the clinical advantage of combining the results from both the CXR and MBW examinations to better understand the magnitude of the [structural lung damage] present in a patient with CF,” the researchers wrote.

“This information can be used as a surrogate to chest CT, or to perform chest CT less frequent, as children are more sensitive to radiation,” they added.

The team noted, however, that MBW examinations also have their disadvantages. They often are limited to tertiary care centers due to the technical challenges to perform them and interpret their results, and they are much more time-consuming relative to chest X-rays.