The research team, led by Elahe Meftah and colleagues at Amir Oncology Teaching Hospital in Shiraz, combed through medical records of immunocompromised children under 18 who were screened for invasive pulmonary aspergillosis between April 2016 and December 2023. Their analysis focused on 141 children classified as having proven or probable disease according to established diagnostic criteria. The median age was just eight years, and nearly two thirds of the patients were male. Only a small fraction, 14.2 percent, had definitively proven infection confirmed by direct demonstration of the fungus, underscoring how difficult this diagnosis remains even in specialized centers. Cases labeled as possible aspergillosis were analyzed separately and descriptively, keeping the main cohort diagnostically rigorous.

One of the study’s central questions was what chest computed tomography actually reveals in children with this infection, and how those images relate to survival. Radiologists reviewed the available scans using predefined criteria, and a clear hierarchy of findings emerged. Pulmonary nodules, rounded shadows that mark where the fungus has invaded lung tissue, were by far the most common abnormality, present in 75 of the 141 patients. Consolidation, the dense opacification of lung tissue typically seen in pneumonia, came second at 44 patients. The famous halo sign, a nodule surrounded by a rim of ground-glass opacity that radiologists consider a hallmark of early invasive aspergillosis, appeared in 37 patients. Ground-glass opacities and pleural effusion, fluid around the lungs, each turned up in 16 patients.

The pattern of co-occurrence was equally informative. When children had nodules, those nodules most frequently appeared alongside the halo sign, with 33 patients showing both features simultaneously. This makes biological sense: the halo represents hemorrhage around a fungal lesion, and its frequent pairing with nodules reflects the angioinvasive nature of Aspergillus, which seeds blood vessels and starves surrounding tissue. For diagnostic purposes, the study confirms that CT remains a cornerstone of disease detection and characterization, giving clinicians a visual map of how far the infection has spread. What the scan could not do, however, was predict who would survive.

That was the study’s most striking twist. Among the 136 patients included in the survival analysis, 41 deaths occurred during follow-up. The researchers estimated survival at 96 percent at four weeks after diagnosis, but that figure fell to 66.3 percent by the end of follow-up, a sobering trajectory that illustrates the delayed toll the infection takes on fragile patients. When the team fed CT variables, including the presence of nodules, the total nodule burden, and nodule size, into multivariable Cox proportional hazards models alongside laboratory markers, none of the radiological features showed a significant association with survival. The pictures told doctors where the fungus was, but not where the patient was headed.

The blood tests told a different story. Higher serum galactomannan, a sugar molecule released by growing Aspergillus hyphae and detected through a widely used enzyme immunoassay, independently predicted mortality, with a hazard ratio of 1.06 and a 95 percent confidence interval of 1.02 to 1.10, statistically significant at p below 0.001. In practical terms, every incremental rise in galactomannan corresponded to a measurable increase in the risk of death, likely reflecting the sheer fungal load multiplying inside the lungs and spreading through the bloodstream. Because galactomannan is shed by viable fungus, serial measurements essentially track the living enemy in real time, a capability no static imaging study can match.

C-reactive protein, the classic inflammatory sentinel produced by the liver in response to systemic inflammation, proved to be an equally powerful prognostic marker. Each unit increase in CRP carried a hazard ratio of 1.02, with a confidence interval of 1.01 to 1.03 and p below 0.001. While a hazard ratio per single unit may sound modest, CRP values in sick children routinely range across hundreds of units, so the cumulative effect on risk is substantial. Elevated CRP in this setting signals an uncontrolled inflammatory storm accompanying the infection, a process known to drive tissue damage and organ failure independent of the pathogen itself. Together, the two biomarkers capture both sides of the lethal equation: how much fungus is present and how violently the body is responding.

The authors’ conclusion is carefully framed and clinically meaningful. Chest CT, they write, primarily supported disease detection and radiologic characterization, whereas serum galactomannan and CRP demonstrated greater prognostic value for mortality risk stratification within diagnosed invasive pulmonary aspergillosis. This distinction matters because diagnostic and prognostic tools serve different purposes at the bedside. A scan answers the question of whether the disease is present and what it looks like; biomarkers answer the question of how the patient is likely to fare. The study suggests that once a diagnosis is established, clinicians should look to repeated blood tests, not follow-up imaging, to gauge trajectory and intensity of therapy.

Several secondary analyses enriched the picture. The researchers examined predictors of nodules and nodule burden, probing which factors drove the most characteristic radiologic manifestation of the disease. While the source data abstracts these details, their inclusion signals the team’s effort to understand the biology behind imaging findings rather than merely cataloging them. Kaplan-Meier survival estimates anchored the mortality analysis, providing clear time-to-event curves that clinicians can interpret intuitively, and the Cox models adjusted for multiple variables simultaneously to isolate the independent contribution of each marker.

The study carries the usual caveats of retrospective, single-center research. All patients came from one oncology hospital in Shiraz, and practice patterns, host populations, and diagnostic thresholds elsewhere may differ. Not every child had a CT scan available for review, and biomarker values were drawn from routine clinical testing rather than a standardized protocol. Still, the cohort size of 141 children with proven or probable disease is substantial for a condition that remains rare and hard to diagnose, and the consistency of the statistical findings lends weight to the conclusions. For a disease in which early risk stratification can mean the difference between aggressive antifungal therapy and a fatal outcome, the message is potent: in children with invasive pulmonary aspergillosis, what is in the blood may matter more than what is on the scan.

Subject of Research: Prognostic value of chest CT findings and serum biomarkers for mortality in pediatric invasive pulmonary aspergillosis

Article Title: Chest CT findings and biomarker predictors of mortality in pediatric invasive pulmonary aspergillosis: a retrospective cohort study

Article References: Meftah, E., Mirbagheri, S. S., Reihani, Y., Jafarian, H., Hamzavi, S. S., Abbasi, A., Khajeh, S., Naseri, A., Nazemosadat, S. M. A., Habibzadeh, A., Haghshenas, A., Abdipour Mehrian, S. R., & Amanati, A. (2026). Chest CT findings and biomarker predictors of mortality in pediatric invasive pulmonary aspergillosis: a retrospective cohort study. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14512-y

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14512-y

Keywords: invasive pulmonary aspergillosis, pediatric oncology, chest CT, galactomannan, C-reactive protein, mortality, fungal infection, immunocompromised children, halo sign, prognostic biomarkers, retrospective cohort, Aspergillus