Signs of Early-onset Lung Disease Seen in Half of CF Infants Monitored

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Researchers have developed a way to monitor the onset and progression of lung disease in young children with cystic fibrosis (CF) for whom lung imaging and diagnostic techniques are not well established.

Testing the approach in 145 CF infants, the researchers found that about half showed signs of early-onset lung disease by age 3, which was linked to clinical features that included pancreatic insufficiency, gastrointestinal or nutritional-related hospitalizations, and blood levels of inflammatory markers.

“This study closes a gap because there has never been a clinical method applicable to identifying early-onset lung disease in children with CF,” the researchers wrote.

The study, “Defining and identifying early-onset lung disease in cystic fibrosis with cumulative clinical characteristics,” was published in Pediatric Pulmonology. 

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Advances in newborn screening have enabled CF diagnoses and earlier interventions to be done sooner. But many infants with CF begin to show signs of accumulating, irreversible lung damage in the first months of life, which can have a significant impact on the disease’s progression into childhood.

Since many approaches for identifying lung disease, such as lung imaging, are not well established in children so young, clinicians lack the tools to monitor the onset and progression of early lung disease in infants, which affects their ability to treat it effectively.

But since children are now often diagnosed so early, this means that an abundance of clinical information is being gathered at each visit to the doctor, the researchers said.

The team sought to leverage this information to establish a way to identify signs of early lung disease in young children and monitor it over time, which they dubbed the CF Early-onset Lung Disease, or CFELD, scoring system.

The scientists used data from the Feeding Infants Right…from the STart (FIRST) study, which is collecting long-term clinical information from CF infants born between 2012–2017 and followed at six U.S. CF centers until age 6. By the end of 2020, 145 children had reached at least age 3 and had completed three full years of follow-up. Data from these children were used in the study.

At each clinical visit, trained coordinators collected detailed information relating to respiratory symptoms, lung exacerbations — bouts of acute symptom worsening — lung infections, and hospitalizations that had occurred since the child’s last visit.

A total of 2,469 questionnaires were collected in the first three years of life. The researchers assigned each child a total CFELD score based on the frequency of eight different lung disease manifestations. These are doctor-reported pulmonary exacerbations, hospitalizations associated with exacerbations, chronic cough, Pseudomonas aeruginosa infection, methicillin-resistant Staphylococcus aureus infection, a combined infection with both P.aeruginosa and S. aureus, hospitalizations due to P.aeruginosa, and other respiratory hospitalizations.

Scores were then used to classify the severity of lung disease as asymptomatic, minimal, mild, moderate, or severe, with more severe disease associated with higher CFELD scores.

The most frequent manifestation of lung disease reported in the infants was doctor-reported pulmonary exacerbations (405 episodes), hospitalizations associated with an exacerbation, and P. aeruginosa infection. During pulmonary exacerbations, the most frequent symptom was cough, which was reported by about 60% of parents by age 3.

A total of 266 respiratory hospitalizations were recorded. The number of doctor-reported pulmonary exacerbations and parent-reported coughs were each highly associated with the number of respiratory hospitalizations, while concurrent P.aeruginosa and S. aureus infections were weakly associated with hospitalizations.

The highest total CFELD score among the infants was 12 out of a possible 15 points. CFELD was deemed asymptomatic in 10% (no signs of respiratory manifestations), minimal in 17%, mild in 29%, moderate in 33%, and severe in 12% of children. The team determined that those in the moderate or severe categories — nearly half of the children — had early-onset lung disease.

A secondary goal of the project was to identify risk factors associated with the early emergence of lung disease.

Having pancreatic insufficiency — deficiency of certain pancreatic enzymes involved in digestion — was linked to higher CFELD scores, according to analyses. Similarly, a hospitalization for gastrointestinal or nutritional problems was predictive of a higher score, as was having Medicaid/public health insurance or elevated blood levels of IL-6, an inflammatory molecule.

In contrast,  elevated IL-10, an anti-inflammatory molecule, was linked to lower scores, as was a longer use of CFTR modulator therapies.

While the findings support using CFELD to monitor lung disease in young CF patients, “more investigations will be needed to determine if our ultimate goal to identify patients at an increased risk for developing early-onset CF lung disease can be achieved across CF centers,” the researchers wrote. “This is increasingly important as new therapies become available to the very young population and will ideally be started before irreversible lung disease develops.”