Survival following lung transplant due to cystic fibrosis (CF) in children ages 10 and younger was similar to survival among older CF children with one key difference, a hospital study suggests.

While recognizing and treating diabetes, infections, and other lung conditions early may prevent or slow lung disease progression, the primary difference in survival was organ rejection starting at 2.5 years after the procedure, with non-adherence to therapeutic regimens playing a role, the researchers said.

Non-adherence remains a major challenge for clinicians managing adolescents, and future pre-adolescent lung transplant candidates should be educated and trained to maintain post-transplant care, “especially during the critical first years after surgery,” they wrote.

The study, “Cystic Fibrosis Lung Transplant Recipients 10 years of age or Younger: Predisposing Factors for End-stage Disease,” was published in Pediatric Pulmonology.

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Advances in therapies, infection prevention and treatment, and nutritional support have altered the natural history of CF lung disease, characterized by the buildup of abnormally thick mucus in the lungs, as well as the intestines, pancreas, and liver.

As a result, lung transplants for children and adolescents with CF are likely to become increasingly less common. Still, more than 100 young people with CF in the U.S. have had a lung transplant over each of the last three decades, making key predictors of advanced lung disease still relevant.

Researchers at the Baylor College of Medicine and Texas Children’s Hospital analyzed the medical records of children ages 10 or younger who underwent transplant at their hospital to identify the factors that predisposed them to lung disease progression and end-stage disease.

Among the 115 CF young people who had double lung transplant between 2002 and 2020, 18 (14%) were 10 and younger (4.2–10.9). Ten of the young patients were male and eight were female. Eleven were residents of Texas, five were from other states, and two came from outside the U.S. (United Arab Emirates and Pakistan). Seven (39%) had Hispanic ethnicity in at least one parent; nine were Caucasian, one was African American, one was Middle Eastern, and one South Asian.

In comparison, among transplant recipients at Texas Children’s Hospital who were 11 and older, 77% were Caucasian, 19% were Hispanic, 3% African American and 1% lived outside the U.S. Among all pediatric CF patients at the hospital, 28.3% were Hispanic and 6.6% African American.

Among U.S. citizens of the younger transplant group, 75% had public healthcare insurance. Across the whole CF center, 34.7% had public insurance. Ten children lived in two-parent households, six single-parent homes, and two lived with their grandparents.

The younger transplant group was “demographically distinct from our CF center in terms of ethnicity, country of origin, and insurance status,” the researchers wrote.

Four patients were hospitalized for chronic lung failure at the time of their transplant, all on noninvasive breathing support (ventilation), reflecting significant disease. Three others received noninvasive ventilation at home, while four were on oxygen supplementation.

In the older transplant group, 34 were hospitalized at the time of their transplant, but only six received non-invasive ventilation, and 13 were on oxygen treatment. Across the general CF population, less than 1% of young people received outpatient oxygen or noninvasive ventilation.

Sputum culture analysis found 10 of the 18 (55%) were infected with methicillin-resistant Staphylococcus aureus (MRSA), six (33%) had Pseudomonas aeruginosa, three with Stenotrophomonas maltophilia, two with Achromobacter xylosoxidans, two with non-tuberculous mycobacteria, and two with significant fungal infections. Among all of the CF patients at the hospital, 18.5% had chronic MRSA infection, and 30% had chronic P. aeruginosa infection.

Despite these findings, the researchers concluded: “… there does not appear to be a clear or obvious microbiologic signature that signals a poor prognosis for young CF patients.”

Eight (44%) of the young patients had a diagnosis of CF-related diabetes (CFRD) before transplant, whereas at any time at the hospital, fewer than 5% within this age group had diabetes.

“It has been known for years that CFRD is a risk factor for more rapid progression of lung disease,” the researchers wrote. “Thus, early detection and treatment for diabetes in the sickest of [prepubescent] CF patients may be indicated and important in preventing relentless progression of advanced lung disease.”

Before transplant, half of the young patients had consolidation in a lobe or the whole lung, which refers to airspaces within the lungs being filled with fluid, immune cells due to inflammation, or other material. This was an “unexpected finding,” the researchers noted. In the older group, only two had a history of severe lobar disease.

Although the children’s weight was generally within normal range, four were relatively short, “suggesting a history of chronic malnutrition in earlier childhood,” the investigators wrote.

All children had feeding tubes at the time of referral except for the two international patients who had feeding tubes implanted shortly after referral due to severe malnutrition.

Although identified risk factors before the transplant may predispose the young patients to higher mortality, survival in the years after transplant compared favorably to the older group.

All survived the procedure, but three died within three years. One died from acute rejection complicated by  stroke while on a heart-lung machine. Two others, who were proved or suspected of not adhering to treatment protocols, had early-onset bronchiolitis obliterans syndrome (BOS), or so-called popcorn lung, a form of chronic rejection after lung transplant.

Five others died between roughly three and 14 years after the transplant, with non-adherence noted in three cases. All met the criteria for BOS.

“The major difference in survival between the younger and older cohorts begins at 2.5 years after transplantation and correlates with the role of chronic allograft [non-self donor] rejection,” the investigators wrote. “Chronic allograft rejection is the major cause of death in all solid organ transplant recipients after three years.”

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