Older age at diagnosis, diabetes, and poorer lung function are all , new research suggests.
Courtesy NHGRI
A growing number of people with cystic fibrosis are diagnosed in adulthood, partly because of increased awareness among physicians of variations in disease presentation, more accessible genotyping, and easier diagnostic criteria.
Adult-diagnosed cystic fibrosis patients generally have a milder form of the disease than that of those diagnosed in childhood; however, less is known about their prognosis and life expectancy.
Researchers reported the outcomes of a retrospective cohort study of 362 adults diagnosed with cystic fibrosis at age 18 years or older. The median age at diagnosis was 34.3 years, and 71% of patients presented with pulmonary and/or gastrointestinal symptoms. The study was published in Annals of the American Thoracic Society.
The patients were followed for a median of 7.7 years, during which time there were 15 lung transplants and 33 deaths without transplant. Overall, 10-year lung transplant–free survival was 87.7%, and 15-year survival was 86.1%.
Those who were diagnosed young and who had higher lung function had the best median survival times. For each 5-year increase in age at diagnosis, the risk of death or transplant increased by 24%, and for each 5% decrease in forced expiratory volume in one second (FEV1), the risk was 35% higher.
Individuals who had diabetes at baseline had a more than fourfold higher risk of death or transplant than did those without diabetes.
“While newborn screening programs will reduce the rate of missed diagnoses in the future, clinicians still need to consider CF as a possible diagnosis if individuals are presenting with suspicious CF symptoms (e.g. GI or pulmonary symptoms) during adulthood, particularly if born prior to the introduction of newborn screening in their jurisdiction,” wrote Sameer Desai, of the University of British Columbia, Vancouver, and his coauthors.
Commenting on the association with diabetes, the authors noted that this finding had some uncertainty but suggested the additional inflammatory burden could increase the risk of death in individuals with cystic fibrosis.
The authors highlighted that fewer than 5% of people with adult-diagnosed cystic fibrosis had two copies of the F508del mutation, which is associated with severe, early-onset disease. However, those who were homozygous for that mutation tended to be diagnosed at a younger adult age, had worse nutritional status and a lower FEV1 percent predicted, compared with the overall adult-diagnosed population.
“This finding suggests potential delays in CF diagnosis for these people leading to worse outcomes,” the authors wrote.
The researchers also identified 25 individuals who had a possible unconfirmed diagnosis based on the most recent cystic fibrosis diagnostic guidelines. These individuals were either asymptomatic or had unknown symptoms, had sweat chlorides at or below 60 mmol/L (where available), and either unknown or two non–cystic fibrosis–causing mutations. They were also more likely to be male, to be nonwhite, to have increased unknown mutations, and to be pancreatic sufficient, compared with individuals with a confirmed diagnosis.
The study looked at whether Pseudomonas aeruginosa and Burkholderia cepacia complex increased the risk of transplant or death, but found these did not significantly predict survival.
“Adult CF clinicians can use this information to educate newly diagnosed adults with CF about their prognosis and to guide treatment decisions, specifically those at high-risk for a worse prognosis,” the authors wrote.
The study was partly funded by the Rare Disease Foundation. Two authors declared support from Cystic Fibrosis Canada, but no other conflicts of interest were declared.
SOURCE: Desai A et al. Ann Am Thorac Soc. 2018 Jun 26. doi: 10.1513/AnnalsATS.201801-037OC.