Association between Initial Disease Presentation, Lung Disease Outcomes, and Survival in Patients with Cystic Fibrosis

Abstract

This US study was conducted to determine whether mode of diagnosis and initial disease presentation influence lung disease and survival in patients with cystic fibrosis. The study population included 27,703 patients reported to the 1986-2000 Cystic Fibrosis Foundation Registry. Patients were segregated into four diagnostic categories: meconium ileus (MI), prenatal/neonatal screening (SCREEN), positive family history (FH), and symptoms other than meconium ileus (SYMPTOM). When compared with patients in the SCREEN group, those in the MI or SYMPTOM group were found to have significantly greater risks of shortened survival, Pseudomonas aeruginosa acquisition, and forced expiratory volume in 1 second (FEV(1)) below 70% of predicted. In the SYMPTOM group, the greatest risks of shortened survival, P. aeruginosa acquisition, and FEV(1) <70% occurred for patients presenting with combined respiratory and gastrointestinal symptoms, followed by respiratory or gastrointestinal symptoms alone; the best outcomes were in patients with other presenting features. Additionally, patients with presumably "severe" genotypes (DeltaF508 plus other class I, II, III mutations in both alleles) had greater risks of shortened survival and P. aeruginosa acquisition compared with patients with presumably "mild" genotypes (class IV or V mutations in one or both alleles).

Guidelines for Implementation of Cystic Fibrosis Newborn Screening Programs: Cystic Fibrosis Foundation Workshop Report

“…Individuals who are diagnosed with CF through NBS have improved nutritional status, 17 better growth, 14 and fewer hospitalizations, [17][18][19] whereas a delayed diagnosis can result in significant cognitive dysfunction 20 and nutritional failure. 4 NBS has been shown to decrease the risk of life-threatening complications 21 or death 21,22 from CF in infancy or early childhood. Families of those with CF also benefit substantially from CF NBS, because they avoid the average 15-month delay between onset of symptoms and diagnosis 17 along with the accompanying anxiety, frustration, and emotional distress.…”

Newborn Screening for Cystic Fibrosis: Evaluation of Benefits and Risks and Recommendations for State Newborn Screening Programs—

“…Similarly, in both the French study and the UKCFD analysis, no differences in lung function were identified between S and non-S cohorts (87,91). Analyses of CFNPR data likewise have found no clear evidence of a benefit of newborn screening or early asymptomatic detection in terms of lung function (26,93). † † Chest radiograph and clinical scores.…”

“…However, this finding was based on less reliable data on diagnosis type from births occurring during the period before screening was widely available; no significant difference in survival between those detected through screening and those detected by symptoms other than meconium ileus was identified among those who received a diagnosis after 1986 (92,93).The survival curves were almost identical between the screened and symptomatic-detection post-1986 diagnosis groups through age 14 years. The analysis does not provide evidence of improved child survival through screening.…”

“…An analysis of CFNPR data reported that although children with early asymptomatic detection had a lower frequency of colonization with this pathogen overall, after state of birth and other variables were controlled for, these children did not have a lower risk (104). Similarly, an analysis of CFNPR data reported that risk of earlier acquisition of P. aeruginosa among children detected symptomatically did not differ significantly from those detected by screening after controlling for confounding variables (e.g., genotype) (93). An analysis of CFNPR data from 2000-2002 determined that 15% of infants with CF detected by newborn screening had positive cultures for P. aeruginosa, compared with 25%-29% among infants detected on the basis of symptoms, but fewer than half of persons with CF detected by symptoms received a diagnosis as infants (27).…”

“…In the United States, analysis of CFNPR data during 1986-2000 identified a higher risk for death among persons with CF detected by symptoms rather than by screening (p<0.05) (92,93). However, this finding was based on less reliable data on diagnosis type from births occurring during the period before screening was widely available; no significant difference in survival between those detected through screening and those detected by symptoms other than meconium ileus was identified among those who received a diagnosis after 1986 (92,93).The survival curves were almost identical between the screened and symptomatic-detection post-1986 diagnosis groups through age 14 years.…”