Is Early Diagnosis of Cystic Fibrosis Beneficial?

Abstract

Source: Wang SS, O’Leary LA, FitzSimmons SC, et al. The impact of early cystic fibrosis diagnosis on pulmonary function in children. J Pediatr. 2002;141:804–810.To determine whether early diagnosis of cystic fibrosis (CF) had an impact on the severity of lung damage at ages 6 to 10 years, investigators from the Centers for Disease Control and the Cystic Fibrosis Foundation retrospectively reviewed patient data gathered by the Cystic Fibrosis Foundation National Patient Registry on 3,625 children whose CF diagnosis was established by 36 months of age between 1982 and 1990 and who were followed regularly through childhood. Patients were categorized into 4 groups according to whether they were diagnosed before or after age 6 weeks and whether they were asymptomatic versus symptomatic at diagnosis. Asymptomatic diagnosis was defined as diagnosis by family history, genotype, prenatal diagnosis, or neonatal screening. Babies diagnosed because of meconium ileus were excluded. The forced expiratory volume in 1 second (FEV1) was used as the primary measurement of lung damage. The registry’s database includes the FEV1 recorded at each patient’s annual visit. Values for FEV1 less than 40% predicted were considered severe, less than 70% were considered moderate, and less than 90% were considered impaired. Factors considered in the analysis included gender, birth year, pancreatic status, geographic location, genotype, and weight and height percentiles. Race, geography, and pancreatic status were included in the final regression analysis.There were 157 children in the early asymptomatic diagnosis (EAD) group, 227 in the early symptomatic diagnosis (ESD) group, 161 in the late asymptomatic diagnosis (LAD) group, and 3,080 in the late symptomatic diagnosis (LSD) group. The median age of diagnosis was 3.6 weeks for the EAD group, 4.2 weeks for the ESD group, 11.4 weeks for the LAD group, and 25 weeks for the LSD group. There were significant differences between the groups for race, year of birth, geography, and growth parameters but no differences for gender, ethnicity, or delta F508 mutations. There was no difference in group mean FEV1 when analyzed for all patients. However, when stratified by birth age (before 1987 and after 1987) the EAD group born after 1987 had higher mean FEV1 values at 6 and 8 years of age (P< 05) than those 05) than those in other groups. A lower percentage of children in the EAD group born after 1987 had moderate to severe lung disease than children in other diagnostic groups (P< 05). Adjusting 05). Adjusting for race, gender, pancreatic status, and place of birth, CF patients 6–10 years of age born after 1987 had a greater likelihood of moderate-to-severe pulmonary disease in the ESD group (Odds Ratio 2.17; 95% CI, 0.91–5.21), the LAD group (OR 2.18; 95% CI, 0.88–5.35), and the LSD group (OR=2.12; 95% CI, 0.97–4.64) compared to the EAD group, all differences that did not achieve statistical significance. The slope of the decline in FEV1 between ages 6 and 10 years appeared parallel in all 4 groups. As expected the EAD group had fewer children with poor growth parameters than the other groups. The authors conclude that early diagnosis of CF is likely to improve pulmonary function later in childhood, a possible outcome of early and aggressive therapy.Pulmonary dysfunction is responsible for the majority of morbidity and mortality in CF, so the suggestion that pulmonary status may be favorably influenced by early diagnosis is encouraging. Although only Wisconsin, Colorado, and Wyoming are currently routinely screening newborns for CF, many other states are considering implementation of screening. One of the barriers to adopting screening for CF has been uncertainty about whether early diagnosis affects outcome. Nutritional benefits of early diagnosis have been documented,1 and this study adds important information suggesting that pulmonary function may also benefit from early diagnosis. The benefits in improved FEV1 were seen only in the children born after 1987, a cut-off year the authors chose only because there appeared to be a natural break around this year. This could be related to important advances in our understanding of the pulmonary patho physiology of CF, more aggressive management of infection, and newer therapeutic options such as nebulized dornase alfa (DNase) and nebulized TOBI.Primary care physicians working in states without newborn CF screening should be alert to a family history suggestive of CF to facilitate prenatal diagnosis and early intervention.