Pulmonary findings in infants with cystic fibrosis during the first year of life: Results from the Baby Observational and Nutrition Study (BONUS) cohort study

Abstract

Importance Treatment recommendations for infants with CF standardize care, but most surveillance or treatment guidance of pulmonary manifestations are consensus-based due to sparse evidence. Objective To report observations about pulmonary correlates of growth and other clinical features in infants with CF. Methods We analyzed data from the prospective Baby Observational and Nutrition Study conducted in 28 centers across the US, including clinical features, medications, guardian diaries of respiratory symptoms, oropharyngeal swab cultures and chest radiographs (CXR) collected over the first year of life. Results Cough was reported in 84% of infants in the first year. Up to 30% had clinically important cough but only 6.3% had crackles; 16.5% had wheeze. Wisconsin CXR score was above 5 in 23% (normal=0; maximum score=100). Pseudomonas was recovered from at least one respiratory culture in 24% of infants and was associated with crackles/wheezes and use of proton pump inhibitors (PPI) (OR=5.47; 95% CI=1.36, 21.92; p=0.02) or PPI plus histamine-2 (H2) blocker (OR=8.2; 95% CI= 2.41, 27.93; p=0.001), but not H2 blocker alone. Hospitalization for respiratory indications occurred in 18% of infants and was associated with crackles/wheeze and abnormal CXR but not low weight, Pseudomonas or use of acid blockade. Conclusions Cough is common in infants with CF, but few present with crackles/wheeze or CXR changes. Pseudomonas is associated with use of PPI or PPI plus H2 blocker, but not with respiratory hospitalization. These observations cannot prove cause and effect but add to our understanding of pulmonary manifestations of CF in infants. Trial registration United Sttes ClinicalTrials.Gov registry (clinicaltrials.gov).

Novel imaging techniques for cystic fibrosis lung disease

“…Studies that have looked at children up to age 3 report an increased prevalence of abnormal scores in older toddlers, 13 suggesting worsening of disease over time. In the BONUS study, investigators support the recommendation for a more sensitive indicator of lung disease in infants, as higher CXR scores were not seen to occur more frequently in infants colonized with Pseudomonas , 12 a known risk factor for disease progression.…”

“…The Baby Observational and Nutrition Study (BONUS), 11 a prospective multicenter study of 231 infants with CF, has provided a wealth of additional information regarding CXR abnormalities detected in infants 12 . The Wisconsin System, a well‐established CXR scoring system, 13 rates each CXR on a scale of 0 to 100, with higher scores indicating more severe disease, and a cut‐off of less than 5 indicating very mild, and likely reversible, disease.…”

“…The Wisconsin System, a well‐established CXR scoring system, 13 rates each CXR on a scale of 0 to 100, with higher scores indicating more severe disease, and a cut‐off of less than 5 indicating very mild, and likely reversible, disease. In the BONUS study, at 1 year of age, the median Wisconsin score was 2.5 (range 0‐12.9), with 9% of infants having a score greater than 5 12 . Thus, with 91% of CXRs of infants with CF showing scores in the normal or very mild disease range, the clinical utility of routine CXR in early CF is uncertain.…”

Disparities in first evaluation of infants with cystic fibrosis since implementation of newborn screening

“…Group 1 infants had more pulmonary exacerbations, which drive pulmonary function decline [ 47 , 48 ]. A prospective study of growth in infants with CF diagnosed via NBS showed no association between low weight and hospitalization [49] , though race and ethnicity of participating infants was not reported in the cohort Group 1: infants categorized as Black/African American, American Indian/ Native Alaskan, Asian, and/or other race, and/or Hispanic ethnicity. Group 2: infants categorized as White and not Hispanic.…”

“…Results: Among 6354 infants, 21% were in Group 1. Group 1 median AFE was 31 days (IQR 19,49) and Group 2 was 22 days (IQR 14,36) (p < .001). Median WFA z-score at 1-2 years was lower in Group 1.…”