METHODS
The design of the CFFPR has previously been described [11]. In brief, individuals who obtain care at CFF accredited Care Centers in the United States are invited to participate in the CFFPR; data are available from 1986 to the present. Nutritional, microbiologic, pulmonary, and medication data from every outpatient encounter are reported, as well as demographic and diagnostic data and hospitalizations. Individuals with CF (parents or guardians in the case of those younger than 18 years of age) provide informed consent to participate. CRMS was added as a diagnostic category in 2010.
We included all individuals in the CFFPR born between 2010 to 2020 with a CF or CRMS diagnosis reported by a CF care center. We then reviewed reported sweat chloride and CFTR genotype data for these individuals to determine if the diagnosis reported by the CF care center agreed with CFF diagnosis guideline criteria [12]. In the event an individual reported multiple sweat chloride values, we used the highest lifetime sweat chloride value ever reported to the CFFPR. We utilized the Clinical and Functional Translation of CFTR Project (CFTR2) to determine the disease liability of CFTR variants [13]. Patients without adequate genetic or sweat chloride data to determine a CFF guideline diagnosis were excluded from the analysis. We previously reported that many infants assigned a clinical diagnosis of CF in the CFFPR by their CF Care Center did not meet diagnostic criteria for CF, but rather met criteria for CRMS [10]. We therefore classified children into four mutually exclusive categories: CF care center report CF and CFF guidelines diagnosis criteria indicate CF (CFc/CFg); CF care center report CRMS but CFF guideline diagnosis criteria indicate CF (CRMSc/CFg); and CF care center reported CF but CFF guideline diagnosis criteria indicate CRMS (CFc/CRMSg); and CF care center reported and CFF guidelines criteria both indicate CRMS (CRSMc/CRMSg). CRMSc/CFg were excluded from the descriptive analysis under the assumption those reported CRMS diagnoses may be data entry errors.
We then compared CFc/CFg children to children classified as CFc/CRMSg and CRMSc/CRMSg in terms of demographic characteristics and clinical characteristics including airway microbiology, anthropometrics, pulmonary function, and health care utilization in the first year of life using data reported 2010-2021. Pulmonary function outcomes were assessed in children ≥6 years using the percent predicted forced expiratory volume in one second (ppFEV1) based on the Global Lung Function Initiative reference equations [14]. We calculated CFFPR participation through 2021 by group. We present the distribution of categorical variables as proportions and continuous variables using the mean and standard deviation. We calculated confidence intervals of the mean when presenting continuous variables by age. Significance testing was performed using chi-square tests of association or ANOVA to detect a difference across the three groups. Analysis was implemented in SAS version 9.4. This analysis was classified as exempt by North Star Institutional Review Board.