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.