Materials and Methods
Patient selection and clinical characteristics: People with CF
seen at Children’s Hospital Colorado (CHCO) from 2004-2016 were
identified by electronic medical records. Individuals were included in
the study if they had a diagnosis of CF (sweat chloride ≥ 60mmol/L
and/or two disease-causing CFTR gene mutations) as established by
Cystic Fibrosis Foundation guidelines and at least 4 airway fungal
cultures (sputum, BAL, and/or fungus positive oropharyngeal (OP)
culture) over two consecutive years, and at least 2 years of clinical
data available after baseline.15 Information included
was patient demographics, CF diagnostic criteria, genotype,
comorbidities including ABPA, asthma, and CF related diabetes (CFRD)
present during the baseline or follow-up periods, lung function, growth
parameters, microbiology culture results, and laboratory results for IgE
and complete blood count with eosinophils. Microbiologic culture data
prior to baseline period was captured starting in 2004. Lung function
results available from children 6 years and older were recorded.CFTR modulators prescribed were recorded, however availability of
approved modulators was limited during the study time. The study was
approved by the Colorado Multiple IRB (#15-2376).
Cultures : Airway samples were collected as part of clinical care
and processed at the CHCO clinical microbiology laboratory following
standard CF culture procedures. Bacterial and fungal cultures are
performed routinely on all sputum and BAL samples.16Oropharyngeal cultures are not routinely plated on fungal media in our
institution’s microbiology lab, therefore result from oropharyngeal
cultures were only included in the analysis if positive for fungi. Two
or more positive cultures within one month of each other were considered
a single positive culture. Fungal detection included any reported fungus
species by our clinical lab, including the labels “yeast” and
“fungus,” which in some instances were reported in this manner.
Defining infection status: Initially we compared patients with no
fungal positive cultures, rare fungus (one positive), intermittent fungi
(≥ 2 positive but < 50% positive), or chronic fungi
(> 2 positive and at least 50% positive); however, given
the limited group sample sizes we chose to dichotomize fungal exposure
to agree with previously published literature and to provide greater
power for group comparisons. Results from cultures over the two-year
baseline period were used to categorize individuals as either havingrare fungus , defined as ≤ 1 positive fungal culture in the
baseline period and no positive fungal cultures recorded prior to
baseline, or frequent fungi , defined as having 2 or more positive
fungal cultures in the baseline period. Definitions were based upon
adaptations from previously published fungal and chronic bacterial
infection studies in CF.7, 17 Given that we defined
fungal exposure for individuals in the baseline period, individuals
could transition groups during the follow-up period (e.g. those
classified as rare could later meet critieria for frequent fungal
infection). Participants were considered rare during follow-up if they
had \(\leq\) 1 positive culture and considered frequent if they met
criteria (\(\geq\) 2 positive cultures) in any year of follow-up.
Chronic P. aeruginosa status during the baseline follow-up period
was defined by Leed’s criteria of > 50% positive cultures
for P. aeruginosa during at least one year. Individuals who met
criteria for chronic P. aeruginosa within any year during the
follow-up period were considered chronically
infected.18 Ever P. aeruginosa status during
the follow up period was defined as isolating P. aeruginosa at
any point in time, regardless of frequency or year.