DISCUSSION
This is the first study investigating associations between
gastrointestinal (GI) symptoms -assessed by the Dutch GI Symptom
Tracker-, anxiety/depression and health-related quality of life (HRQoL)
in Dutch pwCF.
Elevated levels of GI symptoms and anxiety/depression were prevalent in
pwCF. As hypothesized, more GI symptoms were associated with more
symptoms of anxiety, depression and worse HRQoL. In our data, ‘Eating
Challenges’ and ‘Stools’ had the highest/worst scores, highlighting the
severity of these symptoms; both scales were significantly, positively
associated with elevated anxiety, depression and worse HRQoL. In
general, this study provided strong evidence of convergent and divergent
validity, finding statistically significant relationships between GI
symptoms and related domains of HRQoL, but no relationship to CFQ-R
Respiratory Symptoms.
Recent studies have recognized the synergies between psychological
symptoms, specifically depression, and changes in inflammation in the
gut microbiota.12 Our results suggest new targets for
treatment (depression) that may reduce inflammation in the gut and
improve HRQoL in pwCF and vice versa: targeting gut symptoms might
reduce anxiety/depression and improve HRQoL. The treatment of CF has
been transformed by the development of highly effective cystic fibrosis
transmembrane conductance regulator (CFTR) modulators, such as
elexacaftor/ tezacaftor/ivacaftor.34 For many
patients, this has led to improvements in lung function, respiratory
symptoms, and sweat chloride concentrations.35However, the impact of modulators on GI symptoms is relatively
unknown.7, 36 Several studies on gastrointestinal
patient-reported outcome measures (GI-PROMs) in relation to epithelial
transport inhibitors (ETIs) and CFTR-modulators in CF have shown
promising results, including improved intestinal function, hepatobiliary
complications and decreased episodes of GI inflammation, illustrated by
decreased fecal calprotectin levels. 37,38 Although
quality of life may improve for many who started modulator
treatment,39 a variety of negative side effects with
potential impacts on safety and well‐being have been reported, including
neuropsychiatric changes.40 In our study sample, the
majority (68.2 % of adults and 90% of adolescents) used modulators.
Large epidemiologic studies are needed to better characterize these
relationships.
Strengths and limitations should be considered. This is an innovative
pilot study with clinical implications regarding assessing and treating
GI symptoms. This study was limited by a relatively small sample size,
especially of adolescents. A larger sample size would increase the
statistical power of our analyses and improve their generalizability.
However, even with this relatively small sample and an adjustment for
multiple testing by using a significance cut-off value <0.001,
the predicted relationships between GI symptoms and mental health and
quality of life were found to be statistically significant.
Another limitation is that some participants completed the measures
online whereas others completed them in clinic; differences in mode of
administration may have led to response biases. Finally, there is a
possibility of ascertainment bias, given that individuals with fewer
symptoms or lower socioeconomic status may have been less inclined to
share their screening outcomes for research purposes.
Moreover, additional studies are needed to identify and address factors
that might influence GI symptoms, anxiety/depression and HRQoL in pwCF.
In a future study, we plan to investigate the gut microbiome and the
influence of dietary intake to gain insights into their relationship to
GI symptoms. Another future study should examine the complex interplay
between GI symptoms, systemic inflammatory markers and mood disorders in
CF, given that these systems seemed to be linked in the
gut-brain-axis.12
Studying the relationship between these systemic inflammatory markers,
GI symptoms and mood disorders can provide insight in the underlying
mechanisms, identify biomarkers for disease activity and treatment
response, and develop targeted therapeutic interventions. A clear
relationship between gut and brain has been described in other diseases,
like inflammatory bowel disease and functional gastrointestinal
disorders,41, 42 but data on CF and gut-brain-axis is
yet limited.