Introduction: Constipation in people with cystic fibrosis (PwCF) is increasingly recognized as a debilitating aspect of cystic fibrosis pathophysiology in the era of highly effective modulator therapy. Information on the impact of constipation in hospitalized patients with cystic fibrosis (PwCF) is limited. This study aims to characterize the relationship between constipation and its symptoms, complications, and associated healthcare costs in the National Inpatient Sample (NIS) database.

Methods: NIS was queried for discharges of PwCF from the years 2015-2019. Using International Classification of Diseases, Tenth Revision (ICD-10) codes, hospitalized PwCF were split into two cohorts: one with comorbid constipation and one without constipation. The cohorts were matched for Charleston Comorbidity Index, markers of hospitalization severity and demographics (Table 1). We used linear and multivariate regression to evaluate study outcomes, adjusting for gastrointestinal comorbidities, age, and gender. Stata was used for data analysis.

Results: There were 135,860 adult PwCF discharges from hospitals in NIS between 2015 and 2019 and the average length of stay was 8.8 days. 14.0% of discharges included PwCF with comorbid constipation. Of admissions with comorbid constipation, 60.6% were female, mean age was 32.5 and 64.4% had pancreatic insufficiency. After adjustment, constipation was independently associated with increased odds of abdominal pain (aOR 2.3 95% CI: 2.08 - 2.57) and nausea/vomiting (aOR 2.23 95% CI: 2.08 - 2.48) as well as odds of distal intestinal obstructive syndrome (aOR 1.89 95% CI: 1.80 - 1.98), urinary retention (aOR 2.49 95% CI: 2.03 - 3.04), and bowel obstruction (aOR 1.35 95% CI: 1.22 - 1.50) (Table 2). PwCF with constipation had lower odds of death (aOR 0.63 95% CI: 0.50 - 0.79). constipation was independently associated with increased length of stay (10.0 vs.8.6 days SE 0.21) and total charges ($117,417 vs. $103,103 SE 12,308), despite undergoing a similar number of endoscopic procedures (0.14 vs. 0.12 SE 0.009). Increased total charges and length of stay were both independently associated with male gender, decreased age, pancreatic insufficiency, chronic sinusitis, c diff colitis, urban setting, larger hospital and teaching hospital (p<0.01) while gastroesophageal reflux, osteoporosis and overweight/obesity were not.

Discussion: Constipation was present in billing documentation of 14.0% of hospitalizations of PwCF. Comorbid constipation in hospitalized PwCF was independently associated with increased length of stay and costs, as well as increased risk of nausea/vomiting, abdominal pain, distal intestinal obstruction syndrome, urinary retention and bowel obstruction. Further work is required to determine the impact of early recognition and treatment of constipation in hospitalized PwCF.

<b>Table 1. Matched Cohorts of PwCF with and without Constipation</b>. Covariates were not used for matching but were adjusted for with multivariate analysis. Standard deviations depicted in parenthesis next to mean values.

Table 1. Matched Cohorts of PwCF with and without Constipation. Covariates were not used for matching but were adjusted for with multivariate analysis. Standard deviations depicted in parenthesis next to mean values.

<b>Table 2. Multivariate Linear Regression of Outcomes in PwCF and Constipation. </b>Adjusted odds ratios and estimates from multivariate modelling in matched cohorts (matched on income quartile, insurance, race, sepsis, vasopressor use, lung transplant, liver transplant, mechanical ventilation, and CCI (Charleston Comorbidity Index) and adjusting for gender, age, pancreatic insufficiency, GERD, chronic sinusitis, osteoporosis, obesity, overweight, c diff colitis, hospital location, and hospital bed size. *procedures of interest included ERCP, Endoscopy and Colonoscopy.

Table 2. Multivariate Linear Regression of Outcomes in PwCF and Constipation. Adjusted odds ratios and estimates from multivariate modelling in matched cohorts (matched on income quartile, insurance, race, sepsis, vasopressor use, lung transplant, liver transplant, mechanical ventilation, and CCI (Charleston Comorbidity Index) and adjusting for gender, age, pancreatic insufficiency, GERD, chronic sinusitis, osteoporosis, obesity, overweight, c diff colitis, hospital location, and hospital bed size. *procedures of interest included ERCP, Endoscopy and Colonoscopy.

Natale Mazzaferro

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