Fecal Calprotectin and Phenotype Severity in Patients with Cystic Fibrosis: A Systematic Review and Meta-Analysis

Abstract

Inflammation plays an important role in the outcome of patients with cystic fibrosis (CF). It may develop due to cystic fibrosis transmembrane conductance regulator protein dysfunction, pancreatic insufficiency, or prolonged pulmonary infection. Fecal calprotectin (FC) has been used as a noninvasive method to detect inflammation. Therefore, the aim of the current meta-analysis was to investigate the relationship between FC and phenotype severity in patients with CF. In this study, searches were conducted in PubMed, Science Direct, Scopus, and Embase databases up to August 2021 using terms such as “cystic fibrosis,” “intestine,” “calprotectin,” and “inflammation.” Only articles published in English and human studies were selected. The primary outcome was the level of FC in patients with CF. The secondary outcome was the relationship between FC and clinical severity. Statistical analysis was performed using Comprehensive Meta-Analysis software. Of the initial 303 references, only six articles met the inclusion criteria. The mean (95% confidence interval [CI]) level of FC was 256.5 mg/dL (114.1-398.9). FC levels were significantly associated with pancreatic insufficiency (mean, 243.02; 95% CI, 74.3 to 411.6; p =0.005; I 2 =0), pulmonary function (r=–0.39; 95% CI, –0.58 to –0.15; p =0.002; I 2 =60%), body mass index (r=–0.514; 95% CI, 0.26 to 0.69; p <0.001; I 2 =0%), and Pseudomonas colonization (mean, 174.77; 95% CI, 12.5 to 337.02; p =0.035; I 2 =71%). While FC is a reliable noninvasive marker for detecting gastrointestinal inflammation, it is also correlated with the severity of the disease in patients with CF.

Fecal calprotectin in pediatric gastrointestinal diseases: Pros and cons

“…Additionally, fecal calprotectin levels have been found to correlate with markers of nutritional status and pancreatic function, suggesting a link between intestinal inflammation and malnutrition in cystic fibrosis. A meta-analysis by Talebi et al [ 142 ] found that median fecal calprotectin levels were inversely associated with body mass index (BMI) and BMI Z score, reflecting the nutritional status of the patients. However, Adriaanse et al [ 143 ] found this negative correlation in adult patients and not in children.…”

“…However, Adriaanse et al [ 143 ] found this negative correlation in adult patients and not in children. Studies have shown that fecal calprotectin levels are higher in patients with cystic fibrosis and pancreatic insufficiency, indicating a potential association between pancreatic status and intestinal inflammation[ 27 , 142 ]. However, studies also observed increased fecal calprotectin in children with or without pancreatic insufficiency.…”

Probiotics Administration in Cystic Fibrosis: What Is the Evidence?

“…Moreover, gut inflammation seems to influence CF severity, including risk of lung infection and progressive deterioration. In a systematic review of studies regarding fecal calprotectin and phenotype severity in CF patients, Talebi et al reported that there were significant correlations between fecal calprotectin and the factors that characterize a more severe CF phenotype, including colonization by P. aeruginosa , predicted FEV1 <50%, pancreatic insufficiency, and underweight status [ 68 ]. Moreover, reduced gut microbiota diversity has been found associated with lower FEV1 values [ 23 ] and increased risk of pulmonary exacerbations [ 25 ].…”

The NHE3 Inhibitor Tenapanor Prevents Intestinal Obstructions in CFTR-Deleted Mice

“…A recent survey revealed a high rate of abdominal complaints with a likely origin in the lower gut in CF patients not suffering from recurrent DIOS episodes [ 6 ]. Other studies demonstrated a correlation between abdominal symptoms and an increase in inflammatory markers in the stool [ 7 , 8 ], undermining the hypothesis derived from CF animal models that inflammation, secondary to bacterial overgrowth, predisposes to obstructive episodes, disease severity, and abdominal complications [ 9 , 10 , 11 ]. However, this hypothesis has not been validated in animal models or CF patients.…”