Fecal Calprotectin Levels May Signal Pulmonary Exacerbations in CF

Levels seen to climb with flares, then drop after systemic antibiotic treatment

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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An illustration of a child's digestive system.

The levels of fecal calprotectin protein increase during pulmonary exacerbations — times when respiratory symptoms suddenly worsen — then drop within two weeks of systemic antibiotic treatment given children and adolescents with cystic fibrosis (CF), a study from Iran reported.

“Fecal calprotectin level could be considered as a diagnostic tool and an index to follow the response to treatment in CF pulmonary exacerbations,” its researchers wrote.

Findings also support a role for gastrointestinal as well as respiratory system inflammation in these exacerbations, they added.

The study, “The association of fecal calprotectin and respiratory exacerbation in cystic fibrosis patients,” was published in the journal BMC Gastroenterology.

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Pulmonary exacerbations can be common in CF. In deciding whether patients should undergo antibiotic treatment following an exacerbation, clinicians often rely on measures of lung function and, increasingly, evidence of intestinal inflammation, the study noted.

Gastrointestinal symptoms — including nutrient malabsorption, obstruction, and insufficient weight gain — are often among a person’s initial CF symptoms. Looking for disease biomarkers in stool, as a result, is gaining interest as a way to evaluate intestinal inflammation.

Calprotectin is a protein mainly produced by neutrophils, cells that act as “first responders” of the immune system. Calprotectin prevents the growth of bacteria and fungi and has a role in inflammatory processes. Research has shown that elevated inflammatory markers in the blood correlate with disease severity, the scientists noted.

Previous studies also reported that CF patients with pancreatic insufficiency — when the pancreas is unable to release digestive enzymes to break down food in the intestines — have high levels of fecal calprotectin. Calprotectin sputum and blood levels also were shown to decline with antibiotic use for acute CF respiratory exacerbations.

“Moreover, it has been claimed that the fecal calprotectin level could be used to assess the effect of new medications on the intestine of CF patients,” the researchers wrote.

A team associated with academic institutes in Tehran conducted a study to measure calprotectin levels in children with CF before and after systemic antibiotic therapy using amikacin plus azithromycin. The children were followed between 2018 and 2020 at two Tehran hospitals; none had gastroenteritis (stomach flu), or evidence of chronic diarrhea or gastrointestinal bleeding.

Stools from 30 CF children (mean age of 11.5, 53.3% boys) were collected at various time points. Patients mostly were between 13 and 18 years old (46.7%), followed by those ages 7 to 12 (36.7%), and children up to 6 years old (16.7%).

Their most prevalent symptoms at a first hospital admission for an exacerbation were cough (80%), increased sputum (60%), and shortness of breath (50%). Cough (36.7%), increased sputum (20%), and sputum discoloration (20%) were the most frequent clinical signs two weeks after antibiotic treatment.

Within 100 days, 15 children relapsed, with common symptoms again including cough (90%), increased sputum (56.7%), and shortness of breath (46.7%).

Mean fecal calprotectin levels before treatment were 651.13 micrograms per gram of stool (mcg/g), dropping to a mean of 171.81 mcg/g two weeks after treatment. Among the 50% of patients with a recurring flare, a significant rise in levels, to a mean of 607.93 mcg/g, was again recorded.

Higher levels reported in girls than boys at first hospitalization

Further statistical analysis showed a significant association between fecal calprotectin levels and sex, with higher levels in girls than boys at their first hospital admission, 900 mcg/g vs. 400 mcg/g. In both groups, fecal calprotectin levels fell after antibiotic treatment.

With disease recurrence, girls showed a more significant increase in calprotectin levels than did boys.

No association between fecal calprotectin levels and patients’ sex or age was reported two weeks after treatment.

At the first hospital visit, fecal calprotectin levels were significantly lower in children between ages 1 and 6 than in older children. But these levels dropped with antibiotic use in all age groups, reaching a mean of 200 mcg/g. The association between calprotectin levels and sex or age at the first visit was statistically significant.

With a flare relapse, older children (ages 13 to 18) showed a more significant increase in calprotectin levels than did those in younger age groups.

“Our findings revealed that fecal calprotectin modifications are associated with CF pulmonary exacerbations and antibiotic treatment could reduce calprotectin levels,” the researchers wrote.

“Alteration of fecal calprotectin levels in individuals with CF upon systemic antibiotic administration reveals that GI inflammation is a part of a systemic response during a pulmonary exacerbation, contributing to understanding the mechanism and therapeutic approaches,” they added. Lower “levels in response to completed systemic antibiotic therapy for respiratory exacerbation shows that inflammation in the GI tract and the respiratory system is affected, presumably through the role of the intestinal microbiome.”

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