Fecal calprotectin levels tied to poorer lung function in children

Study findings raise possibility of protein originating in lung inflammation

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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A child draws an image of the digestive system on another's child's torso.

Elevated levels of fecal calprotectin, measured over 1.5 years, significantly associated with poorer lung function in children with cystic fibrosis (CF), a European study reports.

Levels of this protein, a biomarker of intestinal inflammation, also correlated with diarrhea in the young patients.

Findings suggest that fecal calprotectin could originate from lung inflammation in CF, a link that warrants further evaluation ideally using new and specific biomarkers, its researchers noted.

The study, “Long-term evaluation of faecal calprotectin levels in a European cohort of children with cystic fibrosis,” was published in the journal Archives of Disease in Childhood.

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Fecal calprotectin levels are a marker of intestinal inflammation

CF is caused by a faulty or missing CFTR protein that normally transports chloride ions across the cell membrane. Without a functioning CFTR protein, a thick and sticky mucus clogs the airways and digestive tract. Patients often develop exocrine pancreatic insufficiency, characterized by an insufficient release of digestive enzymes from the pancreas, resulting in nutrient malabsorption, particularly of fats.

Intestinal inflammation also is a potential culprit of impaired fat absorption, and previous studies reported higher-than-usual levels of fecal calprotectin — a marker of such inflammation — in people with CF. Calprotectin also is produced in the lungs by immune cells called neutrophils as a result of inflammation.

However, “there is not enough evidence on the relationship between elevated levels of fCP [fecal calprotectin] and intestinal dysfunction,” the scientists wrote.

A team led by researchers in Spain evaluated how fecal calprotectin levels vary over time in CF, and how they relate with clinical parameters, including lung and gastrointestinal health.

They analyzed data from children with CF and pancreatic insufficiency who were part of a large, multicenter European project, called MyCyFAPP, which created a model to estimate optimal doses of pancreatic enzyme replacement therapy.

Children were followed between November 2016 and May 2018, and fecal samples were collected over 24 hours at four timepoints. This period preceded the widespread use of CFTR modulator treatment, the study noted.

In total, samples came from 29 children (15 boys and 14 girls) with a mean age of 8.3 years at the start of follow-up. At the time of each collection, levels of fecal calprotectin, the coefficient of fat absorption (CFA) — a measure of how much fat a person absorbs from food and lung function parameters were evaluated.

Additionally, for the last two collections, gastrointestinal (GI) symptoms were assessed using the Pediatric Quality of Life Inventory Gastrointestinal Symptom (PedsQL-GI) questionnaire. Higher scores indicate a better health-related life quality.

Children’s lung function dropped significantly over study’s 1.5 years

Median fecal calprotectin levels significantly increased from 62 micrograms per gram of stool (mcg/g) at the start of the analysis to 256 mcg/g by the end of follow-up, results showed. These levels always were above the upper limit for normal adults, which is 50 mcg/g, the scientists noted.

Fat absorption, as measured by the CFA, was below the 90% clinical target for the first two timepoints, but significantly increased to 94% at the third, and to 95% at the last assessment.

Lung function, however, significantly declined over the 1.5 years of follow-up, as shown by a lower median forced expiratory volume in one second (FEV1), falling from 97% to 87%. FEV1 measures of how much air can be quickly exhaled after a deep breath.

Statistical analysis showed a significant association between elevated fecal calprotectin and lower lung function.

“It is known that calprotectin is also produced in the context of lung inflammation, a condition characterised by decline in lung function and increased sputum production. If swallowed, sputum calprotectin reaches the intestine and is then excreted in faeces,” the scientists wrote. “Therefore, the [fecal calprotectin] values might relate, at least in part, to calprotectin of pulmonary origin.”

Data from the last two measurements also showed that higher fecal calprotectin levels correlated with a lower total mPedsQL-GI score, and, specifically, with diarrhea. No correlations were seen with a child’s age, sex, or nutritional status.

Findings suggest that fecal calprotectin levels in children with CF “are inversely associated with pulmonary function and thus the specificity of [fecal calprotectin] as a marker of intestinal inflammation in paediatric patients with CF warrants further investigation,” the study concluded.