Decreased Fecal Calprotectin Levels in Cystic Fibrosis Patients After Antibiotic Treatment For Respiratory Exacerbation
Decreased Fecal Calprotectin Levels in Cystic Fibrosis Patients After Antibiotic Treatment For Respiratory Exacerbation
Decreased Fecal Calprotectin Levels in Cystic Fibrosis Patients After Antibiotic Treatment For Respiratory Exacerbation
Respiratory Exacerbation
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ABSTRACT
serum calprotectin levels decreased during antibiotic treatment of TABLE 2. Fecal calprotectin, forced expiratory volume in 1 second,
acute pulmonary exacerbations (6,7). and body mass index parameters
The aim of this study was to assess CF patients’ GI inflam-
matory burden as expressed by FC levels before and after systemic Start of treatment End of treatment P
antibiotic treatment for respiratory exacerbation.
FC mean mg/g (range) 421.14 (21–3550) 102.50 (6–627) 0.004
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2017 and December 31, 2017. The study enrolled 14 patients older
than 1 year with CF who were admitted to Carmel Medical Center’s DISCUSSION
Pediatric Department for systemic antibiotic treatment for an acute CF is a multisystem disease with an increased incidence of
respiratory exacerbation. Patients with GI symptoms were GI tract inflammation. The typical triad of mucus stasis, infection,
excluded. The study protocol was approved by the institutional and inflammation occurs in both intestine and respiratory tract.
review board and written consent was obtained from all the adult CFTR gene is highly expressed in the GI tract and other than the
patients and guardians of children and adolescents. basic genetic defect, chronic use of antibiotics and pancreatic
enzymes, altered bowel motility, and gut microbiome have also
Collection of Stool Samples, Procedures, been associated with intestinal inflammation (3,8).
and Definitions As shown by Parisi et al (5) baseline levels of FC are higher
in PI CF patients without respiratory exacerbation. Our study
Stool sample were collected from each of the 14 patients showed that use of systemic antibiotics for treating respiratory
during their hospitalization within the first 24 hours of admission exacerbation was associated with decreased FC levels as compared
and at day 10 to 14 of treatment. Quantification of FC was to pretreatment values.
performed by DiaSorin Liaison and FC levels were expressed in Despite the unknown baseline FC levels, we observed
mg/g (normal FC level is <50 mg/g). decline in FC suggests that treating inflammation in one system
Spirometry was performed in the pulmonary physiology (respiratory) may induce changes within another (GI). CF pulmo-
laboratory. Values of forced expiratory volume in 1 second nary exacerbation may represent part of a systemic inflammatory
(FEV1.0) were expressed as percentage of predicted normal values exacerbation which includes the GI tract, even with no GI com-
when adjusted for age, gender, sex, height, and weight. plaints, possibly representing ‘‘silent’’ GI inflammation. Antibiotic
treatment may alter the microbiome in both organs reducing the
inflammatory burden.
Statistical Analysis Calprotectin can be measured in several body fluids (eg,
Statistical analyses were performed using IBM statistics sputum and blood), and its level in stool may be partially due to
(SPSS) version 22. Wilcoxon sign rank test was used to test swallowed respiratory secretions. We, however, like Adriaanse et al
correlation between FC and other variables. A P value of <0.05 (8), think sputum levels do not grossly change FC levels, most
was considered to be significant. logically because sputum calprotectin protein is being partially
degraded in the GI tract.
The observed decrease in FC levels after 10 to 14 days of
RESULTS antibiotic treatment may result from various possible mechanisms:
First, CF gut dysmotility can be influenced by the prokinetic
Subjects’ Characteristics properties of certain antimicrobial agents (such as erythromycin)
The baseline characteristics of the study subjects are sum- and thus antibiotic treatment of these patients helped promote GI
marized in Table 1. motility thus lowering the inflammatory burden.
Second, small intestinal bacterial overgrowth, a disease state
Fecal Calprotectin and Spirometric Tests in which the bacterial burden in the small intestine exceeds 106
colony-forming units/1 mL in intestinal sampled fluid (9) may
Pretreatment FC levels declined significantly between the contribute to dysmotility. Studies in germ-free rats demonstrated
onset of antibiotic therapy and the second measurement at day 10 to faster small bowel transit compared to those with typical microbial
14 of treatment. Similarly, there was a significant improvement in flora. Intestinal transit through the small bowel was increased or
FEV1.0 between therapy onset and day 10 to 14 of therapy decreased by colonization of the bowel with specific bacterial
(Table 2). species (10). Escherichia coli, which is overabundant in young
children with CF, has been shown to impede intestinal motility (11).
In addition to the unique niche formed by static mucus in the
CF intestine, other factors contribute to microbial dysbiosis in CF
TABLE 1. Patient and sample characteristics for cystic fibrosis patients such as the need for periodic courses of antibiotics in addition to
Median age (y) at time of sample collection, median (range) 25.5 (6–44)
chronic antibacterial therapy to combat airway infection. Even
Sex (m/f) 6/8
when administered by inhalation, significant amounts of antibiotics
Ethnic origin
will be ingested and thus also affect the GI tract flora (12).
Jewish 4
Herein we conclude that dysbiosis, dysmotility, and small
Arabic (Muslim/Christian) 10 (9/1)
intestinal bacterial overgrowth are interconnected and may be
Age of diagnosis, mo, median (range) 9 (0–72)
modified by antimicrobial agents. In this study, patients were
Pancreatic insufficiency, n (%) 14 (100)
treated with systemic courses of different antibiotics for 10 to 14
days. Although the type of antibiotic varied between patients, they
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were mostly broad spectrum antimicrobial agents. Such treatments 2. Farrell PMP, Rosenstein BJB, White TTB, et al. Guidelines for diag-
most likely contribute to differences in gut flora. nosis of cystic fibrosis in newborns through older adults: cystic fibrosis
The study has several limitations including the small number foundation consensus report. J Pediatr 2008;153:S4–14.
of patients, use of different antibiotic regimens, and lack of baseline 3. Werlin SL, Benuri-Silbiger I, Kerem E, et al. Evidence of intestinal
FC levels. Microbiome analysis, which might have provided further inflammation in patients with cystic fibrosis. J Pediatr Gastroenterol
support for our ‘‘changed flora’’ hypothesis, was not performed. Nutr 2010;51:304–8.
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