Direct assessment of gastrointestinal inflammation and mucosal immunity in children with cystic fibrosis.
Fibrosing colonopathy is a recently described complication of cystic fibrosis, of unknown aetiology but possibly related to treatment with high-dose pancreatic enzyme supplements. We have used a whole gut perfusion technique to study subclinical gut inflammation in cystic fibrosis patients; concentrations of haemoglobin, IgG, albumin, alpha-1-antitrypsin, granulocyte elastase, IL1 beta, and IL8 were measured in whole gut lavage fluid: 23 tests were performed in 17 children with cystic fibrosis (20 elective tests, three lavages to treat distal intestinal obstruction syndrome (DIOS)). None has had fibrosing or haemorrhagic colitis. There were 12 tests in control children with constipation or precolonoscopy. Moderately abnormal results were obtained for many of the parameters studied, in specimens from all the cystic fibrosis children; however there were no significant differences between tests on high-dose and low-dose enzyme supplements of the same brand in the five children who had duplicate tests performed electively. The lavage fluid specimens from two cystic fibrosis children were strikingly abnormal in all tests apart from haemoglobin and alpha-1-antitrypsin. These were two of the three children with DIOS, and were also the only cases in the series taking Nutrizym 22. These data suggest that the majority of cystic fibrosis children, including those on high-dose enzyme supplements, do not have clinically significant colitis, but that there is subclinical mucosal inflammation in a minority (two of 17 in this series), for which DIOS and/or Nutrizym 22 treatment may be risk factors. Alternatively, inflammation and dysmotility in the proximal colon may be directly produced by a drug or other agent, producing a clinical syndrome indistinguishable from DIOS. Tests for indices of inflammation in gut lavage fluid offer a new approach to the detection and measurement of iatrogenic intestinal and colonic injury.
Croft
N M
NM
Gastrointestinal Unit, University of Edinburgh, UK.
Marshall
T G
TG
Ferguson
A
A
D000293:Adolescent; D000418:Albumins / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D003092:Colitis / Q000209:etiology / Q000276:immunology; D003550:Cystic Fibrosis / Q000150:complications* / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005767:Gastrointestinal Diseases / Q000209:etiology* / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007415:Intestinal Obstruction / Q000209:etiology / Q000276:immunology; D008297:Male; D009504:Neutrophils / Q000473:pathology; D010194:Pancreatin / Q000009:adverse effects* / Q000627:therapeutic use; D007507:Therapeutic Irrigation; D000515:alpha 1-Antitrypsin / Q000032:analysis
D000418:Albumins; D016207:Cytokines; D007074:Immunoglobulin G; D000515:alpha 1-Antitrypsin; D010194:Pancreatin