Pepsin in bronchoalveolar lavage fluid: a specific and sensitive method of diagnosing gastro-oesophageal reflux–related pulmonary aspiration

doi:10.1016/j.jpedsurg.2005.11.002

Journal of Pediatric Surgery

Volume 41, Issue 2, February 2006, Pages 289-293

https://doi.org/10.1016/j.jpedsurg.2005.11.002 Get rights and content

Abstract

Objectives

Gastro-oesophageal reflux (GOR)–related aspiration is associated with respiratory disease, but the current “gold standard” investigation, the lipid-laden macrophage index (LLMI), is flawed. A specific marker of GOR-related aspiration should originate in the stomach, but not the lung. An assay to detect gastric pepsin in the bronchoalveolar lavage (BAL) of children was developed and validated.

Methods

Gastro-oesophageal reflux was diagnosed in 33 children using intra-oesophageal pH monitoring. Thirteen asymptomatic negative controls requiring endotracheal intubation for elective surgery and 5 positive control patients with observed aspiration were recruited. All subjects received a BAL; the fluid obtained was analysed for the pepsin content and the LLMI.

Results

All subjects in the negative control group were negative for pepsin. The positive control group had a significantly greater median pepsin level (P < .01) compared with negative controls. Patients with proximal oesophageal GOR and chronic cough also had significantly elevated pepsin levels (P = .04). The LLMI was not significantly elevated by the presence of cough or GOR.

Conclusions

This study suggests that GOR-related aspiration plays a role in chronic cough in children with known GOR. Detecting pepsin in BAL fluid may therefore become an important adjunct in patient selection for antireflux surgery.

Section snippets

Methods

Three groups of children younger than 14 years were recruited.

1.
Study group—children undergoing general anaesthesia as part of their routine clinical investigations for symptoms of GOR, with or without respiratory symptoms.
2.
Positive control group—children intubated in the paediatric intensive care unit who had a proven macroscopic aspiration event, that is, with milk having been suctioned from the endotracheal tube after nasogastic feeding.
3.
Negative control group—children, with no history of GOR or

Results

Samples from 74 patients (median age, 5.3 years; IQR, 2.1-9.1 years) were assayed and included in the analysis. The overall median pepsin level was 0 ng/mL (IQR, 0-1.5 ng/mL; range, 0-100 ng/mL), and median LLMI score was 14.5 (IQR, 3.7-44.1; range, 0-137). Fifty-six subjects were recruited into the study group, 5 into the positive control group, and 13 into the negative control group. There was no significant difference in proportion of subjects with pepsin detected (P = .82), the median

Discussion

Gastro-oesophageal reflux–associated respiratory disease is a myriad, and proving cause and effect is problematic. Antireflux surgery is now the third most common major operation carried out in the paediatric population, and respiratory disease is the most common indication. A significant problem, however, for paediatric surgeons is patient selection as diagnosing pulmonary aspiration has been notoriously difficult.

Respiratory symptoms associated with GOR represent a “chicken and egg” dilemma.

References (14)

E.W. Fonkalsrud et al.
Antireflux surgery in children under 3 months of age
J Pediatr Surg
(1999)
D.W. Moote et al.
Increase in gastroesophageal reflux during methacholine-induced bronchospasm
J Allergy Clin Immunol
(1986)
E.W. Fonkalsrud et al.
Gastroesophageal reflux in childhood
Curr Probl Surg
(1996)
S.J. Sontag
Gastroesophageal reflux disease and asthma
J Clin Gastroenterol
(2000)
J.P. Buts et al.
Prevalence and treatment of silent gastro-oesophageal reflux in children with recurrent respiratory disorders
Eur J Pediatr
(1986)
G.O. Andze et al.
Diagnosis and treatment of gastroesophageal reflux in 500 children with respiratory symptoms: the value of pH monitoring
J Pediatr Surg
(1991)
L.E. Mansfield et al.
The role of the vague nerve in airway narrowing caused by intraesophageal hydrochloric acid provocation and esophageal distention
Ann Allergy
(1981)

There are more references available in the full text version of this article.

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: Presented at the 52nd Annual Congress of British Association of Paediatric Surgeons, Dublin, Ireland, July 12-15, 2005.

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BAPS PrizePepsin in bronchoalveolar lavage fluid: a specific and sensitive method of diagnosing gastro-oesophageal reflux–related pulmonary aspiration

Abstract

Objectives

Methods

Results

Conclusions

Section snippets

Methods

Results

Discussion

J Pediatr Surg

J Allergy Clin Immunol

Gastroesophageal reflux in childhood

Curr Probl Surg

Gastroesophageal reflux disease and asthma

J Clin Gastroenterol

Prevalence and treatment of silent gastro-oesophageal reflux in children with recurrent respiratory disorders

Eur J Pediatr

Diagnosis and treatment of gastroesophageal reflux in 500 children with respiratory symptoms: the value of pH monitoring

J Pediatr Surg

The role of the vague nerve in airway narrowing caused by intraesophageal hydrochloric acid provocation and esophageal distention

Ann Allergy

BAPS Prize
Pepsin in bronchoalveolar lavage fluid: a specific and sensitive method of diagnosing gastro-oesophageal reflux–related pulmonary aspiration