Exhaled Breath Condensate Purines Correlate With Lung Function In Infants And Preschoolers

Abstract

Rationale-Although airway inflammation begins early in life in children with chronic respiratory diseases, current methods to assess this inflammation are invasive and entail significant risk. Measurement of exhaled breath condensate (EBC) purines and other biomarkers offer a less invasive method to assess airway inflammation; however, the feasibility and utility of EBC biomarkers in young children has not been established.Methods-EBC was collected from children <3 years old with cystic fibrosis or other lung diseases during clinically indicated infant pulmonary function tests (iPFTs). EBC concentrations of the purine biomarkers adenosine, adenosine monophosphate (AMP) and the dilution marker urea were measured using mass spectrometry.Results-EBC was successfully collected (average volume 330±170 μl) from preschool children (age 2.3 ± 0.8 years) in 15 of 17 iPFTs. No significant changes in oxygen saturation (96.9±1.6 start, 96.8±1.7 end, p=0.389) or respiratory rate (35.2±7.5 start, 34.6±7.9 end, p=0.443) were observed during collection. Adenosine and AMP were successfully measured in 13/15 samples (8 CF). EBC AMP to adenosine ratio (AMP/Ado) negatively correlated with forced expiratory volume at 0.5 seconds (FEV 0.5 , r=−0.71, p<0.01) and positively with the ratio of residual volume to total lung capacity (RV/TLC, r=0.66, p=0.015). These correlations remained statistically significant in the subset with CF.Conclusions-EBC can be safely collected and analyzed in preschool children using commercially available equipment. The EBC AMP/Ado ratio correlates with measures of infant lung function and may be a less invasive means of monitoring airway inflammation in this population.

Inflammatory cytokines in exhaled breath condensate in children with inflammatory bowel diseases

“…Although some correlation between lung function and different EBC biomarkers were reported in children with other respiratory diseases (e.g. cystic fibrosis), this was not the case in our group. None of the EBC biomarkers used in our study was related to any measures of lung function.…”

Airway Drug Pharmacokinetics Via Analysis Of Exhaled Breath Condensate

“…EBC collection is simple and non-invasive in human subjects, and we have routinely collected EBC volumes similar to those analyzed in this study from adults and children [10,18] [22]. Furthermore, the mass spectrometric procedure used in this study was based on the method originally developed to analyze EBC from human subjects [11] and used successfully in many studies [10,18,22].…”

Mapping targetable inflammation and outcomes with cystic fibrosis biomarkers

“…EBC pH has also been shown to be decreased in subjects with CF and change with treatment of an exacerbation . With specialized methods, EBC can even be collected from the youngest children during infant pulmonary function testing (iPFTs) …”

“…The changes in metabolite patterns associated with disease reflect cellular enzymatic activities, which are attractive as therapeutic targets since they can often be inhibited by small molecule therapeutics . Furthermore, the identified metabolites can serve as biomarkers of pathway activity and drug effects, many of which can be readily measured using standard methods even in non‐invasive sample such as EBC . The potential metabolomics has been demonstrated in several studies that find CF specific metabolite patterns in sputum, BALF, blood, and even EBC …”