Dataset Information

Determinants of exhaled breath condensate pH in a large population with asthma.

ABSTRACT:

Background

Exhaled breath condensate (EBC) pH is 2 log orders below normal during acute asthma exacerbations and returns to normal with antiinflammatory therapy. However, the determinants of EBC pH, particularly in stable asthma, are poorly understood. We hypothesized that patients with severe asthma would have low EBC pH and that there would be an asthma subpopulation of patients with characteristically low values.

Methods

We studied the association of EBC pH with clinical characteristics in 572 stable subjects enrolled in the Severe Asthma Research Program. These included 250 subjects with severe asthma, 291 with nonsevere asthma, and 31 healthy control subjects.

Results

Overall, EBC in this population of stable, treated study subjects was not lower in severe asthma (8.02; interquartile range [IQR], 7.61-8.41) or nonsevere asthma (7.90; IQR, 7.52-8.20) than in control subjects (7.9; IQR, 7.40-8.20). However, in subjects with asthma the data clustered below and above pH 6.5. Subjects in the subpopulation with pH < 6.5 had lower fraction of exhaled NO (FeNO) values (FeNO = 22.6 ± 18.1 parts per billion) than those with pH ? 6.5 (39.9 ± 40.2 parts per billion; P < .0001). By multiple linear regression, low EBC pH was associated with high BMI, high BAL neutrophil counts, low prebronchodilator FEV(1) ratio, high allergy symptoms, race other than white, and gastroesophageal reflux symptoms.

Conclusion

Asthma is a complex syndrome. Subjects who are not experiencing an exacerbation but have low EBC pH appear to be a unique subpopulation.

SUBMITTER: Liu L

PROVIDER: S-EPMC3032364 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Publications

Determinants of exhaled breath condensate pH in a large population with asthma.

Liu Lei L Teague W Gerald WG Erzurum Serpil S Fitzpatrick Anne A Mantri Sneha S Dweik Raed A RA Bleecker Eugene R ER Meyers Deborah D Busse William W WW Calhoun William J WJ Castro Mario M Chung Kian Fan KF Curran-Everett Douglas D Israel Elliot E Jarjour W Nizar WN Moore Wendy W Peters Stephen P SP Wenzel Sally S Hunt John F JF Gaston Benjamin B

Chest 20101021 2

<h4>Background</h4>Exhaled breath condensate (EBC) pH is 2 log orders below normal during acute asthma exacerbations and returns to normal with antiinflammatory therapy. However, the determinants of EBC pH, particularly in stable asthma, are poorly understood. We hypothesized that patients with severe asthma would have low EBC pH and that there would be an asthma subpopulation of patients with characteristically low values.<h4>Methods</h4>We studied the association of EBC pH with clinical charac ...[more]

PMID: 20966042

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Project description:BackgroundResearchers investigating lung diseases, such as asthma, have questioned whether certain compounds previously reported in exhaled breath condensate (EBC) originate from saliva contamination. Moreover, despite its increasing use in 'omics profiling studies, the constituents of EBC remain largely uncharacterized. The present study aims to define the usefulness of EBC in investigating lung disease by comparing EBC, saliva, and saliva-contaminated EBC using targeted and untargeted mass spectrometry and the potential of metabolite loss from adsorption to EBC sample collection tubes.MethodsLiquid chromatography mass spectrometry (LC-MS) was used to analyze samples from 133 individuals from three different cohorts. Levels of amino acids and eicosanoids, two classes of molecules previously reported in EBC and saliva, were measured using targeted LC-MS. Cohort 1 was used to examine contamination of EBC by saliva. Samples from Cohort 1 consisted of clean EBC, saliva-contaminated EBC, and clean saliva from 13 healthy volunteers; samples were analyzed using untargeted LC-MS. Cohort 2 was used to compare eicosanoid levels from matched EBC and saliva collected from 107 asthmatic subjects. Samples were analyzed using both targeted and untargeted LC-MS. Cohort 3 samples consisted of clean-EBC collected from 13 subjects, including smokers and non-smokers, and were used to independently confirm findings; samples were analyzed using targeted LC-MS, untargeted LC-MS, and proteomics. In addition to human samples, an in-house developed nebulizing system was used to determine the potential for EBC samples to be contaminated by saliva.ResultsOut of the 400 metabolites detected in both EBC and saliva, 77 were specific to EBC; however, EBC samples were concentrated 20-fold to achieve this level of sensitivity. Amino acid concentrations ranged from 196 pg/mL - 4 μg/mL (clean EBC), 1.98 ng/mL - 6 μg/mL (saliva-contaminated EBC), and 13.84 ng/mL - 1256 mg/mL (saliva). Eicosanoid concentration ranges were an order of magnitude lower; 10 pg/mL - 76.5 ng/mL (clean EBC), 10 pg/mL - 898 ng/mL (saliva-contaminated EBC), and 2.54 ng/mL - 272.9 mg/mL (saliva). Although the sample size of the replication cohort (Cohort 3) did not allow for statistical comparisons, two proteins and 19 eicosanoids were detected in smoker vs. non-smoker clean-EBC.ConclusionsWe conclude that metabolites are present and detectable in EBC using LC-MS; however, a large starting volume of sample is required.

Project description:The lung microbiota is commonly sampled using relatively invasive bronchoscopic procedures. Exhaled breath condensate (EBC) collection potentially offers a less invasive alternative for lung microbiota sampling. We compared lung microbiota samples retrieved by protected specimen brushings (PSB) and exhaled breath condensate collection. We also sought to assess whether aerosolized antibiotic treatment would influence the lung microbiota and whether this change could be detected in EBC. EBC was collected from 6 conscious sheep and then from the same anesthetized sheep during mechanical ventilation. Following the latter EBC collection, PSB samples were collected from separate sites within each sheep lung. On the subsequent day, each sheep was then treated with nebulized colistimethate sodium. Two days after nebulization, EBC and PSB samples were again collected. Bacterial DNA was quantified using 16S rRNA gene quantitative PCR. The V2-V3 region of the 16S rRNA gene was amplified by PCR and sequenced using Illumina MiSeq. Quality control and operational taxonomic unit (OTU) clustering were performed with mothur. The EBC samples contained significantly less bacterial DNA than the PSB samples. The EBC samples from anesthetized animals clustered separately by their bacterial community compositions in comparison to the PSB samples, and 37 bacterial OTUs were identified as differentially abundant between the two sample types. Despite only low concentrations of colistin being detected in bronchoalveolar lavage fluid, PSB samples were found to differ by their bacterial compositions before and after colistimethate sodium treatment. Our findings indicate that microbiota in EBC samples and PSB samples are not equivalent.IMPORTANCE Sampling of the lung microbiota usually necessitates performing bronchoscopic procedures that involve a hospital visit for human participants and the use of trained staff. The inconvenience and perceived discomfort of participating in this kind of research may deter healthy volunteers and may not be a safe option for patients with advanced lung disease. This study set out to evaluate a less invasive method for collecting lung microbiota samples by comparing samples taken via protected specimen brushings (PSB) to those taken via exhaled breath condensate (EBC) collection. We found that there was less bacterial DNA in EBC samples compared with that in PSB samples and that there were differences between the bacterial communities in the two sample types. We conclude that while EBC and PSB samples do not produce equivalent microbiota samples, the study of the EBC microbiota may still be of interest.

Dataset Information

Determinants of exhaled breath condensate pH in a large population with asthma.

Background

Methods

Results

Conclusion

Publications

Determinants of exhaled breath condensate pH in a large population with asthma.

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