Low Exhaled Breath Condensate pH Research Articles

Exhaled breath condensate pH determinants in school-aged children: A population-based study.

Exhaled breath condensate (EBC) pH is a promising biomarker of airway inflammation. Lack of method standardization and interstudy variability precludes its use in clinical practice. While endogenous determinants have been described, underlying mechanisms for variability are mostly unknown. Thus, we aimed to assess the association between asthma and EBC pH in children, while studying potential environmental factors for interstudy variability. A cross-sectional analysis of exhaled breath condensates from 613 children, aged 7-12years, was conducted. Assessments included lung function and airway reversibility, exhaled nitric oxide, allergic sensitization, and body mass index (BMI). Indoor air quality (IAQ) was assessed in children's classrooms during 5school days. Post-deaeration EBC pH showed a bimodal distribution, and the sample was split into acidic and alkaline groups. Regression models were constructed to assess the effects of asthma and asthma adjusted to IAQ parameters on EBC pH. Following adjustment to gender and BMI, asthma was significantly associated with a lower EBC pH in the acidic group. The effect of asthma on EBC pH was independent of IAQ, in both groups. In the acidic group, EBC pH was significantly affected by temperature [β=-0.09 (-0.15, -0.02)] and PM 2.5 concentration [β=-0.16 (-0.32, -0.01)], and in the alkaline group by relative humidity [β=0.07 (0.02, 0.13)] and concentration of endotoxins [β=-0.06 (-0.1, -0.01)]. Our study shows that in addition to individual determinants such as asthma, environmental factors may influence and should be taken into consideration when interpreting EBC pH level in children.

Valor pronóstico del pH en el condensado de aire exhalado y de la fracción exhalada de óxido nítrico en la enfermedad pulmonar intersticial asociada a esclerosis sistémica

IntroductionInterstitial lung disease (ILD) is one of the major causes of death in systemic sclerosis (SSc). This study investigated exhaled breath (EB) and exhaled breath condensate (EBC) biomarkers in patients with SSc and analyzed their role as a prognostic tool in SSc-related ILD. MethodsFraction exhaled nitric oxide (FeNO) and exhaled carbon monoxide (eCO) measured in EB, together with pH, nitrite, nitrate and interleukin-6 levels measured in EBC were prospectively analyzed in 35 patients with SSc. Twelve patients had established ILD by chest high-resolution computed tomography (HRCT), and 23 patients showed no evidence of ILD. EB and EBC biomarkers were determined at inclusion, and pulmonary function tests were annually performed during 4 years of follow-up. ResultsNo differences at baseline biomarkers levels were found between groups. In all patients studied, low EBC pH levels were associated with a decreased diffusing capacity for carbon monoxide (DLCO) during follow-up. Low FeNO levels were correlated with lower forced vital capacity (FVC) at baseline, 4years of follow-up and with a decrease in FVC and DLCO during monitoring. Among ILD patients, high eCO levels were correlated with lower baseline FVC. In the global cohort, a worse progression-free survival was identified in patients with EBC pH values lower than 7.88 and FeNO levels lower than 10.75ppb (Log Rank P=.03 and P<.01, respectively). ConclusionsEB and EBC could help to detect patients likely to present a deterioration on lung function during follow up.

Prognostic Role of Exhaled Breath Condensate pH and Fraction Exhaled Nitric Oxide in Systemic Sclerosis Related Interstitial Lung Disease

IntroductionInterstitial lung disease (ILD) is one of the major causes of death in systemic sclerosis (SSc). This study investigated exhaled breath (EB) and exhaled breath condensate (EBC) biomarkers in patients with SSc and analyzed their role as a prognostic tool in SSc-related ILD. MethodsFraction exhaled nitric oxide (FeNO) and exhaled carbon monoxide (eCO) measured in EB, together with pH, nitrite, nitrate and interleukin-6 levels measured in EBC were prospectively analyzed in 35 patients with SSc. Twelve patients had established ILD by chest high-resolution computed tomography (HRCT), and 23 patients showed no evidence of ILD. EB and EBC biomarkers were determined at inclusion, and pulmonary function tests were annually performed during 4 years of follow-up. ResultsNo differences at baseline biomarkers levels were found between groups. In all patients studied, low EBC pH levels were associated with a decreased diffusing capacity for carbon monoxide (DLCO) during follow-up. Low FeNO levels were correlated with lower forced vital capacity (FVC) at baseline, 4 years of follow-up and with a decrease in FVC and DLCO during monitoring. Among ILD patients, high eCO levels were correlated with lower baseline FVC. In the global cohort, a worse progression-free survival was identified in patients with EBC pH values lower than 7.88 and FeNO levels lower than 10.75ppb (log Rank P=0.03 and P<0.01, respectively). ConclusionsEB and EBC could help to detect patients likely to present a deterioration on lung function during follow up.

Exhaled Breath Condensate pH in Lung Cancer, the Impact of Clinical Factors.

Lung cancer may be associated with airway acidification due to enhanced airway inflammation and oxidative stress. Exhaled breath condensate (EBC) pH is a non-invasive indicator of airway acidity; however, it is still unclear how EBC pH changes in lung cancer. The aim of the study was to investigate EBC pH in lung cancer together with clinical variables. Thirty-five patients with lung cancer and 37 control subjects (21 patients with stable COPD and 16 non-COPD smokers) were enrolled. EBC was collected for pH, which was determined with the argon-purging method, compared among the groups and correlated with clinical variables of patients with lung cancer. No difference was found in EBC pH between patients with lung cancer and control subjects. However, endobronchial tumour localisation, squamous-cell carcinoma subtype and gastro-oesophageal reflux were associated with low EBC pH values. No relationship was observed between EBC pH and the presence of COPD, lung function variables or smoking history. Although, EBC pH is unchanged in lung cancer, lower EBC pH values are associated with distinct phenotypes. Our findings could facilitate further research on airway acidity in lung cancer.

Markers of Inflammation in the Breath in Paediatric Inflammatory Bowel Disease

Breath analysis and exhaled breath condensate (EBC) collection are simple and noninvasive processes whereby inflammatory mediators and other biomarkers can be assessed in diseases that affect the lung. It was hypothesised that markers of epithelial dysfunction and secretion, such as a low pH, 8-isoprostane, and release of epithelial factors such as trefoil factor 2 (TFF2) and mucin, would be elevated in the breath of those with inflammatory bowel disease (IBD). The aim was to compare the levels of these biomarkers in EBC and the fraction of expired nitric oxide (FENO) in children with Crohn disease (CD), in those with asthma, and in normal individuals in a pilot study. EBC was collected from patients in the 3 groups mentioned above in a cross-sectional design. pH, 8-isoprostane, TFF2, and mucin levels were measured in the EBC. Spirometry was performed in asthmatic patients and patients with IBD, whereas FENO and skin prick tests were performed in patients with IBD. Breath samples including EBC were collected from 80 patients (30 CD, 30 asthma, 20 controls). Compared with controls, EBC pH was lower in children with IBD (P < 0.0001) or asthma (P = 0.0041). 8-Isoprostane levels differed between the 3 groups (P < 0.05). EBC TFF2 was mainly less than the limit of detection, whereas mucin levels did not differ significantly between the 3 groups. FENO was measurable in children with IBD, but did not correlate with disease activity or serum markers of inflammation. A lower EBC pH may reflect inflammatory events either in the lung or systemically. 8-Isoprostane, FENO, and mucin were detected for the first time in the EBC of children with IBD. Further studies are required to assess the value of these assessments.

Exhaled Breath Condensate pH Does Not Discriminate Asymptomatic Gastroesophageal Reflux or the Response to Lansoprazole Treatment in Children with Poorly Controlled Asthma

Although exhaled breath condensate (EBC) pH has been identified as an "emerging" biomarker of interest for asthma clinical trials, the clinical determinants of EBC pH remain poorly understood. Other studies have associated acid reflux-induced respiratory symptoms, for example, cough, with transient acidification of EBC. We sought to determine the clinical and physiologic correlates of EBC acidification in a highly characterized sample of children with poorly controlled asthma. We hypothesized that (1) children with asymptomatic gastroesophageal reflux determined by 24-hour esophageal pH monitoring would have a lower EBC pH than children without gastroesophageal reflux, (2) treatment with lansoprazole would alter EBC pH in those children, and (3) EBC acidification would be associated with increased asthma symptoms, poorer asthma control and quality of life, and increased formation of breath nitrogen oxides (NOx). A total of 110 children, age range 6 to 17 years, with poor asthma control and esophageal pH data enrolled in the Study of Acid Reflux in Children with Asthma (NCT00442013) were included. Children submitted EBC samples for pH and NOx measurement at randomization and at study weeks 8, 16, and 24. Serial EBC pH measurements failed to distinguish asymptomatic gastroesophageal reflux and was not associated with breath NOx formation. EBC pH also did not discriminate asthma characteristics such as medication and health care utilization, pulmonary function, and asthma control and quality of life both at baseline and across the study period. Despite the relative ease of EBC collection, EBC pH as a biomarker does not provide useful information of children with asthma who were enrolled in asthma clinical trials.

Exhaled Breath Condensate Ph Is Correlated With Post-exercise Small Airway Obstruction

PURPOSE: It has been shown that individuals with asthma and exercise-induced bronchoconstriction (EIB) exhibit lower exhaled breath condensate (EBC) pH values than healthy individuals. The purpose of this study was to determine if EBC pH was correlated with the degree of airway obstruction following a bronchial hyperresponsiveness challenge. METHODS: Twenty three subjects [15 asthmatics subjects with EIB, as determined by a post-EVH drop of ≥ 10% in FEV1; 8 control subjects (no-asthma/no EIB)] were asked to breathe normally at rest for 10 min wearing a nose clip while their exhaled breath was collected (EcoScreen, Jager, Hoechberg, Germany). The pH of the condensate was measured immediately following collection. Subsequently subjects underwent a eucapnic voluntary hyperventilation (EVH) challenge. The EVH challenge required each subject to hyperventilate for 6 min at a ventilation calculated as 30 × the volume of baseline FEV1, while breathing a gas mixture containing 5% CO2, 21% O2, and balance N2. Pulmonary function was measured pre-EVH and post-EVH at 5, 10, 15, and 20 min. RESULTS: The EBC pH was significantly (p<0.05) lower in the subjects that exhibited EIB (6.83±0.43) as compared to those who did not (7.37±0.32). The EBC pH was not significantly correlated to the post-EVH drop in FEV1 (r=0.048, p=0.827). However, EBC pH was found to be significantly inversely correlated to post challenge drop in FEF25-75% (r=0.579, p=0.004). CONCLUSION: Exhaled breath condensate pH was significantly lower in subjects who exhibit EIB than in healthy control individuals, which may indicate acidification of the airways in individuals with airway hyperresponsiveness. The pH was also inversely related with the post-EVH drop in FEF25-75% indicating that the lower EBC pH in the airways may be indicative of heightened reactivity in the small airways.

Normative values for exhaled breath condensate pH and its relationship to exhaled nitric oxide in healthy African Americans

Exhaled breath condensate (EBC) pH and exhaled nitric oxide (FeNO) have been proposed as markers of asthma severity. EBC pH values below 6.5 have been associated with asthma exacerbations. Protonation of airway nitrite occurs at low pH and may contribute to FeNO. To establish normative EBC pH values and to determine the contribution of EBC pH to FeNO in healthy African Americans. Two hundred seventy healthy African American subjects without asthma between 18 and 40 years old were evaluated. Subjects had simultaneous measurement of EBC pH, EBC nitrite, nitrate, and FeNO. The median EBC pH was 8.14 (interquartile range, 7.83-8.28). Of subjects, 11.9% had an EBC pH < or = 6.5. In subjects with EBC pH values below 6.5, there was an inverse correlation between EBC pH and FeNO (r(2) = 0.158; P = .0245; n = 32). In the entire cohort, there was a direct correlation between EBC pH and EBC nitrite (r(2) = 0.163; P < .0001), but there was no correlation between EBC nitrite and FeNO. In multivariate analyses, EBC pH and nitrite did not contribute significantly to FeNO variation while controlling for other confounders of FeNO. There was an increased prevalence (11.9%) of low EBC pH (less than 6.5) in healthy African American subjects compared with white subjects (<5%). EBC pH and nitrite were directly correlated, but there was no correlation between EBC nitrite and FeNO. FeNO correlated with EBC pH at pH values less than 6.5 in univariate but not multivariate analyses. This suggests that EBC pH and nitrite are not significant determinants of FeNO in healthy subjects.

Healthy African Americans have an Increased Prevalence of Low Exhaled Breath Condensate pH values

Exhaled Breath Condensate (EBC) pH values are used as a marker of disease activity in asthma and other inflammatory conditions. Previous reports of mixed ethnicity cohorts cohorts have shown that only 3-5% of healthy subjects have an EBC pH <6.5.

Long-term repeatability of exhaled breath condensate pH in asthma

Exhaled breath condensate (EBC) is being used increasingly to sample airway fluid. EBC pH may be a biomarker of airway inflammation in asthma. In this study, we assessed the long-term reproducibility of EBC pH in asthma. We examined 31 asthmatic patients and eight healthy subjects three times over a 1-year period (winter, autumn and summer). EBC pH was measured after argon deaeration. Repeatability of pH measurements was assessed using intraclass correlation coefficients (ICC) and the limits of agreement (LOA) between seasons were calculated according to Bland-Altman method. No significant differences in EBC pH between seasons were detected in healthy subjects and asthmatic patients. EBC pH showed high repeatability either in healthy subjects (ICC=0.94) or in asthmatics (ICC=0.97). Variability between seasons was greater in asthmatics than in healthy subjects: winter-autumn LOA -0.68/+0.52 and -0.31/+0.31, autumn-summer LOA -0.75/+0.67 and -0.24/+0.15, winter-summer LOA -0.92/+0.67 and -0.34/+0.23 in asthmatic and healthy subjects, respectively. In a subgroup of 11 asthmatics who remained in stable conditions during the study, no substantially different LOA were observed in EBC pH compared with the whole group of asthmatics. Asthmatic smokers (n=10) tended to have lower EBC pH (7.57+/-0.46) than asthmatic non-smokers (n=21) (7.74+/-0.21; p=0.063) and wider LOA. In conclusion, we demonstrated that EBC pH exhibits good repeatability in long-term assessment. EBC pH in asthmatics tended to fluctuate more than in healthy subjects. However, EBC pH variability in asthma was not influenced by changes in clinical status. Rather, we suggest that cigarette smoke may be implicated in EBC pH variability.

Identification of acid reflux cough using serial assays of exhaled breath condensate pH

BackgroundChronic cough is a common problem, frequently caused or exacerbated by acid reflux. Diagnosis of acid reflux cough is haphazard currently, often relying on long therapeutic trials of expensive medications. We tested the hypothesis that the most relevant mechanistic component of acid reflux in chronic cough is when it rises to the level of the airway where acid can potentially be aspirated. We further wished to determine if multi-sample exhaled breath condensate (EBC) pH profiles can identify chronic cough patients likely to respond to proton pump inhibitor therapy.Methods59 subjects were recruited for this study. Initially we examined EBC pH (gas-standardized with Argon) in the setting of 15 experimental pharyngeal acid challenges to determine duration of EBC acidification. Subsequently, we enrolled 22 healthy subjects to determine a normal multi-sample exhaled breath condensate pH profile over 1–3 days. We additionally obtained multi-sample EBC pH profiles in 22 patients with chronic cough. These samples were timed to occur after coughing episodes. Exhaled breath condensate pH was measured after gas standardization.ResultsWe found that exhaled breath condensate pH is substantially reduced for approximately 15 minutes after pharyngeal acid load. Healthy subjects rarely have any low EBC pH values (defined as < 7.4 based on a normative reference range from 404 healthy subjects). Patients with chronic cough who subsequently responded well to proton pump inhibition (n = 8) invariably had one or more cough episodes associated with EBC acidification. No patient who had normal EBC pH with each of their cough episodes reported a clinically relevant response to proton-pump inhibition.ConclusionPatients whose cough responds to proton pump inhibition have transient exhaled breath condensate acidification with coughing episodes, supporting the role of airway acidification in reflux-triggered cough. Multi-sample EBC pH profiles, involving samples collected immediately subsequent to a coughing episode, may be useful appropriately to direct therapy to those patients with cough who have relevant acid reflux.