Exhaled breath condensate pH in the evaluation of asthma.

As a marker of inflammation, exhaled breath condensate (EBC) pH may be a useful screening tool in the evaluation of asthma, especially in a military recruit population. To evaluate the utility of EBC pH in the diagnosis of asthma, EBC pH levels were determined in basic military trainees prior to an evaluation for asthma that included a history, physical exam, baseline spirometry, and a methacholine or exercise challenge. Of 86 basic trainees who had symptoms suggestive of asthma and underwent methacholine or exercise challenges, 51 (59.3%) had a positive methacholine or exercise challenge and were diagnosed with asthma. The mean EBC pH of the trainees who were diagnosed with asthma (6.39, range 5.91-6.82), was significantly (p < 0.001) lower than those trainees without asthma (6.64, range 6.34-7.18). There was, however, some overlap of the EBC pH values between the two groups. The measurement of EBC pH did show a significant mean difference between asthmatic and nonasthmatic patients in a military recruit population.     

Exhaled breath condensate pH and childhood asthma: unselected birth cohort study

RATIONALE: Exhaled breath condensate pH (EBC-pH) may be useful noninvasive marker for evaluation of patients with asthma. OBJECTIVES: To investigate the relationship between EBC-pH and symptoms suggestive of childhood asthma in an epidemiologic setting and examine its relation to lung function, airway hyperresponsiveness (AHR), and airway inflammation. METHODS: Within the context of a prospective population-based birth cohort, EBC was collected from 630 children at age 8 yr using the RTube (pH measured after deaeration with argon). Lung function was measured by spirometry (FEV1; n = 521) and plethysmography (sRaw; n = 567), and AHR by methacholine challenge (n = 498). Airway inflammation was assessed using exhaled nitric oxide (eNO; n = 305). RESULTS: EBC-pH values ranged widely (4.40-8.29), and did not differ between 54 children with parentally reported asthma and 562 nonasthmatic subjects (median [interquartile range]: 7.75 [7.45-7.85] vs. 7.77 [7.59-7.87]; p = 0.35). There was a trend for lower EBC-pH among current wheezers (n = 98; 7.72 [7.50-7.83]) compared with nonwheezers (n = 532; 7.77 [7.60-7.87]; p = 0.07). Wheeze frequency, severity, and use of antiasthma medication were not associated with EBC-pH. There was no consistent association between EBC-pH and lung function, airway reactivity, and airway inflammation (FEV1, sRaw, PD20 methacholine, or eNO). There was no significant difference in EBC-pH between current wheezers receiving asthma medication who had positive methacholine challenge compared with children without any of these features. CONCLUSIONS: In the epidemiologic setting, EBC-pH does not differ between children with and without parentally reported symptoms suggestive of asthma. We found no consistent association between EBC-pH and lung function, AHR, and airway inflammation in this sample from the general population.     

Exhaled breath condensate nitrite/nitrate and pH in relation to pediatric asthma control and exhaled nitric oxide

BACKGROUND: Combining exhaled breath condensate (EBC) and exhaled nitric oxide (eNO) may be a useful, non-invasive method to assess airway inflammation in pediatric asthma. This cross-sectional study evaluated the relationship of both EBC nitrite/nitrate (NOx) and EBC pH with asthma control and eNO in asthmatic, normal, and atopic children. METHODS: A total of 92 children were recruited, comprising 62 with asthma, 14 with atopy only, and 16 who were normal and non-atopic. All completed a questionnaire for asthma symptoms and control. Variables measured were spirometry, EBC NOx, pH, and eNO. RESULTS: EBC NOx in those with asthma (mean 8.4 microM, CI 7.5-9.4) was significantly elevated when compared with normal (4.8 microM, CI 3.4-6.2, P = 0.0007) and atopic children (6.5 microM, CI 4.0-9.1, P = 0.02). The mean level of eNO was significantly higher in those with asthma (43.7 ppb, CI 34.7-51.1, P < 0.001) and atopy (24 ppb, CI 16.7-31.2, P < 0.05) when compared with normal children (11.5 ppb, CI 6.7-16.2). There was a significantly lower pH in those with asthma and a FEV(1) < 80% predicted (P = 0.03), but no significant overall differences in EBC pH between the three groups of children. There was a significant correlation between eNO and EBC NOx in the group as a whole, but not between eNO and EBC pH. CONCLUSIONS: Mean EBC NOx levels differ between children with asthma, atopy, and those who are normal, but it is not interchangeable with eNO. EBC pH may be an additional marker of asthma control.     

Exhaled breath condensate pH standardised for CO2 partial pressure.

Exhaled breath condensate (EBC) pH is considered to reflect the acid-base balance of the airways. Current pH measurements do not take into account the effect of CO2. The aim of the present study was to determine the effect of condensate CO2 partial pressure on pH and to provide a more precise mode of EBC pH determination. Condensate pH and CO2 partial pressure were measured in parallel from 12 healthy volunteers and 12 asthmatics using a blood gas analyser in neat, argon de-aerated and CO2-loaded samples. The regression analysis was used to test the relationship between pH and CO2, and to calculate the pH at a CO2 level of 5.33 kPa (physiological alveolar CO2 partial pressure). Reproducibility of different pH readings was compared using the Bland-Altman test. Condensate CO2 concentration was variable both in neat and argon de-aerated samples. There was a close negative logarithmic relationship between CO2 and pH. Calculation of pH at a CO2 level of 5.33 kPa provided reproducibility approximately six times as good as that of the currently used measurements. Condensate CO2 partial pressure influences pH measurements. Determination of pH at a standard CO2 level provides the most reproducible condensate pH values to date.     

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.     

Exhaled breath condensate in pulmonary arterial hypertension

Over the last decade, several new agents have been developed for the treatment of pulmonary arterial hypertension (PAH), and blood biomarkers have been developed which aim to monitor such treatment, and which correlate well with physiological parameters, symptoms and mortality. However, little is known regarding biomarkers collected using non-invasive methods such as exhaled breath condensate (EBC). EBC biomarkers show potential as a rapid, repeatable and easy method of sampling the pulmonary vasculature in severely ill patients. The current study aimed to investigate EBC biomarkers in patients with PAH of different aetiologies. We studied 89 patients in four groups: pulmonary arterial hypertension (PAH, n = 30), PAH associated with COPD (COPD/PAH, n = 14), COPD but no PAH (n = 16) and healthy controls (n = 29). Levels of the following EBC markers were measured: amino-terminal pro-brain natriuretic peptide (NT-proBNP), endothelin-1 (ET-1), 6-keto prostaglandin (PG)F(1α), hydrogen peroxide (H(2)O(2)), total oxides of nitrogen (NO(x)), total protein and pH. ET-1 and NT-proBNP were measured in plasma concurrently. Data were analysed with ANOVA or Kruskal Wallis tests where appropriate. Correlations were performed using Pearson's correlation coefficient. NT-proBNP was detectable in EBC and was highest in the PAH group, significantly higher than the COPD/PAH group (194.1 ± 23.3 versus 80.8 ± 22.2 fmol ml(-1), p < 0.05). EBC ET-1 was significantly higher in subjects with PAH (1.53 ± 0.32 fmol ml(-1)) compared to those with COPD/PAH (0.25 ± 0.03 fmol ml(-1), p < 0.05) and controls (0.66 ± 0.18 fmol ml(-1), p < 0.05). 6-keto PGF(1α) was low in the PAH group, significantly lower than the COPD/PAH group (4027 ± 445 versus 8381 ± 1024 pg ml(-1), p < 0.01). EBC biomarkers are measurable in PAH. EBC ET-1 was raised in PAH compared with controls and patients with PAH secondary to COPD, whereas 6-keto PGF(1α) was low. EBC biomarkers may be useful in detection and monitoring of PAH.     

Exhaled breath condensate pH in infants and children with acute and recurrent wheezy bronchitis

The analysis of exhaled breath condensate (EBC) is a promising new method to measure airway inflammation. So far only limited data exist about methodological issues of EBC sampling in infants and young children. We evaluated 18 children with acute wheezy bronchitis (median age 24.3 months (min-max: 4-89.9)), 54 children with recurrent wheezy bronchitis (median age 52.5 months (7.2-94.8)), and 32 healthy controls (median age 49.6 months (25.3-67.8)). EBC was sampled with a modified commercially available EBC-sampler, pH was measured after deaeration. EBC volume was significantly correlated to age (r = 0.56, P < 0.001). EBC pH was significantly decreased in all patients compared to the healthy controls (acute wheezy bronchitis 7.87 (7.16-8.19), P = 0.003, recurrent wheezy bronchitis 7.86 (6.95-8.39), P = 0.002, and healthy controls 8.04 (7.81-8.87), respectively). There were no significant differences of the EBC pH between the disease groups. When divided into different subgroups, an influence of inhaled steroid treatment was found with steroid-naive recurrent wheezers having significantly lower EBC pH levels compared to healthy controls (7.80 (6.95-8.37), P = 0.018), but not so steroid treated (7.94 (7.24-8.39), P = 0.055). Both, recurrent wheezers with or without a positive allergy test had significantly lower EBC pH compared to healthy controls (7.91 (6.95-8.37), P = 0.007 and 7.82 (7.32-8.39), P = 0.005, respectively). This study indicates that EBC can be collected with a modified commercially available EBC sampler in infants and young children. Further studies need to be performed to evaluate the relevance and meaning of pH differences of EBC in this age group.     

Exhaled breath condensate acidification in acute lung injury

Lung injury in ventilated lungs may occur due to local or systemic disease and is usually caused by or accompanied by inflammatory processes. Recently, acidification of exhaled breath condensate pH (EBC-pH) has been suggested as marker of inflammation in airway disease. We investigated pH, ammonia, Lactate, pCO2, HCO3-, IL-6 and IL-8 in EBC of 35 ventilated patients (AECC-classification: ARDS: 15, ALI: 12, no lung injury: 8). EBC-pH was decreased in ventilated patients compared to volunteers (5.85 +/- 0.32 vs. 7.46 +/- 0.48; P < 0.0001). NH4+, lactate, HCO3-, pCO2, IL-6 and IL-8 were analyzed in EBC and correlated with EBC-pH. We observed correlations of EBC-pH with markers of local (EBC IL-6: r = -0.71, P < 0.0001, EBC IL-8: r = -0.68, P < 0.0001) but not of systemic inflammation (serum IL-6, serum IL-8) and with indices of severity of lung injury (Murray's Lung Injury Severity Score; r = -0.73, P < 0.0001, paO2/FiO2; r = 0.54, P < 0.001). Among factors potentially contributing to pH of EBC, EBC-lactate and EBC-NH4+ were found to correlate with EBC-pH. Inflammation-induced disturbances of regulatory mechanisms, such as glutaminase systems may result in EBC acidification. EBC-pH is suggested to represent a marker of acute lung injury caused by or accompanied by pulmonary inflammation.     

呼出气冷凝液检测在呼吸系统疾病中的应用

呼出气冷凝液（ exhaled breath condensate, EBC） 分析是一种新兴的呼吸系统疾病检测手段,通过检测冷凝水中的生化标记物以评价气道炎症或氧化应激水平,由于其具有无创、方便、可重复等特点．被认为具有良好的发展前景。目前EBC检测在慢性阻塞性肺疾病、支气管哮喘、肺癌、间质性肺疾病等多种呼吸系统疾病的诊断、监测及疗效评价中均有相关的研究报道,本文拟对近年来的研究进展作一简要综述。     

Exhaled breath condensate pH is a robust and reproducible assay of airway acidity.

Exhaled breath condensate (EBC) pH is low in several lung diseases and it normalises with therapy. The current study examined factors relevant to EBC pH monitoring. Intraday and intraweek variability were studied in 76 subjects. The pH of EBC collected orally and from isolated lower airways was compared in an additional 32 subjects. Effects of ventilatory pattern (hyperventilation/hypoventilation), airway obstruction after methacholine, temperature (-44 to +13 degrees C) and duration of collection (2-7 min), and duration of sample storage (up to 2 yrs) were examined. All samples were collected with a disposable condensing device, and de-aerated with argon until pH measurement stabilised. Mean EBC pH (n=76 subjects, total samples=741) was 7.7+/-0.49 (mean+/-SD). Mean intraweek and intraday coefficients of variation were 4.5% and 3.5%. Control of EBC pH appears to be at the level of the lower airway. Temperature of collection, duration of collection and storage, acute airway obstruction, subject age, saliva pH, and profound hyperventilation and hypoventilation had no effect on EBC pH. The current authors conclude that in health, exhaled breath condensate pH is slightly alkaline, held in a narrow range, and is controlled by lower airway source fluid. Measurement of exhaled breath condensate pH is a simple, robust, reproducible and relevant marker of disease.     

Exhaled breath condensate analysis in chronic obstructive pulmonary disease

The increasing focus on airway inflammation in the pathogenesis of chronic obstructive pulmonary disease (COPD) has led to development and evolution of tools to measure it. Direct assessment of airway inflammation requires invasive procedures, and hence, has obvious limitations. Non-invasive methods to sample airway secretions and fluids offer exciting prospects. Analysis of exhaled breath condensate (EBC) is rapidly emerging as a novel non-invasive approach for sampling airway epithelial lining fluid and offers a convenient tool to provide biomarkers of inflammation. It has definite advantages that make it an attractive and a feasible option. It is a source of mediators and molecules that are the causes or consequences of the inflammatory process. Measurement of such markers is increasingly being explored for studying airway inflammation qualitatively and quantitatively in research studies and for potential clinical applications. These biomarkers also have the potential to develop into powerful research tools in COPD for identifying various pathways of pathogenesis of COPD that may ultimately provide specific targets for therapeutic intervention. The EBC analysis is still an evolving noninvasive method for monitoring of inflammation and oxidative stress in the airways. The limited number of studies available on EBC analysis in COPD have provided useful information although definite clinical uses are yet to be defined. Evolving technologies of genomics, proteomics, and metabonomics may provide deeper and newer insights into the molecular mechanisms underlying the pathogenesis of COPD.     

Exhaled breath condensate collection in the mechanically ventilated patient

Collection of exhaled breath condensate (EBC) is a non-invasive means of sampling the airway-lining fluid of the lungs. EBC contains numerous measurable mediators, whose analysis could change the management of patients with certain pulmonary diseases. While initially popularized in investigations involving spontaneously breathing patients, an increasing number of studies have been performed using EBC in association with mechanical ventilation. Collection of EBC in mechanically ventilated patients follows basic principles of condensation, but is influenced by multiple factors. Effective collection requires selection of a collection device, adequate minute ventilation, low cooling temperatures, and sampling times of greater than 10?min. Condensate can be contaminated by saliva, which needs to be filtered. Dilution of samples occurs secondary to distilled water in vapors and humidification in the ventilator circuit. Dilution factors may need to be employed when investigating non-volatile biomarkers. Storage and analysis should occur promptly at -70?°C to -80?°C to prevent rapid degradation of samples. The purpose of this review is to examine and describe methodologies and problems of EBC collection in mechanically ventilated patients. A straightforward and safe framework has been established to investigate disease processes in this population, yet technical aspects of EBC collection still exist that prevent clinical practicality of this technology. These include a lack of standardization of procedure and analysis of biomarkers, and of normal reference ranges for mediators in healthy individuals. Once these procedural aspects have been addressed, EBC could serve as a non-invasive alternative to invasive evaluation of lungs in mechanically ventilated patients.     

呼出气冷凝液在慢性阻塞性肺疾病中的研究进展

呼出气冷凝液(exhaled breath condensate,EBC)检测作为一种新的研究肺部疾病的方法,具有无创、简便易行、实时监测、重复性好、患者易耐受等优点.对COPD患者EBC中反映气道炎症、氧化应激状态的生物标记物进行研究有助于COPD的诊断及对药物治疗反应的评估和患者预后的评价.而且EBC中异常炎症介质的研究可能为COPD发病机制开启新思路并发现新的治疗靶点.