Breath Condensate pH in Children With Cystic Fibrosis and Asthma: A New Noninvasive Marker of Airway Inflammation?

doi:10.1378/chest.125.6.2005

Chest

Volume 125, Issue 6, June 2004, Pages 2005-2010

https://doi.org/10.1378/chest.125.6.2005 Get rights and content

Study objectives

The noninvasive assessment and monitoring of airway inflammation could be important in respiratory disease. The pH of exhaled breath condensate (EBC) is a promising marker. Although pH has been measured in the EBC of adults with inflammatory airway diseases, no study has measured this in children.

Design

This study aimed to assess whether there is a change in pH in the EBC of children with cystic fibrosis (CF) and asthma, and to try to determine whether pH could be used as a marker of airway inflammation. Furthermore, the relationships among EBC pH, severity of disease, and oxidative stress were studied.

Patients and methods

We studied 20 children with CF (mean [± SEM] age, 7 ± 3 years), 20 children with asthma (mean age, 7 ± 2 years), and 15 age-matched healthy children (mean age, 7 ± 2 years). The pH of EBC was measured using a pH meter.

Measurements and results

Lower pH values were observed in the EBC of children with CF and asthma compared to control subjects (mean pH, 7.23 ± 0.03 and 7.42 ± 0.01 vs 7.85 ± 0.02, respectively). Furthermore, relationships among EBC pH, severity of asthma, and the presence of an infective exacerbation of CF was found. There was a negative correlation between exhaled pH and exhaled leukotriene B₄ concentrations (r = −0.5; p < 0.005).

Conclusion

We conclude that the measurement of EBC pH may be useful in the evaluation of airway inflammation in children with asthma and CF.

Section snippets

Patients

We studied 20 children with CF (11 male children; mean [± SEM] age, 7 ± 3 years; mean FEV₁, 61 ± 2.4%; mean FVC, 73 ± 2.2%), 20 children with asthma (10 male children; mean age, 7 ± 2 years; mean FEV₁, 69.3 ± 4.2%; and mean FVC, 78.4 ± 2.7%), and 15 healthy children (6 male children; mean age, 7 ± 2 years; mean FEV₁, 102.2 ± 1.8%; mean FVC, 104.1 ± 2.3%) without any history of acute or chronic respiratory symptoms. All of the patients underwent a full history and physical examination. Both

EBC pH

EBC pH was lower in CF children than in healthy control subjects (7.23 ± 0.03 vs 7.85 ± 0.02, respectively; p < 0.0001) [Fig 1, top, A]. The EBC pH of CF patients with an exacerbation was significantly lower than that of stable patients with CF (7.12 ± 0.02 vs 7.31 ± 0.01, respectively; p < 0.0001) [Fig 1, middle, B]. EBC pH was lower in children with asthma compared to healthy control subjects (7.42 ± 0.01 vs 7.85 ± 0.02, respectively; p < 0.0001) [Fig 1, top, A]. A lower pH was observed in

DISCUSSION

The main findings of this study were the existence of a lower EBC pH in children with CF compared with that in asthmatic children. Both groups had a lower EBC pH than did control subjects. EBC LTB₄ and 8-isoprostane concentrations were higher in CF and asthmatic children compared with healthy control subjects. Furthermore, EBC pH and LTB₄ levels were related to the severity of asthma and the presence of an exacerbation of CF. There was no correlation among EBC pH, 8-isoprostane level, and lung

ACKNOWLEDGMENT

Dr. Carpagnano gratefully acknowledges Professor P. Capezzuto for his expert technical assistance.

References (30)

GE Carpagnano et al.
Increased 8-isoprostane and interleukin-6 in breath condensate of obstructive sleep apnea patients
Chest
(2002)
K McRae et al.
Detection of IL-10 in the exhaled breath condensate, plasma and tissue during ischemia-reperfusion injury in experimental lung transplantation [abstract]
J Heart Lung Transplant
(2001)
J Rees et al.
ABC of asthma
(1996)
E Osika et al.
Distinct sputum cytokine profiles in cystic fibrosis and other chronic inflammatory airway disease
Eur Respir J
(1999)
Q Jobsis et al.
Hydrogen peroxide and nitric oxide in exhaled air of children with cystic fibrosis during antibiotic treatment
Eur Respir J
(2000)
SA Kharitonov et al.
Exhaled markers of inflammation
Curr Opin Allergy Clin Immunol
(2001)
B Balint et al.
Increased nitrotyrosine in exhaled breath condensate in cystic fibrosis
Eur Respir J
(2001)
M Corradi et al.
Increased nitrosothiols in exhaled breath condensate in inflammatory airway diseases
Am J Respir Crit Care Med
(2001)
LP Ho et al.
Nitrite levels in breath condensate of patients with cystic fibrosis is elevated in contrast to exhaled nitric oxide
Thorax
(1998)
Z Csoma et al.
Increased leukotrienes in exhaled breath condensate in childhood asthma
Am J Respir Crit Care Med
(2002)

L Scheiderler et al.

Detection of non-volatile macromolecules in breath: a possible diagnostic tool?

Am Rev Respir Dis

(1993)

S Cunningham et al.

Measurement of inflammatory markers in the breath condensate of children with cystic fibrosis

Eur Respir J

(2000)

K Kostikas et al.

PH in Expired breath condensate of patients with inflammatory airway diseases

Am J Respir Crit Care Med

(2002)

Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease (COPD) and asthma

Am Rev Respir Dis

(1987)

National Asthma Education and Prevention Program

Expert panel report 2: guidelines for the diagnosis and management of asthma

(1997)

Cited by (112)

Electrochemical sensing: A prognostic tool in the fight against COVID-19
2021, TrAC - Trends in Analytical Chemistry
The COVID-19 pandemic has devastated the world, despite all efforts in infection control and treatment/vaccine development. Hospitals are currently overcrowded, with health statuses of patients often being hard to gauge. Therefore, methods for determining infection severity need to be developed so that high-risk patients can be prioritized, resources can be efficiently distributed, and fatalities can be prevented. Electrochemical prognostic biosensing of various biomarkers may hold promise in solving these problems as they are low-cost and provide timely results. Therefore, we have reviewed the literature and extracted the most promising biomarkers along with their most favourable electrochemical sensors. The biomarkers discussed in this paper are C-reactive protein (CRP), interleukins (ILs), tumour necrosis factor alpha (TNFα), interferons (IFNs), glutamate, breath pH, lymphocytes, platelets, neutrophils and D-dimer. Metabolic syndrome is also discussed as comorbidity for COVID-19 patients, as it increases infection severity and raises chances of becoming infected. Cannabinoids, especially cannabidiol (CBD), are discussed as a potential adjunct therapy for COVID-19 as their medicinal properties may be desirable in minimizing the neurodegenerative or severe inflammatory damage caused by severe COVID-19 infection. Currently, hospitals are struggling to provide adequate care; thus, point-of-care electrochemical sensor development needs to be prioritized to provide an approximate prognosis for hospital patients. During and following the immediate aftermath of the pandemic, electrochemical sensors can also be integrated into wearable and portable devices to help patients monitor recovery while returning to their daily lives. Beyond the COVID-19 pandemic, these sensors will also prove useful for monitoring inflammation-based diseases such as cancer and cardiovascular disease.
Exhaled Breath Condensate pH Does Not Discriminate Asymptomatic Gastroesophageal Reflux or the Response to Lansoprazole Treatment in Children with Poorly Controlled Asthma
2014, Journal of Allergy and Clinical Immunology: In Practice
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 matrix metalloproteinase-9 (MMP-9) in different biological phenotypes of asthma
2014, European Journal of Internal Medicine
Citation Excerpt :
An increasing interest has been recently generated among non-invasive methods sampling airways by the collection of breath condensate, a sample coming from airways and produced from the condensation of epithelial lining fluid [24]. The breath condensate, which has widely been used for the biological study of several lung conditions, including asthma, is often suggested and resorted to in clinical settings [24]. Notwithstanding several advantages of the breath condensate linked to its non-invasiveness that allow its applicability also during exacerbations and severe forms of asthma, to our knowledge this is the first work where the EBC has been used in the study of airway remodeling.
Airway remodeling is a main feature of asthma. Different biological phenotypes of severe asthma have been recently recognized by the ENFUMOSA study group and among these one is characterized by neutrophilic airway inflammation. Concentrations of MMP-9 in airways have been suggested as a marker to monitor airway remodeling in asthma.
The aim of the present study was to explore airway remodeling in different biological phenotypes of asthma by measuring MMP-9 in EBC and correlating these with other variables.
Sixty consecutive subjects with asthma and 20 healthy controls were enrolled in the study. Exhaled MMP-9, pH and NO levels and inflammatory cells in sputum were measured in all subjects enrolled.
We observed an increase of exhaled MMP-9 in asthmatic subjects compared to controls. Higher exhaled MMP-9 concentrations were described in severe asthmatics compared to mild to moderate especially in those with neutrophilic airway inflammation. We further found a correlation between exhaled MMP-9 and percentage of neutrophils in sputum, FEV_1, exhaled NO and pH.
Our results seem to substantiate the feasibility of measuring exhaled MMP-9 in the breath of asthmatic patients. MMP-9 may be considered a proxy of the amount of the ongoing airway remodeling in asthma. MMP-9 has been shown to be differentially released in different phenotypes of asthma. The measure of exhaled MMP-9 could help to monitor the ongoing airway remodeling, recognize severe stages of asthma, and possibly help determine the appropriate choice of therapy.
Detection of respiratory inflammation biomarkers in non-processed exhaled breath condensate samples using reduced graphene oxide
2022, RSC Advances
A pilot study of total personal exposure to volatile organic compounds among Hispanic female domestic cleaners
2022, Journal of Occupational and Environmental Hygiene
Exhaled breath condensate—a non-invasive approach for diagnostic methods in asthma
2021, Journal of Clinical Medicine

View all citing articles on Scopus

: Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail: [email protected]).

View full text

Chest

Clinical InvestigationsAsthmaBreath Condensate pH in Children With Cystic Fibrosis and Asthma: A New Noninvasive Marker of Airway Inflammation?

Study objectives

Design

Patients and methods

Measurements and results

Conclusion

Section snippets

Patients

EBC pH

DISCUSSION

ACKNOWLEDGMENT

Chest

J Heart Lung Transplant

ABC of asthma

Distinct sputum cytokine profiles in cystic fibrosis and other chronic inflammatory airway disease

Eur Respir J

Hydrogen peroxide and nitric oxide in exhaled air of children with cystic fibrosis during antibiotic treatment

Eur Respir J

Exhaled markers of inflammation

Curr Opin Allergy Clin Immunol

Increased nitrotyrosine in exhaled breath condensate in cystic fibrosis

Eur Respir J

Increased nitrosothiols in exhaled breath condensate in inflammatory airway diseases

Am J Respir Crit Care Med

Nitrite levels in breath condensate of patients with cystic fibrosis is elevated in contrast to exhaled nitric oxide

Thorax

Increased leukotrienes in exhaled breath condensate in childhood asthma

Am J Respir Crit Care Med

Detection of non-volatile macromolecules in breath: a possible diagnostic tool?

Am Rev Respir Dis

Measurement of inflammatory markers in the breath condensate of children with cystic fibrosis

Eur Respir J

PH in Expired breath condensate of patients with inflammatory airway diseases

Am J Respir Crit Care Med

Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease (COPD) and asthma

Am Rev Respir Dis

National Asthma Education and Prevention Program

Expert panel report 2: guidelines for the diagnosis and management of asthma

Clinical Investigations
Asthma
Breath Condensate pH in Children With Cystic Fibrosis and Asthma: A New Noninvasive Marker of Airway Inflammation?