Exhaled air temperature in asthma: methods and relationship with markers of disease

BACKGROUND: Exhaled breath temperature has been proposed as a surrogate marker for the evaluation of airway inflammation in asthmatic patients. OBJECTIVE: The aim of the present study was to extend the investigation of exhaled air temperature as a means for the evaluation of airway inflammation using a professionally developed instrument. METHODS: Fifty-seven children, 41 allergic mild asthmatics and 16 healthy controls have been evaluated. They underwent exhaled air temperature and lung function measurement. The asthmatic children also underwent exhaled nitric oxide measurement, and hypertonic saline sputum induction for the evaluation of eosinophil (EOS) percentage. RESULTS: The level of exhaled temperature was significantly higher in asthmatics than in controls, being 30.18+/-0.14 degrees C vs. 27.47+/-0.24 degrees C (P<0.001). In asthmatic children, a positive relationship was observed between exhaled air temperature and both exhaled nitric oxide (r=0.39; P=0.01) and EOS percentage in samples from induced sputum (rho=0.53; P=0.04). CONCLUSION: The data from the present study support the hypotheses that exhaled breath temperature is related to the degree of airway inflammation in asthma.     

Effects of a leukotriene receptor antagonist on exhaled leukotriene E4 and prostanoids in children with asthma

BACKGROUND: Leukotriene (LT) E(4) and 8-isoprostane concentrations are elevated in exhaled breath condensate in children with asthma. The effects of leukotriene receptor antagonists (LTRAs) on exhaled leukotriene and prostanoids in children with asthma are unknown. OBJECTIVE: (1) To study the effect of montelukast, a LTRA, on exhaled LTE(4), 8-isoprostane, and prostaglandin E(2) in children with asthma and atopic children; (2) to measure exhaled nitric oxide. METHODS: An open-label study with oral montelukast (5 mg once daily for 4 weeks) was undertaken in 17 atopic children with asthma and 16 atopic children without asthma. RESULTS: Pretreatment exhaled LTE(4) (P < .0001) and 8-isoprostane (P < .0001) values were higher in atopic children with asthma than in atopic children without asthma. In atopic children with asthma, montelukast reduced exhaled LTE(4) by 33% (P < .001), and this reduction was correlated with pretreatment LTE(4) values (r = -0.90; P = .0001). Posttreatment exhaled LTE(4) levels in children with asthma were higher than pretreatment LTE(4) values in atopic children without asthma (P < .004). Montelukast had no effect on exhaled LTE(4) in atopic children without asthma (P = .74), or on exhaled 8-isoprostane (atopic children with asthma, P = .94; atopic children without asthma, P = .55) and PGE(2) (atopic children with asthma, P = .56; atopic children without asthma, P = .93) in both groups. In atopic children with asthma, exhaled nitric oxide concentrations were reduced by 27% (P < .05) after montelukast. CONCLUSION: Leukotriene receptor antagonists decrease exhaled LTE(4) in atopic children with asthma. This reduction is dependent on baseline exhaled LTE(4) values. CLINICAL IMPLICATIONS: Measurement of exhaled LTE(4) might help identify children with asthma most likely to benefit from LTRAs.     

The effect of allergic rhinitis on adenosine concentration in exhaled breath condensate

BACKGROUND: Patients with allergic rhinitis (AR) frequently develop asthma. This initiating inflammation in the lower airways may result in increased levels of inflammatory mediators such as adenosine in the exhaled breath. OBJECTIVE: We compared adenosine levels in exhaled breath condensate (EBC) and both exhaled and nasal nitric oxide (NO) levels of AR patients and healthy control subjects. We also tested whether inhalation through inflamed nasal cavity during EBC sampling influences adenosine concentrations in exhaled air. METHODS: Exhaled and nasal NO levels were measured and EBC samples (at oral inhalation) were collected from 27 patients and 15 healthy controls. EBC collection was repeated after 15 min with subjects inhaling through their nose. Adenosine was measured by HPLC and NO was determined by chemiluminescence. RESULTS: The concentration of EBC adenosine was higher in patients with AR than in healthy controls (12.4+/-1.3 nM vs. 6.5+/-0.7 nM, P=0.0019) and this was accompanied by an increase in the concentration of exhaled NO (10.2+/-1.3 ppb vs. 5.3+/-0.5 ppb; P=0.0099, respectively). No difference in nasal NO was detected. EBC adenosine concentration showed a significant positive correlation with the level of exhaled NO. In contrast to healthy control subjects, patients with rhinitis had higher levels of exhaled adenosine when inhaling via the nose instead of the mouth (17.7+/-2.8 nM, P=0.007). CONCLUSION: When compared with healthy subjects, patients with AR exhibit an increased concentration of exhaled adenosine and a related increase in exhaled NO concentration. EBC adenosine is further increased when rhinitis patients inhale through their nose than via their mouth. Our data suggest that non-asthmatic patients with rhinitis may have subclinical inflammation in their lower airways.     

Pediatric biomarkers in asthma: exhaled nitric oxide, sputum eosinophils and leukotriene E4

PURPOSE OF REVIEW: Markers of disease status that provide a numerical measure of disease activity, biomarkers, have come into more routine use in medicine. This is evidenced by troponin and brain natriuretic peptide when measuring cardiac function or glomerular filtration rate in relation to kidney function. Similar markers to assess inflammation in the asthmatic lung have emerged as possible tools to guide treatment. Three biomarkers, fractional exhaled nitric oxide, sputum eosinophils and leukotriene E4 in the urine and exhaled breath condensate, have been heavily investigated. RECENT FINDINGS: Recent literature indicates that exhaled nitric oxide, sputum eosinophils and leukotriene E4 in the urine, and exhaled breath condensate could serve as good markers of inflammation in the asthmatic airway. These markers, when combined with conventional measures of lung function--forced expiratory flow in 1 s, peak flow or methacholine challenge--will be of benefit in improving asthma control in the pediatric population. SUMMARY: Exhaled nitric oxide and urinary leukotriene E4 are relatively easy to attain in the clinical setting. Sputum eosinophils are an excellent tool for assessing inflammation, however sputum induction can be challenging for a young child. Despite small limitations, all three biomarkers are potentially valuable when used in conjunction with conventional methods for airway control.     

Analysis of growth factors and inflammatory cytokines in exhaled breath condensate from asthmatic children

BACKGROUND: Vascular endothelial growth factor (VEGF), AA isoform of platelet-derived growth factor (PDGF-AA), and epidermal growth factor (EGF) are involved in the pathogenesis of airway inflammation in asthma. These molecules are closely associated with cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-4. This study investigates the relation between childhood asthma and levels of these mediators in exhaled breath condensate (EBC). METHODS: EBC was collected from asthmatic children and controls using a disposable collection kit, and the concentrations of VEGF, PDGF-AA, EGF, TNF-alpha and IL-4 in EBC were measured using sandwich enzyme immunoassays. Exhaled nitric oxide concentration was measured by a chemiluminescence analyzer. RESULTS: Thirty-five asthmatic patients aged between 7 and 18 years and 11 controls were recruited. Sixteen patients had intermittent asthma (IA) whereas 19 of them suffered from persistent asthma (PA). A significant correlation was found between IL-4 and TNF-alpha in EBC (rho = 0.374, p = 0.010). PDGF-AA levels in EBC were higher in subjects with diminished FEV1 (p = 0.023) whereas IL-4 concentrations were increased in asthmatics (p = 0.007) as well as subjects with increased plasma total IgE (p = 0.033). Patients with PA receiving high-dose inhaled corticosteroid (ICS) had higher EBC IL-4 concentration than those on low-dose ICS (p = 0.007). Linear regression revealed that PDGF-AA levels in EBC were negatively associated with FEV1 percentage (beta = -0.459, p = 0.006) among the asthmatic patients. CONCLUSIONS: IL-4 in EBC is increased in childhood asthma, and growth factors are detectable in a significant proportion of these children. Increased PDGF-AA is found in asthmatics with more severe airflow limitation.     

Effects of inhaled corticosteroids on exhaled leukotrienes and prostanoids in asthmatic children

BACKGROUND: Lipid mediators play an important pathophysiologic role in atopic asthmatic children, but their role in the airways of atopic nonasthmatic children is unknown. OBJECTIVE: We sought (1) to measure leukotriene (LT) E 4 , LTB 4 , 8-isoprostane, prostaglandin E 2 , and thromboxane B 2 concentrations in exhaled breath condensate in atopic asthmatic and atopic nonasthmatic children; (2) to measure exhaled nitric oxide (NO) as an independent marker of airway inflammation; and (3) to study the effect of inhaled corticosteroids on exhaled eicosanoids. METHODS: Twenty healthy children, 20 atopic nonasthmatic children, 30 steroid-naive atopic asthmatic children, and 25 atopic asthmatic children receiving inhaled corticosteroids were included in a cross-sectional study. An open-label study with inhaled fluticasone (100 microg twice a day for 4 weeks) was undertaken in 14 steroid-naive atopic asthmatic children. RESULTS: Compared with control subjects, exhaled LTE 4 ( P <.001), LTB 4 ( P <.001), and 8-isoprostane ( P <.001) levels were increased in both steroid-naive and steroid-treated atopic asthmatic children but not in atopic nonasthmatic children (LTE 4 , P=.14; LTB 4 , P=.23; and 8-isoprostane, P=.52). Exhaled NO levels were increased in steroid-naive atopic asthmatic children ( P <.001) and, to a lesser extent, in atopic nonasthmatic children ( P <.01). Inhaled fluticasone reduced exhaled NO (53%, P <.0001) and, to a lesser extent, LTE 4 (18%, P <.01) levels but not LTB 4 , prostaglandin E 2 , or 8-isoprostane levels in steroid-naive asthmatic children. Conclusions Exhaled LTE 4 , LTB 4 , and 8-isoprostane levels are increased in atopic asthmatic children but not in atopic nonasthmatic children. In contrast to exhaled NO, these markers seem to be relatively resistant to inhaled corticosteroids.     

Acid-base equilibrium in exhaled breath condensate of allergic asthmatic children

BACKGROUND: The dysregulation of airway pH control may have a role in asthma pathophysiology. The measurement of exhaled breath condensate (EBC) pH and ammonia levels may be used as a noninvasive method to study acid-base status in the airway of asthmatics. METHODS: Exhaled breath condensate from 29 allergic stable asthmatic children and 13 healthy controls was collected by cooling exhaled air during tidal breathing. Ammonia was measured by high-performance liquid chromatography with fluorescence detection. pH was measured after deaeration of EBC samples by bubbling with argon. The children also underwent FENO measurement. RESULTS: Both pH and ammonia values in EBC were significantly lower in the asthmatics than in the control group [pH: ICS-treated (median and interquartile range) 7.70 (7.62-7.74), steroid-naive 7.53 (7.41-7.68), controls 7.85 (7.80-7.90), P <0.01 and P <0.001, respectively; ammonia: ICS-treated 476.17 microM (282.50-594.80), steroid-naive 253.24 microM (173.43-416.08), controls 788.30 microM (587.29-1310.39), P < 0.05 and P <0.001, respectively]. Both pH and ammonia values were higher in ICS-treated than in steroid-naive asthmatic children. There was a significant correlation between EBC pH and ammonia concentrations. CONCLUSIONS: These data show that EBC pH values of stable asthmatic children are lower compared with those of healthy controls and positively correlated with ammonia concentrations, supporting the hypothesis that airway acidification may have a role in the pathobiology of allergic asthma.     

Inflammatory mediators in exhaled breath, induced sputum and saliva

BACKGROUND AND OBJECTIVE: Airway inflammation is assessed to monitor progression, control and treatment of asthma. The collection of exhaled breath condensate (EBC) provides a non-invasive alternative to induced sputum samples for the monitoring of airway inflammation. Both samples can be confounded by salivary contamination. The aim of this study was to compare the levels of inflammatory mediators in samples of EBC, induced sputum and saliva samples from subjects with asthma. METHOD: EBC, saliva and induced sputum samples were collected from subjects with asthma (n=10). Total protein, IL-8, 8-isoprostane and surfactant protein A (SPA) were assessed in each sample. RESULTS: Total protein, IL-8, 8-isoprostane and SPA were detected in all sputum samples. Only total protein and SPA were consistently measured in EBC, with levels at least 100-fold lower than those measured in induced sputum. In saliva, total protein, SPA and 8-isoprostane were detected in all samples, with IL-8 detected in 60% of samples. CONCLUSIONS: Induced sputum is a reliable technique that can be used to assess markers of airway inflammation. While EBC is a simple and inexpensive technique to collect lower airway secretions, the detection of inflammatory mediators is variable, and further work is required to validate this technique to assess inflammatory mediators.     

Exhaled monoxides in asymptomatic atopic subjects

BACKGROUND: Atopy is a genetically determined condition and some atopic people develop airway hyperresponsiveness and sometimes asthma later in life. Since airway inflammation may be present before the onset of clinical symptoms of asthma, early and noninvasive detection of inflammation would be useful in atopic subjects. Mediators produced by activated inflammatory cells may lead to induction of inducible nitric oxide synthase producing nitric oxide (NO) and inducible heme oxygenase releasing carbon monoxide (CO) in the airways. Both monoxides are present in exhaled air and their levels are elevated in asthma reflecting airway inflammation. OBJECTIVE: We have measured exhaled NO and CO levels in atopic and nonatopic healthy non-smoking subjects to determine whether inflammation is present in the airways. METHODS: Exhaled NO was measured by a chemiluminescence analyser and exhaled CO electrochemically and NO in asymptomatic atopic and age-matched nonatopic normal subjects. RESULTS: Exhaled NO and CO levels were both significantly elevated in 15 atopic subjects compared with 40 nonatopic individuals (means +/- SEM: 18.3+/-3.0 p.p.b. vs. 6.3+/-0.3 p.p.b., P< 0.0001 and 4.7+/-0.3 p.p.m. vs 2.8+/-0.2 p.p.m., P = 0.0005, respectively). CONCLUSION: Increase in exhaled monoxide levels may be an early and noninvasive marker of airway inflammation in asymptomatic atopic subjects.     

Cytokines in exhaled breath condensate of children with asthma and cystic fibrosis.

BACKGROUND: Inflammatory mediators in exhaled breath condensate (EBC) indicate ongoing inflammation in the lungs and might differentiate between asthma and cystic fibrosis (CF). OBJECTIVES: To evaluate the presence, concentration, and short-term variability of TH1- and TH2-mediated cytokines (interferon-gamma [IFN-gamma], tumor necrosis factor alpha [TNF-alpha], interleukin 10 [IL-10], IL-5, IL-4, and IL-2) in EBC of children with asthma or CF and in controls and to analyze the discriminating ability of inflammatory markers in EBC between children with asthma or CF and controls. METHODS: Expired air was conducted through a double-jacketed glass tube cooled by circulating ice water. In 33 asthmatic children, 12 children with CF, and 35 control children, EBC was collected during tidal breathing. Cytokines were measured using flow cytometry. RESULTS: Interleukin 2, IL-4, IFN-gamma, and IL-10 were detected in 16%, 16%, 11%, and 9%, respectively, of all samples in asthma and CF. Interleukin 5 and TNF-alpha were not detected in children with CF. Cytokine concentrations did not differ significantly in children with asthma vs CF. In controls, IFN-gamma, TNF-alpha, and IL-10 were detected in 9%, 14%, and 3%, respectively; IL-2, IL-4, and IL-5 were not detected in controls. CONCLUSIONS: Cytokines such as IFN-gamma, TNF-alpha, IL-10, IL-5, IL-4, and IL-2 can be detected in EBC of children with asthma or CF. However, the concentrations found are close to the detection limits of the assay used. These findings emphasize the importance of developing more sensitive techniques for the analysis of EBC and of standardizing the EBC collection method.     

Relationships between adult asthma and oxidative stress markers and pH in exhaled breath condensate: a systematic review

Oxidative stress has a recognized role in the pathophysiology of asthma. Recently, interest has increased in the assessment of pH and airway oxidative stress markers. Collection of exhaled breath condensate (EBC) and quantification of biomarkers in breath samples can potentially indicate lung disease activity and help in the study of airway inflammation, and asthma severity. Levels of oxidative stress markers in the EBC have been systematically evaluated in children with asthma; however, there is no such systematic review conducted for adult asthma. A systematic review of oxidative stress markers measured in EBC of adult asthma was conducted, and studies were identified by searching MEDLINE and SCOPUS databases. Sixteen papers met the inclusion criteria. Concentrations of exhaled hydrogen ions, nitric oxide products, hydrogen peroxide and 8‐isoprostanes were generally elevated and related to lower lung function tests in adults with asthma compared to healthy subjects. Assessment of EBC markers may be a noninvasive approach to evaluate airway inflammation, exacerbations, and disease severity of asthma, and to monitor the effectiveness of anti‐inflammatory treatment regimens. Longitudinal studies, using standardized analytical techniques for EBC collection, are required to establish reference values for the interpretation of EBC markers in the context of asthma.     

Exhaled nitric oxide levels correlate with measures of disease control in asthma

BACKGROUND: Asthma guidelines emphasize maintaining disease control. However, objective measures of asthma disease control are lacking. OBJECTIVE: We sought to examine the relationship between exhaled nitric oxide (NO) levels and measures of asthma disease control versus asthma disease severity. METHODS: We performed a cross-sectional study of 100 patients (age range, 7-80 years) with asthma. We administered a questionnaire to identify characteristics of asthma, performed spirometric testing before and after administration of a bronchodilator, and measured exhaled NO levels in all participants. RESULTS: Exhaled NO was significantly correlated with the following markers of asthma disease control: asthma symptoms within the past 2 weeks (P =.02), dyspnea score (P =. 02), daily use of rescue medications (P =.01), and reversibility of airflow obstruction (P =.02). Exhaled NO levels were not correlated with the following markers of asthma disease severity: history of respiratory failure (P =.20), health care use (P =.08), fixed airflow obstruction (P =.91), or a validated asthma severity score (P =.19). Markers with relevance to both disease control and severity showed either a weak correlation (FEV(1) and FEV(1) percent predicted) or no correlation (controller drug use) with exhaled NO. CONCLUSION: We conclude that exhaled NO levels are correlated predominantly with markers of asthma control rather than asthma severity. Monitoring of exhaled NO may be useful in outpatient asthma management.     

3-Nitrotyrosine, a marker of nitrosative stress, is increased in breath condensate of allergic asthmatic children

BACKGROUND: Asthmatic patients have high exhaled nitric oxide (NO) levels. NO-mediated inflammatory actions are mainly due to NO conversion into reactive nitrogen species, which can lead to nitrotyrosine formation. The aim of this study was to assess 3-nitrotyrosine (3-NT) levels in exhaled breath condensate (EBC) of asthmatic and healthy children and to investigate whether there is any relationship with exhaled NO (FE(NO)) and lung function. METHODS: The study included 20 asthmatic children (10 steroid-naive with intermittent asthma, 10 steroid-treated with unstable persistent asthma) and 18 healthy controls. They underwent FE(NO) measurement, EBC collection and spirometry. 3-NT was measured by a new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method in isotopic dilution. RESULTS: The median EBC concentration of 3-NT (expressed as nitrotyrosine/tyrosine ratio x 100) in asthmatic children was fivefold higher than in healthy subjects [0.23% (0.12-0.32) vs 0.04% (0.02-0.06), P < 0.001] with no difference between steroid-naive and unstable steroid-treated asthmatic patients. FE(NO) levels were higher in asthmatic [44.6 ppb (36.0-66.0)] than in healthy children [7.5 ppb (6.0-8.8), P < 0.001]. No correlation was found among 3-NT, FE(NO) and lung function parameters. CONCLUSION: Nitrotyrosine is high in EBC of asthmatic children and could be considered as a noninvasive marker of nitrosative events in the airways.     

Exhaled bronchial cysteinyl leukotrienes in allergic patients

PURPOSE OF REVIEW: To review the current knowledge of noninvasive monitoring of allergic airway inflammation by analysis of leukotrienes in the exhaled breath condensate. RECENT FINDINGS: Treatment of respiratory allergies involves chronic treatment based on clinical symptoms and pulmonary function tests. Evaluation of local inflammation would be desirable but is currently not feasible because of the difficulty in sampling the airways. Recently, exhaled breath condensate collection and analysis has polarized much interest in the respiratory field. Although some methodological issues are still under scrutiny, airways inflammatory markers can be assayed with this technique. In particular, exhaled breath condensate leukotrienes have been thoroughly investigated in the setting of bronchial asthma and allergic rhinitis in adults and children. Exhaled leukotrienes are increased in patients with asthma and rhinitis during the pollen season, correlate with exacerbations and asthma severity, and are reduced by specific anti-inflammatory treatment and allergen avoidance. SUMMARY: Some issues still prevent the use of exhaled breath condensate in clinical practice but in the research setting it has been proved to be useful for noninvasive monitoring of allergic inflammation in the lung. In particular, exhaled leukotrienes may represent valuable biomarkers for diagnostic and therapeutic purposes in allergic patients.     

Both inflammation and remodeling influence nitric oxide output in children with refractory asthma

BACKGROUND: Exhaled nitric oxide can be used to monitor airway inflammation in asthma. We hypothesized that the strong link between nitric oxide and inflammation may obscure a weaker link with airway remodeling. OBJECTIVE: The aim of this study was to determine whether airway remodeling influenced exhaled nitric oxide in 28 asthmatic children (median age [25th-75th], 11 [10-14] years old) with refractory asthma defined as airflow limitation and/or exacerbations despite high-dose inhaled steroids. METHODS: Multiple-flow analysis of exhaled nitric oxide was used to correlate alveolar nitric oxide concentration and maximal conducting airway nitric oxide output to pulmonary function tests, bronchoalveolar lavage, and bronchial biopsy findings. RESULTS: Nitric oxide measurements were related to inflammation and T(H)1/T(H)2 balance, that is, subepithelial eosinophilic infiltration and eosinophilic cationic protein and IFN-gamma/IL-4 ratio in bronchoalveolar lavage fluids. Nitric oxide measurements were also correlated with several parameters of airway remodeling: alveolar nitric oxide concentration with TGF-beta in bronchoalveolar lavage fluid (r = 0.42, P =.03) and maximal conducting airway nitric oxide output with reticular basement membrane thickness (r = 0.61, P =.0007) and tissue inhibitor of matrix metalloproteinases 1/matrix metalloproteinase 9 ratio in bronchoalveolar lavage fluid (r = 0.43, P =.04). Moreover, alveolar nitric oxide concentration was correlated with MEF(25-75) (r = 0.60, P =.02). CONCLUSIONS: These findings suggest that both subacute inflammation and remodeling influence nitric oxide output in refractory asthma.     

Exhaled leukotrienes and prostaglandins in asthma

BACKGROUND: Most of the studies investigating the role of leukotrienes (LTs) and prostaglandins (PGs) in asthma have used invasive (eg, bronchoalveolar lavage fluid) or semi-invasive (eg, sputum induction) techniques. Others have measured eicosanoids in plasma or urine, probably reflecting systemic rather than lung inflammation. Collection of exhaled breath condensate (EBC) is a noninvasive method to collect airway secretions. OBJECTIVE: We sought to investigate whether eicosanoids are measurable in EBC, to show possible differences in their concentrations in asthmatic patients and healthy subjects, and to investigate whether exhaled eicosanoids correlate with exhaled nitric oxide (NO), a marker of airway inflammation. METHODS: Twelve healthy nonsmokers and 15 steroid-naive patients with mild asthma were studied. Subjects attended on one occasion for pulmonary function tests, collection of EBC, and exhaled NO measurements. Exhaled LTB(4)-like immunoreactivity, LTE(4)-like immunoreactivity, PGE(2)-like immunoreactivity, PGD(2)-methoxime, PGF(2)(alpha)-like immunoreactivity, and thromboxane B(2)-like immunoreactivity were measured by means of enzyme immunoassays. RESULTS: LTE(4)-like immunoreactivity and LTB(4)-like immunoreactivity were detectable in EBC in healthy subjects, and their levels in asthmatic patients were increased about 3-fold (P <.0001) and 2-fold (P <.0005), respectively. Exhaled NO was increased in asthmatic patients compared with healthy subjects (P <.0001). There was a correlation between exhaled LTB(4) and exhaled NO (r = 0.56, P <.04) in patients with asthma. When measurable, prostanoid levels were similar in asthmatic patients and control subjects. CONCLUSIONS: Exhaled LTE(4) and LTB(4) are increased in steroid-naive patients with mild asthma. EBC may be proved to be a novel method to monitor airway inflammation in asthma.     

Exhaled markers of inflammation

Exhaled markers of inflammation allow completely noninvasive monitoring of inflammation and oxidative stress in the respiratory tract in inflammatory lung diseases, including asthma, chronic obstructive pulmonary disease, cystic fibrosis, bronchiectasis and interstitial lung diseases. Such noninvasive techniques are simple to perform, may be repeated frequently and can be applied in children, including neonates and patients with severe disease in whom more invasive procedures are not possible. Several volatile chemicals can be measured in the breath (nitric oxide, carbon monoxide, hydrocarbons), and many nonvolatile molecules (mediators, oxidation and nitration products, proteins) may be measured in exhaled breath condensate.     

Airway inflammation and eotaxin in exhaled breath condensate of patients with severe persistent allergic asthma during omalizumab therapy

PurposeThe central role of IgE in allergic inflammation in asthma has provided a rationale for the development of omalizumab, the humanized monoclonal anti-IgE antibody. The aim of the study was to determine the effect of omalizumab treatment on changes in airway inflammatory process and eotaxin in exhaled breath condensate in patients with persistent severe allergic asthma.Material and MethodsThe study was performed on a group of 19 patients with severe persistent allergic asthma treated with conventional therapy (according to GINA 2006) and with or without omalizumab (9 vs 10 patients). Eotaxin in exhaled breath condensate, exhaled nitric oxide, blood eosinophil count and serum ECP were measured before and after 16 weeks of therapy.ResultsIn the group treated with omalizumab, a statistically significant decrease in the concentrations of eotaxin in EBC, FENO, serum ECP, and blood eosinophil count after 16 weeks of treatment was observed. Statistically significant correlations were revealed between the decrease in eotaxin and the decrease in FENO, serum ECP and blood eosinophil count after omalizumab therapy.ConclusionsDownregulation of eotaxin expression in the airways through limitation of eosinophilic inflammation could be essential in the beneficial effect of anti-IgE therapy with omalizumab in asthma patients.     

Noninvasive methods for the detection of upper and lower airway inflammation in atopic children

BACKGROUND: Exhaled nitric oxide (FE(NO)) and exhaled breath condensate (EBC) are noninvasive methods to assess inflammation. OBJECTIVE: To investigate the role of the FE(NO) and of the EBC pH and IL-5 levels in atopic children. METHODS: We evaluated oral and nasal FE(NO) and the pH and IL-5 of oral and nasal EBC in children with atopic dermatitis (AD; n = 18), allergic rhinitis (AR; n = 18), intermittent asthma (n = 21), moderate persistent asthma (n = 18), and healthy controls (HCs; n = 16). RESULTS: Oral FE(NO) was significantly increased in asthma, whereas the nasal values were increased in AR and asthma in comparison with HCs. The pH of oral EBC was lower in AD and asthma than in AR and HCs, whereas the nasal levels were lower in AD, AR, and asthma than in HCs. The oral IL-5 was higher in AD, AR, and asthma in comparison with HCs, whereas the nasal IL-5 concentrations were higher in asthma and AR than in HCs. In AR, the nasal FE(NO) correlated with the IL-5 values and with the disease duration. In intermittent asthma, oral and nasal pH inversely correlated with the exacerbations, whereas in moderate asthma, the nasal IL-5 positively correlated with exacerbations. In AD, the oral and nasal IL-5 positively correlated with the serum IgE. CONCLUSION: These markers of nasal and bronchial inflammation, accessible with noninvasive techniques, might be useful to identify patients with uncontrolled diseases and to verify the usefulness of new therapeutic approaches. CLINICAL IMPLICATIONS: These markers are useful tools to monitor the upper and lower airway inflammation in atopic children.     

Asthmatic cough and airway oxidative stress

The mechanisms of cough in asthma are unclear. Asthma is associated with an oxidative stress. Many reactive oxygen species sensitize or activate sensory C-fibers which are capable to induce cough. It was hypothesized that oxidative stress in the airways might contribute to the cough severity in asthma. Exhaled breath condensate samples were collected in ten healthy and 26 asthmatic subjects. The concentration of 8-isoprostane was measured. In addition, the subjects filled in Leicester Cough Questionnaire and underwent cough provocation tests with dry air hyperpnoea and hypertonic saline, among other measurements. Among the asthmatic subjects, high 8-isoprostane was associated with severe cough response to hyperpnoea (p=0.001), low Leicester Cough Questionnaire values (indicating severe subjective cough, p=0.02), and usage of combination asthma drugs (p=0.03-0.04). However, the 8-isoprostane concentrations did not differ significantly between the healthy and the asthmatic subjects. Airway oxidative stress may be associated with experienced cough severity and measured cough sensitivity in asthma.