Sara Sánchez-Vidaurre

Impact Of Age on pH, 8-Isoprostane, and Nitrogen Oxides in Exhaled Breath Condensate

BACKGROUND Few studies have addressed the effects of aging on levels of inflammatory markers in exhaled breath condensate (EBC). The aim of this study was to determine whether there are significant age-associated differences in pH, 8-isoprostane, and nitrogen oxide values in EBC from a population of healthy adults. MATERIAL AND METHODS EBC samples were obtained from 75 healthy volunteers aged 18 to 80 years and stratified into five groups according to age (n = 15): 18 to 29, 30 to 39 years, 40 to 49 years, 50 to 59 years, and 60 to 80 years. The following were measured in the samples collected: pH before and after deaeration, nitrite, nitrate, and 8-isoprostane. Differences between the groups were assessed by the Kruskal-Wallis test. RESULTS Significant differences in deaerated pH (p < 0.0001) were found in the group of individuals 60 to 80 years of age as compared to the remaining groups. Significant differences were also found in 8-isoprostane levels between the younger and older groups (18 to 29 years and 30 to 39 years of age; p = 0.006 and p = 0.034, respectively). There were no significant differences in nitrite or nitrate values between younger and older individuals. CONCLUSION The results of this study indicate that pH and 8-isoprostane levels in EBC show a relationship with age. Thus, values obtained in studies with control groups may require adjustment for these factors.

Bronchial inflammation and hyperresponsiveness in well controlled asthma

Little research has been devoted to the characteristics of bronchial inflammation in patients with stable, well controlled asthma.

Sputum Inflammatory Profile Before and After Specific Inhalation Challenge in Individuals with Suspected Occupational Asthma

Background The aim of this study was to establish the sputum inflammatory profile and changes in levels of leukotriene B4 (LTB4) and a panel of Th1/Th2 cytokines in subjects with suspected occupational asthma (OA) following specific inhalation challenge (SIC) to high-molecular-weight (HMW) and low-molecular-weight (LMW) agents. Material and Methods Fifty-one consecutive subjects undergoing SIC for suspected OA were enrolled. Sputum induction was performed the day before and 24 h after exposure to the offending agent. Total and differential cell counts were assessed. LTB4 and a 10 Th1/Th2 cytokines were measured in sputum supernatant. Results Thirty-four patients tested positive to SIC and were diagnosed with OA (in 10 due to HMW agents and in 24 to LMW agents). SIC was negative in 17 subjects. As compared to baseline an increase was found in the percentage of sputum eosinophils and neutrophils, and in IL-10 concentration after SIC (p = 0.0078, p = 0.0195, and p = 0.046, respectively), and a decrease was seen in LTB4 level (p = 0.0078) in patients with OA due to HMW agents. An increase in the percentage of sputum neutrophils after SIC (p = 0.0040) was observed in subjects without OA exposed to LMW agents. IL-8 levels after SIC were higher in patients without OA compared with patients with OA (p = 0.0146). Conclusion When conducting airway inflammation studies in OA, patients should be divided according to the causal agent (HMW or LMW). In OA patients exposed to HMW agents, an increase in the number of neutrophils can be found in parallel to the increase of eosinophils, although this does not contradict an IgE-mediated mechanism. Exposure to LMW agents can result in increased neutrophilic inflammation in patients with airway diseases unrelated to OA. There is variability in the responses observed in patients with OA exposed to LMW agents.

Diagnostic utility of exhaled breath condensate analysis in conjunction with specific inhalation challenge in individuals with suspected work-related asthma

BACKGROUND Establishing the role of exhaled breath condensate (EBC) analysis in work-related asthma (WRA), and more specifically, in conjunction with specific inhalation challenge (SIC), is difficult. OBJECTIVE To measure EBC pH, and nitrite/nitrate concentrations before and after SIC in individuals with suspected WRA exposed to either high-molecular-weight (HMW) or low-molecular-weight (LMW) agents and evaluate whether these changes are useful to distinguish between occupational asthma (OA) and work-exacerbated asthma (WEA). METHODS One hundred twenty-five consecutive workers undergoing SIC were enrolled. Exhaled breath condensate was collected at the end of the baseline day and 24 hours after exposure to the offending agent. In all EBC samples, pH was measured, and nitrite and nitrate concentrations were determined. RESULTS Specific inhalation challenge was positive in 66 individuals, who were then diagnosed with OA. Work-exacerbated asthma was diagnosed in 14, and in 45 patients establishing a direct relationship between the symptoms and work exposure was not possible. In patients with WEA, EBC pH values after SIC were significantly lower than those before SIC (P = .0047). Using the receiver operating characteristic (ROC) curve, we found that an EBC pH decrease of greater than 0.4 units after SIC achieved the most satisfactory sensitivity 79% (confidence interval [CI]: 49-94) and specificity of 100% (CI: 68-100), considering only patients with asthma and without OA. A decrease in EBC pH of 0.4 or more common in those exposed to HMW agents (8/19, 42%) than in those exposed to LMW agents (7/47, 15%). CONCLUSIONS Exhaled breath condensate pH in conjunction with SIC may be useful for diagnosing WEA.

Bronchial inflammation in hypersensitivity pneumonitis after antigen-specific inhalation challenge

The aim of this study is to compare the inflammatory profile before and after specific inhalation challenge (SIC) in induced sputum from patients with hypersensitivity pneumonitis (HP) and to investigate whether different causal antigens define the resulting profile.

Inflamación pulmonar latente en pacientes con esclerosis sistémica

BACKGROUND Induced sputum is a non-invasive method for studying pulmonary inflammation. OBJECTIVES To assess pulmonary inflammation by analysis of induced sputum specimens in patients with systemic sclerosis and lung involvement, and to determine whether there is a correlation with the pulmonary function alterations in these patients. METHODS Twenty-five patients with systemic sclerosis were included (20 women). Patients were divided into 3 groups according to the type of lung involvement: group 1, diffuse interstitial lung disease (n=10); group 2, those with pulmonary arterial hypertension (n=7), and group 3, patients with systemic sclerosis without lung involvement (n=8). All patients underwent a complete lung function study. Induced sputum samples were obtained and differential cell count was performed by optic microscopy. RESULTS The mean percentage of sputum neutrophils was 85%, 71%, and 75% for groups 1, 2, and 3, respectively. A significant negative correlation between sputum total cell count and DLCO was seen in group 1 and group 3 (r=-0.733, P=.016; and r=-0.893, P=.007, respectively). This negative correlation was not observed in group 2. CONCLUSIONS Pulmonary inflammation was present in all patients with systemic sclerosis included in the study, regardless of the presence of documented signs of pulmonary involvement. This finding suggests that induced sputum could be helpful for detecting early abnormalities indicative of subclinical pulmonary involvement in patients with systemic sclerosis.

BALF cytokines in different phenotypes of chronic lung allograft dysfunction in lung transplant patients

The long‐term success of lung transplantation (LT) is limited by chronic lung allograft dysfunction (CLAD). Different phenotypes of CLAD have been described, such as bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). The purpose of this study was to investigate the levels of cytokines and chemokines in bronchoalveolar lavage fluid (BALF) as markers of these CLAD phenotypes. BALF was collected from 51 recipients who underwent (bilateral and unilateral) LT. The study population was divided into three groups: stable (ST), BOS, and RAS. Levels of interleukin (IL)‐4, IL‐5, IL‐6, IL‐10, IL‐13, tumor necrosis factor alpha (TNF‐α), interferon‐gamma (IFN‐γ), and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) were measured using the multiplex technology. BALF neutrophilia medians were higher in BOS (38%) and RAS (30%) than in ST (8%) (P=.008; P=.012). Regarding BALF cytokines, BOS and RAS patients showed higher levels of INF‐γ than ST (P=.02; P=.008). Only IL‐5 presented significant differences between BOS and RAS (P=.001). BALF neutrophilia is as a marker for both CLAD phenotypes, BOS and RAS, and IL‐5 seems to be a potential biomarker for the RAS phenotype.

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

INTRODUCTION Interstitial 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. METHODS Fraction 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. RESULTS No 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). CONCLUSIONS EB and EBC could help to detect patients likely to present a deterioration on lung function during follow up.

FRI0442 Prognostic Role of Exhaled Breath Condensate in Patients with Pulmonary Involvement Associated to Systemic Sclerosis

Background Lung involvement due to interstitial lung disease (ILD) and/or pulmonary arterial hypertension (PAH) is the most important cause of death in systemic sclerosis (SSc). Objectives To assess the clinical usefulness of exhaled breath and exhaled breath condensate (EBC) biomarkers in the study of scleroderma pulmonary involvement (PI), and their correlation with disease progression. Methods Fraction exhaled nitric oxide (FeNO) and exhaled carbon monoxide (eCO) measured in exhaled breath and pH, nitrite, nitrate and interleukin-6 in EBC were prospectively collected from 35 patients with SSc. Fourteen had established PI as presence of ILD or PAH, and 21 patients with no lung involvement. Pulmonary function tests (PFT) and clinical approaches were performed annually during 4 years of follow-up. A progression-free survival (PFS) analysis was performed defining end point as a decrease from baseline FVC of at least 10%, or a 15% diminution in DLCO, or death during follow-up. Results There were no statistical differences in demographic data and the baseline characteristics between both groups. Median (interquartile range, IQR) age was 59.0 (42.0 to 68.0) years. Limited SSc was the most common cutaneous subset (28, 80%). The median of pulmonary duration disease was 1.7 years in PI group. Regarding lung function data at baseline, lower median FVC % and DLCO % values were identified in the PI group (76.5 vs. 94.2, p<0.01) and (45.6 vs. 71.7, p<0.001), respectively. Lower baseline pH levels were found in PI group (7.5 vs 8.0, p=0.04), with no other biomarker differences. Respecting the correlations between EBC biomarkers and PFTs during monitoring, lower pH levels were associated with lower DLCO % at 4 years of follow-up (r=0.45, p=0.01). Reduced FeNO levels were correlated with low FVC % at baseline (r=0.41, p=0.03), 4 years of follow-up (r=0.46, p=0.02) and with a decrease of FVC % (r=0.65, p<0.001) and DCLO % during monitoring (r=0.50, p=0.01). Among the PI patients, high eCO measurements were related to low baseline FVC % (r=0.69, p<0.01), and high IL-6 levels were correlated with low DLCO % at 4 years of follow-up (r= -0.64, p=0.03). The progression-free survival analysis identified that a pH equal or lower than 7.85 showed a decrease in lung function parameters or death during follow-up (log Rank p=0.03). FeNO levels equal or lower than 11.0 ppb were related to worse PFS (log Rank p<0.01) (figure). Conclusions The pH and FeNO levels are implicated in the pathophysiology of the scleroderma lung. Exhaled breath and EBC may reflect the pulmonary inflammation with a non-invasive test, in which the biomarkers are correlated with a different outcome. Disclosure of Interest None declared