Effect of 5-year continuous positive airway pressure treatment on the lipid profile of patients with obstructive sleep apnea: A pilot study.

Continuous positive airway pressure (CPAP) provides a well-documented symptomatic relief for most patients with obstructive sleep apnea (OSA); however, its effect on dyslipidaemia remains contradictory. The aim of this longitudinal pilot study was to investigate the effect of long-term CPAP treatment on the lipid profile of patients with severe OSA. Fasting serum levels of total cholesterol (TC), low- and high-density lipoprotein cholesterol (LDL-C and HDL-C) and triglyceride (TG) were longitudinally measured in 33 OSA patients with an apnea-hypopnea index (AHI) of ≥30 events/hr, at the time of diagnosis (baseline) and at control visits following fixed-pressure CPAP treatment. Compared to baseline values, even as short as a 2-month CPAP therapy resulted in a significant decrease of both TC and LDL-C levels (TC, 5.62 ± 0.22 vs. 5.18 ± 0.21 mmol/L; LDL-C, 3.52 ± 0.19 vs. 3.19 ± 0.2 mmol/L; p < 0.05 for each). These lipid fractions exhibited similar improvements at 6 months and after 5 years of CPAP treatment (TC, 5.1 ± 0.17 mmol/L; LDL-C, 2.86 ± 0.16 mmol/L; p < 0.01 for each). The reduction in lipid levels was greater in younger patients and/or in those who had higher body mass index (BMI) (p < 0.05). There were no significant correlations between AHI and lipid levels (p > 0.05); BMI showed a weak negative association with HDL-C fraction (BMI, r = -0.263, p < 0.05). CPAP therapy had neither short- nor long-term effects on TG and HDL-C levels (p > 0.05). CPAP therapy has a rapid and long-lasting beneficial effect on the lipid profile of patients with severe OSA.

Monitoring Antioxidant Enzyme Activity during Exacerbations of Chronic Obstructive Pulmonary Disease.

Superoxide dismutases (SODs) and catalase (CAT) have been implicated as major antioxidant enzymes of the human lungs. In this study, we investigated whether activities of these enzymes are altered in the airways of patients hospitalized with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). SOD and CAT activities were measured in the sputum, exhaled breath condensate, and serum of 36 COPD patients experiencing a severe exacerbation. Measurements were performed using colorimetric assays in samples collected at the time of hospital admission and at the time of hospital discharge following treatment of AECOPD. For comparison, antioxidants were also assessed in 24 stable COPD patients and 23 healthy control subjects. SOD and CAT activities in sputum were significantly increased in patients with AECOPD compared to those with stable disease (SOD: 0.142 [0.053-0.81] vs. 0.038 [0.002-0.146] U/mL, p < 0.01; CAT: 48.7 [18.7-72.6] vs. 10.2 [2.9-40.6] nmol/min/mL, p < 0.05), while treatment of exacerbation led to a decrease in enzyme activities (SOD: 0.094 [0.046-0.45] U/mL, p < 0.05; CAT: 28.0 [7.3-60.4] nmol/min/mL, p < 0.005). No changes were observed in the serum (p > 0.05). Both SOD and CAT activities significantly correlated with sputum neutrophil and lymphocyte cell counts in patients with AECOPD. Moreover, SOD and CAT values correlated with each other and also with sputum malondialdehyde, an established marker for oxidative stress. Our data demonstrate that sputum antioxidant activity is elevated during COPD exacerbation and suggest that activation of SODs and CAT is an integral part of the human defense mechanism against the increased oxidant production associated with AECOPD.

A European Respiratory Society technical standard: exhaled biomarkers in lung disease.

Breath tests cover the fraction of nitric oxide in expired gas (FeNO), volatile organic compounds (VOCs), variables in exhaled breath condensate (EBC) and other measurements. For EBC and for FeNO, official recommendations for standardised procedures are more than 10 years old and there is none for exhaled VOCs and particles. The aim of this document is to provide technical standards and recommendations for sample collection and analytic approaches and to highlight future research priorities in the field. For EBC and FeNO, new developments and advances in technology have been evaluated in the current document. This report is not intended to provide clinical guidance on disease diagnosis and management.Clinicians and researchers with expertise in exhaled biomarkers were invited to participate. Published studies regarding methodology of breath tests were selected, discussed and evaluated in a consensus-based manner by the Task Force members.Recommendations for standardisation of sampling, analysing and reporting of data and suggestions for research to cover gaps in the evidence have been created and summarised.Application of breath biomarker measurement in a standardised manner will provide comparable results, thereby facilitating the potential use of these biomarkers in clinical practice.

Assessment of the Anti-Aging Klotho Protein in Patients with COPD Undergoing Pulmonary Rehabilitation.

Chronic obstructive pulmonary disease (COPD) is associated with the accelerated aging of the lung. The protein klotho has been implicated in longevity, and there is some evidence that it might be involved in the pathomechanism of chronic respiratory diseases. Therefore, we aimed to examine whether the clinical condition of COPD patients is reflected in plasma klotho concentration. As plasma concentration of the protein is modulated by physiological factors that are generally improved during pulmonary rehabilitation, we hypothesized that a complex rehabilitation program may alter plasma klotho concentration. Blood samples were taken from 31 stable COPD patients. Clinical parameters such as respiratory function, 6-minute walking distance (6MWD), impact of disease (CAT), dyspnea, grip strength, chest expansion and breath holding time, smoking history, and body mass index (BMI) were evaluated. 19 patients who participated in a 3-week inpatient rehabilitation program had blood sample collection on the first, third, and last days of the program and had the above functional measurements before and after rehabilitation. Plasma klotho concentration was assessed by enzyme-linked immunosorbent assay. Klotho levels showed no correlation with clinical parameters (FEV1%, 6MWD, grip strength, CAT, smoking history, p > 0.05). Coefficient of variation of klotho measurements was 4.5% between Day 1 and Day 3. Although the rehabilitation resulted in significant improvements in 6MWD, CAT, grip strength, and chest expansion, klotho levels did not change significantly (510.1 ± 149.9 vs. 504.2 ± 139.8 pg/ml, p > 0.05). Plasma klotho concentration can be reliably measured in stable COPD; however, its levels are not correlated with clinical parameters of patients. Despite functional improvement, klotho level remains unchanged during the rehabilitation program.

Comparison of Airway and Systemic Malondialdehyde Levels for Assessment of Oxidative Stress in Cystic Fibrosis.

INTRODUCTION: Oxidative stress plays a pivotal role in the pathogenesis of cystic fibrosis (CF). In this study, airway and systemic oxidative stress was investigated in CF using malondialdehyde (MDA), an established by-product of polyunsaturated fatty acid peroxidation. METHODS: Exhaled breath condensate (EBC), sputum, and plasma were collected from 40 stable CF patients during routine clinical visits and from 25 healthy controls. MDA was measured by high-performance liquid chromatography. RESULTS: MDA levels in sputum (279.8 ± 14.7 vs. 92.7 ± 9.2 nmol/L, p < 0.0001), EBC (139.9 ± 6.7 vs. 71.5 ± 4.3 nmol/L, p < 0.0001), and plasma (176.1 ± 15.9 vs. 129.6 ± 12.9 nmol/L, p < 0.05) were increased in patients with CF compared to healthy controls. MDA measurement in sputum [area under receiver operating characteristic curve (AUC): 0.977, p < 0.0001] or EBC (AUC: 0.94, p < 0.0001) discriminated between patients and controls with greater accuracy than in plasma (AUC: 0.677, p < 0.05). Sputum and EBC MDA levels were elevated in patients with severe pulmonary dysfunction [forced expiratory volume in 1 s (FEV1) <50 % predicted] compared to those with mild-to-moderate functional impairment (FEV1 ≥50 % predicted) (p < 0.05). MDA concentrations in CF patients colonized either with Pseudomonas aeruginosa or with other bacteria were similar (p = NS). The intra- and inter-assay repeatabilities of MDA measurements was similar in all the three types of samples, while the between-visit variability was higher in plasma. CONCLUSIONS: MDA is a potential new airway marker of oxidative stress in patients with CF. Sputum MDA differentiates best between patients and healthy subjects.

Monitoring oxidative stress during chronic obstructive pulmonary disease exacerbations using malondialdehyde.

BACKGROUND AND OBJECTIVE: Oxidative stress plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). In this longitudinal study changes in the level of malondialdehyde (MDA), an end product of polyunsaturated fatty acid peroxidation, were investigated in the airways of patients with acute exacerbation of COPD (AECOPD). METHODS: Levels of MDA were measured in sputum and exhaled breath condensate (EBC) of 34 COPD patients at the time of hospital admission due to an acute exacerbation of the disease, and again following treatment at the time of hospital discharge. MDA was also assessed in 21 stable patients with COPD and 20 healthy controls. Measurements were performed using high-performance liquid chromatography. RESULTS: Sputum MDA levels were significantly increased in AECOPD (220.0 ± 17.5 nmol/L) compared with stable disease (144.6 ± 14.3 nmol/L, P < 0.01) and healthy controls (85.9 ± 11.3 nmol/L, P < 0.001). MDA levels decreased after treatment (190.7 ± 16.3 nmol/L, P < 0.05). In contrast to sputum, EBC MDA levels were comparable between controls, stable COPD patients and AECOPD patients (73.1 ± 5.1 nmol/L, 96.1 ± 11.6 nmol/L and 93.3 ± 7.6 nmol/L, P = NS). Measurement of MDA had good repeatability in both sputum and EBC, but the between-day variability was considerably higher in EBC. Sputum induction did not influence MDA levels. CONCLUSIONS: MDA in sputum, but not in EBC, appears to be a useful marker for monitoring exacerbation-associated oxidative stress in AECOPD.

Exhaled breath condensate pH decreases during exercise-induced bronchoconstriction.

BACKGROUND AND OBJECTIVE: Exercise-induced bronchoconstriction (EIB) is the temporary narrowing of the airways caused by physical exercise. Its exact pathophysiology is unclear; however, acute changes in airways pH may play a role. Exhaled breath condensate (EBC) pH was suggested as a surrogate indicator for airway acid-base status, but its value is also affected by volatile molecules and respiratory droplet dilution. The aim of the study was to assess changes in EBC pH during EIB. METHODS: Twenty-two asthmatics who reported breathlessness following exercise and 16 healthy individuals participated in the study. Lung function test was performed and exhaled breath samples were collected for pH, dilution factor and volatile compound pattern measurements (Cyranose 320) pre-exercise and at 0, 10, 20 and 30 min after physical exercise challenge. Fractional exhaled nitric oxide was measured before exercise. RESULTS: EIB developed in 13 asthmatic subjects. In these participants, but not in the EIB-negative asthmatics (P = 0.51), EBC pH reduced significantly during exercise (P = 0.01). In addition, changes in EBC pH were related to the degree of bronchospasm in the EIB-positive group (P = 0.01, r = 0.68). Exhaled volatile pattern became altered (P < 0.05) during exercise in all subjects (asthmatics and controls). EBC pH changes were not related to EBC dilution or volatile compound pattern alterations (P > 0.05). CONCLUSIONS: The development of EIB was related to acute changes of EBC pH, which suggest the role of airway pH decrease in the pathophysiology of EIB. Exercise-induced changes in exhaled biomarkers suggest methodological precautions to avoid physical exercise before performing exhaled breath tests.

Sputum eicosanoid profiling in exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Eicosanoids are small lipid molecules with diverse biological functions in the airways. OBJECTIVES: The aim of this study was to investigate changes in leukotriene B4 (LTB4), 8-isoprostane, prostaglandin E2 (PGE2) and cysteinyl-leukotriene (cys-LT) levels in the sputum of patients with chronic obstructive pulmonary disease (COPD) at the onset of a severe exacerbation and during the course of recovery. METHODS: Thirty-seven ex-smoker COPD patients suffering an episode of acute exacerbation were enrolled. Samples were taken (i) on hospital admission and (ii) after regular treatment. Twenty-five stable ex-smoker COPD patients served as controls. Eicosanoids were determined by enzyme immunoassay. RESULTS: Sputum PGE2 [39.8 (13.3-103.3) vs. 5.05 (2.3-12.1) pg/ml, p < 0.001], 8-isoprostane [89.5 (36.9-184.7) vs. 29.7 (13.8-68.8) pg/ml, p < 0.01] and LTB4 [587.7 (252.9-774.8) vs. 276.1 (105.4-594.7) pg/ml, p < 0.05] levels were increased in patients with exacerbation compared to stable subjects. After treatment only PGE2 levels decreased significantly [at discharge: 19.6 (4.6-52.5) pg/ml, p < 0.01], the levels of other eicosanoids remained elevated (p = NS). Sputum cys-LT levels were similar in stable patients and in those with exacerbation and treatment did not influence cys-LTs either. There was a significant correlation between PGE2 and sputum neutrophil and lymphocyte cell counts in patients with exacerbation. CONCLUSIONS: Our results suggest that 8-isoprostane, LTB4 and PGE2 but not cys-LTs may be involved in exacerbation-associated inflammatory processes in the airways of patients with COPD. Validation of PGE2 for use as a biomarker of recovery from an exacerbation requires further studies.

[The impact of the COVID-19 epidemic on the course of the most common respiratory diseases]. / A COVID­19-járvány hatása a leggyakoribb légzoszervi megbetegedések lefolyására.

INTRODUCTION: SARS-CoV-2 has defined our everyday lives over the past three years and by constituting a serious risk factor for patients with pre-existing respiratory illnesses, it placed an unexpected burden on the health care systems worldwide. OBJECTIVE: The aim of this study was to explore the association between COVID-19 and pre-existing respiratory comorbidities such as chronic obstructive pulmonary disease (COPD) and asthma. METHOD: In our current study, we retrospectively processed the data of nearly 29 000 Hungarian patients. RESULTS: We found that COPD was directly associated with the severity of COVID-19 and slightly increased the risk of intensive care unit admission and the need for mechanical ventilation during the SARS-CoV-2 infection. On the other hand, the presence of asthma influenced neither the severity of COVID-19 nor the need for intensive care unit admission or mechanical ventilation significantly. DISCUSSION: International studies suggest that COPD does not significantly increase the risk of SARS-CoV-2 infection. However, the likelihood of hospitalization due to COVID-19 is much higher in COPD patients and the presence of COPD is associated with a more severe disease course. Given the structural alterations and abnormal regeneration processes of the airways that occur during lung injury in COPD patients, these individuals require increased attention and personalized rehabilitation protocols after the onset of the viral infection. CONCLUSION: Altogether, the assessment of clinical manifestations associated with different COPD phenotypes (as well as other chronic lung diseases) and SARS-CoV-2 infection is essential for the implementation of personalized therapeutic approach in the future. Orv Hetil. 2023; 164(2): 51-56.

Single-cell immunophenotyping revealed the association of CD4+ central and CD4+ effector memory T cells linking exacerbating chronic obstructive pulmonary disease and NSCLC.

Introduction: Tobacco smoking generates airway inflammation in chronic obstructive pulmonary disease (COPD), and its involvement in the development of lung cancer is still among the leading causes of early death. Therefore, we aimed to have a better understanding of the disbalance in immunoregulation in chronic inflammatory conditions in smoker subjects with stable COPD (stCOPD), exacerbating COPD (exCOPD), or non-small cell lung cancer (NSCLC). Methods: Smoker controls without chronic illness were recruited as controls. Through extensive mapping of single cells, surface receptor quantification was achieved by single-cell mass cytometry (CyTOF) with 29 antibodies. The CyTOF characterized 14 main immune subsets such as CD4+, CD8+, CD4+/CD8+, CD4-/CD8-, and γ/δ T cells and other subsets such as CD4+ or CD8+ NKT cells, NK cells, B cells, plasmablasts, monocytes, CD11cdim, mDCs, and pDCs. The CD4+ central memory (CM) T cells (CD4+/CD45RA-/CD45RO+/CD197+) and CD4+ effector memory (EM) T cells (CD4+/CD45RA-/CD45RO+/CD197-) were FACS-sorted for RNA-Seq analysis. Plasma samples were assayed by Luminex MAGPIX® for the quantitative measurement of 17 soluble immuno-oncology mediators (BTLA, CD28, CD80, CD27, CD40, CD86, CTLA-4, GITR, GITRL, HVEM, ICOS, LAG-3, PD-1, PD-L1, PD-L2, TIM-3, TLR-2) in the four studied groups. Results: Our focus was on T-cell-dependent differences in COPD and NSCLC, where peripheral CD4+ central memory and CD4+ effector memory cells showed a significant reduction in exCOPD and CD4+ CM showed elevation in NSCLC. The transcriptome analysis delineated a perfect correlation of differentially expressed genes between exacerbating COPD and NSCLC-derived peripheral CD4+ CM or CD4+ EM cells. The measurement of 17 immuno-oncology soluble mediators revealed a disease-associated phenotype in the peripheral blood of stCOPD, exCOPD, and NSCLC patients. Discussion: The applied single-cell mass cytometry, the whole transcriptome profiling of peripheral CD4+ memory cells, and the quantification of 17 plasma mediators provided complex data that may contribute to the understanding of the disbalance in immune homeostasis generated or sustained by tobacco smoking in COPD and NSCLC.

Exhaled breath condensate pH in patients with cystic fibrosis.

OBJECTIVE AND DESIGN: Exhaled breath condensate (EBC) pH has been proposed as a useful, non-invasive marker of airway inflammation in pulmonary diseases. In this study we tested whether cystic fibrosis (CF) is associated with acidification of EBC, when pH is assessed by the CO(2) gas standardization method. METHODS: EBC was collected using two different devices (EcoScreen and R-Tube) in 46 stable CF patients during routine clinical visits and in 28 healthy controls. RESULTS: Mean EBC pH in CF patients and in healthy controls was similar (EcoScreen: CF patients: 6.38 ± 0.03 versus controls: 6.39 ± 0.03, p = 0.699; R-tube: CF patients: 5.94 ± 0.04 versus controls: 6.02 ± 0.03, p = 0.159). Inflammatory cell counts in spontaneously expectorated sputum obtained in a subset of patients (n = 20) showed no correlation with pH values. EBC samples collected with the R-tube were more acidic than those collected with the EcoScreen device (p < 0.001). CONCLUSIONS: Our data suggest that EBC pH does not discriminate between healthy controls and those with CF disease indicating that the clinical applicability of EBC pH measurements for assessing airway inflammation in CF is limited.

[Clinical application of induced and spontaneous sputum in asthma and chronic obstructive pulmonary disease]. / Indukált és spontán köpet klinikai felhasználása asztmában és krónikus obstruktív tüdobetegségben.

In recent years induced sputum analysis has become a non-invasive method for the assessment of airway inflammation in obstructive airway diseases. Sputum induction is safe and well tolerated by the patients. The method has been standardized, and this has markedly improved the quality and reproducibility of sputum samples. Identification of sputum eosinophilia has the greatest clinical relevance as it predicts a favorable response to corticosteroids. Treatment strategy aiming normalisation of sputum eosinophil cell count may reduce the rate of exacerbations in asthma. Profiling inflammatory mediators in sputum supernatant provides new insights into the pathogenesis of asthma and chronic obstructive pulmonary disease. Cell type analysis in spontaneous sputum may also provide much information about inflammatory processes in the airways. Based on the results of clinical studies sputum analysis should be more often used in clinical settings in the future.

[Assessment of airway inflammation in chronic obstructive pulmonary disease: biomarkers in exhaled breath condensate]. / Légúti gyulladás vizsgálata krónikus obstruktív tüdobetegségben: biomarkerek a kilégzett levego kondenzátumában.

Airway inflammation plays a central role in the pathophysiology of chronic obstructive pulmonary disease. Exposure to cigarette smoke induces the recruitment of inflammatory cells in the airways, which in turn produces various cytokines, chemokines, proteases and pro-inflammatory mediators leading ultimately to increased oxidative stress, a protease/anti-protease imbalance and progressive lung tissue injury. Biomarkers may be useful in monitoring airway inflammation and oxidative stress, defining different phenotypes of the disease and evaluating the response of therapies. Exhaled breath condensate collection is a simple and completely non-invasive method of sampling the lower respiratory tract in humans. Exhaled breath condensate may be a rich source of pulmonary biomarkers including hydrogen peroxide, cytokines, metabolites of the arachidonic acid, nitric oxides and the pH. However, the concentration of these biomarkers is often very low, which may cause several problems in their detection. The clinical applicability of exhaled breath condensate biomarkers cannot be assessed until methods of sample collection and analysis have been standardized.

Blood Eosinophils and Exhaled Nitric Oxide: Surrogate Biomarkers of Airway Eosinophilia in Stable COPD and Exacerbation.

In recent years, tremendous efforts have been devoted to characterizing the inflammatory processes in chronic obstructive pulmonary disease (COPD) in order to provide more personalized treatment for COPD patients. While it has proved difficult to identify COPD-specific inflammatory pathways, the distinction between eosinophilic and non-eosinophilic airway inflammation has gained clinical relevance. Evidence has shown that sputum eosinophil counts are increased in a subset of COPD patients and that these patients are more responsive to oral or inhaled corticosteroid therapy. Due to feasibility issues associated with sputum cell profiling in daily clinical practice, peripheral blood eosinophil counts and fractional exhaled nitric oxide levels have been evaluated as surrogate biomarkers for assessing the extent of airway eosinophilia in COPD patients, both in stable disease and acute exacerbations. The diagnostic value of these markers is not equivalent and depends heavily on the patient's condition at the time of sample collection. Additionally, the sensitivity and specificity of these tests may be influenced by the patient's maintenance treatment. Overall, eosinophilic COPD may represent a distinct disease phenotype that needs to be further investigated in terms of prognosis and treatment outcomes.

Sputum Cytokine Profiling in COPD: Comparison Between Stable Disease and Exacerbation.

Purpose: Cytokines are extracellular signaling proteins that have been widely implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). Here, we investigated cytokine expression both at the mRNA and protein level in the sputum of healthy individuals, stable COPD patients, and those experiencing a severe acute exacerbation (AECOPD) requiring hospitalization. Patients and Methods: Sputum was collected in 19 healthy controls, 25 clinically stable COPD patients, and 31 patients with AECOPD. In AECOPD patients sample collection was performed both at the time of hospital admission and at discharge following treatment. Sputum supernatant was analyzed by an antibody microarray detecting 120 cytokines simultaneously, while the mRNA expression of 14 selected cytokines in sputum cells was investigated by real-time PCR (qPCR). Results: Proteomic analysis identified interleukin (IL)-6 and growth-regulated oncogene (GRO)α as the only sputum cytokines that were differentially expressed between stable COPD patients and healthy controls. At the onset of AECOPD, several cytokines exhibited altered sputum expression compared to stable COPD. Recovery from AECOPD induced significant changes in the sputum cytokine protein profile; however, the length of hospitalization was insufficient for most cytokines to return to stable levels. With regard to gene expression analysis by qPCR, we found that bone morphogenetic protein (BMP)-4 was up-regulated, while IL-1α, monokine-induced by interferon-γ (MIG), and BMP-6 were down-regulated at the mRNA level in patients with AECOPD compared to stable disease. Conclusion: The sputum cytokine signature of AECOPD differs from that of stable COPD. Protein level changes are asynchronous with changes in gene expression at the mRNA level in AECOPD. The observation that the levels of most cytokines do not stabilize with acute treatment of AECOPD suggests a prolonged effect of exacerbation on the status of COPD patients.

Assessment of exhaled breath condensate pH in exacerbations of asthma and chronic obstructive pulmonary disease: A longitudinal study.

RATIONALE: Exhaled breath condensate pH has been proposed as a noninvasive marker of airway inflammation. However, due to standardization difficulties in pH measurement techniques, different pH readings were obtained in previous studies. OBJECTIVES: In this longitudinal study we assessed condensate pH in patients with an exacerbation of asthma or chronic obstructive airway disease using the very precise carbon dioxide standardization method that negates the effect of this gas on condensate acidity. METHODS: Condensate pH, fractional exhaled nitric oxide, lung function, and blood gases were measured in 20 nonsmoking patients with asthma and 21 smoking and 17 ex-smoking patients with chronic obstructive airway disease first at hospital admission due to an acute exacerbation of the disease and again at discharge after treatment. Condensate pH was also assessed in 18 smoking and 18 nonsmoking healthy control subjects. MEASUREMENTS AND MAIN RESULTS: In patients with asthma, condensate pH was significantly decreased at the time of exacerbation compared with nonsmoking control subjects and increased with treatment. In patients with chronic obstructive airway disease, condensate pH remained unchanged during exacerbation, both in smokers and ex-smokers. Nevertheless, condensates collected from smokers were more acidic than those of ex-smokers. A similar difference was observed between smoker and nonsmoker healthy control subjects. No correlations were found between condensate pH and fractional exhaled nitric oxide or lung function variables measured either at admission or discharge. CONCLUSIONS: Our data suggest that exacerbation of asthma, but not chronic obstructive airway disease, is associated with acidification of breath condensate.

Analysis of cytokine pattern in exhaled breath condensate of lung transplant recipients with bronchiolitis obliterans syndrome.

INTRODUCTION: Exhaled breath condensate (EBC) analysis is a promising method for investigating airway pathology. In this pilot study we tested the cytokine pattern of EBC of lung transplant patients with and without clinical evidence of bronchiolitis obliterans syndrome (BOS). MATERIALS AND METHODS: Breath condensates collected from eight BOS patients and eight stable BOS-free lung transplant recipients in three consecutive visits were pooled in order to increase protein concentration and were then used for antibody microarray analysis detecting 120 cytokines simultaneously. RESULTS: Nine cytokines exhibited more than twofold increase and four exhibited more than twofold decrease in BOS patients as compared to stable subjects. CONCLUSION: We conclude that inflammatory cytokines are present in EBC of lung transplant recipients, however the potential benefit of detecting the EBC proteome warrants further studies.

Analysis of cytokine pattern in exhaled breath condensate of patients with squamous cell lung carcinoma.

Exhaled breath condensate (EBC) analysis is a promising method for investigating airway pathology. In this study we compared the cytokine pattern of EBC of patients suffering from squamous cell lung carcinoma with that of healthy smokers. Breath condensates collected from 8 smoking lung cancer patients before receiving any anticancer treatment and 8 smokers without any clinical or radiological evidence of pulmonary tumors were used for antibody microarray analysis testing 120 cytokines simultaneously. Ninety-eight cytokines on the array gave a detectable signal in both groups. Cytokine levels were similar across the samples, and none of the cytokines exhibited a significant increase or decrease in cancer patients as compared to healthy subjects with similar smoking status, lung function, and airway inflammation. The results of this pilot study suggest that patients with squamous cell lung carcinoma cannot be distinguished from smokers with no pulmonary tumors based on EBC cytokine signals only.

Low-molecular-weight heparins do not modify obliterative airway disease in rat tracheal allografts.

Immunosuppressive and antiproliferative effects of heparin may be beneficial in the field of solid organ transplantation. The aim of this study was to examine the effect of low-molecular-weight heparin (LMWH) compounds on the development of obliterative airway disease (OAD) in the rat tracheal transplant model. Allogenic heterotopic tracheal transplantations were performed from Brown-Norway into Lewis rats. Recipients were treated either with nadroparin, enoxaparin, parnaparin, or vehicle from day 0 until harvesting at day 7 or 21. Graft rejection was morphometrically assessed to determine the extent of luminal obliteration end epithelial necrosis. All tracheal grafts harvested at day 7 demonstrated nearly equivalent degree of luminal obstruction regardless of treatment regimen. Likewise, at day 21 the extent of airway narrowing and the degree of inflammatory cell infiltration were similar among the groups. Moreover, loss of airway epithelium was not prevented by LMWH treatments. Finally, intragraft mRNA expression for transforming growth factor-ß1 and platelet-derived growth factor-A, interleukin-2, interferon-γ, and monocyte chemoattractant protein-1 did not differ between the groups. In contrast with findings in other animal models, treatment with LMWH preparations did not modify the development of OAD in rat tracheal allografts.