Comparison of two devices and two breathing patterns for exhaled breath condensate sampling.

Analysis of exhaled breath condensate (EBC) is a noninvasive method to access the epithelial lining fluid of the lungs. Due to standardization problems the method has not entered clinical practice. The aim of the study was to assess the comparability for two commercially available devices in healthy controls. In addition, we assessed different breathing patterns in healthy controls with protein markers to analyze the source of the EBC. EBC was collected from ten subjects using the RTube and ECoScreen Turbo in a randomized crossover design, twice with every device--once in tidal breathing and once in hyperventilation. EBC conductivity, pH, surfactant protein A, Clara cell secretory protein and total protein were assessed. Bland-Altman plots were constructed to display the influence of different devices or breathing patterns and the intra-class correlation coefficient (ICC) was calculated. The volatile organic compound profile was measured using the electronic nose Cyranose 320. For the analysis of these data, the linear discriminant analysis, the Mahalanobis distances and the cross-validation values (CVV) were calculated. Neither the device nor the breathing pattern significantly altered EBC pH or conductivity. ICCs ranged from 0.61 to 0.92 demonstrating moderate to very good agreement. Protein measurements were greatly influenced by breathing pattern, the device used, and the way in which the results were reported. The electronic nose could distinguish between different breathing patterns and devices, resulting in Mahalanobis distances greater than 2 and CVVs ranging from 64% to 87%. EBC pH and (to a lesser extent) EBC conductivity are stable parameters that are not influenced by either the device or the breathing patterns. Protein measurements remain uncertain due to problems of standardization. We conclude that the influence of the breathing maneuver translates into the necessity to keep the volume of ventilated air constant in further studies

pH in exhaled breath condensate and nasal lavage as a biomarker of air pollution-related inflammation in street traffic-controllers and office-workers

OBJECTIVE: To utilize low-cost and simple methods to assess airway and lung inflammation biomarkers relatedto air pollution.METHODS: A total of 87 male, non-smorking, healthy subjects working as street traffic-controllers or office-workers were examined to determine carbon monoxide in ixhaled breath and to measure the pH in nasal lavage fluid and exhaled breath condensate. Air pollution exposure was measured by particulate matter concentration, and data were obtained from fixed monitoring stations (8-h work intervals per day, during the 5 consecutive days prior to the study).RESULTS: Exhaled carbon monoxide was two-fold greater in traffic-controllers than in office-workers. The mean pH values were 8.12 in exhaled breath condensate and 7.99 in nasal lavage fluid in office-workers; these values concentrations in both substrates, however, Il-aB and IL-8 were elevated in nasal lavage fluid compared with exhaled breath condensate. The particulate matter concentration weas greater at the workplace of traffic-controllers compared with that of office-workers.CONCLUSION: The pH values of nasal lavage fluid and exhaled breath condensate are important, robust, easy to measure and reproducible biomarkers that can be used to monitor occupational exposure to air pollution. Additionally, traffic-controllers are at an increased risk of airway and lung inflammation during their occupational activities compared with office-workers

The effects of smoking and smoking cessation on nasal mucociliary clearance, mucus properties and inflammation

OBJECTIVE: The aim of the present study was to assess nasal mucociliary clearance, mucus properties and inflammation in smokers and subjects enrolled in a Smoking Cessation Program (referred to as quitters). METHOD: A total of 33 subjects with a median (IQR) smoking history of 34 (20-58) pack years were examined for nasal mucociliary clearance using a saccharine transit test, mucus properties using contact angle and sneeze clearability tests, and quantification of inflammatory and epithelial cells, IL-6 and IL-8 concentrations in nasal lavage fluid. Twenty quitters (mean age: 51 years, 9 male) were assessed at baseline, 1 month, 3 months and 12 months after smoking cessation, and 13 smokers (mean age: 52 years, 6 male) were assessed at baseline and after 12 months. Clinicaltrials.gov: NCT02136550. RESULTS: Smokers and quitters showed similar demographic characteristics and morbidities. At baseline, all subjects showed impaired nasal mucociliary clearance (mean 17.6 min), although 63% and 85% of the quitters demonstrated significant nasal mucociliary clearance improvement at 1 month and 12 months, respectively. At 12 months, quitters also showed mucus sneeze clearability improvement (∼26%), an increased number of macrophages (2-fold) and no changes in mucus contact angle or cytokine concentrations. CONCLUSION: This study showed that smoking cessation induced early improvements in nasal mucociliary clearance independent of mucus properties and inflammation. Changes in mucus properties were observed after only 12 months of smoking cessation

pH in exhaled breath condensate and nasal lavage as a biomarker of air pollution-related inflammation in street traffic-controllers and office-workers

OBJECTIVE: To utilize low-cost and simple methods to assess airway and lung inflammation biomarkers related to air pollution. METHODS: A total of 87 male, non-smoking, healthy subjects working as street traffic-controllers or office-workers were examined to determine carbon monoxide in exhaled breath and to measure the pH in nasal lavage fluid and exhaled breath condensate. Air pollution exposure was measured by particulate matter concentration, and data were obtained from fixed monitoring stations (8-h work intervals per day, during the 5 consecutive days prior to the study). RESULTS: Exhaled carbon monoxide was two-fold greater in traffic-controllers than in office-workers. The mean pH values were 8.12 in exhaled breath condensate and 7.99 in nasal lavage fluid in office-workers; these values were lower in traffic-controllers (7.80 and 7.30, respectively). Both groups presented similar cytokines concentrations in both substrates, however, IL-1β and IL-8 were elevated in nasal lavage fluid compared with exhaled breath condensate. The particulate matter concentration was greater at the workplace of traffic-controllers compared with that of office-workers. CONCLUSION: The pH values of nasal lavage fluid and exhaled breath condensate are important, robust, easy to measure and reproducible biomarkers that can be used to monitor occupational exposure to air pollution. Additionally, traffic-controllers are at an increased risk of airway and lung inflammation during their occupational activities compared with office-workers.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade de São Paulo Faculdade de Medicina Department of PathologyUniversidade de São Paulo Faculdade de Medicina Department of PhysiotherapyPhilipps University Department of PulmonologyLeiden University Medical Center Department of PulmonologyUniversidade Federal de São Paulo (UNIFESP) School of Medicine Department of PneumologyPneumology Division Pneumology DivisionInstituto do Coracao Instituto do CoracaoUniversidade de São Paulo Faculdade de MedicinaUniversidade de São Paulo Faculdade de Medicina Department of Internal MedicineUniversidade de São Paulo Public Health Faculty Department of EpidemiologyUniversidade de São Paulo Institute of Mathematics and StatisticsUNIFESP, School of Medicine Department of PneumologyFAPESP: 07/51605-9FAPESP: 09/50056-7CNPq: 555.223/06-0SciEL

Sex- differences in alpha-1 antitrypsin deficiency:Data from the EARCO Registry

Background: Sex and gender influence many aspects of chronic obstructive pulmonary disease (COPD). Limited data are available on this topic in alpha-1 antitrypsin deficiency (AATD). We therefore aimed to investigate sex issues in the EARCO registry, a prospective, international, observational cohort study.Methods: Baseline data from PiZZ individuals, enrolled in the registry with complete data on sex and smoking history were analysed by group comparisons and binary logistic regression analyses.Results: 1283 patients with AATD, 49.3% women were analysed. Females reported less tobacco consumption (16.8 ± 12.2 vs. 19.6 ± 14.5 PY, p = 0.006), occupational exposures towards gases, dusts or asbestos (p < 0.005 each) and consumed less alcohol (5.5 ± 7.6 vs. 8.4 ± 10.3 u/week, p < 0.001). Females reported COPD (41% vs. 57%, p < 0.001) and liver disease (11% vs. 20%, p < 0.001) less often. However, they had a higher prevalence of bronchiectasis (24% vs. 13%, p < 0.001). Despite better lung function (FEV1%pred. 73.6 ± 29.9 vs. 62.7 ± 29.5, p < 0.001) females reported a similar symptom burden (CAT 13.4 ± 9.5 vs. 12.5 ± 8.9, p = ns) and exacerbation frequency (at least one in the previous year 30% vs. 26%, p = ns) compared to males. In multivariate analyses, female sex was an independent risk factor for exacerbations in the previous year OR 1.6 p = 0.001 in addition to smoking history, COPD, asthma and bronchiectasis and was also identified as risk factors for symptom burden (CAT ≥ 10) OR 1.4 p = 0.014 besides age, BMI, COPD and smoking history.Conclusion: Men had higher rates of COPD and liver disease, women were more likely to have bronchiectasis. Women's higher symptom burden and exacerbation frequency suggest they may need tailored treatment approaches

Detection of volatile organic compounds as potential novel biomarkers for chorioamnionitis - proof of experimental models

Background: Histologic chorioamnionitis is only diagnosed postnatally which prevents interventions. We hypothesized that volatile organic compounds (VOCs) in the amniotic fluid might be useful biomarkers for chorioamnionitis and that VOC profiles differ between amnionitis of different origins. Methods: Time-mated ewes received intra-amniotic injections of media or saline (controls), or live Ureaplasma parvum serovar 3 (Up) 14, 7 or 3d prior to c-section at day 124 gestational age (GA). 100 μg recombinant ovine IL-1α was instilled at 7, 3 or 1d prior to delivery. Headspace VOC profiles were measured from amniotic fluids at birth using ion mobility spectrometer coupled with multi-capillary columns. Results: 127 VOC peaks were identified. 27 VOCs differed between samples from controls and Up- or IL-1α induced amnionitis. The best discrimination between amnionitis by Up vs. IL-1α was reached by 2-methylpentane, with a sensitivity/specificity of 96/95% and a positive predictive value/negative predictive values of 96 and 95%. The concentration of 2-methylpentane in VOCs peaked 7d after intra-amniotic instillation of Up. Discussion: We established a novel method to study headspace VOC profiles of amniotic fluids. VOC profiles may be a useful tool to detect and to assess the duration of amnionitis induced by Up. 2-methylpentane was previously described in the exhalate of women with pre-eclampsia and might be a volatile biomarker for amnionitis. Amniotic fluids analyzed by ion mobility spectrometry coupled with multi-capillary columns may provide bedside diagnosis of amnionitis and understanding inflammatory mechanisms during pregnancy