Exhaled Breath Profiles Before, During and After Exacerbation of COPD: A Prospective Follow-Up Study.

Many patients with chronic obstructive lung disease (COPD) experience exacerbations. The diagnosis of an exacerbation is solely based on symptoms. We hypothesized that exhaled breath profiles, measured by Gas Chromatography-Mass Spectrometry (GC-MS) or electronic nose (eNose), are different between stable disease and exacerbations and may have the potential to serve as biomarkers for COPD exacerbations. In this prospective follow-up study, breath samples were taken during stable COPD, during a subsequent exacerbation and after recovery. Samples were analyzed by GC-MS and eNose. CCQ symptom scores were associated with univariate outcomes of GC-MS and eNose using analysis of covariance (ANCOVA). After multivariate modeling by Principal Component Analysis (PCA), paired student t-tests were performed. Sixty-eight patients were included, 31 had an exacerbation and 16 patients had breath sampled at all three time points. Significant differences were found in breathprints taken during exacerbation as compared to baseline and recovery for both GC-MS and eNose. Breath profiles obtained by GC-MS as well as by eNose showed a correct classification of 71% (10/14) for baseline vs exacerbation and of 78% (11/14) for exacerbation vs recovery. These results provide proof of principle that exhaled breath can serve as a noninvasive biomarker for the diagnosis of COPD exacerbations.

Exhaled breath profiles in the monitoring of loss of control and clinical recovery in asthma.

BACKGROUND: Asthma is a chronic inflammatory airway disease, associated with episodes of exacerbations. Therapy with inhaled corticosteroids (ICS) targets airway inflammation, which aims to maintain and restore asthma control. Clinical features are only modestly associated with airways inflammation. Therefore, we hypothesized that exhaled volatile metabolites identify longitudinal changes between clinically stable episodes and loss of asthma control. OBJECTIVES: To determine whether exhaled volatile organic compounds (VOCs) as measured by gas-chromatography/mass-spectrometry (GC/MS) and electronic nose (eNose) technology discriminate between clinically stable and unstable episodes of asthma. METHODS: Twenty-three patients with (partly) controlled mild to moderate persistent asthma using ICS were included in this prospective steroid withdrawal study. Exhaled metabolites were measured at baseline, during loss of control and after recovery. Standardized sampling of exhaled air was performed, after which samples were analysed by GC/MS and eNose. Univariate analysis of covariance (ANCOVA), followed by multivariate principal component analysis (PCA) was used to reduce data dimensionality. Next paired t tests were utilized to analyse within-subject breath profile differences at the different time-points. Finally, associations between exhaled metabolites and sputum inflammation markers were examined. RESULTS: Breath profiles by eNose showed 95% (21/22) correct classification for baseline vs loss of control and 86% (19/22) for loss of control vs recovery. Breath profiles using GC/MS showed accuracies of 68% (14/22) and 77% (17/22) for baseline vs loss of control and loss of control vs recovery, respectively. Significant associations between exhaled metabolites captured by GC/MS and sputum eosinophils were found (Pearson r≥.46, P<.01). CONCLUSIONS & CLINICAL RELEVANCE: Loss of asthma control can be discriminated from clinically stable episodes by longitudinal monitoring of exhaled metabolites measured by GC/MS and particularly eNose. Part of the uncovered biomarkers was associated with sputum eosinophils. These findings provide proof of principle for monitoring and identification of loss of asthma control by breathomics.

Exhaled air molecular profiling in relation to inflammatory subtype and activity in COPD.

Eosinophilic inflammation in chronic obstructive pulmonary disease (COPD) is predictive for responses to inhaled steroids. We hypothesised that the inflammatory subtype in mild and moderate COPD can be assessed by exhaled breath metabolomics. Exhaled compounds were analysed using gas chromatography and mass spectrometry (GC-MS) and electronic nose (eNose) in 28 COPD patients (12/16 Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I/II, respectively). Differential cell counts, eosinophil cationic protein (ECP) and myeloperoxidase (MPO) were measured in induced sputum. Relationships between exhaled compounds, eNose breathprints and sputum inflammatory markers were analysed and receiver operating characteristic (ROC) curves were constructed. Exhaled compounds were highly associated with sputum cell counts (eight compounds with eosinophils, 17 with neutrophils; p < 0.01). Only one compound (alkylated benzene) overlapped between eosinophilic and neutrophilic profiles. GC-MS and eNose breathprints were associated with markers of inflammatory activity in GOLD stage I (ECP: 19 compounds, p < 0.01; eNose breathprint r = 0.84, p = 0.002) (MPO: four compounds, p < 0.01; eNose r = 0.72, p = 0.008). ROC analysis for eNose showed high sensitivity and specificity for inflammatory activity in mild COPD (ECP: area under the curve (AUC) 1.00; MPO: AUC 0.96) but not for moderate COPD. Exhaled molecular profiles are closely associated with the type of inflammatory cell and their activation status in mild and moderate COPD. This suggests that breath analysis may be used for assessment and monitoring of airway inflammation in COPD.

Sudden infant death syndrome in relation to weather and optimetrically measured air pollution in Taiwan.

OBJECTIVE: To examine the possible role of weather and air pollution in sudden infant death syndrome (SIDS) and suffocation. METHODS: Poisson regression analysis was carried out to measure the association between daily rates of SIDS per 1000 live births and daily average values of visibility and temperature in Taiwan between 1981 and 1991. The optimetrical measure of air pollution was used to represent pollution over a whole area rather than at a point source. RESULTS: Mortality from SIDS per 1000 live births was 3.3 times greater in the lowest category of visibility on the day of death than in the highest category; this rate ratio was 3.4 for the average visibility during the 9 days before death. Adjustment for population size, season, level of urbanization, incidence of deaths from respiratory tract infections, temperature, air pressure, sunshine, rainfall, relative humidity, and windspeed increased these rate ratios to 3.8 and 5.1, respectively. This suggests that the relationship between air pollution and SIDS is not biased by ecological confounders. For temperature the rate ratios were between 3.3 and 4.0. CONCLUSIONS: Our findings confirm the association of climatic temperature and air pollution with SIDS.

Urban-rural and regional differences in infant mortality in Taiwan.

We analyzed data from death certificates for all infant deaths in Taiwan from 1981 to 1988. During this 8-year period, the crude infant mortality rate decreased from 8.9 to 5.3 per 1000 live births. Deaths due to infectious diseases, which constituted a major fraction of this mortality, also declined from 3.4 to 1.2 per 1000 live births. While infant deaths due to nearly all causes declined, deaths due to injury and accidents rose from 0.62 to 0.71 per 1000 live births, and the sudden infant death rate rose from 0.13 to 0.46. Notable geographic differences included a high death rate in the small islands off the coast and in the eastern mountainous counties (9.1-11.2/1000 live births); this rate was twice that in Taipei (4.5/1000 live births). In addition, the level of urbanisation was also an important determinant of death rate; urban areas had much lower rates than rural areas. The highest rate (15.4) was persistently observed in the rural areas where the aboriginal tribes reside. This differential rate between urban and rural areas was most prominent for the vaccine-preventable diseases; the aboriginal areas had rates that were 12.9 times those in the cities. Moreover, since neonatal deaths are severely under-reported in Taiwan, especially in less urbanized areas, our data presumably underestimate the urban-rural health differences. Our findings identify high risk areas for various causes of infant death, and indicate that more targeted intervention such as improving education and health care as well as environmental hygiene in some specific areas may be warranted.

Gender differences in postneonatal infant mortality in Taiwan.

Numerous studies have indicated that gender discrimination influencing child survival is widespread in Asia. Therefore, we have investigated gender and cause-specific postneonatal mortality in Taiwan. Mortality data derived from death certificates and demographic statistics in Taiwan between 1981 and 1990 were analyzed. Postneonatal mortality decreased from 9.4 per 1000 live births to 5.5 per 1000 live births for males, and from 8.3 to 5.0 for females. The trends for cause-specific mortality for male and female infants were similar during the study period. The male-to-female ratio of overall death rates was 1.11. It was slightly higher in cities and lower in rural areas, and lowest in the least developed eastern region of Taiwan. Mortality from congenital diseases had the lowest male-to-female ratio, specifically in the North, the cities and areas of indigenous people. Infectious disease mortality showed low male-to-female ratios in the rural areas and in the eastern region. The place of death from infectious diseases as a measure for the use of sophisticated medical care showed that more female than male deaths occurred at home in the rural areas, cities, and central regions. It was concluded that a high level of socio-economic development created conditions of gender equality, whereas in situations of low socio-economic development males were favoured. The tendency to discriminate according to gender is very subtle in Taiwan, much less so than in other regions of Asia, including Thailand and India.

Exhaled breath analysis with electronic nose technology for detection of acute liver failure in rats.

The aim of this study was to assess the classification accuracy of an e-Nose in detecting acute liver failure (ALF) in rats. Exhaled breath from 14 rats was repeatedly sampled by e-Nose (8 sensors) and an additional external CO2 sensor at three stages: healthy period; portacaval shunt; and during the development of ALF due to surgically induced complete liver ischemia. We performed principal component analysis (PCA) on the (grouped) sensor data in each stage and the classification accuracy of the first two principal components was assessed by the leave-one-out approach. In addition we performed gas chromatography-mass spectrometry (GC-MS) analysis of the exhaled breath from three rats. The first and second principal components from the PCA analysis of e-Nose data accounted for more than 95% variance in the data. Measurements in the ALF stage were contrasted with the measurements in the control stage. Leave-one-out validation showed classification accuracy of 96%. This accuracy was reached after 3h of ALF development, and was reached already after 2h when data of an external CO2 sensor were also included. GC-MS identified 2-butanol, 2-butanone, 2-pentanone and 1-propanol to be possibly elevated in the ALF stage. This is the first study to demonstrate that ALF in rats can be detected by e-Nose data analysis of the exhaled breath. Confirmation of these results in humans will be an important step forward in the non-invasive diagnosis of ALF.

Effect of transportation and storage using sorbent tubes of exhaled breath samples on diagnostic accuracy of electronic nose analysis.

Many (multi-centre) breath-analysis studies require transport and storage of samples. We aimed to test the effect of transportation and storage using sorbent tubes of exhaled breath samples for diagnostic accuracy of eNose and GC-MS analysis. As a reference standard for diagnostic accuracy, breath samples of asthmatic patients and healthy controls were analysed by three eNose devices. Samples were analysed by GC-MS and eNose after 1, 7 and 14 days of transportation and storage using sorbent tubes. The diagnostic accuracy for eNose and GC-MS after storage was compared to the reference standard. As a validation, the stability was assessed of 15 compounds known to be related to asthma, abundant in breath or related to sampling and analysis. The reference test discriminated asthma and healthy controls with a median AUC (range) of 0.77 (0.72-0.76). Similar accuracies were achieved at t1 (AUC eNose 0.78; GC-MS 0.84), t7 (AUC eNose 0.76; GC-MS 0.79) and t14 (AUC eNose 0.83; GC-MS 0.84). The GC-MS analysis of compounds showed an adequate stability for all 15 compounds during the 14 day period. Short-term transportation and storage using sorbent tubes of breath samples does not influence the diagnostic accuracy for discrimination between asthma and health by eNose and GC-MS.

[Contribution to clinic and pathohistology of keratotorus (author's transl)]. / Beitrag zur Klinik und Pathohistologie des Keratotorus.

In a case of keratotorus on both sides with extreme thinning of the cornea first a lamellar and in a second sitting a perforating keratoplasty was performed. Surgical approach and postoperative results are discussed.

[Development of the retrocorneal membrane following trauma]. / Zur Entstehung der retrokornealen Membran nach Trauma.

The authors report on 48 eyes drawn from the histological material of Hamburg University Eye Clinic, which were enucleated because of painful secondary narrow-angle glaucoma, phthisis bulbi resulting from accidents, or iatrogenic trauma, and which were found to have a retrocorneal membrane. The clinical and histopathological pictures are presented and the pathogenesis is discussed.

Capillary zone electrophoresis and ion-exchange capillary electrochromatography: analytical tools for probing the Hanford nuclear site environment.

Ion-exchange capillary electrochromatography (IE-CEC) is a relatively new separation technique based on the combination of ion-exchange chromatographic and electrophoretic separation mechanisms. IE-CEC offers both the efficiency of capillary electrophoresis and the selectivity and sample capacity of ion-exchange chromatography. The utility of the method was examined with I- and IO3-, which are common constituents of nuclear wastes at Hanford, Washington and other U.S. Department of Energy (DoE) sites, and ReO4-, a surrogate for TcO4-. The advantages and limitations of IE-CEC relative to capillary zone electrophoresis (CZE) are explored. The chief advantages are increased loading capacity and an alternative selectivity to that of CZE, in addition to increased efficiency (relative to conventional ion-exchange chromatography). The run-to-run reproducibility of IE-CEC, however, was found to be a limitation of the technique.

Risk factors of sudden infant death in Chinese babies.

The influence of social and biologic factors on sudden infant death was studied in a large Chinese population. Data from all birth certificates in Taiwan from 1988 to 1992 were merged with death certificate data for postneonatal deaths from sudden infant death syndrome and suffocation. The Cox's proportional hazard model was used to compute multivariate adjusted relative risk estimates and 95% confidence intervals. Age difference of parents of more than 10 years was associated with a relative risk (RR) of 1.8 (multivariate adjusted, 95% confidence interval (CI) 1.3-2.3). Better than elementary education for the father was protective (adjusted RR 0.8, 95% CI 0.7-1.0, p < 0.05), and college education of the mother elevated the risk (adjusted RR 1.2, 95% CI 1.0-1.4, p < 0.05). Infants born second to fourth had an adjusted RR of 1.7 (95% CI 1.5-1.9), and infants born fifth or higher had a RR of 2.3 (95% CI 1.5-3.4). The multivariate adjusted RR for low birth weight and prematurity were 2.3 (95% CI 1.9-2.8) and 1.2 (95% CI 1.0-1.5), respectively. Data from this 5-year cohort in Taiwan emphasize biologic and social variables as important risk factors of sudden infant death in Chinese babies.