Effect of TGF-ß1 on eosinophils to induce cysteinyl leukotriene E4 production in aspirin-exacerbated respiratory disease.

Cysteinyl leukotriene (cysLT) overproduction and eosinophil activation are hallmarks of aspirin-exacerbated respiratory disease (AERD). However, pathogenic mechanisms of AERD remain to be clarified. Here, we aimed to find the significance of transforming growth factor beta 1 (TGF-ß1) in association with cysteinyl leukotriene E4 (LTE4) production, leading to eosinophil degranulation. To evaluate levels of serum TGF-ß1, first cohort enrolled AERD (n = 336), ATA (n = 442) patients and healthy control subjects (HCs, n = 253). In addition, second cohort recruited AERD (n = 34) and ATA (n = 25) patients to investigate a relation between levels of serum TGF-ß1 and urinary LTE4. The function of TGF-ß1 in LTE4 production was further demonstrated by ex vivo (human peripheral eosinophils) or in vivo (BALB/c mice) experiment. As a result, the levels of serum TGF-ß1 were significantly higher in AERD patients than in ATA patients or HCs (P = .001; respectively). Moreover, levels of serum TGF-ß1 and urinary LTE4 had a positive correlation (r = 0.273, P = .037). In the presence of TGF-ß1, leukotriene C4 synthase (LTC4S) expression was enhanced in peripheral eosinophils to produce LTE4, which sequentially induced eosinophil degranulation via the p38 pathway. When mice were treated with TGF-ß1, significantly induced eosinophilia with increased LTE4 production in the lung tissues were noted. These findings suggest that higher levels of TGF-ß1 in AERD patients may contribute to LTE4 production via enhancing LTC4S expression which induces eosinophil degranulation, accelerating airway inflammation.

Biomarker as a research tool in linking exposure to air particles and respiratory health.

UNLABELLED: Some of the environmental toxicants from air pollution include particulate matter (PM10), fine particulate matter (PM2.5), and ultrafine particles (UFP). Both short- and long-term exposure could result in various degrees of respiratory health outcomes among exposed persons, which rely on the individuals' health status. METHODS: In this paper, we highlight a review of the studies that have used biomarkers to understand the association between air particles exposure and the development of respiratory problems resulting from the damage in the respiratory system. Data from previous epidemiological studies relevant to the application of biomarkers in respiratory system damage reported from exposure to air particles are also summarized. RESULTS: Based on these analyses, the findings agree with the hypothesis that biomarkers are relevant in linking harmful air particles concentrations to increased respiratory health effects. Biomarkers are used in epidemiological studies to provide an understanding of the mechanisms that follow airborne particles exposure in the airway. However, application of biomarkers in epidemiological studies of health effects caused by air particles in both environmental and occupational health is inchoate. CONCLUSION: Biomarkers unravel the complexity of the connection between exposure to air particles and respiratory health.

Prenatal sonographic chest and lung measurements for predicting severe pulmonary hypoplasia in left-sided congenital diaphragmatic hernia.

To assess the prenatal evaluation of lung hypoplasia in congenital diaphragmatic hernia (CDH), we attempted to measure the right lung area/thorax area ratio (rLT ratio) in normal fetuses and in seven cases of left-sided CDH. In addition, we analyzed early neonatal blood gas data, which were compared with the prenatal evaluation. The rLT ratio was significantly (p<0.05) higher in normal fetuses (0.27+/-0.02) than in CDH (0.14+/-0.18). The values of PaO(2), arterial-alveolar oxygen difference (A-aDO(2)) and oxygenation index (OI) showed no significant relationship with the rLT ratio in CDH at the early neonatal period. Three infants with CDH survived and showed significant higher values of rLT ratio compared with those in nonsurvived infants (p<0.05). All of the rLT ratios in nonsurvived infants were <0.11. PaO(2) at the early neonatal period was significantly (p<0.05) higher, and both A-aDO(2) and OI were significantly (p<0.05) lower in survived infants than in nonsurvived infants. These results indicated that prenatal evaluation of rLT ratio is useful to predict the severity of lung hypoplasia in infants with left-sided CDH, and blood gas analysis at early neonatal period is also useful to predict the neonatal outcome.

Diagnostic yield of the lactate stress test in 160 patients with suspected respiratory chain disorder.

Aim of the present study was to investigate the diagnostic yield of the lactate-stress-test in unselected patients with suspected respiratory-chain disorder (RCD). Serum lactate was determined before, during and after a 15-minute, constant 30W workload on a bicycle in 48 controls and 160 patients with suspected RCD. 122 had definite RCD, 38 neurological disorders other than RCD. The sensitivity, specificity, positive predictive value, negative predictive value and pre-test likelihood of the test was 69, 74, 89, 42 and 76% respectively. In conclusion, the lactate-stress-test proved a powerful tool to assess impaired oxidative metabolism in RCDs.