The infusion of menthol into the esophagus evokes cold sensations in healthy subjects but induces heartburn in patients with gastroesophageal reflux disease (GERD).

Recent studies in animal models have reported that some afferent fibers innervating the esophagus express the cold receptor TRPM8. In the somatosensory system the stimulation of TRPM8 leads to cold sensations and in certain circumstances alleviates pain. It is therefore hypothesized in this paper that the esophageal infusion of the TRPM8 activator menthol evokes cold sensations from the esophagus and alleviates heartburn in humans. The esophageal infusion of menthol (3 mM, 20 min) evoked cold sensations in 11 of 12 healthy subjects. In striking contrast, the esophageal infusion of menthol evoked heartburn in 10 of 10 patients with gastroesophageal reflux disease (GERD). In healthy subjects the cold sensation evoked by menthol was perceived only as a minor discomfort as evaluated by the visual analog scale (VAS score 1.9 ± 0.3 on the scale 1-10). However, in patients with GERD the menthol-induced heartburn was perceived as painful (VAS score 5.6 ± 0.6, P < 0.01 compared to healthy subjects). It is concluded that the sensations evoked by esophageal infusion of menthol change from relatively nonpainful cold sensations in healthy subjects to painful heartburn sensations in patients with GERD. These qualitative and quantitative changes indicate substantial alterations in afferent signaling mediating sensations from the esophagus in patients with GERD.

Cough reflex sensitivity does not correlate with the esophageal sensitivity to acid in patients with gastroesophageal reflux disease.

The sensitization of cough reflex observed in patients with gastroesophageal reflux disease (GERD) is attributed to activation of vagal C-fibers innervating the esophagus by acid, while the heartburn in GERD is mediated by esophageal acid sensitive C-fibers derived from (dorsal root ganglia) DRG. Here we explored the relationship between cough reflex sensitivity (CRS) and esophageal sensitivity to acid. We evaluated CRS to capsaicin inhalation and esophageal sensitivity to acid (intensity of heartburn evoked by esophageal infusions of acid pH = 3, 2 and 1) in patients with GERD and chronic heartburn before and 3 months after proton pump inhibitor (PPI) treatment. There was no correlation between CRS and esophageal sensitivity to acid at any pH tested. PPI treatment substantially reduced esophageal sensitivity to acid but did not affect CRS. We conclude that a simple direct relationship between CRS and esophageal sensitivity to acid is unlikely. The results indicate that spinal and vagal afferent pathways from the esophagus are probably influenced separately in subjects with GERD.

Structure of vagal afferent nerve terminal fibers in the mouse trachea.

The structure of primary afferent nerve terminals profoundly influences their function. While the complex vagal airway nerve terminals (stretch receptors, cough receptors and neuroepithelial bodies) were thoroughly characterized, much less is known about the structure of airway nerves that do not form distinct complex terminals (often termed free nerve fibers). We selectively induced expression of GFP in vagal afferent nerves in the mouse by transfection with AAV-GFP virus vector and visualized nerve terminals in the trachea by whole organ confocal imaging. Based on structural characteristics we identified four types of vagal afferent nerve fiber terminals in the trachea. Importantly, we found that distinct compartments of tracheal tissue are innervated by distinct nerve fiber terminal types in a non-overlapping manner. Thus, separate terminal types innervate tracheal epithelium vs. anterolateral tracheal wall containing cartilaginous rings and ligaments vs. dorsal wall containing smooth muscle. Our results will aid the study of structure-function relationships in vagal airway afferent nerves and regulation of respiratory reflexes.

Impact of Air Pollution on Age and Gender Related Increase in Cough Reflex Sensitivity of Healthy Children in Slovakia.

BACKGROUND: Numerous studies show higher cough reflex sensitivity (CRS) and cough outcomes in children compared to adults and in females compared to males. Despite close link that exists between cough and environment the potential influence of environmental air pollution on age- and gender -related differences in cough has not been studied yet. PURPOSE: The purpose of our study was to analyse whether the effects of exposure to environmental tobacco smoke (ETS) from parental smoking and PM10 from living in urban area are implied in age- and gender-related differences in cough outcomes of healthy, non-asthmatic children. Assessment of CRS using capsaicin and incidence of dry and wet cough was performed in 290 children (mean age 13.3 ± 2.6 years (138 females/152 males). RESULTS: CRS was significantly higher in girls exposed to ETS [22.3 µmol/l (9.8-50.2 µmol/l)] compared to not exposed girls [79.9 µmol/l (56.4-112.2 µmol/l), p = 0.02] as well as compared to exposed boys [121.4 µmol/l (58.2-253.1 µmol/l), p = 0.01]. Incidence of dry cough lasting more than 3 weeks was significantly higher in exposed compared to not exposed girls. CRS was significantly higher in school-aged girls living in urban area [22.0 µmol/l (10.6-45.6 µmol/l)] compared to school-aged girls living in rural area [215.9 µmol/l (87.3-533.4 µmol/l); p = 0.003], as well as compared to teenage girls living in urban area [108.8 µmol/l (68.7-172.9 µmol/l); p = 0.007]. No CRS differences were found between urban and rural boys when controlled for age group. No CRS differences were found between school-aged and teenage boys when controlled for living area. CONCLUSIONS: Our results have shown that the effect of ETS on CRS was gender specific, linked to female gender and the effect of PM10 on CRS was both gender and age specific, related to female gender and school-age. We suggest that age and gender related differences in incidence of cough and CRS might be, at least partially, ascribed to the effect of environmental pollutants. The role of age and gender in the effect of air pollution on cough strongly suggest some interplay of development with biological and behavioral factors.

Relationship between variation of seasonal temperature and extent of occupational exposure to phthalates.

Spot urine samples were collected in summer and winter season to examine the association between temperature variation and phthalate concentration in an occupationally exposed group. We analysed samples by high-performance liquid chromatography with mass spectrometry (HPLC-MS/MS) to determine the concentrations of four phthalate metabolites: mono (2-ethylhexyl) phthalate (MEHP), monobutyl phthalate (MnBP), monoethyl phthalate (MEP), and monoisononyl phthalate (MiNP). We observed significantly higher urinary concentrations of all monitored phthalate metabolites collected during the summer in occupationally exposed group (MEP p < 0.0015, MiNP p < 0.0001, MnBP p < 0.00019, and MEHP p < 0.05); however, in general, population was noticed this difference only for MEHP (p < 0.05) in winter season. We conclude that increasing indoor and outdoor temperature is related to phthalate exposure in specific types of work environment.

Use of selected prediction equations (CG, MDRD4, CKD-EPI) in improving glomerular filtration rate assessment in clinical practice in Slovakia.

Our study aimed to establish the best prediction equation for different age ranges in estimating Glomerular Filtration Rate (GFR) in clinical practice in Slovakia. The GFR by 24-hour creatinine clearance (Ccr) and the estimated GFR (eGFR) using the Cockcroft-Gault (CG), the four-variable Modification of Diet in Renal Disease (MDRD4) and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations were obtained in adults aged 30-80 (n = 433, 10-years intervals). The correlation between these prediction equations and Ccr was evaluated. Errors in prediction equations were detected by moving average and by comparisons of the formulas for GFR < 1.5 ml/s and > 1.5 ml/s. The best correlations were established between Ccr and MDRD4 for women (r = 0.7790) and men (r = 0.8009), and between Ccr and CKD-EPI for women (r = 0.7780) and men (r = 0.8002) in the 60-69 age range. High correlation was also established between Ccr and CG (r = 0.8655) and MDRD4 (r = 0.8713) for men in the 40-49 age range. With the exception of the 30-40 age range, a low prediction error was observed for each age range in both genders when GFR was < 1.5 ml/s. We recommend utilization of the MDRD4 and CG equations for men (40-49 years) and MDRD4 and CKD-EPI for women and men (60-69 years), as preferred substitutes for Ccr.