Nasal flaring as a clinical sign of respiratory acidosis in patients with dyspnea.

OBJECTIVE: To determine whether the presence of nasal flaring is a clinical sign of respiratory acidosis in patients attending emergency departments for acute dyspnea. METHODS: Single-center, prospective, observational study of patients aged over 15 requiring urgent attention for dyspnea, classified as level II or III according to the Andorran Triage Program and who underwent arterial blood gas test on arrival at the emergency department. The presence of nasal flaring was evaluated by two observers. Demographic and clinical variables, signs of respiratory difficulty, vital signs, arterial blood gases and clinical outcome (hospitalization and mortality) were recorded. Bivariate and multivariate analyses were performed using logistic regression models. RESULTS: The sample comprised 212 patients, mean age 78years (SD=12.8), of whom 49.5% were women. Acidosis was recorded in 21.2%. Factors significantly associated with the presence of acidosis in the bivariate analysis were the need for pre-hospital medical care, triage level II, signs of respiratory distress, presence of nasal flaring, poor oxygenation, hypercapnia, low bicarbonates and greater need for noninvasive ventilation. Nasal flaring had a positive likelihood ratio for acidosis of 4.6 (95% CI 2.9-7.4). In the multivariate analysis, triage level II (aOR 5.16; 95% CI: 1.91 to 13.98), the need for oxygen therapy (aOR 2.60; 95% CI: 1.13-5.96) and presence of nasal flaring (aOR 6.32; 95% CI: 2.78-14.41) were maintained as factors independently associated with acidosis. CONCLUSIONS: Nasal flaring is a clinical sign of severity in patients requiring urgent care for acute dyspnea, which has a strong association with acidosis and hypercapnia.

Aleteo nasal como factor pronóstico de mortalidad en el paciente con disnea grave / Nasal flaring as a predictor of mortality in patients with severe dyspnea

Objetivos: Determinar si la presencia de aleteo nasal es un factor de gravedad clínica y pronóstico de mortalidad hospitalaria en el paciente que consulta en urgencias por disnea. Método: Estudio prospectivo observacional un céntrico. Se incluyeron pacientes mayores de 15 años, que demandaron atención urgente por disnea, catalogados como niveles II y III por el Modelo Andorrano de Triaje (MAT). Se evaluó la presencia de aleteo nasal por dos observadores. Se recogieron variables demográficas, clínicas, signos de dificultad respiratoria, signos vitales, gasometría arterial y evolución clínica (ingreso hospitalario y mortalidad). Se realizaron análisis bivariantes y multivariantes con modelos de regresión logística. Resultados: Se incluyeron 246 pacientes, de edad media ± DE 77 (13) años (DE: 13,2) y un 52% de mujeres. Un19,5% presentaron aleteo nasal. Los pacientes con aleteo nasal tuvieron mayor gravedad en el triaje, más taquipnea, peor oxigenación, más acidosis y más hipercapnia. En el análisis bivariante los factores pronósticos de mortalidad hospitalaria fueron la edad (OR 1,05; IC95%: 1,01-1,10), la atención prehospitalaria por el servicio emergencias médicas (OR 3,97; IC95%: 1,39-11,39), el nivel de triaje II (OR 4,19; IC95%: 1,63-10,78), la presencia de signos de dificultad respiratoria como el aleteo nasal (OR 3,79; IC 95%: 1,65-8,69), la presencia de acidosis (OR 7,09; IC95%: 2,97-16,94) y la hipercapnia (OR 2,67; IC95%: 1,11-6,45). En el análisis multivariante, la edad, el nivel de triaje y el aleteonasal se mantuvieron como factores pronósticos independientes de mortalidad (AU)

Objective: To determine whether the presence of nasal flaring is a clinical sign of severity and a predictor of hospital mortality in emergency patients with dyspnea. Methods: Prospective, observational, single-center study. We enrolled patients older than 15 years of age who required attention for dyspnea categorized as level II or III emergencies according to the Andorran Medical Triage system. Two observers evaluated the presence of nasal flaring. We recorded demographic and clinical variables, including respiratory effort, vital signs, arterial blood gases, and clinical course (hospital admission and mortality). Bivariable analysis was performed and multivariable logistic regression models were constructed. Results: We enrolled 246 patients with a mean (SD) age of 77 (13) years; 52% were female. Nasal flaring was present in 19.5%. Patients with nasal flaring had triage levels indicating greater severity and they had more severe tachypnea, worse oxygenation, and greater acidosis and hypercapnia. Bivariable analysis detected that the following variables were associated with mortality: age (odds ratio [OR], 1.05; 95% CI, 1.01–1.10), prehospital care from the emergency medical service (OR, 3.97; 95% CI, 1.39–11.39), triage level II (OR, 4.19; 95% CI, 1.63–10.78), signs of respiratory effort such as nasal flaring (OR, 3.79; 95% CI, 1.65–8.69), presence of acidosis (OR, 7.09; 95% CI, 2.97–16.94), and hypercapnia (OR, 2.67; 95% CI, 1,11–6,45). The factors that remained independent predictors of mortality in the multivariable analysis were age, severity (triage level), and nasal flaring. Conclusions: In patients requiring emergency care for dyspnea, nasal flaring is a clinical sign of severity and a predictor of mortality (AU)

[Nasal flaring as a predictor of mortality in patients with severe dyspnea]. / Aleteo nasal como factor pronóstico de mortalidad en el paciente con disnea grave.

OBJECTIVES: To determine whether the presence of nasal flaring is a clinical sign of severity and a predictor of hospital mortality in emergency patients with dyspnea. MATERIAL AND METHODS: Prospective, observational, single-center study. We enrolled patients older than 15 years of age who required attention for dyspnea categorized as level II or III emergencies according to the Andorran Medical Triage system. Two observers evaluated the presence of nasal flaring. We recorded demographic and clinical variables, including respiratory effort, vital signs, arterial blood gases, and clinical course (hospital admission and mortality). Bivariable analysis was performed and multivariable logistic regression models were constructed. RESULTS: We enrolled 246 patients with a mean (SD) age of 77 (13) years; 52% were female. Nasal flaring was present in 19.5%. Patients with nasal flaring had triage levels indicating greater severity and they had more severe tachypnea, worse oxygenation, and greater acidosis and hypercapnia. Bivariable analysis detected that the following variables were associated with mortality: age (odds ratio [OR], 1.05; 95% CI, 1.01-1.10), prehospital care from the emergency medical service (OR, 3.97; 95% CI, 1.39-11.39), triage level II (OR, 4.19; 95% CI, 1.63-10.78), signs of respiratory effort such as nasal flaring (OR, 3.79; 95% CI, 1.65-8.69), presence of acidosis (OR, 7.09; 95% CI, 2.97-16.94), and hypercapnia (OR, 2.67; 95% CI, 1,11-6,45). The factors that remained independent predictors of mortality in the multivariable analysis were age, severity (triage level), and nasal flaring. CONCLUSION: In patients requiring emergency care for dyspnea, nasal flaring is a clinical sign of severity and a predictor of mortality.

OBJETIVO: Determinar si la presencia de aleteo nasal es un factor de gravedad clínica y pronóstico de mortalidad hospitalaria en el paciente que consulta en urgencias por disnea. METODO: Estudio prospectivo observacional unicéntrico. Se incluyeron pacientes mayores de 15 años, que demandaron atención urgente por disnea, catalogados como niveles II y III por el Modelo Andorrano de Triaje (MAT). Se evaluó la presencia de aleteo nasal por dos observadores. Se recogieron variables demográficas, clínicas, signos de dificultad respiratoria, signos vitales, gasometría arterial y evolución clínica (ingreso hospitalario y mortalidad). Se realizaron análisis bivariantes y multivariantes con modelos de regresión logística. RESULTADOS: Se incluyeron 246 pacientes, de edad media ± DE 77 (13) años (DE: 13,2) y un 52% de mujeres. Un 19,5% presentaron aleteo nasal. Los pacientes con aleteo nasal tuvieron mayor gravedad en el triaje, más taquipnea, peor oxigenación, más acidosis y más hipercapnia. En el análisis bivariante los factores pronósticos de mortalidad hospitalaria fueron la edad (OR 1,05; IC95%: 1,01-1,10), la atención prehospitalaria por el servicio emergencias médicas (OR 3,97; IC95%: 1,39-11,39), el nivel de triaje II (OR 4,19; IC95%: 1,63-10,78), la presencia de signos de dificultad respiratoria como el aleteo nasal (OR 3,79; IC 95%: 1,65-8,69), la presencia de acidosis (OR 7,09; IC95%: 2,97- 16,94) y la hipercapnia (OR 2,67; IC95%: 1,11-6,45). En el análisis multivariante, la edad, el nivel de triaje y el aleteo nasal se mantuvieron como factores pronósticos independientes de mortalidad. CONCLUSIONES: El aleteo nasal es un signo clínico de gravedad y predictor de mortalidad en los pacientes que demandan atención urgente por disnea.

Direct stimulatory effect of ghrelin on pituitary release of LH through a nitric oxide-dependent mechanism that is modulated by estrogen.

Ghrelin, a gut peptide with key actions on food intake and GH secretion, has been recently recognized as potential regulator of reproductive function. Thus, in adult female rats, ghrelin has been proven to modulate GnRH/LH secretion, with predominant inhibitory effects in vivo. We analyze herein potential direct pituitary effects of ghrelin on basal and GnRH-stimulated gonadotropin secretion in prepubertal female rats, and its interplay with ovarian inputs, nitric oxide (NO), and hypothalamic differentiation. In the experimental setting, pituitaries from intact and ovariectomized prepubertal female rats were challenged with ghrelin in vitro and LH secretion was monitored. Our results demonstrate that 1) ghrelin consistently stimulated in vitro pituitary LH secretion under different experimental conditions; 2) the sensitivity to ghrelin, expressed either as the minimal effective dose or the amplitude of the LH response, was modulated by ovarian inputs; 3) the blockade of estrogen action significantly augmented the stimulatory effect of ghrelin; 4) the stimulatory effect of ghrelin on LH secretion required proper NO synthesis; and 5) the ability of ghrelin to elicit LH secretion in vitro was preserved after alteration (masculinization) of brain sexual differentiation. Overall, our present data reinforce the concept that ghrelin participates in the control of LH secretion, with potential stimulatory actions at the pituitary level that require the presence of NO and are modulated by ovarian signals.

Expression of hypothalamic KiSS-1 system and rescue of defective gonadotropic responses by kisspeptin in streptozotocin-induced diabetic male rats.

Hypogonadotropism is a common feature of uncontrolled diabetes, for which the ultimate mechanism remains to be elucidated. Kisspeptins, ligands of G protein-coupled receptor 54 (GPR54) encoded by the KiSS-1 gene, have recently emerged as major gatekeepers of the gonadotropic axis. Alteration in the hypothalamic KiSS-1 system has been reported in adverse metabolic conditions linked to suppressed gonadotropins, such as undernutrition. However, its potential contribution to defective gonadotropin secretion in diabetes has not been evaluated. We report herein analyses of luteinizing hormone (LH) responses to kisspeptin and hypothalamic expression of the KiSS-1 gene in streptozotocin (STZ)-induced diabetic male rats. In addition, functional studies involving kisspeptin replacement or continuous administration of leptin and insulin to diabetic male rats are presented. Kisspeptin administration evoked robust LH and testosterone bursts and enhanced postgonadectomy LH concentrations, despite prevailing attenuation of gonadotropic axis in diabetic animals. In addition, hypothalamic KiSS-1 mRNA levels were unambiguously decreased in diabetic male rats, and the postorchidectomy rise in KiSS-1 mRNA was severely blunted. Repeated administration of kisspeptin to diabetic rats evoked persistent LH and testosterone responses and partially rescued prostate and testis weights. In addition, central infusion of leptin, but not insulin, was sufficient to normalize hypothalamic KiSS-1 mRNA levels, as well as LH and testosterone concentrations. In summary, we provide evidence for altered expression of the hypothalamic KiSS-1 system in a model of uncontrolled diabetes. This observation, together with the ability of exogenous kisspeptin to rescue defective LH responses in diabetic rats, unravel the physiopathological implication, and potential therapeutic intervention, of the KiSS-1 system in altered gonadotropin secretion of type 1 diabetes.

Effects of ghrelin upon gonadotropin-releasing hormone and gonadotropin secretion in adult female rats: in vivo and in vitro studies.

A reproductive facet of ghrelin, a stomach-derived orexigenic peptide involved in energy homeostasis, has been recently suggested, and predominantly inhibitory effects of ghrelin upon luteinizing hormone (LH) secretion have been demonstrated in rat models. Yet, the modulatory actions of ghrelin on the gonadotropic axis remain scarcely evaluated. We report herein a detailed analysis of the effects of ghrelin upon LH and follicle-stimulating hormone (FSH) secretion in the female rat, using a combination of in vivo and in vitro approaches. Intracerebroventricular administration of ghrelin (3 nmol/rat) evoked a significant inhibition of LH secretion in cyclic female rats throughout the estrous cycle (proestrus afternoon, estrus, metestrus), as well as in ovariectomized females. In good agreement, gonadotropin-releasing hormone (GnRH) secretion by hypothalamic fragments from ovariectomized females was significantly inhibited by ghrelin. In contrast, ghrelin dose-dependently stimulated basal LH and FSH secretion by pituitary tissue in vitro; a phenomenon that was proven dependent on the phase of estrous cycle, as it was neither detected at estrus nor observed after ovariectomy. Conversely, GnRH-stimulated LH secretion in vitro was persistently inhibited by ghrelin regardless of the stage of the cycle, whereas stimulated FSH secretion was only inhibited by ghrelin at estrus. In addition, cyclic fluctuations in mRNA levels of growth hormone secretagogue receptor (GHS-R)1a, i.e. the functional ghrelin receptor, were observed in the pituitary, with low values at estrus and metestrus. GHS-R1a mRNA levels, however, remained unchanged after ovariectomy. In summary, our data illustrate a complex mode of action of ghrelin upon the gonadotropic axis, with predominant inhibitory effects at central (hypothalamic) levels and upon GnRH-induced gonadotropin secretion, but direct stimulatory actions on basal LH and FSH secretion. Overall, our results further document the reproductive role of ghrelin, which might be relevant for the integrated control of energy balance and reproduction.

Ghrelin effects on gonadotropin secretion in male and female rats.

Ghrelin is a 28-amino acid peptide primarily involved in the control of food intake and growth hormone secretion. The present experiments were carried out to analyze the potential involvement of ghrelin in the control of gonadotropin secretion. Prepubertal intact and gonadectomized female and male rats, cyclic rats in diestrus, lactating rats and aged female rats were i.c.v. injected with ghrelin (3 nmol/rat) and blood samples were obtained by decapitation 15 min later. In addition, we analyzed the effects of ghrelin on in vitro basal and luteinizing hormone-releasing hormone (LHRH)-stimulated gonadotropin secretion. Our present results indicate that ghrelin inhibited luteinizing hormone (LH) secretion in vivo in prepubertal males as well as gonadectomized males and females, whereas follicle-stimulating hormone (FSH) remained unaffected. In vitro, ghrelin stimulated the secretion of both gonadotropins, and differentially modulated the response to LHRH; the LH response was inhibited, while the FSH response was enhanced. Overall, our current data open up the possibility that ghrelin may be involved in the control of LH secretion, and in the dissociation of both gonadotropins that takes place in many physiological, pathological and experimental situations.

Ghrelin inhibits prolactin secretion in prepubertal rats.

Ghrelin, a novel 28-amino-acid peptide primarily expressed in stomach and hypothalamus, has recently emerged as the endogenous ligand for the GH-secretagogue receptor with ability to stimulate GH secretion in humans and rats. In addition, ghrelin also stimulates prolactin (PRL) secretion in humans. However, its role in the regulation of PRL secretion in rats remains largely unknown. In this context, the present experiments were carried out to analyze the effects of ghrelin on PRL secretion in male and female rats. In detail, the ontogeny and potential sexual dimorphism in the PRL response to ghrelin was evaluated. In addition, the hypothalamic and/or pituitary site of primary action of ghrelin, as well as the possible interactions between ghrelin and other neurotransmitters, as nitric oxide, dopamine, serotonin or excitatory amino acids, in the precise control of PRL secretion were assessed. Experiments were conducted in prepubertal male and female animals. Systemic (i.p.) and central (i.c.v.) administration of ghrelin significantly inhibited PRL secretion. Such an inhibitory effect became evident after day 10 of age, was similar in males and females, and was also observed in hyperprolactinemic aged female rats. In contrast, however, challenge of pituitary samples in vitro with increasing doses of ghrelin (10(-9)-10(-7)M) failed to inhibit PRL secretion. Analysis of interactions between ghrelin and other systems involved in the control of PRL secretion revealed that neither blockade of dopaminergic receptors with domperidone, nor enhancement of serotoninergic tone with fluoxetine + 5-hydroxytryptophan altered the inhibitory response to ghrelin in terms of PRL secretion. Similarly, blockade of nitric oxide synthases with L-nitro-arginine-methyl ester failed to modify the magnitude of ghrelin-induced inhibition of PRL secretion, whereas ghrelin was unable to further decrease serum PRL levels after activation of ionotropic excitatory amino acid receptors by administration of NMDA or AMPA. In conclusion, our data indicate that ghrelin is able to inhibit PRL secretion in male and female rats, likely through an extrapituitary primary site of action that is independent of nitric oxide, dopamine, and serotonin systems.