Low levels of miR-143-3p are associated with severe chronic rhinosinusitis with nasal polyps.

microRNAs (miRNAs) are small, single-stranded, non-coding RNA molecules that regulate post-transcriptional gene expression. Accumulating evidence suggests their involvement in regulating various biological and pathological processes, including inflammation. Studies have revealed distinct expression patterns of miRNAs in Chronic Rhinosinusitis with (CRSwNP) and without (CRSsNP) nasal polyps (1). Specifically, miR-155 and miR-21 have been observed to be upregulated in CRSwNP, increasing and attenuating the expression of pro-inflammatory cytokines, respectively (2,3). Conversely, the downregulation of miR-34, miR-449, and members of the miR-200 family has been associated with impaired ciliogenesis and the regulation of epithelial-mesenchymal transition, respectively (4,5). Nonetheless, the direct role of miRNAs in CRSwNP is still being investigated.

Weight Loss and Vitamin D Improve Hyporesponsiveness to Corticosteroids in Obese Asthma.

BACKGROUND AND OBJECTIVES: Obesity negatively impacts on the response of asthma patients to inhaled corticosteroids. The mechanisms underlying this impact are unknown. Objective: To demonstrate that the poor response to inhaled corticosteroids in obese asthma patients is associated with impaired anti-inflammatory activity of corticosteroids and vitamin D deficiency, both of which are improved by weight loss. METHODS: The study population comprised 23 obese asthma patients (OA) (18 females; median (IQR) age 56 [51-59] years), 14 nonobese asthma patients (NOA) (11 females; 53 [43-60] years), 15 obese patients (OP) (13 females; 47 [45-60] years), and 19 healthy controls (HC) (14 females; 43 [34-56] years). Ten OA and 11 OP were evaluated at baseline (V1) and 6 months after bariatric surgery (V2). Corticosteroid response was measured using dexamethasone-induced inhibition of peripheral blood mononuclear cell (PBMC) proliferation. Lung function and serum levels of leptin, adiponectin, and vitamin D were measured at V1 and V2. RESULTS: We found a reduced response to dexamethasone in PBMCs of OP and OA with respect to NOA and HC; this inversely correlated with the adiponectin/leptin ratio and vitamin D levels. Bariatric surgery improved corticosteroid responses in OP and OA and normalized the adiponectin/leptin ratio and vitamin D levels. Exposure of PBMCs to vitamin D potentiated the antiproliferative effects of corticosteroids. Dexamethasone and vitamin D induced similar MKP1 expression in OP and OA. CONCLUSION: The efficacy of weight loss to improve symptoms and lung function in OA may be due, at least in part, to the recovered anti-inflammatory effects of corticosteroids. Vitamin D deficiency may contribute to corticosteroid hyporesponsiveness in OA.

Weight Loss and Vitamin D Improve Hyporesponsiveness to Corticosteroids in Obese Asthma

Background: Obesity negatively impacts on the response of asthma patients to inhaled corticosteroids. The mechanisms underlying this impact are unknown. Objective: To demonstrate that the poor response to inhaled corticosteroids in obese asthma patients is associated with impaired anti-inflammatory activity of corticosteroids and vitamin D deficiency, both of which are improved by weight loss. Methods: The study population comprised 23 obese asthma patients (OA) (18 females; median (IQR) age 56 [51-59] years), 14 nonobese asthma patients (NOA) (11 females; 53 [43-60] years), 15 obese patients (OP) (13 females; 47 [45-60] years), and 19 healthy controls (HC) (14 females; 43 [34-56] years). Ten OA and 11 OP were evaluated at baseline (V1) and 6 months after bariatric surgery (V2). Corticosteroid response was measured using dexamethasone-induced inhibition of peripheral blood mononuclear cell (PBMC) proliferation. Lung function and serum levels of leptin, adiponectin, and vitamin D were measured at V1 and V2. Results: We found a reduced response to dexamethasone in PBMCs of OP and OA with respect to NOA and HC; this inversely correlated with the adiponectin/leptin ratio and vitamin D levels. Bariatric surgery improved corticosteroid responses in OP and OA and normalized the adiponectin/leptin ratio and vitamin D levels. Exposure of PBMCs to vitamin D potentiated the antiproliferative effects of corticosteroids. Dexamethasone and vitamin D induced similar MKP1 expression in OP and OA. (AU)

Antecedentes: La obesidad tiene un impacto negativo en la respuesta del asma a los corticosteroides inhalados por mecanismos desconocidos. Objetivo: Demostrar que la mala respuesta a los corticosteroides inhalados en pacientes obesos asmáticos se asocia con una actividad antiinflamatoria alterada de los corticosteroides, así como también a la deficiencia de vitamina D, ambos mejorados por la pérdida de peso. Métodos: 23 obesos asmáticos (OA) (18 mujeres; mediana de edad [rango intercuartílico] 56 [51-59] años), 14 asmáticos no obesos (NOA) (11 mujeres; 53 [43-60] años), 15 obesos (O) (13 mujeres; 47 [45-60] años), y 19 controles sanos (HC) (14 mujeres; 43 [34-56] años) fueron incluidos. Se evaluaron 10 pacientes OA y 11 O al inicio (V1) y seis meses después (V2) de cirugía bariátrica. La respuesta a los corticosteroides se midió mediante la inhibición con dexametasona de la proliferación de células mononucleares de sangre periférica (PBMC). La función pulmonar, los niveles séricos de leptina, adiponectina y vitamina D se midieron en V1 y V2. Resultados: Encontramos una respuesta reducida a la dexametasona en PBMC de pacientes O y OA con respecto a los NOA y HC, que se correlacionó de forma inversamente proporcional con la relación adiponectina/leptina y los niveles de vitamina D. La cirugía bariátrica mejoró las respuestas de los corticosteroides en los grupos de pacientes O y OA, y normalizó la relación adiponectina/leptina y los niveles de vitamina D. La exposición de las PBMC a la vitamina D potenció los efectos antiproliferativos de los corticosteroides. La dexametasona y la vitamina D indujeron una expresión similar de MKP-1 en los pacientes O y OA. (AU)