RESUMEN
INTRODUCTION: Chronic cough is a common clinical problem and there is a shortage of effective treatments for it. Within the group of transient receptor potential ion channels a receptor for the cooling substance menthol has been identified. This study aimed to assess whether pre-inhalation of dissolved, nebulised menthol could increase capsaicin cough thresholds and influence spirometric values. METHODS: Fourteen patients with chronic cough and airway sensitivity to environmental irritants and 15 control subjects were tested on three occasions. Each one inhaled a 1 mL of nebulised menthol solution of 0.5% or 1% or placebo (saline with 0.05% menthol) at each visit in a randomized and double-blind order. They were then provoked by capsaicin inhalation. RESULTS: Patients' cough thresholds differed significantly from the controls' on all three provocations (P < 0.0001). After inhalation of 1% menthol, the patients' cough thresholds were significantly higher (P < 0.02) compared to after placebo inhalation and to after 0.5% menthol inhalation (P < 0.05). The patients' peak inspiratory flows were significantly reduced after inhalation of the placebo (saline) (P < 0.05) but not after inhalation of 0.5% or 1% menthol. Forced inspiratory flows 50% were lowered after inhalation of placebo and of 0.5% menthol (P < 0.05) but not after 1% menthol. Among the controls, forced inspiratory flows 50% were lowered after only placebo inhalation (P < 0.05). CONCLUSIONS: In patients with chronic cough, pre-inhalation of menthol reduces cough sensitivity to inhaled capsaicin and influences inspiratory flows. The findings may provide scientific support for the common practice of using menthol as a reliever for variant airway discomfort. The use of menthol in different cigarette brands could be questioned since it could conceal the natural irritation following smoking.
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Antitusígenos/uso terapéutico , Tos/prevención & control , Inhalación/efectos de los fármacos , Mentol/uso terapéutico , Administración por Inhalación , Adulto , Anciano , Antitusígenos/administración & dosificación , Capsaicina , Enfermedad Crónica , Tos/inducido químicamente , Tos/fisiopatología , Método Doble Ciego , Femenino , Humanos , Irritantes/efectos adversos , Masculino , Mentol/administración & dosificación , Persona de Mediana Edad , Espirometría/métodosRESUMEN
Several studies have demonstrated the importance of Rho-kinase in the modulation of smooth muscle contraction, airway hyperresponsiveness, and inflammation. However, the effects of repeated treatment with a specific inhibitor of this pathway have not been previously investigated. We evaluated the effects of repeated treatment with Y-27632, a highly selective Rho-kinase inhibitor, on airway hyperresponsiveness, oxidative stress activation, extracellular matrix remodeling, eosinophilic inflammation, and cytokine expression in an animal model of chronic airway inflammation. Guinea pigs were subjected to seven ovalbumin or saline exposures. The treatment with Y-27632 (1 mM) started at the fifth inhalation. Seventy-two hours after the seventh inhalation, the animals' pulmonary mechanics were evaluated, and exhaled nitric oxide (E(NO)) was collected. The lungs were removed, and histological analysis was performed using morphometry. Treatment with Y-27632 in sensitized animals reduced E(NO) concentrations, maximal responses of resistance, elastance of the respiratory system, eosinophil counts, collagen and elastic fiber contents, the numbers of cells positive for IL-2, IL-4, IL-5, IL-13, inducible nitric oxide synthase, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, transforming growth factor-ß, NF-κB, IFN-γ, and 8-iso-prostaglandin F2α contents compared with the untreated group (P < 0.05). We observed positive correlations among the functional responses and inflammation, remodeling, and oxidative stress pathway activation markers evaluated. In conclusion, Rho-kinase pathway activation contributes to the potentiation of the hyperresponsiveness, inflammation, the extracellular matrix remodeling process, and oxidative stress activation. These results suggest that Rho-kinase inhibitors represent potential pharmacological tools for the control of asthma.
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Amidas/farmacología , Antiasmáticos/farmacología , Matriz Extracelular/metabolismo , Estrés Oxidativo/efectos de los fármacos , Piridinas/farmacología , Quinasas Asociadas a rho/antagonistas & inhibidores , Remodelación de las Vías Aéreas (Respiratorias)/efectos de los fármacos , Resistencia de las Vías Respiratorias/efectos de los fármacos , Amidas/uso terapéutico , Animales , Antiasmáticos/uso terapéutico , Asma/tratamiento farmacológico , Asma/inmunología , Asma/metabolismo , Asma/fisiopatología , Colágeno/metabolismo , Dinoprost/análogos & derivados , Dinoprost/metabolismo , Evaluación Preclínica de Medicamentos , Tejido Elástico/metabolismo , Elasticidad , Eosinófilos/inmunología , Eosinófilos/patología , Eosinófilos/fisiología , Cobayas , Inhalación/efectos de los fármacos , Interleucina-2/metabolismo , Pulmón/efectos de los fármacos , Pulmón/inmunología , Pulmón/patología , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Piridinas/uso terapéutico , Quinasas Asociadas a rho/metabolismoRESUMEN
BACKGROUND: Allergic rhinitis (AR) is commonly associated with olfactory loss, although the mechanism is not well studied. This study was designed to determine the effect of mometasone furoate (MF) on olfactory loss in seasonal AR (SAR) and study its effect on inflammation in the olfactory region. METHODS: We performed a randomized, double-blind, placebo-controlled, parallel clinical trial in 17 patients with SAR who had symptoms of impaired olfaction. Subjects received MF or placebo for 2 weeks during their allergy season. Before and after treatment, we measured nasal peak inspiratory flow (NPIF), chemosensory quality of life, and objective olfactory function (the University of Pennsylvania Smell Identification Test). Additionally, nasal cytology samples were obtained from each visit, and a unilateral endoscopic biopsy specimen of the olfactory epithelium was obtained at the end of the study and scored for inflammation. RESULTS: Treatment with MF was associated with improved nasal symptoms (p < 0.015), NPIF (p < 0.04), reduced nasal inflammation (p < 0.05), and chemosensory-specific quality of life (p < 0.03). Histological analysis of the olfactory region reveals fewer eosinophils in the MF group when compared with placebo (p < 0.012). We found no improvement in objective olfactory function (p > 0.05). CONCLUSION: The use of MF in SAR is associated with reduced eosinophilic inflammation in the olfactory region and improved symptoms of AR. The presence of eosinophils in the olfactory area in SAR may indicate a direct, deleterious effect of inflammation on olfactory epithelium in this disease. In this study we show that inflammation in SAR can affect the olfactory cleft, implicating a direct role for allergic inflammation in smell loss. Treatment with intranasal steroids is associated with decreased inflammation in the olfactory region in humans. This treatment is also associated with improved olfactory quality of life.
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Cavidad Nasal/patología , Mucosa Olfatoria/patología , Rinitis Alérgica Estacional/inmunología , Administración Intranasal , Adulto , Agnosia , Alérgenos/inmunología , Ambrosia , Eosinófilos/patología , Femenino , Humanos , Inflamación , Inhalación/efectos de los fármacos , Masculino , Persona de Mediana Edad , Furoato de Mometasona , Cavidad Nasal/inmunología , Mucosa Olfatoria/inmunología , Poaceae , Polen/inmunología , Pregnadienodioles/administración & dosificación , Pregnadienodioles/efectos adversos , Calidad de Vida , Recuperación de la Función , Rinitis Alérgica Estacional/diagnóstico , Rinitis Alérgica Estacional/tratamiento farmacológico , Rinitis Alérgica Estacional/patología , Rinitis Alérgica Estacional/fisiopatologíaRESUMEN
OBJECTIVE: We investigated whether hyperbaric oxygen (HBO2) treatment is able to cause any changes in the nasal peak inspiratory flow (NPIF) values of patients submitted to this therapy. STUDY DESIGN: NPIF was measured in a group of 13 patients who were submitted to at least 10 sessions of 75 minutes long HBO2 treatments over a period of 20 days. HBO2 was prescribed to the patients to treat hearing loss, diabetic ulcers or chronic inflammatory disease. Three timings were chosen to perform the NPIF measurements: during HBO2, five minutes before and five minutes after the treatment. METHODS: For NPIF evaluation, the highest inspiratory flow of three inspirations was recorded. To search for statistical differences between NPIF measurements at the three different timings of the HBO2 treatment, we have analysed the data using the repeated measures ANOVA test with the Epsilon lower bound correction for the F ratio. RESULTS: NPIF values were significantly higher when the patients were inside the HBO2 chamber when compared with NPIF measurements obtained in the same individuals five minutes before starting or five minutes after ending the treatment. A small but significant increase in NPIF values was detected in patients five minutes after stopping the HBO2 treatment, in comparison with values obtained five minutes before initiating the therapy. NPIF values remained stable along the 10 HBO2 sessions, i.e. with repetition of the HBO2 treatments, NPIF values were not further enhanced. CONCLUSIONS: Exposure to HBO2 causes significant improvement in nasal air flow. This increase is restricted mostly to the period that the patients are inside the hyperbaric chamber. Further investigations are needed to determine the relative contributions of enhancement in air pressure and in oxygen concentration (that characterize HBO2) in the enhancement of nasal air flow. The herein finding may be helpful in future investigations on the treatment of nasal or sinus diseases.
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Oxigenoterapia Hiperbárica , Inhalación/fisiología , Nariz/fisiología , Adulto , Anciano , Análisis de Varianza , Femenino , Humanos , Inhalación/efectos de los fármacos , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
INTRODUCTION: The impact on tracheal anatomy and respiratory function of recombinant human (rh)TSH-stimulated (131)I therapy in patients with goiter is not clarified. METHODS: In a double-blinded design, patients (age 37-87 yr) with a large multinodular goiter (range, 99-440 ml) were randomized to placebo (n = 15) or 0.3 mg rhTSH (n = 14) 24 h before (131)I therapy. The smallest cross-sectional area of the trachea (SCAT; assessed by magnetic resonance imaging) and the pulmonary function were determined before, 1 wk, and 12 months after therapy. RESULTS: Data on goiter reduction have been reported previously. In the placebo group, no significant changes in the lung function or SCAT were found throughout the study. In the rhTSH group, a slight decrease was observed in the forced vital capacity 1 wk after therapy, whereas the mean individual change in SCAT was significantly increased by 10.5% (95% confidence interval = 0.9-20.0%). A further increase in SCAT to 117 +/- 36 mm(2) (P = 0.005 compared with 92 +/- 38 mm(2) at baseline) was seen at 12 months, corresponding to a mean of 31.4% (95% confidence interval = 16.0-46.8%). The expiratory parameters did not change significantly, whereas forced inspiratory flow at 50% of the vital capacity (FIF50%) increased from initially 3.34 +/- 1.33 liters/sec to ultimately 4.23 +/- 1.88 liters/sec (P = 0.015) in the rhTSH group, corresponding to a median increase of 24.6%. By 12 months, the relative improvements in FIF50% and in SCAT were inversely correlated to the respective baseline values (FIF50%: r = -0.47, P = 0.012; SCAT: r = -0.57, P = 0.001). CONCLUSION: On average, neither compression of the trachea nor deterioration of the pulmonary function was observed in the acute phase after rhTSH-augmented (131)I therapy. In the long term, tracheal compression is diminished, and the inspiratory capacity improved, compared with (131)I therapy alone.
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Bocio Nodular/tratamiento farmacológico , Bocio Nodular/radioterapia , Inhalación/efectos de los fármacos , Inhalación/efectos de la radiación , Radioisótopos de Yodo/uso terapéutico , Tirotropina/uso terapéutico , Tráquea/patología , Adulto , Anciano , Anciano de 80 o más Años , Obstrucción de las Vías Aéreas/tratamiento farmacológico , Obstrucción de las Vías Aéreas/etiología , Obstrucción de las Vías Aéreas/fisiopatología , Obstrucción de las Vías Aéreas/radioterapia , Quimioterapia Adyuvante , Método Doble Ciego , Femenino , Bocio Nodular/complicaciones , Bocio Nodular/patología , Humanos , Capacidad Inspiratoria/efectos de los fármacos , Capacidad Inspiratoria/efectos de la radiación , Masculino , Persona de Mediana Edad , Tamaño de los Órganos/efectos de los fármacos , Tamaño de los Órganos/efectos de la radiación , Placebos , Proteínas Recombinantes/uso terapéutico , Tráquea/fisiopatología , Enfermedades de la Tráquea/tratamiento farmacológico , Enfermedades de la Tráquea/etiología , Enfermedades de la Tráquea/fisiopatología , Enfermedades de la Tráquea/radioterapia , Resultado del TratamientoRESUMEN
Dopamine (DA) is a free radical scavenger that attenuates apoptosis. We studied the effects of normal saline (NS) and DA on diaphragm apoptotic protein expression following 60 min of inspiratory resistance loading in rats. We tested for 27 apoptotic-related proteins and found 12 in the diaphragm. Of the 12 proteins, superoxide dismutase copper zinc (SOD [CuZn]) and proprioceptive event related potential (PERP) were significantly higher in the DA group than in the NS and sham groups (p = .002, p = .007). DA group diaphragms had significantly greater expression of SOD (CuZn) than the NS (p = .005) and sham group diaphragms (p = .003). Likewise, the DA group had significantly greater expression of PERP than the NS group (p = .008). These results suggest that DA decreases diaphragm apoptosis through elevated expression of SOD (CuZn). The identification of 12 apoptotic-related proteins will assist investigators as they study diaphragm apoptosis.