ABSTRACT
BACKGROUND: Increasing evidence points to a potential role for members of the transient receptor potential family of cation channels on several features of asthmatic disease. The cough sensitivity to inhaled capsaicin is known to reflect the reactivity of these airway sensory nerves. OBJECTIVE: The aim was to study, among patients having a positive methacholine provocation and diagnosed with asthma, capsaicin cough sensitivity, sensitivity to methacholine, and levels of exhaled nitric oxide before and after treatment with inhaled steroids, and further, to measure the self-reported impact from environmental irritants. METHODS: Eighteen steroid-naïve patients with a positive methacholine test underwent capsaicin inhalation provocation on two occasions, before and after regular use of inhaled steroids over at least 3 months. Comparisons were made to 21 healthy controls. Sensitivity to methacholine and levels of exhaled nitric oxide were measured before and after the treatment. The participants also answered a validated questionnaire regarding environmental irritants. RESULTS: The patients displayed higher capsaicin cough sensitivity than the controls before the treatment period, but not afterward. Before treatment, capsaicin cough answer correlated significantly with levels of exhaled nitric oxide, but not with methacholine sensitivity. After treatment with inhaled corticosteroids, the capsaicin cough sensitivity and the inflammatory parameters were normalized. In comparison to the control group, the patients reported more affective reactions to and behavioral disruptions induced by environmental irritants. CONCLUSIONS: In steroid-naïve patients with a positive methacholine test, there is a link between that part of the airway inflammation that is reflected by exhaled nitric oxide and that followed by an augmented reactivity of capsaicin-sensitive sensory nerves. This association disappears after steroid treatment.
Subject(s)
Adrenal Cortex Hormones/administration & dosage , Asthma/diagnosis , Asthma/drug therapy , Irritants/adverse effects , Administration, Inhalation , Adolescent , Adult , Asthma/immunology , Bronchial Hyperreactivity/etiology , Bronchial Hyperreactivity/physiopathology , Bronchial Provocation Tests , Capsaicin , Case-Control Studies , Confidence Intervals , Environmental Pollutants/adverse effects , Female , Follow-Up Studies , Humans , Linear Models , Male , Methacholine Chloride , Middle Aged , Prospective Studies , Risk Assessment , Severity of Illness Index , Spirometry/methods , Statistics, Nonparametric , Treatment Outcome , Young AdultABSTRACT
Alterations in placental transport may contribute to accelerated fetal growth in pregnancies complicated by diabetes. We studied the activity of the syncytiotrophoblast amino acid transporter system A and the transport of the essential amino acids leucine, lysine, and taurine. Syncytiotrophoblast microvillous plasma membranes (MVMs) and basal plasma membranes (BMs) were isolated from placentas obtained from normal pregnancies and pregnancies complicated by gestational diabetes mellitus (GDM) and type 1 diabetes, with and without large-for-gestational-age (LGA) fetuses. Amino acid transport was assessed using radio-labeled substrates and rapid filtration techniques. System A activity in MVM was increased (65-80%, P < 0.05) in all groups with diabetes independent of fetal overgrowth. However, MVM system A activity was unaffected in placentas of normal pregnancies with LGA fetuses. MVM leucine transport was increased in the GDM/LGA group. In BMs, amino acid transport was unaffected by diabetes. In conclusion, diabetes in pregnancy is associated with an increased system A activity in MVM, and MVM leucine transport is increased in the GDM/LGA group. We suggest that these changes result in an increased uptake of neutral amino acids across MVM, which may be used in placental metabolism or be delivered to the fetus. The increased MVM leucine uptake in the GDM/LGA group may contribute to accelerated fetal growth in these patients.
