Cough Reflex Sensitivity in Asthmatic Children.

New knowledge about the neural aspects of cough has revealed a complex network of pathways that initiate cough. The effect of inflammation on cough neural processing occurs at multiple peripheral and central sites within the nervous system. Evidence exists that direct or indirect neuroimmune interaction induces a complex response, which can be altered by mediators released by the sensory or parasympathetic neurons and vice versa. The aim of this study was to clarify changes of cough reflex sensitivity - the activity of airway afferent nerve endings - in asthmatic children.25 children with asthma and 15 controls were submitted to cough reflex sensitivity measurement - capsaicin aerosol in doubling concentrations (from 0.61 to 1250 µmol/l) was inhaled by a single breath method. Concentrations of capsaicin causing two (C2) and five coughs (C5) were reported. Asthmatic children' (11 boys and 14 girls, mean age 9 ± 1 yrs) cough reflex sensitivity (geometric mean, with the 95 % CI) for C2 was 4.25 (2.25-8.03) µmol/l vs. control C2 (6 boys and 9 girls, mean age 8 ± 1 yrs) was 10.61 (5.28-21.32) µmol/l (p=0.024). Asthmatic children' C5 was 100.27 (49.30-203.93) µmol/l vs. control C5 56.53 (19.69-162.35) µmol/l (p=0.348). There was a statistically significant decrease of C2 (cough threshold) in the asthmatic patients relative to controls (p-value for the two-sample t-test of log(C2) for the one-sided alternative, p-value = 0.024). The 95 % confidence interval for the difference of the mean C2 in asthma vs. control, [1.004, 6.207]. For C5, the difference was not statistically significant (p-value = 0.348). There was a statistically significant decrease of cough reflex sensitivity (the activity of airway afferent nerve endings) - C2 value in the asthmatic children relative to controls.

Vagus Nerves Provide a Robust Afferent Innervation of the Mucosa Throughout the Body of the Esophagus in the Mouse.

The vagal afferent nerves regulate swallowing and esophageal motor reflexes. However, there are still gaps in the understanding of vagal afferent innervation of the esophageal mucosa. Anatomical studies found that the vagal afferent mucosal innervation is dense in the upper esophageal sphincter area but rare in more distal segments of the esophagus. In contrast, electrophysiological studies concluded that the vagal afferent nerve fibers also densely innervate mucosa in more distal esophagus. We hypothesized that the transfection of vagal afferent neurons with adeno-associated virus vector encoding green fluorescent protein (AAV-GFP) allows to visualize vagal afferent nerve fibers in the esophageal mucosa in the mouse. AAV-GFP was injected into the vagal jugular/nodose ganglia in vivo to sparsely label vagal afferent nerve fibers. The esophageal tissue was harvested 4-6 weeks later, the GFP signal was amplified by immunostaining, and confocal optical sections of the entire esophagi were obtained. We found numerous GFP-labeled fibers in the mucosa throughout the whole body of the esophagus. The GFP-labeled mucosal fibers were located just beneath the epithelium, branched repeatedly, had mostly longitudinal orientation, and terminated abruptly without forming terminal structures. The GFP-labeled mucosal fibers were concentrated in random areas of various sizes in which many fibers could be traced to a single parental axon. We conclude that the vagus nerves provide a robust afferent innervation of the mucosa throughout the whole body of the esophagus in the mouse. Vagal mucosal fibers may contribute to the sensing of intraluminal content and regulation of swallowing and other reflexes.

Relationship between cough reflex sensitivity and body mass index in children with chronic cough - a pilot study.

Obesity is characterized by chronic, low-grade systemic inflammation. Obesity may also be associated with chronic cough. The aim of this pilot study was to clarify relation of cough reflex sensitivity and body mass index (BMI) in children with chronic cough. Altogether 41 children having symptoms of chronic cough were submitted to cough reflex sensitivity measurement. We assessed the relation of cough reflex sensitivity (CKR) due to BMI. Cough reflex sensitivity was defined as the lowest capsaicin concentration which evoked two (C2) or five (C5) coughs. Capsaicin aerosol in doubling concentrations (from 0.61 to 1250 micromol/l) was inhaled by a single breath method (KoKo DigiDoser; nSpire heath Inc, Louisville, CO, USA), modified by the addition of an inspiratory flow regulator valve (RIFR; nSpire heath Inc, Louisville, CO, USA). BMI was calculated. Pulmonary function was within normal range. Concentrations of capsaicin causing two (C2) and five coughs (C5) were reported. Children (22 boys and 19 girls, mean age 6.8 years) cough reflex sensitivity (median, with the Inter-Quartile Range) for C2 was 19.5 (73.4) micromol/l; for C5 it was 78.1 (605.5) micromol/l. We have noticed statistically significant relation of the cough reflex sensitivity (C5) and body mass index (P<0.0001); however, the effect size was small, R2=0.03. Increase of body mass index in one unit is associated with -34.959 micromol/l decrease of C5. We did not find a statistically significant relation between C2 and BMI (P=0.41). The median value of CKR (C2) in boys is not statistically significantly different than the median value of CKR (C2) in girls (P-value 0.5). The median value of CKR (C5) in boys is not statistically significantly different than the median value of CKR (C5) in girls (P-value 0.5). Increase of body mass index in children suffering from chronic cough relates to decrease of cough reflex sensitivity (C5 value).

Cough reflex sensitivity and fractional exhaled nitric oxide in children with asthma.

Individual studies have suggested the utility of fractional exhaled nitric oxide (FeNO) measurement in detecting cough-variant asthma and eosinophilic bronchitis in patients with chronic cough. The aim of this study was to clarify a correlation of cough reflex sensitivity and fractional exhaled nitric oxide in asthmatic children. 25 children with asthma and 15 controls were submitted to cough reflex sensitivity measurement - capsaicin aerosol in doubling concentrations (from 0.61 to 1250 micromol/l) was inhaled by a single breath method. Concentrations of capsaicin causing two (C2) and five coughs (C5) were reported. Fractional exhaled nitric oxide (FeNO) measurement was included. Asthmatic children' (11 boys and 14 girls, mean age 9+/-1 years) and control group (unconfirmed diagnosis of asthma) (6 boys and 9 girls, mean age 8+/-1 years) were included into the study. FeNO vs. C2 in asthma (Spearman´s rank correlation: -0.146, p=0.49); FENO vs. C5 in asthma (Spearman´s rank correlation: -0.777, p=0.71). We found that there is no correlation between cough reflex sensitivity and fractional exhaled nitric oxide either in children with asthma or in the control group.

The effect of adenoidectomy on cough reflex sensitivity in atopic children.

The aim of this study was to determine whether cough sensitivity is changed after adenoidectomy in atopic children with chronic cough. 21 Children having symptoms of chronic cough and adenoid hypertrophy verified by nasal fiberoptic endoscopy were submitted to cough sensitivity measurement before and after adenoidectomy. Their pulmonary function was within normal range. Concentrations of capsaicin causing two (C2) and five coughs (C5) were reported. Children' (14 boys and 7 girls, mean age 6,52 yrs) cough sensitivity (geometric mean, with 95% CI) for C2 was preoperatively (before adenoidectomy) 19.95 (9.95-39.98) micromol/l vs. children' C2 postoperatively 14.04 (7.16-27.55) (P = .083 for Wilcoxon paired two sample test). Children' C5 was preoperatively 86.26 (39.25-189.57) micromol/l vs. C5 postoperatively 95.23 (46.33-195.75) micromol/l (P = .794 for Wilcoxon paired two sample test). We conclude that cough sensitivity for C2 and C5 was not significantly changed after adenoidectomy in atopic children with chronic cough.

Cough reflex sensitivity after exercise challenge testing in children with asthma.

Bronchial challenge tests are commonly used in clinical medicine and research. The aim of this study was to clarify changes of cough reflex sensitivity before and after exercise challenge testing in asthma children. 42 asthmatic children were submitted to cough reflex sensitivity measurement - capsaicin aerosol in doubling concentrations (from 0.61 to 1250 micromol/l) was inhaled by a single breath method - before and after exercise challenge testing. Concentrations of capsaicin causing two (C2) and five coughs (C5) were reported. Children' (31 boys and 11 girls, mean age 14.05 ±â€¯2.08 yrs) cough reflex sensitivity (median, with the 95% CI) for C2 was before exercise challenge testing 9.77 (6.10-10.99) micromol/l vs. children' C2 after it 7.32 (6.10-14.65) (P = 0.58 for the Wilcoxon two sample paired test). Children' C5 was before exercise challenge testing 19.53 (14.65-80.57) micromol/l vs. C5 after it 39.06 (24.42-58.59) micromol/l (P = 0.09 for the Wilcoxon two sample paired test). We conclude that cough reflex sensitivity was not significantly changed after exercise challenge testing in children with asthma.

Growth and obesity and its association with plasma level of steroid hormones and insulin-like growth factor-I (IGF-I) in Slovak female students.

The aim of the present study was to examine the possible role of steroid hormones and insulin-like growth factor 1 (IGF-I) in the control of human growth and obesity. We measured plasma level of progesterone, testosterone, estradiol and IGF-I in 301 young women at different stages of their ovarian cycle, and compared them to the standard morphometric indexes of their growth and obesity - body height, body weight, abdomen circumstance and waist to hip ratio (WHR). The ovarian cycle-dependent changes in plasma progesterone and estradiol, but not in testosterone and IGF-I level were found. Young women with higher body height had significantly higher plasma level of estradiol, testosterone and IGF-I, but not of progesterone, compared to subjects with lower body height in both follicular and luteal phases of the ovarian cycle. Subjects with a higher body weight had significantly higher plasma estradiol and progesterone, but not testosterone and IGF-I than subjects with lower body weight in both follicular and luteal phases of ovarian cycle. Women with a higher abdomen circumference had significantly lower plasma estradiol, but not the other hormones than the subjects with lower abdomen circumference. Women with higher WHR index had significantly higher plasma level of estradiol, but not other hormones than subjects with lower WHR index in both follicular and luteal phases of ovarian cycle. The present observations suggests: (1) that luteal phase of the women ovarian cycle is characterised by a dramatically increase in both progesterone and estradiol, but not in testosterone and IGF-I release, (2) that in human females growth can be up-regulated by testosterone, estradiol and IGF-I, but not by progesterone, (3) that body mass can be up-regulated by progesterone and estradiol, but not by testosterone or IGF-I, and (4) that women obesity (high WHR, but not abdomen circumference) can be promoted by estradiol, but not by other steroid hormones or IGF-I (Tab. 1, Fig. 4, Ref. 45).

Deep nasal inspirations increase the cough threshold in children with mild asthma.

Asthma is a chronic inflammatory disease characterized by bronchospasms accompanied with frequent coughing, the pathogenesis of which is not clear. In healthy adults deep inspirations (DIs) provide a protective effect against bronchoconstriction triggered by methacholine inhalation, which correlates with the number of accompanying cough efforts. The aim was to study the effect of deep nasal inspirations representing the voluntary equivalent of the sniff-like aspiration reflex on the capsaicin-induced cough in children with mild asthma. The cough reflex sensitivity to capsaicin was determined using a compressed air-driven nebulizer in 21 children (8 girls and 13 boys of median age 13.3 year) suffering from mild asthma (FEV(1)∼80%). The effect of five previous DIs through the nose was examined on the elicitability of two and five or more cough efforts (C2, C5). Under control conditions, the concentration of 20.86 (14.58-29.8) µmol/l of capsaicin provoked two cough efforts (C2). After five DIs similar reaction required significantly higher concentrations of capsaicin: 29.02 (18.88-44.6) µmol/l; P=0.016. Five or more cough efforts (C5) were not significantly changed after previous DIs 161.49 (77.31-337.33) µmol/l and without DIs 141.52 (68.77-291); P=0.54. A series of five deep inspirations decreases the cough reflex sensitivity to evoke two efforts (C2) in children with mild asthma. The inhibitory effect of similar DIs disappeared after repeated applications of increasing doses of capsaicin, aiming to evoke five or more cough efforts, suggesting a reflex character of protective effect of DIs.

Distinction of cough from other sounds produced by daily activities in the upper airways.

OBJECTIVES: The aim of this study was to validate the successfulness of our developed system for distinction between cough and other sounds which are present in daily human activities from the upper airways. BACKGROUND: To date, methods used for monitoring of cough sound were primarily subjective. A reliable measure of cough is needed so that the severity of cough in various patients and the effectiveness of treatment can be assessed. METHODS: Sounds of induced cough and sneezing, voluntary throat and nasopharynx clearing, forced ventilation and laughing, snoring, eructation, loud swallowing, and nasal blowing were studied. Characteristics of the sound events in 20 volunteers were calculated using the time-domain, spectral and non-linear analysis. The classification tree was constructed for classification between cough and non-cough sounds. We have validated the usefulness of our developed algorithm against subjective cough counts, which were performed by two trained observers. RESULTS: The value of sensitivity for distinction between cough and other sounds was 86% and the value of specificity was 91%. The value of sensitivity for distinction between voluntary and induced cough sounds was 96% and specificity was 43%. The value of sensitivity between cough sounds and voluntary throat clearing was 96% and specificity was 85%. The value of sensitivity between cough sounds and induced sneezing was 95% and specificity was 93%. CONCLUSION: We have developed an algorithm for distinction between cough and other sounds with a relatively high degree of accuracy (Tab. 1, Fig. 5, Ref. 15).