The impact of ATP-sensitive potassium channel modulation on mitochondria in a Parkinson's disease model using SH-SY5Y cells depends on their differentiation state.

Inward rectifying potassium channels sensitive to ATP levels (KATP) have been the subject of investigation for several decades. Modulators of KATP channels are well-established treatments for metabolic as well as cardiovascular diseases. Experimental studies have also shown the potential of KATP modulation in neurodegenerative disorders. However, to date, data regarding the effects of KATP antagonists/agonists in experiments related to neurodegeneration remain inconsistent. The main source of confusion in evaluating available data seems to be the choice of experimental models. The present study aims to provide a comprehensive understanding of the effects of both opening and blocking KATP channels in two forms of SH-SY5Y cells. Our results offer valuable insights into the significance of metabolic differences between differentiated and non-differentiated SH-SY5Y cells, particularly in the context of glibenclamide and diazoxide effects under normal conditions and during the initiation of pathological events simulating Parkinson's disease in vitro. We emphasize the analysis of mitochondrial functions and changes in mitochondrial network morphology. The heightened protein expression of KATP channels identified in non-differentiated SH-SY5Y cells seems to be a platform for a more significant impact of KATP modulators in this cell type. The efficiency of rotenone treatment in inducing morphological changes in the mitochondrial network depends on the differentiation status of SH-SY5Y cells.

Association of selected inflammatory biomarkers with cough reflex sensitivity in asthmatic children.

Bronchial asthma is the most common chronic respiratory disease of childhood. Cough is one of its defining symptoms. This study investigated the associations between selected inflammatory biomarkers and cough reflex sensitivity after capsaicin inhalation in children with mild and moderate well-controlled type 2 endotype asthma compared with non-asthmatic probands. Sensitivity to the cough reflex was measured by recording the cough response after capsaicin inhalation. The sandwich ELISA method was used to measure serum concentrations of the investigated potential inflammatory biomarkers (interleukin 13, interleukin 1beta, eosinophil-derived neurotoxin). The acquired data were statistically evaluated according to descriptive analyses for summarization and comparison between cough reflex sensitivity parameters and individual biomarker values in the observed and control groups modeled by a simple linear regression model. Statistical significance was defined as p<0.05. We showed a statistically significant association (p-value 0.03) between cough reflex sensitivity - C2 value (capsaicin concentration required for two cough responses) and interleukin 1beta serum concentrations in the asthma group compared with the control group of non-asthmatic children. Our results support the possibility of interleukin 1beta as a potential additive inflammatory biomarker used in clinical practice in children with asthma because of its correlation with the activity of the afferent nerve endings in the airways.

Upper Airway Cough Syndrome in Pathogenesis of Chronic Cough.

Cough is one of the most important defensive reflexes. However, extensive non- productive cough is a harmful mechanism leading to the damage of human airways. Cough is initiated by activation of vagal afferents in the airways. The site of their convergence is particularly the nucleus of the solitary tract (nTS). The second-order neurons terminate in the pons, medulla and spinal cord and there is also the cortical and subcortical control of coughing.Upper airway cough syndrome (UACS) - previously postnasal drip syndrome - is one of the most common causes of chronic cough together with asthma and gastroesophageal reflux. The main mechanisms leading to cough in patients with nasal and sinus diseases are postnasal drip, direct irritation of nasal mucosa, inflammation in the lower airways, upper airway inflammation and the cough reflex sensitization. The cough demonstrated by UACS patients is probably due to hypersensitivity of the upper airways sensory nerve or lower airways sensory nerve, or a combination of both. Further studies are needed to clarify this mechanism.

Biomarkers of Bronchial Asthma.

Asthma is a complex disease with a variable course. Efforts to identify biomarkers to predict asthma severity, the course of disease and response to treatment have not been very successful so far. Biomarker research has expanded greatly with the advancement of molecular research techniques. An ideal biomarker should be suitable to identify the disease as well the specific endotype/phenotype, useful in the monitoring of the disease and to determine the prognosis, easily to obtain with minimum discomfort or risk to the patient. An ideal biomarker should be suitable to identify the disease as well the specific endotype/phenotype, useful in the monitoring of the disease and to determine the prognosis, easily to obtain with minimum discomfort or risk to the patient - exhaled breath analysis, blood cells and serum biomarkers, sputum cells and mediators and urine metabolites could be potential biomarkers of asthma bronchiale. Unfortunately, at the moment, an ideal biomarker doesn't exist and the overlap between the biomarkers is a reality. Using panels of biomarkers could improve probably the identification of asthma endotypes in the era of precision medicine.

Itch and Cough - Similar Role of Sensory Nerves in Their Pathogenesis.

Itch is the most common chief complaint in patients visiting dermatology clinics and is analogous to cough and also sneeze of the lower and upper respiratory tract, all three of which are host actions trying to clear noxious stimuli. The pathomechanisms of these symptoms are not completely determined. The itch can originate from a variety of etiologies. Itch originates following the activation of peripheral sensory nerve endings following damage or exposure to inflammatory mediators. More than one sensory nerve subtype is thought to subservepruriceptive itch which includes both unmyelinated C-fibers and thinly myelinated Adelta nerve fibers. There are a lot of mediators capable of stimulating these afferent nerves leading to itch. Cough and itch pathways are mediated by small-diameter sensory fibers. These cough and itch sensory fibers release neuropeptides upon activation, which leads to inflammation of the nerves. The inflammation is involved in the development of chronic conditions of itch and cough. The aim of this review is to point out the role of sensory nerves in the pathogenesis of cough and itching. The common aspects of itch and cough could lead to new thoughts and perspectives in both fields.

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.

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.

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.

Acidification of the oesophagus acutely increases the cough sensitivity in patients with gastro-oesophageal reflux and chronic cough.

Gastro-oesophageal reflux disease (GORD) is one of the most common causes of chronic cough; however, the mechanisms by which GOR initiates coughing are incompletely understood. We address the hypothesis that acidification of oesophagus acutely increases the cough reflex sensitivity in patients with GORD and chronic cough. Nine patients with GORD with chronic cough and 16 patients with GORD without cough were recruited. In a randomized double blind study, saline and acid (HCl, 0.1 mol L(-1)) were separately infused into oesophagus via naso-oesophageal catheter. Cough reflex sensitivity to inhaled capsaicin was determined immediately after completion of each infusion. Infusion of acid into oesophagus increased capsaicin cough reflex sensitivity in patients with GORD and chronic cough. In contrast, acid had no effect on the cough sensitivity in patients with GORD without cough. In a separate study, acid infusion into oesophagus did not affect the cough sensitivity in 18 healthy subjects. We conclude that acid in the oesophagus acutely increases the cough reflex sensitivity to capsaicin in patients with GORD and chronic cough. This phenomenon may contribute to the pathogenesis of cough due to GORD.

Cough reflex sensitivity testing in in seasonal allergic rhinitis patients and healthy volunteers.

Dysfunction of upper and lower airways frequently coexists, and they appear to share key elements of pathogenesis. The interrelationship between upper and lower airway manifestations of allergy remains still incompletely investigated. Little is known about the critical factors that determine airway afferent nerve endings reactivity (cough sensitivity) in patients with allergic rhinitis. Subclinical inflammatory changes within the lower airways and/or chronic upper airway cough syndrome (previously referred to as postnasal drip syndrome) are probably responsible for this effect. The aim of this study was to evaluate capsaicin cough sensitivity in pollen sensitive patients with seasonal allergic rhinitis without treatment out of a grass pollen season time using the European Respiratory Society (ERS) guidelines on the assessment of cough. Cough sensitivity was defined as the lowest capsaicin concentration which evoked two (C2) or five (C5) coughs. Capsaicin aerosol in doubling concentrations (from 0.49 to 1000 micromol/l) was inhaled by a single breath method (KoKo DigiDoser; nSpire heath Inc, Louisville, CO), modified by the addition of an inspiratory flow regulator valve (RIFR; nSpire heath Inc, Louisville, CO). The seasonal rhinitis subjects (5M, 7F; mean age 23 yr) had not been complaining primarily about coughing. Their pulmonary function was within normal range. Concentrations of capsaicin causing two (C2) and five coughs (C5) were reported. Volunteers' (5M, 7F, mean age 23 yr) cough sensitivity (geometric mean and 95 % CI) for C2 was 16.5 (4.1-67.0) micromol/l vs. allergic rhinitis patients' C2 3.5 (1.9 - 6.4) (P= 0.018). Volunteers' C5 was 132.4 (41.3 - 424.5) micromol/l vs. allergic rhinitis patients' C5 13.1 (6.0 - 28.6) micromol/l (P= 0.013). We conclude that airway afferent nerve endings reactivity in pollen sensitive subjects suffering from seasonal allergic rhinitis was significantly increased out of pollen season compared with healthy volunteers.

Tussigenic agents in the measurement of cough reflex sensitivity.

Different inhalation methods are used for cough reflex sensitivity (CRS) measurement. The single-breath method of tussigenic agent aerosol inhalation is widely used now. Comparison of two tussigenic agents--citric acid and capsaicin--in cough reflex sensitivity measurement was used in healthy volunteers. In 17 healthy volunteers (7 M, 10 F; mean age 21 years) without respiratory tract infection in last 3 weeks, without cardiovascular, allergic, respiratory metabolic diseases, and with normal spirometry, cough reflex sensitivity was examined by nebuliser ProvoJet Ganshorn Medizin Elektronic, Germany) with doubled concentrations of capsaicin (SIGMA) from 0.49 to 1000 micromol/l and citric acid (LACHEMA) concentrations of 1, 3, 10, 30, 100, 300, 1000 micromol/l. Cough reflex sensitivity was defined as the lowest concentration of tussigenic agents which elicited 2 and 5 coughs (C2, C5). Geometric mean and 95% confidence interval (CI) of citric acid C2 was 454.5 (284.8-725.4) mmol/l in 88.2% of volunteers; citric acid C5 was 1000 micromol/l (0) in 47.1% of volunteers. Capsaicin C2 was 23.5 (8.2-67.5) micromol/l in 100% of volunteers and C5 was 263.7 (111.2-625.1) micromol/l in 76.5% of volunteers. We conclude that capsaicin single-breath test is more relevant for cough reflex sensitivity measurement in healthy volunteers than citric acid cough test.

Changes of cough reflex sensitivity induced by cancer radiotherapy of chest and neck regions.

It is reasonable to suppose that airway mucosa can be damaged by irradiation applied to chest and neck regions. The inflammatory process is a consequence of an injury. Airway inflammation is one mechanism responsible for cough induction. So, one can suppose that radiotherapy (RT) focused on the patients' chest or neck may injure airway mucosa, which might change sensitivity of the nerve-endings mediating the cough reflex. The purpose of this study was to examine cough reflex sensitivity (CRS) in patients who underwent RT in the chest and neck regions. CRS test using capsaicin was performed in patients with breast cancer (Group A, n=19), and with lung or neck cancer in (Group B, n=14) who underwent RT. Capsaicin aerosol in doubled concentrations (0.49-1000 microM) was inhaled by a single breath. CRS was defined as the lowest capsaicin concentration that evoked 2 or more coughs (C2). Radiation doses ranged from 40 to 70 Gy. Capsaicin cough challenge was performed before and then in the 2(nd) and 5(th) week of RT. We observed a significantly reduced value of C2, i.e., increased cough reflex sensitivity, in Group B in the 2(nd) week of RT (P= 0.04). We conclude that CRS in the lung or neck cancer patients undergoing RT is significantly enhanced, which could result from injury to the nerve endings in airway mucosa.

The effects of nasal histamine challenge on cough reflex in healthy volunteers.

UNLABELLED: The aim of the study was to investigate the effects of nasal histamine on the intensity of cough reflex and the effects of intensified nasal breathing following the nasal histamine challenge on cough sensitivity (CS) in humans. 20 volunteers (mean age 23, nonsmokers, no history of nasal or respiratory system diseases and atopy) were recruited to the study. Baseline CS was determined in all subjects. 2 days later the subjects (n = 20) were challenged with nasal histamine (8 mg/ml, 0.1 ml) and the number of coughs was determined after four consecutive single-breath inhalations of capsaicin C2 concentration during the period of the most intensive nasal symptoms (sneezing, itching of the nose). The same capsaicin C2 challenge was performed after nasal saline challenge two days later. One week later CS was determined after nasal histamine challenge with subsequent 10 min of intensified breathing (5-6 sniff-like aspirations to total lung capacity per minute) through the nose and mouth in randomized order in ten volunteers, and with a two-day interval between the challenges. The same manoeuvres after intranasal saline challenge were performed in volunteers of the control group (n = 10). The number of coughs after nasal histamine was significantly higher than that after intranasal saline challenge (8(6-10) vs 5(3-7); p = 0.038(. CS was not significantly different between the baseline challenge and challenges after nasal histamine followed by the intensified nasal and mouth breathing ((2.21 (1.8-2.62) vs 2.04 (1.57-2.51) vs 2.05 (1.6-2.5) log(10) of capsaicin concentration in mumol.l(-1); p = 0.09). CONCLUSIONS: During the period of maximum nasal symptoms after nasal histamine challenge the cough response to inhaled capsaicin was enhanced. Capsaicin cough sensitivity measured after a 10-min. intensified nasal breathing after nasal histamine challenge, compared to a previous measurement of CS, remain unchanged.

Cough sensitivity in allergic rhinitis.

The objective of this study was to evaluate capsaicin cough sensitivity in pollen sensitive patients with allergic rhinitis at the time of grass pollen season and out of it. Cough reflex sensitivity was defined as the lowest capsaicin concentration that evoked 2 or more coughs (C2). Capsaicin aerosol in doubled concentrations (from 0.02 to 200 micromol) was inhaled by a single breath. Two groups of pollen sensitive rhinitis subjects and a group of healthy controls were studied. The C2 for the 23 pollen sensitive patients of the first group, studied out of pollen season (January-February), was 0.22 micromol/l (0.06-0.76) (geometric mean + 95% CI), which was substantially lower than the 4.29 micromol/l (2.54-7.26) in 24 healthy volunteers (P=0.0001). In another group of 15 pollen sensitive patients, C2 was 0.84 micromol/l (0.14-5.20) out of pollen season and 0.11 micromol/l (0.03-0.33) during the pollen season (May-June) (P=0.04). We conclude that pollen-sensitive subjects who suffer of seasonal allergic rhinitis have significantly greater capsaicin cough sensitivity, regardless of them being in or out of pollen season. Subclinical inflammatory changes in the lower airways are probably responsible for this effect.

Effects of intranasal histamine on the cough reflex in subjects with allergic rhinitis.

In the present study we investigated the effects of nasal histamine on the intensity of coughing and the effects of intensified nasal breathing following nasal histamine on cough sensitivity (CS) in 14 subjects with seasonal allergic rhinitis. The study consisted of two parts performed one week apart. First, baseline CS to capsaicin was determined, followed by intranasal histamine challenge (4 mg/ml, 0.1 ml) and the count of the number of coughs to inhaled capsaicin on the background of most intensive nasal symptoms (sneezing, itching, rhinorrhea, and nasal blockage) evoked by histamine. In the second part, CS was determined after intranasal histamine followed by 10 min of intensified nasal breathing through the nose or mouth in a randomized order at 2-day intervals. The number of coughs induced after intranasal histamine was significantly higher, compared with intranasal saline, [9 (7-12) vs. 4.5 (4-6), P<0.001]. CS also was significantly increased after nasal histamine, but nasal intensified breathing failed to cause any changes in CS. We conclude that stimulation of nasal mucosa with histamine enhanced the cough response in subjects with allergic rhinitis.

Induced sputum eosinophils, bronchial reactivity, and cough sensitivity in subjects with allergic rhinitis.

Some patients with allergic rhinitis and no clinical evidence of asthma exhibit bronchial hyperresponsiveness. In the present study, induced sputum and acetylcholine and capsaicin challenges were assessed in four groups of adult subjects: allergic rhinitis (AR), allergic rhinitis with lower airway symptoms (ARLA), mild stable asthma (BA), and healthy volunteers (C) to correlate lower airway inflammatory markers with bronchial and cough reactivity. Patients with AR (n = 13) and ARLA (n = 11) did not take any anti-inflammatory drugs. Those with BA (n = 9) used inhaled corticosteroids and C (n = 10) were respiratory symptoms free. The patients underwent capsaicin cough challenge and sputum induction with hypertonic saline during the first visit, and acetylcholine bronchial challenge on a separate day. We found that the percentage of eosinophils in induced sputum was significantly higher in patients with AR, ARLA, and BA than in C 14.5 +/-1.8(SE) vs. 13.5 +/-2.9 vs. 13.9 +/-4.0 vs. 3.6 +/-0.8 %, respectively (P=0.012). In contrast, acetylcholine PD(20) in patients with AR, ARLA, and BA was significantly lower than in C 5.6 +/-0.9 vs. 4.1 +/-0.4 vs. 2.8 +/-0.4 vs. 12.9 +/-2.7 mg, respectively (P=0.0001). Neither the eosinophil percentage nor PD20, nor cough sensitivity appreciably differed across the patients groups. Sputum eosinophils correlated significantly with the acetylcholine PD(20) (r=0.37, P=0.016). We conclude that eosinophilic inflammation of lower airways and increased bronchial reactivity were present in adult patients with allergic rhinitis.

Effects of intranasal capsaicin challenge on cough reflex in healthy human volunteers.

Rhinosinusitis is the most common cause of chronic cough. There is clinical experience that cough can be elicited from lower airways including the larynx. However, there is no experimental evidence, that afferent nerve endings localized in the nose or sinuses can directly mediate the cough reflex. Stimulation of nasal afferents affects breathing pattern (apnea) and bronchial smooth muscles (nasobronchial reflex). The question arises of whether stimulation of nasal afferents could also interfere with the cough reflex. Intranasal capsaicin enhances the cough response in cats and guinea pigs. In the present study we address the problem of modulation of the cough response by intranasal capsaicin challenge in humans. Twelve healthy volunteers were recruited for the study. The effect of intranasal capsaicin (25 microl, 750 microM) and the airway cough threshold were determined at the start of the experiment. After that, cough response was provoked by inhalation of a tussigen during stimulation of nasal afferents with capsaicin and in control conditions in a randomized order. The cough response provoked during intranasal capsaicin was significantly enhanced compared with that during control conditions. Thus, the result was similar to that obtained in previous animal studies. The enhancement of the cough response could be explained by a facilitating interaction between the afferent information of nasal origin and the central neuronal network responsible for creation of cough pattern.