Capsaicin-induced cough in humans.

We have evaluated the properties of capsaicin as a selective cough-inducing agent in healthy human subjects. Despite frequent coughing, the subjects could inhale repeated breaths of capsaicin aerosol during 60 s without difficulty. Cough started immediately on inhalation and was most intense during the first 30 s. Cough always disappeared promptly when the capsaicin inhalation was terminated. The cough response was well reproducible and concentration-dependent up to 10 microM; at higher concentrations there was a distinct plateau of the cough response. Specific airway conductance was not changed 3 min after 50 microM capsaicin. Capsaicin (> or = 10 microM) had a burning taste, but there were no visual signs of pharyngitis or laryngitis. Citric acid (nebulized solutions 0.125 to 32%) had a choking effect and could be administered only as single breaths. There was no correlation between the cough response to citric acid and to capsaicin. Inhaled lidocaine (20 and 80 mg from nebulized solutions) caused a dose-dependent inhibition of capsaicin-induced cough. Lidocaine suppressed citric acid-induced cough as effectively as capsaicin-induced cough. In conclusion, we have characterized capsaicin-induced cough and demonstrated that it can be a useful tool in the study of cough reactivity and for evaluation of antitussive agents in humans. Capsaicin may be complementary to citric acid and may offer experimental advantages over this traditional tussive stimulus.     

Nonadrenergic bronchodilation in normal subjects

To investigate whether bronchial C-fiber stimulation induced by capsaicin inhalation evokes nonadrenergic inhibitory (NAI) system bronchodilation, we studied partial and maximal expiratory flow-volume (PEFV and MEFV) curves in 5 normal subjects after inhalation of oxitropium bromide and propranolol. PGF2 alpha (1 mg/ml inhaled for 5 min) was administered to induce bronchoconstriction. Then aerosolized capsaicin was inhaled (2.4 x 10(-9) mol) to stimulate bronchial C-fibers. PGF2 alpha produced significant bronchoconstriction; FEV1 and flow during a PEFV curve at 30% forced vital capacity (V30p) decreased over a 15-min period. Capsaicin induced significant bronchodilation; V30p increased for 2 to 6 min (0.001 less than p less than 0.02), and FEV1 increased for 2 to 4 min (p less than 0.05) when compared with saline-ethanol (vehicle of capsaicin) inhalation. After treatment with the ganglionic blocking agent hexamethonium, the significant bronchodilator response disappeared. These results suggest that the NAI system has a distinct bronchodilator action in human subjects in vivo, and that the bronchial C-fiber receptors may be involved in the reflex pathway for NAI system bronchodilation in humans.     

Safety of capsaicin cough challenge testing

BACKGROUND: Capsaicin, the pungent extract of red peppers, has achieved widespread use in clinical research because it induces cough in a dose-dependent and reproducible manner. Although > 2 decades of experience has led investigators to consider capsaicin cough challenge testing a safe diagnostic modality, this issue has not been specifically addressed in the literature. STUDY OBJECTIVES: To review the published experience with capsaicin inhalation challenge testing in terms of safety. DESIGN: Literature review and personal communication with study authors. SETTING: Academic medical center. RESULTS: One hundred twenty-two published studies since 1984 described 4,833 subjects (4,374 adults, 459 children) undergoing capsaicin cough challenge, with no serious adverse events reported. Subjects included healthy volunteers as well as patients with asthma, COPD, pathologic cough, and other respiratory conditions. Minor complaints described in a small fraction of studies consisted mainly of transient throat irritation. Personal communication with the authors of > 90% of the studies confirmed an absence of any serious adverse events. Furthermore, these investigators have performed thousands of additional capsaicin challenge studies not reported in the literature, also without any associated serious adverse events. CONCLUSIONS: A review of the 20-year clinical experience has failed to uncover a single serious adverse event associated with capsaicin cough challenge testing in humans. Given the need for better antitussive therapies, capsaicin represents a vital component of future scientific inquiry in the field of cough.     

Capsaicin induction of esophageal symptoms in different phenotypes of gastroesophageal reflux disease

"Background: Type 1 vanilloid receptors (TRPV1) have been described on esophageal afferent sensitive neurons. Stimulation of TRPV1 receptors with capsaicin may induce heartburn. Capsaicin is the pungent component of chili and the most extensively studied TRPV1 agonist. Objectives: To investigate the effect of esophageal stimulation with intraesophageal capsaicin administration on induction of esophageal symptoms and on esophageal chemo-sensitization to acid in different gastroesophageal reflux disease (GERD) phenotypes. Methods: Healthy volunteers and patients with GERD (non-erosive [NERD], erosive GERD [EE] and Barrett's esophagus [BE]) were prospectively studied. All subjects were randomized to receive either intraesophageal perfusion capsaicin or saline 0.9%. Thirty minutes after saline or capsaicin infusion an acid perfusion test of HCl was performed. A week later, a crossover phase with capsaicin versus saline was performed. Five symptoms were evaluated every 5 min during the first 30 minutes after capsaicin, saline, and acid perfusion: chest burning, chest pain, heartburn, epigastric burning, and epigastric pain Results: 17 healthy subjects and 31 GERD patients (10 NERD, 11 EE, and 10 BE) were included. Twenty- eight (90%) of GERD and 6 (35%) of healthy subjects had esophageal symptoms after capsaicin perfusion. Mean for the 5 evaluated symptoms induced by capsaicin was significantly higher in the GERD group compared to the control group. The highest symptom severity was in the erosive subgroup. Capsaicin decreased the 5 symptoms induced by acid perfusion in both healthy volunteers and GERD patients. Total score of esophageal symptom severity (produced by acid perfusion) was significantly reduced by capsaicin infusion in the BE group. Conclusions: Capsaicin induces esophageal and gastric symptoms in healthy volunteers and GERD patients. Capsaicin reduces esophageal chemosensitivity to acid, especially in patients with BE. "     

Effect of capsaicin on airway responsiveness to hypertonic saline challenge in asthmatic and non-asthmatic children

Recurrent cough and asthma are common problems in children. In the evaluation of children with recurrent cough, the sequential measurements of airway responsiveness (AR) and capsaicin cough receptor sensitivity may be useful. However, the effect of capsaicin on AR induced by an indirect stimulus such as hypertonic saline (HS) is not known. Current evidence suggests that a common pathway is involved in both capsaicin and HS challenges. This study was designed to determine whether inhalation of capsaicin for the cough receptor sensitivity test before HS challenge will alter AR of asthmatic and non-asthmatic children to that challenge. Twenty-one children (12 asthmatics, 9 non-asthmatics; mean age, 11.3 years) performed the HS challenge alone or 2 min after capsaicin inhalation on 2 different days in random order. The end point of the capsaicin inhalation was when ≥5 coughs were stimulated from a single inhalation. The power of the study was >90% at a significance level of 0.05. Capsaicin inhalation prior to HS challenge did not alter the AR of normal children. In the asthmatic group, the PD₁₅ (provocation dose causing a fall in forced expiratory volume in 1 s of ≥15% from the baseline) without prior inhalation of capsaicin (mean, 2.44 ± SEM 1.21 ml) was not significantly different from that when HS challenge was performed after capsaicin inhalation (mean, 2.19 ± SEM 0.83 ml). The mean of the difference in log PD₁₅ of the HS challenge with and without capsaicin was −0.02 (95% Cl, −0.16, 0.12), i.e. within the equivalence range of the HS challenge in children with asthma. We conclude that in normal and asthmatic children, capsaicin inhalation does not alter AR to HS; consequently the capsaicin cough sensitivity test can be performed validly before an HS challenge. Pediatr. Pulmonol. 1997; 23:412–416. © 1997 Wiley-Liss, Inc.     

Relationship between self-reported odor intolerance and sensitivity to inhaled capsaicin: proposed definition of airway sensory hyperreactivity and estimation of its prevalence

STUDY OBJECTIVES: The aim of this study was to investigate the relationship between the behavioral consequences of self-reported odor sensitivity with the chemical sensitivity scale for sensory hyperreactivity (CSS-SHR) and cough sensitivity to inhaled capsaicin. We also wanted to estimate the prevalence of airway sensory hyperreactivity (SHR), which was defined as a positive CSS-SHR score in combination with a positive capsaicin inhalation test result. DESIGN: A general population-based study with randomly selected individuals after stratification for age and gender. SETTING: Sk?vde Central Hospital, Departments of Lung Medicine and Otorhinolaryngology, Sweden. PARTICIPANTS: A total of 693 randomly selected individuals from a population-based study in which 595 persons (86%) responded to the CSS-SHR questionnaire. INTERVENTIONS: The individuals were divided into four groups with different odor sensitivity according to their CSS-SHR score. Of these, 137 individuals were randomly recruited for the capsaicin inhalation test. Capsaicin inhalation was performed with concentrations of 0.4 and 2.0 mumol/L in a randomized order. The number of coughs were registered and counted for 10 min from the start of each inhalation. MEASUREMENTS AND RESULTS: Of the 137 individuals who were recruited for the capsaicin inhalation test, 103 (75%) participated. Sixteen individuals had increased cough sensitivity and fulfilled the criteria for a positive capsaicin inhalation test result. Of the individuals with a positive capsaicin inhalation test result, > 80% also had a positive CSS-SHR score. Only 5% of the individuals with a negative CSS-SHR score had a positive capsaicin inhalation test result. The order of inhaled capsaicin concentration was found to influence the results. The prevalence of SHR with the definition given above was estimated to be 6.3% in this general population. CONCLUSIONS: A high CSS-SHR score was found to be directly related to the sensitivity for inhaled capsaicin, which made it possible to relate subjective data to objective findings.     

Capsaicin inhibits airway hyperresponsiveness but not lipoxygenase activity or eosinophilia after repeated aerosolized antigen in guinea pigs

To evaluate the role of tachykinins in airway hyperresponsiveness following repeated aerosolized antigen challenge in guinea pigs, we treated 12 guinea pigs with capsaicin (105.6 mg cumulative dose given subcutaneously over 5 days) after sensitization to ovalbumin (OA) and before three repeated OA aerosol challenges per wk for 4 to 5 wk. Ten guinea pigs received identical OA sensitization and challenges without capsaicin treatment, and four of eight nonsensitized controls received capsaicin followed by saline challenges. Capsaicin treatment did not alter antibody responses to OA as assessed by passive cutaneous anaphylaxis, nor did it alter lipoxygenase products from OA-stimulated bronchial tissue in vitro. Capsaicin completely inhibited the increased pulmonary resistance (RL) to acetylcholine produced by repeated aerosolized OA, whereas it did not alter baseline RL or acetylcholine responses of controls. Capsaicin did not alter airway eosinophilia induced by repeated aerosolized OA. We conclude that neuropeptides play an important role in antigen-induced airway hyperresponsiveness without altering antibody levels, lipoxygenase mediator production, or airway eosinophilia.     

Chemical nociception in the jejunum induced by capsaicin

BACKGROUND AND AIMS: Chemonociception in the human small intestine has not been studied extensively. Although capsaicin can cause intestinal sensations, it is not known if this is due to stimulation of chemoreceptors or to motor changes. Our aims were to evaluate motor activity during capsaicin induced nociception and to compare qualities of jejunal nociception induced by capsaicin and mechanical distension. METHODS: Twenty nine healthy subjects swallowed a tube with a perfusion site at the ligament of Treitz and, 7 cm distally, a barostat balloon. Phasic motor activity was measured around the perfusion site and the balloon. Capsaicin solutions (40, 200, and 400 microg/ml) 2.5 ml/min were perfused for 60 minutes or until severe discomfort occurred. A graded questionnaire for seven different sensations was completed every 10 minutes and after capsaicin perfusion was replaced by saline perfusion because of severe discomfort. Sensations arising from pressure controlled distensions were assessed before and after capsaicin perfusion when sensations had stopped (n = 19), or during capsaicin administration when no discomfort was reported (n = 5). RESULTS: Capsaicin perfusion induced feelings of pressure, cramps, pain, and warmth. The quality and abdominal location of these sensations were similar to those induced by distension, except for warmth (p<0.01) and pressure (p<0.05). Seven of 12 subjects receiving 40 microg/ml capsaicin and all subjects receiving higher capsaicin concentrations developed discomfort. Perfusion had to be stopped after 55 (3.3), 15 (5.7), and 10 (2.2) minutes with 40, 200, and 400 microg/ml capsaicin, respectively, whereafter the sensations disappeared within 10 minutes. Repeated capsaicin (200 microg/ml) applications significantly reduced the time until discomfort occurred (p = 0.01). Jejunal tone was not altered by capsaicin but phasic activity proximal to the perfusion site was reduced during capsaicin induced discomfort (p<0.001). Pain thresholds during distensions were not different before and after capsaicin perfusion. CONCLUSION: Despite the similarities in abdominal localisation and perceptional quality of capsaicin and distension induced sensations, our results rule out the fact that abdominal discomfort evoked by capsaicin involves sensitisation of mechanoreceptors or an increase in phasic and tonic motor activity. Capsaicin evokes abdominal sensations by stimulation of chemoreceptors which proves the existence of chemonociception in the human small intestine.     

The urge-to-cough and cough motor response modulation by the central effects of nicotine

The urge-to-cough is a respiratory sensation that precedes the cough motor response. Since affective state modulates the perception of respiratory sensations such as dyspnoea, we wanted to test whether nicotine, an anxiolytic, would modulate the urge-to-cough and hence, the cough motor response. We hypothesized that withdrawal from and administration of nicotine in smoking subjects would modulate their anxiety levels, urge-to-cough and cough motor response to capsaicin stimulation. Twenty smoking (SM) adults (8F, 12M; 22 ± 3 years; 2.9 ± 2.0 pack years) and matched non-smoking (NS) controls (22 ± 2 years) were presented with randomized concentrations of capsaicin (0–200 μM) before and after nicotine (SM only) gum and/or placebo (SM and NS) gum. Subjects rated their urge-to-cough using a Borg scale at the end of each capsaicin presentation. Cough number and cough motor pattern were determined from airflow tracings. Subjects completed State-Trait Anxiety Inventory (STAI) questionnaires before and after gum administration. SM subjects that withdrew from cigarette smoking for 12 h exhibited an increase in anxiety scores, a greater number of coughs and higher urge-to-cough ratings compared to NS subjects. Administration of nicotine gum reduced anxiety scores, cough number and urge-to-cough ratings to match the NS subjects. There was no effect of placebo gum on any of the measured parameters in the SM and NS groups. The results from this study suggest that modulation of the central neural state with nicotine withdrawal and administration in young smoking adults is associated with a change in anxiety levels which in turn modulates the perceptual and motor response to irritant cough stimulants.     

Capsaicin inhalation test for identification of sensory hyperreactivity

BACKGROUND: Patients with upper and lower airway symptoms and with pronounced sensitivity to chemical odours, such as perfumes, flower scents and tobacco smoke, have been suggested to have sensory hyperreactivity (SHR). The symptoms have been difficult to identify with physiological measurements and the effects of various medications are doubtful. However, these patients have been found to be more sensitive to inhalation of capsaicin than healthy people. The aim of this study was to establish limit values with the capsaicin inhalation test in patients with SHR. METHODS: Ninety-five consecutive patients with upper and lower airway problems, who were admitted for allergy testing, underwent a capsaicin inhalation test with three different concentrations. The number of coughs was registered during each challenge. Score systems were used for symptoms and influence on social life of sensitivity to odours. In relation to scored symptoms, the patients were grouped as SHR or not, and compared with 73 healthy controls. RESULTS: All patients and controls coughed on capsaicin in a dose-dependent manner. Symptom score of odour sensitivity in patients was positively correlated to the response of the test. Out of 95 patients, 15 (16%) were scored to SHR. Patients with SHR reacted more to the capsaicin inhalation test than the other patients and the healthy controls. The limit values for a positive capsaicin inhalation test for the SHR were determined to be 10, 35 and 55 coughs at 0.4, 2.0 and 10 microM capsaicin, respectively. CONCLUSION: The capsaicin inhalation test well reflects the degree of airway sensitivity to chemicals and to what extent the social life is influenced. The cut-off values of the test can distinguish patients with pronounced sensitivity to odours.     

Neural basis of egalitarian behavior

Individuals are willing to sacrifice their own resources to promote equality in groups. These costly choices promote equality and are associated with behavior that supports cooperation in humans, but little is known about the brain processes involved. We use functional MRI to study egalitarian preferences based on behavior observed in the "random income game." In this game, subjects decide whether to pay a cost to alter group members' randomly allocated incomes. We specifically examine whether egalitarian behavior is associated with neural activity in the ventromedial prefrontal cortex and the insular cortex, two regions that have been shown to be related to social preferences. Consistent with previous studies, we find significant activation in both regions; however, only the insular cortex activations are significantly associated with measures of revealed and expressed egalitarian preferences elicited outside the scanner. These results are consistent with the notion that brain mechanisms involved in experiencing the emotional states of others underlie egalitarian behavior in humans.     

Capsaicin cough sensitivity is decreased in smokers

Although capsaicin provocation has been used to evaluate treatment against cough, which is one of the most common respiratory symptoms, there are still methodological considerations that are not fully known. Capsaicin stimulates the unmyelinated slow C-fibres of the sensory nervous system, which leads to coughing. Smoking often leads to respiratory symptoms with cough and phlegm. The aim of this study was to examine the effect of smoking on capsaicin provocation. Subjectively healthy smokers and non-smokers were challenged with capsaicin in increasing doses. The coughs were counted and irritation of the lower airways was graded on a symptom score. Smokers reacted to provocation with significantly fewer coughs, but there was no difference regarding other symptoms. These results are in agreement with the hypothesis that nicotine inhibits or blocks C-fibres of the sensory nervous system of the lower respiratory tract. Clinically, this may serve to explain increasing airway symptoms that are often seen after cessation of smoking.     

Acute response to 3.0 ppm formaldehyde in exercising healthy nonsmokers and asthmatics

Formaldehyde is an ubiquitous industrial and indoor air pollutant to which millions are daily exposed. Because of the paucity of scientific data concerning the inhalation toxicity of this compound in humans, we determined the symptoms and alterations in pulmonary function resulting from inhalation for 1 h of 3 parts per million formaldehyde in a controlled environmental chamber. The protocol consisted of randomized exposure of each subject to clean air or 3.0 ppm HCHO on 2 separate days. Twenty-two healthy normal subjects engaged in intermittent heavy exercise (VE = 65 L/min) and 16 asthmatic subjects performed intermittent moderate exercise (VE = 37 L/min). Symptoms and pulmonary function were assessed during the time course of exposure; nonspecific airway reactivity was assessed after exposure. Both groups exhibited similar, significant (p less than 0.01) increases in perceived odor, nose/throat irritation, and eye irritation throughout the exposure. The normal group had the following statistically significant (p less than 0.02) lower pulmonary functions after 55 min of exposure to formaldehyde as compared to clean air: 3.8% in FEV1, 2.6% in FVC, and 2.8% in FEV3. The asthmatic group showed no statistically significant decrements in pulmonary function. Five of 38 subjects studied had decrements in FEV1 greater than 10%. In conclusion, acute exposure to 3 ppm HCHO produced: consistent irritant symptoms in both normal and asthmatic subjects, small decreases in pulmonary function in normal subjects engaging in heavy exercise, and clinically significant responses (defined here as decrements in FEU1 greater than 10) in 13% of the study population.(ABSTRACT TRUNCATED AT 250 WORDS)     

Restoration of cough reflex in lung transplant recipients

BACKGROUND: Lung transplantation involves vagal nerve interruption resulting in sensory airway denervation and impairment of the cough reflex. Following lung transplantation, it is unclear whether functional recovery of the cough reflex occurs over time. Our objective was to evaluate the afferent limb of the cough reflex in lung transplant recipients. METHODS: The assessment of cough reflex involved upper airway anesthesia, conscious sedation, and fiberoptic bronchoscopy; the biopsy forceps and a 5% dextrose solution were applied through the bronchoscope to the airway mucosa at the main carina, proximal and distal to the anastomosis. A cross-sectional group of seven subjects underwent a single assessment, while eight subjects in a longitudinal group underwent assessment at 1.5 and 12 months. Cough frequency was determined by counting the number of audible coughs and abdominal muscle contractions measured with a surface electromyogram recorder. The airway anastomosis from deceased subjects in the longitudinal group was examined for nerves. RESULTS: All seven subjects from the cross-sectional group demonstrated a similar cough frequency after mechanical and chemical irritation of all airway sites. All subjects in the longitudinal group who were evaluated at 1.5 weeks had a cough response at all sites except distal to the anastomosis. Twelve months after transplantation, cough was present at all sites. Immunohistochemical staining for protein gene product 9.5, low-affinity neurotrophin, and vanilloid receptors demonstrated nerves in subepithelial regions proximal and distal to the airway anastomosis. CONCLUSION: In human lung transplant recipients, recovery of the cough reflex was noted 12 months after lung transplantation.     

Functional magnetic resonance imaging of odor identification: the effect of aging.

BACKGROUND: Sense of smell declines with age and impairment in olfaction has been observed in some neurodegenerative disorders such as Alzheimer's disease. Functional neuroimaging techniques enable researchers to observe brain regions activated by olfactory stimuli. METHODS: We gave three mainly olfactory-mediated odors (limonene, methylsalicylate, and eugenol) to six young and six elderly subjects and observed the areas activated by using blood oxygen level dependent contrast functional magnetic resonance imaging. RESULTS: The group mapping of young subjects showed extensive activation in the orbitofrontal cortex, commonly believed to be the olfactory cortex, some limbic areas (the hippocampus and the thalamus), regions involved with gustatory sensation (the anterior insula and the inferior postcentral gyrus), superior and inferior temporal gyri, and cerebellum. In the elderly group, only the left inferior temporal gyrus and the primary visual cortex reached accepted significance levels. CONCLUSIONS: We have therefore confirmed previous reports of brain regions involved in olfactory processing in young volunteers and demonstrated decreased activation in elderly volunteers.     

Gastroprotection induced by capsaicin in healthy human subjects

AIM: To evaluate the gastro-protectlve effect of capsaicin against the ethanol- and indomethacin (IND)-induced gastric mucosal damage in healthy human subjects. METHODS: The effects of small doses (1-8 μg/mL, 100 mL) of capsaicin on the gastric acid secretion basal acid output (BAO) and its electrolyte concentration, gastric transmucosal potential difference (GTPD), ethanol- (5 mL 300 mL/L i.g.) and IND- (3×25 mg/d) induced gastric mucosal damage were tested in a randomized, prospective study of 84 healthy human subjects. The possible role of desensitization of capsaicin-sensitive afferents was tested by repeated exposures and during a prolonged treatment. RESULTS: Intragastric application of capsaicin decreased the BAO and enhanced "non-parietal" component, GTPD in a dose-dependent manner. The decrease of GTPD evoked by ethanol was inhibited by the capsaicin application, which was reproducible. Gastric microbleeding induced by IND was inhibited by co-administration with capsaicin, but was not influenced by two weeks pretreatment with a daily capsaicin dose of 3x400 μg i.g. CONCLUSION: Capsaicin in low concentration range protects against gastric injuries induced by ethanol or IND, which is attributed to stimulation of the sensory nerve endings.     

Cough and glottic-stop reflex sensitivity in health and disease

STUDY OBJECTIVES: Little is known about the normal ranges and repeatability of cough reflex sensitivity measurements, or the relationship of cough reflex sensitivity to other upper airway reflexes in subjects with chronic dry cough. We set out to define the normal range of cough reflex sensitivity and its repeatability in health and disease, and to assess its relationship to the glottic-stop reflex. DESIGN: Prospective, cross-sectional study. SUBJECTS AND METHODS: We measured capsaicin cough reflex sensitivity in 134 healthy subjects and 88 patients with respiratory disease, and assessed the repeatability over 2 weeks in a subgroup of individuals (healthy subjects, 15; chronic cough patients, 15). In another subgroup (healthy patients, 16; chronic cough patients, 14), we measured the sensitivity of the glottic-stop reflex (using inhaled ammonia). RESULTS: Capsaicin cough sensitivity varied widely in the population of healthy subjects, and there was considerable overlap of cough reflex sensitivity between healthy control subjects and patients with cough. The intraclass correlation coefficients for repeatability of cough sensitivity (concentration of capsaicin that causes two coughs, and concentration of capsaicin that causes five coughs) were 0.89 and 0.88, respectively. Patients with chronic cough had a significantly more sensitive glottic-stop reflex than healthy subjects (glottic-stop sensitivity threshold, 483 ppm vs 1,029 ppm, respectively; p = 0.01), and there was a significant positive correlation between glottic-stop and cough reflex sensitivity (r = 0.5; p < 0.01). CONCLUSIONS: We have shown a wide variation of cough reflex sensitivity in healthy subjects, although the measurement does have good 2-week repeatability. There was a reasonably close relationship between cough sensitivity and glottic-stop reflex sensitivity, indicating either that the cough reflex and the glottic-stop reflex share a common pathway or that subjects who have a chronic cough have a global abnormality of upper airway reflexes.     

Cough reflex sensitivity in cigarette smokers

STUDY OBJECTIVES: To evaluate cough reflex sensitivity in a population of young, healthy, male cigarette smokers. DESIGN: Cross-sectional comparison. SETTING: Academic medical center. PARTICIPANTS: Twenty healthy, male current-smokers (mean [+/- SEM] age, 32.2 +/- 1.2 years). MEASUREMENTS: Subjects underwent baseline spirometry followed by capsaicin cough challenge testing, which involved the inhalation of capsaicin in ascending, doubling concentrations until the concentrations inducing two or more coughs (C(2)) and those inducing five or more coughs (C(5)) were reached. The data were compared to those from a group of 50 healthy, male nonsmokers who had undergone identical cough challenge testing. RESULTS: The two groups did not differ in terms of age or baseline pulmonary function. Cough sensitivity was significantly diminished in the current-smokers compared to control subjects. The mean (+/- SEM) log C(2) values in smokers and nonsmokers were 1.26 +/- 0.13 and 0.81 +/- 0.08, respectively (p = 0.004). The mean log C(5) values in smokers and nonsmokers were 2.03 +/- 0.10 and 1.20 +/- 0.08, respectively (p < 0.000001). CONCLUSIONS: Cough reflex sensitivity is significantly diminished in young, healthy, male current-smokers compared to a similar population of nonsmokers. The mechanism of cough suppression in smokers remains speculative but may involve long-term tobacco smoke-induced desensitization of the cough receptors within the airway epithelium.     

Language processing in the occipital cortex of congenitally blind adults

Humans are thought to have evolved brain regions in the left frontal and temporal cortex that are uniquely capable of language processing. However, congenitally blind individuals also activate the visual cortex in some verbal tasks. We provide evidence that this visual cortex activity in fact reflects language processing. We find that in congenitally blind individuals, the left visual cortex behaves similarly to classic language regions: (i) BOLD signal is higher during sentence comprehension than during linguistically degraded control conditions that are more difficult; (ii) BOLD signal is modulated by phonological information, lexical semantic information, and sentence-level combinatorial structure; and (iii) functional connectivity with language regions in the left prefrontal cortex and thalamus are increased relative to sighted individuals. We conclude that brain regions that are thought to have evolved for vision can take on language processing as a result of early experience. Innate microcircuit properties are not necessary for a brain region to become involved in language processing.     

Nonadrenergic, noncholinergic airway inhibitory nerves.

Nonadrenergic, noncholinergic (NANC) nerves, which cause relaxation of airway smooth muscle, have been described in several species including man. Stimulation of efferent vagus nerves during cholinergic and adrenergic blockade induces a pronounced bronchodilation in the cat. In more recent studies in man, capsaicin inhalation or mechanical irritation of the larynx, under conditions of cholinergic and adrenergic blockade, have been shown to cause a transient bronchodilator response. There is some evidence that neuropeptides such as vasointestinal peptide (VIP) or peptide histidine methionine (PHM) may be the neurotransmitter of NANC nerves, but this is not conclusive. Nitric oxide may be another neurotransmitter. In mild asthma, the NANC bronchodilator response is similar to that observed in normal subjects; on the other hand, a reduction in VIP immunoreactivity has been reported in more severe patients. The contribution of NANC dilator nerves in pathophysiological situations is not known, but their effect may be modulated during allergic responses. Use of antagonists or inhibitors of putative neurotransmitters, and molecular biological techniques will be useful in defining both the physiological and pathophysiological roles of NANC inhibitory nerves in the airways.