Peijun Gui

Perception of urge-to-cough and dyspnea in healthy smokers with decreased cough reflex sensitivity

BackgroundAlthough cigarette smoking has been implicated as an important risk factor for the development of respiratory symptoms, the perceptional aspects of two symptoms in smokers have not been fully elucidated. Therefore, we simultaneously evaluated the cough reflex sensitivity, the cognition of urge-to-cough and perception of dyspnea in both healthy smokers and non-smokers.MethodsFourteen male healthy never-smokers and 14 age-matched male healthy current-smokers were recruited via public postings. The cough reflex sensitivity and the urge-to-cough were evaluated by the inhalation of citric acid. The perception of dyspnea was evaluated by Borg scores during applications of external inspiratory resistive loads.ResultsThe cough reflex threshold to citric acid, as expressed by the lowest concentration of citric acid that elicited two or more coughs (C2) and the lowest concentration of citric acid that elicited five or more coughs (C5) in smokers was significantly higher than in non-smokers. The urge-to-cough log-log slope in smokers was significantly milder than that of non-smokers. There were no significant differences in the urge-to-cough threshold between non-smokers and smokers. There were no significant differences in perceptions of dyspnea between non-smokers and smokers.ConclusionsThe study showed that decreased cough reflex sensitivity in healthy smokers was accompanied by a decreased cognition of urge-to-cough whereas it was not accompanied by the alternation of perception of dyspnea. Physicians should pay attention to the perceptual alterations of cough in smokers.

Effect of cigarette smoking on cough reflex induced by TRPV1 and TRPA1 stimulations

BACKGROUND Recent studies have shown that neurogenic inflammation induced by cigarette smoke is inhibited by TRPA1 antagonist, but not by TRPV1 antagonist. Since cough reflex sensitivity is known to be modified by smoking status, we investigated the effects of cigarette smoking on TRPA1- and TRPV1-induced cough and urge-to-cough in healthy males. METHODS Twenty-six healthy never-smokers and 30 healthy current smokers were recruited via public postings. Cough reflex thresholds and urge-to-cough were evaluated by inhalation of capsaicin, a TRPV1 agonist, and cinnamaldehyde, a TRPA1 agonist. The cough reflex thresholds were defined as the lowest concentrations of capsaicin and cinnamaldehyde that elicited two or more coughs (C(2)) and five or more coughs (C(5)), respectively. The urge-to-cough was evaluated using the modified Borg scale. RESULTS In capsaicin-induced cough, the cough reflex thresholds, as expressed by C(2) and C(5), in current smokers were significantly higher than those in never-smokers (p<0.01 and p<0.001, respectively). The urge-to-cough log-log slopes in current smokers were significantly lower than those of never-smokers (p<0.001). There were no significant differences in the thresholds of the urge-to-cough between never-smokers and current smokers. In cinnamaldehyde-induced cough, there were no significant differences in cough reflex thresholds in C(2) and C(5) between never-smokers and current smokers, nor were there any significant differences in urge-to-cough log-log slope between never-smokers and current smokers. There were no significant differences in the thresholds of the urge-to-cough between never-smokers and current smokers. CONCLUSION The study suggests that smoking has a differential effect on cough responses between TRPV1 and TRPA1 stimulations.

Aging deteriorated perception of urge-to-cough without changing cough reflex threshold to citric acid in female never-smokers

BackgroundThe effect of aging on the cognitive aspect of cough has not been studied yet. The purpose of this study is to investigate the aging effect on the perception of urge-to-cough in healthy individuals.MethodsFourteen young, female, healthy never-smokers were recruited via public postings. Twelve elderly female healthy never-smokers were recruited from a nursing home residence. The cough reflex threshold and the urge-to-cough were evaluated by inhalation of citric acid. The cough reflex sensitivities were defined as the lowest concentration of citric acid that elicited two or more coughs (C2) and five or more coughs (C5). The urge-to-cough was evaluated using a modified the Borg scale.ResultsThere was no significant difference in the cough reflex threshold to citric acid between young and elderly subjects. The urge-to-cough scores at the concentration of C2 and C5 were significantly smaller in the elderly than young subjects. The urge-to-cough log-log slope in elderly subjects (0.73 ± 0.71 point · L/g) was significantly gentler than those of young subjects (1.35 ± 0.53 point · L/g, p < 0.01). There were no significant differences in the urge-to-cough threshold estimated between young and elderly subjects.ConclusionsThe cough reflex threshold did not differ between young and elderly subjects whereas cognition of urge-to-cough was significantly decreased in elderly subjects in female never-smokers. Objective monitoring of cough might be important in the elderly people.

Gender differences in perceptions of urge to cough and dyspnea induced by citric acid in healthy never smokers.

BACKGROUND The mechanism of the gender difference in cough reflex threshold has not been clearly elucidated. In the present study, we evaluated gender differences in the cough reflex threshold along with the perceptions of respiratory sensations, urge to cough, and dyspnea. METHODS Nineteen male and 20 female healthy never smokers were recruited through public postings. The cough reflex threshold and the urge to cough were evaluated by inhalation of citric acid. The perception of dyspnea was evaluated by Borg scores during applications of external inspiratory resistive loads. RESULTS The cough reflex threshold and suprathreshold to citric acid in women, as expressed by the log transformation of the lowest concentration of citric acid that elicited two or more and five or more coughs, was significantly lower than that in men. The urge-to-cough log-log slope in women (1.47 ± 0.81 point × L/g) was significantly steeper than in men (0.96 ± 0.28 point × L/g; P < .03). There were no significant differences in the urge-to-cough threshold estimated between men and women. The slope of the dyspnea Borg score change during the external inspiratory resistive loads is steeper in women (0.17 ± 0.04 point/cm H₂O/L/s) than that in men (0.13 ± 0.05 point/cm H₂O/L/s; P < .01). The urge-to-cough slope significantly correlated with the perception of dyspnea slope (r = 0.537; P < .01). CONCLUSIONS The gender difference in cough reflex threshold accompanied the gender difference in amplification rate of respiratory sensations in the same direction. The higher central gain for common pathways for respiratory sensations may play a role in lower cough reflex threshold in women. Further studies are needed to elucidate this issue.

Thermal Taste and Anti-Aspiration Drugs: A Novel Drug Discovery Against Pneumonia

Despite the development of strong antibiotics, the pneumonia death is increasing all over the world in these decades. Among the people who died of pneumonia, the majority were 65 years old or over. Although pneumonia is recently categorized into several entities, aspiration pneumonia includes all entities. Therefore, targeting dysphagia and aspiration to treat pneumonia is a promising strategy and anti-aspiration drugs will be a part of pneumonia treatment. The swallowing reflex in elderly people was temperature-sensitive and the improvement of swallowing reflex by temperature stimuli could be mediated by the thermosensing TRP channels at pharynx. The administration of capsaicin as an agonist stimulus of TRPV1, a warm temperature receptor, decreased the delay in swallowing reflex. Red wine polyphenols improved swallowing reflex by enhancing TRPV1 response. Food with menthol, agonist of TRPM8 which is a cold temperature receptor, also decreased the delay in swallowing reflex. Olfactory stimulation such as black pepper was useful to improve the swallowing reflex for people with low ADL levels or with decreased consciousness. Thus, recent advancement of geriatrics found several anti-aspiration drugs such as thermosensing TRP channel agonists, black pepper odor, amantadine, cilostazol, theophylline and angiotensin- converting enzymes inhibitors. Thermosensing TRP channel agonists include capsaicin, capsiate, menthol, and red wine polyphenols. Controls of swallowing are mediated by various stages of neural system from peripheral sensory nerves to the entire cerebral cortex. Each anti-aspiration drug acts on various sites of neural axis of swallowing reflex. The combination of various anti-aspiration drugs may improve dysphagia and prevent aspiration pneumonia.

Chronic inflammation, lymphangiogenesis, and effect of an anti-VEGFR therapy in a mouse model and in human patients with aspiration pneumonia

Chronic inflammation induces lymphangiogenesis and blood vessel remodelling. Since aged pneumonia patients often have repeated episodes of aspiration pneumonia, the pathogenesis may involve chronic inflammation. For lymphangiogenesis, VEGFR‐3 and its ligand VEGF‐C are key factors. No previous studies have examined chronic inflammation or vascular changes in aspiration pneumonia or its mouse models. In lung inflammation, little is known about the effect of blocking VEGFR‐3 on lung lymphangiogenesis and, moreover, its effect on the disease condition. This study aimed to establish a mouse model of aspiration pneumonia, examine the presence of chronic inflammation and vascular changes in the model and in patients, and evaluate the effect of inhibiting VEGFR‐3 on the lymphangiogenesis and disease condition in this model. To induce aspiration pneumonia, we repeated inoculation of pepsin at low pH and LPS into mice for 21–28 days, durations in which bronchioalveolar lavage and plasma leakage in the lung suggested the presence of exaggerated inflammation. Conventional and immunohistochemical analysis of tracheal whole mounts suggested the presence of chronic inflammation, lymphangiogenesis, and blood vessel remodelling in the model. Quantitative RT‐PCR of the trachea and lung suggested the involvement of lymphangiogenic factor VEGF‐C, VEGFR‐3, and pro‐inflammatory cytokines. In the lung, the aspiration model showed the presence of chronic inflammation and exaggerated lymphangiogenesis. Treatment with the VEGFR inhibitor axitinib or the VEGFR‐3 specific inhibitor SAR131675 impaired lymphangiogenesis in the lung and improved oxygen saturation in the aspiration model. Since the lung is the main site of aspiration pneumonia, the changes were intensive in the lung and mild in the trachea. Human lung samples also showed the presence of chronic inflammation and exaggerated lymphangiogenesis, suggesting the relevance of the model to the disease. These results suggest lymphatics in the lung as a new target of analysis and therapy in aspiration pneumonia. Copyright

Inhibitory effect of cervical trachea and chest wall vibrations on cough reflex sensitivity and perception of urge-to-cough in healthy male never-smokers

BackgroundNon-pharmacological options for symptomatic management of cough are desired. Although chest wall mechanical vibration is known to ameliorate cough reflex sensitivity, the effect of mechanical vibrations on perceptions of urge-to-cough has not been studied. Therefore, we investigated the effect of mechanical vibration of cervical trachea, chest wall and femoral muscle on cough reflex sensitivity, perceptions of urge-to-cough as well as dyspnea.MethodsTwenty-four healthy male never-smokers were investigated for cough reflex sensitivity, perceptions of the urge-to-cough and dyspnea with or without mechanical vibration. Cough reflex sensitivity and urge-to-cough were evaluated by the inhalation of citric acid. The perception of dyspnea was evaluated by Borg scores during applications of external inspiratory resistive loads. Mechanical vibration was applied by placing a vibrating tuning fork on the skin surface of cervical trachea, chest wall and femoral muscle.ResultsCervical trachea vibration significantly increased cough reflex threshold, as expressed by the lowest concentration of citric acid that elicited five or more coughs (C5), and urge-to-cough threshold, as expressed by the lowest concentration of citric acid that elicited urge-to-cough (Cu), but did not significantly affect dypnea sensation during inspiratory resistive loading. On the other hand, the chest wall vibration not only significantly increased C5 and Cu but also significantly ameliorated the load-response curve of dyspnea sensation.ConclusionsBoth cervical and trachea vibrations significantly inhibited cough reflex sensitivity and perception of urge-to-cough. These vibration techniques might be options for symptomatic cough management.

Effect of Short-Term Exposure to High Particulate Levels on Cough Reflex Sensitivity in Healthy Tourists: A Pilot Study

Background: Previous studies have reported a relationship between particulate air pollution and respiratory symptoms or decline in lung function, but information about acute effects of short-term exposure to airborne particulate matter (PM) on cough and pulmonary function is scarce. Objective: To investigate the effect of short-term exposure to high concentrations of PM on the cough reflex threshold, urge-to-cough, pulmonary function, and cough-related quality of life in a group of healthy non-resident volunteers visiting Beijing, China. Methods: Seventeen healthy residents of Sendai, Japan, who planned to attend a meeting in Beijing, were recruited. We checked local air quality and measured cough reflex thresholds, urge-to-cough, pulmonary function, and Leicester Cough Questionnaire-acute (LCQ-acute) scores in the volunteers before, during, and after their trip to Beijing. Results: The PM2.5 and PM10 concentrations in Beijing were significantly higher than those in Japan on the measurement days. Cough reflex thresholds, expressed as nebulized citric acid concentrations required to induce ≥ 2 and ≥ 5 coughs, were significantly lower during the stay in Beijing than before or after the visit. Vital capacity, forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC were significantly lower during the stay in Beijing than before the trip. Similarly, the urge-to-cough threshold was significantly lower during the stay in Beijing than after the trip, as was the total LCQ-acute score. Conclusion: We tentatively concluded that short-term exposure to high PM concentrations may have adverse effects on cough reflex and urge-to-cough thresholds, pulmonary function, and cough-related quality of life.

Gender differences in the effect of urge‐to‐cough and dyspnea on perception of pain in healthy adults

Previous studies have reported that respiratory sensations, such as urge‐to‐cough and dyspnea, have an inhibitory effect on pain. Considering the existence of gender differences in both urge‐to‐cough and pain, it is conceivable that a gender difference also exists in the analgesia induced by urge‐to‐cough. In this study, we evaluated gender differences in the pain perception response to urge‐to‐cough, as well as to dyspnea. Twenty‐seven male and 26 female healthy nonsmokers were originally enrolled. Citric acid challenge was used to induce the urge‐to‐cough sensation, and dyspnea was elicited by inspiratory loaded breathing. Before and during inductions of these two respiratory sensations, perception of pain was assessed by the thermal pain threshold, and differences between men and women were compared. The thermal pain threshold in women (43.83 ± 0.17°C) was significantly lower than that in men (44.75 ± 0.28°C; P < 0.05) during the baseline period. Accompanying increases in both citric acid concentration and inspiratory resistive load, thermal pain threshold values significantly increased in both men and women. The average thermal pain threshold changes for comparable increases in the urge‐to‐cough Borg score were parallel between men and women. Furthermore, the mean value of the thermal pain threshold plotted against the dyspnea Borg score also showed no significant gender difference. These results demonstrate that although gender differences exist in respiratory sensations, that is, urge‐to‐cough and dyspnea, the inhibitory effects of these respiratory sensations on the perception of pain are not significantly different between the sexes.