感冒后咳嗽敏感性及气道神经源性炎症改变

目的观察感冒后咳嗽患者(cough post infectious,CPI)的咳嗽敏感性以及气道分泌物神经肽变化,探讨其可能的发病机制。方法以2005年1~6月于广州呼吸疾病研究所慢性咳嗽专科门诊诊断10例CPI患者(CPI组)及10名正常志愿者(正常对照组)为研究对象,通过辣椒素咳嗽激发试验测定气道咳嗽敏感性;观察诱导痰细胞总数以及细胞分类比例;测定痰上清液P物质(SP)、神经肽A(NKA)、神经肽B(NKB)及降钙素基因相关肽(CGRP);检测诱导痰细胞SP、NKA及SP受体(NK-1)的表达,并进行分析比较。结果CPI组咳嗽阈值lgC5为1.16±0.61,明显低于正常对照组(2.64±0.28)(P<0.001)。CPI组诱导痰细胞总数(WBC)及细胞分类比例与正常对照组差异均无显著性意义。CPI组诱导痰上清液SP质量浓度为(516.3±494.2)ng/L,显著高于正常对照组[(141.7±34.5)ng/L,P<0.05];CGRP质量浓度为(141.2±80.8)ng/L,显著高于正常对照组[(74.3±38.2)ng/L,P<0.05];而2组间NKA、NKB的质量浓度差异均无显著性意义。CPI组痰细胞SP、NK-1蛋白的表达分别为1.86±0.81和1.20±0.75,显著高于正常对照组的(0.65±0.44和0.27±0.24)(P<0.01);而2组间NKA蛋白表达差异无显著性意义。结论CPI患者的咳嗽敏感性增高,并伴随气道神经源性炎症,提示其与CPI发病相关。     

慢性咳嗽患者咳嗽激发试验的意义

目的 初步观察咳嗽激发试验在不同性别、病程、病因的慢性咳嗽患者中的差异,以期为进一步评价咳嗽激发试验的临床意义及对临床诊疗慢性咳嗽提供启迪和帮助.方法 选择进行了咳嗽激发试验并最终确诊为上气道咳嗽综合征(UACS)、咳嗽变异性哮喘(CVA)、胃食管反流性咳嗽(GERC)的慢性咳嗽患者108例,分析咳嗽激发试验在不同病因、病程、性别的慢性咳嗽患者间的差异.结果 108例慢性咳嗽患者中UACS 76例,CVA 19例,GERC 13例.咳嗽敏感性阈值的对数(lgC5)女性患者(1.80)显著低于男性(2.40,P<0.05);病程≥12个月患者lgC5(1.80)显著低于病程<12个月的患者(2.40,P<0.05);不同病因患者lgC5存在显著差异,其中GERC患者的lgC5(1.49)显著低于CVA(2.40,P<0.05)和UACS(2.40,P<0.05)患者.结论 不同病因、病程、性别的慢性咳嗽患者咳嗽敏感性均存在差异,咳嗽激发试验在慢性咳嗽病因诊断中具有重要价值.

Abstract：

Objective Preliminary study of the cough reflex sensitivity test in chronic cough patients with different gender,disease duration and causes to evaluate the clinical diagnostic significance of the test and further provide some information for the treatment of chronic cough.Methods Totally 108 chronic cough patients in our hospital were enrolled in the study with the final diagnosis of upper airway cough syndrome(UACS),cough variant asthma(CVA)and gastroesophageal reflux cough(GERC).They all went through the cough reflex sensitivity test and the retrospective analysis of the results was made.Results In 108 patients with chronic cough(76 UACS,19 CVA and 13 GERC),lgC5 was significantly slower in the female(1.80)than the male(2.40,P<0.05)and in the patients with cough duration over 12 months(1.80)than those with cough duration under 12 months(2.40,P<0.05).Cough sensitivity in patients with different causes was significantly different(P<0.05)with lower lgC5 in GERC patients(1.49)than CVA (2.40,P<0.05)and UACS(2.40,P<0.05)patients.Conclusion Cough sensitivity is different in chronic cough patients with different gender,disease duration and causes.Cough reflex sensitivity test is of great value in the etiology diagnosis of chronic cough.     

Effect of smoking cessation on cough reflex sensitivity.

Recent studies have shown that cigarette smokers have diminished cough reflex sensitivity compared with nonsmokers. The current authors proposed a mechanism of chronic cigarette smoke-induced desensitisation of airway cough receptors. To investigate this hypothesis, cough sensitivity to inhaled capsaicin (C5) in chronic smokers was measured both while they were actively smoking and 2, 6, 12 and 24 weeks after smoking cessation. In total, 29 subjects underwent baseline capsaicin challenge while smoking and 2 weeks after smoking cessation. Mean+/-sem log C5 fell from 1.86+/-0.12 to 1.60+/-0.12, demonstrating significant enhancement of cough reflex sensitivity. Of the total, 20, 18 and 14 subjects successfully abstained from smoking for 6, 12 and 24 weeks, respectively. Mean log C5 values after 12 and 24 weeks of smoking cessation were significantly diminished from baseline. In a control group of smokers, mean log C5 did not decrease from baseline after 6, 12 and 24 weeks. Overall, the log C5 profile of the smoking cessation group showed a clear, linearly decreasing trend over time compared with the control group. Even after many years of smoking, cough sensitivity is enhanced as early as 2 weeks after smoking cessation. Given the importance of an intact cough reflex, these changes may provide clinical benefit.     

Effect of guaifenesin on cough reflex sensitivity

BACKGROUND: Guaifenesin, a commonly used agent for the treatment of cough, is termed an expectorant since it is believed to alleviate cough discomfort by increasing sputum volume and decreasing its viscosity, thereby promoting effective cough. Despite its common usage, relatively few studies, yielding contrasting results, have been performed to investigate the action and efficacy of guaifenesin. STUDY OBJECTIVES: To evaluate the effect of guaifenesin on cough reflex sensitivity. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Academic medical center. PARTICIPANTS: Fourteen subjects with acute viral upper respiratory tract infection (URI) and 14 healthy volunteers. INTERVENTIONS: On 2 separate days, subjects underwent capsaicin cough challenge 1 to 2 h after receiving a single, 400-mg dose (capsules) of guaifenesin or matched placebo. Measurements and results: The concentration of capsaicin inducing five or more coughs (C(5)) was determined. Among subjects with URI, mean (+/- SEM) log C(5) after guaifenesin and placebo were 0.92 +/- 0.17 and 0.66 +/- 0.14, respectively (p = 0.028). No effect on cough sensitivity was observed in healthy volunteers. CONCLUSIONS: Our results demonstrate that guaifenesin inhibits cough reflex sensitivity in subjects with URI, whose cough receptors are transiently hypersensitive, but not in healthy volunteers. Possible mechanisms include a central antitussive effect, or a peripheral effect by increased sputum volume serving as a barrier shielding cough receptors within the respiratory epithelium from the tussive stimulus.     

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

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.     

Ethnic and gender differences in cough reflex sensitivity.

BACKGROUND: Although recent studies have suggested that the cough reflex is more sensitive in women than in men, ethnic differences in cough reflex sensitivity have not previously been investigated. OBJECTIVES: To evaluate ethnic and gender differences in cough reflex sensitivity. METHODS: We performed capsaicin cough challenge testing in 182 healthy volunteers of three distinct ethnic groups: Caucasian (white, non-Hispanic, of European origin), Indian (originating from the Indian subcontinent) and Chinese. The concentration of capsaicin inducing 2 or more (C2) and 5 or more coughs (C5) was determined in each subject. RESULTS: Mean (+/-SEM) values for log C5 demonstrated that, within each ethnic group, the cough reflex was more sensitive in women: p = 0.00002 for Caucasian subjects; p = 0.003 for Indian volunteers; and p = 0.002 for Chinese subjects. Examination of C2 data yielded similar results. When subjects were evaluated by gender, multivariate analysis of variance demonstrated no ethnic differences in sensitivity to capsaicin. CONCLUSION: Our data do not support the presence of significant ethnic differences in cough reflex sensitivity, but do confirm previous data demonstrating lower cough thresholds in women.     

Sex-related differences in cough reflex sensitivity in patients with chronic cough

Among patients attending specialist cough clinics there is an excess of females, but the reason for this sex difference is unknown. We tested the hypothesis that the sensitivity of the cough reflex is greater in female compared with male patients with chronic cough. Inhalation cough challenges with capsaicin and citric acid were performed in a large group of patients with chronic cough. The concentrations of tussive agent causing two (C2) and five (C5) coughs were calculated. Measurements of capsaicin cough reflex sensitivity (median [interquartile range]) were significantly lower for female patients compared with male patients (C2: 1.9 [0.5 to 5.5] versus 5.3 [2.2 to 11.5] micro M, p = 0.0026; C5: 8.6 [2.2 to 34.0] versus 51.2 [7.2 to > 100] micro M, p = 0.0007). Similarly for citric acid challenge, values were significantly lower for female compared with male patients (C2: 53.5 [17.3 to 145.4] versus 118.1 [41.4 to 381.7] mM, p = 0.0064; C5: 300.0 [97.1 to > 1,000] versus 830.4 [300.0 to > 1,000] mM, p = 0.032). There were significant correlations between capsaicin and citric acid C2 values (r(s) = 0.54, p < 0.0001) and C5 values (r(s) = 0.57, p < 0.0001). These findings indicate a sex difference in cough sensitivity in patients with chronic cough, as previously reported in healthy volunteers. This may explain the female preponderance in cough clinics.     

Cough reflex sensitivity and airway inflammation in patients with chronic cough due to non-acid gastro-oesophageal reflux

Background and objective: The aim of this study was to explore the pathogenesis of chronic cough caused by non‐acid reflux. Methods: Seven patients with chronic cough due to non‐acid reflux, 12 patients with chronic cough due to acid reflux, 10 patients with gastro‐oesophageal reflux disease without cough and 12 healthy volunteers were recruited for the study. All subjects underwent oesophageal multi‐channel intraluminal impedance measurements combined with pH monitoring, and assessment of cough reflex sensitivity to capsaicin and induced sputum cytology. The concentrations of substance P, mast cell tryptase, prostaglandin D2 and histamine in induced sputum were measured by ELISA. Results: Cough threshold C2 and C5 did not differ between patients with chronic cough due to non‐acid or acid reflux, but the values were significantly lower than those for patients with gastro‐oesophageal reflux disease without cough and healthy volunteers. Weakly acidic reflux episodes were obviously more frequent in patients with chronic cough due to non‐acid reflux than in the other three groups. Sputum substance P and mast cell tryptase concentrations were remarkably increased in patients with chronic cough, but were similar for those with cough due to non‐acid or acid reflux. There were significant inverse correlations between substance P levels and cough threshold C2 or C5 in patients with cough due to non‐acid or acid reflux, and between mast cell tryptase levels and cough threshold C2 in patients with cough due to acid reflux. Conclusions: Chronic cough due to non‐acid reflux may be related to cough reflex hypersensitivity caused by neurogenic airway inflammation and mast cell activation, in which weakly acidic reflux is possibly a major factor.     

Effects of pirfenidone on increased cough reflex sensitivity in guinea pigs

Pirfenidone, an antifibrotic drug with anti-inflammatory and antioxidant effects, delays fibrosis in idiopathic pulmonary fibrosis (IPF). Patients with IPF have a greater cough reflex sensitivity to inhaled capsaicin than healthy people, and cough is an independent predictor of IPF disease progression; however, the effects of pirfenidone on cough reflex sensitivity are unknown.After challenge with an aerosolized antigen in actively sensitized guinea pigs, pirfenidone was administered intraperitoneally, and the cough reflex sensitivity was measured at 48 h after the challenge. Bronchoalveolar lavage (BAL) was performed, and the tracheal tissue was collected.Pirfenidone suppressed the capsaicin-induced increase in cough reflex sensitivity in a dose-dependent manner. Additionally, increased levels of prostaglandin E₂, substance P, and leukotriene B₄, but not histamine, in the BAL fluid were dose dependently suppressed by pirfenidone. The decrease in neutral endopeptidase activity in the tracheal tissue was also alleviated by pirfenidone treatment. The total number of cells and components in the BAL fluid was not influenced.These results suggest that pirfenidone ameliorates isolated cough based on increased cough reflex sensitivity associated with allergic airway diseases, and potentially relieve chronic cough in IPF patients who often have increased cough reflex sensitivity. Prospective studies on cough-relieving effects of pirfenidone in patients with IPF are therefore warranted.     

蛋白激酶C通道对正常与致敏豚鼠气道张力的影响

探讨蛋激酶信号通道对正常和卵蛋白致敏豚鼠离体气管条和肺条张力的调节作用是否有差异。方法应用卵蛋白腹腔敏复制豚鼠哮喘模型，取气管条与肺条测定气道平滑肌的张力。     

Sensitivity of the cough reflex in patients with chronic cough.

Cough may occur in association with excess bronchial secretions and may, therefore, be productive. However, in a proportion of patients the cough is non-productive and a possible association with an enhanced response of the cough reflex has been postulated. Using the irritant capsaicin, the sensitivity of the cough reflex was measured in 363 individuals. A questionnaire was used to divide subjects into three groups: Group A) non-coughing controls; Group B) subjects with non-productive cough; and Group C) subjects with productive cough. The group means (+/- 99% confidence interval (CI)) of the log capsaicin concentration causing two or more coughs (C2) for groups A, B, C were 0.98 (+/- 0.08), 0.64 (+/- 0.09) and 1.04 (+/- 0.23), respectively. The log capsaicin concentration causing five or more coughs (C5) for groups A, B, C were 1.78 (+/- 0.1), 1.16 (+/- 0.12) and 1.54 (+/- 0.25), respectively. Group B was significantly more sensitive to inhaled capsaicin than the other groups (p less than 0.01). No significant difference was observed between groups A and C. Some differences were found when subgroups were examined within groups B and C. In group B, patients with post-nasal drip were found to have a normal sensitivity of the cough reflex and were, therefore, different from the remainder of patients with non-productive cough. In group C, patients with bronchiectasis and current infection showed an increase in the sensitivity of their cough reflex. It is concluded that cough can occur in association with either excess mucus production leading to productive cough or an increase in the sensitivity of the cough reflex, possibly leading to non-productive cough.     

Effects of macrolides on antigen-induced increases in cough reflex sensitivity in guinea pigs

BackgroundMacrolides are antibiotics that have anti-inflammatory activities. Hence, they are used for both acute and chronic inflammatory airway diseases. However, the effects of these agents on allergic airway disorders presenting with an isolated chronic cough, such as non-asthmatic eosinophilic bronchitis and eosinophilic tracheobronchitis with cough hypersensitivity (atopic cough), still remain to be elucidated.ObjectiveTo determine if macrolides are effective in the management of chronic cough caused by eosinophilic airway inflammation.MethodsThe cough reflex sensitivity to inhaled capsaicin was measured at 48 h after challenge with an aerosolized antigen in actively sensitized guinea pigs. The 14-, 15- or 16-membered macrolides (erythromycin, azythromycin, or josamycin, respectively) were given intraperitoneally every 12 h after the antigen challenge. Bronchoalveolar lavage and the resection of the tracheal tissue were performed immediately after the measurement of the cough response to capsaicin.ResultsThe antigen-induced increase in the number of coughs elicited by capsaicin inhalation was significantly reduced by treatments with erythromycin and azythromycin, but not with josamycin. Erythromycin dose-dependently inhibited the increases in the substance P, prostaglandin E₂ and leukotriene B₄ levels, but not the histamine levels, in the bronchoalveolar lavage fluid. However, erythromycin did not influence the antigen-induced decrease in the neutral endopeptidase (NEP) activity in the tracheal tissue.ConclusionsBoth 14- and 15-membered, but not 16-membered, macrolides could reduce the antigen-induced cough reflex hypersensitivity by inhibiting the antigen-induced release of the afferent sensory nerve sensitizers. These macrolides may be therapeutically useful for the treatment of isolated chronic cough based on cough reflex hypersensitivity in allergic airway diseases such as non-asthmatic eosinophilic bronchitis and atopic cough.     

冷刺激人体食道对咳嗽敏感性和气道功能的影响

目的通过比较正常人和慢性咳嗽患者冷刺激食道前后咳嗽敏感性、肺功能的变化来探讨冷刺激与咳嗽的关系。方法对慢性咳嗽患者按慢性咳嗽病因诊断程序进行病因诊断,分为胃食管反流性咳嗽组(GERC组)和非胃食管反流性咳嗽组(非GERC组),同时入选正常人作为对照。首先对所有受试者检测肺通气功能、气道阻力和辣椒素咳嗽敏感性,间隔24 h后,受试者取坐位,记录10 min内的咳嗽次数,再经鼻饲管灌注0℃生理盐水300 ml,持续15 min。记录刺激过程中和刺激结束后10 min内的咳嗽次数,刺激结束40 min后所有受试者需再次检测肺通气功能、气道阻力和咳嗽敏感性。比较冷刺激前后咳嗽次数、咳嗽敏感性、肺通气功能和气道阻力的变化。咳嗽敏感性检测采用辣椒素定量吸入激发试验,结果以诱发≥5次咳嗽的最低激发浓度的对数值(Lg C5)表示。结果纳入试验的慢性咳嗽患者共17例,其中GERC 8例,非GERC 9例,同时纳入正常人9例。三组受试者在年龄、性别、咳嗽病程上没有显著差异。冷刺激食道前GERC、非GERC和正常受试者的10 min咳嗽次数分别为4.5(0~20)、7(0~35)、0(0~2),刺激食道后10 min的咳嗽次数分别为9(0~25)、11(0~70)、0(0~5),刺激前后比较均无显著变化(P0.05)。冷刺激食道前GERC、非GERC和正常受试者的咳嗽敏感性(Lg C5)分别为1.34(0.29~3.00)、3.00(1.19~3.00)、3.00(3.00~3.00),刺激食道后咳嗽敏感性分别为1.50(0.59~3.00)、3.00(0.59~3.00)、3.00(2.70~3.0),刺激前后比较均无显著变化(P0.05)。冷刺激食道后慢性咳嗽患者呼吸阻抗Zrs较刺激前显著增高[3.75±0.91(cm H_2O)·L~(-1)·S~(-1)vs.3.46±0.78(cm H_2O)·L~(-1)·S~(-1),P0.05],以GERC患者冷刺激后呼吸阻抗增高为主[3.94±1.04(cm H_2O)·L~(-1)·S~(-1)vs.3.44±0.83(cm H_2O)·L~(-1)·S~(-1),P0.05]。冷刺激食道前后GERC、非GERC和正常受试者的其它气道阻力指标和肺通气功能指标均无显著变化(P0.05)。结论冷刺激食道可以增高GERC患者的呼吸阻抗,但对咳嗽敏感性和肺通气功能无明显影响。     

Breathing pattern, lung inflation reflex and airway tone in acrylamide neuropathy

Slowly adapting pulmonary stretch receptors (SARs) participate in numerous respiratory reflexes, including the Hering-Breuer lung inflation reflex (HBR), and reflex control of respiratory rate and depth. In addition, SAR discharge may modulate airway tone. We studied the effect of acrylamide neuropathy, which causes reversible dysfunction of SARs and their myelinated vagal afferents, on the breathing pattern, HBR and airway tone in conscious dogs. As neuropathy evolved, breathing became slow and deep, and both the apnoeic and bronchodilatory responses to lung inflation were markedly reduced, findings consistent with SAR dysfunction. Recovery of clinical neuropathy and respiratory reflexes followed acrylamide withdrawal. Despite the obvious abnormalities of SAR-mediated reflexes in acrylamide-affected dogs, airway tone remained normal and sinus arrhythmia prominent in the presence of neuropathy, suggesting that small diameter vagomotor efferents are relatively resistant to acrylamide. Acrylamide neuropathy provides a useful preparation for the study of vagomotor function in animals in which feedback from myelinated pulmonary afferents is attenuated.     

Changes in cough reflex sensitivity after cessation and resumption of cigarette smoking

Previous studies have shown that healthy cigarette smokers have diminished cough reflex sensitivity compared to healthy nonsmokers. We have recently demonstrated that cough reflex sensitivity is enhanced soon after smoking cessation, suggesting that diminished cough sensitivity in smokers results from chronic cigarette smoke-induced desensitization of airway cough receptors. In this study, we evaluated cough reflex sensitivity to capsaicin (C(5)) in 11 chronic smokers who had discontinued smoking for at least 2 weeks, and then resumed smoking. Two weeks after smoking cessation there was a significant enhancement of cough reflex sensitivity; mean (+/-SEM) log C(5) decreased from 1.77+/-0.18 to 1.47+/-0.14 (p=0.01). All subjects resumed smoking after 2-12 weeks of abstinence. Repeat capsaicin cough challenge was performed 14-23 days after resumption of smoking. Mean log C(5) increased compared to the last value obtained during the smoking cessation period: 1.42+/-0.15 vs. 1.77+/-0.16 (p=0.0004). Mean log C(5) after resumption of smoking returned to almost exactly the baseline value. Our findings suggest that the sensitivity of airway cough receptors is a dynamic phenomenon, promptly affected and modulated by changes in environmental conditions, such as the presence or absence of cigarette smoke.     

Effect of the cyclooxygenase-2 inhibitor celecoxib on bronchial responsiveness and cough reflex sensitivity in asthmatics

Cyclooxygenase (COX), an essential enzyme in the pathway of prostaglandin formation from arachidonic acid, exists in two isoforms. Cyclooxygenase-1 (COX-1) is expressed under normal physiologic conditions, whereas COX-2, the inducible isoform, is associated with inflammation. Recent studies have linked COX-2 induction to the asthmatic inflammatory response, but potentially beneficial results, such as enhanced production of antiinflammatory and bronchoprotective substances, may also occur. The aim of the present study was to investigate the effect of selective COX-2 inhibition on bronchial responsiveness and cough reflex sensitivity. Eight adult subjects with stable asthma underwent spirometry, bronchoprovocation challenge with methacholine, and cough challenge testing with capsaicin, before and after a 7 day course of the COX-2 inhibitor celecoxib (200 mg orally, twice daily) and placebo, in a randomized, double-blind, crossover fashion. No significant changes in pulmonary function, bronchial responsiveness, or cough reflex sensitivity were induced by celecoxib. It appears, therefore, that 1 week of therapy with celecoxib does not significantly affect basal airway tone, nor the afferent airway receptors controlling bronchoconstriction and cough. However, the results of this trial cannot be extrapolated to subjects with severe asthma, or those suffering an asthmatic exacerbation. In such conditions of enhanced inflammatory response, the role of selective COX-2 inhibition remains to be elucidated. Copyright Academic Press.     

Daily oral care and cough reflex sensitivity in elderly nursing home patients

BACKGROUND: Intensive oral care can reduce the incidence of pneumonia in elderly nursing home patients, but the mechanism is unknown. OBJECTIVE: To explore the effects of intensive oral care on impaired cough reflex sensitivity, which is a known risk factor of aspiration pneumonia. METHODS: Cough reflex sensitivity to citric acid was measured in elderly nursing home patients, who were randomly assigned to the intervention group (n = 30) and the control group (n = 29). The patients in the intervention group had their teeth and gingiva cleaned by caregivers after every meal for 1 month. The patients in the control group performed their own oral care during the same period. Serum substance P (SP) concentration, cognitive function, and activities of daily living (ADL) were also assessed. RESULTS: In the intervention group, cough reflex sensitivity at 30 days showed significantly higher sensitivity than baseline (p < 0.01). At 30 days, the cough reflex sensitivities in the intervention group were significantly higher than that of the control group (p < 0.05). Compared with the control group, the odds ratio of improvement of cough reflex sensitivity was 5.3 (95% confidence interval, 1.7 to 16.0; p < 0.005) for the intervention group. One month of intensive oral care did not have a significant effect on serum SP concentration, cognitive function, and ADL. CONCLUSION: Intensive oral care may reduce the incidence of pneumonia by improving cough reflex sensitivity in elderly nursing home patients.     

Encoding of the cough reflex

Coughing can be both voluntarily induced and involuntarily initiated by activation of vagal afferent nerves innervating the airways and lungs. Centrally, cough is regulated at the level of the brainstem through integration of vagal afferent nerve input by relay neurones in the nucleus tractus solitarius (nTS). Projections to and from the nTS add further complexity to cough regulation, as do the profound influences of psychological and social factors known to regulate cough. Peripherally, both neuronal and non-neuronal elements in the airways regulate the excitability of the vagal afferent nerve terminals regulating cough. These multiple levels of integration and encoding of the cough reflex may render this defensive respiratory response highly susceptible to modulation both by disease processes and through therapeutic intervention.     

The cough reflex in animals: relevance to human cough research

All mammalian species studied cough or display some similar respiratory reflex upon aerosol challenge with tussigenic stimuli such as citric acid or capsaicin. Animals cough to the same stimuli that evoke coughing in humans, and therapeutic agents that display antitussive effects in human studies also prevent coughing in animals. The many invasive procedures and complementary in vitro studies possible in animals but not readily reproduced in human subjects, along with the proven predictive value of cough studies in animals, provide the rationale for animal modeling of human cough. The advantages and disadvantages of studying cough in animals are discussed.