Clinical Characteristic Of Gastro-esophageal Reflux Related Cough And Effects Of Esophageal Perfusion With Cold Water And Alcohol On Airway Function In Human Beings

BackgroundGastro-esophageal reflux(GER) is an important etiological factor inducing chronic cough.Compared with the other etiological factors, GER related cough (GERC) is prone to be misdiagnosed. Anti-reflux therapy is the major method for GERC, but some patients are refractory to anti-reflux treatment. So identifing the clinical characteristics for the diagnosis of GERC and investigating the indication for the outcome of anti-reflux theraphy are very important.The reflux contents stimulate the receptors of the distal esophagus and induce neurogenic inflammation by oesophage-tracheobronchial reflex may play an important role in the pathogensis of GERC. We speculate that intra-oesophageal perfusion with cold water, alcohol or other different physical-chemical solutions could induce airway neurogenic inflammation and cough by oesophage-tracheobronchial reflex. We often see cough caused or worsen by food in daily life. Furthermore, in animal models, we had confirmed infusion of cold, hot normal saline or ethanol solutions respectively into the esophagus significantly increased plasma extravasation and substance P(SP) level in the airway. However,no one had done this research on human beings.ObjectiveIn present study, we identify the clinical characteristics for the diagnosis of GERC and investigate the indication for the outcome of anti-reflux theraphy. Furthermore, we investigate the relationship between diet and cough by intra-oesophageal perfusion with cold water and alcohol. PartⅠCinical characteristics and prognostic prediction of gastro-esophageal reflux related coughObjectiveTo identify the clinical characteristics for the diagnosis of GERC and investigate the indication for the outcome of anti-reflux theraphy.MethodsGERC were diagnosed by a validated systematic diagnostic protocol. The clinical characteristics such as time, character, causative factor and associated manifestations of cough were compared with those of non-GER induced cough(NGERC). The Demeester score and the symptom association probability(SAP) of 24-hour esophageal pH monitoring were analysed in GERC patients. Patients with GER related cough or cough complicating GER received anti-reflux therapy. The clinical characteristics and the data of 24-hour ambulatory esophageal pH measurement were compared among completely relieved, partial relieved and no response patients after anti-reflux therapy.Results1. 71 patients met the GERC criteria and were fully evaluated. 73 NGERC patients were included as control group. In GERC patients, the prevalence of daily cough occurred in 71.8%, cough associated with meals in 49.3%, cough with regurgitation associated symptom in 62.4%, and a history of gastropathy in 42.3% was significantly higher than that in NGER patients (P<0.01, P<0.05).2. The specificity of cough associated with meals was the highest(80.8%). The Youden index of cough associated with meals(0.30) and cough with regurgitation associated sysmptom(0.34) was better than others.3. 55 GERC patients received the 24-hour esophageal pH monitoring, in which the Demeester score and other refluxing index of distant terminal except SAP were obviously higher than proximal terminal(P<0.01).4. The cough score during the night(1.26±1.34) of completely relived patients was significantly lower than no response patients(2.15±1.54, P<0.01).The visual analogue scale(5.48±1.81) of completely relived GERC patients was significantly lower than partly relived (7.50±1.90) and no response patients(7.44±1.59,P<0.01).5. The proportion of SAP≥95% in completely relived patients(61.5%) was significantly higher than partly relived group(27.6%,χ²=6.425,P<0.05). The rate of cough associated with regurgitation associated symptom, Demeester score≥12.7,acid exposure times≥4% in completely(65.7%,76.9%,42.3%)and partly relived patients(61.1%,78.6%,51.7%) was significantly higher than no response group(P<0.01).6. Regurgitation associated symptom and Demeester score were correlated well with anti-reflux treatment. (P<0.05)Conclusion` Daily cough, cough associated with meals, reflux associated symptoms and a history of gastric disease are of diagnostic value for GERC. Regurgitation associated symptom and Demeester score are two predictor of anti-reflux treatment.PartⅡEffects of esophageal cold and alcohol perfusion on airway function and cough sensitivityObjectiveTo assess the effect of lower esophageal cold water and alcohol instillation on airway function and cough sensitivity in normal people and chronic cough patients.MethodsPatients with chronic cough due to gastroesophageal reflux disease(GERC) or non GER(NGERC) were enrolled in our study, healthy people as control group. Six subgroups were established according to different intervention:GERC with cold perfusion, NGERC with cold perfusion, normal people with cold perfusion, GERC with alcohol perfusion, NGERC with alcohol perfusion, normal people with alcohol perfusion. All the subjects were performed through a nasal feeding tube to perfused esophagas with 0-4℃water(300ml,15min) or 42% alcohol(10ml,10min). The cough sensitivity, airway resistance, lung function and mediators of inflammation in induced sputum were measured 24h before and 40min after cold instillation(10min after alcohol instillation). The cough was recorded 10min before and after perfusion. The IL-8 and SP concentration in induced sputum was measured with Enzyme-Linked Immunosorbent Assay (ELISA).Results1. The cough recording of chronic cough patients after cold or alcohol perfusion was showing a tendency to increase.2. In GERC patients, the Zrs(total resistance of the respiratory system) was significantly increase in after cold instillation[3.94±1.04(cmH2O)·L^-1·S^-1] than before cold instillation [3.44±0.83 (cmH2O)·L^-1·S^-1, P<0.05 ]. However, no significant change was found in alcohol instillation.3. The cough sensitivity, FEV1, FVC, Fres or R5 of total airway resistance, R20 of central resistance, R5-R20 of peripheral resistance showed no significant diference in before and after cold, alcohol instillation (P>0.05).4. The concentration of SP in the sputum supernatant was significantly higher in GERC group[772.51(range, 343.73¹037.02)pg/ml] and NGERC group [895.04(range, 205. 31¹768.39) pg/ml] than those in normal control group [421.15(range, 28.02 ⁹11.67)pg/ml, P<0.05]. However, there was no marked IL-8 difference among these groups.5. The concentration of IL-8 in sputum supernatant significantly decreased after alcohol instillation[291.26(range, 61.02¹052.34) pg/ml] than before alcohol instillation [649.41- (range, 9.86²082.02) pg/ml, P<0.05]. But, this change didn't occurred in cold perfusion.6. The concentration of SP in sputum supernatant showed no significant diference in before and after cold perfusion,as well as alcohol instillation.ConclusionEsophageal cold water and alcohol perfusion showed a tendency to increase cough in chronic cough patients. Effects of esophageal cold water perfusion can increase airway resistance of GERC patients.