Esophageal Acid Infusion Research Articles

Noctural Asthma: Role of Nocturnal Gastroesophageal Reflux

Gastroesophageal reflux (GER) is common in those with asthma, with 77% of asthmatics complaining of heartburn, with 41% experiencing reflux-associated respiratory symptoms. Likewise, 24% of those with asthma that is difficult to control have “clinically silent” GER. There are no studies examining nocturnal reflux symptoms in asthmatics. Esophageal dysmotility is also common, and abnormal esophageal acid contact times on 24h esophageal pH tests were found in 82% of asthmatics examined consecutively. Most asthmatics with GER also have abnormal esophageal acid contact times while in the supine position, reflecting sleep time. Endoscopic evidence of esophagitis was found in 43% of asthmatics. Two mechanisms of bronchoconstriction induced by esophageal acid have been proposed: a vagally mediated reflex, by which esophageal acid in the distal esophagus causes reflex bronchoconstriction, and microaspiration. Although there is conflicting evidence, distal esophageal acid causes a decrease in peak expiratory flow rates, an increase in respiratory resistance, and an increase in minute ventilation. If microaspiration is present, there is further augmentation of this airway response. Although only a few studies have been performed in those with nocturnal asthma with GER, one study in a pediatric population showed that esophageal acid infusions caused more airway responses at 04:00 than at 24:00. Also, asthmatic children with nocturnal asthma symptoms have a higher re-flux score, with a positive correlation between reflux score and nighttime-associated wheezing. Despite these findings in children, a study performed in sleeping adults with nocturnal asthma noted no alterations in airflow resistance with esophageal acid, concluding that GER contributed little to the nocturnal worsening of asthma. There are also gastroesophageal circadian issues that may influence GER in asthmatics. Gastric acid secretion peaks at approximately 21:00, and gastric emptying is delayed when a meal is given at 20:00 versus 08:00. Esophageal acid clearance is delayed significantly during sleep, and acid clearance occurs during arousals. Upper esophageal sphincter (UES) pressure also decreases with sleep onset, which may predispose to microaspiration. Further research is needed to clarify what role nocturnal reflux has on nocturnal asthma and airway inflammation and whether circadian rhythm factors alter airway responses to esophageal acid.

ESOPHAGEAL REFLEX CAN REDUCE CORONARY BLOOD FLOW.

Is it heartburn or angina? This dilemma often stumps clinicians, possibly because the answer is all of the above for some patients. This study tested the impact of esophageal acid infusions on coronary blood flow in 14 patients with coronary artery …

Gastroesophageal Reflux-Induced Bronchoconstriction: Is Microaspiration a Factor?

Study objective To evaluate the role of microaspiration in gastroesophageal reflux-induced bronchoconstriction. Design Prospective study blinded to the subject. Setting Outpatient laboratory of a 908-bed university hospital. Participants Thirty nonsmoking adults divided into two groups: asthmatics with reflux (AR), 20; and subjects with gastroesophageal reflux (R), 10. Interventions Dual esophageal pH probe placed. Esophageal infusions of normal saline solution, 0.1N hydrochloric acid, then normal saline solution, each lasting 18 min, were followed by two 20-min recovery periods. Subjects remained in the supine position throughout. Spirometry and specific airway resistance (SRaw) performed at baseline, after each esophageal infusion and recovery period. Proximal esophageal acid exposure, a requirement for microaspiration, was assessed by the proximal esophageal pH probe. Results Peak expiratory flow rate (PEF) decreased with esophageal acid in the AR group and did not recover immediately despite esophageal acid clearance with a significant main effect of subject groups (p<0.021) by repeated measures analysis of covariance. This decrease in PEF was not associated with the presence of proximal esophageal acid exposure (p=0.618). Specific airway resistance increased in the AR group with esophageal acid and worsened despite acid clearance, especially during the second recovery phase, with a significant phase (p<0.009) and group by treatment effect (p<0.009). The presence of proximal esophageal acid exposure was not associated with this deterioration in SRaw (p=1.0). Conclusions Esophageal acid infusions given in the supine position caused a decrease in PEF and an increase in SRaw in the asthma with reflux group, which did not improve despite acid clearance. These responses were not dependent on proximal esophageal acid exposure. Also, SRaw continued to worsen during the recovery phase in the AR group, which may represent a delayed bronchoconstrictor effect. These data suggest that microaspiration does not play a significant role in esophageal acid-induced bronchoconstriction. To evaluate the role of microaspiration in gastroesophageal reflux-induced bronchoconstriction. Prospective study blinded to the subject. Outpatient laboratory of a 908-bed university hospital. Thirty nonsmoking adults divided into two groups: asthmatics with reflux (AR), 20; and subjects with gastroesophageal reflux (R), 10. Dual esophageal pH probe placed. Esophageal infusions of normal saline solution, 0.1N hydrochloric acid, then normal saline solution, each lasting 18 min, were followed by two 20-min recovery periods. Subjects remained in the supine position throughout. Spirometry and specific airway resistance (SRaw) performed at baseline, after each esophageal infusion and recovery period. Proximal esophageal acid exposure, a requirement for microaspiration, was assessed by the proximal esophageal pH probe. Peak expiratory flow rate (PEF) decreased with esophageal acid in the AR group and did not recover immediately despite esophageal acid clearance with a significant main effect of subject groups (p<0.021) by repeated measures analysis of covariance. This decrease in PEF was not associated with the presence of proximal esophageal acid exposure (p=0.618). Specific airway resistance increased in the AR group with esophageal acid and worsened despite acid clearance, especially during the second recovery phase, with a significant phase (p<0.009) and group by treatment effect (p<0.009). The presence of proximal esophageal acid exposure was not associated with this deterioration in SRaw (p=1.0). Esophageal acid infusions given in the supine position caused a decrease in PEF and an increase in SRaw in the asthma with reflux group, which did not improve despite acid clearance. These responses were not dependent on proximal esophageal acid exposure. Also, SRaw continued to worsen during the recovery phase in the AR group, which may represent a delayed bronchoconstrictor effect. These data suggest that microaspiration does not play a significant role in esophageal acid-induced bronchoconstriction.

407-1 Cardio-Oesophageal Reflex: A Mechanism for “Linked Angina” in Patients with Angiographically Proven Coronary Artery Disease

We have shown previously that oesophageal acid stimulation can reduce coronary blood flow in syndrome X patients suggesting the presence of a cardio-oesophageal reflex in humans. The presence of such a reflex in patients with coronary artery disease could explain the mechanism of “linked angina”. To investigate this hypothesis we studied the effect of oesophageal acid stimulation on coronary blood flow in 14 patients with angiographically documented significant (&gt;50% stenosis) coronary artery disease (CAD) and 18 heart transplant patients (HT). A fine tube was introduced through the patient's nose in to the distal oesophagus. A 3.6F intracoronary Doppler catheter was positioned in the proximal left anterior descending coronary artery. Coronary blood flow was calculated from measurements of coronary flow velocities and arterial cross-sectional area from quantitative angiography. Oesophageal instillation of 0.1 M hydrochloric acid and 0.9% saline was performed in random, double-blind fashion (60 ml over 5 minutes) and the measurements were repeated after each infusion. Nine patients in the CAD group reported their usual chest pain on acid instillation but none experienced any pain after saline infusion. None of the patients in the HT group experienced any chest pain on acid or saline infusion. There were no significant difference in systemic haemodynamics after the infusions in both groups. The coronary blood flow (CBF) was significantly reduced by acid oesophageal stimulation in the CAD group [CBF pre-acid 70.4 ± 14.3, CBF post-acid 46.4 ± 19.1 ml/min (p &lt; 0.01)]. However, there was no significant difference in the CBF on saline infusion [73.5 ± 15.3 versus 72.5 ± 14 ml/min]. CBF in the HT group was unaffected by acid or saline infusion. In the 9 CAD patients who experienced angina on oesophageal acid infusion there was a significant reduction in CBF from 73.4 ± 12.9 to 34.6 ± 4.7 ml/min. However, in the 5 CAD patients who did not have any chest pain the CBF was unaffected by acid infusion [65.1 ± 16.7 versus 67.5 ± 16.7 ml/min] . Oesophageal acid stimulation can produce angina and significantly reduce coronary blood flow. The lack of any significant effect in the HT group, in whom the heart is denervated, suggests a neural reflex. The presence of such a reflex may be a mechanism for “Linked Angina” in patients with coronary artery disease.

Cardiac and Respiratory Reactivity to Gastroesophageal Reflux: Experimental Data in Infants

Gastroesophageal reflux associated with apnea and/or bradycardia induces both dilatation of the esophagus and abrupt intrusion of acid content in it. To evaluate the relative importance of these two types of stimulation on cardiac and respiratory responses, a series of experimental protocols were designed, in which we evaluated the influence of esophageal dilatation alone, acid infusion alone and both stimulations simultaneously. The passage of a volume in the lower third of the esophagus (n = 14) during reflux was simulated by balloon dilation; the passage of acid gastric juice during reflux was simulated by an esophageal acid infusion test, within the physiological range (n = 8; duration = 5 min; pH = 2.2). Cardiac, respiratory and arousal responses were compared during a control period and during the distal balloon dilatation and esophageal saline and acid infusion periods. Distal esophageal balloon dilatation and acid infusion induced significant prolongation of the RR interval and of the duration of the respiratory cycle. The presence of the esophageal catheter did not lead to continuous vagal stimulation. Simultaneous stimulation by balloon dilatation and acid infusion provoked cardiac responses that were above the level reached by each stimulation separately. Behavioral and electroencephalographic observations demonstrate significantly more frequent and longer arousal responses during the acid infusion than during control and saline infusion periods. We conclude that distal esophageal balloon dilatation and acid infusion elicit significant cardiac and respiratory responses in newborns during active sleep.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac, respiratory, and arousal responses to an esophageal acid infusion test in near-term infants during active sleep.

This study was designed to determine the cardiac, respiratory, and arousal responses to an esophageal acid infusion test in near-term infants free from neurological, gastroesophageal, and cardiopulmonary disease at time of testing during active sleep. Eight infants (gestational age 28-37.5 weeks, postconceptional age 36-40 weeks) were tested. Using standardized procedures and timing, we compared the cardiac, respiratory and arousal responses during a control period and during distal esophageal saline and acid infusion periods. The duration of each of these periods was 5 min. The pH of the acid infusion was 2.2. We found that this mild distal esophageal acid infusion test induced significant prolongation of the interval between successive electrocardiogram R waves compared with control and saline infusion periods (806.5 +/- 145.7 ms, 478.8 +/- 49.4 ms, and 468.8 +/- 37.2 ms, respectively; p less than 0.01) and of the duration of the respiratory cycle (2.9 +/- 0.7 s, 1.5 +/- 0.3 s, and 1.5 +/- 0.2 s, respectively; p less than 0.01). Esophageal acid infusion elicited significant electroencephalogram (EEG) arousal responses. The number of the EEG arousals was significantly increased during the acid period as compared with control and saline infusion periods (2.9 +/- 1.4, 0.5 +/- 0.5, and 0.4 +/- 0.5, respectively; p less than 0.01). Total arousal duration was significantly increased during acid as compared with control and saline infusion periods (42 +/- 17.5 s, 4.5 +/- 5.1 s, and 3.5 +/- 5.0 s, respectively; p less than 0.01). We conclude that distal esophageal acid stimulation elicits significant cardiac, respiratory, and EEG arousal responses in near-term infants during active sleep.

Cardiac, Respiratory, and Arousal Responses to an Esophageal Acid Infusion Test in Near‐Term Infants During Active Sleep

SummaryThis study was designed to determine the cardiac, respiratory, and arousal responses to an esophageal acid infusion test in near‐term infants free from neurological, gastroesophageal, and cardiopulmonary disease at time of testing during active sleep. Eight infants (gestational age 28–37.5 weeks, postconceptional age 36–40 weeks) were tested. Using standardized procedures and timing, we compared the cardiac, respiratory and arousal responses during a control period and during distal esophageal saline and acid infusion periods. The duration of each of these periods was 5 min. The pH of the acid infusion was 2.2. We found that this mild distal esophageal acid infusion test induced significant prolongation of the interval between successive electrocardiogram R waves compared with control and saline infusion periods (806.5± 145.7 ms, 478.8± 49.4 ms, and 468.8± 37.2 ms, respectively; p &lt; 0.01) and of the duration of the respiratory cycle (2.9± 0.7 s, 1.5± 0.3 s, and 1.5± 0.2 s, respectively; p &lt; 0.01). Esophageal acid infusion elicited significant electroencephalogram (EEG) arousal responses. The number of the EEG arousals was significantly increased during the acid period as compared with control and saline infusion periods (2.9± 1.4, 0.5± 0.5, and 0.4± 0.5, respectively; p &lt; 0.01). Total arousal duration was significantly increased during acid as compared with control and saline infusion periods (42± 17.5 s,4.5± 5.1 s, and 3.5± 5.0 s, respectively; p &lt; 0.01). We conclude that distal esophageal acid stimulation elicits significant cardiac, respiratory, and EEG arousal responses in near‐term infants during active sleep.

Esophageal Function and Gastroesophageal Reflux during Sleep and Waking in Patients with Chronic Obstructive Pulmonary Disease

This study was conducted to assess esophageal function and pulmonary resistance changes with esophageal acidification in patients with COPD. Twelve patients with COPD and a mean age of 55.6 years were studied. Each patient underwent standard esophageal manometry, 24-h ambulatory pH testing, esophageal acid clearance evaluation during sleep, and an assessment of pulmonary resistance with and without esophageal acid perfusion. Neither airway resistance nor conductance was altered by the esophageal acid infusion; LES pressures were normal and esophageal contractile pressures were mildly decreased. Acid exposure in the upright and supine positions was within normal limits. Acid clearance during sleep was similar to that in normal subjects; however, acid clearance during waking appeared to be somewhat prolonged in the COPD patients. We conclude that patients with COPD do not have a bronchoconstrictive reflex to distal esophageal acidification, and esophageal function in these patients appears to be relatively normal.

Effect of Esophageal Acid Exposure on Upper Esophageal Sphincter Pressure

To investigate the relationship between gastroesophageal reflux and upper esophageal sphincter (UES) pressure, total esophageal acid exposure times on 23‐hour ambulatory pH monitoring were compared with UES manometric results in 98 subjects, 85 with laryngopharyngeal symptoms and 13 asymptomatic controls. There was no correlation of acid exposure time with tonic UES pressure nor with any UES wet swallow parameter. The response of the UES to acute upper esophageal acid infusion was assessed in another 13 patients by a sleeve catheter. There was no significant increase of tonic sleeve UES pressure during acid infusion. In contrast to most previous reports, our results indicate that esophageal acid exposure, whether acute or chronic, has little influence on the UES.

Esophageal dysfunction and chest pain in patients with mitral valve prolapse: A prospective study utilizing provocative testing during esophageal manometry

purpose: The cause of chest discomfort in patients with mitral valve prolapse (MVP) remains unknown. Our aim was to determine prospectively the incidence of esophageal disorders and abnormal responses to edrophonium chloride and esophageal acid infusions in patients with MVP and troublesome non-ischemic chest pain. patients and methods: After coronary artery disease was excluded, 20 patients with MVP and chest pain underwent esophageal manometry and provocative testing with edrophonium chloride and acid infusion. Seven patients with MVP but without chest pain served as control subjects; they also underwent esophageal manometry with provocative testing. results: Esophageal manometry revealed esophageal disorders in 16 patients: diffuse esophageal spasm in 14 patients, nutcracker esophagus in one, and hypotensive lower esophageal sphincter in one. Esophageal motility was normal in four patients. Injection of edrophonium and acid infusion tests evoked typical chest disomfort in three of 18 and five of 19 patients, respectively. In six of seven control subjects with MVP but with no chest discomfort, esophageal motility was normal and provocative testing did not produce chest discomfort (p <0.05 versus results in patients). conclusion: Esophageal disorders were common and may account for chest discomfort in certain patients with MVP and persistent chest pain syndromes.

Gastroesophageal reflux in patients with asthma and chronic bronchitis.

To determine the relationship between gastroesophageal (GE) reflux and pulmonary disease, we studied 21 asthmatics, 30 chronic bronchitics, 6 patients with GE reflux and no pulmonary symptoms, and 10 control subjects; GE reflux was diagnosed by pH monitoring and GE scintiscanning. Frequency of GE reflux in the asthmatics was 57%; in the chronic bronchitics it was 56%. Pulmonary function tests did not show any differences between patients with or without reflux. The GE reflux episodes were more numerous but shorter in asthmatics than in chronic bronchitics. Patients with digestive symptoms alone were no different from chronic bronchitics with respect to reflux. The mechanism whereby reflux triggers pulmonary problems was investigated using the following 2 tests: scintiscan for pulmonary aspiration, and esophageal acid infusion (0.1N HCl). Six pulmonary aspirations were detected. Only asthmatics, with or without reflux, showed any significant variations in maximal expiratory flow at 50% and 25% of VC after HCl infusion. Thus, our results show that asthmatics differ from chronic bronchitics by the characteristics of their reflux.