Ronald W. Alexander

Duodenogastroesophageal reflux: Relationship to pH and importance in Barrett's esophagus

BACKGROUND/AIMS Several reports suggest that duodenogastroesophageal reflux may produce esophagitis, Barretts esophagus, and esophageal adenocarcinoma. The purpose of this study was to understand better the relationship of pH (< 4 and > 7), duodenogastroesophageal reflux, and fasting bile acid concentrations in producing esophageal damage. METHODS Using a spectrophotometric technique to measure bile reflux, four groups were studied: healthy subjects, reflux patients, patients with Barretts esophagus, and patients with esophageal symptoms after partial gastrectomy. RESULTS Simultaneous 24-hour pH and bile monitoring of distal esophagus found close association between total percent of time pH < 4 and duodenogastroesophageal reflux (r = 0.78; P < 0.001) but a poor relationship (r = -0.06) with total percent of time pH > 7, suggesting that the term alkaline reflux is a misnomer. Duodenogastroesophageal reflux increased significantly with the severity of reflux disease, being greatest in patients with Barretts esophagus and comparable with that in patients with partial gastrectomy. Fasting bile acid concentrations did not distinguish patients with Barretts esophagus from those with reflux. Rather, increased quantity of acid reflux was the single factor most characterizing patients with Barretts esophagus. Omeprazole (20 mg twice daily) normalized acid reflux parameters (13.8% +/- 1.6% to 0.8% +/- 0.6%) and significantly (P < 0.001) decreased duodenogastroesophageal reflux (32.8% +/- 6.9% to 4.7% +/- 1.7%). CONCLUSIONS Acid reflux is the primary factor in the development of Barretts esophagus. Bile reflux parallels acid reflux and, at best, may have a synergistic role. Aggressive acid suppression with omeprazole markedly decreases both.

Asthma and gastroesophageal reflux : Acid suppressive therapy improves asthma outcome

PURPOSE To determine (1) the appropriate omeprazole (Prilosec) dose required for adequate acid suppression in asthmatics with gastroesophageal reflux, (2) whether aggressive acid suppressive therapy of gastroesophageal reflux improves asthma outcome in asthmatics with gastroesophageal reflux, (3) the time course of asthma improvement, and (4) demographic, esophageal, or pulmonary predictors of a positive asthma response to antireflux therapy. PATIENTS AND METHODS Thirty nonsmoking adult asthmatics with gastroesophageal reflux (asthma defined by American Thoracic Society criteria and reflux defined by symptoms and abnormal 24-hour esophageal pH testing) were recruited from the outpatient clinics of a 900-bed university hospital. Patients underwent baseline studies including a demographic questionnaire, esophageal manometry, dual-probe 24-hour esophageal pH test, barium esophogram, and pulmonary spirometry. During the 4-week pretherapy phase, patients recorded reflux and asthma symptom scores and peak expiratory flow rates (PEFs) upon awakening, 1 hour after dinner, and at bedtime. Patients began 20 mg/d omeprazole, and the dose was titrated until acid suppression was documented by 24-hour pH test. Patients remained on this acid suppressive dose for 3 months. Responders were identified by a priori definitions: asthma symptom reduction by >20% and/or PEF increase by >20%. Asthma symptom scores, PEFs baseline and posttherapy pulmonary spirometry were analyzed. RESULTS Twenty-two (73%) patients were asthma symptom and /or PEF responders: 20 (67%) were asthma symptom responders, and 6 (20%) were PEF responders. Responders reduced their asthma symptoms by 57% (P<0.001), improved their morning and night PEFs by 8% and 9% (both P <0.005), and had improvement in forced expiratory volume at 1 second (P <0.02), mean forced expiratory flow during the middle half (25% to 75%) of the forced vital capacity (P <0.04), and peak expiratory flow (P <0.01) with acid suppressive therapy. Mean acid suppressive dose of omeprazole was 27 mg/d (+/-2.2) with 27% (8) patients requiring more than 20 mg/d. The presence of regurgitation or excessive proximal esophageal reflux predicted asthma response with 100% sensitivity, 100% negative predictive value, specificity of 44% and a positive predictive value of 79%. CONCLUSIONS Acid suppressive therapy with omeprazole improves asthma symptoms and/or PEFs by >20% and improves pulmonary function in 73% of asthmatics with gastroesophageal reflux after 3 months of acid suppressive therapy. Many asthmatics (27%) required >20 mg/d of omeprazole to suppress acid. The presence of regurgitation and/or excessive proximal esophageal reflux predicts a positive asthma outcome.

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.

Gastroesophageal Reflux-induced Bronchoconstriction

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.

Localized congenital hepatic fibrosis presenting as an abdominal mass

A six month old male with a liver mass localized to the right lobe that had the histological features of congenital hepatic fibrosis is presented. The mass was resected and the patient was asymptomatic 10 months after surgery. This case serves to further broaden the range of lesions with the histological features of congenital hepatic fibrosis; only one other example of localized congenital hepatic fibrosis has been previously reported.

Serial 7s and Alphabet Backwards as brief measures of information processing speed

The construct and discrimant validity of Serial 7s and Alphabet Backwards as measures of information processing speed were examined. In Study 1, seven commonly used speeded neuropsychological measures, including Serial 7s and Alphabet Backwards, were subjected to factor analysis. Two factors emerged. Factor 1 was labeled visual-motor scanning speed. Factor 2 was labeled information processing speed and included Serial 7s and Alphabet Backwards. Study 2 compared 42 cardiac transplant candidates and 46 age, education, and IQ matched college student controls on Serial 7s and Alphabet Backwards. The cardiac patients were significantly slower on both Serial 7s and Alphabet Backwards but did not make more errors. These results suggest that Serial 7s and Alphabet Backwards can be used as brief and technically simple measures of information processing speed.

Clinical Investigations: Airways ObstructionGastroesophageal 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.