Susan M. Harding

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.

Spironolactone reduces severity of obstructive sleep apnoea in patients with resistant hypertension: A preliminary report

Obstructive sleep apnoea (OSA) and hyperaldosteronism are very common in subjects with resistant hypertension. We hypothesized that aldosterone-mediated chronic fluid retention may influence OSA severity in patients with resistant hypertension. We tested this in an open-label evaluation by assessing the changes in the severity of OSA in patients with resistant hypertension after treatment with spironolactone. Subjects with resistant hypertension (clinical blood pressure (BP) ⩾140/90 mm Hg on ⩾3 antihypertensive medications, including a thiazide diuretic and OSA (defined as an apnoea–hypopnoea index (AHI) ⩾15) had full diagnostic, polysomnography before and 8 weeks after spironolactone (25–50 mg a day) was added to their ongoing antihypertensive therapy. In all, 12 patients (mean age 56 years and body mass index 36.8 kg m–2) were evaluated. After treatment with spironolactone, the AHI (39.8±19.5 vs 22.0±6.8 events/h; P<0.05) and hypoxic index (13.6±10.8 vs 6.7±6.6 events/h; P<0.05), weight and clinic and ambulatory BP were significantly reduced. Plasma renin activity (PRA) and serum creatinine were significantly higher. This study provides preliminary evidence that treatment with a mineralocorticoid receptor antagonist substantially reduces the severity of OSA. If confirmed in a randomized assessment, it will support aldosterone-mediated chronic fluid retention as an important mediator of OSA severity in patients with resistant hypertension.

24-h Esophageal pH Testing in Asthmatics: Respiratory Symptom Correlation with Esophageal Acid Events

BACKGROUND Gastroesophageal reflux (GER) may be a trigger for asthma and may be clinically silent. Twenty-four-hour esophageal pH testing accurately diagnoses GER in asthmatics. There are no reports correlating respiratory symptoms with esophageal acid events. This study examines the prevalence and severity of GER in asthmatics with and without reflux symptoms and examines respiratory symptom correlation with esophageal acid. METHODS All esophageal manometry and 24-h esophageal pH tests performed were reviewed in asthmatics who met entrance criteria from July 1, 1989, through November 1, 1994. GER was present if esophageal pH tests were abnormal. Results of esophageal tests were compared for asthmatics with reflux symptoms and GER and asthmatics without reflux symptoms and GER. Respiratory symptoms correlated with esophageal acid events if the esophageal pH was < 4 simultaneously with the respiratory event or within 5 min before its onset. RESULTS Of 199 asthmatics who qualified for analysis, 164 (82%) had reflux symptoms. The results of 24-h esophageal pH tests were abnormal in 118 of 164 asthmatics with reflux symptoms (72%), compared with 10 of 35 asthmatics without reflux symptoms (29%). Among asthmatics with GER, 119 of 151 respiratory symptoms (78.8%) were associated with esophageal acid. Seventy-six of 84 reported coughs (90.5%) were associated with esophageal acid. Theophylline did not alter esophageal parameters. CONCLUSIONS There is a strong correlation between esophageal acid events and respiratory symptoms in asthmatics with GER. Respiratory symptom correlation with esophageal acid events further supports that GER may be a trigger for asthma.

Gastroesophageal reflux and asthma: Insight into the association☆☆☆★

Gastroesophageal reflux (GER) is a potential trigger of asthma. GER symptoms are more prevalent in asthma patients compared with control populations, with a prevalence of approximately 75%. GER symptoms are associated with respiratory symptoms and inhaler use. GER may also occur without esophageal symptoms. Abnormal esophageal acid contact times are also more prevalent in patients with asthma compared with control populations, with a prevalence of 80%. Pathophysiologic mechanisms of esophageal acid-induced bronchoconstriction include a vagally mediated reflex, heightened bronchial reactivity, and microaspiration. Esophageal acid may increase minute ventilation without evidence of bronchoconstriction. Esophageal acid is associated with the release of substance P in the bronchial mucosa, resulting in airway edema. Medical antireflux therapy with proton pump inhibitors results in asthma symptom improvement in approximately 70% of patients, similar to surgical results. Predictors of asthma response include the presence of regurgitation, proximal acid reflux, esophagitis healing with therapy, reflux-associated respiratory symptoms, or nocturnal asthma. Management of GER in adult patients with asthma should include a 3-month trial of high-dose proton pump inhibitor while monitoring asthma outcome. GER should be considered as a potential asthma trigger in all patients.

Clinical InvestigationsAsthma24-h Esophageal pH Testing in Asthmatics: Respiratory Symptom Correlation with Esophageal Acid Events

BACKGROUND Gastroesophageal reflux (GER) may be a trigger for asthma and may be clinically silent. Twenty-four-hour esophageal pH testing accurately diagnoses GER in asthmatics. There are no reports correlating respiratory symptoms with esophageal acid events. This study examines the prevalence and severity of GER in asthmatics with and without reflux symptoms and examines respiratory symptom correlation with esophageal acid. METHODS All esophageal manometry and 24-h esophageal pH tests performed were reviewed in asthmatics who met entrance criteria from July 1, 1989, through November 1, 1994. GER was present if esophageal pH tests were abnormal. Results of esophageal tests were compared for asthmatics with reflux symptoms and GER and asthmatics without reflux symptoms and GER. Respiratory symptoms correlated with esophageal acid events if the esophageal pH was < 4 simultaneously with the respiratory event or within 5 min before its onset. RESULTS Of 199 asthmatics who qualified for analysis, 164 (82%) had reflux symptoms. The results of 24-h esophageal pH tests were abnormal in 118 of 164 asthmatics with reflux symptoms (72%), compared with 10 of 35 asthmatics without reflux symptoms (29%). Among asthmatics with GER, 119 of 151 respiratory symptoms (78.8%) were associated with esophageal acid. Seventy-six of 84 reported coughs (90.5%) were associated with esophageal acid. Theophylline did not alter esophageal parameters. CONCLUSIONS There is a strong correlation between esophageal acid events and respiratory symptoms in asthmatics with GER. Respiratory symptom correlation with esophageal acid events further supports that GER may be a trigger for asthma.

Sleep and hypertension.

Ambulatory BP studies indicate that even small increases in BP, particularly nighttime BP levels, are associated with significant increases in cardiovascular morbidity and mortality. Accordingly, sleep-related diseases that induce increases in BP would be anticipated to substantially affect cardiovascular risk. Both sleep deprivation and insomnia have been linked to increases in incidence and prevalence of hypertension. Likewise, sleep disruption attributable to restless legs syndrome increases the likelihood of having hypertension. Observational studies demonstrate a strong correlation between the severity of obstructive sleep apnea (OSA) and the risk and severity of hypertension, whereas prospective studies of patients with OSA demonstrate a positive relationship between OSA and risk of incident hypertension. Intervention trials with continuous positive airway pressure (CPAP) indicate a modest, but inconsistent effect on BP in patients with severe OSA and a greater likelihood of benefit in patients with most CPAP adherence. Additional prospective studies are needed to reconcile observational studies suggesting that OSA is a strong risk factor for hypertension with the modest antihypertensive effects of CPAP observed in intervention studies.

Gastroesophageal reflux, asthma, and mechanisms of interaction

Gastroesophageal reflux (GER) is a potential trigger of asthma. The esophagus and lung interact through a variety of mechanisms. Esophageal acid-induced bronchoconstriction can be provoked by a vagally mediated reflex, whereby acid in the distal esophagus produces airway responses; by neural enhancement of bronchial reactivity, whereby esophageal acid augments airway hyperresponsiveness; or by microaspiration, in which small amounts of esophageal acid in the upper airway cause significant airway responses. Interestingly, even in the microaspiration model, the vagus nerve plays a significant role. Neurogenic inflammation in the lung may occur with either vagally mediated mechanisms or with microaspiration. The prevalence of reflux symptoms, esophagitis, and abnormal esophageal acid contact time is higher in patients with asthma than in control populations. Potential mechanisms, whereby asthma may predispose to the development of GER, include autonomic dysregulation, an increased pressure gradient differential between the thorax and the abdomen, a high prevalence of hiatal hernia, alterations in crural diaphragm function, and bronchodilator medication use. Further research will help define how the esophagus and lung interact.

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.

Recent Clinical Investigations Examining the Association of Asthma and Gastroesophageal Reflux

For more than a decade, investigations have examined the association between asthma and gastroesophageal reflux (GER), and have demonstrated that the presence of esophageal acid events is associated with respiratory symptoms. The most current research shows that GER is prevalent in patients with asthma, that esophageal acid may alter bronchial hyperresponsiveness, and that medical or surgical GER therapy may improve asthma outcome in selected asthma patients. Further research will build on our current knowledge base and, hopefully, enable us to better identify those patients with asthma who will most benefit from reflux therapy.

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.