Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017168 (gastroesophageal reflux disease)
 11,783 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Extensive evidence links cardiovascular disease and sleep disordered breathing. OSA has adverse effects on blood pressure, cardiovascular status,and mortality. Effective CPAP therapy can improve blood pressure and cardiac function in patients who have OSA. Patients who have congestive heart failure have a high prevalence of sleep-disordered breathing, with OSA occurring in 30% of such patients and Cheyne-Stokes respiration in 40%.CPAP is the preferred mode of therapy for both types of sleep-disordered breathing in patients who have coexistent congestive heart failure. Nocturnal worsening of asthma is a common manifestation of this disease that indicates increased disease severity. Therapy focuses on judicious use of long-acting bronchodilators, and the presence of OSA should also be considered. COPD is frequently associated with impaired sleep, likely because of chronic dyspnea and sleep-associated hypoxemia. Appropriate therapy again includes long-acting bronchodilators and possibly nocturnal supplemental oxygen. Gastroesophageal reflux during sleep may lead to prolonged episodes of esophageal acid exposure and may be a common sequela of OSA, perhaps triggering nocturnal worsening of asthma. Endstage renal disease and chronic dialysis are commonly associated with a host of troublesome sleep problems,including OSA, RLS, PLMD, and daytime sleepiness.
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PMID:Sleep and medical disorders. 1593 98

We report 13 severely disabled children with acute respiratory distress syndrome, who were treated at the Department of Pediatrics, Niigata City General Hospital between 1995 and 2002. The children ranged in age from 1 year to 16 years. All were non-ambulant. Chronic aspiration and gastro-esophageal reflux were recognized in 12 patients. Patients had the rapid onset of dyspnea refractory to oxygen therapy. Diffuse bilateral lung infiltrates were present on chest X-ray. Predisposing events included sepsis (3 patients), pneumomia (7 patients), pancreatitis (1 patient) and two children with other infections. All required mechanical ventilation for periods of 3-26 days and received oxygen for 5-64 days. Steroid therapy and surfactant therapy were given to eight and three patients, respectively. Only one patient developed an air leak complication. Despite intensive care, three children died, one underwent tracheostomy and nine recovered completely. Acute respiratory distress syndrome is a commonly recognized cause of acute respiratory failure following a variety of insults. It is characterized by the acute onset of dyspnea refractory to oxygen therapy, and diffuse lung infiltrates. Children with severe motor and intellectual disabilities had various complications. In this study, chronic aspiration and gastro-esophageal reflux are considered to be one of predisposing factors triggering acute respiratory distress syndrome in children with severe motor and intellectual disabilities. Although acute respiratory distress syndrome was considered to be a not infrequent occurrence, its mortality rate might be low despite the severity of the disease in children with severe motor and intellectual disabilities. Acute respiratory distress syndrome can be a complication seen in severely disabled children.
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PMID:Acute respiratory distress syndrome in children with severe motor and intellectual disabilities. 1647 54

The exact pathophysiologic mechanisms of esophageal cell damage and carcinogenesis by gastroesophageal reflux are not clearly understood. The aim of this study was to evaluate the damage to the esophageal epithelium that occurs after acid reflex and mixed acid and bile reflux by assessing histopathology, reactive oxygen species, and DNA damage. Eighty 10-week-old male Sprague-Dawley rats were divided into two groups, an acid reflux group and a mixed (acid/bile) reflux group. Acid reflux was achieved by esophagogastroplasty in which mixed reflux was encouraged via esophagoduodenal anastomosis. Each group contained a control subgroup that underwent sham laparotomy alone. The rats were killed 3, 6, 9, and 12 months after surgery. Malondialdehyde, protein carbonyl content, and DNA damage were determined in lymphocytes. Histopathologic analysis was performed according to the histologic activity index. Inflammation, ulcer, and regeneration in both reflux groups were significantly increased in the esophagus at 3, 6, 9, and 12 months compared with the control group. Mucosal damage was greater in the mixed reflux group compared with the gastric reflux group. Malondialdehyde and carbonyl content in the serum, and DNA damage in lymphocytes, were significantly increased in both reflux groups. At 9 and 12 months, oxidative damage was increased in the mixed reflux group compared with the acid reflux group. Oxygen-derived free radicals seem to be one of the important mediators in the evaluation and generation of reflux esophagitis. The impact of oxygen free radicals, as demonstrated in this study, can be evaluated by assessing the damage that they incur to lipid membranes, serum proteins, and circulating lymphocyte DNA. Serum malondialdehyde and carbonyl content as well as lymphocyte DNA damage were significantly increased in the setting of acid and mixed acid/bile reflux in these rodent models. Further, these serum and lymphocytic changes were associated with esophageal ulceration, inflammation, and regeneration. Evaluation of such markers as serum malondialdehyde and carbonyl content as well as evaluation of lymphocyte DNA might prove to be useful investigations in patients with precancerous and cancerous conditions in addition to conventional methods of diagnosis. Further studies, both animal and human are warranted.
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PMID:Oxidative damage in an experimentally induced gastric and gastroduodenal reflux model. 1622 42

The oxidation of proteins may play an important role in the pathogenesis of chronic inflammatory lung diseases, and may contribute to lung damage. However, the extent of oxidation and the distribution among proteins are not known for most pediatric lung diseases. In this work, protein oxidation was assessed as protein carbonyls. Bronchoalveolar lavages (BAL) from children with chronic lung diseases were investigated by dot-blot assay for content and for pattern of distribution of oxidized proteins by two-dimensional (2D) electrophoresis and Western blotting. Significantly higher levels of protein oxidation than in healthy controls were determined in groups of patients with interstitial lung disease, gastro-esophageal reflux disease, and pulmonary alveolar proteinosis. The proteins most sensitive to oxidation were serum albumin, surfactant protein A, and alpha1-antitrypsin. Our data show increased oxidative stress in lungs of children with chronic pulmonary diseases, with significant interindividual variations. The extent of protein oxidation was proportional to the count of neutrophilic granulocytes in BAL fluid. These findings strongly support the concept that an abundance of reactive oxygen species produced during neutrophilic inflammation may be a deleterious factor, leading to pulmonary damage in these patients.
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PMID:Protein oxidation by chronic pulmonary diseases in children. 1627 Mar 27

The transient receptor potential vanilloid 1 (TRPV1) is an excitatory cation channel, rather selectively expressed in a subpopulation of nociceptive, primary sensory neurons that promote neurogenic inflammation via neuropeptide release. TRPV1 is activated by noxious temperature, low extracellular pH and diverse lipid derivatives, and is uniquely sensitive to vanilloid molecules, including capsaicin. TRPV1 expression and sensitivity is highly regulated by diverse G protein-coupled and tyrosine kinase receptors. Other exogenous or endogenous chemical agents, including reactive oxygen species, ethanol and hydrogen sulphide sensitize/activate TRPV1. In the airways, TRPV1 agonists cause cough, bronchoconstriction, microvascular leakage, hyperreactivity and hypersecretion. Patients with asthma and chronic obstructive pulmonary disease are more sensitive to the tussive effect of TRPV1 agonists and TRPV1 activation may contribute to respiratory symptoms caused by acidic media present in the airways during asthma exacerbation, gastroesophageal reflux induced asthma or in other conditions. TRPV1 antagonists may be useful in the treatment of these diseases.
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PMID:The transient receptor potential vanilloid 1: role in airway inflammation and disease. 1646 49

Gastroesophageal reflux disease (GERD) afflicts approximately 20% of adults in the United States on a weekly basis and 40% on a monthly basis, and is also a trigger for asthma. The prevalence of GERD is higher in asthmatics compared to control groups, with 77% of asthma patients having reflux symptoms and 82% of asthmatics having abnormal esophageal acid contact times on 24-hour esophageal pH testing. Esophageal acid elicits respiratory responses including decreases in airflow, oxygen saturation, and increases in respiratory resistance, minute ventilation, and respiratory rate. Mechanisms of esophageal acid-induced bronchoconstriction include a vagally-mediated reflex, heightened bronchial reactivity, and microaspiration. Esophageal acid also produces airway neurogenic inflammatory responses with the release of substance P, tachykinins, nitric oxide, and other cytokines. Predisposing factors to GERD development in asthmatics include autonomic dysregulation, an increased pressure gradient between the thorax and the abdomen, a high prevalence of hiatal hernia, and altered crural diaphragm function. Theophylline may also potentiate GERD. Therapy of GERD improves asthma outcome. In combined studies examining 326 medically treated asthma patients, asthma symptoms improved in 69% of patients. Surgical therapy trials in 417 asthma patients show asthma symptoms improved in 79%. Management strategies for GERD in asthmatics with reflux symptoms include utilizing an empiric trial of a proton pump inhibitor for three months while measuring asthma outcomes. Since GERD may be clinically ''silent'' in asthma patients, consider 24-hour esophageal pH testing in severe asthma patients who do not have GERD symptoms. Future research will develop the association between asthma and GERD.
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PMID:The potential role of gastroesophageal reflux in asthma. 1649 63

Apnea of prematurity (AOP) is found in >50% of premature infants and is almost universal in infants who are <1000 g at birth. The literature clearly defines clinically significant apnea in infants (breathing pauses that last for >20 seconds or for >10 seconds if associated with bradycardia or oxygen desaturation), but there is no consensus about the duration of apnea, the degree of change in oxygen saturation, or severity of bradycardia that should be considered pathologic. Although caregivers are able to respond successfully to apnea events with drugs (as well as physical and mechanical interventions) in the NICU, it remains unproven whether such interventions have any long-term effects. One of the most effective drugs, caffeine citrate, is currently labeled for short-term use only and within a limited gestational-age population. Clinicians often use off-label drugs that have been approved for gastroesophageal reflux disease, which is common in premature infants, with the belief that such treatments also have an impact on AOP, although this link has never been demonstrated. Key treatment issues include (1) lack of standardization for definition, diagnosis, and treatment of AOP, (2) unproven benefit of intervention, (3) lack of real-time data documenting AOP events, (4) unevaluated sustained treatment improvement at 7 days or later, (5) failure to address confounding conditions, (6) unsubstantiated AOP-gastroesophageal reflux disease relationship, and (7) undetermined role of AOP affecting long-term neurodevelopmental outcomes. In addressing study-design issues, the pulmonary group identified (1) key questions about neonatal apnea, (2) methodologic requirements for study, (3) appropriate outcome measures, and (4) ethical considerations for future studies. This article describes a sample framework for the study of apnea in neonates and identifies future research needs. Plenary-session discussion points are also listed.
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PMID:Summary proceedings from the apnea-of-prematurity group. 1677 22

Barrett's esophagus (BE) patients demonstrate a higher distal esophageal acid exposure profile than other gastroesophageal reflux disease patients. Cellular oxidative stress has been proposed to contribute to the development of BE and esophageal adenocarcinoma. However, a relationship between low esophageal pH and oxidative stress has yet to be elucidated. The aim of this study was to determine the duration of low pH exposure in the esophagus of BE patients compared to those with erosive esophagitis (EE) and to test if brief exposure to low pH leads to the induction of reactive oxygen species (ROS). Seventy-three patients with BE or EE were evaluated by 24-hour esophageal pH monitoring and the percentage of time during which there was exposure to pH < or = 4 and pH < or = 2 was recorded. In vitro, Seg-1 and Het-1A cells were evaluated after brief exposure to pH4 or pH2 by flow cytometry and fluorescent microscopy for the production of ROS. BE patients demonstrated a significantly higher exposure to low pH values (pH < or = 2) than EE patients. The mean percent total time, duration and mean number of reflux episodes at pH < or = 2 were 2.8 +/- 0.53%, 28.8 +/- 3.6 seconds and 79 +/- 11.4 episodes in BE patients, whereas in EE patients they were significantly less, 1.16 +/- 0.3%, 15.6 +/- 1.2 seconds and 48.3 +/- 8.8 episodes, respectively (P < 0.05). In vitro experiments indicate that esophageal cells, when exposed to pH 2, produce ROS. In vitro studies using brief pH 2 exposure are biologically relevant to the clinical situation. Our studies indicate that such exposure induces oxidative stress. This stress may cause DNA damage, mutations and progression to cancer.
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PMID:Esophageal acid exposure at pH < or = 2 is more common in Barrett's esophagus patients and is associated with oxidative stress. 1698 34

Concerns regarding gastroesophageal reflux (GER) and associated apnea episodes result in some practitioners having convalescent, prematurely born infants sleep in the prone position. We have tested the hypothesis that such infants would not suffer from clinically important acid GER or associated apnea episodes more in the supine compared with the prone position. Lower esophageal pH was measured and videopolysomnographic recordings of nasal airflow, chest and abdominal wall movements, electrocardiographic activity, and oxygen saturation were made on two successive days of 21 premature infants (median gestational age 28 wk) at a median postmenstrual age (PMA) of 36 wk. On each day, the infants were studied prone and supine. The acid reflux index was higher in the supine compared with the prone position (median 3% versus 0%, p = 0.002), but was low in both positions. The number of obstructive apnea episodes per hour was higher in the supine position (p = 0.008). There were, however, no statistically significant correlations between the amount of acid GER and the number of either obstructive or total apnea episodes in either the supine or prone position. Supine compared with prone sleeping neither increases clinically important acid GER nor obstructive apnea episodes associated with acid GER in asymptomatic, convalescent, prematurely born infants.
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PMID:Acid gastroesophageal reflux in convalescent preterm infants: effect of posture and relationship to apnea. 1780 96

Oropharyngeal aspiration (OPA) of food and fluids is known to be associated with pneumonia in dysphagic children with neurological disease and direct causality is often assumed. However, little is known about the relationship between OPA and pneumonia in medically complex children when other possible risk factors for pneumonia are considered. We examined the association of World Health Organization (WHO)-defined pneumonia in a heterogeneous group of children with swallowing dysfunction identified by a videofluoroscopic swallow study (VFSS). A retrospective chart review of 150 children (aged 2 weeks to 20 years) was undertaken to determine the relationship between pneumonia and (i) type of swallowing dysfunction (including OPA), (ii) consistency of aspirated food/fluid, and (iii) other factors including multisystem involvement and age (<or=1 year or >1 year). In univariate analysis, the odds ratio (OR) for pneumonia was significantly increased in children with post-swallow residue (PSR) (OR 2.5) or aspiration on thin fluids (OR 2.4), but not with aspiration of thick fluids or purees. In multi-logistic regression, type of swallowing dysfunction or aspirated food/fluid were no longer significant. Instead, pneumonia was significantly associated with diagnosis of asthma (OR 13.25), Down syndrome (OR 22.10), gastroesophageal reflux disease (GERD) (OR 4.28), or history of LRTI (OR 8.28), moist cough (OR 9.17) or oxygen supplementation (OR 6.19). Children with multisystem involvement demonstrated a higher association with pneumonia, but no difference was found for age. We conclude that the impact of OPA on development of pneumonia is considerably reduced once other factors in children with multisystem involvement are taken into account.
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PMID:Oropharyngeal aspiration and pneumonia in children. 1789 17


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