Laurence A. Bradley

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.

Normal 24-hr ambulatory esophageal pH values. Influence of study center, pH electrode, age, and gender.

Although the most sensitive and specific test for diagnosing gastroesophageal reflux disease, normal standards for prolonged esophageal pH monitoring are based on small sample sizes with questions raised about the effects of pH electrode, older age, gender, and methods of data analysis on pH variables. Recently three groups have established normal data bases using similar methodology. Multiple regression and nonparametric analyses showed that the values for the six traditional pH parameters were comparable across study centers. Therefore, the groups were combined for a total study population of 110 healthy subjects (47 men, 63 women, mean age 38 years with a range of 20–84 years). Further nonparametric analyses revealed the following: (1) type of pH electrode (antimony vs glass) is not significantly related to parameters of physiologic acid reflux; (2) age is not independently related to pH parameters; (3) men tend to have more physiologic reflux than women; and (4) older men tend to experience longer episodes of reflux than younger men and women. There was a significant effect of gender and a significant interaction between age and gender on the number of episodes >5 min (P=0.008). Nearly significant differences were found for percentage of total acid exposure time (P=0.03), total reflux episodes (P=0.02), and the longest reflux episode (P=0.02). We believe these normal esophageal pH values can be used confidently as standards in any laboratory, and consideration should be given to developing separate standards for men and women.

Esophageal Chest Pain: Current Controversies in Pathogenesis, Diagnosis, and Therapy

PURPOSE To evaluate the importance of esophageal abnormalities as a potential cause of recurrent noncardiac chest pain. DATA IDENTIFICATION We discuss the rapidly evolving new knowledge in this field after analyzing the literature in English published since 1979. STUDY SELECTION We reviewed 117 articles on recurring chest pain and paid specific attention to the following nine controversial issues: the potential mechanisms of esophageal pain, the differentiation of cardiac and esophageal causes, the evaluation of new esophageal motility disorders, the use of esophageal tests in evaluating noncardiac chest pain, the usefulness of techniques for prolonged monitoring of intraesophageal pressure and pH, the relation of psychologic abnormalities to esophageal motility disorders, the possible mechanisms for decreased visceral pain thresholds in these patients, the relation of esophageal chest pain to the irritable bowel syndrome, and the appropriate therapies for these patients. RESULTS OF DATA SYNTHESIS Through our review of the literature, we identified areas of concordance and disagreement. These areas are discussed and an overall perspective is provided. CONCLUSIONS Continuing attempts to develop rational diagnostic and therapeutic approaches to patients with noncardiac chest pain should include a multidisciplinary approach involving basic scientists, gastroenterologists, psychologists, and other clinical experts in the field of pain research.

Pathophysiology of Fibromyalgia

This article reviews the biologic, genetic, and environmental factors that may contribute to the pathophysiology of fibromyalgia. As an affective spectrum disorder, fibromyalgia may share these causal factors with a number of related and co-occurring pain conditions, such as irritable bowel syndrome or temporomandibular disorder. There is strong evidence that cardinal pain symptoms of fibromyalgia may be due to alterations in central processing of sensory input, along with aberrations in the endogenous inhibition of pain. Genetic research has shown familial aggregation of fibromyalgia and other related disorders such as major depressive disorder. Exposure to physical or psychosocial stressors, as well as abnormal biologic responses in the autonomic nervous system and neuroendocrine responses, may also contribute to dysfunctional pain processing. As fibromyalgia research continues to progress, it is expected that the pathophysiology of this disorder will be further elucidated, leading to more rational and targeted strategies for the treatment of patients with this condition.

Altered pain perception and psychosocial features among women with gastrointestinal disorders and history of abuse: A preliminary model

OBJECTIVES To evaluate the relationships between sexual/physical abuse, pain perception, environmental events, coping strategies, and psychiatric morbidity in a sample of female patients with painful gastrointestinal disorders. PATIENTS Fifty paid volunteers from a tertiary care center including 13 patients with gastroesophageal reflux disease (GERD), 26 with noncardiac chest pain (NCCP), and 11 with irritable bowel syndrome (IBS). MEASUREMENTS (1) Sexual and physical abuse interview questions; (2) Structured psychiatric interview; (3) Self-report questionnaires: demographics, clinical pain measurement, Millon Behavioral Health Inventory, Hassles and Uplifts Scales, Sickness Impact Profile, Life Experiences Survey, Pain Beliefs and Perceptions Inventory, and Coping Strategies Questionnaire; (4) Pain Perception and Sensory Decision Theory tasks. RESULTS Fifty-six percent of the sample reported a history of sexual/physical abuse. Abuse was significantly more prevalent among patients with GERD (92%) and IBS (82%) compared with those with NCCP (27%). Abused patients, relative to nonabused patients, had significantly lower pain threshold levels in response to finger pressure stimuli and significantly lower cognitive standards for judging stimuli as noxious. Abused patients reported significantly higher levels of functional disability and a significantly greater number of psychiatric disorders, minor daily hassles, and pain syndromes unrelated to gastrointestinal disorders. In addition, abused patients more frequently blamed themselves for their pain and reported significantly greater use of maladaptive pain coping strategies than nonabused patients. CONCLUSION These data suggest that the relationships between abuse, disability, multiple pain syndromes, and health care seeking behavior are mediated by abnormal pain perception, psychiatric disorders, disruption of physical function, and environmental stressors.

The secondary prevention of low back pain: a controlled study with follow-up

&NA; The current investigation studied the effectiveness of a secondary prevention program for nurses with back pain who were deemed at risk for developing a chronic problem. A 2 × 3 repeated measures design was employed with 2 groups and 3 assessment periods. The treatment group received an intervention designed to reduce current problems, but above all to prevent reinjury and minor pains from becoming chronic medical problems, and it included a physical and behavioral therapy package. The control group was placed on a waiting‐list. Results indicated that the treatment group had significantly greater improvements than the control group for pain intensity, anxiety, sleep quality and fatigue ratings, observed pain behavior, activities, mood, and helplessness. These differences were generally maintained at the 6 month follow‐up. In addition, the treatment group broke a trend for increasing amounts of pain‐related absenteeism, while the control group did not. Taken as a whole, the results suggest that a secondary prevention program aimed at altering life style factors may represent an effective method for dealing with musculoskeletal pain problems.

The symptom index. Differential usefulness in suspected acid-related complaints of heartburn and chest pain.

The symptom index is a quantitative measure developed for assessing the relationship between gastroesophageal reflux and symptoms. Controversy exists, however, over its accuracy and the appropriate threshold for defining acid-related symptoms of heartburn and chest pain. Therefore, a retrospective review was done of 153 consecutive patients referred to our esophageal laboratory. Three groups were identified: patients with normal 24-hr pH tests and no esophagitis, patients with abnormal 24-hr pH tests and no esophagitis, and patients with abnormal 24 hr pH values and endoscopic esophagitis. If symptoms occurred during the pH study, a symptom index (number of acid related symptoms/total number of symptoms x 100%) was calculated separately for heartburn and chest pain. Heartburn and chest pain episodes were similar among the three groups. However, the mean symptom index for heartburn was significantly (P<0.001) higher in the patient groups with abnormal pH values [abnormal pH/no esophagitis: 70±7.1% (±se); abnormal pH/esophagitis: 85±4.6%] as compared to those with normal studies, ie, functional heartburn (26±10.7%). The mean symptom index for chest pain was similar for all three groups. Using receiver operating characteristic curves, a heartburn symptom index≥50% had excellent sensitivity (93%) and good specificity (71%) for acid reflux disease, especially if patients complain of multiple episoldes of heartburn. In contrast, an optimal symptom index threshold for defining acid-related chest pain episodes could not be defined.

Psychological comparison of patients with nutcracker esophagus and irritable bowel syndrome

Recent evidence suggests that psychological factors may affect esophageal as well as intestinal motility. To study this further, we compared the psychological profiles of 20 irritable bowel patients and 20 patients with recurrent noncardiac chest pain associated with high-amplitude peristaltic contractions in the distal esophagus, the “nutcracker esophagus.” Three control groups with 20 patients each also were evaluated. The Millon Behavioral Health Inventory was administered to all subjects. This is a 150-item self-report instrument developed to assess psychological impact of medical illnesses in nonpsychiatric populations. The nutcracker and irritable bowel patients differed significantly (P<0.05) from controls on scales of gastrointestinal susceptiblity and somatic anxiety, suggesting that these patients react to psychological stress with an increase in symptom frequency and severity. They also tend to be hypochondriacal and seek early medical care. Irritable bowel patients, however, have a more generalized disorder, as they also scored significantly higher (P<0.05) than the other groups on three general measures of depression and anxiety. Conclusion: as previously observed in the irritable bowel syndrome, emotional factors may modulate pain perception in the nutcracker esophagus. Simple psychometric instruments like the Millon Behavioral Health Inventory may be useful in identifying these patients who may benefit from psychotropic drugs or behavior modification.

A multi-center evaluation of the McGill Pain Questionnaire: results from more than 1700 chronic pain patients

&NA; We argue that the conflicting results reported in previous studies examining the factor structure of the McGill Pain Questionnaire Pain Rating Index (PRI) can be explained by differences in the patient samples and statistical analyses used across studies. In an effort to clarify the factor structure of the PRI, 3 different factor models were compared using confirmatory factor analysis in 2 samples of low‐back pain patients (N = 1372) and in a third sample of patients suffering from other chronic pain problems (N = 423). A 4‐factor model, similar to those obtained in previous studies where multiple criteria were used to determine the number of factors extracted, best explained covariation among PRI subclasses. However, relatively high interfactor correlations (approximately two‐thirds of the variance explained by the best fitting factor structure was common variance) cast doubt on the discriminant validity of PRI subscales; examination of relationships between the PRI and MMPI subscales also failed to provide evidence of the discriminant validity or clinical utility of PRI subscales. Reducing the information from the 10 PRI sensory subclasses to a single subscale score may seriously limit the usefulness of the PRI. Alternate methods of using PRI data are suggested.

Stress induces alteration of esophageal pressures in healthy volunteers and non-cardiac chest pain patients.

The present study was designed to explore the relationship between psychological stress and esophageal motility disorders. Nineteen non-cardiac chest pain patients (10 with the nutcracker esophagus and nine with normal baseline manometry) and 20 healthy control subjects were administered two acute stressors: intermittent bursts of white noise and difficult cognitive problems. The results indicated that the esophageal contraction amplitudes and levels of anxiety-related behaviors of non-cardiac chest pain patients and control subjects were significantly greater during the stressors than during baseline periods. All patients demonstrated significantly greater (P<0.01) increases in contraction amplitude and anxiety-related behavior during cognitive problems than during the noise stressor. The nutcracker esophagus patients showed a greater increase in contraction amplitude during the problems (23.50±9.42 mm Hg, ¯X ±SE) than control subjects (P<0.01), while the amplitude changes of chest pain patients with normal baseline manometry were not significantly greater than that of control subjects (9.00±1.91 mm Hg). The present results identified an increase in contraction amplitude as the primary esophageal response to stress. The possible interaction of esophageal contraction abnormalities, psychological stress, and the perception of chest pain is discussed.