Effects of esophageal acid perfusion on airway hyperresponsiveness in patients with bronchial asthma

STUDY OBJECTIVES: The effects of gastroesophageal reflux on airway hyperresponsiveness in patients with bronchial asthma have yet to be studied in significant detail. The purpose of the present study was to determine how esophageal acid perfusion could change airway responsiveness in patients with bronchial asthma. PATIENTS AND INTERVENTIONS: In seven patients with bronchial asthma (mean +/- SD age, 55.1 +/- 6.4 years; four women and three men), esophageal pH was monitored by a pH meter and airway responsiveness was evaluated by aerosol inhalation of methacholine, during esophageal perfusion through an esophageal tube filled with either saline solution or 0. 1N hydrochloric acid (HCl), the order of which was selected at random, in 1-week intervals. Spirometry was also performed during esophageal pH monitoring. RESULTS: A significant decrease in the geometric mean of airway sensitivity or the concentration of methacholine causing a 35% fall in respiratory conductance was observed during esophageal HCl perfusion compared with that of saline solution perfusion (p < 0.01 or p < 0.003), although no significant changes were observed in vital capacity, FEV(1), peak expiratory flow, respiratory resistance, or slope of respiratory conductance during the periods of saline solution and HCl perfusion. CONCLUSION: We concluded that an increase in airway hyperresponsiveness was induced when HCl stimulated the esophagus in patients with bronchial asthma. These results suggest that esophageal reflux is one of the important factors that aggravate asthmatic status.     

Intraesophageal perfusion of acid increases the bronchomotor response to methacholine and to isocapnic hyperventilation in asthmatic subjects

Gastroesophageal reflux (GER) has been shown to be more frequent in people with asthma, but the mechanism by which it might aggravate asthmatic symptoms remains unclear. We compared the effects on maximal expiratory flow at 50% of VC (MEF50) of esophageal perfusion of hydrochloric acid (HCl) and of normal saline (NaCl) in 12 asthmatic subjects chosen at random. In all subjects, HCl perfusion did not change MEF50 but potentiated the bronchoconstriction induced by isocapnic hyperventilation of dry air (maximal decrease in MEF50 = 44 +/- 7% with HCl versus 22 +/- 5% with NaCl; p less than 0.001) or methacholine (provocative dose producing a 20% decrease in FEV1 = 349 +/- 99 micrograms with HCl versus 496 +/- 119 micrograms with NaCl; p less than 0.01). Seven of the asthmatic subjects were found to have GER on esophageal pH monitoring. In these subjects, HCl alone decreased MEF50 slightly but significantly (-17.5 +/- 5.5%; p less than 0.05), possibly reflecting the higher degree of basal bronchial hyperreactivity observed in this group. Thus, perfusion of acid into the distal esophagus caused slight but significant bronchoconstriction in asthmatic subjects with GER and increased the bronchoconstriction produced by isocapnic hyperventilation and by methacholine in asthmatic subjects without regard for the presence of GER.     

Omeprazole reduces the response to capsaicin but not to methacholine in asthmatic patients with proximal reflux

OBJECTIVE: To study the relationships between airway responsiveness to methacholine and capsaicin, proximal or distal reflux and the effects of short-term acid inhibition. MATERIAL AND METHODS: Twenty-nine asthmatics, not taking steroids regularly, underwent respiratory symptom measurements, 24-h dual-probe pH monitoring, and challenges with methacholine and capsaicin. Challenges and symptom measurements were repeated after 12 days' omeprazole treatment (20 mg b.i.d.). The results (median and range) were expressed as PD20 methacholine (mg) and PD5 capsaicin (dose causing five coughs, nmol). RESULTS: Seventeen patients presented pathological reflux in the distal esophagus, and 17 in the proximal esophagus. At baseline no correlation was found between PD20 or PD5 and reflux. Treatment with omeprazole did not change bronchial responsiveness to methacholine (basal: 0.16 mg, 0.02-1.27; omeprazole: 0.15 mg, 0.02-1.60); omeprazole decreased the tussive response to capsaicin (basal: 0.08 nmol, 0.08-2.46; omeprazole: 0.61 nmol, 0.08-9.84, p<0.001) only in patients with pathological reflux. The decrease was positively correlated with proximal acid exposure (r2=0.70, p<0.001). Omeprazole reduced asthma symptoms in patients with proximal reflux, cough in those with proximal or distal reflux. CONCLUSIONS: In asthmatics, inhibition of gastric acid secretion does not influence bronchial hyperresponsiveness but decreases tussive sensitivity and this effect is related to proximal reflux.     

Omeprazole reduces the response to capsaicin but not to methacholine in asthmatic patients with proximal reflux

Objective. To study the relationships between airway responsiveness to methacholine and capsaicin, proximal or distal reflux and the effects of short-term acid inhibition. Material and methods. Twenty-nine asthmatics, not taking steroids regularly, underwent respiratory symptom measurements, 24-h dual-probe pH monitoring, and challenges with methacholine and capsaicin. Challenges and symptom measurements were repeated after 12 days’ omeprazole treatment (20 mg b.i.d.). The results (median and range) were expressed as PD20 methacholine (mg) and PD5 capsaicin (dose causing five coughs, nmol). Results. Seventeen patients presented pathological reflux in the distal esophagus, and 17 in the proximal esophagus. At baseline no correlation was found between PD20 or PD5 and reflux. Treatment with omeprazole did not change bronchial responsiveness to methacholine (basal: 0.16 mg, 0.02–1.27; omeprazole: 0.15 mg, 0.02–1.60); omeprazole decreased the tussive response to capsaicin (basal: 0.08 nmol, 0.08–2.46; omeprazole: 0.61 nmol, 0.08–9.84, p<0.001) only in patients with pathological reflux. The decrease was positively correlated with proximal acid exposure (r²=0.70, p<0.001). Omeprazole reduced asthma symptoms in patients with proximal reflux, cough in those with proximal or distal reflux. Conclusions. In asthmatics, inhibition of gastric acid secretion does not influence bronchial hyperresponsiveness but decreases tussive sensitivity and this effect is related to proximal reflux.     

支气管哮喘患者与胃食管返流的症状相关性

目的　探讨胃食管返流 (GER)与成人中、重度支气管哮喘的症状相关性 ,了解 2 4h食管pH监测对哮喘合并GER的诊断价值及抗返流治疗对合并GER的哮喘患者症状的影响。方法　对 2 6例常规治疗后仍有顽固性咳嗽等症状的成人哮喘患者进行 2 4h食管pH监测 ,严格记录监测期间患者出现的各种症状 ,每小时记录 1次呼气峰流速 (PEF)。筛选出适当病例分组抗返流治疗并观察疗效。结果　 2 6例中有 15例DeMeester总积分≥ 14 72 ,2例虽DeMeester总积分 <14 72 ,但咳嗽与返流的症状相关概率 (SAP)≥ 95 % ,共筛选出 17例。将 17例患者随机分为治疗组 (9例 )和对照组 (8例 )。经抗返流治疗后 ,治疗组咳嗽、胸闷和胸骨后烧灼感等症状均较对照组有明显改善 ,2 4hPEF波动率治疗前 [(3 8± 8) % ]、后 [(16± 3 ) % ]比较差异有显著性 (P <0 0 5 )。结论　 (1)中、重度支气管哮喘患者具有较高的GER发生率 (5 8% )。 (2 ) 2 4h食管pH监测有助于了解哮喘患者的症状与GER的相关性。 (3 )对于有GER并与哮喘症状密切相关的患者 ,抗返流治疗可显著地改善其症状及PEF波动率     

The association of gastroesophageal reflux with bronchial asthma. Can asthma also trigger reflux?

BACKGROUND/AIMS: The frequency of gastroesophageal reflux (GER) among asthmatic patients was found to range from 34% to 89% at different locations. The aims of this study have been to determine the frequency of GER in patients with asthma in the Saudi environment, to ascertain the main mechanism whereby GER triggers asthma, and to seek any evidence whether asthma can also trigger GER. METHODOLOGY: Fifty asthmatic patients were consecutively recruited as they reported to King Fahd Hospital of the University (KFHU), Al-Khobar, Saudi Arabia, in the period from February 2000 to February 2001; their mean age +/- SD was 38.0 +/- 9.8 years. Twenty-two subjects without asthma or GER served as controls; their mean age +/- SD was 29.4 +/- 8.6. Both groups were subjected to a questionnaire, esophageal manometry, dual probe ambulatory 24-hour pH monitoring, and pulmonary function tests. RESULTS: Among the asthmatic group 22 patients (44%) had GER. Accordingly, the asthmatic patients were divided into two groups: asthmatic with GER (n=22), and asthmatic without GER (n=28). Hoarseness of voice and nocturnal symptoms were found to be significant predictors for the presence of GER in asthmatics. Manometry revealed that asthmatic patients with GER had higher gastric pressure (11.4 +/- 4.0 mmHg vs. 8.4 +/- 2.8 mmHg; p=0.006) and lower resting pressure at the lower esophageal sphincter (LES) (21.2 +/- 8.7 mmHg vs. 28.2 +/- 9.3 mmHg; p=0.013) when compared with controls, both factors favoring the occurrence of reflux. With regard to pH data, acid reflux occurred both at the distal and proximal esophagus but the percent total acid exposure time was about 7 times longer at the distal than at the proximal esophagus (5.80 vs. 0.9). In addition, gastric pressure was positively and significantly correlated with distal esophageal acid exposure time and the DeMeester score, negatively correlated with spirometric parameters in asthmatic patients, as well as found to be a significant predictor of the severity of asthma (p=0.006). CONCLUSIONS: Forty-four percent of the sample of asthmatic patients reporting to KFHU had GER. Since distal esophageal total acid exposure time was nearly 7 times longer than at the proximal esophagus, the main mechanism for GER triggering asthma is the vagally mediated reflex initiated by acid in the distal esophagus. In addition, the positive correlation of increased gastric pressure with the distal esophageal acid exposure time and the DeMeester score, its negative correlation with spirometric parameters and being a significant predictor of asthma severity suggest that severe asthma may trigger or aggravate GER.     

Gastroesophageal reflux and bronchial responsiveness: correlation and the effect of fundoplication

BACKGROUND: A causal relationship between gastroesophageal reflux (GER) and asthma has been suggested. Should this be the case, one could expect treatment of GER to diminish bronchial sensitivity. There has been a lack of trials evaluating the efficacy of antireflux surgery on airway reactivity. OBJECTIVES: To investigate the correlation between GER and bronchial responsiveness, and to determine the efficacy of Nissen fundoplication on bronchial responsiveness and pulmonary function. METHODS: A methacholine inhalation challenge was performed on 15 consecutive GER patients preoperatively and approximately 5 months after Nissen fundoplication. Airway responsiveness was quantified with a dose-response slope (DRS), calculated by dividing the decrease in FEV(1) (%) with the dose of methacholine administered (micromoles). RESULTS: A positive correlation between the severity of distal esophageal reflux and bronchial responsiveness was found (r = 0.83, p < 0.001). There was an improvement in FEV(1) after fundoplication (p = 0.03). All 3 asthmatic patients participating in the study presented with bronchial hyperresponsiveness (BHR) which improved clearly in all of these patients after fundoplication. This resulted in an apparent trend for DRS to improve when the entire study population was considered (p = 0.12). CONCLUSIONS: According to the current study there seems to be a positive correlation between the severity of distal esophageal reflux and bronchial responsiveness. These data suggest that operative treatment of GER may ameliorate BHR in asthmatic patients. Moreover, the results of the present study suggest that fundoplication may improve pulmonary function in patients with GER.     

Bronchial Responsiveness During Esophageal Acid Infusion

Among the possible mechanisms explaining the worsening of asthma due to gastroesophageal reflux disease (GERD) is the increase in bronchial hyperresponsiveness. The effects of GERD on bronchial hyperresponsiveness in patients with bronchial asthma have yet to be studied in significant detail. The aim of this study was to determine the effects of esophageal acid perfusion on bronchial responsiveness to bradykinin in patients with both asthma and GERD. In 20 patients with asthma and GERD disease, esophageal pH was monitored with a pH meter and bronchial responsiveness was evaluated by aerosol inhalation of bradykinin during esophageal acid perfusion and, 24 h earlier or later the patients were submitted to another bronchial provocation test without acid infusion. No significant changes were observed in FEV₁, FEF_25-75%, FVC, or PEF during acid perfusion. The response to the bronchial provocation test did not differ between the control day and the day of acid infusion (p = 0.61). The concentration provoking a 20% fall in FEV₁ (geometric mean ± geometric SD) was 1.09 ± 5.84 on the day of acid infusion and 0.98 ± 5.52 on the control day. There is no evidence that acid infusion changes bronchial responsiveness to bradykinin. These findings strongly question the significance of acid infusion as a model to study the pathogenesis of GERD-induced asthma.     

Gastroesophageal reflux in infants with wheezing.

The relation between silent gastroesophageal reflux (GER) and respiratory problems such as persistent wheezing in infants is not well-established. Between January 1994 and June 1997, we evaluated the incidence of GER in 84 otherwise healthy infants referred to the Pediatric Pulmonary Medicine Division at Kosair Children's Hospital for evaluation of daily wheezing, and we followed their clinical course for 18 months. All underwent 24-hr esophageal pH studies to evaluate GER. The pH probe study was performed at a mean age of 8.74 +/- 4.6 months. Infants with a positive GER study were treated with an H2 receptor antagonist (H2RA) and a prokinetic agent for a mean of 5.6 +/- 2.4 months. At first follow-up visit 3 weeks after esophageal pH studies infants treated with an H2RA and those who did not have GER but continued with daily wheezing were started on flunisolide nasal solution (0.025%) delivered by nebulizer (125 mcg t.i.d.). Infants in both groups were followed every 1-2 months for a mean of 18 months and if clinically improved, attempts to decrease their daily asthma medications were made. Fifty-four of 84 (64%) had positive esophageal pH studies (GER-positive group), and 24 of them (44%) had no gastrointestinal symptoms suggestive of GER. Thirty patients had normal esophageal pH studies (GER-negative group). Twenty-two of these 30 (73%) infants without GER required nebulized flunisolide, compared to 13 of 54 (24%) infants with GER (P < 0.0005). Thirty-five of 54 (64.8%) infants with GER were able to discontinue all daily asthma medications within 3 months of starting antireflux therapy, while none of the infants without GER were able to discontinue daily asthma medications during the follow-up period (P < 0.0005). We conclude that silent GER is common in infants with daily wheezing, and controlling GER improves morbidity and decreases the need for daily asthma medications.     

Frequency of gastroesophageal reflux disease in nonatopic children with asthma-like airway disease

Gastroesophageal reflux disease (GERD) is commonly associated with asthma; however, frequency in nonatopic children with asthmatic symptoms is unknown. The aim of this study was to determine the frequency of gastroesophageal reflux (GER) in nonatopic children with asthma-like airway disease that recur despite conventional asthma treatment and to evaluate the clinical response to lansoprazole treatment. Twenty-five nonatopic children aged between 1 and 16 years who have asthma-like airway disease and 25 healthy children were included in the study. All cases underwent 24 h pH monitoring with dual sensor catheters. Additionally, acid suppressor treatment was administered to patients diagnosed as having GERD and clinical response was evaluated. Major symptoms encountered in the patient group included wheezing and cough (88%, and 32%, respectively). Reflux episodes were more common in distal esophagus during the prone position (reflux index (RI) of 11.5+/-10.3 vs. 16.2+/-9.4 during supine vs. prone). All distal esophageal parameters were significantly higher in the patient group except number of reflux episodes lasting longer than 5 min (RI of 13.3+/-13.1 vs. 3.9+/-2.9 in the patient vs. control groups, respectively). There was a significant improvement in symptoms and requirement for medication with treatment (number of systems decreased from 2.3+/-0.6 to 0.4+/-0.6, P=0.00). In conclusion, GERD is significantly more common in nonatopic children with asthma-like airway disease compared to the controls and clinical improvement is significant after acid suppressor treatment. Thus, we suggest that children followed-up with the diagnosis of nonatopic asthma with recurrent exacerbations despite adequate asthma treatment have a high frequency of GER and that lansoprazole treatment may be considered early in management.     

Capsaicin induction of esophageal symptoms in different phenotypes of gastroesophageal reflux disease

"Background: Type 1 vanilloid receptors (TRPV1) have been described on esophageal afferent sensitive neurons. Stimulation of TRPV1 receptors with capsaicin may induce heartburn. Capsaicin is the pungent component of chili and the most extensively studied TRPV1 agonist. Objectives: To investigate the effect of esophageal stimulation with intraesophageal capsaicin administration on induction of esophageal symptoms and on esophageal chemo-sensitization to acid in different gastroesophageal reflux disease (GERD) phenotypes. Methods: Healthy volunteers and patients with GERD (non-erosive [NERD], erosive GERD [EE] and Barrett's esophagus [BE]) were prospectively studied. All subjects were randomized to receive either intraesophageal perfusion capsaicin or saline 0.9%. Thirty minutes after saline or capsaicin infusion an acid perfusion test of HCl was performed. A week later, a crossover phase with capsaicin versus saline was performed. Five symptoms were evaluated every 5 min during the first 30 minutes after capsaicin, saline, and acid perfusion: chest burning, chest pain, heartburn, epigastric burning, and epigastric pain Results: 17 healthy subjects and 31 GERD patients (10 NERD, 11 EE, and 10 BE) were included. Twenty- eight (90%) of GERD and 6 (35%) of healthy subjects had esophageal symptoms after capsaicin perfusion. Mean for the 5 evaluated symptoms induced by capsaicin was significantly higher in the GERD group compared to the control group. The highest symptom severity was in the erosive subgroup. Capsaicin decreased the 5 symptoms induced by acid perfusion in both healthy volunteers and GERD patients. Total score of esophageal symptom severity (produced by acid perfusion) was significantly reduced by capsaicin infusion in the BE group. Conclusions: Capsaicin induces esophageal and gastric symptoms in healthy volunteers and GERD patients. Capsaicin reduces esophageal chemosensitivity to acid, especially in patients with BE. "     

The effect of altering airway tone on the sensitivity of the cough reflex in normal volunteers.

Cough is frequently the presenting symptom of bronchial asthma, although cough can result from a wide variety of other respiratory disease. Treatment of chronic cough has proved extremely difficult. It has been suggested that treatment with bronchodilators may reduce the symptom of cough. In this study the effect of altering airway tone on the sensitivity of the cough reflex was determined. Twelve normal, healthy volunteers took part. The number of coughs following inhalations of single breaths of doubling concentrations of capsaicin (1.95-500 microM) was recorded before and after doses of salbutamol, methacholine and saline which altered forced expiratory volume in one second (FEV1) by 6.2 +/- 2.6%, -8.8 +/- 3.2% and -0.18 +/- 1.38%, respectively. In a further study the cough response was recorded before and after doses of salbutamol and ipratropium bromide, both of which reduced baseline respiratory resistance and resistance measured after capsaicin. Ipratropium bromide, salbutamol and methacholine, despite having significant effects on airway tone, did not change the sensitivity of capsaicin-induced cough. Thus, if bronchodilator drugs are antitussive in non-asthmatic patients, then this is unlikely to be due to an effect on the sensitivity of the cough reflex.     

食管内灌酸对慢性咳嗽患者气道阻力与咳嗽敏感性的影响

目的观察向食管下段灌注盐酸对慢性咳嗽患者咳嗽症状、咳嗽敏感性和气道阻力的影响。方法17例慢性咳嗽患者经鼻插入5F胃管至食管下段,注入0．1N盐酸共10min,于灌酸前后测量肺通气功能、气道阻力和辣椒素咳嗽激发试验,记录灌酸期间患者自觉症状、咳嗽次数。比较灌酸前后咳嗽症状、咳嗽敏感性和肺通气功能、气道阻力的变化。结果灌酸后呼吸阻抗Zrs、中央气道阻力R20显著增高,差异有统计学意义（P〈0．05）;第1秒钟用力呼气容积（FEV1）,用力肺活量（FVC）、共振频率（Fres）及外周气道阻力（R5-R20）无显著性变化（P〉0．05）;灌酸前后患者咳嗽敏感性也无显著性差异。相关分析显示,远端电极多项反流指标与灌酸总量呈显著负相关（P〈0．05）,而与停止灌酸后pH值恢复正常的时间呈显著正相关（P〈0．05或P〈0．01）。结论向慢性咳嗽患者食管下段灌注盐酸可使气道阻力增加,尤其是中央气道阻力,这可能与胃食管反流诱发咳嗽有关。     

Chronic cough as the sole presenting manifestation of gastroesophageal reflux

Nine patients complaining only of chronic cough of unknown cause were prospectively studied with prolonged esophageal pH monitoring (EPM) before and after cough had disappeared as a complaint in order to determine if and why gastroesophageal reflux (GER) was causing their coughs. Coughs disappeared as a complaint an average of 161 +/- 75 days after medical therapy for GER. Comparisons of pretreatment and post-treatment EPM data revealed the following: numbers of coughs (p = 0.029), total refluxes (p = 0.001), refluxes greater than or equal to 5 min (p = 0.019), and reflux-induced coughs (p = 0.005) had significantly decreased in the distal esophagus, and total refluxes (p = 0.05) had significantly decreased in the proximal esophagus. During the entire study period, the number of coughs were significantly correlated with the number of total refluxes (p = 0.039), longest reflux (p = 0.019), number of refluxes greater than or equal to 5 min (p = 0.006), and percent of total time that pH was less than 4 (p = 0.017) in the distal esophagus. On the basis of these results, we conclude that (1) cough can be the sole presenting manifestation of GER, and it gradually responds to standard GER therapy; (2) prolonged EPM is safe, well-tolerated, and extremely useful in diagnosing clinically silent GER; (3) the mechanism by which GER causes cough is related to a critical number and/or duration of reflux episodes in the distal and/or proximal esophagus.     

A guinea pig model for cough variant asthma and role of tachykinins

Cough variant asthma is known as a major cause of chronic cough. Fundamental features of cough variant asthma are prolonged nonproductive cough responding to bronchodilator therapy, no history of wheezing or dyspnea attack, normal cough sensitivity, and slightly increased bronchial responsiveness. Animal model of cough variant asthma has not been reported. The aim of this study was to establish an animal model for studying detailed pathophysiology of cough variant asthma. Bronchial responsiveness to methacholine and cough reflex sensitivity to capsaicin were measured 72 hours after antigen (ovalbumin, OA) inhalation in actively sensitized guinea pigs. Next, cough number and specific airway resistance (sRaw) were measured during 20 minutes following reinhalation of OA solution, which was carried out 72 hours after the first OA inhalation, and then total cell number and cell differentials in bronchoalveolar lavage fluid (BALE) were measured. Bronchial responsiveness to methacholine, but not cough reflex sensitivity to capsaicin, was significantly increased 72 hours after the first inhalation of OA solution. Number of coughs, sRaw and total cell number in BALF increased significantly by the OA reinhalation, and the cough number and the increase in sRaw were significantly suppressed by beta2 agonist, procaterol. FK224, a specific neurokinin (NK) receptor antagonist, did not significantly influence the OA reinhalation-induced cough and increase in sRaw and total cell number in BALF in this model In conclusion, pathophysiologic feature of this animal model is similar to that of clinical cough variant asthma. Tachykinins may not play an important part in antigen-induced cough associated with bronchoconstriction and airway inflammation in cough variant asthma.     

Cough sensitivity in pure cough variant asthma elicited using continuous capsaicin inhalation.

BACKGROUND: Cough variant asthma has recently been described, mainly as airway inflammation in relation to bronchial asthma, but the relationship between the two types of asthma remains unclear. Further studies of cough receptor sensitivity are necessary to fully characterize cough variant asthma. METHODS: We assessed the relevance of testing cough sensitivity using an Astograph with continuous capsaicin inhalation, and compared the results with those obtained using intermittent inhalation. We showed the clinical applicability of testing cough sensitivity (0.156-80 microM capsaicin; five or more coughs, 1 minute of continuous inhalation at each concentration) using this method. We compared cough sensitivity among patients with pure cough variant asthma who did not develop bronchial asthma after an observation period of at least 1 year, patients with bronchial asthma and healthy individuals. RESULTS: The continuous cough sensitivity test using the Astograph was reproducible and reliable. Cough sensitivity in patients with pure cough variant asthma was significantly higher than that in healthy individuals. CONCLUSIONS: The cough sensitivity of patients with cough variant asthma is not necessarily identical to that of healthy individuals.     

Effect of long-term treatment with sodium cromoglycate on nonspecific bronchial hyperresponsiveness in asthma

Several studies in the past have demonstrated a reduction in nonspecific bronchial hyperresponsiveness subjects with seasonal extrinsic asthma after long-term treatment with sodium cromoglycate. Since sodium cromoglycate is an effective drug in the prophylactic treatment of all types of asthma, we assessed the effect of a three-month treatment on nonspecific bronchial hyperresponsiveness in 11 patients with perennial asthma. Bronchial responsiveness was determined by histamine bronchoprovocation test, using SGaw as the index of lung function and expressed as PD35SGaw. During the run-in period of one month when sodium cromoglycate was not used, the histamine PD35SGaw decreased significantly from 0.15 +/- 0.30 to 0.09 +/- 0.29 mg/ml (p less than 0.001). After three months of treatment with the drug, bronchial hyperresponsiveness was reduced significantly; the PD35SGaw was 0.21 +/- 0.29 mg/ml (p less than 0.001). It was concluded that long-term treatment of patients with perennial asthma with sodium cromoglycate results in reduced bronchial hyperresponsiveness.     

The effect of jejunal meal feeding on gastroesophageal reflux

BACKGROUND: Postprandial gastric distention is frequently associated with transient lower esophageal sphincter relaxation and gastroesophageal reflux (GER). Since the role of nutrient perfusion into the jejunum in inducing GER is not well understood, we studied the effect of jejunal feeding on GER through a percutaneous gastrojejunal tube in patients with and without reflux esophagitis. METHODS: Nine stroke patients with reflux esophagitis were fed through a percutaneous gastrojejunal tube with either a liquid meal (2 kcal/2 ml/min) or saline for 2 h randomly on 2 separate days. An esophageal pH probe was placed 5 cm above the gastroesophageal junction to detect acid reflux. Six stroke patients without esophagitis were enrolled as controls. RESULTS: In both the patients with esophagitis and the controls, esophageal acid exposure (15.3% (4.9%-28.2%) versus 2.7% (0.0%-10.8%), P=0.003; 5.9% (0.5%-6.7%) versus 0.0% (0.0%-1.5%), P = 0.01) and events of acid reflux (5 (1-16) versus 2 (0-8), P = 0.02; 12 (3-17) versus 1 (0-4), P = 0.02) were significantly greater during jejunal meal feeding than during saline infusion. Furthermore, in the reflux patients, but not in the controls, acid clearance time was also greater during jejunal meal feeding than during saline infusion (2.9 min (0.5-9.6 min) versus 0.7 min (0.0-4.3 min), P = 0.04). CONCLUSIONS: We therefore conclude that jejunal nutrient infusion without gastric distention can induce GER in both patients with reflux esophagitis and controls. This implies that GER induced by jejununal nutrients may in part explain the incapability of jejunal tube feeding to prevent gastropulmonary aspiration in patients at risk.     

Chronic cough. The spectrum and frequency of causes, key components of the diagnostic evaluation, and outcome of specific therapy

A successful, systematic, anatomic, diagnostic protocol for evaluating patients with chronic cough was presented in 1981. To determine whether it was still valid, we prospectively evaluated, over a 22-month interval, 102 consecutive and unselected immunocompetent patients complaining of cough an average of 53 +/- 97 months (range, 3 wk to 50 yr). Utilizing the anatomic, diagnostic protocol modified to include prolonged esophageal pH monitoring (EPM), the causes of cough were determined in 101 of 102 (99%) patients, leading to specific therapy that was successful in 98%. Cough was due to one condition in 73%, two in 23%, and three in 3%. Postnasal drip syndrome was a cause 41% of the time, asthma 24%, gastroesophageal reflux (GER) 21%, chronic bronchitis 5%, bronchiectasis 4%, and miscellaneous conditions 5%. Cough was the sole presenting manifestation of asthma and GER 28 and 43% of the time, respectively. While history, physical examination, methacholine inhalational challenge (MIC), and EPM yielded the most frequent true positive results, MIC was falsely positive 22% of the time in predicting that asthma was the cause of cough. Laboratory testing was particularly useful in ruling out suspected possibilities. We conclude that the anatomic diagnostic protocol is still valid and that it has well-defined strengths and limitations.     

Effects of ipratropium bromide nebulizer solution with and without preservatives in the treatment of acute and stable asthma.

In a recent study, it was suggested that the preservatives in ipratropium bromide nebulizer solution may cause a paradoxic bronchoconstrictor response in 20 percent or more of patients with stable asthma. The frequency of this response in patients with acute asthma is unknown. The aim of this study was to examine the acute effects of the usual dose of nebulized ipratropium bromide (0.25 mg) in patients with either stable or acute asthma using formulations with and without added preservatives. Twenty-five patients with stable asthma and 25 patients with acute asthma were studied. Each subject was given preservative-containing ipratropium bromide, preservative-free ipratropium bromide, pH 7 preservative-free ipratropium bromide, and saline solution in random order using a double-blind crossover technique with at least 4 h between drug administrations. Very frequent measurements of FEV1 were made for 30 min after each drug administration and then 5 mg of albuterol was nebulized and the FEV1 was measured again after another 30 min. Changes in FEV1 were expressed as a percentage of the predicted FEV1. Paradoxic bronchoconstriction to ipratropium was detected in only one patient with acute asthma (12 percent fall in FEV1) but in none of the patients with stable asthma. A 6 percent fall in FEV1 change occurred with the saline solution in this subject suggesting that the response may have been a nonspecific one due to increased bronchial responsiveness. The mean response (+/- 1 SD) to albuterol plus either preservative-containing ipratropium, preservative-free ipratropium, or pH7 preservative-free ipratropium was significantly greater (p less than 0.05) than the response to albuterol alone both in the patients with acute asthma (25 +/- 12 percent, 27 +/- 15 percent, 26 +/- 15 percent, and 20 +/- 15 percent, respectively) and stable asthma (26 +/- 7 percent, 25 +/- 8 percent, 24 +/- 6 percent, and 22 +/- 9 percent) supporting the use of ipratropium bromide as an additional bronchodilator in patients with asthma who do not show a satisfactory response to nebulized beta-adrenergic agonist.