Bronchial hyperresponsiveness in subjects with gastroesophageal reflux

BACKGROUND: The relationship between gastroesophageal reflux (GER) and asthma has been widely studied in the last years. GER may interfere with airway reactivity and aggravate or even induce asthma. OBJECTIVE: To assess the prevalence of bronchial hyperresponsiveness (BHR) in patients with GER disease with a view to judging the potential influence of GER on BHR. METHODS: 30 patients with GER disease and no clinical evidence of asthma and 30 normal subjects underwent a methacholine bronchial challenge. The methacholine concentration that caused a 20% fall in the FEV(1) (PC20) was used to assess bronchial responsiveness. RESULTS: In the GER group 11 subjects of the 30 studied showed a PC20 methacholine equal to or less than 8 mg/ml while in the control group only 2 subjects had a PC20 methacholine equal to or less than 8 mg/ml (p < 0.01; ANOVA test). CONCLUSIONS: Subjects with GER had a greater increase in airway reactivity when inhaling methacholine compared to disease-free normal subjects.     

Effects of esophageal acid perfusion on cough responsiveness in patients with bronchial asthma

STUDY OBJECTIVES: The effect of gastroesophageal reflux (GER) on cough responsiveness in patients with bronchial asthma has yet to be studied in significant detail. The purpose of this study was to assess the effect of distal esophageal acid perfusion on cough responsiveness in patients with bronchial asthma. PATIENTS AND INTERVENTIONS: In seven patients with mild persistent bronchial asthma (mean +/- SD age, 57.7 +/- 3.7 years; four women and three men), esophageal pH was monitored by a pH meter and cough responsiveness was evaluated by single-breath aerosol inhalation of capsaicin with increasing dosage from 0.30 to 9.84 nmol. Simultaneously, esophageal perfusion was performed through an esophageal tube filled with either saline solution or 0.1 N hydrochloric acid (HCl), the order of which was selected at random, in 1-week intervals. Results were expressed as the lowest concentration of capsaicin eliciting three coughs (PD3). Spirometry was also performed during esophageal pH monitoring. RESULTS: A significant decrease in the geometric mean of log PD3 was observed during distal esophageal HCl perfusion (0.45 +/- 0.04 nmol) compared with that of the saline solution perfusion (0.04 +/- 0.06 nmol) [p < 0.01]. However, no significant changes were observed either in FVC, FEV1, or peak expiratory flow during the periods of the saline solution or HCl perfusion. CONCLUSION: The present data demonstrate that an increase in cough responsiveness may be induced when HCl stimulates the distal portion of esophagus in patients with bronchial asthma, suggesting that the GER would be one of the important factors that influence asthmatic status.     

Repeatability of histamine bronchial challenge and comparability with methacholine bronchial challenge in a population of Australian schoolchildren

To measure the repeatability of the bronchial challenge test and the comparability of histamine and methacholine as provoking agents, we studied a population sample of children and conducted histamine bronchial challenge tests on each of 3 consecutive days followed by a methacholine bronchial challenge on the fourth day. Bronchial responsiveness was measured using the rapid inhalation method. A total of 393 children had satisfactory bronchial challenge data for all 4 days. The measurements derived from the dose-response curve were the PD20 FEV1, which was measured as the provoking dose causing a 20% fall in FEV1, and the dose-response slope (DRS), which was measured as the percentage fall in FEV1 at final dose/total dose administered. Children who had a PD20 FEV1 were categorized as having bronchial hyperresponsiveness (BHR). The percentage of children with BHR each day was between 7 and 11. One-third of the children with BHR reacted only to histamine or methacholine. The within-subject range for histamine PD20 FEV1 values compared with methacholine suggested that histamine and methacholine are not directly comparable bronchial challenge agents. The dose-response slope values, which could be obtained for all children, had slightly better repeatability than PD20 FEV1 values. Because DRS values obtain data for the entire sample, have good repeatability, and are equally repeatable in children with normal responsiveness or bronchial hyperresponsiveness, they should prove more useful than PD20 FEV1 values for measuring bronchial responsiveness in populations.     

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.     

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.     

Bronchial hyperresponsiveness and exhaled nitric oxide in patients with cardiac disease

BACKGROUND: Increased concentrations of exhaled nitric oxide (NO) correlate with increased airway inflammation and measurement of exhaled NO is a noninvasive method for the management of bronchial asthma. In various cardiac diseases, bronchial hyperresponsiveness is observed, as is bronchial asthma. However, there have been few studies on the relationship between exhaled NO and bronchial responsiveness in cardiac diseases. OBJECTIVE: The aim of this study was to clarify the association between exhaled NO and bronchial hyperresponsiveness in patients with cardiac disease. METHODS: We measured expired NO and bronchial responsiveness to inhaled methacholine in 19 patients with cardiac diseases and 17 with bronchial asthma. We divided the cardiac disease patients into two groups according to their bronchial responsiveness to inhaled methacholine: BHR(+) group consisted of 12 patients with bronchial hyperresponsiveness and BHR(-) group consisted of 7 patients without bronchial hyperresponsiveness. RESULTS: The concentration of exhaled NO in the asthmatic patients was significantly higher than that in the BHR(+) and BHR(-) groups (142.0 +/- 17.0, 33.6 +/- 6.4 and 42.3 +/- 10.3 ppb, respectively, p < 0.01). There was no significant difference in exhaled NO between BHR(+) and BHR(-) groups. There were also no significant differences in the parameters of bronchial hyperresponsiveness between the cardiac BHR(+) and bronchial asthma groups. These results indicate that bronchial hyperresponsiveness in patients with cardiac diseases is not a consequence of eosinophilic inflammation or of exhaled NO. CONCLUSION: We conclude that bronchial hyperresponsiveness in patients with cardiac diseases can occur independently of NO production.     

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.     

Bronchial responsiveness to exercise after human cardiopulmonary transplantation

Heart-lung transplant (HLT) recipients characteristically display marked bronchial hyperresponsiveness (BHR) to inhaled methacholine, but their bronchial responsiveness (BR) to exercise has not been reported. We measured BR to exercise in 13 stable HLT recipients, 13 normal control (NC) subjects and 13 asthmatic patients (AS). All subjects exercised for eight minutes on a bicycle ergometer at a work level designed to obtain and maintain 80 percent maximum heart rate, or to tolerance. The postexercise fall in FEV1 was equivalent in the HLT group and the NC group (0 +/- 0.2 L vs 0 +/- 0.2 L:p = NS) in contrast to the AS group (-0.6 +/- 0.5 L:p less than 0.01). Stable HLT recipients do not exhibit BHR to exercise at tolerable work loads. This observation supports the hypothesis that BHR to methacholine after HLT is due to denervation hypersensitivity of muscarinic receptors rather than other causes.     

Bronchial responsiveness to adenosine 5'-monophosphate (AMP) and methacholine differ in their relationship with airway allergy and baseline FEV(1)

Bronchial hyperresponsiveness (BHR) and inflammation are central hallmarks of asthma. Studies in patients with asthma suggest that BHR to adenosine 5'-monophosphate (AMP) is a better marker of bronchial inflammation than BHR to methacholine. The association between markers of airway inflammation and BHR to methacholine and AMP in a population of young adults, with mild symptoms if any, was evaluated. A total of 230 subjects who participated in a follow-up study on occupational allergy were included. Before exposure to occupational allergens, subjects completed a questionnaire on respiratory symptoms and were tested for atopy, blood eosinophilia (> or =275/mm(3)), and BHR to methacholine and AMP (> or =15% fall in FEV(1)). Risk estimates were expressed as prevalence ratios (PR) and 95% confidence intervals (95% CI). Dose-response slopes (DRS) for methacholine and AMP were compared between healthy control subjects, self-reported allergic rhinitis, and allergic asthma. BHR to AMP was associated with allergic rhinitis (PR 2.51, 95% CI: 1.22;5.17), allergic asthma (PR 4.38, 95% CI: 1.98;9.66), with atopy (PR 3.87, 95% CI: 1.76;8.52), and blood eosinophilia (PR 3.57, 95% CI: 1.48;8.77), but not with baseline FEV(1). BHR to methacholine was inversely related to prechallenge FEV(1) (PR 0.97, 95% CI: 0.96;0.99). For both methacholine and AMP the geometric mean DRS increased along the axis asymptomatic-allergic rhinitis-allergic asthma, but for AMP the increase was the strongest. In this population study among young adults, BHR to AMP refers to allergic background of airway lability and BHR to methacholine is related to a diminished airway caliber.     

Duodenogastroesophageal reflux: results of medical treatment and antireflux surgery

BACKGROUND/AIMS: Recent studies have shown that reflux of the duodenal content to the esophagus plays an important role in esophageal mucosal damage. The aim of the study is to compare the duodenogastroesophageal (DGER) reflux with the severity of reflux esophagitis and evaluate its response to either medical and/or antireflux surgery. METHODOLOGY: Ninety-six patients with DGER were subjected to thorough history, upper GI endoscopy, barium study, esophageal manometry and 24-hr esophageal pH metry combined with Bilitec 2000. Medical treatment was given for all, while Nissen fundoplication was done for 28 patients. All patients were evaluated after Nissen fundoplication and treatment. RESULTS: The age of studied patients was 36.26+/-12.7 years with male to female ratio 2:1. The chief symptom was heartburn in 73 (76%) patients. Upper GI endoscopy revealed, 30 (31.2%) patients had grade I reflux, 30 (31.2%) patients had grade II reflux, 7 patients had grade III reflux, 5 patients had grade VI reflux, Barrett's esophagus in 14 patients (14.5%), hiatus hernia (HH) in 26 (27%) patients. Barium study revealed that, 40 (41.6%) patients had evidence of reflux, while 34 (35.4%) patients had reflux with HH. Esophageal motility revealed the mean LESP (12.7+/-7.6), 68 patients (70.8%) had normotensive body while ineffective esophageal body motility was encountered in 28 (29.1%) patients. Esophageal 24-hr pH study and Bilitec 2000 revealed that 54 (56.2%) patients had bile reflux with pathological acid reflux, while 42 (43.7%) patients had bile reflux in alkaline pH. Medical treatment gave excellent to good response in 68 (70.8%) patients, while Nissen fundoplication was done for 28 (29.2%) patients. Endoscopic examination 6 months after Nissen fundoplication showed marked improvement in endoscopic injury. Barium study after Nissen fundoplication revealed repair of HH and control of GERD in all patients except one. Esophageal motility, 24 hr pH study and Bilitec 2000, after 6 months of Nissen shows high significant increase in LESP, decrease in acid and bile reflux. No significant difference between open or laparoscopic fundoplication in LESP, acid and bile reflux. CONCLUSIONS: DGER in acid medium is more injurious to the esophagus than DGER in alkaline pH. The severity of esophageal injury does not correlate with the severity of acid or bile reflux but has a direct correlation with impaired distal esophageal motility. Medical treatment gives satisfactory control of symptoms and healing of esophageal lesion in 70% of DGER. The response to medical treatment does not depend on the severity of esophageal injury but depends on the severity of bile and acid reflux. Nissen fundoplication in refractory patients, either open or laparoscopic, was effective in control of heartburn in 95% of patients contrary to 50% in mixed symptoms.     

Bronchial hyperreactivity in patients with mitral stenosis before and after successful percutaneous mitral balloon valvulotomy

OBJECTIVES: We aimed to identify the bronchial response to inhaled methacholine in patients with mitral stenosis (MS) and to clarify whether or not the bronchial hyperreactivity (BHR) is reversible after percutaneous mitral balloon valvulotomy (PBMV). PATIENTS AND SETTING: Thirty patients with MS and 28 age-matched healthy control subjects were prospectively evaluated with pulmonary function tests and methacholine challenge. The productive concentration of methacholine causing 20% decrease in FEV(1) (PC(20)) was calculated and used as a parameter of bronchial responsiveness. BHR was defined as a PC(20) < 8 mg/mL. Mean pulmonary artery pressure (PAP) and mean pulmonary capillary wedge pressure (PCWP) were recorded in all patients through a Swan-Ganz balloon-tipped catheter. Sixteen patients underwent PMBV, and a methacholine test was repeated after each procedure. RESULTS: Bronchial response to methacholine was significantly increased in patients with MS, so that 53% of them had BHR, whereas all control subjects were nonresponders. The PC(20) was closely correlated with the PAP (r = - 0.777; p < 0.001), PCWP (r = - 0.723; p < 0.001), and mitral valve area (MVA; r = 0.676; p < 0. 001). Balloon valvulotomy was successfully performed in all of the 16 patients, and the cardiac parameters (MVA, PAP, and PCWP) significantly improved after the procedure. In contrast, no significant changes were shown in pulmonary function test variables (total lung capacity, vital capacity [VC], FEV(1), and FEV(1)/VC). Although significant improvement was observed in the mean PC(20) values (from 4.97 +/- 5.24 to 7.47 +/- 6.96 mg/mL; p = 0.0006), BHR was completely eliminated in only one patient. CONCLUSIONS: Our data shows that BHR is fairly common among patients with MS, and severity of bronchial responsiveness is significantly correlated with the severity of MS. Moreover, PMBV leads to significant reduction in pulmonary congestion and a consequent improvement in BHR.     

Partial fundoplications for gastroesophageal reflux disease: indications and current status.

The Nissen fundoplication, and in particular the laparoscopic Nissen fundoplication, has received widespread acceptance as the most definitive therapy for gastroesophageal reflux disease. There remains, however, certain patients who do better with a less aggressive surgical augmentation of the lower esophageal sphincter. Partial fundoplications originated in the early 1960s as an alternative procedure to the Nissen, which was associated with moderately high rates of postoperative side effects. These "more physiologic" procedures have proved successful in the treatment of reflux disease in patients with poor or no esophageal motility. In particular, the use of partial fundoplications in association with Heller's myotomy for achalasia has been demonstrated to be well tolerated and to reduce the risk of late dysphasia resulting from uncontrolled gastroesophageal reflux (GER). The use of partial fundoplications in GER patients with normal motility, however, has been less successful. High recurrence rates are documented by many centers with the main cause appearing to be related to a less competent neo-lower esophageal sphincter and a higher rate of wrap herniation. This has led to the current practice of a "tailored approach" to reflux disease, in which all patients receive a thorough preoperative physiologic evaluation to determine the best antireflux procedure for the individual. This is generally a Nissen repair for those with normal motility and either an extrashort "floppy" Nissen or a partial wrap for those with impaired peristalsis.     

胃食管吻合术联合Nissen胃底折叠术对食管中段癌患者术后胃食管反流的影响

目的探讨胃食管吻合术联合Nissen胃底折叠术对食管中段癌术后患者胃食管反流的影响。 方法选取2015年9月至2017年3月,新疆维吾尔自治区人民医院住院并行食管癌切除术31例食管中段癌患者的临床资料。根据手术方式分为2组,即接受胃食管吻合术联合Nissen胃底折叠术15例（观察组）,接受胃食管吻合术16例（对照组）,术后2周待患者恢复正常的胃肠道功能后采用pH动态监测仪对其进行24 h pH监测,术后1、3、6、12个月依据胃食管反流病调查问卷（GerdQ）对患者的胃食管反流相关症状进行评分,比较2组患者术后胃食管反流发生情况。 结果2组患者均未出现死亡病例,且术后均未发生有吻合口瘘及胸胃排空障碍等并发症;观察组患者术后2周24 h酸反流次数显著少于对照组、最长酸反流时间和pH值<4的总时间短于对照组,DeMeester评分显著低于对照组,组间比较均有统计学意义（P<0.05）;观察组术后3、6、12个月胃食管反流病调查问卷（GerdQ）评分显著低于对照组,组间比较均有统计学意义（P<0.05）。 结论胃食管吻合术联合Nissen胃底折叠术对食管癌切术后的胃食管反流病情起到更为理想的控制效果,为食管中段癌患者术中吻合术式的选择提供一定参考价值。     

Effects of bronchial obstruction on lower esophageal sphincter motility and gastroesophageal reflux in patients with asthma

The relationship between gastroesophageal reflux and asthma remains unclear. The aim of this study was to analyze the effect of bronchial obstruction on lower esophageal sphincter (LES) motility and reflux in patients with asthma. LES motility and esophageal pH were assessed in eight subjects with intermittent asthma and eight healthy volunteers during three consecutive 30-minute periods: baseline, methacholine-induced bronchospasm, and after inhalation of the beta2-agonist salbutamol. Healthy subjects inhaled 2 mg of methacholine, whereas subjects with asthma inhaled the dose of methacholine causing a 15% fall in FEV(1), as determined by a previous methacholine challenge. LES motility, esophageal pH, and FEV(1) were not significantly different between the three periods in healthy subjects. In patients with asthma, methacholine induced a 21.9 +/- 2.6% decrease in FEV(1) and a concomitant increase in the rate of transient LES relaxation (TLESR) and reflux episodes. Inhalation of salbutamol decreased the rate of TLESRs but not the number of reflux episodes. We conclude that in patients with asthma, methacholine-induced bronchospasm increases the rate of TLESR and the number of reflux episodes. These results support the belief that, in asthma, bronchial obstruction may be responsible for reflux or may aggravate reflux through a mechanism that remains to be further clarified.     

Objective assessment of gastroesophageal reflux after extended Heller myotomy and total fundoplication for achalasia with the use of 24‐hour combined multichannel intraluminal impedance and pH monitoring (MII‐pH)

SUMMARY. This study aims to evaluate by the use of 24‐hour combined multichannel intraluminal impedance and pH monitoring (MII‐pH) the efficacy of the Nissen fundoplication in controlling both acid and nonacid gastroesophageal reflux (GER) in patients that underwent Heller myotomy for achalasia. It has been demonstrated that fundoplication prevents the pathologic acid GER after Heller myotomy, but no objective data exists on the efficacy of this antireflux surgery in controlling all types of reflux events. The study population consisted of 20 patients that underwent laparoscopic Heller myotomy and Nissen fundoplication for achalasia. All patients were investigated with manometry and MII‐pH. MII‐pH showed no evidence of postoperative pathologic GER. The overall number of GER episodes was normal in both the upright and recumbent position. This reduction was obtained because of the postoperative control of both the acid and nonacid reflux episodes. The Nissen fundoplication adequately controls both acid and nonacid GER after extended Heller myotomy. Further controls with MII‐pH are warranted to check at a longer follow‐up for the efficacy of this antireflux procedure in achalasic patients.     

Esophageal acid perfusion, airway function, and symptoms in asthmatic patients with marked bronchial hyperreactivity

It is believed that GER can trigger asthma by the stimulation of acid-sensitive receptors in the esophagus. The aim of this study was to determine whether esophageal acid stimulation in asthmatic patients can provoke clinically detectable bronchospasm and if a possible response is correlated to bronchial reactivity. Eight patients with chronic asthma and GER disease were investigated on three occasions with a histamine challenge test followed by acid provocation of the esophagus. Assessment of bronchial function was made by FEV1, chest auscultation, and respiratory symptoms. While symptoms and signs of bronchoconstriction induced by esophageal acid stimulation were not detected clinically on any occasion, there was a significant correlation between histamine reactivity and the subclinical bronchospasm following acid provocation. It is concluded that esophageal acid stimulation during daytime in the majority of asthmatic patients is not a strong and immediate trigger of asthma.     

The MVV/FEV1 ratio in normal and asthmatic subjects

We compared the ratio of maximal voluntary ventilation/forced expiratory volume in one second (MVV/FEV1) in normal individuals and asthmatic subjects. Our hypothesis was that MVV/FEV1 would be lower in asthmatic subjects. We also compared MVV/FEV1 results with the effects of deep inspiration (DI) on bronchomotor tone and with methacholine responsiveness. In normal subjects, MVV/FEV1 was higher than that in asthmatic subjects. Specific conductance (SGaw) increased after a single DI or an MVV maneuver in normal individuals. An MVV maneuver caused SGaw to decrease in asthmatic subjects. In asthmatic subjects, there was a significant correlation between MVV/FEV1 ratio and magnitude of decrease in SGaw after an MVV maneuver. Results of methacholine testing indicated that asthmatic subjects with low MVV/FEV1 ratios were more responsive to methacholine than those whose MVV/FEV1 ratios were within normal range. We conclude that MVV/FEV1 ratios are abnormally low in many asthmatic subjects and that low MVV/FEV1 ratios may indicate increased bronchial responsiveness to methacholine.     

Azithromycin reduces bronchial hyperresponsiveness and neutrophilic airway inflammation in asthmatic children: a preliminary report.

Macrolide antibiotics have immunomodulatory effects that may be beneficial to patients with chronic inflammatory pulmonary conditions. The aim of this study was to evaluate the effects of azithromycin on lung function, bronchial hyperresponsiveness (BHR), and airway inflammation in asthmatic children. Sixteen asthmatic children were treated with either azithromycin or placebo for 8 weeks. Lung function, BHR expressed as the dose-response slope (DRS) of forced expiratory volume in 1 second (FEV1) fall after hypertonic saline inhalation (DRS), and induced sputum were evaluated at baseline and after treatment. No significant change was observed in lung function before and after treatment. DRS (percent fall of FEV1/mL) decreased from (X +/- SD) 2.75 +/- 2.12 to 1.42 +/- 1.54 (p = 0.02) in azithromycin-treated children but not in the placebo group, which was 1.48 +/- 1.75 at baseline and 1.01 +/- 1.38 at the end of the study period. Neutrophil leukocytes decreased significantly in the azithromycin-treated group from 10 +/- 5.3% to 2.2 +/- 2.4% (p < 0.01) but not in the placebo group, with 7.2 +/- 4.2% at baseline and 3.3 +/- 3.6% at the end of the study. A short course of azithromycin is associated with amelioration of BHR and reduction in airway neutrophil infiltration in some children with asthma.     

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.     

Gastroesophageal 99mTc scintigraphy in gastroesophageal reflux

The aim of this study was to compare gastroesophageal 99mTc scintiscanning (GES), the pH reflux test (TRA) and esophageal manometry in the assessment of gastroesophageal reflux (GER). GES was performed after oral intake of sulfur colloid labeled with 99m technetium and 300 ml of water. Calculation of an index of reflux gave a semi-quantitative assessment of the GER. Sixty patients with symptoms of GER (typical in 51 cases, atypical in 9 cases) had the three tests. A GES was also performed in 17 normal volunteers and in 12 patients of the series after fundoplication. The diagnostic specificity of GES was 1.0 in GER. GES was less frequently positive than the pH reflux test in GER (68.6 p. 100 versus 80.4 p. 100) but the difference was not significant. These two tests were more sensitive than manometry. The index of reflux was higher in patients than in control subjects (p less than 0.0005) and returned to normal values after fundoplication. A correlation between the index of reflux and the stage of pH-reflux test was observed. It is suggested that GES can be used in the initial assessment of GER as an alternative to TRA and performed repeatedly during the follow-up of patients treated surgically.