Gastroesophageal reflux disease and asthma are both quite common the world over, and they can coexist. However, the nature of the relationship between these two diseases remains unclear. In this study, we review controversial aspects of the relationships among asthma, airway hyperresponsiveness, and gastroesophageal reflux disease in adults and in children.

Keywords: Asthma; Bronchial hyperreactivity; Gastroesophageal reflux.

Objective: To identify this vagal reflex using bronchial provocation tests in patients with gastroesophageal reflux disease. Methods: The study group was composed of 10 patients presenting endoscopic evidence of hiatal hernia or gastroesophageal reflux disease, and the control group consisted of 11 patients presenting no evidence of either condition. All subjects were submitted to bronchial provocation with carbachol. Results: The provocation test was positive in 5 (50%) of the study group patients and 3 (27%) of the control group patients (p = 0.64). Conclusion: The hypothesis that the airways of patients with gastroesophageal reflux disease (and no history of asthma-like respiratory symptoms) might be more responsive than those of individuals without the disease remains unproven.

Keywords: Asthma/complications; Gastroesophageal reflux/complications; Hernia hiatal; Peak expiratory flow rate; Bronchial hyperreactivity; Forced expiratory volume; Carbachol/diagnostic use

Gastroesophageal reflux disease often presents as heartburn and acid reflux, the so-called "typical" symptoms. However, a subgroup of patients presents a collection of signs and symptoms that are not directly related to esophageal damage. These are known collectively as the extraesophageal manifestations of gastroesophageal reflux disease. Principal among such manifestations are bronchospasm, chronic cough and laryngitis, which are classified as atypical symptoms. These manifestations comprise a heterogeneous group. However, some generalizations can be made regarding all of the subgroups. First, although the correlation between gastroesophageal reflux disease and the extraesophageal manifestations has been well established, a cause-and-effect relationship has yet to be definitively elucidated. In addition, the main proposed pathogenic mechanisms of extraesophageal reflux are direct injury of the extraesophageal tissue (caused by contact with gastric acid) and the esophagobronchial reflex, which is mediated by the vagus nerve. Furthermore, gastroesophageal reflux disease might not be considered in the differential diagnosis of patients presenting only the atypical symptoms. In this article, we review the extraesophageal manifestations of gastroesophageal reflux disease, discussing its epidemiology, pathogenesis, diagnosis and treatment. We focus on the most extensively studied and well-established presentations.

Keywords: Gastroesophageal reflux/complications; Asthma; Laryngitis; Cough; Fundoplication; Respiration disorders/etiology

Objective: To determine the prevalence of gastroesophageal reflux disease (GERD) and to evaluate its clinical presentation, as well as the esophageal function profile in patients with idiopathic pulmonary fibrosis (IPF). Methods: In this prospective study, 28 consecutive patients with IPF underwent stationary esophageal manometry, 24-h esophageal pH-metry and pulmonary function tests. All patients also completed a symptom and quality of life in GERD questionnaire. Results: In the study sample, the prevalence of GERD was 35.7%. The patients were then divided into two groups: GERD+ (abnormal pH-metry; n = 10) and GERD− (normal pH-metry; n = 18). In the GERD+ group, 77.7% of the patients presented at least one typical GERD symptom. The pH-metry results showed that 8 (80%) of the GERD+ group patients had abnormal supine reflux, and that the reflux was exclusively in the supine position in 5 (50%). In the GERD+ and GERD− groups, respectively, 5 (50.0%) and 7 (38.8%) of the patients presented a hypotensive lower esophageal sphincter, 7 (70.0%) and 10 (55.5%), respectively, presenting lower esophageal dysmotility. There were no significant differences between the groups regarding demographic characteristics, pulmonary function, clinical presentation or manometric findings. Conclusions: The prevalence of GERD in the patients with IPF was high. However, the clinical and functional characteristics did not differ between the patients with GERD and those without.

Keywords: Pulmonary fibrosis; Gastroesophageal reflux; Prevalence; Manometry; Esophageal pH monitoring.

Objective: To assess the esophageal function profile and the prevalence of gastroesophageal reflux (GER) in lung transplant candidates. Methods: From July of 2005 to November of 2006, a prospective study was conducted involving 55 candidates for lung transplantation at the Santa Casa de Misericórdia Hospital in Porto Alegre, Brazil. Prior to transplantation, patients underwent outpatient stationary esophageal manometry and 24-h esophageal pH-metry using one and two electrodes. Results: Abnormal esophageal manometry was documented in 80% of the patients, and 24% of the patients presented pathological acid reflux. Digestive symptoms presented sensitivity and specificity for GER of 50% and 61%, respectively. Of the patients with chronic obstructive pulmonary disease, 94% presented abnormal esophageal manometry, and 80% presented lower esophageal sphincter hypotonia, making it the most common finding. Patients with bronchiectasis presented the highest prevalence of GER (50%). Conclusions: In patients with advanced lung disease, GER is highly prevalent. In the population studied, digestive symptoms of GER were not predictive of pathological acid reflux. The role that GER plays in chronic rejection should be examined and clarified in future studies.

Keywords: Gastroesophageal reflux; Lung transplantation; Manometry; Esophageal pH monitoring.

Objective: To examine the relationship between gastroesophageal reflux (GER) and COPD exacerbations. Methods: We conducted a systematic search of various electronic databases for articles published up through December of 2012. Studies considered eligible for inclusion were those dealing with COPD, COPD exacerbations, and GER; comparing at least two groups (COPD vs. controls or GER vs. controls); and describing relative risks (RRs) and prevalence ratios-or ORs and their respective 95% CIs (or presenting enough data to allow further calculations) for the association between GER and COPD-as well as exacerbation rates. Using a standardized form, we extracted data related to the study design; criteria for GER diagnosis; age, gender, and number of participants; randomization method; severity scores; methods of evaluating GER symptoms; criteria for defining exacerbations; exacerbation rates (hospitalizations, ER visits, unscheduled clinic visits, prednisone use, and antibiotic use); GER symptoms in COPD group vs. controls; mean number of COPD exacerbations (with symptoms vs. without symptoms); annual frequency of exacerbations; GER treatment; and severity of airflow obstruction. Results: Overall, GER was clearly identified as a risk factor for COPD exacerbations (RR = 7.57; 95% CI: 3.84-14.94), with an increased mean number of exacerbations per year (mean difference: 0.79; 95% CI: 0.22-1.36). The prevalence of GER was significantly higher in patients with COPD than in those without (RR = 13.06; 95% CI: 3.64-46.87; p < 0.001). Conclusions: GER is a risk factor for COPD exacerbations. The role of GER in COPD management should be studied in greater detail.

Keywords: Pulmonary disease, chronic obstructive; Gastroesophageal reflux; Meta-analysis; Risk factors; Evidence-based medicine.

Gastroesophageal reflux (GER) is a common cause of chest affections and symptoms, such as chronic cough, asthma, respiratory infections, pulmonary fibrosis and chest pain. Relief after medical or surgical antireflux therapy is variable. Twenty-four hour pH monitoring has been considered the gold standard for the diagnosis of gastroesophageal reflux disease (GERD). The use of 2 or more pH sensors in different locations within the esophagus is a reliable method for the diagnosis of more severe GER and enables aspiration of the airways and lungs. The purpose of this study was to determine whether the height at which reflux is detected within the esophagus is an indicator of surgical, as opposed to medical, antireflux therapy. In a series of 35 patients with cough as a sole presentation of GER the levels of reflux within the esophagus were correlated to the outcome after medical or surgical antireflux therapy. The studies and surgical procedures were performed in the affiliated hospitals of the Federal and Catholic Universities of Pelotas - RS. Chi-square and Mann-Whitney-U test were used to perform statistical analysis. The present study showed that gastroesophageal reflux into either the distal or the proximal esophagus can cause chronic cough. The height of reflux is an important predictor of response to antireflux therapy. Patients with proximal reflux treated medically do poorly. Surgical therapy is consistently associated with a good outcome, regardless of the height to which reflux occurs, particularly in patients with proximal reflux. Overall, surgical therapy provides the best outcome in all patients with chronic cough due to gastroesophageal reflux.

Keywords: Chronic cough. Gastroesophageal reflux disease. Esophageal pH monitoring.

Background: The relationship between asthma and gastroesophageal reflux is, as yet, not completely understood. Among the mechanisms thought to be responsible for gastroesophageal reflux-related worsening of asthma symptoms are the vagovagal reflex and microaspiration. Objective: To assess forced expiratory volume in one second after acid infusion. Method: This study investigated the effect of acid infusion in 13 volunteers with moderate asthma and gastroesophageal reflux. Spirometry was performed before and after insertion of an 8F nasogastric tube and a pH meter. After 15 minutes of saline solution infusion into the midpoint between the upper esophageal sphincter and lower esophageal sphincter, and again after 15 minutes of esophageal acidification (with hydrochloric acid) of the same area, forced expiratory volume in one second was reassessed. Acidification was repeated every 5 minutes until forced expiratory volume in one second values stabilized (variation: < 5%). Results: Mean forced expiratory volume in one second values remained stable during the tube insertion, saline infusion, initial hydrochloric acid infusion and subsequent hydrochloric acid infusion procedures (p = 0.72). Lower forced expiratory volume in one second values were seen resulting from the tube insertion in two patients (drops of 11% and 22%, respectively), after saline infusion in another two (drops of 13% and 14%) and after acid infusion in 1 (a drop of 22%). Conclusion: Esophageal acidification over short periods does not lead to spirometric alterations in a group of asthmatics with gastroesophageal reflux. However, in some cases, simple esophageal procedures or infusions result in bronchospasm.

Keywords: Key words: Asthma. Gastroesophageal reflux. Respiratory function tests. Endoscopy/methods.

Objectives: To determine the effect that the treatment of GERD has on the clinical management, as well as the respiratory function, of patients with asthma and to evaluate the clinical characteristics of this group of patients. Methods: Patients with asthma and concomitant GERD, documented using 24 h pH-metry, were evaluated by means of quality of life questionnaires, as well as questionnaires related to respiratory and digestive symptoms. In addition, esophageal manometry, spirometry and the determination of peak expiratory flow were also performed prior to and after the study. Forty-nine individuals who were diagnosed with GERD by means of 24 h esophageal pH-metry were selected and participated in a clinical randomized double-blind placebo-controlled study, involving the administration of 40 mg/day of pantoprazol for 12 consecutive weeks. Results: Forty-four individuals completed the study (n = 22 per group). There was significant improvement in the scores for respiratory symptoms and quality of life only in the group that received pantoprazol (p = 0.01 and p = 0.001, respectively). No respiratory function parameters changed in either group. Conclusions: In this study, the effective treatment of GERD improved patient quality of life, and the symptoms of asthma significantly decreased in the group that received the medication. There were no changes in pulmonary function parameters.

Keywords: Asthma; Gastroesophageal reflux/treatment; Diagnosis; Antacids.

Objective: Current debates on the bronchodilator response in COPD patients and whether the variation in FEV1 can be considered as an indicator of complete reversibility in such patients motivated us to conduct this study. The objective of the study was to determine the effect of albuterol on the resistive and reactive properties of the respiratory system in COPD patients. Methods: We evaluated 70 patients with COPD, divided into two groups based on spirometry findings: bronchodilator (BD)-negative (n = 39); and BD-positive (n = 31). We used the forced oscillation technique (FOT) to evaluate the following parameters: resistance at the intercept (R0), associated with the total resistance of the respiratory system; mean resistance (Rm), associated with central airway resistance; dynamic compliance (Cdyn); and the slope of resistance (S) and mean reactance (Xm), both of which are associated with the homogeneity of the respiratory system. Results: The use of albuterol resulted in significant reductions in R0 (p < 0.00002) and Rm (p < 0.0002). There were also significant increases in S (p < 0.0001), Cdyn (p < 0.0001) and Xm (p < 0.00004). These modifications occurred in both groups, the changes in FOT parameters being greater than those observed for spirometric parameters. Conclusions: The use of albuterol improved the resistive and reactive properties of the respiratory system of the COPD patients under study. These changes occurred regardless of the FEV1-based classification, thereby indicating that the use of this parameter in isolation might not suffice to identify the physiological effects involved.

Keywords: Pulmonary disease, chronic obstructive; Bronchodilator agents; Spirometry; Albuterol.

Objective: To assess airway hyperresponsiveness to 4.5% hypertonic saline solution in comparison to that obtained through challenge with other bronchoconstriction agents and in relation to patient allergic sensitization. Methods: A cross-sectional, experimental study was conducted, initially involving 85 subjects. After exclusions, the final sample consisted of 62 patients, divided into two groups: a study group of those with asthma (n = 45) and a control group of those with no asthma or allergies (n = 17). Hypertonic saline was nebulized using an ultrasonic nebulizer and administered successively for 0.5, 1, 2, 4 and 8 minutes until a drop in forced expiratory volume in one second of = 15% was achieved in relation to the baseline value. The level of specific immunoglobulin E to Dermatophagoides pteronyssinus level was determined by ImmunoCAP assay and was considered positive when > 0.35 kU/L. Results: In the 36 asthma group subjects presenting a response, the mean drop in forced expiratory volume in one second after hypertonic saline nebulization was 27.4%. None of control group subjects (immunoglobulin E < 0.35 kU/L) presented a positive response to hypertonic saline. The mean forced expiratory volume in one second for control group subjects was 9%. The results of a bronchial provocation test were negative in 9 of the asthma group subjects. The frequency of bronchial provocation test positivity was higher in the subjects presenting elevated levels of specific immunoglobulin E, indicating that there is a relationship between bronchial hyperresponsiveness and the level of specific immunoglobulin E. The sensitivity and specificity of the test were 80% and 92%, respectively. Conclusion: Bronchial provocation with hypertonic saline presents satisfactory sensitivity and specificity. Therefore, in addition to being a low cost procedure that requires very little equipment, it is a useful means of assessing hyperresponsiveness in children and adolescents.

Keywords: Bronchial provocation tests; Bronchial hyperreactivity; Saline solution, hypertonic; Administration, inhalation;

Objective: To investigate the effects of airway obstruction on albuterol-mediated variations in the resistive and elastic properties of the respiratory system of adult patients with asthma. Methods: This study comprised 24 healthy controls and 69 patients with asthma, all of whom were nonsmokers. The patients were divided into three groups according to the severity of airway obstruction (mild, moderate or severe). Each of the three groups was divided into two subgroups according to the bronchodilator response (BR): positive (BR+) or negative (BR−). These measurements were conducted before and after albuterol use (300 µg). Airway obstruction was determined by means of spirometry, and the resistive and elastic properties were determined by means of the forced oscillation technique. Results: The resistance at the intercept (R0) presented greater reductions in the groups with higher obstruction. This reduction was more evident in the BR+ subgroups than in the BR− subgroups (p < 0.02 and p < 0.03, respectively). There was a significant difference between the control group and the BR+ subgroup with severe obstruction (p < 0.002). The reductions in dynamic elastance (Edyn) were significantly greater in proportion to the degree of obstruction, in the BR− subgroups (p < 0.03), and in the BR+ subgroups (p < 0.003). The reductions in Edyn were significantly greater in the BR− subgroup with moderate obstruction (p < 0.008) and in the BR+ subgroup with severe obstruction (p < 0.0005) than in the control group. Conclusions: In patients with asthma, increased airway obstruction results in greater reductions in R0 and Edyn after albuterol use. These reductions are greater among BR+ patients than among BR− patients.

Keywords: Asthma; Bronchodilator agents; Respiratory mechanics; Spirometry; Albuterol.

Continuous positive airway pressure (CPAP) is the gold standard for the treatment of obstructive sleep apnea (OSA). Although CPAP was originally applied with a nasal mask, various interfaces are currently available. This study reviews theoretical concepts and questions the premise that all types of interfaces produce similar results. We revised the evidence in the literature about the impact that the type of CPAP interface has on the effectiveness of and adherence to OSA treatment. We searched the PubMed database using the search terms "CPAP", "mask", and "obstructive sleep apnea". Although we identified 91 studies, only 12 described the impact of the type of CPAP interface on treatment effectiveness (n = 6) or adherence (n = 6). Despite conflicting results, we found no consistent evidence that nasal pillows and oral masks alter OSA treatment effectiveness or adherence. In contrast, most studies showed that oronasal masks are less effective and are more often associated with lower adherence and higher CPAP abandonment than are nasal masks. We concluded that oronasal masks can compromise CPAP OSA treatment adherence and effectiveness. Further studies are needed in order to understand the exact mechanisms involved in this effect.

Keywords: Sleep apnea, obstructive; Continuous positive airway pressure; Masks.