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Eapen AA, Gupta MR, Lockey RF, Bardin PG, Baptist AP. Gastroesophageal reflux disease, laryngopharyngeal reflux, and vocal cord dysfunction/inducible laryngeal obstruction-overlapping conditions that affect asthma. J Allergy Clin Immunol 2024; 154:1369-1377. [PMID: 39426423 DOI: 10.1016/j.jaci.2024.10.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Revised: 10/04/2024] [Accepted: 10/10/2024] [Indexed: 10/21/2024]
Abstract
Asthma is a chronic lung condition that may be affected by numerous medical comorbidities. Such comorbidities can influence the presentation and even the severity of asthma. Alternatively, asthma may be misdiagnosed as a comorbidity when symptoms overlap. The 3 medical conditions that commonly affect asthma management are gastroesophageal reflux disease, laryngopharyngeal reflux, and vocal cord dysfunction/inducible laryngeal obstruction). These conditions can be difficult to distinguish from one another, as well as from asthma itself. In this review, the epidemiology, pathophysiology, symptomatology, and diagnostic considerations of each condition in both adult and pediatric populations are discussed. Treatment options, as well as how such options may influence asthma outcomes, are included. Finally, knowledge gaps in each area are highlighted, as a better understanding of the optimal diagnostic and therapeutic approaches will allow for improved individualized care of patients with asthma.
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Affiliation(s)
- Amy A Eapen
- Division of Allergy and Clinical Immunology, Department of Internal Medicine, Henry Ford Health + Michigan State University, Detroit, Mich
| | - Meera R Gupta
- Division Immunology, Allergy, and Retrovirology, Texas Children's Hospital and Baylor College of Medicine, Houston, Tex
| | - Richard F Lockey
- Division of Allergy and Immunology, Department of Internal Medicine, University of South Florida Morsani College of Medicine, Tampa, Fla
| | - Philip G Bardin
- Monash Lung Sleep Allergy & Immunology, Melbourne, Australia; Hudson Institute, Melbourne, Australia; Monash Hospital and University, Melbourne, Australia
| | - Alan P Baptist
- Division of Allergy and Clinical Immunology, Department of Internal Medicine, Henry Ford Health + Michigan State University, Detroit, Mich.
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2
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McDonald VM, Hamada Y, Agusti A, Gibson PG. Treatable Traits in Asthma: The Importance of Extrapulmonary Traits-GERD, CRSwNP, Atopic Dermatitis, and Depression/Anxiety. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE 2024; 12:824-837. [PMID: 38278324 DOI: 10.1016/j.jaip.2024.01.020] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Revised: 12/14/2023] [Accepted: 01/02/2024] [Indexed: 01/28/2024]
Abstract
Treatable traits is a personalized medicine approach to the management of airway disease. Assessing traits within the 3 domains of pulmonary, extrapulmonary, and behavioral/lifestyle/risk factor traits, and applying targeted treatments to effectively manage these traits, enables a holistic and personalized approach to care. Asthma is a heterogeneous and complex airway disease that is frequently complicated by several extrapulmonary traits that impact asthma outcomes and predict future outcomes. We propose that the identification of extrapulmonary and behavioral risk factor traits and the implementation of targeted therapy will lead to improved management of people with asthma. Furthermore, many extrapulmonary traits present as "connected comorbidities"; that is, they coexist with asthma, have an impact on asthma, and effective treatment improves both asthma and the comorbidity or the comorbidities may share a similar mechanism. In this review, we explore this concept and look at atopic dermatitis, chronic rhinosinusitis with nasal polyps, gastroesophageal reflux disease, anxiety, and depression as treatable traits of asthma and how these can be managed using this approach.
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Affiliation(s)
- Vanessa M McDonald
- Centre of Excellence in Treatable Traits, College of Health, Medicine and Wellbeing, University of Newcastle, New Lambton Heights, NSW, Australia; Department of Respiratory and Sleep Medicine, John Hunter Hospital, New Lambton Heights, NSW, Australia.
| | - Yuto Hamada
- Centre of Excellence in Treatable Traits, College of Health, Medicine and Wellbeing, University of Newcastle, New Lambton Heights, NSW, Australia; Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital, Kanagawa, Japan
| | - Alvar Agusti
- Respiratory Institute, Hospital Clinic, Universitat de Barcelona, IDIBAPS, CIBERES, Barcelona, Spain
| | - Peter G Gibson
- Centre of Excellence in Treatable Traits, College of Health, Medicine and Wellbeing, University of Newcastle, New Lambton Heights, NSW, Australia; Department of Respiratory and Sleep Medicine, John Hunter Hospital, New Lambton Heights, NSW, Australia
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Khan J, Moran B, McCarthy C, Butler MW, Franciosi AN. Management of comorbidities in difficult and severe asthma. Breathe (Sheff) 2023; 19:230133. [PMID: 38020342 PMCID: PMC10644109 DOI: 10.1183/20734735.0133-2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Accepted: 10/03/2023] [Indexed: 12/01/2023] Open
Abstract
Difficult-to-treat and severe asthma are challenging clinical entities. In the face of suboptimal asthma control, the temptation for clinicians is to reflexively escalate asthma-directed therapy, including increasing exposure to corticosteroids and commencement of costly but potent biologic therapies. However, asthma control is objectively and subjectively assessed based on measurable parameters (such as exacerbations or variability in pulmonary physiology), symptoms and patient histories. Crucially, these features can be confounded by common untreated comorbidities, affecting clinicians' assessment of asthma treatment efficacy.
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Affiliation(s)
- Jehangir Khan
- University College Dublin, Dublin, Ireland
- St Vincent's University Hospital, Dublin, Ireland
- Shared first authorship
| | - Barry Moran
- St Vincent's University Hospital, Dublin, Ireland
- Shared first authorship
| | - Cormac McCarthy
- University College Dublin, Dublin, Ireland
- St Vincent's University Hospital, Dublin, Ireland
| | - Marcus W. Butler
- University College Dublin, Dublin, Ireland
- St Vincent's University Hospital, Dublin, Ireland
- Shared senior authorship
| | - Alessandro N. Franciosi
- University College Dublin, Dublin, Ireland
- St Vincent's University Hospital, Dublin, Ireland
- Shared senior authorship
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Bouriez D, Belaroussi Y, Boubaddi M, Martre P, Najah H, Berger P, Gronnier C, Collet D. Laparoscopic fundoplication for para-oesophageal hernia repair improves respiratory function in patients with dyspnoea: a prospective cohort study. Surg Endosc 2022; 36:7266-7278. [PMID: 35732837 PMCID: PMC9216289 DOI: 10.1007/s00464-022-09127-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Accepted: 02/07/2022] [Indexed: 01/20/2023]
Abstract
Background Dyspnoea in patients with a para-oesophageal hernia (PEH) occurs in 7% to 32% of cases and is very disabling, especially in elderly patients, and its origin is not well defined. The present study aims to assess the impact of PEH repair on dyspnoea and respiratory function. Methods From January 2019 to May 2021, all consecutive patients scheduled for PEH repair presenting with a modified Medical Research Council (mMRC) score ≥ 2 for dyspnoea were included. Before and 2 months after surgery, dyspnoea was assessed by both the dyspnoea visual analogue scale (DVAS) and the mMRC scale, as well as pulmonary function tests (PFTs) by plethysmography. Results All 43 patients that were included had pre- and postoperative dyspnoea assessments and PFTs. Median age was 70 years (range 63–73.5 years), 37 (86%) participants were women, median percentage of the intrathoracic stomach was 59.9% (range 44.2–83.0%), and median length of hospital stay was 3 days (range 3–4 days). After surgery, the DVAS decreased statistically significant (5.6 [4.7–6.7] vs. 3.0 [2.3–4.4], p < 0.001), and 37 (86%) patients had a clinically significant decrease in mMRC score. Absolute forced expiratory volume in one second (FEV1), total lung capacity, and forced vital capacity also statistically significantly increased after surgery by an average of 11.2% (SD 17.9), 5.0% (SD 13.9), and 10.7% (SD 14.6), respectively. Furthermore, from the subgroup analysis, it was identified that patients with a lower preoperative FEV1 were more likely to have improvement in it after surgery. No correlation was found between improvement in dyspnoea and FEV1. There was no correlation between the percentage of intrathoracic stomach and dyspnoea or improvement in PFT parameters. Conclusion PEH repair improves dyspnoea and FEV1 in a statistically significant manner in a population of patients presenting with dyspnoea. Patients with a low preoperative FEV1 are more likely to have improvement in it after surgery.
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Affiliation(s)
- Damien Bouriez
- Esophagogastric Surgery Unit, Haut Lévêque Hospital, CHU Bordeaux, Bordeaux, France
| | - Yaniss Belaroussi
- Thoracic Surgery Unit, Haut Lévêque Hospital, CHU Bordeaux, Bordeaux, France
- INSERM, Bordeaux Population Health Research Center, ISPED, University of Bordeaux, 33076, Bordeaux, France
| | - Mehdi Boubaddi
- Esophagogastric Surgery Unit, Haut Lévêque Hospital, CHU Bordeaux, Bordeaux, France
| | - Paul Martre
- Esophagogastric Surgery Unit, Haut Lévêque Hospital, CHU Bordeaux, Bordeaux, France
| | - Haythem Najah
- Esophagogastric Surgery Unit, Haut Lévêque Hospital, CHU Bordeaux, Bordeaux, France
| | - Patrick Berger
- Pulmonary Function Tests Department, Haut Lévêque Hospital, CHU Bordeaux, Bordeaux, France
- University of Bordeaux, Bordeaux, France
| | - Caroline Gronnier
- Esophagogastric Surgery Unit, Haut Lévêque Hospital, CHU Bordeaux, Bordeaux, France.
- University of Bordeaux, Bordeaux, France.
- INSERM, U1053, Bordeaux, France.
| | - Denis Collet
- Esophagogastric Surgery Unit, Haut Lévêque Hospital, CHU Bordeaux, Bordeaux, France
- University of Bordeaux, Bordeaux, France
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5
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Launois C, Mulette P, Ancel J, Dury S, Hagenburg J, Lebargy F, Dormoy V, Deslee G, Perotin JM. [Treatment of GERD in asthma]. Rev Mal Respir 2021; 38:733-742. [PMID: 34016495 DOI: 10.1016/j.rmr.2021.04.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Accepted: 03/25/2021] [Indexed: 11/28/2022]
Abstract
Gastro-oesophageal reflux disease (GORD) is one of the most frequent conditions associated with asthma. GORD has an impact on asthma control and quality of life of asthmatic patients. Its treatment relies on lifestyle modifications, anti-acidic treatment with proton pump inhibitors (PPI) and/or surgical management by fundoplication in some situations. The impact of lifestyle modifications has not been analysed on asthma outcomes alone. Several randomised controlled trials assessed the efficacy of PPI on asthma control, peak expiratory flow and/or quality of life. The impact of fundoplication in asthma has mainly been analysed in retrospective or prospective observational studies. This review highlights the limited impact of GORD treatment on asthma control. Current guidelines are to restrict GORD treatment in asthma to asthmatic patients with actual symptomatic GORD. Given the lack of controlled studies, the place of surgical management of GORD in asthma is currently not defined.
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Affiliation(s)
- C Launois
- Service des maladies respiratoires, CHU de Reims, 45, rue Cognacq-Jay, 51092 Reims cedex, France
| | - P Mulette
- Service des maladies respiratoires, CHU de Reims, 45, rue Cognacq-Jay, 51092 Reims cedex, France
| | - J Ancel
- Service des maladies respiratoires, CHU de Reims, 45, rue Cognacq-Jay, 51092 Reims cedex, France
| | - S Dury
- Service des maladies respiratoires, CHU de Reims, 45, rue Cognacq-Jay, 51092 Reims cedex, France; EA 4683, université de Reims Champagne-Ardenne, 51092 Reims, France
| | - J Hagenburg
- Service des maladies respiratoires, CHU de Reims, 45, rue Cognacq-Jay, 51092 Reims cedex, France
| | - F Lebargy
- Service des maladies respiratoires, CHU de Reims, 45, rue Cognacq-Jay, 51092 Reims cedex, France; EA 4683, université de Reims Champagne-Ardenne, 51092 Reims, France
| | - V Dormoy
- Inserm UMR-S 1250, P3Cell, université de Reims Champagne-Ardenne, 51092 Reims, France
| | - G Deslee
- Service des maladies respiratoires, CHU de Reims, 45, rue Cognacq-Jay, 51092 Reims cedex, France; Inserm UMR-S 1250, P3Cell, université de Reims Champagne-Ardenne, 51092 Reims, France
| | - J-M Perotin
- Service des maladies respiratoires, CHU de Reims, 45, rue Cognacq-Jay, 51092 Reims cedex, France; Inserm UMR-S 1250, P3Cell, université de Reims Champagne-Ardenne, 51092 Reims, France.
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6
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Bardin PG, Rangaswamy J, Yo SW. Managing comorbid conditions in severe asthma. Med J Aust 2019; 209:S11-S17. [PMID: 30453867 DOI: 10.5694/mja18.00196] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2018] [Accepted: 11/20/2018] [Indexed: 12/26/2022]
Abstract
Asthma care has increasingly focused on personalised management for severe asthma, and recognition of the role and importance of comorbid conditions has increased. Severe asthma can be crippling; associated comorbid conditions often play a key role in the significant disease morbidity and frequently contribute to a severe and difficult-to-treat asthma phenotype. Comorbid conditions can be broadly grouped as being either airway-related or airway-unrelated. Airway-related comorbid conditions with the greatest impact are allergic rhinitis, chronic rhinosinusitis, vocal cord dysfunction, lung fungal sensitisation and underlying structural lung disease. The most important airway-unrelated comorbid conditions are obesity, obstructive sleep apnoea, gastro-oesophageal reflux disease and anxiety and depression. A diagnostic and management algorithm for comorbid conditions in severe asthma is outlined. It concentrates initially on the group with common comorbid conditions that can be managed in primary care. If asthma remains troublesome, emphasis can shift to identifying uncommon and more complex factors. The algorithm allows for personalised diagnostic and management pathways to be implemented. Personalised diagnosis and management of comorbid conditions are essential to achieving effective and improved outcomes for patients with severe asthma.
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Affiliation(s)
- Philip G Bardin
- Monash Lung and Sleep, Monash Hospital and University, Melbourne, VIC
| | | | - Shaun W Yo
- Monash Lung and Sleep, Monash Hospital and University, Melbourne, VIC
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Tariq K, Schofield JPR, Nicholas BL, Burg D, Brandsma J, Bansal AT, Wilson SJ, Lutter R, Fowler SJ, Bakke, Caruso M, Dahlen B, Horváth I, Krug N, Montuschi P, Sanak M, Sandström T, Geiser T, Pandis I, Sousa AR, Adcock IM, Shaw DE, Auffray C, Howarth PH, Sterk PJ, Chung KF, Skipp PJ, Dimitrov B, Djukanović R. Sputum proteomic signature of gastro-oesophageal reflux in patients with severe asthma. Respir Med 2019; 150:66-73. [PMID: 30961953 DOI: 10.1016/j.rmed.2019.02.008] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2018] [Revised: 01/30/2019] [Accepted: 02/04/2019] [Indexed: 01/08/2023]
Abstract
Gastro-oesophageal reflux disease (GORD) has long been associated with poor asthma control without an established cause-effect relationship. 610 asthmatics (421 severe/88 mild-moderate) and 101 healthy controls were assessed clinically and a subset of 154 severe asthmatics underwent proteomic analysis of induced sputum using untargeted mass spectrometry, LC-IMS-MSE. Univariate and multiple logistic regression analyses (MLR) were conducted to identify proteins associated with GORD in this cohort. When compared to mild/moderate asthmatics and healthy individuals, respectively, GORD was three- and ten-fold more prevalent in severe asthmatics and was associated with increased asthma symptoms and oral corticosteroid use, poorer quality of life, depression/anxiety, obesity and symptoms of sino-nasal disease. Comparison of sputum proteomes in severe asthmatics with and without active GORD showed five differentially abundant proteins with described roles in anti-microbial defences, systemic inflammation and epithelial integrity. Three of these were associated with active GORD by multiple linear regression analysis: Ig lambda variable 1-47 (p = 0·017) and plasma protease C1 inhibitor (p = 0·043), both in lower concentrations, and lipocalin-1 (p = 0·034) in higher concentrations in active GORD. This study provides evidence which suggests that reflux can cause subtle perturbation of proteins detectable in the airways lining fluid and that severe asthmatics with GORD may represent a distinct phenotype of asthma.
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Affiliation(s)
- K Tariq
- NIHR Southampton Respiratory Biomedical Research Centre, University Hospital Southampton, Southampton, UK; Clinical Experimental Sciences Unit, Faculty of Medicine, University of Southampton, University Hospital Southampton, South Academic Block, Southampton, UK
| | - J P R Schofield
- NIHR Southampton Respiratory Biomedical Research Centre, University Hospital Southampton, Southampton, UK; Centre for Proteomic Research, University of Southampton, Highfield, Southampton, UK
| | - B L Nicholas
- NIHR Southampton Respiratory Biomedical Research Centre, University Hospital Southampton, Southampton, UK; Clinical Experimental Sciences Unit, Faculty of Medicine, University of Southampton, University Hospital Southampton, South Academic Block, Southampton, UK
| | - D Burg
- NIHR Southampton Respiratory Biomedical Research Centre, University Hospital Southampton, Southampton, UK; Centre for Proteomic Research, University of Southampton, Highfield, Southampton, UK
| | - J Brandsma
- NIHR Southampton Respiratory Biomedical Research Centre, University Hospital Southampton, Southampton, UK
| | | | - S J Wilson
- NIHR Southampton Respiratory Biomedical Research Centre, University Hospital Southampton, Southampton, UK
| | - R Lutter
- AMC, Department of Experimental Immunology, University of Amsterdam, Amsterdam, the Netherlands; AMC, Department of Respiratory Medicine, University of Amsterdam, Amsterdam, the Netherlands
| | - S J Fowler
- Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester and University Hospital of South Manchester, NHS Foundation Trust, Manchester, UK
| | - Bakke
- Department of Clinical Science, University of Bergen, Bergen, Norway
| | - M Caruso
- Dept. of Clinical and Experimental Medicine Hospital University, Policlinico-Vittorio Emanuele, University of Catania, Catania, Italy
| | - B Dahlen
- Division of Respiratory Medicine and Allergy, Department of Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden
| | - I Horváth
- Dept. of Pulmonology, Semmelweis University, Budapest, Hungary
| | - N Krug
- Fraunhofer Institute for Toxicology and Experimental Medicine Hannover, Hannover, Germany
| | - P Montuschi
- Dept. of Pharmacology, Faculty of Medicine, Catholic University of the Sacred Heart, Rome, Italy
| | - M Sanak
- Division of Molecular Biology and Clinical Genetics, Medical College, Jagiellonian University Medical College, Krakow, Poland
| | - T Sandström
- Dept. of Medicine, Dept of Public Health and Clinical Medicine Respiratory Medicine Unit, Umeå University, Umeå, Sweden
| | - T Geiser
- University Hospital Bern, Bern, Switzerland
| | - I Pandis
- Data Science Institute, Imperial College, London, UK
| | - A R Sousa
- Respiratory Therapeutic Unit, GSK, Stockley Park, UK
| | - I M Adcock
- Cell and Molecular Biology Group, Airways Disease Section, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London, UK
| | - D E Shaw
- Respiratory Research Unit, University of Nottingham, Nottingham, UK
| | - C Auffray
- European Institute for Systems Biology and Medicine, CNRS-ENS-UCBL-INSERM, Lyon, France
| | - P H Howarth
- NIHR Southampton Respiratory Biomedical Research Centre, University Hospital Southampton, Southampton, UK; Clinical Experimental Sciences Unit, Faculty of Medicine, University of Southampton, University Hospital Southampton, South Academic Block, Southampton, UK
| | - P J Sterk
- AMC, Department of Respiratory Medicine, University of Amsterdam, Amsterdam, the Netherlands
| | - K F Chung
- Airways Disease, National Heart and Lung Institute, Imperial College, London & Royal Brompton NIHR Biomedical Research Unit, London, United Kingdom
| | - P J Skipp
- Centre for Proteomic Research, University of Southampton, Highfield, Southampton, UK
| | - B Dimitrov
- NIHR Southampton Respiratory Biomedical Research Centre, University Hospital Southampton, Southampton, UK
| | - R Djukanović
- NIHR Southampton Respiratory Biomedical Research Centre, University Hospital Southampton, Southampton, UK; Clinical Experimental Sciences Unit, Faculty of Medicine, University of Southampton, University Hospital Southampton, South Academic Block, Southampton, UK.
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Asthma under control is inversely related with erosive esophagitis among healthy adults. PLoS One 2019; 14:e0210490. [PMID: 30615668 PMCID: PMC6322772 DOI: 10.1371/journal.pone.0210490] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2018] [Accepted: 12/23/2018] [Indexed: 12/15/2022] Open
Abstract
Background Some recent studies suggested that reflux esophagitis is positively correlated with asthma. However, there are debates on this issue. The aim of this study is to clarify the true association between reflux esophagitis and asthma in a large population. Methods Medical records of subjects who received health surveillance checkup between January 2005 and December 2011 were reviewed. Their endoscopic findings, medical history, body mass index, and smoking history were analyzed. Erosive esophagitis was defined as endoscopically detected mucosal break at the Z-line, irrespective of reflux symptom. Information about asthma history was obtained from their questionnaires and medical records. Results Out of the total 15,999 patients, 986 had erosive esophagitis and 376 had asthma. In this population, erosive esophagitis was inversely related with asthma in univariable analysis (OR, 0.586; 95% CI, 0.342–1.003, p = 0.049). In multivariable analysis, asthma was demonstrated as an independent negative risk factor for erosive esophagitis (OR, 0.472; 95% CI, 0.257–0.869, p = 0.016), under adjustment with age (OR, 1.000; 95% CI, 0.994–1.006, p = 0.977), male sex (OR, 2.092; 95% CI, 1.683–2.601, p < 0.001), body mass index (OR, 1.115; 95% CI, 1.090–1.141, p < 0.001), smoking (OR, 1.584; 95% CI, 1.318–1.902, p < 0.001), and urban residence (OR, 1.363; 95% CI, 1.149–1.616, p < 0.001). Likewise, erosive esophagitis was shown to be an independent negative risk factor for asthma (OR, 0.558; 95% CI, 0.324–0.960, p = 0.035) under adjustment with age (OR, 1.025; 95% CI, 1.015–1.034, p <0.001), male sex (OR, 0.861; 95% CI, 0.691–1.074, p = 0.185), and body mass index (OR, 1.067; 95% CI, 1.030–1.106, p < 0.001) in multivariable analysis. Conclusions Contrary to previous studies, this large scale data showed inverse association between erosive esophagitis and asthma. Further studies investigating the clear mechanism of this phenomenon are warranted.
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9
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Broers C, Tack J, Pauwels A. Review article: gastro-oesophageal reflux disease in asthma and chronic obstructive pulmonary disease. Aliment Pharmacol Ther 2018; 47:176-191. [PMID: 29193245 DOI: 10.1111/apt.14416] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2017] [Revised: 05/29/2017] [Accepted: 10/20/2017] [Indexed: 12/13/2022]
Abstract
BACKGROUND When gastro-oesophageal reflux is causing symptoms or lesions in the oesophagus, this is referred to as gastro-oesophageal reflux disease (GERD). GERD can manifest itself through typical symptoms (heartburn, regurgitation) or may lead to extra-oesophageal symptoms. Extra-oesophageal manifestations of GERD gained increasing attention over the last decade, especially respiratory disorders, because of the prevalent co-occurrence with GERD. The role of GERD in the pathogenesis of respiratory disorders has become a topic of intense discussion. AIM To provide an overview of the current knowledge on the role of GERD in asthma and chronic obstructive pulmonary disease (COPD). METHODS PubMed was searched for relevant articles using the keywords: GERD, asthma, COPD, prevalence, treatment. Case reports were excluded, only English language articles were considered. RESULTS Estimates for the prevalence of GERD in asthma range from 30% to 90%, compared to an average of 24% in controls. In COPD patients, the prevalence of GERD ranges from 19% to 78% compared to an average of 18% in controls. These data indicate an increased prevalence of GERD in patients with asthma and COPD, although causality is not established and GERD treatment yielded inconsistent effects. Literature supports GERD as a risk factor for COPD-exacerbations and a predictor of the 'frequent-exacerbator'-phenotype. CONCLUSIONS Despite the high prevalence of GERD in asthma and COPD, a causal link is lacking. The results of anti-reflux therapy on pulmonary outcome are inconsistent and contradictory. Future studies will need to identify subgroups of asthmatics and COPD patients that may benefit from anti-reflux therapy (nocturnal or silent reflux).
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Affiliation(s)
- C Broers
- Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium
| | - J Tack
- Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium.,Department of Gastroenterology, Leuven University Hospitals, Leuven, Belgium
| | - A Pauwels
- Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium
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10
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Abd-El-Hafeez AM, Fouad SA. Endoscopic prevalence of different grades of gastroesophageal reflux in adult asthmatics with or without reflux symptoms. THE EGYPTIAN JOURNAL OF BRONCHOLOGY 2016. [DOI: 10.4103/1687-8426.184357] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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11
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Kim C, Ouyang W, Dass C, Zhao H, Criner GJ. Hiatal Hernia on Chest High-Resolution Computed Tomography and Exacerbation Rates in COPD Individuals. CHRONIC OBSTRUCTIVE PULMONARY DISEASES-JOURNAL OF THE COPD FOUNDATION 2016; 3:570-579. [PMID: 28848881 DOI: 10.15326/jcopdf.3.2.2015.0158] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Background: Gastroesophageal reflux disease (GERD) is associated with frequent chronic obstructive pulmonary disease (COPD) exacerbations. Hiatal hernia (HH) contributes to GERD pathogenesis and is identifiable on chest high-resolution computed tomography (HRCT). We hypothesize that the presence of an HH on HRCT identifies those at increased risk for acute exacerbation of COPD. Methods: We retrospectively reviewed a prospectively enrolled cohort of smokers with and without airflow obstruction. HHs were identified visually on inspiratory HRCT. Individuals' demographic and clinical information was compared with secondary analysis performed using a propensity score generated matched cohort. Results: There were 523 COPD individuals and 607 unobstructed smokers. COPD individuals had more HHs than unobstructed smokers, (11.6% versus 6.1%, p < 0.001). COPD individuals with hernias were older, female, overweight and GERD positive as compared to those without hernia. There was no difference in self-reported exacerbation rates or hospitalizations per year, but similar severity of obstruction, smoking rates and long-term oxygen use. Analysis with the matched cohort revealed no significant difference in exacerbation rates. Conclusions: Presence of HHs on inspiratory HRCT scan did not predict worse symptoms or exacerbation rate in COPD individuals. Those with HHs were older, more obese, and predominantly female compared to those without HHs.
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Affiliation(s)
- Cynthia Kim
- Department of Pulmonary and Critical Care Medicine, Temple University Hospital, Philadelphia, Pennsylvania.,Co-first Authors
| | - Wei Ouyang
- Department of Radiology, Temple University Hospital, Philadelphia, Pennsylvania.,Co-first Authors
| | - Chandra Dass
- Department of Radiology, Temple University Hospital, Philadelphia, Pennsylvania
| | - Huaqing Zhao
- Temple Clinical Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania
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Naik RD, Vaezi MF. Extra-esophageal gastroesophageal reflux disease and asthma: understanding this interplay. Expert Rev Gastroenterol Hepatol 2015; 9:969-82. [PMID: 26067887 DOI: 10.1586/17474124.2015.1042861] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Gastroesophageal reflux disease (GERD) is a condition that develops when there is reflux of stomach contents, which typically manifests as heartburn and regurgitation. These esophageal symptoms are well recognized; however, there are extra-esophageal manifestations of GERD, which include asthma, chronic cough, laryngitis and sinusitis. With the rising incidence of asthma, there is increasing interest in identifying how GERD impacts asthma development and therapy. Due to the poor sensitivity of endoscopy and pH monitoring, empiric therapy with proton pump inhibitors (PPIs) is now considered the initial diagnostic step in patients suspected of having GERD-related symptoms. If unresponsive, diagnostic testing with pH monitoring off therapy and/or impedance/pH monitoring on therapy, may be reasonable in order to assess for baseline presence of reflux with the former and exclude continued acid or weakly acid reflux with the latter tests. PPI-unresponsive asthmatics, without overt regurgitation, usually have either no reflux or causes other than GERD. In this group, PPI therapy should be discontinued. In those with GERD as a contributing factor acid suppressive therapy should be continued as well as optimally treating other etiologies requiring concomitant treatment. Surgical fundoplication is rarely needed but in those with a large hiatal hernia, moderate-to-severe reflux by pH monitoring surgery might be helpful in eliminating the need for high-dose acid suppressive therapy.
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Affiliation(s)
- Rishi D Naik
- Division of Gastroenterology, Hepatology, and Nutrition, Center for Swallowing and Esophageal Disorders, Digestive Disease Center, Vanderbilt University Medical Center, 1660 TVC, Nashville, TN 37232-5280, USA
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Ishizuka T, Hisada T, Kamide Y, Aoki H, Seki K, Honjo C, Sakai H, Kadowaki M, Umeda Y, Morikawa M, Anzai M, Ameshima S, Ishizaki T, Dobashi K, Yamada M, Kusano M. The effects of concomitant GERD, dyspepsia, and rhinosinusitis on asthma symptoms and FeNO in asthmatic patients taking controller medications. J Asthma Allergy 2014; 7:131-9. [PMID: 25228816 PMCID: PMC4161609 DOI: 10.2147/jaa.s67062] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
Abstract
Background Losing the sense of smell, which suggests eosinophilic rhinosinusitis, is a subjective symptom, sometimes reported in asthmatic patients taking controller medication. Upper abdominal symptoms, suggesting gastroesophageal reflux disease (GERD) or functional dyspepsia, occur also in these patients. However, the relationship between these symptoms, concomitant with asthma, and the intensity of eosinophilic airway inflammation remains obscure. Objective To assess the symptoms of asthma and rhinosinusitis, and to examine the relationship between the symptoms and bronchial inflammation, a new questionnaire, the G scale, was developed. To investigate the effects of GERD, dyspepsia, and rhinosinusitis on asthma symptoms and bronchial inflammation, the symptoms of asthma and rhinosinusitis obtained by the G scale, upper abdominal symptoms obtained by the modified F scale, a questionnaire for GERD and dyspepsia, and fractional exhaled nitric oxide (FeNO) were analyzed. Methods A prospective, observational study was performed in four hospitals in Gunma prefecture, and a retrospective analysis was done using data obtained from five hospitals in Gunma prefecture and Fukui prefecture, Japan. A total of 252 patients diagnosed as having asthma participated in the prospective study. Results The frequency of daytime phlegm or losing the sense of smell had a positive correlation with FeNO levels in asthmatic patients taking controller medication. Upper abdominal symptoms, as well as symptoms suggesting rhinitis, were well correlated with asthma symptoms. However, neither upper abdominal symptoms nor rhinitis symptoms increased FeNO levels, which reflect eosinophilic airway inflammation during treatment for asthma. On the other hand, the degree of upper abdominal symptoms or dyspepsia symptoms had a weak but significant negative correlation with FeNO levels. Conclusion Daytime phlegm and losing the sense of smell suggest that eosinophilic airway inflammation persists, despite anti-inflammatory therapy, in patients with asthma. Although rhinitis and GERD made the subjective symptoms of asthma worse, they did not seem to enhance eosinophilic airway inflammation.
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Affiliation(s)
- Tamotsu Ishizuka
- Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan ; Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Takeshi Hisada
- Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Yosuke Kamide
- Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Haruka Aoki
- Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Kaori Seki
- Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Chisato Honjo
- Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Hiroyuki Sakai
- Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Maiko Kadowaki
- Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Yukihiro Umeda
- Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Miwa Morikawa
- Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Masaki Anzai
- Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Shingo Ameshima
- Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Takeshi Ishizaki
- Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Kunio Dobashi
- Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Masanobu Yamada
- Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Motoyasu Kusano
- Department of Endoscopy and Endoscopic Surgery, Gunma University Hospital, Maebashi, Japan
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14
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Mirić M, Turkalj M, Nogalo B, Erceg D, Perica M, Plavec D. Lung diffusion capacity in children with respiratory symptoms and untreated GERD. Med Sci Monit 2014; 20:774-81. [PMID: 24816214 PMCID: PMC4026150 DOI: 10.12659/msm.890336] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Gastroesophageal reflux disease (GERD) is associated with many respiratory disorders, among which, chronic cough, laryngitis, and asthma are among the most common. We investigated lung function, including gas diffusion capacity, in children with poor asthma control or chronic laryngitis with untreated GERD. MATERIAL AND METHODS A total of 71 children, aged 6-17 years, with chronic respiratory and other symptoms suggestive for GERD, were enrolled and divided into 2 groups: chronic laryngitis and asthma. Participants underwent 24-hour pH monitoring and lung function assessment, measurement of single-breath diffusing capacity of the lung for carbon monoxide (DLCO), and fraction of exhaled nitric oxide (FENO) measurement. RESULTS 24-hour pH monitoring was positive for GERD in 92.1% of preselected children with asthma and 90.1% of children with chronic recurrent laryngitis. All flows (PEF, MEF75, MEF50, and MEF25) were significantly lower in the asthma group, while FENO and DLCO were significantly lower in the laryngitis group. A significant inverse relationship was found between DLCO and all reflux indexes in the laryngitis group. Each unit change of Johnson-DeMeester score and Boix-Ochoa score increased the odds for significantly lower DLCO in laryngitis patients by 3.9% and 5.5%, respectively. CONCLUSIONS In children with uncontrolled asthma and chronic laryngitis, the regurgitation of gastric contents due to GERD contributes to poor asthma control and aggravation of chronic laryngitis. Despite having normal lung function, the gas diffusion capacity should be controlled in patients with GERD and chronic laryngitis, and it might be the very first abnormality in distal airways.
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Affiliation(s)
- Mirjana Mirić
- Department for Anesthesiology, Reanimatology and Intensive Care Medicine, University Hospital Center Zagreb, Zagreb, Croatia
| | - Mirjana Turkalj
- Department of Pediatric Allergology and Pulmonology, Children's Hospital Srebrnjak, Reference Center for Clinical Immunology in Children Aappointed by the Ministry of Health and Social Welfare of the Republic of Croatia, Zagreb, Croatia
| | - Boro Nogalo
- Department of Pediatric Allergology and Pulmonology, Children's Hospital Srebrnjak, Reference Center for Clinical Immunology in Children Aappointed by the Ministry of Health and Social Welfare of the Republic of Croatia, Zagreb, Croatia
| | - Damir Erceg
- Department of Pediatric Allergology and Pulmonology, Children's Hospital Srebrnjak, Reference Center for Clinical Immunology in Children Aappointed by the Ministry of Health and Social Welfare of the Republic of Croatia, Zagreb, Croatia
| | - Marija Perica
- Department of Pediatric Allergology and Pulmonology, Children's Hospital Srebrnjak, Reference Center for Clinical Immunology in Children Aappointed by the Ministry of Health and Social Welfare of the Republic of Croatia, Zagreb, Croatia
| | - Davor Plavec
- Department of Pediatric Allergology and Pulmonology, Children's Hospital Srebrnjak, Reference Center for Clinical Immunology in Children Aappointed by the Ministry of Health and Social Welfare of the Republic of Croatia, Zagreb, Croatia
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Abstract
Asthma has many triggers including rhinosinusitis; allergy; irritants; medications (aspirin in aspirin-exacerbated respiratory disease); and obesity. Paradoxic vocal fold dysfunction mimics asthma and may be present along with asthma. This article reviews each of these triggers, outlining methods of recognizing the trigger and then its management. In many patients more than one trigger may be present. Full appreciation of the complexity of these relationships and targeted therapy to the trigger is needed to best care for the patient with asthma.
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Affiliation(s)
- Justin C. McCarty
- Lake Erie of Osteopathic Medicine, 5000 Lakewood Ranch Boulevard, Bradenton, FL 34211–4909, USA
| | - Berrylin J. Ferguson
- UPMC Mercy, University of Pittsburgh School of Medicine, 1400 Locust Street, Suite B11500, Pittsburgh, PA 15219, USA
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16
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Amarasiri DL, Pathmeswaran A, de Silva HJ, Ranasinha CD. Response of the airways and autonomic nervous system to acid perfusion of the esophagus in patients with asthma: a laboratory study. BMC Pulm Med 2013; 13:33. [PMID: 23724936 PMCID: PMC3682888 DOI: 10.1186/1471-2466-13-33] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2012] [Accepted: 05/29/2013] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Gastro-esophageal reflux disease (GERD) predisposes to airway disease through a vagally-mediated esophago-bronchial reflex. This study investigates this vagal response to esophageal acid perfusion. METHODS 40 asthmatics with mild stable asthma participated. Each subject underwent spirometry and autonomic function testing (valsalva maneuver, heart rate response to deep breathing and to standing from supine position) four times: a) before intubation, b) after intubation, and then immediately after perfusion with, in random order, c) concentrated lime juice solution (pH 2-3) and d) 0.9% saline. Subjects were blinded to the solution perfused. RESULTS Asthmatics were of mean (SD) age 34.3 years (1.3), and 67.5% of them were females. pH monitoring demonstrated that 20 subjects had abnormal reflux and 20 did not. In each group 10 subjects had a positive GERD symptom score. Following perfusion with acid compared to saline, all subjects showed significant decreases in FEV1 and PEFR and significant increases in the mean valsalva ratio and heart rate difference on deep breathing from baseline values, but no changes in FVC or heart rate ratio on standing. There were no significant differences in any of the parameters between subjects with and without reflux. CONCLUSIONS Acid stimulation of the distal esophagus results in increased parasympathetic activity and concomitant broncho-constriction in asthmatics irrespective of their reflux state. This strengthens the hypothesis that GER triggers asthma-like symptoms through a vagally mediated esophago-bronchial reflex and encourages a possible role for anti-cholinergic drugs in the treatment of reflux-associated asthma.
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17
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Aras G, Kanmaz D, Kadakal F, Purisa S, Sonmez K, Tuncay E, Ozdemir A. Gastroesophageal reflux disease in our asthma patients: the presence of dysphagia can influence pulmonary function. Multidiscip Respir Med 2012; 7:53. [PMID: 23244779 PMCID: PMC3558373 DOI: 10.1186/2049-6958-7-53] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2012] [Accepted: 11/30/2012] [Indexed: 12/21/2022] Open
Abstract
Background The prevalence of Gastroesophageal Reflux Disease (GERD) in Turkey is reported as 11.6%. Studies of pulmonary function in asthmatics have demonstrated a correlation between lung resistance and the occurrence of spontaneous gastroesophageal reflux. Few studies have included measures of lung diffusing capacity for carbon monoxide. The aim of this study is to assess whether asthma patients had worse lung function and gas diffusion according to diversity of GERD symptoms they concurrently experienced. The secondary aim of the study is to determine the frequency and different faces of GERD in our asthma patients compared to healthy controls. Methods Sixty consecutive asthma patients evaluatd at the pulmonary specialty outpatient clinic were included in the study. The control group included 60 healthy volunteers who had normal pulmonary function and routine laboratory tests. A modified version of a self-reported questionnaire developed by Locke and associates at the Mayo Clinic was conducted face-to-face with consecutive asthma patients and control subjects. Pulmonary function measurements were taken using spirometry. DLCO (mL/dk/mmHg) and DLCO/VA (DLCO adjusted according to alveolar volume) were measured using a single-breath technique. Statistical analyses were performed using the SPSS 17.0 statistical software. Results DLCO and DLCO/VA were significantly lower in asthma patients who had dysphagia symptoms. Frequent and significant acid regurgitations were seen in 28.33% (n = 17) of patients in the study group and 6.7% (n = 4) of patients in the control group. Severe, troublesome heartburn symptoms were reported by 28.2% (n = 17) of patients in the study group and 16.7% (n = 10) of subjects in the control group. Dysphagia was detected in 38.3% (n = 23) of all asthma cases and in 1.7% (n = 1) of the subjects in the control group. Conclusions There were many faces of gastroesophageal reflux disease in our asthmatic patients. Dysphagia was the only GERD symptom influencing on pulmonary function tests, while gastroesophageal reflux symptoms and nocturnal awakening attacks were common in this study.
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Affiliation(s)
- Gulfidan Aras
- Yedikule Chest Disease and Surgery Education and Research Hospital, Istanbul, Turkey.
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18
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Saber H, Ghanei M. Extra-esophageal manifestations of gastroesophageal reflux disease: controversies between epidemiology and clicnic. Open Respir Med J 2012; 6:121-6. [PMID: 23166570 PMCID: PMC3499735 DOI: 10.2174/1874306401206010121] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2012] [Revised: 10/04/2012] [Accepted: 10/04/2012] [Indexed: 12/14/2022] Open
Abstract
Gastroesophageal reflux disease (GERD) is widely associated with asthma, chronic cough, and laryngitis.
Many studies have focused on acidic reflux; however, acid is just one of many factors that can cause pulmonary injury.
The discrepancy between the high frequency of GERD in asthmatic patients and the ineffective reflux therapy outcomes
in these patients suggests that GERD may cause injury through other mechanisms, such as pepsinogen, pepsin, bile salts,
or other components of reflux materials, instead of the acid. Research using appropriate and innovative methodologies to
investigate these potential inflammatory agents in patients with GERD is required to determine the underlying factors
associated with pulmonary disorders in these patients.
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Affiliation(s)
- Hamid Saber
- Faculty of medicine, Mashhad University of Medical Sciences, Mashhad, Iran
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19
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Amarasiri DL, Pathmeswaran A, Dassanayake AS, de Silva AP, Ranasinha CD, de Silva HJ. Esophageal motility, vagal function and gastroesophageal reflux in a cohort of adult asthmatics. BMC Gastroenterol 2012; 12:140. [PMID: 23057471 PMCID: PMC3527260 DOI: 10.1186/1471-230x-12-140] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2011] [Accepted: 10/04/2012] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Asthmatics are known to have esophageal hypomotility. Vagal hypofunction and prolonged intra-esophageal acidification cause esophageal hypomotility. The contribution of gastroesophageal reflux (GER) and vagal function to esophageal motility in asthmatics is unclear. We studied the relationship between esophageal motility, GER and vagal function in a cohort of adult asthmatics. METHODS Thirty mild, stable asthmatics (ATS criteria) and 30 healthy volunteers underwent 24-hour ambulatory esophageal monitoring, manometry, autonomic function testing and GER symptom assessment. 27 asthmatics underwent gastroscopy. A vagal function score calculated from 3 tests (valsalva maneuver, heart rate response to deep breathing and to standing from supine position) was correlated with esophageal function parameters. RESULTS Asthmatics (mean age 34.8 (SD 8.4), 60% female) had more frequent GERD symptoms than controls (mean age 30.9 (SD 7.7), 50% female). 10/27 asthmatics had esophageal mucosal damage, 22 showed hypervagal response, none had a hyperadrenergic response. 14 asthmatics had ineffective esophageal motility. Higher GERD-score asthmatics had significantly fewer peristaltic and more simultaneous contractions than controls, and higher esophageal acid contact times than those with lower scores. All reflux parameters were significantly higher and acid clearance time prolonged in asthmatics than controls (p < 0.001, Mann-Whitney U test). There was no correlation between vagal function score and esophageal function parameters. CONCLUSIONS A cohort of adult asthmatics was found to have peristaltic dysfunction and pathological GER, but otherwise normal esophageal motility. The peristaltic dysfunction seems to be associated with vagal hyperreactivity rather than vagal hypofunction.
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Affiliation(s)
- D Lakmali Amarasiri
- Department of Physiology, Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka.
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20
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Abstract
Gastroesophageal reflux disease (GERD) may make asthma difficult to control and may be a potential risk factor for frequent asthma exacerbations, but the mechanisms of the relationship between GERD and not well-controlled asthma remain unclear. The aim of this study was to explore the association of GERD with asthma control in adults. Patients with asthma were consecutively recruited, and Asthma Control Test (ACT) and Reflux Diagnostic Questionnaire scores were determined. The patients were categorized into not well-controlled asthma and well-controlled asthma groups according to the ACT score. Univariate and multivariate logistic regression analyses were performed to evaluate the relationship between GERD and not well-controlled asthma. Seven hundred and sixty-eight patients with asthma were enrolled. The mean ACT score was 18.2 ± 3.6, and there were 161 (21.0%) patients with not well-controlled asthma. The Reflux Diagnostic Questionnaire score was 10.5 ± 4.7, and 212 (27.6%) patients were complicated by GERD. Multivariate logistic regression analyses revealed the independent association of GERD with not well-controlled asthma (odds ratio, 3.12; 95% confidence interval, 1.53-4.88) after other established contributors to asthma control were adjusted. In conclusion, there is an association of GERD with not well-controlled asthma, independent of other potential contributors to asthma control.
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Affiliation(s)
- B Liang
- Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
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Johannessen R, Petersen H, Olberg P, Johnsen G, Fjøsne U, Kleveland PM. Airway symptoms and sleeping difficulties in operated and non-operated patients with gastroesophageal reflux disease. Scand J Gastroenterol 2012; 47:762-9. [PMID: 22571295 DOI: 10.3109/00365521.2012.683041] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Anti-reflux treatment studies have not succeeded in proving a causal relationship between gastroesophageal reflux disease (GERD), airway symptoms and sleeping difficulties. In a recent follow-up study we showed that patients operated for GERD have significantly less heartburn/acid regurgitation symptoms than matched non-operated patients. These two groups probably had different degrees of reflux over a long period of time. It is thus hypothesized that operated patients would report less airway symptoms and sleeping difficulties than comparable non-operated patients. A new follow-up study of the same patients was therefore conducted. MATERIAL AND METHODS A total of 179 patients operated for GERD and 179 matched non-operated patients with confirmed GERD were sent the Reflux, Airway & Sleep Questionnaire (RASQ), which is a new, validated questionnaire dealing with heartburn/acid regurgitation, airway symptoms, and sleeping difficulties. Answers are given on a 7-point Likert scale and the assessment period is 1 year. RESULTS Response rates were 68% in both groups. Operated patients reported significantly less reflux symptoms than non-operated patients (p < 0.001). Patients in the surgery group also reported less symptoms in two subscales of the RASQ dealing with airway symptoms: Laryngopharyngitis (p = 0.04) and Bronchitis (p = 0.01). There was a tendency toward less sleeplessness in operated patients, but this was not statistically significant. Snoring was less bothersome in operated patients (p = 0.02). CONCLUSIONS Patients operated for GERD have less heartburn/acid regurgitation symptoms and less airway symptoms than non-operated patients. The findings lend support to the hypothesis of a causal relationship between gastroesophageal reflux, airway symptoms, and sleeping difficulties.
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Affiliation(s)
- Rune Johannessen
- Department of Cancer Research and Molecular Medicine, Unit for Gastroenterology, Norwegian University of Science and Technology, Trondheim, Norway.
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Yu H, Li Q, Zhou X, Kolosov VP, Perelman JM. Transient receptor potential vanilloid 1 receptors mediate acid-induced mucin secretion via Ca2+ influx in human airway epithelial cells. J Biochem Mol Toxicol 2012; 26:179-86. [PMID: 22566028 DOI: 10.1002/jbt.20413] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2011] [Revised: 08/09/2011] [Accepted: 08/20/2011] [Indexed: 12/20/2022]
Abstract
Mucin hypersecretion is a key pathological feature of inflammatory respiratory diseases. Previous studies have reported that acids (gastroesophageal reflux or environmental exposure) induce many respiratory symptoms and are implicated in the pathophysiology of obstructive airway diseases. To understand these mechanisms, we measured acid-induced mucin secretion in human bronchial epithelial cells. In the present study, acid induced inward currents of transient receptor potential vanilloid (TRPV)1 and mucin 5AC (MUC5AC) secretion dose dependently, which were inhibited by TRPV1 antagonist capsazepine in a concentration-dependent manner. TRPV1 agonist capsaicin mediated a concentration-dependent increase in TRPV1 inward currents and MUC5AC secretion. Furthermore, capsaicin enhanced acid-induced TRPV1 inward currents and MUC5AC secretion. Acid-induced Ca(2+) influx was prevented by capsazepine dose dependently and enhanced by capsaicin. Pretreatment only with capsaicin also increased the Ca(2+) concentration in a concentration-dependent manner. These data suggest that pharmacological inhibition of calcium-permeable TRPV1 receptors could be used to prevent acid-induced mucin secretion, thereby providing a potential mechanism to reduce their toxicity.
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Affiliation(s)
- Hongmei Yu
- Division of Respiratory Medicine, Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, People's Republic of China
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23
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Lee YB, Lim JH, Choi YJ, Kim JY, Son JH, Choi SM, Jo HJ, Shin CM, Lee SH, Park YS, Hwang JH, Kim JW, Jeong SH, Kim N, Lee DH, Jung HC, Song IS. [Effects of proton pump inhibitors in asthmatics with gastroesophageal reflux disease]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2012; 58:178-83. [PMID: 22042417 DOI: 10.4166/kjg.2011.58.4.178] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
BACKGROUND/AIMS Gastroesophageal reflux disease (GERD) is common in asthma patients. Proton pump inhibitor (PPI) therapy improves symptoms of asthma in some patients. The objective of this study was to investigate endoscopic findings of GERD in asthma patients and to assess the effect of gastric acid suppression with the PPIs on symptom improvement and pulmonary function. METHODS From 105 consecutive patients with GERD symptoms during follow up for asthma, 45 patients were enrolled. Patients enrolled to this study were asked about GERD symptoms before and after treating with PPI. Endoscopic findings were described according to Los Angeles classification. The improvement of asthma symptoms and follow-up pulmonary function test were investigated after administration of PPIs. RESULTS Esophageal symptoms such as heartburn and acid reflux were present in 25 patients (55.6%), and patients without esophageal symptoms were 20 (44.4%). The degree of endoscopic abnormality was not significantly different between groups with or without esophageal symptoms. The improvement of symptoms was seen in 44 patients (97.8%) except 1 patient after administration of PPIs. The number of patients classified to the low-dose group was 7 patients (15.6%) and that of patients classified to the standard-dose group was 38 patients (84.4%). The follow-up pulmonary function test, peak expiratory flow rate (L/sec) was improved in 3 patients (3 of 7, 42.9%) of the low-dose group, and in 24 patients (24 of 38, 63.2%) of the standard-dose group. The improvement of ventilatory function was not significantly different according to dose of PPIs. CONCLUSIONS Treatment with PPIs is expected to improve subjective symptoms and ventilatory function in asthma patients.
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Affiliation(s)
- Yun Bin Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
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Deeb AS, Al-Hakeem A, Dib GS. Gastroesophageal reflux in children with refractory asthma. Oman Med J 2011; 25:218-21. [PMID: 22043341 DOI: 10.5001/omj.2010.60] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2010] [Accepted: 03/04/2010] [Indexed: 11/03/2022] Open
Abstract
OBJECTIVES To investigate the association between clinical and macroscopic findings of GER and severity of refractory asthma (statistical study). METHODS A prospective study in a university-based practice of 75 children who were diagnosed with refractory asthma because they exhibited no satisfactory response for at least three months of treatment. Medical history, physical examination, spirometrical measurements and prick skin test were conducted on all patients. Endoscopic and macroscopic evaluations for esophagitis were performed on all patients regardless of the presence of GER symptoms. RESULTS Endoscopy was done for 75 children with refractory asthma. GER was symptomatic in 65% of all patients with no statistical significance (p>0.05) and the most frequent symptom was abdominal pain (67%). The frequency of these symptoms was 50% in mild asthma, 58% in moderate asthma and 72% in severe asthma with no statistical significance (p>0.05). The frequency of macroscopic esophagitis was 71%, distributed in three asthmatic groups as in order of 75% in mild asthma, 58.3% in moderate asthma and 76.6% in severe asthma (p>0.05). Regarding the relationship between GER and nocturnal attacks or spasmodic cough, the frequency of the latest was 66.7%. The differences have no statistical significance regarding GER symptoms (p>0.05), but they are statistically significant regarding the reflux esophagitis (p<0.05). Also endoscopic reflux was as frequent as76.3% in non allergic patients, and this result is statistically significant (p<0.05). CONCLUSION In spite of the fact that there was no relationship between the severity of asthma and the symptoms of GER, or its endoscopic findings, the frequency of GER in asthmatic children was higher than its frequency in other children.
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Affiliation(s)
- Alaa S Deeb
- Department of Pediatrics, Tishreen University, Syrian Arab Republic
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Shimizu Y, Dobashi K, Mori M. Exhaled breath marker in asthma patients with gastroesophageal reflux disease. J Clin Biochem Nutr 2011; 41:147-53. [PMID: 18299708 PMCID: PMC2243245 DOI: 10.3164/jcbn.2007020] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2007] [Accepted: 06/21/2007] [Indexed: 01/14/2023] Open
Abstract
Prevention of acid is important in gastroesophageal reflex disease (GERD)-related asthma therapy. Proton pump inhibitors (PPI) and H2-receptor blockers have been reported as useful therapies for improving asthma symptoms. GERD prevalence is high in asthma; however, methods for validating GERD existence based on questionnaire, endoscopic examination and 24h-pH monitoring do not directly determine GERD influence on the airway. Exhaled breath condensate analysis is a novel and non-invasive tool for assessing information directly from the airway. Breath collected by cooling can be applied to pH, 8-isoprostane and cytokine analysis in patients with GERD-related asthma, and the pH and 8-isoprostane levels have been shown to reflect the effects of PPI therapy in these patients. Although the analysis of cooled breath has not yet been established in a clinical setting, this method is expected to provide a novel tool for monitoring airway acidification associated with GERD.
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Affiliation(s)
- Yasuo Shimizu
- Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, 3-39-15 Showa-machi, Maebashi, Gunma 371-8511, Japan
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Zhu JC, Becerril G, Marasovic K, Ing AJ, Falk GL. Laparoscopic repair of large hiatal hernia: impact on dyspnoea. Surg Endosc 2011; 25:3620-6. [DOI: 10.1007/s00464-011-1768-0] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2010] [Accepted: 05/05/2011] [Indexed: 01/01/2023]
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Kwiecien J, Machura E, Halkiewicz F, Karpe J. Clinical features of asthma in children differ with regard to the intensity of distal gastroesophageal acid reflux. J Asthma 2011; 48:366-73. [PMID: 21385116 DOI: 10.3109/02770903.2011.561513] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
BACKGROUND The prevalence of gastroesophageal reflux (GER) in children with asthma is higher than in healthy controls, but the nature and direction of this association is unclear. OBJECTIVE The aim of our study was to assess the relationship between esophageal acid exposure and the clinical features of asthma in children. METHODS In total, 66 children (mean age 122.8 months [SD 44.89 months]) with chronic pulmonary symptoms, fulfilling diagnostic criteria of persistent asthma, underwent 24-hour esophageal pH monitoring and answered a detailed questionnaire-based survey. The questionnaire topics included environmental factors, familial history, current and previous clinical symptoms, atopy, asthma severity, and medication. RESULTS Abnormal results of 24-hour esophageal pH monitoring were found in 28 out of 66 children (42.4%). Age, sex, severity of asthma, environmental factors, spirometry results, and the type of medication did not correlate with esophageal acid exposure. However, children with abnormal pH results developed asthma significantly earlier (asthma onset 3.63 years [SD 2.52 years] vs 5.77 years [SD 3.82 years]; p < .01). Nonatopic individuals had more intensive esophageal acid exposure than atopic ones (Boix-Ochoa score 28.19 [SD 18.26] vs 18.26 [SD 12.84]; p < .048). The intensity of GER was also significantly correlated with frequent or difficult-to-control nighttime asthma attacks. CONCLUSIONS There are differences in clinical features of asthma in children with regard to the intensity of esophageal acid exposure. Symptoms of asthma in nonatopic individuals with early onset and difficult-to-control nighttime asthma attacks suggest the possibility of concomitant, clinically relevant GER.
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Affiliation(s)
- Jaroslaw Kwiecien
- Department of Pediatrics, Medical University of Silesia, Zabrze, Poland.
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BPCO e malattie dell’apparato digerente. ITALIAN JOURNAL OF MEDICINE 2011. [DOI: 10.1016/j.itjm.2011.01.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
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Kunsch S, Gross V, Neesse A, Sohrabi K, Nell C, Gress TM, Ellenrieder V, Koehler U. Combined lung-sound and reflux-monitoring: a pilot study of a novel approach to detect nocturnal respiratory symptoms in gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2011; 33:592-600. [PMID: 21204887 DOI: 10.1111/j.1365-2036.2010.04559.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Increased prevalence of respiratory symptoms has been commonly reported in patients with gastro-oesophageal reflux disease (GERD). AIM To introduce a novel Lung-Sound-Monitoring device that allows simultaneous measurement of both nocturnal respiratory symptoms and episodes of acidic and biliary refluxes. METHODS Nocturnal respiratory symptoms (coughing and wheezing) were continuously recorded in 20 healthy subjects and 30 reflux patients with respiratory symptoms in parallel to combined pH-monitoring and Bilitec measurement. RESULTS Analysis could be completed in 20 healthy subjects and in 25 patients with reflux. A clear temporal correlation to reflux phases was detected in 49% of coughing and 41% of wheezing events, respectively. Moreover, 89% of the coughing and 100% of the wheezing events succeeded reflux episodes. Finally, the technique was capable of assessing a statistically significant difference between patients and controls regarding the occurrence of these symptoms. CONCLUSIONS Our pilot study establishes the Lung-Sound-Monitoring system as a unique tool to measure objectively the temporal correlation between gastroesophageal reflux and the appearance of respiratory symptoms. It represents a useful technique to identify patients with respiratory symptoms due to reflux, and therefore allows one to determine and quantify the impact of therapeutic interventions such as antireflux therapy on respiratory symptoms.
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Affiliation(s)
- S Kunsch
- Department of Gastroenterology, Endocrinology and Metabolism, Philipps-University of Marburg, Germany
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Aras G, Yelken K, Kanmaz D, Develioglu O, Mavis O, Gultekin E, Igdem AA, Purisa S. Erosive esophagitis worsens reflux signs and symptoms in asthma patients without affecting pulmonary function tests. J Asthma 2010; 47:1101-5. [PMID: 21039214 DOI: 10.3109/02770903.2010.519077] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVES To determine whether erosive esophagitis (EO) worsens reflux signs and symptoms and affects pulmonary function test in asthma patients. METHODS Sixty asthma patients with gastroesophageal and laryngopharyngeal reflux symptoms were included. Spirometry, reversibility test, esophagogastroscopy, laryngoscopy, and esophagogastroscopic biopsies were conducted. RESULTS EO was diagnosed in 25% (n = 15) of the patients. The remaining 45 patients were placed into the non-erosive esophagitis (NEO) group. Of the 15 EO patients, grade 1 esophagitis was identified in 75% (n = 9), grade 2 in 12.5% (n = 3), and grade 3 in 12.5% (n = 3). Pulmonary function test results were not significantly different between the EO and NEO groups. Gastroesophageal and laryngopharyngeal reflux symptoms such as regurgitation, dysphagia, dyspnea, globus sensation, dysphonia, and sore throat were more frequent in EO patients than in the NEO group. The reflux finding score (RFS) was 7.33 and 4.55 in EO and NEO patients, respectively (p < .001). Posterior commissure hypertrophy was the most common laryngoscopic finding in both of the groups followed by diffuse laryngeal edema, erythema, and pseudosulcus. CONCLUSIONS Gastroesophageal and laryngopharyngeal reflux symptoms were more frequent in EO patients than in the NEO group. The laryngoscopic findings of laryngopharyngeal reflux were more severe and the RFS was significantly higher in EO patients than in NEO patients. The presence of EO seems to be associated with an increase in reflux without affecting pulmonary function as EO did not cause a significant decrease in pulmonary function tests.
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Affiliation(s)
- Gulfidan Aras
- Department of Otolaryngology, Medicine Faculty, Gazioamanpasa Universitesi Tip Fakultesi KBB ABD., Tokat, Turkey
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McCallister JW, Parsons JP, Mastronarde JG. The relationship between gastroesophageal reflux and asthma: an update. Ther Adv Respir Dis 2010; 5:143-50. [PMID: 20926507 DOI: 10.1177/1753465810384606] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Asthma and gastroesophageal reflux disease (GERD) are both common conditions and, hence, they often coexist. However, asthmatics have been found to have a much greater prevalence of GERD symptoms than the general population. There remains debate regarding the underlying physiologic mechanism(s) of this relationship and whether treatment of GERD actually translates into improved asthma outcomes. Based on smaller trials with somewhat conflicting results regarding improved asthma control with treatment of GERD, current guidelines recommend a trial of GERD treatment for symptomatic asthmatics even without symptoms of GERD. However, recently a large multicenter trial demonstrated that the treatment of asymptomatic GERD with proton-pump inhibitors did not improve asthma control in terms of pulmonary function, rate of asthma exacerbations, asthma-related quality of life, or asthma symptom frequency. These data suggest empiric treatment of asymptomatic GERD in asthmatics is not a useful practice. This review article provides an overview of the epidemiology and pathophysiologic relationships between asthma and GERD as well as a summary of current data regarding links between treatment of GERD with asthma outcomes.
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Affiliation(s)
- Jennifer W McCallister
- The Ohio State University Medical Center, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Columbus, Ohio 43210, USA
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Khoshoo V, Mohnot S, Haydel R, Saturno E, Edell D, Kobernick A. Bronchial hyperreactivity in non-atopic children with asthma and reflux: effect of anti-reflux treatment. Pediatr Pulmonol 2009; 44:1070-4. [PMID: 19830719 DOI: 10.1002/ppul.21094] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
INTRODUCTION The prevalence of bronchial hyperreactivity (BHR) or the effect of anti-reflux treatment on BHR in children with asthma and gastroesophageal reflux disease (GERD) is not known. METHODS Thirty non-atopic children with persistent asthma were studied. Extended esophageal pH monitoring was used to diagnose GERD and methacholine challenge test (MCT) was used as a marker of BHR and performed before and 2 years after anti-GERD treatment. RESULTS Of the 21 patients positive for GERD (group A), 15 had positive MCT suggesting BHR. Of the 9 patients negative for GERD (group B), 5 had positive MCT. On repeat testing 2 years later, 11/15 group A patients and 3/5 group B patients tested negative for BHR. Group A patients were receiving fewer asthma medications and experienced fewer exacerbations than Group B patients. CONCLUSIONS BHR is prevalent in children with asthma and GERD and improves with anti-GERD treatment.
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Allen GB, Leclair TR, von Reyn J, Larrabee YC, Cloutier ME, Irvin CG, Bates JHT. Acid aspiration-induced airways hyperresponsiveness in mice. J Appl Physiol (1985) 2009; 107:1763-70. [PMID: 19797689 DOI: 10.1152/japplphysiol.00572.2009] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The role of gastroesophageal reflux and micro-aspiration as a trigger of airways hyperresponsiveness (AHR) in patients with asthma is controversial. The role of acid reflux and aspiration as a direct cause of AHR in normal subjects is also unclear. We speculated that aspiration of a weak acid with a pH (1.8) equivalent to the upper range of typical gastric contents would lead to AHR in naive mice. We further speculated that modest reductions in aspirate acidity to a level expected during gastric acid suppression therapy (pH 4.0) would impede aspiration-induced AHR. BALB/c female mice were briefly anesthetized with isoflurane and allowed to aspirate 75 microl of saline with HCl (pH 1.8, 4.0, or 7.4) or underwent sham aspiration. Mice were re-anesthetized 2 or 24 h later, underwent tracheostomy, and were coupled to a mechanical ventilator. Forced oscillations were used to periodically measure respiratory impedance (Zrs) following aerosol delivery of saline and increasing doses of methacholine to measure for AHR. Values for elastance (H), airways resistance (R(N)), and tissue damping (G) were derived from Zrs. Aspirate pH of 1.8 led to a significant overall increase in peak R(N), G, and H compared with pH 4.0 and 7.4 at 2 and 24 h. Differences between pH 7.4 and 4.0 were not significant. In mice aspirating pH 1.8 compared with controls, airway lavage fluid contained more neutrophils, higher protein, and demonstrated higher permeability. We conclude that acid aspiration triggers an acute AHR, driven principally by breakdown of epithelial barrier integrity within the airways.
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Affiliation(s)
- Gilman B Allen
- Department of Medicine, Vermont Lung Center, University of Vermont, Burlington, Vermont, USA.
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DiMango E, Holbrook JT, Simpson E, Reibman J, Richter J, Narula S, Prusakowski N, Mastronarde JG, Wise RA. Effects of asymptomatic proximal and distal gastroesophageal reflux on asthma severity. Am J Respir Crit Care Med 2009; 180:809-16. [PMID: 19661245 DOI: 10.1164/rccm.200904-0625oc] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
RATIONALE Silent gastroesophageal reflux (GER) is common in patients with asthma, but it is unclear whether GER is associated with worse asthma symptoms or reduced lung function. OBJECTIVES To determine in patients with poorly controlled asthma, whether proximal or distal esophageal reflux is associated with asthma severity, symptoms, physiology, or functional status. METHODS Baseline asthma characteristics were measured in patients with asthma enrolled in a multicenter trial assessing the effectiveness of esomeprazole on asthma control. All participants underwent 24-hour esophageal pH probe monitoring. Lung function, methacholine responsiveness, asthma symptoms, and quality-of-life scores were compared in subjects with and without GER. MEASUREMENTS AND MAIN RESULTS Of 304 participants with probe recordings, 53% had reflux. Of 242 participants with recordings of proximal pH, 38% had proximal reflux. There was no difference in need for short-acting bronchodilators, nocturnal awakenings, dose of inhaled corticosteroid, use of long-acting beta-agonists, lung function, or methacholine reactivity between individuals with and without proximal or distal GER. Participants with GER reported more use of oral corticosteroids and had worse asthma quality of life and subjects with proximal GER had significantly worse asthma quality of life and health-related quality of life compared with participants without GER. CONCLUSIONS Asymptomatic GER is not associated with distinguishing asthma symptoms or lower lung function in individuals with suboptimal asthma control who are using inhaled corticosteroids. Patients with proximal reflux report significantly worse asthma and health-related quality of life despite lack of physiologic impairment or increase in asthma symptoms. Clinical trial registered with www.clinicaltrials.gov (NCT00069823).
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Affiliation(s)
- Emily DiMango
- Columbia University, College of Physicians and Surgeons, New York, New York, USA.
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Dal Negro RW, Tognella S, Micheletto C, Sandri M, Guerriero M. A MCh test pre-post esophageal acidification in detecting GER-related asthma. J Asthma 2009; 46:351-5. [PMID: 19484668 DOI: 10.1080/02770900802712955] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
The direct effect of gastro-esophageal reflux (GER) on lung function is still debated. Objective. To investigate the role of esophageal acidification in affecting airway response to MCh in GER-related versus atopic asthmatics and to assess specificity and sensitivity of events. Subjects. A total of 56 never-smoking, mild asthmatics: 27 non-atopic asthmatics and acid GER (GER+ve) and 29 atopic asthmatics without any GER (GER-ve). Methods. Each subject performed an MCh challenge in baseline (MCh(b)), and 30 minutes after an acid drink (125 mL at pH = 2; MCh(ac)), one day apart. PD(20)FEV(1) MCh(b) and MCh(ac) were compared by estimating the area under the ROC curve (AU-ROC). Results. GER+ve and GER-ve subjects (well matched in baseline) had a different duration of esophageal acid contact (24-hour monitoring; pH-24h AU(4)), and PD(20)FEV(1) MCh(ac) (both p < 0.001). AU-ROC was 86.3% (76% to 97%, 95%CI). Sensitivity and specificity of changes were 82.8% (72.9% to 92.7%, 95%CI) and 85.2% (75.9% to 94.5%, 95%CI), respectively. The difference in MCh threshold that maximized both the sensitivity and specificity level was 100 mu g. Conclusions. The esophageal acidification identified GER-related asthma with a good level of both sensitivity and specificity by enhancing the MCh response only in the presence of acid GER. Data are supporting the effectiveness of this procedure for clinical purposes.
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American Lung Association Asthma Clinical Research Centers, Mastronarde JG, Anthonisen NR, Castro M, Holbrook JT, Leone FT, Teague WG, Wise RA. Efficacy of esomeprazole for treatment of poorly controlled asthma. N Engl J Med 2009; 360:1487-99. [PMID: 19357404 PMCID: PMC2974569 DOI: 10.1056/nejmoa0806290] [Citation(s) in RCA: 244] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Collaborators] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
BACKGROUND Gastroesophageal reflux is common among patients with asthma but often causes mild or no symptoms. It is not known whether treatment of gastroesophageal reflux with proton-pump inhibitors in patients who have poorly controlled asthma without symptoms of gastroesophageal reflux can substantially improve asthma control. METHODS In a parallel-group, double-blind trial, we randomly assigned 412 participants with inadequately controlled asthma, despite treatment with inhaled corticosteroids, and with minimal or no symptoms of gastroesophageal reflux to receive either 40 mg of esomeprazole twice a day or matching placebo. Participants were followed for 24 weeks with the use of daily asthma diaries, spirometry performed once every 4 weeks, and questionnaires that asked about asthma symptoms. We used ambulatory pH monitoring to ascertain the presence or absence of gastroesophageal reflux in the participants. The primary outcome was the rate of episodes of poor asthma control, as assessed on the basis of entries in asthma diaries. RESULTS Episodes of poor asthma control occurred with similar frequency in the placebo and esomeprazole groups (2.3 and 2.5 events per person-year, respectively; P=0.66). There was no treatment effect with respect to individual components of the episodes of poor asthma control or with respect to secondary outcomes, including pulmonary function, airway reactivity, asthma control, symptom scores, nocturnal awakening, or quality of life. The presence of gastroesophageal reflux, which was documented by pH monitoring in 40% of participants with minimal or no symptoms, did not identify a subgroup of patients that benefited from treatment with proton-pump inhibitors. There were fewer serious adverse events among patients receiving esomeprazole than among those receiving placebo (11 vs. 17). CONCLUSIONS Despite a high prevalence of asymptomatic gastroesophageal reflux among patients with poorly controlled asthma, treatment with proton-pump inhibitors does not improve asthma control. Asymptomatic gastroesophageal reflux is not a likely cause of poorly controlled asthma. (ClinicalTrials.gov number, NCT00069823.)
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Affiliation(s)
| | | | | | - Mario Castro
- Washington University School of Medicine, St. Louis, MO
| | - Janet T. Holbrook
- The Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD
| | - Frank T. Leone
- The University of Pennsylvania School of Medicine, Philadelphia, PA
| | | | - Robert A. Wise
- Johns Hopkins University School of Medicine, Baltimore, MD
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Collaborators
N A Hanania, M Sockrider, L Giraldo, R Valdez, E Flores, J Reibman, E DiMango, L Rogers, C Cammarata, K Carapetyan, J Sormillon, E Simpson, L Williams, J Sundy, G Dudek, R Newton, A Dugdale, W G Teague, A Fitzpatrick, S Khatri, R Patel, J Peabody, E Hunter, D Whitlock, L Smith, J Moy, E Naureckas, C S Olopade, J Hixon, A Brees, G Rivera, S Sietsema, V Zagaja, M Busk, C Williams, P Puntenney, N Busk, F Leone, M Hayes-Hampton, W R Summer, G Meyaski, S Wenzel, R Katial, L Lopez, J Lima, K Blake, A Santos, K Vega, L Lambiase, T Langford, D Schaeffer, J Lang, M McRae, J Karpel, R Cohen, R Ramdeo, C G Irvin, A E Dixon, D A Kaminsky, R Colletti, S M Burns, L M Bourassa, S E Lang, L V Griffes, R Pratt, K B Nakos, K J Girard, J Mastronarde, K McCoy, J Parsons, J Drake, R Compton, L Raterman, D Cosmar, L B Gerald, W C Bailey, S Erwin, A Kelley, D Laken, A Wanner, R Lockey, E Mendes, S McCullough, B Fimbel, M Grandstaff, M N Blumenthal, G Brottman, J Hagen, A Decker, D Lascewski, S Kelleher, K Bachman, C Quintard, C Sherry, G Salzman, D Pyszczynski, P Haney, M Castro, L Bacharier, K Sumino, M E Scheipeter, J Tarsi, S Wasserman, J Ramsdell, J Vitin, T Tucker, N Anthonisen, R Wise, J Holbrook, E Brown, D Amend-Libercci, K Barry, M Daniel, A Lears, G Leatherman, C Levine, R Masih, S Modak, D Nowakowski, N Prusakowski, D Shade, C Shiflett, E Sugar, J Richter, N Anthonisen, E Lancet, A Santos, V Taggart, N Edelman, R Wise, J Holbrook, N Hanania, L Williams, G Teague, L Smith, M Busk, F Leone, J Karpel, W Summer, M Blumenthal, J Lima, R Katial, C Irvin, J Reibman, A Dozor, J Mastronarde, M Castro, L Gerald, G Salzman, A Wanner, S Wasserman, S Lazarus, W Calhoun, P Kahrilas, B McWilliams, A Rogatko, C Sorkness, E Lancet, R Vento, N Edelman, S Rappaport, G Pezza, V Taggart, G Weinmann, G Snider, N Anthonisen, M Castro, J Fish, D Ingbar, S Jenkinson, D Mannino, H Perlstadt, L Rosenwasser, J Samet, D Schraufnagel, J Smith, L Smith, T Standiford, A Wanner, T Weaver,
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Peterson KA, Samuelson WM, Ryujin DT, Young DC, Thomas KL, Hilden K, Fang JC. The role of gastroesophageal reflux in exercise-triggered asthma: a randomized controlled trial. Dig Dis Sci 2009; 54:564-71. [PMID: 18688720 DOI: 10.1007/s10620-008-0396-6] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2008] [Accepted: 06/18/2008] [Indexed: 12/12/2022]
Abstract
BACKGROUND Exercise-triggered asthma (ETA) develops when physical activity triggers asthma symptoms during or directly after exercise. In patients prone to symptoms of supra-esophageal reflux, exercise may trigger gastroesophageal reflux (GER), resulting in such symptoms. AIMS To determine the prevalence of abnormal pH in patients with ETA and to determine whether acid suppression improves symptoms in ETA patients. METHODS We performed a randomized double-blind trial of rabeprazole versus placebo in the treatment of patients with ETA. Patients underwent treadmill protocol to determine their VO(2 max). Next, pH testing was initiated while undergoing a 30-min treadmill program exercising them at 65% of their VO(2 max). They were subsequently randomized to rabeprazole or placebo for 10 weeks. At the end of 10 weeks, exercise testing was repeated. RESULTS A total of 31 patients completed the study (20 asthmatics, 11 non-asthmatics). Twenty-two out of 30 (73%) subjects had abnormal pH studies. For all subjects, rabeprazole improved symptoms more than placebo (P = 0.03). The association was stronger in the pH-positive group (P = 0.009). CONCLUSION Acid reflux is common in ETA patients. Many patients with exercise-related respiratory symptoms are misdiagnosed as chronic asthmatics. Exercise-related symptoms improve with the use of acid suppression. This study suggests that ETA patients may benefit from acid suppression.
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Affiliation(s)
- Kathryn A Peterson
- Division of Gastroenterology, University of Utah Health Sciences Center, Salt Lake City, UT 84132, USA.
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Cheung TK, Lam B, Lam KF, Ip M, Ng C, Kung R, Wong BCY. Gastroesophageal reflux disease is associated with poor asthma control, quality of life, and psychological status in Chinese asthma patients. Chest 2008; 135:1181-1185. [PMID: 19118263 DOI: 10.1378/chest.08-1702] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022] Open
Abstract
BACKGROUND Both asthma and gastroesophageal reflux disease (GERD) are common, often coexist, and have significant impact on a patient's quality of life. Our aim was to determine the prevalence of GERD in asthmatic patients at a major hospital in Hong Kong, and to examine the impact of GERD and its association with asthma control. METHODS Patients with asthma who attended the respiratory clinic at Queen Mary Hospital, Hong Kong, were recruited. Demographic data were collected, and a validated Chinese GERD questionnaire was used. The Medical Outcomes Study 36-item short form (SF-36) was used to assess quality of life, and the Hospital Anxiety and Depression Scale (HADS) was used to assess psychological status. Asthma control was assessed by the asthma control test. RESULTS A total of 218 patients were recruited; 40.4% of asthmatic patients (88 patients) had GERD, as defined by the GERD questionnaire. Compared with those patients without GERD, those with GERD had significantly worse asthma control (p = 0.022), worse quality of life in all domains of the SF-36 (all p < 0.01), and more anxiety (6.82 vs 4.90, respectively; p < 0.001) and depression (6.09 vs 4.05, respectively; p < 0.001) as reflected by HADSs. CONCLUSIONS A significant proportion of asthmatic patients in Hong Kong have GERD, and this is associated with poorer asthmatic control, quality of life, and psychological status.
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Affiliation(s)
- Ting Kin Cheung
- Department of Medicine, University of Hong Kong, Hong Kong, People's Republic of China
| | - Bing Lam
- Department of Medicine, University of Hong Kong, Hong Kong, People's Republic of China; Department of Statistics and Actuarial Science, University of Hong Kong, Hong Kong, People's Republic of China
| | - Kam Fai Lam
- Department of Medicine, University of Hong Kong, Hong Kong, People's Republic of China
| | - Mary Ip
- Department of Medicine, University of Hong Kong, Hong Kong, People's Republic of China
| | - Connie Ng
- Department of Medicine, University of Hong Kong, Hong Kong, People's Republic of China
| | - Roger Kung
- Department of Medicine, University of Hong Kong, Hong Kong, People's Republic of China
| | - Benjamin C Y Wong
- Department of Medicine, University of Hong Kong, Hong Kong, People's Republic of China.
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Fernández R, Galera A, Casal J, Rodríguez-Cintrón W. An uncommon cause of uncontrolled asthma: case report. J Asthma 2008; 45:766-9. [PMID: 18972292 DOI: 10.1080/02770900802252101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Bronchial asthma is one of the most common chronic conditions seen by any health care professional. Multiple stimuli may lead to acute airway hyperresponsiveness and an exacerbation of the disease, gastroesophageal reflux disease being one of them. We report the case of an elderly patient with chronic gastroesophageal reflux disease who secondarily developed a tracheoesophageal fistula, resulting in recurrent exacerbations of previously well-controlled asthma. After endoscopic correction of the fistula, the patient's respiratory disease improved dramatically, with essentially no exacerbations requiring urgent care or hospitalization.
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Affiliation(s)
- Ricardo Fernández
- Fellowship Training Program, San Juan City Hospital, San Juan, Puerto Rico
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Abstract
BACKGROUND A methacholine challenge may be used in confirming the diagnosis of asthma, occupational asthma, or reactive airways dysfunction syndrome (RADS) through identification of bronchial hyperreactivity (BHR). While sensitivity of the test in diagnosing clinically significant asthma is excellent, specificity of the test is poor. Since there are many conditions which have been associated with BHR, a positive test must be interpreted cautiously. METHODS This paper reviews potential causes of a positive methacholine challenge other than asthma or RADS which have been reported in the medical literature. RESULTS Factors which may be associated with a positive methacholine test include test methodology, normal variation of BHR in the general population, and numerous medical conditions. CONCLUSIONS In cases of inhalation exposure evaluations, alternative explanations must be considered when determining whether a causal association exists between the exposure and a positive methacholine test result.
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Affiliation(s)
- David J Hewitt
- Center for Toxicology and Environmental Health, LLC, North Little Rock, Arkansas.
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42
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Galmiche JP, Zerbib F, Bruley des Varannes S. Review article: respiratory manifestations of gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2008; 27:449-64. [PMID: 18194498 DOI: 10.1111/j.1365-2036.2008.03611.x] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Respiratory manifestations represent one of the most prevalent and difficult-to-manage extra-oesophageal syndromes of gastro-oesophageal reflux disease. AIMS To review the epidemiology, pathophysiological mechanisms and therapeutic outcomes of reflux-related respiratory disorders. METHODS Search of the literature published in English using PubMed database. RESULTS There is a discrepancy between the high prevalence of reflux in asthmatics and the limited efficacy of antireflux therapies. Asthma per se may cause reflux. Patients with difficult-to-treat asthma and/or nocturnal symptoms should be screened for reflux. Reflux can induce chronic cough through different mechanisms including micro-aspiration and both local and central reflexes. Cough and reflux may precipitate each other. A meta-analysis found no significant difference between placebo and proton pump inhibitors in the resolution of cough. Encouraging results have been reported, following antireflux surgery in patients selected on the basis of pH-impedance monitoring. Attention has been drawn to obstructive sleep apnoea syndrome. CONCLUSIONS The role of gastro-oesophageal reflux disease in the pathogenesis of miscellaneous respiratory disorders has been discussed for decades and established in asthma and cough. However, no major therapeutic advances have been reported recently. Future trials should concentrate on patient selection and the control of efficacy using recently developed technologies, such as pH-impedance monitoring.
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Affiliation(s)
- J P Galmiche
- CHU Nantes, Service Hépato-Gastroentérologie, Institut des Maladies de l'Appareil Digestif and Institut National de Santé et de Recherche Médicale, Nantes, France.
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43
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Araujo ACS, Aprile LRO, Dantas RO, Terra-Filho J, Vianna EO. Bronchial responsiveness during esophageal acid infusion. Lung 2008; 186:123-8. [PMID: 18297339 DOI: 10.1007/s00408-008-9072-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2007] [Accepted: 01/16/2008] [Indexed: 11/25/2022]
Abstract
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 FEV(1), 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 FEV(1) (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.
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Affiliation(s)
- Ana Carla S Araujo
- Pulmonary Division, Department of Medicine, University of São Paulo Medical School at Ribeirão Preto, Ribeirão Preto, SP 14048-900, Brazil
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44
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Nordenstedt H, Lagergren J. Environmental factors in the etiology of gastroesophageal reflux disease. Expert Rev Gastroenterol Hepatol 2008; 2:93-103. [PMID: 19072373 DOI: 10.1586/17474124.2.1.93] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Gastroesophageal reflux disease (GERD) is currently one of the most common health problems in the Western world, affecting up to 20% of the adult population weekly and 50% monthly. It generates substantial suffering among patients as well as significant costs to both patients and society in general. GERD can further result in serious complications such as esophageal strictures, Barrett's esophagus and esophageal adenocarcinoma. This review discusses the current knowledge on risk factors and potential protective factors in the development of GERD.
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Affiliation(s)
- Helena Nordenstedt
- Unit of Esophageal and Gastric Research, Department of Molecular Medicine and Surgery, P9:03, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
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45
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Long MD, Shaheen NJ. Extra-esophageal GERD: clinical dilemma of epidemiology versus clinical practice. Curr Gastroenterol Rep 2007; 9:195-202. [PMID: 17511916 DOI: 10.1007/s11894-007-0018-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/15/2023]
Abstract
Gastroesophageal reflux disease (GERD) is a common disorder. A significant percentage of patients with GERD may experience extra-esophageal manifestations, such as asthma, cough, and laryngitis. Epidemiologic studies consistently demonstrate strong associations between GERD and potential extra-esophageal manifestations. However, randomized controlled studies evaluating the use of proton-pump inhibitors for treatment of extra-esophageal GERD have inconsistent results. In asthma, few randomized controlled studies have shown improvement in objective measures, such as forced expiratory volume or peak flow. For chronic cough, studies are all small and have not demonstrated consistent improvement with acid suppression. Even a recent well-designed large randomized controlled study in laryngitis demonstrated no difference in resolution of symptoms with acid suppression. Given the examples from the literature, the current treatment of extra-esophageal symptoms with acid suppression is controversial. Although improvement in symptoms has been shown in case series, it has not been consistent in randomized controlled studies. We offer potential explanations for the discrepancy between the epidemiologic associations and the lack of response to therapy in clinical trials.
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Affiliation(s)
- Millie D Long
- Center for Esophageal Diseases and Swallowing, University of North Carolina-Chapel Hill, Campus Box 7080, Chapel Hill, NC 27599-7080, USA
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Sharma B, Sharma M, Daga MK, Sachdev GK, Bondi E. Effect of omeprazole and domperidone on adult asthmatics with gastroesophageal reflux. World J Gastroenterol 2007; 13:1706-10. [PMID: 17461474 PMCID: PMC4146950 DOI: 10.3748/wjg.v13.i11.1706] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To study the effect of combined omeprazole (Ome) and domperidone (Dom) therapy on asthma symptoms and pulmonary function in asthmatics with gastroesophageal reflux.
METHODS: We selected 198 asthmatics with gastroesophageal reflux diagnosed by 24-h esophageal pH monitoring to receive Ome 20 mg twice daily and Dom 10 mg three times daily or placebo for 16 wk (1:1 double-blind randomization). Spirometry was done at baseline and after 16 wk of treatment. The primary outcome measures were: mean daily daytime and nighttime asthma symptom scores. Mean daily reflux symptom scores, albuterol use as rescue medication (number of puffs), daytime and nighttime peak expiratory flow rate (PEFR), postbronchodilator forced expiratory volume in 1 second (FEV1) and postbronchodilator forced vital capacity (FVC) were secondary outcome measures.
RESULTS: Comparison of mean change from baseline between antireflux therapy and placebo groups revealed significant reduction in daytime asthma symptom score (17.4% vs 8.9%), nighttime asthma symptom score (19.6% vs 5.4%), reflux symptom score (8.7% vs 1.6%) and rescue medication use (23.2% vs 3.1%) after antireflux therapy compared to mean change in placebo group (P < 0.001). There was significant improvement in morning PEFR (7.9% vs 0.2%), evening PEFR (9.8% vs 0.5%), FEV1 (11.1% vs 3.78%) and FVC (9.3% vs 1.52%) in the antireflux therapy group compared to placebo on comparing the mean change from baseline after 16 wk (P < 0.01).
CONCLUSION: Combined therapy with Ome and Dom in adult asthmatics with gastroesophageal reflux may be beneficial by reducing asthma symptoms, rescuing medication use, and improving pulmonary function.
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Affiliation(s)
- Bhavneesh Sharma
- Brookdale University Hospital and Medical Center, Division of Pulmonary and Critical Care Medicine, State University of New York, Brooklyn, New York 11212, USA.
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Ferrari M, Benini L, Brotto E, Locatelli F, De Iorio F, Bonella F, Tacchella N, Corradini G, Lo Cascio V, Vantini I. Omeprazole reduces the response to capsaicin but not to methacholine in asthmatic patients with proximal reflux. Scand J Gastroenterol 2007; 42:299-307. [PMID: 17354108 DOI: 10.1080/00365520600883777] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
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.
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Affiliation(s)
- Marcello Ferrari
- Dipartimento di Scienze Biomediche e Chirurgiche, Università di Verona, Italy.
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48
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Patterson RN, Johnston BT, Ardill JES, Heaney LG, McGarvey LPA. Increased tachykinin levels in induced sputum from asthmatic and cough patients with acid reflux. Thorax 2007; 62:491-5. [PMID: 17251314 PMCID: PMC2117233 DOI: 10.1136/thx.2006.063982] [Citation(s) in RCA: 76] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Acid reflux may aggravate airway disease including asthma and chronic cough. One postulated mechanism concerns a vagally-mediated oesophageal-tracheobronchial reflex with airway sensory nerve activation and tachykinin release. AIM To test the hypothesis that patients with airways disease and reflux have higher airway tachykinin levels than those without reflux. METHODS Thirty-two patients with airways disease (16 with mild asthma and 16 non-asthmatic subjects with chronic cough) underwent 24 h oesophageal pH monitoring. Acid reflux was defined as increased total oesophageal acid exposure (% total time pH<4 of >4.9% at the distal probe). All subjects underwent sputum induction. Differential cell counts and concentrations of substance P (SP), neurokinin A (NKA), albumin and alpha2-macroglobulin were determined. RESULTS SP and NKA levels were significantly higher in patients with reflux than in those without (SP: 1434 (680) pg/ml vs 906 (593) pg/ml, p=0.026; NKA: 81 (33) pg/ml vs 52 (36) pg/ml, p=0.03). Significantly higher tachykinin levels were also found in asthmatic patients with reflux than in asthmatic patients without reflux (SP: 1508 (781) pg/ml vs 737 (512) pg/ml, p=0.035; NKA: median (interquartile range 108 (85-120) pg/ml vs 75 (2-98) pg/ml, p=0.02). In patients with asthma there was a significant positive correlation between distal oesophageal acid exposure and SP levels (r=0.59, p=0.01) and NKA levels (r=0.56, p=0.02). Non-significant increases in SP and NKA were measured in patients with cough with reflux (SP: 1534.71 (711) pg/ml vs 1089 (606) pg/ml, p=0.20; NKA: 56 (43) pg/ml vs 49 (17) pg/ml, p=0.71). No significant difference in differential cell counts or any other biochemical parameter was noted between study groups. CONCLUSION This study demonstrates increased airway tachykinin levels in patients with asthma and cough patients with coexistent acid reflux. This suggests airway sensory nerve activation in this population.
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Affiliation(s)
- Robert N Patterson
- Department of Medicine, Queen's University Belfast, and Regional Respiratory Centre, Belfast City Hospital, Grosvenor Road, Belfast BT12 6BJ, UK
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Abstract
Gastroesophageal reflux disease has frequently been implicated in a wide variety of complications beyond the esophagus. These so-called "extraesophageal" disorders range from diseases of the respiratory tract, such as asthma and bronchitis, to more remote sites and conditions such as otitis and dental erosion. Many articles proposing a link between reflux disease and a multitude of extraesophageal complications have been published, but indisputable evidence that these conditions are caused by reflux disease is rare. Much of the support for a link between reflux disease and a number of extraesophageal complications is based on the observation that reflux disease frequently coexists with other disorders. A causal link is difficult to prove, however, and this review aims to critically evaluate the available evidence, looking, where possible, at longitudinal studies, expert diagnoses, and response to acid-suppressive therapy as a means of determining the true relationship between GERD and its putative extraesophageal complications.
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Affiliation(s)
- Nimish Vakil
- University of Wisconsin Medical School, Madison, USA.
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50
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Babu AN, Nicolls MR. Critical pathways leading to obliterative bronchiolitis in lung allografts. Curr Opin Organ Transplant 2006. [DOI: 10.1097/01.mot.0000244650.00717.9c] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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