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Tanvir F, Nijjar GS, Aulakh SK, Kaur Y, Singh S, Singh K, Singla A, Sandhu APS, Luthra S, Antaal H. Gastroesophageal Reflux Disease: New Insights and Treatment Approaches. Cureus 2024; 16:e67654. [PMID: 39314570 PMCID: PMC11417972 DOI: 10.7759/cureus.67654] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/23/2024] [Indexed: 09/25/2024] Open
Abstract
Gastroesophageal reflux disease (GERD) remains a significant global health concern, with increasing prevalence and a substantial impact on quality of life. This narrative review explores recent advances in our understanding of GERD pathophysiology, diagnosis, and management. The complex interplay of factors contributing to GERD, including lower esophageal sphincter dysfunction, transient sphincter relaxations, and esophageal motility disorders, is discussed. Emerging diagnostic techniques, such as high-resolution manometry and impedance-pH monitoring, have enhanced our ability to accurately identify and characterize GERD. The review highlights the evolving landscape of GERD treatment, from conventional approaches like lifestyle modifications and proton pump inhibitors to novel strategies including potassium-competitive acid blockers, endoscopic therapies, and minimally invasive surgical techniques. The potential role of the microbiome in GERD pathogenesis and as a therapeutic target is examined. The concept of personalized medicine in GERD management is explored, considering genetic factors, biomarkers, and individual patient profiles. Complications of GERD, including erosive esophagitis, Barrett's esophagus, and esophageal adenocarcinoma, are reviewed, emphasizing the importance of early detection and appropriate management. The economic burden and impact on the quality of due to GERD are also addressed. This comprehensive review underscores the multifaceted nature of GERD and the need for a personalized, multidisciplinary approach to its management. It highlights ongoing research efforts and emerging therapies that promise to improve outcomes for GERD patients, while also identifying areas requiring further investigation to optimize diagnosis and treatment strategies.
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Affiliation(s)
- Fnu Tanvir
- Internal Medicine, Government Medical College Amritsar, Amritsar, IND
| | | | - Smriti Kaur Aulakh
- Internal Medicine, Sri Guru Ram Das University of Health Sciences and Research, Amritsar, IND
| | - Yasmeen Kaur
- Internal Medicine, Government Medical College Amritsar, Amritsar, IND
| | - Sumerjit Singh
- Radiology, Government Medical College Amritsar, Amritsar, IND
| | | | - Abhinandan Singla
- Internal Medicine, Government Medical College Amritsar, Amritsar, IND
| | - Ajay Pal Singh Sandhu
- Internal Medicine, Sri Guru Ram Das University of Health Sciences and Research, Amritsar, IND
| | - Shivansh Luthra
- Internal Medicine, Government Medical College Amritsar, Amritsar, IND
| | - Harman Antaal
- Internal Medicine, Government Medical College Patiala, Patiala, IND
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Lupu VV, Miron I, Tarca E, Trandafir LM, Anton-Paduraru DT, Moisa SM, Starcea M, Cernomaz A, Miron L, Lupu A. Gastroesophageal Reflux in Children with Asthma. CHILDREN (BASEL, SWITZERLAND) 2022; 9:children9030336. [PMID: 35327708 PMCID: PMC8947462 DOI: 10.3390/children9030336] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Revised: 02/18/2022] [Accepted: 02/23/2022] [Indexed: 11/16/2022]
Abstract
Background: Nowadays it is considered that a specific causal relationship exists between asthma and gastroesophageal reflux (GER), because of the aspiration of gastric refluate which leads to and maintain spasticity even real crisis of paroxystic expiratory dyspnea. This study explores this relationship and evaluates the results after treatment. Methods: 56 children diagnosed with asthma, hospitalized in a regional center of pediatric gastroenterology in Northeast Romania, underwent 24-hour continuous esophageal pH monitoring in order to establish the presence of GER. The Boix-Ochoa score was used to interpret the results. Proton pump inhibitors were administered to those with GER and the patients were reevaluated after 2 months. Results: 39 patients (69.64%) had GER, with a Boix-Ochoa score above normal (N < 11.99), and 17 patients (30.36%) had normal score. After administering proton pump inhibitors for 2 months, 7 patients still had high Boix-Ochoa score (17.95%). The result of this analysis shows that the presence of asthma increases the chance of GER by 2.86 times. Conclusions: In children with asthma we have to look for GER in order to treat, because it can help the treatment of asthma or even solve some cases resistant to standard treatment.
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Affiliation(s)
- Vasile Valeriu Lupu
- Pediatrics Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (V.V.L.); (I.M.); (L.M.T.); (D.-T.A.-P.); (M.S.); (A.L.)
| | - Ingrith Miron
- Pediatrics Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (V.V.L.); (I.M.); (L.M.T.); (D.-T.A.-P.); (M.S.); (A.L.)
| | - Elena Tarca
- Department of Surgery II—Pediatric Surgery, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
- Correspondence: (E.T.); (S.M.M.); (A.C.)
| | - Laura Mihaela Trandafir
- Pediatrics Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (V.V.L.); (I.M.); (L.M.T.); (D.-T.A.-P.); (M.S.); (A.L.)
| | - Dana-Teodora Anton-Paduraru
- Pediatrics Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (V.V.L.); (I.M.); (L.M.T.); (D.-T.A.-P.); (M.S.); (A.L.)
| | - Stefana Maria Moisa
- Pediatrics Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (V.V.L.); (I.M.); (L.M.T.); (D.-T.A.-P.); (M.S.); (A.L.)
- Correspondence: (E.T.); (S.M.M.); (A.C.)
| | - Magdalena Starcea
- Pediatrics Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (V.V.L.); (I.M.); (L.M.T.); (D.-T.A.-P.); (M.S.); (A.L.)
| | - Andrei Cernomaz
- 3rd Medical Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania;
- Correspondence: (E.T.); (S.M.M.); (A.C.)
| | - Lucian Miron
- 3rd Medical Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania;
| | - Ancuta Lupu
- Pediatrics Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (V.V.L.); (I.M.); (L.M.T.); (D.-T.A.-P.); (M.S.); (A.L.)
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Reyes-García J, Carbajal-García A, Montaño LM. Transient receptor potential cation channel subfamily V (TRPV) and its importance in asthma. Eur J Pharmacol 2022; 915:174692. [PMID: 34890545 DOI: 10.1016/j.ejphar.2021.174692] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Revised: 12/03/2021] [Accepted: 12/06/2021] [Indexed: 12/18/2022]
Abstract
Transient receptor potential (TRP) ion channels play critical roles in physiological and pathological conditions. Increasing evidence has unveiled the contribution of TRP vanilloid (TRPV) family in the development of asthma. The TRPV family is a group (TRPV1-TRPV6) of polymodal channels capable of sensing thermal, acidic, mechanical stress, and osmotic stimuli. TRPVs can be activated by endogenous ligands including, arachidonic acid derivatives or endocannabinoids. While TRPV1-TRPV4 are non-selective cation channels showing a predominance for Ca2+ over Na + influx, TRPV5 and TRPV6 are only Ca2+ permeable selective channels. Asthma is a chronic inflammatory bronchopulmonary disorder involving airway hyperresponsiveness (AHR) and airway remodeling. Patients suffering from allergic asthma display an inflammatory pattern driven by cytokines produced in type-2 helper T cells (Th2) and type 2 innate lymphoid cells (ILC2s). Ion channels are essential regulators in airway smooth muscle (ASM) and immune cells physiology. In this review, we summarize the contribution of TRPV1, TRPV2, and TRPV4 to the pathogenesis of asthma. TRPV1 is associated with hypersensitivity to environmental pollutants and chronic cough, inflammation, AHR, and remodeling. TRPV2 is increased in peripheral lymphocytes of asthmatic patients. TRPV4 contributes to ASM cells proliferation, and its blockade leads to a reduced eosinophilia, neutrophilia, as well as an abolished AHR. In conclusion, TRPV2 may represent a novel biomarker for asthma in children; meanwhile, TRPV1 and TRPV4 seem to be essential contributors to the development and exacerbations of asthma. Moreover, these channels may serve as novel therapeutic targets for this ailment.
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Affiliation(s)
- Jorge Reyes-García
- Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, CDMX, México.
| | - Abril Carbajal-García
- Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, CDMX, México.
| | - Luis M Montaño
- Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, CDMX, México.
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Die induzierbare laryngeale Obstruktion (ILO) – Ursachen, klinische Präsentation, Diagnostik und Therapie. Monatsschr Kinderheilkd 2021. [DOI: 10.1007/s00112-021-01159-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
ZusammenfassungWiederholt episodenhaft auftretende Atemnot ist im Kindes- und Jugendalter ein häufiges Symptom. Neben anstrengungsinduzierter Bronchialobstruktion im Rahmen eines Asthma bronchiale ist eine funktionelle Genese eine sehr häufige Differenzialdiagnose. Dennoch wird diese Diagnose häufig nicht oder mit langer Latenz gestellt. Unter dem Oberbegriff „ILO“ („inducible laryngeal obstruction“) werden sowohl funktionelle supraglottische Obstruktionen durch Kollaps der Knorpelstrukturen als auch Dysfunktionen auf Glottisebene wie „vocal cord dysfunction“ (VCD) subsumiert. Körperliche Anstrengung ist ein häufiger Auslöser; es werden jedoch auch Beschwerdebilder ohne Anstrengungsbezug beobachtet. Es wird der Erkenntnisstand zur Pathophysiologie referiert und die klinische Präsentation beschrieben. Ein wesentlicher Fokus des Artikels liegt im Folgenden auf der Darstellung eines sinnvollen und Ressourcen-orientierten diagnostischen Vorgehens. Der CLE-Test („continuous laryngoscopy exercise test“) als Provokationsmethode unter Wach-Videolaryngoskopie ist der Goldstandard, jedoch wird diese Diagnostik im deutschsprachigen Raum nicht flächendeckend vorgehalten. Dieses Positionspapier stellt daher die diagnostische Wertigkeit verschiedener anderer Diagnostik-Algorithmen und anamnestischer Informationen heraus. Ein weiterer Schwerpunkt des Papiers besteht in der detaillierten Vorstellung geeigneter atemphysiotherapeutischer Interventionen.
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Akinola MA, Oyedele TA, Akande KO, Oluyemi OY, Salami OF, Adesina AM, Adebajo AD. Gastroesophageal reflux disease: prevalence and Extraesophageal manifestations among undergraduate students in South West Nigeria. BMC Gastroenterol 2020; 20:160. [PMID: 32456613 PMCID: PMC7251857 DOI: 10.1186/s12876-020-01292-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2019] [Accepted: 05/05/2020] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND The reflux of noxious contents of the stomach may cause oesophageal and extra-oesophageal complications either by direct contact of aspirated gastric refluxate with the upper airway or by a vago-vagal reflex. This study aimed to determine the prevalence of gastroesophageal disease (GERD) and extraesophageal manifestations among undergraduate students in a tertiary institution in Nigeria. METHODS This is a cross-sectional study involving undergraduate students in a private University in Nigeria. Study proforma had three parts. Part A consisted of self-administered questionnaire designed to obtain students biodata. Part B consisted of standard Carlsson-Dent questionnaire. A score of 4 and above on Carlsson- Dent questionnaire was considered diagnostic of gastroesophageal reflux symptoms (GERD). Thereafter those who had GERD were further questioned and examined for extra-oesophageal symptoms of GERD. RESULTS The total number of the study participants was 647, out of which 212 (32.8%) had GERD. One hundred and forty-four (67.9%) and 86 (32.1%) females and male had GERD respectively (p = 0.13). The extraesophageal symptoms found in those with GERD were, dysphagia, coated tongue, nocturnal cough, xerostomia, lump in the throat, asthma-like symptoms, recurrent sore throat, frequent throat clearing, halithosis and dental erosion among others. CONCLUSION GERD is common among this study population, with a prevalence rate of 32.8%. Only age showed significant predictor for GERD. Varying extra-oesophageal manifestations were found in those with GERD.
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Affiliation(s)
- Moses Ayodele Akinola
- Ben Carson School of Medicine, Babcock University, Ilishan- Remo, Ogun State Nigeria
| | - Titus Ayodeji Oyedele
- Ben Carson School of Medicine, Babcock University, Ilishan- Remo, Ogun State Nigeria
| | - Kolawole Oluseyi Akande
- Gastroenterology Unit, Department of Medicine, College of Medicine, University of Ibadan, Ibadan, Oyo State Nigeria
| | | | | | - Alaba Moses Adesina
- Ben Carson School of Medicine, Babcock University, Ilishan- Remo, Ogun State Nigeria
| | - Adedeji David Adebajo
- Ben Carson School of Medicine, Babcock University, Ilishan- Remo, Ogun State Nigeria
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Wang YT, Tsai MC, Wang YH, Wei JCC. Association Between Proton Pump Inhibitors and Asthma: A Population-Based Cohort Study. Front Pharmacol 2020; 11:607. [PMID: 32457614 PMCID: PMC7227244 DOI: 10.3389/fphar.2020.00607] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2019] [Accepted: 04/17/2020] [Indexed: 12/13/2022] Open
Abstract
Objective The relationship between proton pump inhibitors (PPIs) and asthma is controversial. The goal of this study was to determine the association between PPI use in non-asthma subjects and their subsequent asthma prevalence. Design Nationwide, population-based cohort study. Methods We conducted a nationwide, population-based retrospective cohort study using data from the National Health Insurance Research Database (NHIRD) of Taiwan from 1999 to 2013. We identified 24,077 adult patients with PPI use for more than 3 months and 24,077 controls matched by propensity score on a one-to-one ratio for age, gender, comorbidities (hypertension, hyperlipidemia, gastroesophageal reflux disease, allergic rhinitis, atopic dermatitis, peptic ulcer disease, diabetes, and sleep apnea syndrome), and medications (histamine 2 receptor antagonists [H2RA], nonsteroidal anti-inflammatory drugs [NSAIDs], and acetaminophen). The cumulative asthma incidence for the two cohorts in the follow-up period was estimated with the Kaplan-Meier method, and the difference was examined using the log-rank test. Multivariate Cox regression models were used to calculate the adjusted hazard ratios (HR). Results The overall incidence of asthma was 1.58-fold greater in the PPI cohort than in the non-PPI cohort (13.3 versus 8.4 per 1,000 person-years), with an adjusted HR of 1.76 (95% confidence interval [CI], 1.64-1.88). In patients without previous peptic ulcer disease, the adjusted HR of asthma associated with PPIs was higher than in the non-PPI group (1.95; 95% CI, 1.80-2.11). The risk of asthma due to PPI use was also more significant in patients not receiving H2RA (1.81; 95% CI, 1.66-1.96), NSAIDs (1.93; 95% CI, 1.73-2.15), and acetaminophen (1.88; 95% CI, 1.70-2.08). Conclusions This population base study demonstrated that patients with long-duration of PPI use are at a higher risk of developing asthma, regardless of age, gender, comorbidities, and medications.
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Affiliation(s)
- Yao-Tung Wang
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.,School of Medicine, Chung Shan Medical University, Taichung, Taiwan.,Division of Pulmonary Medicine, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Ming-Chang Tsai
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.,School of Medicine, Chung Shan Medical University, Taichung, Taiwan.,Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Yu-Hsun Wang
- Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - James Cheng-Chung Wei
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.,Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.,Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan.,Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan
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DEL GRANDE LM, HERBELLA FAM, KATAYAMA RC, SCHLOTTMANN F, PATTI MG. THE ROLE OF THE TRANSDIAPHRAGMATIC PRESSURE GRADIENT IN THE PATHOPHYSIOLOGY OF GASTROESOPHAGEAL REFLUX DISEASE. ARQUIVOS DE GASTROENTEROLOGIA 2018; 55Suppl 1:13-17. [DOI: 10.1590/s0004-2803.201800000-39] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/22/2018] [Accepted: 01/29/2018] [Indexed: 12/15/2022]
Abstract
ABSTRACT Gastroesophageal reflux disease (GERD) is the most common disease of the upper gastrointestinal tract in the Western world. GERD pathophysiology is multifactorial. Different mechanisms may contribute to GERD including an increase in the transdiaphragmatic pressure gradient (TPG). The pathophysiology of GERD linked to TPG is not entirely understood. This review shows that TPG is an important contributor to GERD even when an intact esophagogastric barrier is present in the setting of obesity and pulmonary diseases.
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Bloom CI, Nissen F, Douglas IJ, Smeeth L, Cullinan P, Quint JK. Exacerbation risk and characterisation of the UK's asthma population from infants to old age. Thorax 2017; 73:313-320. [PMID: 29074814 DOI: 10.1136/thoraxjnl-2017-210650] [Citation(s) in RCA: 117] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2017] [Revised: 09/14/2017] [Accepted: 10/09/2017] [Indexed: 01/08/2023]
Abstract
BACKGROUND Few studies have examined the characteristics of a general asthma population; most have focused on more severe patients or severe exacerbations. METHODS This population-based cohort study, from April 2007 to September 2015, used linked primary and secondary care electronic healthcare records (Clinical Practice Research Datalink, Hospital Episode Statistics). Characteristics of four age cohorts, 'Under 5s', '5 to 17s', '18 to 54s', '55+', were described. Exacerbation risk factors, including asthma severity (measured by the British Thoracic Society (BTS) stepwise approach), were assessed using Poisson regression. RESULTS 424 326 patients with current asthma were eligible (n, median follow-up: 'Under 5s'=17 320, 1 year; '5 to 17s'=82 707, 3.3 years; '18 to 54s'=210 724, 4 years; '55+'=113 575, 5.1 years). Over 60% of the total study population had mild asthma (BTS steps 1/2). There were differences between the cohort's characteristics, including by gender, disease severity and exacerbation pattern. The rate of exacerbations was highest in the oldest cohort and lowest in the '5 to 17s' cohort (rate per 10 person-years (95% CI), 'Under 5s'=4.27 (4.18 to 4.38), '5 to 17s'=1.48 (1.47 to 1.50), '18 to 54s'=3.22 (3.21 to 3.24), '55+'=9.40 (9.37 to 9.42)). In all cohorts, exacerbation rates increased with increasing asthma severity, after adjusting for confounders including gender, socioeconomic status, smoking, body mass index, atopy, rhinitis, gastro-oesophageal reflux, anxiety, depression and COPD. CONCLUSION The majority of UK patients with asthma had mild asthma and did not experience an exacerbation during follow-up. Patients aged ≥55 years had the lowest proportion with mild asthma and highest rate of exacerbations; the opposite was found in patients aged between 5 and 18 years.
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Affiliation(s)
- Chloe I Bloom
- Department of Respiratory Epidemiology, Occupational Medicine and Public Health, NHLI, Imperial College London, London, UK
| | - Francis Nissen
- Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK
| | - Ian J Douglas
- Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK
| | - Liam Smeeth
- Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK
| | - Paul Cullinan
- Department of Respiratory Epidemiology, Occupational Medicine and Public Health, NHLI, Imperial College London, London, UK
| | - Jennifer K Quint
- Department of Respiratory Epidemiology, Occupational Medicine and Public Health, NHLI, Imperial College London, London, UK
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Bar-Sever Z. Scintigraphic Evaluation of Gastroesophageal Reflux and Pulmonary Aspiration in Children. Semin Nucl Med 2017; 47:275-285. [PMID: 28417856 DOI: 10.1053/j.semnuclmed.2016.12.001] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Gastroesophageal reflux (GER) and pulmonary aspiration are encountered in children of all ages. Signs, symptoms, and complications vary from mild and transient to severe life-threatening conditions. This review will present relevant clinical information on these conditions as well as common diagnostic procedures. The role of scintigraphic techniques used in the evaluation of these conditions will be discussed in detail including protocols and performance in comparison to other diagnostic methods.
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Affiliation(s)
- Zvi Bar-Sever
- Department of nuclear medicine, Schneider Children's Medical Center, Petah Tikva, Israel.
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10
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Porsbjerg C, Menzies-Gow A. Co-morbidities in severe asthma: Clinical impact and management. Respirology 2017; 22:651-661. [DOI: 10.1111/resp.13026] [Citation(s) in RCA: 121] [Impact Index Per Article: 15.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2016] [Revised: 02/08/2017] [Accepted: 02/08/2017] [Indexed: 12/17/2022]
Affiliation(s)
- Celeste Porsbjerg
- Respiratory Research Unit, Department of Respiratory Medicine; Bispebjerg University Hospital; Copenhagen Denmark,
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Jaimchariyatam N, Haprasert P, Gonchanvit S, Wongtim S. Observational study of omeprazole for gastroesophageal reflux on pulmonary function in adult asthmatics. ASIAN BIOMED 2017. [DOI: 10.5372/1905-7415.0902.379] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Abstract
Background
Asthma is a chronic inflammatory disease of airways. Gastroesophageal reflux disease (GERD) is known to be associated with worsening asthma. We hypothesized that treatment of GERD in asthmatics will improve asthma control and quality of life. We reviewed our experience of treatment of GERD in asthmatics in Thailand.
Objectives
To study the effects of omeprazole for treatment of GERD in patients with poorly controlled asthma on pulmonary function tests and asthma control test (ACT) scores.
Methods
This study was conducted at King Chulalongkorn Memorial Hospital between August 2009 and December 2010. Patients with partly controlled and uncontrolled asthma who were found to have GERD by 24 hour esophageal pH monitoring were administered omeprazole 40 mg per day for 8 weeks. Pulmonary function tests and ACT scores before and after treatment were compared at 4-weeks and 8-weeks follow up.
Results
Twenty four patients were included in this study. None of them had asthmatic attacks during the study. After 4 and 8 weeks of omeprazole treatment, the mean FEV1 (2.20 ± 0.64 L, 2.36 ± 0.58 L, respectively) and the mean ACT score (20.82 ± 3.30, 23.00 ± 1.69, respectively) were significantly higher than the pretreatment values (mean FEV1 1.99 ± 0.56 L and ACT score 16.36 ± 3.97) (P < 0.05).
Conclusion
High-dose omeprazole may improve pulmonary function and the level of asthma control in Thai patients with partly controlled or uncontrolled asthma and coexisting GERD.
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Affiliation(s)
- Nattapong Jaimchariyatam
- Division of Pulmonary and Critical Care Medicine , Department of Medicine, Faculty of Medicine , Chulalongkorn University , Bangkok 10330 , Thailand
- Excellence Center for Sleep Disorders , King Chulalongkorn Memorial Hospital, Thai Red Cross Society , Bangkok 10330 , Thailand
| | - Phurin Haprasert
- Division of Pulmonary and Critical Care Medicine , Department of Medicine, Faculty of Medicine , Chulalongkorn University , Bangkok 10330 , Thailand
| | - Sutep Gonchanvit
- Gastrointestinal Motility Research Unit , Division of Gastroenterology, Department of Medicine, Faculty of Medicine , Chulalongkorn University , Bangkok 10330 , Thailand
| | - Somkiat Wongtim
- Division of Pulmonary and Critical Care Medicine , Department of Medicine, Faculty of Medicine , Chulalongkorn University , Bangkok 10330 , Thailand
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Inhaled Beta Agonist Bronchodilator Does Not Affect Trans-diaphragmatic Pressure Gradient but Decreases Lower Esophageal Sphincter Retention Pressure in Patients with Chronic Obstructive Pulmonary Disease (COPD) and Gastroesophageal Reflux Disease (GERD). J Gastrointest Surg 2016; 20:1679-82. [PMID: 27350150 DOI: 10.1007/s11605-016-3192-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2016] [Accepted: 06/13/2016] [Indexed: 01/31/2023]
Abstract
BACKGROUND Chronic obstructive pulmonary disease (COPD) patients have a high incidence of gastroesophageal reflux disease (GERD) whose pathophysiology seems to be linked to an increased trans-diaphragmatic pressure gradient and not to a defective esophagogastric barrier. Inhaled beta agonist bronchodilators are a common therapy used by patients with COPD. This drug knowingly not only leads to a decrease in the lower esophageal sphincter (LES) resting pressure, favoring GERD, but also may improve ventilatory parameters, therefore preventing GERD. AIMS This study aims to evaluate the effect of inhaled beta agonist bronchodilators on the trans-diaphragmatic pressure gradient and the esophagogastric barrier. METHODS We studied 21 patients (mean age 67 years, 57 % males) with COPD and GERD. All patients underwent high-resolution manometry and esophageal pH monitoring. Abdominal and thoracic pressure, trans-diaphragmatic pressure gradient (abdominal-thoracic pressure), and the LES retention pressure (LES basal pressure-transdiaphragmatic gradient) were measured before and 5 min after inhaling beta agonist bronchodilators. RESULTS The administration of inhaled beta agonist bronchodilators leads to the following: (a) a simultaneous increase in abdominal and thoracic pressure not affecting the trans-diaphragmatic pressure gradient and (b) a decrease in the LES resting pressure with a reduction of the LES retention pressure. CONCLUSION In conclusion, inhaled beta agonist bronchodilators not only increase the thoracic pressure but also lead to an increased abdominal pressure favoring GERD by affecting the esophagogastric barrier.
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Pathophysiology of Gastroesophageal Reflux in Patients with Chronic Pulmonary Obstructive Disease Is Linked to an Increased Transdiaphragmatic Pressure Gradient and not to a Defective Esophagogastric Barrier. J Gastrointest Surg 2016; 20:104-10; discussion 110. [PMID: 26403715 DOI: 10.1007/s11605-015-2955-4] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2015] [Accepted: 09/14/2015] [Indexed: 01/31/2023]
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14
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Kirenga BJ, Schwartz JI, de Jong C, van der Molen T, Okot-Nwang M. Guidance on the diagnosis and management of asthma among adults in resource limited settings. Afr Health Sci 2015; 15:1189-99. [PMID: 26958020 PMCID: PMC4765426 DOI: 10.4314/ahs.v15i4.18] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Optimal management of asthma in resource limited settings is hindered by lack of resources, making it difficult for health providers to adhere to international guidelines. The purpose of this review is to identify steps for asthma diagnosis and management in resource limited settings. METHODS Review of international asthma guidelines and other published studies on diagnosis and management of asthma. RESULTS We establish that clinical diagnosis of asthma can be made if recurrent respiratory symptoms especially current wheeze or wheeze in the last 12 months are present. Presence of a trigger, other allergic diseases, personal or family history of asthma; clinical improvement and increase in the peak flow and forced expiratory volume in one second of ≥12% after salbutamol administration increases the likelihood of asthma. At diagnosis severity grading, patient education, removal or reduction of trigger should be done. Follow up 2-6 weeks and assessment of control during therapy is essential. Therapy should be adjusted up or down depending on control levels. Patients should be instructed to increase the frequency of their bronchodilators and/or steroids therapy when they start to experience worsening symptoms. CONCLUSION Good quality asthma care can be achieved in resource limited settings by use of clinical data and simple tests.
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Affiliation(s)
- Bruce J Kirenga
- Pulmonology unit, Department of Medicine, Makerere University College of Health sciences/Mulago Hospital
- Department of General Practice, Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | | | - Corina de Jong
- Department of General Practice, Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Thys van der Molen
- Department of General Practice, Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Martin Okot-Nwang
- Pulmonology unit, Department of Medicine, Makerere University College of Health sciences/Mulago Hospital
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15
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Ciorba A, Bianchini C, Zuolo M, Feo CV. Upper aerodigestive tract disorders and gastro-oesophageal reflux disease. World J Clin Cases 2015; 3:102-11. [PMID: 25685756 PMCID: PMC4317603 DOI: 10.12998/wjcc.v3.i2.102] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2014] [Revised: 09/20/2014] [Accepted: 10/28/2014] [Indexed: 02/05/2023] Open
Abstract
A wide variety of symptoms and diseases of the upper aerodigestive tract are associated to gastro-oesophageal reflux disease (GORD). These disorders comprise a large variety of conditions such as asthma, chronic otitis media and sinusitis, chronic cough, and laryngeal disorders including paroxysmal laryngospasm. Laryngo-pharyngeal reflux disease is an extraoesophageal variant of GORD that can affect the larynx and pharynx. Despite numerous research efforts, the diagnosis of laryngopharyngeal reflux often remains elusive, unproven and controversial, and its treatment is then still empiric. Aim of this paper is to review the current literature on upper aerodigestive tract disorders in relation to pathologic gastro-oesophageal reflux, focusing in particular on the pathophysiology base and results of the surgical treatment of GORD.
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16
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Canning BJ, Chang AB, Bolser DC, Smith JA, Mazzone SB, McGarvey L. Anatomy and neurophysiology of cough: CHEST Guideline and Expert Panel report. Chest 2014; 146:1633-1648. [PMID: 25188530 PMCID: PMC4251621 DOI: 10.1378/chest.14-1481] [Citation(s) in RCA: 178] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2014] [Accepted: 07/21/2014] [Indexed: 12/11/2022] Open
Abstract
Bronchopulmonary C-fibers and a subset of mechanically sensitive, acid-sensitive myelinated sensory nerves play essential roles in regulating cough. These vagal sensory nerves terminate primarily in the larynx, trachea, carina, and large intrapulmonary bronchi. Other bronchopulmonary sensory nerves, sensory nerves innervating other viscera, as well as somatosensory nerves innervating the chest wall, diaphragm, and abdominal musculature regulate cough patterning and cough sensitivity. The responsiveness and morphology of the airway vagal sensory nerve subtypes and the extrapulmonary sensory nerves that regulate coughing are described. The brainstem and higher brain control systems that process this sensory information are complex, but our current understanding of them is considerable and increasing. The relevance of these neural systems to clinical phenomena, such as urge to cough and psychologic methods for treatment of dystussia, is high, and modern imaging methods have revealed potential neural substrates for some features of cough in the human.
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Affiliation(s)
| | - Anne B Chang
- Queensland Children's Respiratory Centre, Royal Children's Hospital, Brisbane, QLD, Australia, Child Health Division, Menzies School of Health, Darwin, NT, Australia
| | - Donald C Bolser
- Department of Physiological Sciences, University of Florida, Gainesville, FL
| | - Jaclyn A Smith
- Centre for Respiratory and Allergy, University of Manchester, Manchester, England
| | - Stuart B Mazzone
- School of Biomedical Sciences, University of Queensland, Brisbane, QLD, Australia
| | - Lorcan McGarvey
- Centre for Infection and Immunity, The Queen's University of Belfast, Belfast, Northern Ireland.
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17
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Goseva Z, Gjorcev A, Jovanovska-Janeva E, Arbutina S. Gastroesophageal Reflux Symptoms in Patients with Chronic Obstructive Pulmonary Disease. Open Access Maced J Med Sci 2014. [DOI: 10.3889/oamjms.2014.080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
BACKGROUND: It is known that there is some relation between airways obstruction and gastroesophageal reflux symptoms (GER) symptoms in patients with chronic obstructive pulmonary disease (COPD).AIM: The aim was to determine frequency of GER symptoms and correlation with pulmonary function tests in patients with COPD.MATERIAL AND METHODS: The study included 58 patients. First group had 20 patients with mild COPD, second group had 18 patients with moderate COPD and third group had 20 patients with severe COPD. We had also a control group with 12 healthy subjects. All subjects completed their self-reported questionnaire about symptoms like: acid-regurgitation, heartburn, dysphagia, dyspnea and chronic cough.RESULTS: COPD patients with airways obstruction and significant GER symptoms had their respiratory symptoms associated with reflux events. More of COPD patients had significant GER symptoms defined as regurgitation and dysphagia once or more per week. Patients with FEV1 less than 50% showed more prevalent GER symptoms compared to those with values of FEV1 grater then 50%.CONCLUSION: GER symptoms are more prevalent in patients with severe airways obstruction when compared to less airways obstructed group and controls. We could suggest an association between the degree of airways obstruction in patients with COPD and the increased rate of GER symptoms.
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18
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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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19
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Bediwy AS, Al-Biltagi M, Amer HG, Saeed NK. Combination therapy versus monotherapy for gastroesophageal reflux in children with difficult-to-treat bronchial asthma. EGYPTIAN JOURNAL OF CHEST DISEASES AND TUBERCULOSIS 2014. [DOI: 10.1016/j.ejcdt.2013.10.014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022] Open
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20
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Shimizu Y, Dobashi K, Kusano M, Mori M. Different gastoroesophageal reflux symptoms of middle-aged to elderly asthma and chronic obstructive pulmonary disease (COPD) patients. J Clin Biochem Nutr 2012; 50:169-75. [PMID: 22448100 PMCID: PMC3303481 DOI: 10.3164/jcbn.11-75] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2011] [Accepted: 07/06/2011] [Indexed: 12/21/2022] Open
Abstract
Symptomatic differences and the impact of gastroesophageal reflux disease (GERD) have not been clarified in patients with asthma and chronic obstructive pulmonary disease (COPD). The purpose of this study is to assess the differences of GERD symptoms among asthma, COPD, and disease control patients, and determine the impact of GERD symptoms on exacerbation of asthma or COPD by using a new questionnaire for GERD. A total of 120 subjects underwent assessment with the frequency scale for the symptoms of GERD (FSSG) questionnaire, including 40 age-matched patients in each of the asthma, COPD, and disease control groups. Asthma and control patients had more regurgitation-related symptoms than COPD patients (p<0.05), while COPD patients had more dysmotility-related symptoms than asthma patients (p<0.01) or disease control patients (p<0.01). The most distinctive symptom of asthma patients with GERD was an unusual sensation in the throat, while bloated stomach was the chief symptom of COPD patients with GERD, and these symptoms were associated with disease exacerbations. The presence of GERD diagnosed by the total score of FSSG influences the exacerbation of COPD. GERD symptoms differed between asthma and COPD patients, and the presence of GERD diagnosed by the FSSG influences the exacerbation of COPD.
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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
- Jobu Hospital for Respiratory Disease, 586-1 Taguchi-machi, Maebashi, Gunma 371-0048, Japan
- Department of Pulmonary Medicine, Maebashi Red Cross Hospital, 3-21-36 Asahi-cho Maebashi, Gunma 371-0014, Japan
| | - Kunio Dobashi
- Gunma University School of Health Sciences, 3-39-15 Showa-machi, Maebashi, Gunma 371-8511, Japan
| | - Motoyasu Kusano
- Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, 3-39-15 Showa-machi, Maebashi, Gunma 371-8511, Japan
| | - Masatomo Mori
- 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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21
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Ummarino D, Miele E, Masi P, Tramontano A, Staiano A, Vandenplas Y. Impact of antisecretory treatment on respiratory symptoms of gastroesophageal reflux disease in children. Dis Esophagus 2012; 25:671-7. [PMID: 22236501 DOI: 10.1111/j.1442-2050.2011.01301.x] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The effect of antisecretory treatment on extraesophageal symptoms of gastroesophageal reflux disease was evaluated. Seventy-eight children presenting with typical and extraesophageal symptoms of gastroesophageal reflux disease underwent a multichannel intraluminal impedance and pH monitoring (MII/pH). Children with a positive MII/pH were randomly treated with proton pump inhibitors (PPIs) or histamine H(2) -receptor antagonists (H(2) RAs) during 3 months. At the end of the treatment period, all patients were recalled. A second treatment period of 3 months was given to those patients who were not symptom-free after 3 months. Thirty-five of the forty-one (85.4%) children with a pathologic MII/pH presented with extraesophageal symptoms and were treated with PPIs (omeprazole; n:19) or H(2) RAs (ranitidine; n:16) for 12 weeks. After 3 months, 11/19 (57.9%) PPI-treated patients had a complete resolution of symptoms; 6/8 nonresponders were treated with PPI for another 3 months and became all symptom-free. The other two underwent a Nissen fundoplication. Only 5/16 (31.2 %) patients treated with H(2) RAs had a complete resolution of symptoms after 3 months; 1/11 was treated again with H(2) RAs during 3 months, and 10/11 were changed to PPIs. In 3/10, a partial resolution of symptoms was achieved, while in 7/10, a complete remission was obtained (P < 0.05). Antisecretory reflux treatment improves extraesophageal reflux symptoms. The efficacy of PPIs is superior to that of H(2) RAs in these children.
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Affiliation(s)
- D Ummarino
- Department of Pediatrics, University of Naples Federico II, Naples, Italy
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22
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Abstract
Dual pH-multichannel intraluminal impedance (pH-MII) is a sensitive tool for evaluating overall gastroesophageal reflux disease, and particularly for permitting detection of nonacid reflux events. pH-MII technology is especially useful in the postprandial period or at other times when gastric contents are nonacidic.pH-MII was recently recognized by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition as being superior to pH monitoring alone for evaluation of the temporal relation between symptoms and gastroesophageal reflux. In children, pH-MII is useful to correlate symptoms with reflux (particularly nonacid reflux), to quantify reflux during tube feedings and the postprandial period, and to assess efficacy of antireflux therapy. This clinical review is simply an evidence-based overview addressing the indications, limitations, and recommended protocol for the clinical use of pH-MII in children.
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23
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Sasaki T, Nakayama K, Yasuda H, Yamaya M. A new strategy with proton pump inhibitors for the prevention of acute exacerbations in COPD. Ther Adv Respir Dis 2011; 5:91-103. [PMID: 21285157 DOI: 10.1177/1753465810392264] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
Acute exacerbations of chronic obstructive pulmonary disease (COPD), an acute worsening of respiratory symptoms, generally result in a poor prognosis. Successful prevention and management of such exacerbations is thus important for patient care. Viral infection, primarily with rhinovirus (RV), is the foremost cause of exacerbations in COPD patients. Proton pump inhibitors (PPIs) have been reported to inhibit RV infection in human airway epithelial cells in vitro. Furthermore, clinical trials of PPIs in patients with COPD resulted in a reduction in rates of both common cold and COPD exacerbations. In this review, we discuss the significance of COPD exacerbations, summarize a published trial of the effect of low-dose PPIs on COPD exacerbations, and postulate a mechanism for this effect.
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Affiliation(s)
- Takahiko Sasaki
- Department of Respiratory Medicine, Tohoku University School of Medicine, Sendai 980-8574, Japan.
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24
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Ladanchuk TC, Johnston BT, Murray LJ, Anderson LA. Risk of Barrett's oesophagus, oesophageal adenocarcinoma and reflux oesophagitis and the use of nitrates and asthma medications. Scand J Gastroenterol 2010; 45:1397-403. [PMID: 20626305 DOI: 10.3109/00365521.2010.503968] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE To investigate the relationship between use of asthma medication and nitrates and risk of reflux oesophagitis, Barrett's oesophagus and oesophageal adenocarcinoma. MATERIAL AND METHODS Data were collected on use of asthma medication and nitrates at least 1 year before interview from patients with reflux oesophagitis, Barrett's oesophagus and oesophageal adenocarcinoma. Associations between use of asthma medications and nitrates and the risk of reflux oesophagitis, Barrett's oesophagus and oesophageal adenocarcinoma were estimated using multiple logistic regression. RESULTS Nine hundred and forty-one subjects were recruited: 230 reflux oesophagitis, 224 Barrett's oesophagus, 227 oesophageal adenocarcinoma patients and 260 population controls. Barrett's oesophagus patients were more likely than controls to have had a diagnosis of asthma (odds ratio 2.15, 95% confidence interval 1.15-4.03) and to have used asthma medications (odds ratio 2.13, 95% confidence interval 1.09-4.16). No significant associations were observed between use of asthma medication or nitrates and reflux oesophagitis or oesophageal adenocarcinoma. CONCLUSIONS Gastro-oesophageal reflux symptoms appear to confound the association between asthma medication use and Barrett's oesophagus. However, it is possible that asthma medications may increase the risk of Barrett's oesophagus by other mechanisms.
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Affiliation(s)
- Todd C Ladanchuk
- Centre for Public Health, Queen's University, and Royal Group of Hospitals, Belfast, Northern Ireland, UK
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25
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Premkumar LS, Sikand P. TRPV1: a target for next generation analgesics. Curr Neuropharmacol 2010; 6:151-63. [PMID: 19305794 PMCID: PMC2647151 DOI: 10.2174/157015908784533888] [Citation(s) in RCA: 85] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2007] [Revised: 10/17/2007] [Accepted: 11/11/2007] [Indexed: 12/11/2022] Open
Abstract
Transient Receptor Potential Vanilloid 1 (TRPV1) is a Ca2+ permeant non-selective cation channel expressed in a subpopulation of primary afferent neurons. TRPV1 is activated by physical and chemical stimuli. It is critical for the detection of nociceptive and thermal inflammatory pain as revealed by the deletion of the TRPV1 gene. TRPV1 is distributed in the peripheral and central terminals of the sensory neurons and plays a role in initiating action potentials at the nerve terminals and modulating neurotransmitter release at the first sensory synapse, respectively. Distribution of TRPV1 in the nerve terminals innervating blood vessels and in parts of the CNS that are not subjected to temperature range that is required to activate TRPV1 suggests a role beyond a noxious thermal sensor. Presently, TRPV1 is being considered as a target for analgesics through evaluation of different antagonists. Here, we will discuss the distribution and the functions of TRPV1, potential use of its agonists and antagonists as analgesics and highlight the functions that are not related to nociceptive transmission that might lead to adverse effects.
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Affiliation(s)
- Louis S Premkumar
- Department of Pharmacology, Southern Illinois University School of Medicine Springfield, IL 62702, USA.
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26
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[Lung diseases and gastro-oesophageal reflux disease]. REVISTA PORTUGUESA DE PNEUMOLOGIA 2009; 15:899-921. [PMID: 19649547 DOI: 10.1016/s0873-2159(15)30185-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Gastro -oesophageal Reflux Disease is a consequence of pathological reflux from stomach to oesophagus. Whenever the refluxed contents extended beyond the oesophagus itself, is called Extraoesophageal Reflux Disease. The author proposes a review about pulmonary disorders and gastroesophageal reflux. Previously, it is evaluated in an abridged way, the concepts of each diseases and after that, in a systematic form, it is discussed the prevalence of gastro -oesophageal reflux in lung diseases, all the mechanisms studies and the impact of gastro -oesophageal treatment on lung disorders. The author concludes that is undeniable the link between Gastro -oesophageal reflux and lung diseases and further reaserch is mandatory in order to corroborate this association.
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Sasaki T, Nakayama K, Yasuda H, Yoshida M, Asamura T, Ohrui T, Arai H, Araya J, Kuwano K, Yamaya M. A randomized, single-blind study of lansoprazole for the prevention of exacerbations of chronic obstructive pulmonary disease in older patients. J Am Geriatr Soc 2009; 57:1453-7. [PMID: 19515110 DOI: 10.1111/j.1532-5415.2009.02349.x] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
OBJECTIVES To investigate whether proton pump inhibitor (PPI) therapy reduces the frequency of common colds and exacerbations in patients with chronic obstructive pulmonary disease (COPD). DESIGN Twelve-month, randomized, observer-blind, controlled trial. SETTING A university hospital and three city hospitals in Miyagi prefecture in Japan. PARTICIPANTS One hundred patients with COPD (mean age +/- SD 74.9 +/- 8.2) participated. They were all ex-smokers and had received conventional therapies for COPD, including smoking cessation and bronchodilators. Patients with gastroesophageal reflux disease or gastroduodenal ulcer were excluded. INTERVENTION Patients were randomly assigned to conventional therapies (control group) or conventional therapies plus PPI (lansoprazole 15 mg/d; PPI group) and observed for 12 months. MEASUREMENTS Frequency of common colds and COPD exacerbations. RESULTS The number of exacerbations per person in a year in the PPI group was significantly lower than that in the control group (0.34 +/- 0.72 vs 1.18 +/- 1.40; P<.001). The adjusted odds ratio with logistic regression for having exacerbation (> or =once/year) in the PPI group compared with the control group was 0.23 (P=.004). In contrast, there was no significant difference in the numbers of common colds per person per year between the PPI group and the control group (1.22 +/- 2.09 vs 2.04 +/- 3.07; P=.12). PPI therapy significantly reduced the risk of catching frequent common colds (> or =3 times/year), the adjusted odds ratio of which was 0.28 (P=.048). CONCLUSION In this single-blind, nonplacebo-controlled trial, lansoprazole was associated with a significant decrease in COPD exacerbations. More definitive clinical trials are warranted.
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Affiliation(s)
- Takahiko Sasaki
- Department of Geriatric and Gerontology, School of Medicine, Tohoku University, Sendai, Japan
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28
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Machado MDM, Cardoso PFG, Ribeiro IOES, Zamin Júnior I, Eilers RJ. Esophageal manometry and 24-h esophageal pH-metry in a large sample of patients with respiratory symptoms. J Bras Pneumol 2009; 34:1040-8. [PMID: 19180339 DOI: 10.1590/s1806-37132008001200009] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2008] [Accepted: 04/22/2008] [Indexed: 11/22/2022] Open
Abstract
OBJECTIVE To determine the prevalence of gastroesophageal reflux disease (GERD) and to evaluate the esophageal motor profile of patients with respiratory symptoms referred to a digestive motility referral center for esophageal function testing. METHODS The results of esophageal manometry and 24-h esophageal pH-metry were analyzed.The inclusion criterion was presenting respiratory symptoms, with or without accompanying digestive symptoms. RESULTS Of the 1,170 patients included in the study, 602 (51.5%) reported having digestive and respiratory symptoms (DRS group), and 568 (48.5%) reported having only respiratory symptoms (RS group). Asthma was diagnosed in 142 patients in the RS group (RS-A subgroup) and in 201 of those in the DRS group (DRS-A). Of the 346 cases of esophageal dysmotility, hypomotility was found in 175 (14.3% and 15.6% in the DRS and RS groups, respectively), and lower esophageal sphincter (LES) hypotonia was found in 411 (40.3% and 30.2%, respectively). Hypotonia correlated with GERD. Exposure of the distal esophagus to acid was markedly abnormal in the supine position. The prevalence of GERD in the sample as a whole, the RS-A/DRS-A subgroups and the RS-A subgroup alone was 39.8%, 44.0% and 35.2%, respectively CONCLUSIONS Hypotonic LES was the most common abnormality and correlated with GERD. Although GERD was more evident in the DRS group, approximately one third of the patients in the RS group also presented GERD (silent GERD). The findings suggest that GERD can be an extrapulmonary cause of chronic respiratory symptoms unresponsive to conventional therapy.
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Affiliation(s)
- Mirna da Mota Machado
- Laboratório de Motilidade Digestiva, Santa Casa de Porto Alegre, Porto Alegre, RS, Brasil
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29
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Abstract
The term aspiration lung disease describes several clinical syndromes, with massive aspiration and chronic lung aspiration being at two extremes of the clinical spectrum. Over the years, significant advances have been made in understanding the mechanisms underlying dysphagia, gastroesophageal function, and airway protective reflexes and new diagnostic techniques have been introduced. Despite this, characterizing the presence or absence of aspiration, and under what circumstances a child might be aspirating what, is extremely challenging. Many children are still not adequately diagnosed or treated for aspiration until permanent lung damage has occurred. A multidisciplinary approach is mandatory for a correct diagnosis in addition to timely and appropriate care.
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Affiliation(s)
- Fernando M de Benedictis
- Division of Pediatric Medicine, Department of Pediatrics, Salesi Children's University Hospital, Ancona, Italy.
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30
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Laforest L, Van Ganse E, Devouassoux G, Osman LM, Pison C, El Hasnaoui A, Bauguil G, Chamba G. Factors influencing dispensing of psychotropic medications to patients with asthma: a community pharmacy-based survey. Ann Allergy Asthma Immunol 2008; 100:230-6. [PMID: 18426142 DOI: 10.1016/s1081-1206(10)60447-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
BACKGROUND To our knowledge, the use of psychotropic medications (antidepressant, anxiolytic, and hypnotic agents) in patients with asthma has not been extensively explored. OBJECTIVE To identify factors associated with the use of these medications in patients with asthma. METHODS Regular customers (aged 18-50 years) of 348 pharmacies in 9 French regions were consecutively recruited from November 2003 to June 2004. Patients with a prescription for an asthma medication were included. Patients completed a questionnaire, complemented by the computerized records of their therapy dispensed in the past 12 months. Asthma control was measured with the Asthma Control Test. RESULTS Among 886 patients (mean age, 37.4 years; 55.0% female), during the 12 months before the survey, the proportions who received at least 1 U of anxiolytic, antidepressant, and hypnotic agents were 25.6%, 13.7%, and 13.0%, respectively. Higher dispensing levels of antidepressant, anxiolytic, and hypnotic agents were observed with decreasing asthma control (P < .001 for each drug class). Other correlates of receiving any of these classes included older age, female sex, smoking status, and dispensing of antireflux treatment (P < .001 for all). These results were confirmed in multivariate analyses. CONCLUSIONS Psychotropic drugs were commonly dispensed to patients with asthma, and correlates of receiving these drugs were identified in this population. The high use of psychotropic medication, particularly in patients with poorly controlled asthma, is of concern.
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31
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Soest EMV, Dieleman JP, Kuipers EJ. The effect of anticholinergic agents on gastro-oesophageal reflux and related disorders. Expert Opin Drug Saf 2008; 7:173-80. [DOI: 10.1517/14740338.7.2.173] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
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Appel JZ, Lee SM, Hartwig MG, Li B, Hsieh CC, Cantu E, Yoon Y, Lin SS, Parker W, Davis RD. Characterization of the innate immune response to chronic aspiration in a novel rodent model. Respir Res 2007; 8:87. [PMID: 18042282 PMCID: PMC2213655 DOI: 10.1186/1465-9921-8-87] [Citation(s) in RCA: 64] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2007] [Accepted: 11/27/2007] [Indexed: 01/14/2023] Open
Abstract
Background Although chronic aspiration has been associated with several pulmonary diseases, the inflammatory response has not been characterized. A novel rodent model of chronic aspiration was therefore developed in order to investigate the resulting innate immune response in the lung. Methods Gastric fluid or normal saline was instilled into the left lung of rats (n = 48) weekly for 4, 8, 12, or 16 weeks (n = 6 each group). Thereafter, bronchoalveolar lavage specimens were collected and cellular phenotypes and cytokine concentrations of IL-1alpha, IL-1beta, IL-2, IL-4, IL-6, IL-10, GM-CSF, IFN-gamma, TNF-alpha, and TGF-beta were determined. Results Following the administration of gastric fluid but not normal saline, histologic specimens exhibited prominent evidence of giant cells, fibrosis, lymphocytic bronchiolitis, and obliterative bronchiolitis. Bronchoalveolar lavage specimens from the left (treated) lungs exhibited consistently higher macrophages and T cells with an increased CD4:CD8 T cell ratio after treatment with gastric fluid compared to normal saline. The concentrations of IL-1alpha, IL-1beta, IL-2, TNF-alpha and TGF-beta were increased in bronchoalveolar lavage specimens following gastric fluid aspiration compared to normal saline. Conclusion This represents the first description of the pulmonary inflammatory response that results from chronic aspiration. Repetitive aspiration events can initiate an inflammatory response consisting of macrophages and T cells that is associated with increased TGF-beta, TNF-alpha, IL-1alpha, IL-1beta, IL-2 and fibrosis in the lung. Combined with the observation of gastric fluid-induced lymphocyitic bronchiolitis and obliterative bronchiolitis, these findings further support an association between chronic aspiration and pulmonary diseases, such as obliterative bronchiolitis, pulmonary fibrosis, and asthma.
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Affiliation(s)
- James Z Appel
- Transplant Immunobiology Laboratory, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
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Di Lorenzo G, Mansueto P, Esposito-Pellitteri M, Ditta V, Castello F, Lo Bianco C, Leto-Barone MS, Di Fede G, Traverso M, Rotolo G, Vigneri S, Rini G. The characteristics of different diagnostic tests in adult mild asthmatic patients: comparison with patients with asthma-like symptoms by gastro-oesophageal reflux. Respir Med 2007; 101:1455-61. [PMID: 17360170 DOI: 10.1016/j.rmed.2007.01.014] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2006] [Revised: 11/26/2006] [Accepted: 01/21/2007] [Indexed: 12/25/2022]
Abstract
BACKGROUND Diagnosing asthma cannot be always easy. It is important to consider the validity of the diagnostic tests, and/or how much more commonly they are positive in patients with asthma compared to healthy subjects and, particularly, to patients with asthma-like symptoms. OBJECTIVE To evaluate the validity of diagnostic tests for asthma, in terms of sensitivity, specificity, positive and negative predictive values, in patients with bronchial asthma compared to patients affected by gastro-oesophageal reflux disease (GERD) with asthma-like symptoms, and healthy control subjects without asthma and gastro-oesophageal reflux (GER). DESIGN Single-center, cross-sectional, observational study. PATIENTS We studied 60 patients with mild asthma, 30 patients with GERD and asthma-like symptoms and 25 healthy control subjects. MEASUREMENTS We measured provocative concentration of methacholine causing a 20% fall in the forced expiratory volume in 1s (MCh PC(20)/FEV(1)), the amplitude percent mean of peak expiratory flow (A%M of PEF), derived from twice-daily readings for >2 weeks, the FEV(1)/forced vital capacity (FEV(1)/FVC) ratio, the eosinophil count in blood and in induced sputum and the serum eosinophil cationic protein (ECP) levels. RESULTS FEV(1)/FVC ratio, A%M of PEF, blood eosinophils counts and serum ECP levels were less sensitive and specific when the reference population was composed of patients with asthma-like symptoms by GER. While, MCh PC(20)/FEV(1) and induced sputum eosinophils count were the most sensitive (both 90%) and specific (89% and 92%, respectively) tests. CONCLUSION Our findings demonstrate that MCh PC(20)/FEV(1) and the induced sputum eosinophil count are the most useful objective tests in patients with mild asthma. All patients with asthma presented both an MCh PC(20)/FEV(1) <1500 microg and eosinophils count in the induced sputum >1%.
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Affiliation(s)
- Gabriele Di Lorenzo
- Dipartimento di Medicina Clinica e delle Patologie Emergenti, Università degli Studi di Palermo, Via del Vespro no. 141, 90127 Palermo, Italy.
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Dore MP, Pedroni A, Pes GM, Maragkoudakis E, Tadeu V, Pirina P, Realdi G, Delitala G, Malaty HM. Effect of antisecretory therapy on atypical symptoms in gastroesophageal reflux disease. Dig Dis Sci 2007; 52:463-8. [PMID: 17211695 DOI: 10.1007/s10620-006-9573-7] [Citation(s) in RCA: 64] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2006] [Accepted: 08/15/2006] [Indexed: 02/07/2023]
Abstract
The effect of proton pump inhibitor (PPI) therapy on extraesophageal or atypical manifestations of gastroesophageal reflux disease (GERD) remains unclear. This study aimed to evaluate the prevalence of atypical manifestations in patients with acid reflux disease and the effect of PPI treatment. Patients with symptoms and signs suggestive of reflux were enrolled. Erosive esophagitis was stratified using the Los Angeles classification. Demographic data and symptoms were assessed using a questionnaire and included typical symptoms (heartburn, regurgitation, dysphagia, odynophagia), and atypical symptoms (e.g., chest pain, sialorrhea, hoarseness, globus sensation, chronic coughing, episodic bronchospasm, hiccup, eructations, laryngitis, and pharyngitis). Symptoms were reassessed after a 3-month course of b.i.d. PPI therapy. A total of 266 patients with a first diagnosis of GERD (erosive, 166; non-erosive, 100) were entered in the study. Presentation with atypical symptoms was approximately equal in those with erosive GERD and with non-erosive GERD, 72% vs 79% (P = 0.18). None of the study variables showed a significant association with the body mass index. PPI therapy resulted in complete symptom resolution in 69% (162/237) of the participants, 12% (28) had improved symptoms, and 20% (47) had minimal or no improvement. We conclude that atypical symptoms are frequent in patients with GERD. A trial of PPI therapy should be considered prior to referring these patients to specialists.
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Affiliation(s)
- Maria Pina Dore
- Istituto di Clinica Medica, Università di Sassari, Viale San Pietro 8, Sassari, Italy.
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Shimizu Y, Dobashi K, Kobayashi S, Ohki I, Tokushima M, Kusano M, Kawamura O, Shimoyama Y, Utsugi M, Mori M. High prevalence of gastroesophageal reflux disease with minimal mucosal change in asthmatic patients. TOHOKU J EXP MED 2006; 209:329-36. [PMID: 16864955 DOI: 10.1620/tjem.209.329] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
It is known that the prevalence of gastroesophageal reflux disease (GERD) in asthmatic patients is high. Although an endoscopic diagnosis of GERD based on the established Los Angeles (LA) classification requires the detection of erosive mucosal breaks, there are patients with GERD who have prominent erythema of the esophageal membrane without erosive mucosal breaks. Non-erosive mucosal change denotes the minimal change of the discoloring type of reflux esophagitis. This study was undertaken to determine the prevalence of GERD in asthmatic patients using the LA classification with the inclusion of minimal change, compared to the prevalence determined using the established LA classification without minimal change. The presence of GERD in asthmatic patients (n = 78), non-asthmatic disease control patients (n = 56), and healthy subjects (n = 150) was evaluated by endoscopic examination. The frequency of GERD in asthmatic patients based on the LA classification with minimal change was higher (54/78, 69.2%) than in asthmatic patients based on the LA classification without minimal change (37/78, 47.4%) (p < 0.05). The prevalence of GERD in asthmatic patients (69.2%) was higher than that in disease control patients (17/56, 30.4%) and healthy subjects (27/150, 18.0%) based on the LA classification with minimum change. These data indicate that asthmatic patients have a high frequency of GERD. In addition, without the inclusion of minimum change to the diagnosis of GERD, the prevalence of GERD appears to be underestimated in asthmatic patients. Therefore, physicians should carefully observe asthmatic patients with minimal change on endoscopy.
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Affiliation(s)
- Yasuo Shimizu
- Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Japan.
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Rascon-Aguilar IE, Pamer M, Wludyka P, Cury J, Coultas D, Lambiase LR, Nahman NS, Vega KJ. Role of Gastroesophageal Reflux Symptoms in Exacerbations of COPD. Chest 2006; 130:1096-101. [PMID: 17035443 DOI: 10.1378/chest.130.4.1096] [Citation(s) in RCA: 114] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022] Open
Abstract
BACKGROUND AND AIMS The impact of gastroesophageal reflux disease (GERD) on exacerbations of COPD has never been evaluated. The aims of this investigation were to determine the prevalence of gastroesophageal reflux (GER) symptoms in COPD patients and the effect of GER on the rate of exacerbations of COPD per year. METHODS A questionnaire-based, cross sectional survey was performed. Subjects were recruited from the outpatient pulmonary clinics at the University of Florida Health Science Center/Jacksonville. Included patients had an established diagnosis of COPD. Exclusion criteria were respiratory disorders other than COPD, known esophageal disease, active peptic ulcer disease, Zollinger-Ellison syndrome, mastocytosis, scleroderma, and current alcohol abuse. Those meeting criteria and agreeing to participate were asked to complete the Mayo Clinic GERD questionnaire by either personal/telephone interview. Clinically significant reflux was defined as heartburn and/or acid regurgitation weekly. Other outcome measures noted were frequency and type of COPD exacerbations. Statistical analysis was performed using the Fisher exact test for categorical data and the independent t test for interval data. RESULTS Eighty-six patients were enrolled and interviewed (mean age, 67.5 years). Male patients accounted for 55% of the study group. Overall, 37% of patients reported GER symptoms. The mean FEV(1) percentage of predicted was similar in those with or without GER. The rate of exacerbations of COPD was twice as high in patients with GER symptoms compared to those without GER symptoms (3.2/yr vs 1.6/yr, p = 0.02). CONCLUSIONS The presence of GER symptoms appears to be associated with increased exacerbations of COPD.
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Affiliation(s)
- Ivan E Rascon-Aguilar
- University of Florida Health Science Center/Jacksonville, Division of Gastroenterology, 4555 Emerson Expressway, Suite 300, Jacksonville, FL 32207, USA
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Ylitalo R, Lindestad P, Hertegård S. Pharyngeal and laryngeal symptoms and signs related to extraesophageal reflux in patients with heartburn in gastroenterology practice: a prospective study. Clin Otolaryngol 2006; 30:347-52. [PMID: 16209677 DOI: 10.1111/j.1365-2273.2005.00996.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
OBJECTIVES To describe pharyngeal and laryngeal symptoms and findings in correlation to extraesophageal reflux (EER) in patients with heartburn. DESIGN A prospective study. SETTING Patients referred to Department of Gastroenterology, Karolinska University Hospital Huddinge. PARTICIPANTS Forty-three patients with chronic heartburn as the primary symptom, subdivided on the basis of oesophageal manometry to have gastro-oesophageal reflux disease (GORD) (n = 25) or not (n = 18). MAIN OUTCOME MEASURES Laryngeal video recordings of 43 patients were examined off-line. The occurrence of symptoms and laryngeal pathology were correlated to the results of 24-h double-probe pH monitoring. RESULTS Pharyngeal or laryngeal symptoms occurred often or quite often in 72% (18 of 25) of the GORD patients and 61% (11 of 18) of the patients without GORD. EER occurred in 73% (16 of 22) of the GORD patients with laryngeal symptoms and in 38% (6 of 16) of those without GORD but with laryngeal symptoms (P = 0.047). In the multivariate analysis the odds for hoarseness was 17 times higher if the patient had heartburn more than five times a day, compared with patients with heartburn less than once a day (OR 17.8, CI 1.7-405.9; P = 0.01). Cohen's kappa for intrarater reliability was 0.851 (P = 0.001). Laryngeal pathology was found in 56% of the GORD patients and 44% patients without GORD. There was no significant difference in the occurrence of any specific symptom or finding between the patients with and without GORD, nor with and without EER. CONCLUSIONS Although GORD together with laryngeal symptoms seem to be predictive of EER, there are no specific pharyngeal and laryngeal symptoms or findings that would help distinguishing patients with EER from those without. However, the more frequent the heartburn to the more frequent is hoarseness.
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Affiliation(s)
- R Ylitalo
- Department of Logopedics and Phoniatrics B 69, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden.
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Geppetti P, Materazzi S, Nicoletti P. The transient receptor potential vanilloid 1: role in airway inflammation and disease. Eur J Pharmacol 2006; 533:207-14. [PMID: 16464449 DOI: 10.1016/j.ejphar.2005.12.063] [Citation(s) in RCA: 142] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/13/2005] [Indexed: 12/25/2022]
Abstract
The transient receptor potential vanilloid 1 (TRPV1) is an excitatory cation channel, rather selectively expressed in a subpopulation of nociceptive, primary sensory neurons that promote neurogenic inflammation via neuropeptide release. TRPV1 is activated by noxious temperature, low extracellular pH and diverse lipid derivatives, and is uniquely sensitive to vanilloid molecules, including capsaicin. TRPV1 expression and sensitivity is highly regulated by diverse G protein-coupled and tyrosine kinase receptors. Other exogenous or endogenous chemical agents, including reactive oxygen species, ethanol and hydrogen sulphide sensitize/activate TRPV1. In the airways, TRPV1 agonists cause cough, bronchoconstriction, microvascular leakage, hyperreactivity and hypersecretion. Patients with asthma and chronic obstructive pulmonary disease are more sensitive to the tussive effect of TRPV1 agonists and TRPV1 activation may contribute to respiratory symptoms caused by acidic media present in the airways during asthma exacerbation, gastroesophageal reflux induced asthma or in other conditions. TRPV1 antagonists may be useful in the treatment of these diseases.
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Affiliation(s)
- Pierangelo Geppetti
- Clinical Pharmacology Unit, Department of Critical Care Medicine and Surgery, University of Florence, Italy.
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Abstract
OBJECTIVES To describe the anatomy and neurophysiology of the cough reflex. METHODS A review of the literature was carried out using PubMed and the ISI Web of Knowledge from 1951 to 2004. Most of the referenced studies were carried out in animals CONCLUSIONS Studies carried out in animals provide suggestive but inconclusive evidence that C-fibers and rapidly adapting receptors (RARs) arising from the vagus nerves mediate coughing. Recent studies also have suggested that a vagal afferent nerve subtype that is not readily classified as a RAR or a C-fiber may play an important role in regulating cough. Afferent nerves innervating other viscera, as well as somatosensory nerves innervating the chest wall, diaphragm, and abdominal musculature also likely play a less essential but important accessory role in regulating cough. The responsiveness and morphology of the airway vagal afferent nerve subtypes and the extrapulmonary afferent nerves that regulate coughing are described.
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Effros RM, Casaburi R, Su J, Dunning M, Torday J, Biller J, Shaker R. The effects of volatile salivary acids and bases on exhaled breath condensate pH. Am J Respir Crit Care Med 2005; 173:386-92. [PMID: 16284109 PMCID: PMC2662940 DOI: 10.1164/rccm.200507-1059oc] [Citation(s) in RCA: 79] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
RATIONALE Recent studies have reported acidification of exhaled breath condensate (EBC) in inflammatory lung diseases. This phenomenon, designated "acidopnea," has been attributed to airway inflammation. OBJECTIVES To determine whether salivary acids and bases can influence EBC pH in chronic obstructive pulmonary disease (COPD). METHODS Measurements were made of pH, electrolytes, and volatile bases and acids in saliva and EBC equilibrated with air in 10 healthy subjects and 10 patients. RESULTS The average EBC pH in COPD was reduced (normal, 7.24 +/- 0.24 SEM; range, 6.11-8.34; COPD, 6.67 +/- 0.18; range, 5.74-7.64; p = 0.079). EBCs were well buffered by NH(4)(+)/NH(3) and CO(2)/HCO(3)(-) in all but four patients, who had NH(4)(+) concentrations under 60 micromol/L, and acetate concentrations that approached or exceeded those of NH(4)(+). Saliva contained high concentrations of acetate (approximately 6,000 micromol/L) and NH(4)(+) (approximately 12,000 micromol/L). EBC acetate increased and EBC NH(4)(+) decreased when salivary pH was low, consistent with a salivary source for these volatile constituents. Nonvolatile acids did not play a significant role in determining pH of condensates because of extreme dilution of respiratory droplets by water vapor (approximately 1:12,000). Transfer of both acetic acid and NH(3) from the saliva to the EBC was in the gas phase rather than droplets. CONCLUSIONS EBC acidification in COPD can be affected by the balance of volatile salivary acids and bases, suggesting that EBC pH may not be a reliable marker of airway acidification. Salivary acidification may play an important role in acidopnea.
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Affiliation(s)
- Richard M Effros
- Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1124 West Carson Street, Torrance, CA 90502-2064, USA.
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Nonalloimmune mechanisms contributing to lung allograft dysfunction: a potential role for gastroesophageal reflux disease. Curr Opin Organ Transplant 2005. [DOI: 10.1097/01.mot.0000169366.00143.73] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Effros RM, Su J, Casaburi R, Shaker R, Biller J, Dunning M. Utility of exhaled breath condensates in chronic obstructive pulmonary disease: a critical review. Curr Opin Pulm Med 2005; 11:135-9. [PMID: 15699785 DOI: 10.1097/00063198-200503000-00006] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE OF REVIEW Evaluation of the utility of exhaled breath condensates in chronic obstructive pulmonary disease. RECENT FINDINGS Exhaled breath condensates have recently been introduced as a simple, noninvasive method of sampling respiratory fluid in inflammatory lung disorders, including chronic obstructive pulmonary disease. Increases in condensate concentrations of at least 12 markers of inflammation have been reported in these disorders. Furthermore, condensate pH appears to be decreased in both chronic obstructive lung disease and bronchial asthma. This has been referred to as acidopnea and could reflect airway acidification by inflammatory cells. Although safer and more convenient than bronchoalveolar lavage, interpretation of condensate data is complicated by uncertainty regarding the source of condensate solutes and by variable dilution of respiratory droplets from condensed water vapor, which represents more than 99.9% of condensate volumes. This dilution can be estimated from the dilution of plasma constituents such as urea or electrolytes. Because the principal buffer in condensate is NH4, much of which is derived from bacterial degradation of urea in the mouth, condensate pH measurements may not provide accurate estimates of airway pH. Nevertheless, acidification of condensate may be indicative of gastroesophageal reflux, which frequently occurs in obstructive lung diseases and may contribute to cough and bronchospasm. SUMMARY It is too early to tell how useful condensate studies will be to pulmonary investigators and clinicians. Realization of the enormous potential of this approach will require a thorough understanding of the manner in which these solutions are generated and how they should be analyzed.
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Affiliation(s)
- Richard M Effros
- Department of Medicine, Harbor-UCLA Medical Center, Torrance, California, USA.
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Abstract
Asthma is a well-recognized disease and one of the most common illnesses in childhood. More recently, gastroesophageal reflux disease has increasingly been appreciated as a common daily occurrence in children and adolescents. These two diagnoses often present in tandem, with their coexistence being more frequent than would be expected for a chance occurrence. The mainstay of asthma management is the regulation and control of chronic airway hyperreactivity and inflammation. Children who do not respond to standard asthma regimens should be evaluated for other sources of their pulmonary symptoms, most notably gastroesophageal reflux. Baseline assessment of pulmonary function tests followed by an empiric trial of proton pump inhibitor therapy, using double the standard doses commonly used in acid-related disorders and administered for 3 months, is a cost-effective, noninvasive diagnostic strategy. Children who fail to exhibit pulmonary symptom improvement should be evaluated for both medication compliance and proper administration. Twenty-four-hour esophageal pH monitoring with concurrent dairy recordings of their symptoms is recommended to ascertain adequacy of acid suppression and confirm the diagnosis in those who continue to have symptoms. Children with acid-related causes of their pulmonary symptoms often require long-term treatment. Studies have confirmed the efficacy, safety, and tolerability of proton pump inhibitors in the treatment of children and adolescents. Surgery should be reserved for those with severe disease and those who are unable to comply with pharmacologic treatment.
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Affiliation(s)
- Benjamin D Gold
- Department of Pediatrics, Division of Pediatric Gastroenterology and Nutrition, Emory University School of Medicine, Atlanta, Georgia 30322, USA
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Abstract
Gastroesophageal reflux disease (GERD) may manifest as laryngitis, asthma, cough, or noncardiac chest pain. Diagnosing these extraesophageal manifestations may be difficult for primary care physicians because most patients do not have heartburn or regurgitation. Diagnostic tests have low specificity, and a cause-and-effect association between GERD and extraesophageal symptoms is difficult to establish. Response to aggressive acid suppression is often the best indication of GERD etiology in a patient with extraesophageal symptoms.
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Affiliation(s)
- Michael F Vaezi
- Center for Swallowing and Esophageal Disorders, Department of Gastroenterology and Hepatology, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
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