Diagnosis and minimally invasive treatment of gastroesophageal reflux disease in patients with advanced lung disease

Abstract

Biomechanical damage to the respiratory epithelium by acidic refluxate and endopeptidases (such as activated pepsin) are thought to be key mechanisms by which gastroesophageal reflux disease (GERD) contributes to the development and worsening of chronic respiratory disorders. These chronic disorders include chronic cough, asthma, suppurative lung diseases, chronic obstructive pulmonary disease, and idiopathic pulmonary fibrosis (IPF). In such patients, acid suppression therapy to treat GERD and associated respiratory symptoms has produced controversial results, as these treatments decrease the acidity of the refluxate but do not prevent gastroesophageal reflux and aspiration itself. Consequently, mechanical control of GERD through laparoscopic and endoscopic procedures is a plausible option to halt the progression of such chronic respiratory disorders. This article provides an overview of GERD diagnosis and therapeutic alternatives (i.e., pharmacological therapy, antireflux surgery, and other minimally invasive procedures) in the context of advanced pulmonary disease, particularly IPF.

Keywords

Antireflux surgery / fundoplication / gastroesophageal reflux / GERD / lung diseases / respiratory diseases / pulmonary fibrosis / respiratory aspiration

References

[1] Antunes C,Curtis SA.Gastroesophageal Reflux Disease. [Updated 2022 May 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441938/ [accessed 27 April 2025]

[2] Eusebi LH,Yuan Y,Bazzoli F.Global prevalence of, and risk factors for, gastro-oesophageal reflux symptoms: a meta-analysis.Gut2018;67:430-40

[3] Dunbar KB.Gastroesophageal reflux disease.Ann Intern Med2024;177:ITC113-28

[4] Lee JS.The Role of Gastroesophageal reflux and microaspiration in idiopathic pulmonary fibrosis.Clin Pulm Med2014;21:81-5 PMCID:PMC3979481

[5] Ghisa M,Savarino V.Idiopathic pulmonary fibrosis and GERD: links and risks.Ther Clin Risk Manag2019;15:1081-93 PMCID:PMC6733342

[6] Latorre-Rodríguez AR,Omar A,Mittal SK.Pulmonary and esophageal function in lung transplantation: Fundamental principles and clinical application.Transplant Rev (Orlando)2024;38:100796

[7] Masuda T,Kovács B.Foregut function before and after lung transplant.J Thorac Cardiovasc Surg2019;158:619-29

[8] Gao F,Shang ZM.The prevalence of gastro-esophageal reflux disease and esophageal dysmotility in Chinese patients with idiopathic pulmonary fibrosis.BMC Gastroenterol2015;15:26 PMCID:PMC4349612

[9] Gaude GS.Pulmonary manifestations of gastroesophageal reflux disease.Ann Thorac Med2009;4:115-23 PMCID:PMC2714564

[10] Baqir M,Vu AN.Idiopathic pulmonary fibrosis and gastroesophageal reflux disease: a population-based, case-control study.Respir Med2021;178:106309 PMCID:PMC7938662

[11] Méthot D, Leblanc É, Lacasse Y. Meta-analysis of gastroesophageal reflux disease and idiopathic pulmonary fibrosis.Chest2019;155:33-43

[12] Raghu G,Yang S.High prevalence of abnormal acid gastro-oesophageal reflux in idiopathic pulmonary fibrosis.Eur Respir J2006;27:136-42

[13] Johannson KA,Ravaglia C.Erice ILD Working GroupAntacid therapy in idiopathic pulmonary fibrosis: more questions than answers?.Lancet Respir Med2017;5:591-8

[14] Lee JS,Elicker BM.Gastroesophageal reflux therapy is associated with longer survival in patients with idiopathic pulmonary fibrosis.Am J Respir Crit Care Med2011;184:1390-4 PMCID:PMC3262030

[15] Irwin RS.Chronic cough due to gastroesophageal reflux disease: ACCP evidence-based clinical practice guidelines.Chest2006;129:80S-94S

[16] Tokayer AZ.Gastroesophageal reflux disease and chronic cough.Lung2008;186 Suppl 1:S29-34

[17] Bremner RM.Esophageal symptoms and selection of diagnostic tests. In Yeo CJ, Editor. Shackelford’s Surgery of the Alimentary Tract, 2 Volume Set: Amsterdam: Elsevier; 2019. pp. 44-56.

[18] Ciovica R,Klingler A,Schwab GP.Laparoscopic antireflux surgery provides excellent results and quality of life in gastroesophageal reflux disease patients with respiratory symptoms.J Gastrointest Surg2005;9:633-7

[19] Matyásová Z,Matulová M et al.The relation of GERD, bronchial asthma and the upper respiratory tract.Vnitr Lek2005;51(12):1341-1350

[20] Raghu G,Yow E.Laparoscopic anti-reflux surgery for the treatment of idiopathic pulmonary fibrosis (WRAP-IPF): a multicentre, randomised, controlled phase 2 trial.Lancet Respir Med2018;6:707-14

[21] D'Ovidio F,Hadjiliadis D.Prevalence of gastroesophageal reflux in end-stage lung disease candidates for lung transplant.Ann Thorac Surg2005;80:1254-60

[22] Hathorn KE,Lo WK.Role of gastroesophageal reflux disease in lung transplantation.World J Transplant2017;7:103-16 PMCID:PMC5409910

[23] Lo WK,Goldberg HJ,Chan WW.Pre-transplant impedance measures of reflux are associated with early allograft injury after lung transplantation.J Heart Lung Transplant2015;34:26-35

[24] Razia D,Bansal S.Association between antibodies against lung self-antigens and gastroesophageal reflux in lung transplant candidates.Semin Thorac Cardiovasc Surg2023;35:177-86

[25] Sweet MP,Leard L.The prevalence of distal and proximal gastroesophageal reflux in patients awaiting lung transplantation.Ann Surg2006;244:491-7 PMCID:PMC1856564

[26] Leung R,Sharma NS,Chan WW.Esophageal function and reflux evaluations in lung transplantation: a nationwide survey of UNOS-Accredited Transplant Centers in the United States.Clin Transl Gastroenterol2023;14:e00641 PMCID:PMC10749699

[27] Cantu E 3rd,Hartwig MG.J. Maxwell chamberlain memorial paper. early fundoplication prevents chronic allograft dysfunction in patients with gastroesophageal reflux disease.Ann Thorac Surg2004;78:1142-51; discussion 1142

[28] Davidson JR,Kumar S.Fundoplication to preserve allograft function after lung transplant: Systematic review and meta-analysis.J Thorac Cardiovasc Surg2020;160:858-66

[29] Robertson AG,Ward C.Anti-reflux surgery in lung transplant recipients: outcomes and effects on quality of life.Eur Respir J2012;39:691-7

[30] Biswas Roy S,Serrone R.Early fundoplication is associated with slower decline in lung function after lung transplantation in patients with gastroesophageal reflux disease.J Thorac Cardiovasc Surg2018;155:2762-2771.e1

[31] Snell GI,Weill D.Report of the ISHLT working group on primary lung graft dysfunction, part I: definition and grading-A 2016 Consensus Group statement of the International Society for Heart and Lung Transplantation.J Heart Lung Transplant2017;36:1097-103

[32] Hirji SA,Englum BR.Lung transplantation delays gastric motility in patients without prior gastrointestinal surgery - a single-center experience of 412 consecutive patients.Clin Transplant2017;31

[33] Masuda T,Csucska M.Esophageal aperistalsis and lung transplant: Recovery of peristalsis after transplant is associated with improved long-term outcomes.J Thorac Cardiovasc Surg2020;160:1613-26

[34] Howland AM.Gastroesophageal reflux disease management and chronic use of proton pump inhibitors.JAAPA2023;36:1-6

[35] Katz PO,Schnoll-Sussman FH,Yadlapati R.ACG Clinical Guideline for the diagnosis and management of gastroesophageal reflux disease.Am J Gastroenterol2022;117:27-56 PMCID:PMC8754510

[36] Shin JM.Pharmacology of proton pump inhibitors.Curr Gastroenterol Rep2008;10:528-34 PMCID:PMC2855237

[37] Yadlapati R,Pandolfino JE.CGIT GERD Consensus Conference ParticipantsAGA Clinical practice update on the personalized approach to the evaluation and management of GERD: expert review.Clin Gastroenterol Hepatol2022;20:984-994.e1 PMCID:PMC9838103

[38] Zhang H,Ni Z.A meta-analysis and systematic review of the efficacy of twice daily PPIs versus once daily for treatment of gastroesophageal reflux disease.Gastroenterol Res Pract2017;2017:9865963 PMCID:PMC5585660

[39] Rackoff A,Hila A,Tutuian R.Histamine-2 receptor antagonists at night improve gastroesophageal reflux disease symptoms for patients on proton pump inhibitor therapy.Dis Esophagus2005;18:370-3

[40] Ghebre YT.Idiopathic pulmonary fibrosis: novel concepts of proton pump inhibitors as antifibrotic drugs.Am J Respir Crit Care Med2016;193:1345-52 PMCID:PMC4910893

[41] Yoshida N,Tanaka Y.A new mechanism for anti-inflammatory actions of proton pump inhibitors--inhibitory effects on neutrophil-endothelial cell interactions.Aliment Pharmacol Ther2000;14 Suppl 1:74-81

[42] Khor YH,Ghazipura M.Antacid medication and antireflux surgery in patients with idiopathic pulmonary fibrosis: a systematic review and meta-analysis.Ann Am Thorac Soc2022;19:833-44

[43] Raghu G,Spada C,Pellegrini CA.Sole treatment of acid gastroesophageal reflux in idiopathic pulmonary fibrosis: a case series.Chest2006;129:794-800

[44] Costabel U,Crestani B.Anti-acid therapy in idiopathic pulmonary fibrosis: insights from the INPULSIS® trials.Respir Res2018;19:167 PMCID:PMC6122773

[45] Kreuter M,Wuyts W.Antacid therapy and disease progression in patients with idiopathic pulmonary fibrosis who received pirfenidone.Respiration2017;93:415-23 PMCID:PMC5452370

[46] Kreuter M,Renzoni E.Antacid therapy and disease outcomes in idiopathic pulmonary fibrosis: a pooled analysis.Lancet Respir Med2016;4:381-9

[47] Sigterman KE,Bonis PA,Numans ME.Short-term treatment with proton pump inhibitors, H2-receptor antagonists and prokinetics for gastro-oesophageal reflux disease-like symptoms and endoscopy negative reflux disease.Cochrane Database Syst Rev2013;2013:CD002095 PMCID:PMC7066537

[48] Kinoshita Y,Ishihara S.Advantages and disadvantages of long-term proton pump inhibitor use.J Neurogastroenterol Motil2018;24:182-96 PMCID:PMC5885718

[49] Fackler WK,Vaezi MF.Long-term effect of H2RA therapy on nocturnal gastric acid breakthrough.Gastroenterology2002;122:625-32

[50] Yadlapati R.Proton pump inhibitor-refractory gastroesophageal reflux disease.Med Clin North Am2019;103:15-27 PMCID:PMC6260943

[51] Mandel KG,Brodie DA.Review article: alginate-raft formulations in the treatment of heartburn and acid reflux.Aliment Pharmacol Ther2000;14:669-90

[52] Ren LH,Qian LJ,Gu M.Addition of prokinetics to PPI therapy in gastroesophageal reflux disease: a meta-analysis.World J Gastroenterol2014;20:2412-9 PMCID:PMC3942846

[53] Leiman DA,Morgan S.Alginate therapy is effective treatment for GERD symptoms: a systematic review and meta-analysis.Dis Esophagus2017;30:1-9 PMCID:PMC6036656

[54] Xi L,Zhang H,Li Y.The treatment efficacy of adding prokinetics to PPIs for gastroesophageal reflux disease: a meta-analysis.Esophagus2021;18:144-51

[55] Biswas M,Shetty YC,Ingawale S.Prescription pattern & adverse drug reactions of prokinetics.Indian J Med Res2019;149:748-54 PMCID:PMC6755782

[56] Costabel U,Cottin V.Pirfenidone in idiopathic pulmonary fibrosis: expert panel discussion on the management of drug-related adverse events.Adv Ther2014;31:375-91 PMCID:PMC4003341

[57] Pan L,Chen Y,Limb SL.Effect of pirfenidone on gastric emptying in a rat model.Pulm Pharmacol Ther2018;51:41-7

[58] Raghu G,Richeldi L.Idiopathic pulmonary fibrosis (an update) and progressive pulmonary fibrosis in adults: an official ATS/ERS/JRS/ALAT clinical practice guideline.Am J Respir Crit Care Med2022;205:e18-47 PMCID:PMC9851481

[59] Frazzoni M,Conigliaro R,Melotti G.Laparoscopic fundoplication for gastroesophageal reflux disease.World J Gastroenterol2014;20:14272-9 PMCID:PMC4202356

[60] Salvador R,Capovilla G.Antireflux Surgery’s Lifespan: 20 years after laparoscopic fundoplication.J Gastrointest Surg2023;27:2325-35 PMCID:PMC10661768

[61] Linden PA,Yeap BY.Laparoscopic fundoplication in patients with end-stage lung disease awaiting transplantation.J Thorac Cardiovasc Surg2006;131:438-46

[62] Raghu G,Collins BF.Laparoscopic anti-reflux surgery for idiopathic pulmonary fibrosis at a single centre.Eur Respir J2016;48:826-32

[63] Callahan ZM,Su B,Ujiki M.Outcomes after anti-reflux procedures: Nissen, Toupet, magnetic sphincter augmentation or anti-reflux mucosectomy?.Surg Endosc2023;37:3944-51

[64] Canto MI,Parker B.Outcomes of transoral incisionless fundoplication (TIF 2.0): a prospective multicenter cohort study in academic and community gastroenterology and surgery practices (with video).Gastrointest Endosc2025;101:90-102.e1

[65] Fass R,Scotti DJ.Systematic review and meta-analysis of controlled and prospective cohort efficacy studies of endoscopic radiofrequency for treatment of gastroesophageal reflux disease.Surg Endosc2017;31:4865-82

[66] Rodríguez L,Gómez B.Two-year results of intermittent electrical stimulation of the lower esophageal sphincter treatment of gastroesophageal reflux disease.Surgery2015;157:556-67

[67] Halpern SE,Jawitz OK.Safety and efficacy of an implantable device for management of gastroesophageal reflux in lung transplant recipients.J Thorac Dis2021;13:2116-27 PMCID:PMC8107527

[68] Kolbeinsson HM,Banks-Venegoni A,Scheeres DE.Treatment of gastroesophageal reflux disease after lung transplant using radiofrequency ablation to the lower esophageal sphincter (stretta procedure).Am Surg2022;88:1663-8

[69] Latorre-Rodríguez AR,Mittal SK.Magnetic sphincter augmentation may limit access to magnetic resonance imaging.Dis Esophagus2023;36:doad032

[70] Ardila-Gatas J,Nor Hanipah Z.Bariatric surgery in patients with interstitial lung disease.Surg Endosc2019;33:1952-8

[71] Yuce TK,Merkow RP,Bilimoria KY.Post-operative complications and readmissions following outpatient elective Nissen fundoplication.Surg Endosc2020;34:2143-8 PMCID:PMC7382912

[72] Carr ZJ,Chavez-Duarte J,Oprea A.Perioperative management of patients with idiopathic pulmonary fibrosis undergoing noncardiac surgery: a narrative review.Int J Gen Med2022;15:2087-100 PMCID:PMC8882471