Relationship Between GERD Comorbidity and The Severity of Nocturnal Asthma Symptoms: A Systematic Review
Keywords:
Nocturnal asthma, GERD, gastroesophageal reflux, sleep, proton pump inhibitors, fundoplication, obstructive sleep apneaAbstract
Background: Gastroesophageal reflux disease (GERD) and asthma are common comorbid conditions, but the specific impact of GERD on the severity of nocturnal asthma symptoms remains debated.
Methods: This systematic review synthesized evidence from 80 studies, including randomized controlled trials (RCTs), etc. We focused on the prevalence of GERD in asthma, the strength of association with nocturnal symptoms, pathophysiological mechanisms, and treatment outcomes.
Results: The weighted average prevalence of GERD symptoms in asthma patients was 59.2% vs. 38.1% in non-asthmatics (p<0.001). Nocturnal GERD (nGER) was independently associated with new asthma onset (OR 2.3, 95% CI 1.1–4.9) and incident wheeze (OR 2.18, 95% CI 1.60–2.98). Bidirectional epidemiological data showed GERD increased asthma risk (HR 1.46, 95% CI 1.42–1.49) and asthma increased GERD risk (HR 1.36, 95% CI 1.33–1.39). Mechanistically, esophageal acid perfusion induced bronchoconstriction via vagal reflex and microaspiration. Surgical antireflux therapy reduced nocturnal exacerbations (74.9% improvement vs. 9.1% with medical therapy, p<0.001). However, proton pump inhibitors (PPIs) showed no significant improvement in morning PEF (WMD 8.68 L/min, 95% CI -2.02 to 19.37, p=0.11) in unselected asthmatics. Obesity and obstructive sleep apnea (OSA) were major confounders; in obese asthmatics, OSA rather than GERD drove nocturnal symptoms.
Discussion: The apparent paradox between strong epidemiological associations and weak PPI treatment effects is explained by non-acid reflux mechanisms, patient heterogeneity, and colinear comorbidities.
Conclusion: Nocturnal GERD significantly increases asthma severity and incidence, but PPI therapy benefits only symptomatic, confirmed GERD subgroups. Surgical fundoplication and CPAP (in OSA+GERD) improve nocturnal asthma outcomes.
References
Havemann B, Henderson C, El‐Serag H (2007) The association between gastro-oesophageal reflux disease and asthma: a systematic review. Gut. https://doi.org/10.1136/gut.2007.122465
Gorban V, Kovrigina IV, Gorban EV, et al (2023) Syntropy of bronchial asthma and gastroesophageal reflux disease: pathogenetic features and possibilities of minimally invasive diagnostics at the outpatient stage. South Russian Journal of Therapeutic Practice. https://doi.org/10.21886/2712-8156-2023-4-2-25-34
Emilsson Ö, Bengtsson A, Franklin K, et al (2012) Nocturnal gastro-oesophageal reflux, asthma and symptoms of OSA: a longitudinal, general population study. European Respiratory Journal. https://doi.org/10.1183/09031936.00052512
Fakhraei RM, Lindberg E, Benediktsdóttir B, et al (2023) Gastroesophageal reflux and snoring are related to asthma and respiratory symptoms: Results from a Nordic longitudinal population survey. Respiratory Medicine. https://doi.org/10.1016/j.rmed.2023.107495
Alhajery M (2024) The Nocturnal Nexus: A Systematic Review of the Association Between Night-time Asthma and GERD Incidence. Journal of Pioneering Medical Science. https://doi.org/10.61091/jpms2024130613
DiMango E, Holbrook J, Simpson E, et al (2009) Effects of asymptomatic proximal and distal gastroesophageal reflux on asthma severity. American Journal of Respiratory and Critical Care Medicine. https://doi.org/10.1164/rccm.200904-0625OC
Dixon A, Clerisme-Beaty E, Sugar E, et al (2011) Effects of Obstructive Sleep Apnea and Gastroesophageal Reflux Disease on Asthma Control in Obesity. Journal of Asthma. https://doi.org/10.3109/02770903.2011.601778
Zheng Z, Luo Y, Li J, Gao J (2021) Randomised trials of proton pump inhibitors for gastro-oesophageal reflux disease in patients with asthma: an updated systematic review and meta-analysis. BMJ Open. https://doi.org/10.1136/bmjopen-2020-043860
Gibson P, Henry R, Coughlan J (2003) Gastro-oesophageal reflux treatment for asthma in adults and children. Cochrane Database of Systematic Reviews. https://doi.org/10.1002/14651858.CD001496
Sontag S, O'connell S, Khandelwal S, et al (2003) Asthmatics with gastroesophageal reflux: Long term results of a randomized trial of medical and surgical antireflux therapies. American Journal of Gastroenterology. https://doi.org/10.1111/j.1572-0241.2003.07503.x
Crnčević-Urek M (2008) Učinak omeprazola na simptome astme u bolesnika s astmom i GERB-om
Shigemitsu H, Afshar K (2007) Nocturnal asthma. Current opinion in pulmonary medicine. https://doi.org/10.1097/MCP.0b013e328010a890
Sontag S, O'connell S, Khandelwal S, et al (2003) Asthmatics with gastroesophageal reflux: long term results of a randomized trial of medical and surgical antireflux therapies. The American Journal of Gastroenterology. https://doi.org/10.1016/S0002-9270(03)00283-1
Hamed NF, AlAlwan A, Alqahtani FJ, et al (2025) The Bidirectional Relationship Between Gastroesophageal Reflux Disease (GERD) and Asthma in Pediatric and Adult Populations: A Systematic Review. Cureus. https://doi.org/10.7759/cureus.99995
Yap HS, Hnin K, Tin K, et al (2014) Gastro-oesophageal reflux (GOR) treatment for asthma in adults and children: A cochrane systematic review. European Respiratory Journal
Rui L (2010) Effects of continuous positive airway pressure treatment on patients of obstructive sleep apnea syndrome accompanying with asthma. BMJ. https://doi.org/10.3760/CMA.J.ISSN.1671-7368.2010.08.008
Mallah N, Turner J, González-Barcala F, Takkouche B (2021) Gastroesophageal reflux disease and asthma exacerbation: A systematic review and meta‐analysis. Pediatric Allergy and Immunology. https://doi.org/10.1111/pai.13655
Canale C, Young D, Koelliker E, et al (2004) Silent Gastroesophageal Reflux and Asthma: The Value of Empiric Acid Suppression Therapy. Chest. https://doi.org/10.1378/CHEST.126.4_MEETINGABSTRACTS.705S
Grandes XA, Manjunatha RT, Habib S, et al (2022) Gastroesophageal Reflux Disease and Asthma: A Narrative Review. Cureus. https://doi.org/10.7759/cureus.24917
Rogers L (2016) Role of Sleep Apnea and Gastroesophageal Reflux in Severe Asthma. Immunology and allergy clinics of North America. https://doi.org/10.1016/j.iac.2016.03.008
Paoletti G, Melone G, Ferri S, et al (2020) Gastroesophageal reflux and asthma: when, how, and why. Current Opinion in Allergy and Clinical Immunology. https://doi.org/10.1097/ACI.0000000000000705
Greenberg H, Cohen R (2012) Nocturnal asthma. Current opinion in pulmonary medicine. https://doi.org/10.1097/MCP.0b013e32834d098e
Kim SY, Min C, Oh D, Choi H (2019) Bidirectional association between GERD and asthma: Two longitudinal follow-up studies using a national sample cohort. Journal of Allergy and Clinical Immunology: In Practice. https://doi.org/10.1016/j.jaip.2019.10.043
Mathew JL, Singh M, Mittal S (2004) Gastro-oesophageal reflux and bronchial asthma: current status and future directions. Postgraduate medical journal. https://doi.org/10.1136/pgmj.2004.019265
Ahmed Z, Rehman MHU, Rehman FA, et al (2025) Association Between Gastroesophageal Reflux Disease and Chronic Respiratory Symptoms: A Systematic Review of Recent Clinical Evidence and Therapeutic Implications. Cureus. https://doi.org/10.7759/cureus.91372
McCallister J, Parsons JP, Mastronarde J (2011) The relationship between gastroesophageal reflux and asthma: an update. Therapeutic Advances in Respiratory Disease. https://doi.org/10.1177/1753465810384606
Parsons JP, Mastronarde J (2010) Gastroesophageal reflux disease and asthma. Current opinion in pulmonary medicine. https://doi.org/10.1097/MCP.0b013e328332ca2f
Fass R, Achem S, Harding S, et al (2004) Review article: supra‐oesophageal manifestations of gastro‐oesophageal reflux disease and the role of night‐time gastro‐oesophageal reflux. Alimentary Pharmacology and Therapeutics. https://doi.org/10.1111/j.1365-2036.2004.02253.x
Ateş F, Vaezi M (2014) Insight Into the Relationship Between Gastroesophageal Reflux Disease and Asthma. Gastroenterology & hepatology
Dumra H, Sainani R, Pratap N, et al (2023) Expert Recommendations on Optimizing the Diagnosis and Management of Gastroesophageal Reflux Disease Associated with Comorbidities in the Indian Population. Journal of Association of Physicians of India. https://doi.org/10.59556/japi.71.0269
Bansal V, Hajifathalian K, Mittal A, et al (2016) Gastroesophageal Reflux Disease (GERD) Is Associated with Worse Outcomes in Patients with Asthma Presenting to the Emergency Department: 496. The American Journal of Gastroenterology. https://doi.org/10.14309/00000434-201610001-00496
Durrani S, Mukkada V, Guilbert T (2018) Eosinophilic Esophagitis: an Important Comorbid Condition of Asthma? Clinical reviews in allergy and immunology. https://doi.org/10.1007/s12016-018-8670-7
Hungin A, Raghunath A, Wiklund I (2005) Beyond heartburn: a systematic review of the extra-oesophageal spectrum of reflux-induced disease. Family Practice. https://doi.org/10.1093/FAMPRA/CMI061
Patel G, Peters AT (2019) Comorbidities associated with severe asthma. Journal of Precision Respiratory Medicine. https://doi.org/10.2500/jprm.2019.190006
Kaplan A, Szefler S, Halpin D (2020) Impact of comorbid conditions on asthmatic adults and children. npj Primary Care Respiratory Medicine. https://doi.org/10.1038/s41533-020-00194-9
Messmann H, Ell C, Fein M, et al (2005) Themenkomplex VI: Barrett-Ösophagus. Zeitschrift für Gastroenterologie. https://doi.org/10.1055/s-2005-857876
Amarasiri DL, Pathmeswaran A, Silva H de, Ranasinha C (2013) Response of the airways and autonomic nervous system to acid perfusion of the esophagus in patients with asthma: a laboratory study. BMC Pulmonary Medicine. https://doi.org/10.1186/1471-2466-13-33
Launois C, Mulette P, Ancel J, et al (2021) [Treatment of GERD in asthma]. Revue des maladies respiratoires. https://doi.org/10.1016/j.rmr.2021.04.013
Raherison C (2010) [Epidemiology of asthma and COPD in France]. Revue des maladies respiratoires. https://doi.org/10.1016/j.rmr.2010.01.012
Wang X, Wang Y, Bu Y, et al (2025) Association of gastroesophageal reflux disease with the incidence of pulmonary disease. Frontiers in Cell and Developmental Biology. https://doi.org/10.3389/fcell.2025.1552126
Awad T, Ayoub AS, Mohammad S, El-Naggar M (2019) Study of Chest Disorders in Non-Smoker Patients Complaining of Gastroesophageal Reflux Disease. The Medical journal of Cairo University. https://doi.org/10.21608/mjcu.2019.59519
Kharaba Z, Burns G, Ward C, et al (2019) A proof of concept study describing extraoesophageal reflux in patients with obstructive sleep apnoea and asthma and the effects of continuous positive airway pressure. Sleep and control of breathing. https://doi.org/10.1183/13993003.congress-2019.pa890
Kurin M, Shibli F, Kitayama Y, et al (2021) Sorting out the Relationship between Gastroesophageal Reflux Disease and Sleep. Current Gastroenterology Reports. https://doi.org/10.1007/s11894-021-00815-4
Althoff M, Ghincea A, Wood L, et al (2021) Asthma and Three Colinear Comorbidities: Obesity, OSA, and GERD. Journal of Allergy and Clinical Immunology: In Practice. https://doi.org/10.1016/j.jaip.2021.09.003
Solidoro P, Patrucco F, Fagoonee S, Pellicano R (2017) Asthma and gastroesophageal reflux disease: a multidisciplinary point of view. Minerva Medica. https://doi.org/10.23736/S0026-4806.17.05181-3
Cazzola M, Rogliani P, Ora J, et al (2022) Asthma and comorbidities: recent advances. Polish Archives of Internal Medicine. https://doi.org/10.20452/pamw.16250
Pardo-Manrique V, Ibarra-Enríquez CD, Serrano CD, et al (2024) Asthma and obstructive sleep apnea: Unveiling correlations and treatable traits for comprehensive care. Chronic Respiratory Disease. https://doi.org/10.1177/14799731241251827
Griffiths T, Nassar M, Soubani A (2020) Pulmonary manifestations of gastroesophageal reflux disease. Expert Review of Respiratory Medicine. https://doi.org/10.1080/17476348.2020.1758068
Bongiovanni A, Parisi G, Scuderi M, et al (2019) Gastroesophageal reflux and respiratory diseases: does it exist a real link? Minerva Pediatrica. https://doi.org/10.23736/S0026-4946.19.05531-2
Eapen AA, Gupta M, Lockey R, et al (2024) Gastroesophageal reflux disease, laryngopharyngeal reflux, and vocal cord dysfunction/Inducible laryngeal obstruction - overlapping conditions that impact asthma. Journal of Allergy and Clinical Immunology. https://doi.org/10.1016/j.jaci.2024.10.006
Ciorba A, Bianchini C, Pelucchi S, Pastore A (2007) Gastroesophageal reflux and its possible role in the pathogenesis of upper aerodigestive tract disorders. Minerva Gastroenterologica e Dietologica
Vakil N (2006) The Frontiers of Reflux Disease. Digestive Diseases and Sciences. https://doi.org/10.1007/s10620-005-9049-1
Okwara NC, Chan WW-Y (2021) Sorting out the Relationship Between Esophageal and Pulmonary Disease. Gastroenterology Clinics of North America. https://doi.org/10.1016/j.gtc.2021.08.006
Groen J, Smout A (2003) Supra-oesophageal manifestations of gastro-oesophageal reflux disease. European Journal of Gastroenterology and Hepathology. https://doi.org/10.1097/00042737-200312000-00013
Emilsson Ö, Gíslason Þ, Olin A, et al (2013) Biomarkers for Gastroesophageal Reflux in Respiratory Diseases. Gastroenterology Research and Practice. https://doi.org/10.1155/2013/148086
Ahn K, Penn R, Rattan S, et al (2022) Mendelian Randomization Analysis Reveals a Complex Genetic Interplay Among Atopic Dermatitis, Asthma, and GERD. American Journal of Respiratory and Critical Care Medicine. https://doi.org/10.1164/rccm.202205-0951OC
Thomas M, Price D (2008) Impact of comorbidities on asthma. Expert Review of Clinical Immunology. https://doi.org/10.1586/1744666X.4.6.731
Chipps B, Haselkorn T, Paknis B, et al (2017) More than a decade follow‐up in patients with severe or difficult‐to‐treat asthma: The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) II. Journal of Allergy and Clinical Immunology. https://doi.org/10.1016/j.jaci.2017.07.014
Matsumoto-Sasaki M, Suzuki M, Kimura H, et al (2022) Association of longitudinal changes in quality of life with comorbidities and exacerbations in patients with severe asthma. Allergology International. https://doi.org/10.1016/j.alit.2022.05.009
Inayat N, Rizvi N, Shah R, Soomro M (2015) FREQUENCY OF GASTRO-ESOPHAGEAL REFLUX SYMPTOMS IN ASTHMATIC PATIENTS. Pakistan Journal of Chest medicine
Yu S, Yang J, Li J, et al (2017) The effect of esophageal acid exposure on airway responsiveness and pulmonary function in asthmatic females. https://doi.org/10.3877/CMA.J.ISSN.1674-6899.2017.04.006
Ghassap SA, Rashad AI, Alamri SA, Alrakhimy HD (2018) Asthma and Chronic Obstructive Pulmonary Disease (COPD): Gastro-Oesophageal Reflux Disease (GERD). International Journal of Health Sciences. https://doi.org/10.53730/ijhs.v2ns1.15217
Wong B, Kinoshita Y (2006) Systematic review on epidemiology of gastroesophageal reflux disease in Asia. Clinical Gastroenterology and Hepatology. https://doi.org/10.1016/J.CGH.2005.10.011
Rosyid A, Yohanes LW, Miftahussurur M, Bakhtiar A (2024) Effect of GERD on response to asthma treatment: A literature review. World Journal of Advanced Research and Reviews. https://doi.org/10.30574/wjarr.2024.24.3.3834
Liou A, Grubb JR, Schechtman K, Hamilos D (2003) Causative and contributive factors to asthma severity and patterns of medication use in patients seeking specialized asthma care. Chest. https://doi.org/10.1378/CHEST.124.5.1781
Hait E, McDonald DR (2018) Impact of Gastroesophageal Reflux Disease on Mucosal Immunity and Atopic Disorders. Clinical reviews in allergy and immunology. https://doi.org/10.1007/s12016-018-8701-4
Ragnoli B, Pochetti P, Raie A, Malerba M (2021) Interrelationship Between Obstructive Sleep Apnea Syndrome and Severe Asthma: From Endo-Phenotype to Clinical Aspects. Frontiers in Medicine. https://doi.org/10.3389/fmed.2021.640636
Gaude G (2009) Pulmonary manifestations of gastroesophageal reflux disease. Annals of Thoracic Medicine. https://doi.org/10.4103/1817-1737.53347
Broers C, Tack J, Pauwels A (2018) Review article: gastro‐oesophageal reflux disease in asthma and chronic obstructive pulmonary disease. Alimentary Pharmacology and Therapeutics. https://doi.org/10.1111/apt.14416
Sun Y-G, Zhang L-Y (2025) Chronic Rhinosinusitis, Asthma, and Gastroesophageal Reflux: Epidemiology, Pathophysiology, and Comorbidity. Allergy Medicine. https://doi.org/10.1016/j.allmed.2025.100036
Ruigómez A, Rodriguez LA, Wallander M, et al (2005) Gastroesophageal reflux disease and asthma: a longitudinal study in UK general practice. Chest. https://doi.org/10.1378/CHEST.128.1.85
Cazzola M, Segreti A, Calzetta L, Rogliani P (2013) Comorbidities of asthma: current knowledge and future research needs. Current opinion in pulmonary medicine. https://doi.org/10.1097/MCP.0b013e32835b113a
Huggins S (2008) The role of gastroesophageal reflux disease in asthma. Journal of the American Academy of Nurse Practitioners. https://doi.org/10.1111/j.1745-7599.2008.00313.x
Pearson JP, Parikh S, Orlando R, et al (2011) Review article: reflux and its consequences – the laryngeal, pulmonary and oesophageal manifestations. Alimentary Pharmacology and Therapeutics. https://doi.org/10.1111/j.1365-2036.2011.04581.x
Teodorescu M, Consens F, Bria W, et al (2009) Predictors of habitual snoring and obstructive sleep apnea risk in patients with asthma. Chest. https://doi.org/10.1378/chest.08-1273
Durazzo M, Lupi G, Cicerchia F, et al (2020) Extra-Esophageal Presentation of Gastroesophageal Reflux Disease: 2020 Update. Journal of Clinical Medicine. https://doi.org/10.3390/jcm9082559
Ledford D, Lockey R (2013) Asthma and comorbidities. Current Opinion in Allergy and Clinical Immunology. https://doi.org/10.1097/ACI.0b013e32835c16b6
Ghisa M, Coletta MD, Barbuscio I, et al (2019) Updates in the field of non-esophageal gastroesophageal reflux disorder. Expert Review of Gastroenterology & Hepatology. https://doi.org/10.1080/17474124.2019.1645593
Ip S, Chung M, Moorthy D, et al (2011) Comparative Effectiveness of Management Strategies for Gastroesophageal Reflux Disease: Update
Albuquerque J, Pizzichini E, Pizzichini M (2011) Gastroesophageal reflux disease and airway hyperresponsiveness: concomitance beyond the realm of chance?* Doença do refluxo gastroesofágico e hiperresponsividade das vias aéreas: coexistência além da chance? https://doi.org/10.1590/S1806-37132011000500017
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