Does gastroesophageal reflux predispose to

Rhinosinusitis?

Predispone el reflujo gastroesofagico a

Rinosinusitis?
Chronic rhinosinusitis in adults, according to EPOS 2012, is defined as
inflammation of the nose and the paranasal sinuses characterised by:
Nasal blockage/obstruction
Nasal congestion or rhinorrhea(anterior/posterior nasal drip)
±facial pain/pressure
±Smell reduction or loss

Endoscopic signs:
Nasal polyps, and/or Mucopurulent discharge, mainly from middle meatus, and/or
Mucosa obstruction/edema mainly on middle meatus

CT changes:
Changes on the mucosa within ostio-meatal complex, and/or paranasal sinuses

Duration of the disease

≥12 weeks without complete resolution of symptoms.
RECENT DATA HAVE DEMONSTRATED THAT CRS AFFECTS
APPROXIMATELY 5–15% OF THE GENERAL POPULATION BOTH IN
EUROPE AND THE USA.
 PREDISPOSING FACTORS
• Upper respiratory tract infections
• Allergic rhinitis
• Anatomic abnormalities
• Concha bullosa
• Nasal polyposis
• Septal deviation
• Tumors
• Foreign bodies
• Systemic processes
• Disorders of ciliary motility
• Cystic fibrosis
• Wegener’s granulomatosis
• Immunodeficiency disorders
• Vasomotor reactivity
• Other
• Smoking
• Swimming and diving
• Overuse of nasal sprays
• Environmental irritants
• ?Gastroesophageal reflux
 Gastro-oesophageal reflux disease (GERD) is defined by
the reflux of gastric contents, resulting in troublesome
symptoms or complications.
Symptoms include heartburn and regurgitation, as well as
extra-oesophageal complaints and complications.

Vakil N, van Zanten SV, Kahrilas P, Dent J, Jones R. Global Consensus Group. The Montreal definition and classification of
gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol. 2006;101(8):1900-20.
PREVALENCE OF GERD IN THE GENERAL POPULATION IS
ESTIMATED AT 10-20%
 PROPOSED EXTRAESOPHAGEAL COMPLICATIONS OF GERD

• Pulmonary
• Asthma
• Chronic cough
• Aspiration pneumonia
• Sleep apnea
• Pulmonary fibrosis
• Subglottic stenosis
• Chronic obstructive lung disease
• Pharynx/larynx
• Hoarseness
• Posterior laryngitis
• Vocal cord granulomas, ulcers,
• nodules
• Paroxysmal laryngospasm
• Cancer
• Globus sensation
• Frequent throat clearing
• Lateral neck pain
• Sore throat
• Excessive phlegm
• Oral cavity
• Dental erosions
• Halitosis
• Buccal/tongue burning
• Nasal/sinus/middle ear
• Chronic sinusitis
• Chronic serous otitis media
• Other
• Torticollis
• Atrial dysrhythmias
• Sudden infant death syndrome

Poelmans J, Tack J. Extraoesophageal manifestations of gastro-oesophageal reflux disease. Gut 2005; 54: 1492–9.
A clear aetiological role for GERD has been identified in chronic
cough, laryngeal complaints, asthma and dental erosions. In other
conditions, such as CRS, any such role is putative and remains
highly ambiguous

S.R. Leason, H.P. Barham, G. Oakley et al.Association of gastro-oesophageal reflux and chronic rhinosinusitis: systematic review
and meta-analysis. Rhinology 2017;55: 3-16.
 It is difficult to establish a direct relationship between CRS and
GERD, since both entities are highly prevalent, which makes it
easier for them to coexist independently.

Prevalence in general populations:

CRS: 15 – 20%
GERD: 10 – 20%

Wong IW, Omari TI, Myers JC, Rees G, Nair SB, JamiesonGG, et al. Nasopharyngeal pH monitoring in chronic sinus-itis patients using a
novel four channel probe. Laryngoscope.2004;114:1582-5

El-Serag HB, Sweet S, Winchester CC, Dent J. Update on the epidemiology of gastrooesophageal reflux disease: a systematic review. Gut.
2014;63(6):871-80.
SOME THEORIES ON THE RELATIONSHIP BETWEEN GERD
AND CRS HAVE BEEN PROPOSED:

1. direct exposure of the nasal and nasopharyngeal mucosa to

gastric acid. It is known that pH variations affect ciliary
motility and morphology in the respiratory mucosa which
could cause obstruction of sinus ostia and recurrent
infections.

• Loehrl TA, Smith TL, Darling RJ, Torrico L, Prieto TE, ShakerR, et al. Autonomic dysfunction, vasomotor rhinitis, and
extraesophageal manifestations of gastroesophageal reflux.Otolaryngol Head Neck Surg. 2002;126:382-7.

• Delehaye E, Dore MP, Bozzo C, Mameli L, Delitala G, MeloniF. Correlation between nasal mucociliary clearance time and
gastroesophageal reflux disease: our experience on 50 patients.Auris Nasus Larynx. 2009;36:157-61.
 2. a relationship mediated by the vagus nerve, a mechanism
already proven in the lower airway and in the nasal
mucosa of patients with rhinitis, but not in patients with
CRS. Dysfunction of the autonomic nervous system can
lead to reflex sinonasal swelling and inflammation, and
consequent blockage of the ostia.

Wong IWY, Rees G, Greiff L, Myers JC, Jamieson GG, Wormald PJ. Gastroesophageal reflux disease and chronic sinusitis: in search of
an esophageal-nasal reflex. Am J Rhinol Allergy.2010;24:255-9.

Vaezi MF, Hagaman DD, Slaughter JC, Tanner SB, Duncavage JA, Allocco CT, et al. Proton pump inhibitor therapy improves symptoms
in postnasal drainage. Gastroenterology. 2010;139(6):1887–93.
 3. direct role of Helicobacter pylori (H. pylori)

Koc C, Arikan OK, Atasoy P, Aksoy A. Prevalence of Helicobacter pylori in patients with nasal polyps: a preliminary
report.Laryngoscope. 2004;114:1941-4.

Morinaka S, Ichimiya M, Nakamura H. Detection of Helicobacter pylori in nasal and maxillary sinus specimens from patients with
chronic sinusitis. Laryngoscope. 2003;113:1557-63.

Ozdek A, Cirak MY, Samim E, Bayiz U, Safak MA, Turet S. A possible role of Helicobacter pylori in chronic rhinosinusitis: a
preliminary report. Laryngoscope. 2003;113:679-82.
BASED ON THESE THEORIES WHAT IS FOUND IN RECENT
LITERATURE ON THE GERD / CRS RELATIONSHIP?
 1. EPIDEMIOLOGICAL ASSOCIATION BETWEEN GASTRO-
ESOPHAGEAL REFLUX (GERD) AND CHRONIC RHINOSINUSITIS
(CRS)
Tan BK, Chandra RK, Pollak J, et al. Incidence and associated premorbid diagnoses of patients with chronic rhinosinusitis. J Allergy Clin
Immunol. 2013;131(5):1350-60.

GERD prevalence significantly greater with CRSwNP (176/595, 29.6%) and CRSsNP
(2220/7523, 29.0%) than without CRS (1666/8118, 20.5%). The epidemiological
association was statistically significant
El-Serag HB, Gilger M, Kuebeler M,Rabeneck L. Extraesophageal associations of gastroesophageal reflux disease in children without
neurologic defects. Gastroenterology. 2001;121(6):1294-9.

RS prevalence significantly greater with GERD (83/1980, 4.2%), than without GERD
(107/7920,1.4%). The epidemiological association was statistically significant .
Ruhl CE, Sonnenberg A, Everhart JE.Hospitalization with respiratory disease following hiatal hernia and reflux esophagitis in a prospective,
population-based study. Ann Epidemiol. 2001;11(7):477-83.

RS incidence not significantly different with GERD (8/537, 0.2%) or without GERD (63/6391,
0.1%).
The potentially pathogenic role of GERD was supported by Ruigomez, who found
increased incidence of sinusitis in the year after GERD diagnosis than among age
and sex matched controls.

Ruigomez A, Garcia Rodriguez LA, Wallander MA, Johansson S, Graffner H, Dent J. Natural history of gastro-oesophageal reflux disease
diagnosed in general practice. Aliment Pharmacol Ther. 2004;20(7):751-60.
EPIDEMIOLOGICALLY, RECENT LITTERATURE, SHOW AN
ASSOCIATION OF GERD WITH CRS AND THIS REAFFIRMS THE
COMMON BELIEF THAT PREVALENCE OF CRS IS INCREASED
AMONG GERD SUFFERERS.
HOWEVER, THIS ALONE DOES NOT EXPLAIN THE NATURE OF THE
ASSOCIATION.
2. DIRECT EXPOSURE OF THE NASAL AND NASOPHARYNGEAL
MUCOSA TO GASTRIC ACID
Ozmen S, Yucel OT, Sinici I, et al. Nasal pepsin assay and pH monitoring in chronic rhinosinusitis. Laryngoscope. 2008;118(5):890-4.

Hypopharyngeal reflux significantly more prevalent with CRS (29/33, 88%) than
without CRS (11/20, 55%). Pepsin significantly more prevalent in nasal aspirates
with CRS (27/33, 82%), than without CRS (10/20, 50%). All with intranasal pepsin
had hypopharyngeal reflux.
DelGaudio JM. Direct nasopharyngeal reflux of gastric acid is a contributing factor in refractory chronic rhinosinusitis.
Laryngoscope. 2005;115(6):946-57.

Nasopharyngeal reflux with pH <4 significantly more prevalent with CRS (15/38,
39%) than with no CRS following FESS (1/10, 10%) or no history of CRS (2/20,
10%). Nasopharyngeal reflux with pH < 5 significantly more common with CRS
(29/38, 76%) or no CRS following FESS (5/10 (50%) than with no history of CRS
(3/20, 15%). Esophageal reflux more prevalent with CRS (25/38,66%) than with no
CRS following FESS (3/10, 30%) or no history of CRS (7/20, 35%).
 Bhawana GS, Kumar S, Kumar A. Alkaline pH in middle meatus in cases of chronic rhinosinusitis. Am J Otolaryngol.2014;35(4):496-9.

The middle meatus was more alkaline with CRS (pH 7.81+/-0.83) than without
CRS (pH7.35+/-0.82)
Loehrl TA, Samuels TL, Poetker DM, ToohillRJ, Blumin JH, Johnston N. The role of extraesophageal reflux in medicallyand surgically
refractory rhinosinusitis. Laryngoscope. 2012;122(7):1425-30.

Intranasal pepsin in all nasal aspirates (5/5) with CRS, but none without CRS
(0/5). Pepsin not found in nasopharyngeal tissue of any CRS subjects (0/5)
Durmus R, Naiboglu B, Tek A, et al. Doesreflux have an effect on nasal mucociliary transport? Acta Oto-Laryngol. 2010;130(9):1053-7

No significant difference in saccharine clearance with GERD (12.70+/-3.43min) or

without GERD (13.10+/-3.34min)
Dinis PB, Subtil J. Helicobacter pylori and laryngopharyngeal reflux in chronic rhinosinusitis. Otolaryngol Head Neck Surg. 2006; 134
( 1) : 67-72.

Pepsin and pepsinogen I concentrations in nasopharyngeal tissue not statistically

different with CRS or normal nasal mucosa. No tissue concentration exceeded the
serum concentration;
DIRECT NASOPHARYNGEAL REFLUX IS SIGNIFICANTLY MORE
FREQUENT WITH THAN WITHOUT CRS.
THE NASAL MUCOSA LACKS THE PROTECTIVE MECHANISMS
PRESENT MORE DISTALLY AGAINST INJURY FROM REFLUX,
WHICH WOULD LOWER THE THRESHOLD FOR INJURY.
STANDARD PH STUDIES TYPICALLY CONSIDER THAT PH BELOW 4
TO BE PATHOLOGIC, BUT EVEN A REFLUX LESS ACID MAY BE
PATHOLOGIC IN THE PROXIMAL AIRWAY.
 3. DIRECT ROLE OF HELICOBACTER PYLORI (H. PYLORI)
Vceva A, Danic D, Vcev A, et al. The significance of Helicobacter pylori in patients with nasal polyposis. Med Glas (Zenica).2012;9(2):281-6.

Intranasal H. pylori PCR positive in significantly more subjects with nasal polyps
(10/35, 28.6%) than normal nasal mucosa (0/30, 0%). Anti-H. pylori antibodies
were found in significantly more subjects with nasal polyps (30/35, 85.7%) than
normal nasal mucosa (16/30, 53.3%). All those with positive PCR also had
positive antibody testing.
Burduk PK, Kaczmarek A, Budzynska A,Kazmierczak W, Gospodarek E.Detection of Helicobacter pylori and cagA gene in nasal polyps and
benign laryngeal diseases. Arch Med Res. 2011;42(8):686-9.

H. pylori DNA in all with CRSc (20/20) and with normal nasal mucosa (10/10).
None had cagA positive H. pylori detected.
Cvorovic L, Brajovic D, Strbac M, Milutinovic Z, Cvorovic V. Detection of Helicobacter pylori in nasal polyps: preliminaryreport. J
Otolaryngol Head Neck Surg. 2008;37(2):192-5.

H. pylori in 6/23 (26%) with CRSwNP; No H.pylori in normal nasal mucosa (0/15,
0%).
Ozyurt M, Gungor A, Ergunay K, Cekin E, Erkul E, Haznedaroglu T. Real-time PCR detection of Helicobacter pylori and virulence-
associated cagA in nasal polyps and laryngeal disorders. Otolaryngol Head Neck Surg. 2009;141(1):131-5 .

H. pylori DNA in 19/32 (59%) with CRSwNP and 19/27 (70%) with normal nasal
mucosa (no statistically significant). In both groups, most H. pylori was cagA
positive (15/19 vs 17/19).

Kim HY, Dhong HJ, Chung SK, Chung KW,Chung YJ, Jang KT. Intranasal Helicobacter pylori colonization does not correlate with the
severity of chronic rhinosinusitis. Otolaryngol Head Neck Surg. 2007;136(3):390-5.

H. pylori in 12/48 (25%) with CRS and 1/29 (3.5%) with normal nasal mucosa by
both rapid urease and histochemical testing (statistically significant).

Koc C, Arikan OK, Atasoy P, Aksoy A. Prevalence of Helicobacter pylori in patients with nasal polyps: a preliminary report.
Laryngoscope. 2004;114(11):1941-4.

H. pylori in 6/30 (20%) with nasal polyps by histochemical and serum antibody
testing. No H. pylori in normal nasal mucosa (0/20, 0%).
A POTENTIALLY PATHOGENIC ROLE OF H. PYLORI IN SINONASAL
INFLAMMATION HAS BEEN SUGGESTED BY PREVIOUS AUTHORS.
INDEED, H. PYLORI IS STRONGLY PATHOGENIC FOR GASTRIC
ULCERS, GASTRITIS AND GASTRIC CANCERS. HOWEVER, ANY
PATHOGENIC ROLE REMAINS UNCERTAIN AND NO STUDIES TO
OUR KNOWLEDGE HAVE DIRECTLY EXAMINED A POTENTIAL
MECHANISM IN CRS. IT IS POSSIBLE THAT THE INTRANASAL
PRESENCE OF H. PYLORI IS NOT PATHOGENIC, BUT IS FACILITATED
BY PRE-EXISTING CHRONIC INFLAMMATORY CHANGES.
THE INTRANASAL PRESENCE OF H. PYLORI MAY BE A MARKER OF
NASOPHARYNGEAL REFLUX, OR IT MAY INDICATE THAT THE NASAL
CAVITY IS A RESERVOIR FOR THE BACTERIA.
 4. RELATIONSHIP MEDIATED BY THE VAGUS NERVE
Wong IWY, Rees G, Greiff L, Myers JC, Jamieson GG, Wormald PJ. Gastroesophageal reflux disease and chronic sinusitis: in search of
an esophageal-nasal reflex. Am J Rhinol Allergy.2010;24:255-9

No significant increase in nasal airflow resistance, nasal mucus production or

sinonasal symptoms following esophageal infusion with saline or hydrochloric
acid.

Vaezi MF, Hagaman DD, Slaughter JC, Tanner SB, Duncavage JA, Allocco CT, et al. Proton pump inhibitor therapy improves
symptoms in postnasal drainage. Gastroenterology. 2010;139(6):1887–93.

Alleviation of post-nasal drip and other typical upper airway symptoms

in patients with CRS by anti-reflux therapy, in randomized controlled studies,
indicate a possible reflex interaction between gastroesophageal reflux and the
nasal cavity
INDIRECT ACTION OF ESOPHAGEAL REFLUXATE ON THE
AIRWAY THROUGH A NEUROLOGICAL PATHWAY HAS BEEN
DEMONSTRATED IN THE LOWER AIRWAYS.
IN UPPER AIRWAYS, DECREASED SYMPATHETIC FUNCTION HAS
BEEN FOUND WITH CONCOMITANT GERD. IT IS BELIEVED THAT
THE SYMPATHETIC SYSTEM INCREASES NASAL PATENCY, WHILE
PARASYMPATHETIC DRIVE CREATES RESISTANCE AND
RHINORRHEA.
 USE OF PPI THERAPY IN CRS

Pincus RL, Kim HH, Silvers S, Gold S. A study of the link between gastric reflux and chronic sinusitis in adults. Ear Nose Throat J.
2006;85:174-8.

Durmus R, Naiboglu B, Tek A, Sezikli M, Cetinkaya ZA, Toros SZ,et al. Does reflux have an effect on nasal mucociliary transport.Acta
Otolaryngol. 2010;130:1053-7.

Zelenik K, formanek M, Matousek P, Kominek P. Chronic rhinosinusitis and extraesophageal reflux: Who is the candidate for
antireflux treatment? Am J Rhinol & All. 2016;30:5-9.

Current studies available in the literature are conflicting as to the

effect of PPI therapy in symptom improvement in patients with
CRS. In addition, CRS or reflux diagnoses were not confirmed by
complementary tests, which makes the real interpretation of the
results difficult.
Zeng Hong W, Xiu Ping Y, Xun N, Xi Yue X, Xiong C. The relationship between obstructive sleep apnea hypopnea syndrome
and gastroesophageal reflux disease: a meta-analysis. Sleep and Breathing: 1-9, Published on line 09 July 2018,
https://doi.org/10.1007/s11325-018-1691-x

This meta-analysis provided direct evidence of the GERD participation in

OSAS pathogenesis and suggested that in treatment of OSAS, the GERD
should not be neglected in clinical practice.
 CONCLUSION
There is a significant body of evidence demonstrating an
association between GERD and CRS. While CRS is a multifactorial
process, the evidence suggests that GERD does play a role in
refractory CRS.
According to the studies found in the literature, it was concluded
that there appears to be relative prevalence of refluxin patients
with difficult to control CRS. However, controlled studies with a
significant number of patients are lacking to confirm this
hypothesis. Similarly, there are few studies that specifically assess
the impact of treatment of reflux in symptom improvement in
patients with CRS.