Laryngopharyngeal reflux

Last updated
Laryngopharyngeal reflux
Other namesExtraesophageal reflux disease (EERD), [1] Silent reflux, [2] and Supra-esophageal reflux [3]
Pharynx (PSF).png
Sagittal illustration of the anterior portion of the human head and neck. In LPR, the pharynx (1), oropharynx (2) and larynx (3) are exposed to gastric contents that flow upward through the esophagus (4).
Specialty Gastroenterology   OOjs UI icon edit-ltr-progressive.svg

Laryngopharyngeal reflux (LPR) or laryngopharyngeal reflux disease (LPRD) is the retrograde flow of gastric contents into the larynx, oropharynx and/or the nasopharynx. [4] [5] LPR causes respiratory symptoms such as cough and wheezing [6] and is often associated with head and neck complaints such as dysphonia, globus pharyngis, and dysphagia. [7] LPR may play a role in other diseases, such as sinusitis, otitis media, and rhinitis, [7] and can be a comorbidity of asthma. [6] While LPR is commonly used interchangeably with gastroesophageal reflux disease (GERD), it presents with a different pathophysiology. [8]

Contents

LPR reportedly affects approximately 10% of the U.S. population. However, LPR occurs in as many as 50% of individuals with voice disorders. [9]

Signs and symptoms

Extraesophageal symptoms result from exposure of the upper aerodigestive tract to gastric contents. This causes a variety of symptoms, including hoarseness, postnasal drip, sore throat, difficulty swallowing, indigestion, wheezing, globus pharyngeus, and chronic throat-clearing. Some people with LPR have heartburn, while others have little to no heartburn as refluxed stomach contents do not remain in the esophagus long enough to irritate the surrounding tissue. [10] Individuals with more severe forms of LPR may experience abrasion of tooth enamel due to intermittent presence of gastric contents in the oral cavity. [11]

Additionally, LPR can cause inflammation in the vocal tract which results in the symptom of dysphonia or hoarseness. Hoarseness is considered to be one of the primary symptoms of LPR and is associated with complaints such as strain, vocal fatigue, musculoskeletal tension, and hard glottal attacks, [12] all of which can reduce a person's ability to communicate effectively. [13] Moreover, LPR patients may try to compensate for their hoarseness by increasing muscular tension in their vocal tract. This hyper-functional technique adopted in response to the inflammation caused by LPR can lead to a condition called muscle tension dysphonia and may persist even after the hoarseness and inflammation has disappeared. A speech–language pathologist will often need to be involved to help resolve this maladaptive, compensatory pattern through the implementation of voice therapy. [14]

LPR presents as a chronic and intermittent disease in children. [4] LPR in children and infants tends to manifest with a unique set of symptoms. [15] Symptoms seen in children with LPR include a cough, hoarseness, stridor, sore throat, asthma, vomiting, globus sensation, wheezing, aspiration and recurrent pneumonia. [15] Common symptoms of LPR in infants include wheezing, stridor, persistent or recurrent cough, apnea, feeding difficulties, aspiration, regurgitation, and failure to thrive. [15] Moreover, LPR in children is commonly concomitant with laryngeal disorders such as laryngomalacia, subglottic stenosis, and laryngeal papillomatosis. [4]

Relationship to GERD

Illustration of the superior view of the larynx. Tissues lining laryngeal structures, including the vocal folds, may be damaged in LPR. Illu larynx.jpg
Illustration of the superior view of the larynx. Tissues lining laryngeal structures, including the vocal folds, may be damaged in LPR.

LPR is often regarded as a subtype of GERD that occurs when stomach contents flow upward through the esophagus and reach the level of the larynx and pharynx. However, LPR is associated with a distinct presentation of symptoms. [11] LPR and GERD frequently differ in the relative prevalence of heartburn and throat clearing. While heartburn is present in over 80% of GERD cases, it occurs in only 20% of LPR cases. Throat clearing shows the opposite prevalence pattern, occurring in approximately 87% of LPR cases and in fewer than 5% of GERD cases. [9] Unlike GERD, LPR also poses a risk for bronchitis or pneumonitis as reflux of stomach acid to the level of the larynx can result in aspiration. [16] LPR is also commonly associated with erythema, or redness, as well as edema in the tissues of the larynx that are exposed to gastric contents. [11] In contrast, most cases of GERD are nonerosive, with no apparent injury to the mucosal lining of the esophageal tissue exposed to the refluxed material. [17]

Differences in the molecular structure of the epithelial tissue lining the laryngopharyngeal region may be partly responsible for the different symptomatic manifestations of LPR in comparison to GERD. In contrast to the resistant stratified squamous epithelium lining the esophagus, the larynx is lined by ciliated respiratory epithelium, which is more fragile and susceptible to damage. While the epithelium lining the esophagus is capable of withstanding as many as 50 instances of exposure to gastric contents each day, which is the uppermost estimate considered to be within the range of normal physiologic functioning, injury to laryngeal epithelium can occur following exposure to only small amounts of acidic gastric contents. [9]

Diagnosis

LPR presents with non-specific symptoms and signs that make differential diagnosis difficult to achieve. Furthermore, symptoms of the disorder overlap greatly with symptoms of other disorders. Therefore, LPR is under-diagnosed and under-treated. [18] As there are multiple potential etiologies for the respiratory and laryngeal symptoms of LPR, diagnosing LPR based on symptoms alone is unreliable. Laryngoscopic findings such as erythema, edema, laryngeal granulomas, and interarytenoid hypertrophy have been used to establish the diagnosis; however, these findings are nonspecific and have been described in the majority of asymptomatic subjects undergoing laryngoscopy. [19] Response to acid-suppression therapy has been suggested as a diagnostic tool for confirming diagnosis of LPR, but studies have shown that the response to empirical trials of such therapy (as with proton-pump inhibitors) in these patients is often disappointing. [20] Several studies have emphasized the importance of measuring proximal esophageal, or ideally pharyngeal acid exposure, in patients with clinical symptoms of LPR to document reflux as the cause of the symptoms. [21] [22]

Additionally, several potential biomarkers of LPR have been investigated. These include inflammatory cytokines, carbonic anyhydrase, E-cadherin and mucins; however, their direct implications in LPR are still being established. [23] The presence of pepsin, an enzyme produced in the stomach, in the hypopharynx has also become an increasingly researched biomarker for LPR. [24] [25] Research suggests that the stomach enzyme pepsin plays a crucial role in the complex mechanism behind LPR. [26] Once present in the larynx pepsin is active at a low pH, but persists even when inactive. [27] Pepsin can manifest both extracellularly and intracellularly; however, damage is realized differently in these two environments. [27] Intracellularly, pepsin enters the laryngeal tissue through endocytosis and causes damage that accumulates over time. [27] Pepsin has implications on cellular transcription and therefore, gene expression, which subsequently leads to the recruitment of inflammatory cells, but inhibition of protective mechanisms such as growth factors. [27] Structurally, pepsin plays a role in increasing viscosity of the vibratory portion of the vocal folds and decreasing cellular water retention, which reduces the overall thickness of the vocal folds. [27] These morphological changes result in decreased vibratory amplitude, increasing demands for initiating vibration and ultimately, impacting voice quality. [27]

Before a diagnosis can be made, a physician will need to record the patient's medical history and ask for details about the presenting symptoms. Questionnaires such as the Reflux Symptom Index (RSI), Quality-of-Life Index (QLI) for LPR, Glottal Closure/Function Index (GCI) and Voice Handicap Index (VHI) can be administered to gain information about the patient's medical history as well as their symptomatology. [8] A physical examination will then need to be performed with particular concentration around the head and neck. A scope with a specialized camera lens made of fiber optic strands is gently fed down the throat and feeds back images to a monitor. This provides a clear view of the throat and larynx. Signs of LPR include redness, swelling, and obvious irritation. Other, more invasive tests, such as fibre-optic transnasal laryngoscopy, 24-hour ambulatory dual probe pHmetry, pharyngeal pHmetry, transnasal esophagoscopy (TNE) and biopsy may be used. [8] A noninvasive test for diagnosis of LPR is the collection of refluxate where the refluxed material is collected and analyzed. [8] Another noninvasive diagnostic test that can be used is an empirical trial of proton-pump inhibitor therapy; however, this test is mostly successful in diagnosing GERD. [8]

There is no agreed-upon assessment technique to identify LPR in children. [4] Of the debated diagnostic tools, multichannel intraluminal impedance with pH monitoring (MII-pH) is used as it recognizes both acid and non-acid reflux. [4] A more common technique that is used is 24-hour dual probe pH monitoring. Both of these tools are expensive and are therefore not widely used. [4]

Treatment

Management of symptoms for patients within this subgroup of the GERD spectrum is difficult. Once these patients are identified, behavioural and dietary changes are advised. Dietary modifications may include limiting the intake of chocolate, caffeine, acidic food and liquids, gaseous beverages and foods high in fat. [23] [28] Behavioral changes may include weight loss, cessation of smoking, limiting alcohol consumption and avoiding the ingestion of food shortly before bed. [23] Lifestyle changes in children diagnosed with LPR include dietary modifications to avoid foods that will aggravate reflux (e.g., chocolate or acidic and spicy food), altering positioning (e.g., sleeping on your side), modifying the textures of foods (e.g., thickening feeds to heighten awareness of the passing bolus), and eliminating the intake of food before bed. [15]

Proton-pump inhibitors (PPIs) are the leading pharmaceutical intervention chosen for the relief and reduction of LPR and are typically recommended for ongoing use twice a day for a period of 3–6 months. [23] [29] PPIs have been shown to be ineffective in very young children and are of uncertain efficacy in older children, for whom their use has been discouraged. [30] [ dubious – discuss ] While PPIs may provide limited clinical benefits in some adults, there is insufficient evidence to support routine use. [30] [31] [ dubious – discuss ] Many studies show that PPIs are not more effective than placebos in treating LPR. [32] [33] Alginate products show great promise, as they can form a temporary foam barrier at the LES to block acid and pepsin from refluxing. [34]

When medical management fails, Nissen fundoplication can be offered. [35] However, patients should be advised that surgery may not result in complete elimination of LPR symptoms and even with immediate success, recurrence of symptoms later on is still possible. [28]

One way to assess treatment outcomes for LPR is through the use of voice quality measures. [12] Both subjective and objective measures of voice quality can be used to assess treatment outcomes. Subjective measures include scales such as the Grade, Roughness, Breathiness, Asthenia, Strain Scale (GRBAS); the Reflux Symptom Index; the Voice Handicap Index (VHI); and a voice symptom scale. Objective measures often rely on acoustic parameters such as jitter, shimmer, signal-to-noise ratio, and fundamental frequency, among others. [12] Aerodynamic measures such as vital capacity and maximum phonation time (MPT) have also been used as an objective measure. [12] However, there is not yet a consensus on how best to use the measures or which measures are best to assess treatment outcomes for LPR. [34]

Procedures

There is tentative evidence from non-controlled trials that oral neuromuscular training may improve symptoms. [36] This has been approved by the UK National Health Service (NHS) for supply on prescription from 1 May 2022. [37]

Cancer risk

Although tobacco smoking is the most recognized risk factor for hypopharyngeal cancer, biliary reflux has recently been implicated in hypopharyngeal squamous cell carcinoma. [38] [39] Weakly acidic bile may increase the risk for hypopharyngeal carcinogenesis by inducing DNA damage. [40] DNA damage, such as DNA strand breaks, can be induced by the bile acid glycochenodeoxycholic acid present in reflux. [41]

History

LPR was not discussed as a separate condition from GERD until the 1970s and 1980s. [11] However, at around the same time that GERD was first recognized as a clinical entity in the mid-1930s, a link between gut symptoms and airway disease was suggested. Later, acid-related laryngeal ulcerations and granulomas were reported in 1968. [42] Subsequent studies suggested that acid reflux might be a contributory factor in other laryngeal and respiratory conditions. In 1979, the link between these airway symptoms and reflux of gastric contents was first documented. At the same time, treatment of reflux disease results was shown to eliminate these airway symptoms. [43]

Related Research Articles

<span class="mw-page-title-main">Larynx</span> Voice box, an organ in the neck of amphibians, reptiles, and mammals

The larynx, commonly called the voice box, is an organ in the top of the neck involved in breathing, producing sound and protecting the trachea against food aspiration. The opening of larynx into pharynx known as the laryngeal inlet is about 4–5 centimeters in diameter. The larynx houses the vocal cords, and manipulates pitch and volume, which is essential for phonation. It is situated just below where the tract of the pharynx splits into the trachea and the esophagus. The word 'larynx' comes from the Ancient Greek word lárunx ʻlarynx, gullet, throat.ʼ

<span class="mw-page-title-main">Pepsin</span> Enzyme

Pepsin is an endopeptidase that breaks down proteins into smaller peptides and amino acids. It is one of the main digestive enzymes in the digestive systems of humans and many other animals, where it helps digest the proteins in food. Pepsin is an aspartic protease, using a catalytic aspartate in its active site.

<span class="mw-page-title-main">Reinke's edema</span> Medical condition

Reinke's edema is the swelling of the vocal cords due to fluid (edema) collected within the Reinke's space. First identified by the German anatomist Friedrich B. Reinke in 1895, the Reinke's space is a gelatinous layer of the vocal cord located underneath the outer cells of the vocal cord. When a person speaks, the Reinke's space vibrates to allow for sound to be produced (phonation). The Reinke's space is sometimes referred to as the superficial lamina propria.

Heartburn, also known as pyrosis, cardialgia or acid indigestion, is a burning sensation in the central chest or upper central abdomen. Heartburn is usually due to regurgitation of gastric acid into the esophagus. It is the major symptom of gastroesophageal reflux disease (GERD).

<span class="mw-page-title-main">Gastroesophageal reflux disease</span> Medical condition

Gastroesophageal reflux disease (GERD) or gastro-oesophageal reflux disease (GORD) is a chronic upper gastrointestinal disease in which stomach content persistently and regularly flows up into the esophagus, resulting in symptoms and/or complications. Symptoms include dental corrosion, dysphagia, heartburn, odynophagia, regurgitation, non-cardiac chest pain, extraesophageal symptoms such as chronic cough, hoarseness, reflux-induced laryngitis, or asthma. In the long term, and when not treated, complications such as esophagitis, esophageal stricture, and Barrett's esophagus may arise.

<span class="mw-page-title-main">Hiatal hernia</span> Type of hernia

A hiatal hernia or hiatus hernia is a type of hernia in which abdominal organs slip through the diaphragm into the middle compartment of the chest. This may result in gastroesophageal reflux disease (GERD) or laryngopharyngeal reflux (LPR) with symptoms such as a taste of acid in the back of the mouth or heartburn. Other symptoms may include trouble swallowing and chest pains. Complications may include iron deficiency anemia, volvulus, or bowel obstruction.

<span class="mw-page-title-main">Laryngitis</span> Medical condition

Laryngitis is inflammation of the larynx. Symptoms often include a hoarse voice and may include fever, cough, pain in the front of the neck, and trouble swallowing. Typically, these last under two weeks.

<span class="mw-page-title-main">Nissen fundoplication</span> Surgical procedure to treat gastric reflux and hiatal hernia

A Nissen fundoplication, or laparoscopic Nissen fundoplication when performed via laparoscopic surgery, is a surgical procedure to treat gastroesophageal reflux disease (GERD) and hiatal hernia. In GERD, it is usually performed when medical therapy has failed; but, with a Type II (paraesophageal) hiatus hernia, it is the first-line procedure. The Nissen fundoplication is total (360°), but partial fundoplications known as Thal, Belsey, Dor, Lind, and Toupet fundoplications are alternative procedures with somewhat different indications and outcomes.

<span class="mw-page-title-main">Bogart–Bacall syndrome</span> Voice disorder caused by abuse or overuse of the vocal cords

Bogart–Bacall syndrome (BBS) is a voice disorder that is caused by abuse or overuse of the vocal cords.

A hoarse voice, also known as dysphonia or hoarseness, is when the voice involuntarily sounds breathy, raspy, or strained, or is softer in volume or lower in pitch. A hoarse voice can be associated with a feeling of unease or scratchiness in the throat. Hoarseness is often a symptom of problems in the vocal folds of the larynx. It may be caused by laryngitis, which in turn may be caused by an upper respiratory infection, a cold, or allergies. Cheering at sporting events, speaking loudly in noisy situations, talking for too long without resting one's voice, singing loudly, or speaking with a voice that is too high or too low can also cause temporary hoarseness. A number of other causes for losing one's voice exist, and treatment is generally by resting the voice and treating the underlying cause. If the cause is misuse or overuse of the voice, drinking plenty of water may alleviate the problems.

<span class="mw-page-title-main">Laryngospasm</span> Involuntary contraction of the vocal folds restricting inhalation

Laryngospasm is an uncontrolled or involuntary muscular contraction (spasm) of the vocal folds. It may be triggered when the vocal cords or the area of the trachea below the vocal folds detects the entry of water, mucus, blood, or other substance. It may be associated with stridor or retractions.

<span class="mw-page-title-main">Laryngomalacia</span> Medical condition

Laryngomalacia is the most common cause of chronic stridor in infancy, in which the soft, immature cartilage of the upper larynx collapses inward during inhalation, causing airway obstruction. It can also be seen in older patients, especially those with neuromuscular conditions resulting in weakness of the muscles of the throat. However, the infantile form is much more common. Laryngomalacia is one of the most common laryngeal congenital disease in infancy and public education about the signs and symptoms of the disease is lacking.

<span class="mw-page-title-main">Globus pharyngis</span> "Lump in the throat" sensation

Globus pharyngis, globus hystericus or globus sensation is the persistent but painless sensation of having a pill, food bolus, or some other sort of obstruction in the throat when there is none. Swallowing is typically performed normally, so it is not a true case of dysphagia, but it can become quite irritating. It is common, with 22–45% of people experiencing it at least once in their lifetime.

Stretta is a minimally invasive endoscopic procedure for the treatment of gastroesophageal reflux disease (GERD) that delivers radiofrequency energy in the form of electromagnetic waves through electrodes at the end of a catheter to the lower esophageal sphincter (LES) and the gastric cardia – the region of the stomach just below the LES. The energy heats the tissue, ultimately causing it to swell and stiffen; the way this works was not understood as of 2015, but it was thought that perhaps the heat causes local inflammation, collagen deposition and muscular thickening of the LES and that it may disrupt the nerves there.

<span class="mw-page-title-main">Contact granuloma</span> Medical condition

Contact granuloma is a condition that develops due to persistent tissue irritation in the posterior larynx. Benign granulomas, not to be confused with other types of granulomas, occur on the vocal process of the vocal folds, where the vocal ligament attaches. Signs and symptoms may include hoarseness of the voice, or a sensation of having a lump in the throat, but contact granulomas may also be without symptoms. There are two common causes associated with contact granulomas; the first common cause is sustained periods of increased pressure on the vocal folds, and is commonly seen in people who use their voice excessively, such as singers. Treatment typically includes voice therapy and changes to lifestyle factors. The second common cause of granulomas is gastroesophageal reflux and is controlled primarily through the use of anti-reflux medication. Other associated causes are discussed below.

<span class="mw-page-title-main">Hypopharyngeal cancer</span> Medical condition

Hypopharyngeal cancer is a disease in which malignant cells grow in the hypopharynx the area where the larynx and esophagus meet.

Vocal cord dysfunction (VCD) is a pathology affecting the vocal folds characterized by full or partial vocal fold closure causing difficulty and distress during respiration, especially during inhalation.

<span class="mw-page-title-main">Esophageal pH monitoring</span>

Esophageal pH monitoring is the current gold standard for diagnosis of gastroesophageal reflux disease (GERD). It provides direct physiologic measurement of acid in the esophagus and is the most objective method to document reflux disease, assess the severity of the disease and monitor the response of the disease to medical or surgical treatment. It can also be used in diagnosing laryngopharyngeal reflux.

Flexible Endoscopic Evaluation of Swallowing with Sensory Testing (FEESST), or laryngopharyngeal sensory testing, is a technique used to directly examine motor and sensory functions of swallowing so that proper treatment can be given to patients with swallowing difficulties to decrease their risk of aspiration and choking. FEESST was invented by Dr. Jonathan E. Aviv MD, FACS in 1993, and has been used by otolaryngologists, pulmonologists, gastroenterologists, intensivists and speech-language pathologists for the past 20 years.

<span class="mw-page-title-main">Acid peptic diseases</span> Overview of the acid peptic diseases of the stomach and gastrointestinal tract

Acid peptic diseases, such as peptic ulcers, Zollinger-Ellison syndrome, and gastroesophageal reflux disease, are caused by distinct but overlapping pathogenic mechanisms involving acid effects on mucosal defense. Acid reflux damages the esophageal mucosa and may also cause laryngeal tissue injury, leading to the development of pulmonary symptoms.

References

  1. ↑ Kahrilas PJ (October 2000). "Maximizing outcome of extraesophageal reflux disease". Am J Manag Care. 6 (16 Suppl): S876–82. PMID   11184658.
  2. ↑ Koufman JA (2002). "Laryngopharyngeal reflux is different from classic gastroesophageal reflux disease". Ear, Nose, & Throat Journal. 81 (9 Suppl 2): 7–9. PMID   12353431.
  3. ↑ Zerbib F, Stoll D (2010). "Management of laryngopharyngeal reflux: an unmet medical need". Neurogastroenterol Motil. 22 (2): 109–12. doi:10.1111/j.1365-2982.2009.01437.x. PMID   20067549. S2CID   39810748.
  4. 1 2 3 4 5 6 Galluzzi, F; Schindler, A; Gaini, RM; Garavello, W (October 2015). "The assessment of children with suspected laryngopharyngeal reflux: An Otorhinolaringological perspective". International Journal of Pediatric Otorhinolaryngology. 79 (10): 1613–9. doi:10.1016/j.ijporl.2015.07.037. PMID   26279249.
  5. ↑ Li, Y; Xu, G; Zhou, B; et al. (June 2022). "Effects of acids, pepsin, bile acids, and trypsin on laryngopharyngeal reflux diseases: physiopathology and therapeutic targets". European Archives of Oto-rhino-laryngology. 279 (6): 2743–2752. doi:10.1007/s00405-021-07201-w. PMC   9072476 . PMID   34860271.
  6. 1 2 Cazzola, M; Segreti, A; Calzetta, L; Rogliani, P (January 2013). "Comorbidities of asthma: current knowledge and future research needs". Current Opinion in Pulmonary Medicine. 19 (1): 36–41. doi: 10.1097/MCP.0b013e32835b113a . PMID   23114561. S2CID   20667404.
  7. 1 2 Dhillon, VK; Akst, LM (August 2016). "How to Approach Laryngopharyngeal Reflux: An Otolaryngology Perspective". Current Gastroenterology Reports. 18 (8): 44. doi:10.1007/s11894-016-0515-z. PMID   27417389. S2CID   7007929.
  8. 1 2 3 4 5 Johnston, Nikki; Dettmar, Peter W.; Strugala, Vicki; Allen, Jacqui E.; Chan, Walter W. (October 2013). "Laryngopharyngeal reflux and GERD". Annals of the New York Academy of Sciences. 1300 (1): 71–79. Bibcode:2013NYASA1300...71J. doi:10.1111/nyas.12237. PMID   24117635. S2CID   29120054.
  9. 1 2 3 Vaezi, M. F. (2009). Extraesophageal Reflux. San Diego, CA: Plural Publishing. ISBN   9781597567541.
  10. ↑ "Laryngopharyngeal Reflux ("Silent Reflux"): The Basics". jamiekoufman.com. 2010. Retrieved 20 January 2014.
  11. 1 2 3 4 5 Sataloff, R. T.; Katz, P. O.; Hawkshaw, M.; Sataloff, D. (2013). Reflux Laryngitis and Related Disorders (4 ed.). San Diego, CA: Plural Publishing. ISBN   9781597566384.
  12. 1 2 3 4 Lechien, JR; Finck, C; Costa de Araujo, P; Huet, K; Delvaux, V; Piccaluga, M; Harmegnies, B; Saussez, S (January 2017). "Voice outcomes of laryngopharyngeal reflux treatment: a systematic review of 1483 patients". European Archives of Oto-rhino-laryngology. 274 (1): 1–23. doi:10.1007/s00405-016-3984-7. PMID   27007132. S2CID   22602348.
  13. ↑ Lechien, Jérôme R.; Huet, Kathy; Khalife, Mohamad; Fourneau, Anne-Françoise; Delvaux, Véronique; Piccaluga, Myriam; Harmegnies, Bernard; Saussez, Sven (2016). "Impact of laryngopharyngeal reflux on subjective and objective voice assessments: a prospective study". Journal of Otolaryngology - Head & Neck Surgery. 45 (1): 59. doi: 10.1186/s40463-016-0171-1 . PMC   5101798 . PMID   27825368.
  14. ↑ Thayer, Sataloff, Robert (2013). Reflux laryngitis and related disorders. Katz, Philip O., 1953-, Hawkshaw, Mary, Sataloff, Dahlia (Fourth ed.). San Diego. ISBN   9781597565387. OCLC   882106592.{{cite book}}: CS1 maint: location missing publisher (link) CS1 maint: multiple names: authors list (link)
  15. 1 2 3 4 Venkatesan, NN; Pine, HS; Underbrink, M (August 2013). "Laryngopharyngeal reflux disease in children". Pediatric Clinics of North America. 60 (4): 865–78. doi:10.1016/j.pcl.2013.04.011. PMC   4036798 . PMID   23905824.
  16. ↑ Kasper, D. L.; Fauci, A. A.; Hauser, S. L.; Longo, D. L.; Jameson, J. L.; Loscalzo, J. (2015). Harrison's Principles of Internal Medicine (19 ed.). New York: McGraw Hill Education. ISBN   978-0071748902.
  17. ↑ Hershcovici, Tiberiu; Fass, Ronnie (2010). "Nonerosive Reflux Disease (NERD) - An Update". Journal of Neurogastroenterology and Motility. 16 (1): 8–21. doi:10.5056/jnm.2010.16.1.8. PMC   2879816 . PMID   20535321.
  18. ↑ Fraser-Kirk, K (2017). "Laryngopharyngeal reflux: A confounding cause of aerodigestive dysfunction". Australian Family Physician. 46 (1): 34–39. PMID   28189129.
  19. ↑ Hicks, DM.; Ours, TM.; Abelson, TI.; Vaezi, MF.; Richter, JE. (Dec 2002). "The prevalence of hypopharynx findings associated with gastroesophageal reflux in normal volunteers". J Voice. 16 (4): 564–79. doi:10.1016/S0892-1997(02)00132-7. PMID   12512644.
  20. ↑ Vaezi, MF.; Richter, JE.; Stasney, CR.; Spiegel, JR.; Iannuzzi, RA.; Crawley, JA.; Hwang, C.; Sostek, MB.; Shaker, R. (Feb 2006). "Treatment of chronic posterior laryngitis with esomeprazole". Laryngoscope. 116 (2): 254–60. doi:10.1097/01.mlg.0000192173.00498.ba. PMID   16467715. S2CID   34010200.
  21. ↑ Sun G, Muddana S, Slaughter JC, et al. (August 2009). "A new pH catheter for laryngopharyngeal reflux: Normal values". Laryngoscope. 119 (8): 1639–43. doi: 10.1002/lary.20282 . PMID   19504553. S2CID   5146973.
  22. ↑ Ayazi S, Hagen JA, Zehetner J, et al. (March 2010). "Proximal esophageal pH monitoring: improved definition of normal values and determination of a composite pH score". J. Am. Coll. Surg. 210 (3): 345–50. doi:10.1016/j.jamcollsurg.2009.12.006. PMID   20193899.
  23. 1 2 3 4 Campagnolo, AM; Priston, J; Thoen, RH; Medeiros, T; Assunção, AR (April 2014). "Laryngopharyngeal reflux: diagnosis, treatment, and latest research". International Archives of Otorhinolaryngology. 18 (2): 184–91. doi:10.1055/s-0033-1352504. PMC   4297018 . PMID   25992088.
  24. ↑ Johnston, Nikki; Ondrey, Frank; Rosen, Rachel; Hurley, Bryan P.; Gould, Jon; Allen, Jacquie; DelGaudio, John; Altman, Kenneth W. (2016-10-01). "Airway reflux". Annals of the New York Academy of Sciences. 1381 (1): 5–13. Bibcode:2016NYASA1381....5J. doi:10.1111/nyas.13080. ISSN   1749-6632. PMID   27310222. S2CID   13782557.
  25. ↑ Calvo-Henríquez, Christian; Ruano-Ravina, Alberto; Vaamonde, Pedro; Martínez-Capoccioni, Gabriel; Martín-Martín, Carlos (2017-06-06). "Is Pepsin a Reliable Marker of Laryngopharyngeal Reflux? A Systematic Review". Otolaryngology–Head and Neck Surgery. 157 (3): 385–391. doi:10.1177/0194599817709430. PMID   28585488. S2CID   20488665.
  26. ↑ Dev Bardhan, Karna (2012). "Reflux Revisited: Advancing the Role of Pepsin". International Journal of Otolaryngology. 2012: 1–13. doi: 10.1155/2012/646901 . PMC   3216344 . PMID   22242022.
  27. 1 2 3 4 5 6 Lechien, Jerome R.; Saussez, Sven; Harmegnies, Bernard; Finck, Camille; Burns, James A. (November 2017). "Laryngopharyngeal Reflux and Voice Disorders: A Multifactorial Model of Etiology and Pathophysiology". Journal of Voice. 31 (6): 733–752. doi:10.1016/j.jvoice.2017.03.015. ISSN   0892-1997. PMID   28438489.
  28. 1 2 Yuksel, Elif S.; Vaezi, Michael F. (2013). "Therapeutic Strategies for Laryngeal Manifestations of Gastroesophageal Reflux Disease". Journal of Clinical Gastroenterology. 47 (3): 195–204. doi:10.1097/mcg.0b013e31827458f9. PMID   23340061. S2CID   24572758.
  29. ↑ Wei, Chunhui (2016-11-01). "A meta-analysis for the role of proton pump inhibitor therapy in patients with laryngopharyngeal reflux". European Archives of Oto-Rhino-Laryngology. 273 (11): 3795–3801. doi:10.1007/s00405-016-4142-y. ISSN   0937-4477. PMID   27312992. S2CID   23356047.
  30. 1 2 Chang AB, Lasserson TJ, Gaffney J, Connor FL, Garske LA (2011). "Gastro-oesophageal reflux treatment for prolonged non-specific cough in children and adults". The Cochrane Database of Systematic Reviews. 2011 (1): CD004823. doi:10.1002/14651858.CD004823.pub4. PMC   6885040 . PMID   21249664. S2CID   2584390.
  31. ↑ Chan WW, Chiou E, Obstein KL, Tignor AS, Whitlock TL (2011). "The efficacy of proton pump inhibitors for the treatment of asthma in adults: a meta-analysis". Archives of Internal Medicine. 171 (7): 620–9. doi: 10.1001/archinternmed.2011.116 . PMID   21482834.
  32. ↑ Reimer, Christina; Bytzer, Peter (2008-02-01). "Management of laryngopharyngeal reflux with proton pump inhibitors". Therapeutics and Clinical Risk Management. 4 (1): 225–233. doi: 10.2147/TCRM.S6862 . ISSN   1176-6336. PMC   2503658 . PMID   18728712.
  33. ↑ nutritistceo (2022-10-23). "Laryngopharyngeal Reflux aka LPR - Why alginate therapy is the best treatment for it". Nutritist. Retrieved 2022-11-18.
  34. 1 2 Bardhan, Karna Dev; Strugala, Vicki; Dettmar, Peter W. (2012). "Reflux revisited: advancing the role of pepsin". International Journal of Otolaryngology. 2012: 646901. doi: 10.1155/2012/646901 . ISSN   1687-921X. PMC   3216344 . PMID   22242022.
  35. ↑ Ford CN (September 2005). "Evaluation and management of laryngopharyngeal reflux". JAMA. 294 (12): 1534–40. doi: 10.1001/jama.294.12.1534 . PMID   16189367. S2CID   20257577.
  36. ↑ Clinical and technical evidence - IQoro for hiatus hernia (Report). National Institute for Health and Care Excellence. 6 March 2019. MIB176.
  37. ↑ "Innovative IQoro neuromuscular treatment device achieves NHS prescription status". Advances in Clinical Neuroscience and Rehabilitation (ACNR). 25 March 2022.
  38. ↑ Vageli DP, Doukas PG, Doukas SG, Tsatsakis A, Judson BL. Noxious Combination of Tobacco Smoke Nitrosamines with Bile, Deoxycholic Acid, Promotes Hypopharyngeal Squamous Cell Carcinoma, via NFκB, In Vivo. Cancer Prev Res (Phila). 2022 May 3;15(5):297-308. doi: 10.1158/1940-6207.CAPR-21-0529. PMID 35502554
  39. ↑ Sasaki CT, Doukas SG, Costa J, Vageli DP. Biliary reflux as a causal factor in hypopharyngeal carcinoma: New clinical evidence and implications. Cancer. 2019 Oct 15;125(20):3554-3565. doi: 10.1002/cncr.32369. Epub 2019 Jul 16. PMID 31310330
  40. ↑ Vageli DP, Doukas SG, Doukas PG, Judson BL. Bile reflux and hypopharyngeal cancer (Review). Oncol Rep. 2021 Nov;46(5):244. doi: 10.3892/or.2021.8195. Epub 2021 Sep 24. PMID 34558652; PMCID: PMC8485019
  41. ↑ Sandner A, Illert J, Koitzsch S, Unverzagt S, Schön I. Reflux induces DNA strand breaks and expression changes of MMP1+9+14 in a human miniorgan culture model. Exp Cell Res. 2013 Nov 15;319(19):2905-15. doi: 10.1016/j.yexcr.2013.09.004. Epub 2013 Sep 25. PMID 24075964
  42. ↑ Cherry, J.; Margulies, SI. (Nov 1968). "Contact ulcer of the larynx". Laryngoscope. 78 (11): 1937–40. doi:10.1288/00005537-196811000-00007. PMID   5722896. S2CID   35965963.
  43. ↑ Pellegrini, CA.; DeMeester, TR.; Johnson, LF.; Skinner, DB. (Jul 1979). "Gastroesophageal reflux and pulmonary aspiration: incidence, functional abnormality, and results of surgical therapy". Surgery. 86 (1): 110–9. PMID   36677.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.