Laryngeal Mucosa Alterations in Mice Model of Gastroesophageal Reflux: Effects of Topical Protection

Figueiredo, Aline Almeida; Sales, Thiago M.; Nicolau, Lucas Antônio Duarte; Nunes, André Alencar Araripe; Costa‐Filho, Humberto B.; Moreira, Rhubens L. R.; Nascimento, Renata R.; Sousa, Maria Klayre Araújo de; Silva, Lorena D.; Carmo-Neto, João P.; Sidou, Flávio M. N. O.; Paula, Suliana Mesquita; Medeiros, Jand Venes R.; Silva, Durcilene Alves da; Sifrim, Daniel; Souza, Marcellus H.

doi:10.1002/lary.28597

Cited by 8 publications

(30 citation statements)

References 35 publications

(95 reference statements)

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“…Two independent risk factors require attention. To avoid serious complications, thorough and accurate management can enable early detection 33 and diagnosis of problems so that they can be actively addressed. In the future, with the help of fiberoptic bronchoscopy and ultrasound, laryngeal masks could be used more widely and safely.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Flexible Laryngeal Mask Ventilation in Otologic Surgery: A Retrospective Analysis

Liu¹,

Xi²,

Cui³

et al. 2022

RMHP

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Background Flexible laryngeal mask airways (FLMAs) ventilation have been widely used as airway devices during general anesthesia, especially in otologic surgery. However, the current literature reports that the clinical success and failure rates for FLMA usage are quite different, and there remains a paucity of data regarding factors associated with FLMA failure and complications related to FLMA usage. Purpose To evaluate the success and failure rates of FLMA usage in otologic surgery, the factors associated with FLMA failure and complications related to FLMA usage. Patients and Methods All patients who underwent otologic surgery, including middle ear and mastoid procedures, under general anesthesia at a large tertiary general hospital from 2015 to 2019 were reviewed. The primary outcome was the FLMA failure rate, defined as any airway event requiring device removal and tracheal intubation, including primary and secondary failure. The secondary outcomes were specific clinical factors, including patient sex, age, weight, American Society of Anesthesiologists (ASA) classification, body mass index (BMI) and duration of surgery, which were analyzed as related risk factors. Results Among 5557 patients with planned FLMA use, the final success rate was 98.5%. Sixty-seven percent of the failures occurred during initial introduction of the FLMA, 8% occurred after head and neck rotation, and 25% occurred during the procedures. Two independent clinical factors associated with FLMA failure were male sex and age. Respiratory complications were observed in 0.61% of patients, and the rate of severe nerve and tissue damage associated with FLMA use was 0.05. Conclusion This study demonstrates a high success rate of 98.5% for FLMA use in adults undergoing otologic surgery with rare adverse airway events and injuries complications. Two independent risk factors require attention and thorough and accurate management is necessary for every clinician.

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Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Flexible Laryngeal Mask Ventilation in Otologic Surgery: A Retrospective Analysis

Liu¹,

Xi²,

Cui³

et al. 2022

RMHP

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“…For this reason, the time involved on inflammatory response establishment of each organ is different too. For laryngeal inflammation, the 3rd day is the recommendation according to Figueiredo et al and the 7th day is recommended for esophageal evaluation of inflammation and mucosal barrier according to Silva et al 14,25 Isolation and Purification of Angico Gum (Anadenanthera colubrina)…”

Section: Methodsmentioning

confidence: 99%

“…MPO is present in neutrophil azurophilic granules and has been used as an indicator of neutrophilic infiltration including laryngeal tissue as described by Figueiredo and colleagues. 14 The larynx (pool of three samples) and esophagus samples were homogenized in potassium phosphate buffer (PBS, pH 6.0) with 0.5% hexadecitrimethylammonium bromide (HTAB) and centrifuged at 4,500 rpm for 15 minutes. MPO activity was tested by measuring the change in absorbance at 450 nm using o-dianisidine dihydrochloride and 1% hydrogen peroxide, and the results were expressed as units of MPO per milligram of tissue (U/mg of tissue).…”

Section: Mpo Activitymentioning

confidence: 99%

“…14 Figueiredo et al observed that the use of cashew gum prevented the loss of integrity of the laryngeal mucosa against a solution that simulates gastric content in vitro; in addition, the in vivo application of cashew gum in the GERD model also reduced inflammation and prevented the loss of integrity of the laryngeal mucosa. 14,15 Given these premises, the use of polysaccharides derived from natural products has the potential to assist in the treatment of LPR. The angico gum (Anadenanthera colubrina) biopolymers have multiple pharmacological properties such as antimicrobial, [17][18][19] wound healing, 20 anti-inflammatory, 21 and antinociceptive 22 properties; in addition, it provides actions specific to the gastrointestinal tract like antidiarrheal effect 23 and esophageal mucosal protection.…”

Section: Introductionmentioning

confidence: 99%

“…9,10 This medication forms a barrier at the lower esophageal sphincter preventing refluxate from entering the esophagus and also creates a layer over the mucosa of the esophagus, thereby reducing contact with gastric juice. [10][11][12][13][14][15] It also has the ability to inhibit the action of pepsin and protect the human esophageal mucosa from acid-induced damage for a prolonged period. 12,13 Recently, Ciprandi and colleagues showed, in an interesting study, that alginate was effective and safe in laryngopharyngeal reflux treatment over enrolled patients, which corroborates protective role also in laryngeal tissue.…”

Section: Introductionmentioning

confidence: 99%

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Laryngeal and Esophageal Mucosal Protection Using the Angico Gum Biopolymer in a Mouse Model of Reflux

et al. 2022

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Objective: This study aimed to evaluate the in vivo protective effect of the angico gum biopolymer in reducing the inflammatory response and preserving the integrity of the laryngeal and esophageal mucosa.Study Design: Animal study. Methods: A murine surgical model of gastroesophageal reflux disease was accomplished and subsequently treated with angico gum or omeprazole. On days 3 and 7 post surgery, samples of the larynx and esophagus, respectively, were collected to measure the level of inflammation (wet weight and myeloperoxidase activity) and mucosal integrity (transepithelial electrical resistance and mucosal permeability to fluorescein).Results: Angico gum and omeprazole decreased laryngeal inflammation (wet weight and myeloperoxidase activity) and dramatically improved the integrity of the laryngeal mucosa. It also reduced inflammation (decreased wet weight and myeloperoxidase activity) of the esophagus and preserved the barrier function (inferred by assessing the integrity of the mucosa).Conclusion: This study demonstrates the protective effect of angico gum in an experimental gastroesophageal reflux disease model. Angico gum attenuates inflammation and impairment of the mucosal barrier function not only in the larynx but also in the esophagus.

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Oral and Inhaled Fosamprenavir Reverses Pepsin‐Induced Damage in a Laryngopharyngeal Reflux Mouse Model

et al. 2022

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Objective More than 20% of the US population suffers from laryngopharyngeal reflux. Although dietary/lifestyle modifications and alginates provide benefit to some, there is no gold standard medical therapy. Increasing evidence suggests that pepsin is partly, if not wholly, responsible for damage and inflammation caused by laryngopharyngeal reflux. A treatment specifically targeting pepsin would be amenable to local, inhaled delivery, and could prove effective for endoscopic signs and symptoms associated with nonacid reflux. The aim herein was to identify small molecule inhibitors of pepsin and test their efficacy to prevent pepsin‐mediated laryngeal damage in vivo. Methods Drug and pepsin binding and inhibition were screened by high‐throughput assays and crystallography. A mouse model of laryngopharyngeal reflux (mechanical laryngeal injury once weekly for 2 weeks and pH 7 solvent/pepsin instillation 3 days/week for 4 weeks) was provided inhibitor by gavage or aerosol (fosamprenavir or darunavir; 5 days/week for 4 weeks; n = 3). Larynges were collected for histopathologic analysis. Results HIV protease inhibitors amprenavir, ritonavir, saquinavir, and darunavir bound and inhibited pepsin with IC50 in the low micromolar range. Gavage and aerosol fosamprenavir prevented pepsin‐mediated laryngeal damage (i.e., reactive epithelia, increased intraepithelial inflammatory cells, and cell apoptosis). Darunavir gavage elicited mild reactivity and no discernable protection; aerosol protected against apoptosis. Conclusions Fosamprenavir and darunavir, FDA‐approved therapies for HIV/AIDS, bind and inhibit pepsin, abrogating pepsin‐mediated laryngeal damage in a laryngopharyngeal reflux mouse model. These drugs target a foreign virus, making them ideal to repurpose. Reformulation for local inhaled delivery could further improve outcomes and limit side effects. Level of evidence NA. Laryngoscope, 133:S1–S11, 2023

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Laryngeal Mucosa Alterations in Mice Model of Gastroesophageal Reflux: Effects of Topical Protection

Cited by 8 publications

References 35 publications

Efficacy and Safety of Flexible Laryngeal Mask Ventilation in Otologic Surgery: A Retrospective Analysis

Efficacy and Safety of Flexible Laryngeal Mask Ventilation in Otologic Surgery: A Retrospective Analysis

Laryngeal and Esophageal Mucosal Protection Using the Angico Gum Biopolymer in a Mouse Model of Reflux

Oral and Inhaled Fosamprenavir Reverses Pepsin‐Induced Damage in a Laryngopharyngeal Reflux Mouse Model

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