Epithelium, Cilia, and Mucus: Their Importance in Chronic Rhinosinusitis

Antunes, Marcelo B.; Gudis, David A.; Cohen, Noam A.

doi:10.1016/j.iac.2009.07.004

Cited by 97 publications

(122 citation statements)

References 68 publications

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“…Mucociliary stasis is a common finding of CRS, which propagates the disease because the stagnant mucus can harbor infection and sustain inflammatory mediators. 494 Although there does not seem to be a detectable difference between baseline CBF in CRS patients and control patients, cilia from CRS patients show an attenuated response to substances that reliably increase CBF in controls. 564,565 This blunted response to ciliostimulatory substances may underlie the perpetuation of pathology in CRS.…”

Section: Discussionmentioning

confidence: 94%

“…Genetic and acquired defects in mucociliary flow are associated with a high incidence of CRS, and these entail variations in viscosity and ciliary activity. [493][494][495][496] Beneath the mucus reside the epithelial cells (ECs), which are linked by tight and adherens junctions. Tight and adherens junctions comprise the apical junctional complex (AJC), creating a relatively impermeable barrier.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

International Consensus Statement on Allergy and Rhinology: Rhinosinusitis

Orlandi

Kingdom

Hwang

et al. 2016

Int Forum Allergy Rhinol

Self Cite

559

888

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Background:The body of knowledge regarding rhinosinusitis (RS) continues to expand, with rapid growth in number of publications, yet substantial variability in the quality of those presentations. In an effort to both consolidate and critically appraise this information, rhinologic experts from around the world have produced the International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR:RS). Methods:Evidence-based reviews with recommendations (EBRRs) were developed for scores of topics, using previously reported methodology. Where existing evidence was insufficient for an EBRR, an evidence-based review (EBR) was produced. The sections were then synthesized and the entire manuscript was then reviewed by all authors for consensus. Results:The resulting ICAR:RS document addresses multiple topics in RS, including acute RS (ARS), chronic RS (CRS) with and without nasal polyps (CRSwNP and CRSsNP), recurrent acute RS (RARS), acute exacerbation of CRS (AE-CRS), and pediatric RS. Conclusion:As a critical review of the RS literature, ICAR:RS provides a thorough review of pathophysiology and evidence-based recommendations for medical and surgical treatment. It also demonstrates the significant gaps in our understanding of the pathophysiology and optimal management of RS. Too o en the foundation upon which these recommendations are based is comprised of lowerlevel evidence. It is our hope that this summary of the evidence in RS will point out where additional research efforts may be directed. C 2016 ARS-AAOA, LLC. Key Words:rhinosinusitis; chronic rhinosinusitis; acute rhinosinusitis; recurrent acute rhinosinusitis; evidence-based medicine; systematic review; endoscopic sinus surgery List of Abbreviations Used

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

International Consensus Statement on Allergy and Rhinology: Rhinosinusitis

Orlandi

Kingdom

Hwang

et al. 2016

Int Forum Allergy Rhinol

Self Cite

559

888

View full text Add to dashboard Cite

show abstract

“…The principal physical defense against these inhaled insults is mucociliary clearance (MCC), which has 2 components, mucus production and mucus transport (1, 2). Coordinated ciliary beating transports debris-laden mucus from both the upper and lower respiratory passages toward the oropharynx, from which it is cleared by expectoration or swallowing (3). Ciliary beating accelerates in response to multiple host and environmental stimuli (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) through several second messenger pathways including intracellular Ca 2+ (15)(16)(17) and NO production (8,18,19).…”

Section: Introductionmentioning

confidence: 99%

T2R38 taste receptor polymorphisms underlie susceptibility to upper respiratory infection

Lee

Xiong²,

Kofonow³

et al. 2012

J. Clin. Invest.

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500

1,003

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Innate and adaptive defense mechanisms protect the respiratory system from attack by microbes. Here, we present evidence that the bitter taste receptor T2R38 regulates the mucosal innate defense of the human upper airway. Utilizing immunofluorescent and live cell imaging techniques in polarized primary human sinonasal cells, we demonstrate that T2R38 is expressed in human upper respiratory epithelium and is activated in response to acyl-homoserine lactone quorum-sensing molecules secreted by Pseudomonas aeruginosa and other gram-negative bacteria. Receptor activation regulates calcium-dependent NO production, resulting in stimulation of mucociliary clearance and direct antibacterial effects. Moreover, common polymorphisms of the TAS2R38 gene were linked to significant differences in the ability of upper respiratory cells to clear and kill bacteria. Lastly, TAS2R38 genotype correlated with human sinonasal gram-negative bacterial infection. These data suggest that T2R38 is an upper airway sentinel in innate defense and that genetic variation contributes to individual differences in susceptibility to respiratory infection.

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“…Mucociliary clearance is the primary physical defense against inhaled pathogens, toxins, and particulates in the respiratory system (1) and is complemented by the generation of antimicrobial peptides (AMPs) and radicals that contribute to mucosal innate immunity and maintenance of a clean airway (2). Defining the signaling pathways underlying these processes is critical for understanding and developing therapeutics for respiratory diseases, including chronic rhinosinusitis (CRS), a disease affecting nearly 35 million Americans, with an aggregated cost of $6 billion annually, and accounting for 1 in 5 antibiotic prescriptions in adults (3)(4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

Bitter and sweet taste receptors regulate human upper respiratory innate immunity

Lee¹,

Kofonow²,

Rosen³

et al. 2014

J. Clin. Invest.

Self Cite

366

639

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Bitter taste receptors (T2Rs) in the human airway detect harmful compounds, including secreted bacterial products. Here, using human primary sinonasal air-liquid interface cultures and tissue explants, we determined that activation of a subset of airway T2Rs expressed in nasal solitary chemosensory cells activates a calcium wave that propagates through gap junctions to the surrounding respiratory epithelial cells. The T2R-dependent calcium wave stimulated robust secretion of antimicrobial peptides into the mucus that was capable of killing a variety of respiratory pathogens. Furthermore, sweet taste receptor (T1R2/3) activation suppressed T2R-mediated antimicrobial peptide secretion, suggesting that T1R2/3-mediated inhibition of T2Rs prevents full antimicrobial peptide release during times of relative health. In contrast, during acute bacterial infection, T1R2/3 is likely deactivated in response to bacterial consumption of airway surface liquid glucose, alleviating T2R inhibition and resulting in antimicrobial peptide secretion. We found that patients with chronic rhinosinusitis have elevated glucose concentrations in their nasal secretions, and other reports have shown that patients with hyperglycemia likewise have elevated nasal glucose levels. These data suggest that increased glucose in respiratory secretions in pathologic states, such as chronic rhinosinusitis or hyperglycemia, promotes tonic activation of T1R2/3 and suppresses T2R-mediated innate defense. Furthermore, targeting T1R2/3-dependent suppression of T2Rs may have therapeutic potential for upper respiratory tract infections.

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Epithelium, Cilia, and Mucus: Their Importance in Chronic Rhinosinusitis

Cited by 97 publications

References 68 publications

International Consensus Statement on Allergy and Rhinology: Rhinosinusitis

International Consensus Statement on Allergy and Rhinology: Rhinosinusitis

T2R38 taste receptor polymorphisms underlie susceptibility to upper respiratory infection

Bitter and sweet taste receptors regulate human upper respiratory innate immunity

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