xRead - Nasal Obstruction (September 2024) Full Articles

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International consensus statement on rhinosinusitis

to grow robust biofilms in vitro , 610 while those patients were also at a higher risk for needing surgical intervention for their disease. 611 Bitter taste testing for the presence of T2R38 could potentially predict CRS severity or necessity of treatment, 612 and bitter compounds themselves could serve as therapeutic agents by directly activating the host immune response against biofilm formation in CRS. 613–615 Further clinical studies are needed in this realm.

Conventional treatment requires physical removal or dis ruption of the biofilm matrix which can be accomplished with surgical intervention and aggressive irrigations, however too aggressive of an antibiofilm intervention may leave the epithelium compromised. 578,589,590 Antibiotics such as ceftazidime, piperacillin, ciprofloxacin, and vancomycin are ineffective when given systemically at typical concentrations and higher concentrations of these compounds are often not clinically safe, sometimes requiring a 60-1000 fold increase in dosing to achieve an effect. 591,592 Topical therapy may be a more effective approach. Mupirocin has been shown to reduce biofilm mass, 592 but it is unclear if there is a maintained effect after antibiotic application has ceased. 593 Macrolides inhibit quorum sensing in P. aeruginosa , and their pre scription may become a useful therapeutic strategy for treating biofilm-associated CRS. 584 Combination therapies that have synergistic antimicrobial effects are a promising avenue of research. A ciprofloxacin and ivacaftor eluting stent reduces P. aeruginosa biofilm formation in vitro . 594 Furosemide, which acts as a cation channel blocker, also reduces biofilm size. 595 Corticosteroids have shown some inhibitory effect against S. aureus biofilm formation specifically, 596 while another study demonstrated that cor ticosteroids were effective against S. aureus, P. aeruginosa , and S. epidermidis biofilm formation. 597 Other less conventional treatments have been trialed, with varying degrees of success. Bacteriophages have been shown to reduce the biofilm burden of Pseudomonas aerug inosa clinical isolates from CRS patients. 598 Colloidal silver (CAg) 599 as well as a topical nitric oxide donor 600 reduce S. aureus biofilm burden. Detergent agents have appre ciable biofilm-disrupting effects, but currently are not in use due to several side effects, including ciliary toxicity and reversible hyposmia. 589,590,601–604 Photodynamic ther apy has demonstrated promising efficacy in reducing pre formed biofilms in vitro and preliminary toxicity studies have not shown deleterious side effects. 605,606 Lastly, low frequency ultrasound treatments also seem effective in reducing biofilms, also without observed side effects. 607 A promising new approach to understanding biofilms involves bitter taste receptors in the upper respiratory tract. Acyl-homoserine lactones (AHLs) produced by gram-negative bacteria serve as biofilm “quorum-sensing molecules,” and these molecules are ligands for airway bit ter taste chemoreceptors. 608 Detection of these molecules allows the host to mount an innate defensive response before the bacteria reach the density required for biofilm formation. 609 One of these bitter taste receptors, T2R38, is activated by AHLs and has downstream effects of increased MCC and bactericidal nitric oxide (NO) pro duction. Microbial swabs from CRS patients with a non functional mutation in the T2R38 gene were more likely

Biofilms as a Contributing Factor for CRSsNP Aggregate Grade of Evidence: C (Level 3: 2 studies, Level 4: 5 studies; Table IX-4).

IX.C.3 Contributing Factors for CRS: Fungus Because of limited data, CRSsNP and CRSwNP are com bined in this analysis. A broad range of opinions have been expressed on poten tial roles for fungus in the pathogenesis of CRS, ranging from “all forms of CRS are caused by fungus” to “fun gus has no role in CRS.” 616,617 Although a recent Cochrane review found no evidence for the efficacy of anti-fungal treatment in CRS, 618 there is some room for nuance and discussion. Fungal spores are ubiquitous in the environment and not surprisingly detected from the nasal cavity of both CRS patients and normal controls. 619 Aspergillus, Cla dosporium, Candida, Aureobasidium, and Alternaria are the most frequently recovered fungal species from nasal lavages and swabs from the middle meati. 620,621 When maxillary sinus secretions were sampled specifically, fungi were detected in only 20% of controls vs in over 80% of CRSwNP patients. 622 However, the presence of fungi seen in the sinuses of CRS patients may be explained by delayed MCC, and may therefore be a downstream effect of inflam mation rather than a cause. In the same study that specifi cally sampled the sinus cavity rather than the nasal cavity for the presence of fungi, T helper 2 cell memory for the specific fungal species found in the sinus cavity was noted in 100% of AFRS and 65% of other CRSwNP patients, but in 0% of control subjects. 622 These findings support a possible role of fungi in the Type 2 immune response characteristic ofCRSwNP. Sinonasal epithelial cells have a robust innate immune response against fungi. Immunologic responses to fungi have been observed in CRS patients. Sinonasal