Glucocorticoid receptor isoform expression in peripheral blood mononuclear leukocytes of patients with chronic rhinosinusitis

Background

In several inflammatory disorders, altered peripheral blood mononuclear leukocyte (PBML) glucocorticoid (GC) receptor isoform expression has been associated with GC resistance and disease severity. However, it is unclear if PBML GC receptor isoforms are expressed differentially and are associated with worsened disease severity in chronic rhinosinusitis (CRS).

Methods

PBMLs were isolated from control (n = 8), CRS without nasal polyps (CRSsNP) (n = 8), atopic CRS with nasal polyps (CRSwNP) (n = 8), non‐atopic CRSwNP (n = 8), and allergic fungal rhinosinusitis (AFRS) (n = 8) patients. Demographics, atopic status, asthmatic status, 22‐item Sino‐Nasal Outcome Test (SNOT‐22) scores, Lund‐Kennedy nasal endoscopy scores, Lund‐Mackay sinus computed tomography (CT) scores, Kennedy Osteitis scores, and GC utilization 6 months postoperatively were collected. Intracellular immunostaining was then performed for functional GC receptor α (GCRα) and nonfunctional GC receptor β (GCRβ), followed by flow cytometry analysis of geometric mean fluorescent intensity (MFI) and the percentage of cells expressing each GC receptor isoform.

Results

Compared to controls, each CRS subtype had decreased PBML GCRα and GCRα:GCRβ MFI expression, but no difference in GCRβ expression. Decreasing PBML GCRα in AFRS was associated with increasing Lund‐Mackay sinus CT scores (r = ?0.880, p =0.004). No significant associations were found between GC receptor isoform expression and other clinical measures.

Conclusion

CRS patients have reduced functional PBML GCRα expression and decreased GCRα:GCRβ compared to controls. Reductions in GCRα in AFRS are associated with worsening Lund‐Mackay sinus CT scores. The clinical implications of decreased functional GC receptor expression merits further investigation.

     

Nitric oxide‐releasing microparticles as a potent antimicrobial therapeutic against chronic rhinosinusitis bacterial isolates

Background

Bacteria, particularly in the biofilm state, may be implicated in the pathogenesis of chronic rhinosinusitis (CRS) and enhance antibiotic resistance. Nitric oxide (NO) is a gaseous immunomodulator with antimicrobial activity and a short half‐life, complicating achievement of therapeutic concentrations. We hypothesized that a novel microparticle‐based delivery platform, which allows for adjustable release of NO, could exhibit potent antibacterial effects.

Methods

Porous organosilica microparticles (SNO‐MP) containing nitrosylated thiol groups were formulated. Dissociation of the nitrosothiol groups generates NO at body temperature. The susceptibility of bacterial isolates from CRS patients to SNO‐MP was evaluated through a colony forming unit (CFU) assay. Serial dilutions of SNO‐MP in triplicate were incubated with isolates in suspension for 6 hours followed by plating on tryptic soy agar and overnight incubation followed by CFU quantification. Statistical analysis was performed with SPSS using one‐way analysis of variance with Bonferroni correction.

Results

SNO‐MP displayed antibacterial activity against gram‐positive (methicillin‐resistant and ‐sensitive Staphylococcus aureus) and gram‐negative (Pseudomonas aeruginosa, Enterobacter aerogenes, and Proteus mirabilis) isolates. SNO‐MP induced dose‐dependent reductions in CFU across all strains. Compared with controls and blank nanoparticles, SNO‐MP (10 mg/mL) induced a 99.99%‐100% reduction in CFU across all isolates, equivalent to a 5–9 log kill (p < 0.005). There was no statistically significant difference in CFU concentration between controls and blank microparticles.

Conclusion

SNO‐MP demonstrates potent bactericidal effect against antibiotic‐resistant CRS bacterial strains.

     

Efficacy of nasal irrigation with 200 μg/mL amphotericin B after functional endoscopic sinus surgery: a randomized,placebo‐controlled,double‐blind study

Background

Previous studies have shown controversial results of topical amphotericin B (AMB) nasal irrigation for chronic rhinosinusitis (CRS). The purpose of this study was to evaluate the efficacy of 200 μg/mL AMB nasal irrigation as an adjuvant therapy after functional endoscopic sinus surgery (FESS).

Methods

Patients with CRS who had received FESS for treatment were recruited and assigned to 1 of 2 groups at random at 1 month postsurgery. In the AMB group patients received nasal irrigation with 200 μg/mL of AMB for 2 months on a daily basis. In the control group normal saline irrigation was given instead. Before FESS and before and after nasal irrigation, patients’ sinonasal symptoms were assessed through a questionnaire that was a Taiwanese version of the 22‐item Sino‐Nasal Outcome Test (TWSNOT‐22). In addition, patients received endoscopic examination, acoustic rhinometry, smell test, saccharine transit test, and bacterial cultures obtained from their middle meati.

Results

A total of 73 patients completed the study between December 2014 and January 2017. Among them, 37 received nasal irrigation with AMB solution, and 36 with saline. In the AMB group, scores of TWSNOT‐22 dropped significantly after irrigation compared with before (p = 0.005). In the control group, TWSNOT‐22 scores did not changed after irrigation (p = 0.451). However, there were no significant differences in TWSNOT‐22, endoscopic score, smell test, saccharine transit test, and bacterial culture rate after irrigation between 2 groups.

Conclusion

Our study showed that in post‐FESS care, nasal irrigation with 200 μg/mL of AMB did not provide additional benefit compared with saline irrigation.     

Comparing the efficacy of Silastic and gloved‐Merocel middle meatal spacers for functional endoscopic sinus surgery: a randomized controlled trial

Background

Spacers are inserted into the middle meatal space (MMS) following functional endoscopic sinus surgery (FESS) to prevent lateralization of the middle turbinate, scarring, and synechiae. Our objective was to determine if the incidence of postoperative synechiae, facial pain/discomfort, pain during spacer removal, scarring, and discharge differed between nasal cavities receiving Silastic or gloved‐Merocel (GM) spacers following FESS.

Methods

A double‐blind, randomized controlled trial (RCT) was conducted in adults requiring bilateral FESS for chronic rhinosinusitis (CRS) ± nasal polyposis. Participants served as their own controls, with each subject receiving both a Silastic and GM spacer. Spacers were inserted into the MMS during FESS and left in situ for 6 days. Participants were reviewed at 6 days, 5 weeks, and 12 weeks postoperatively. The presence of synechiae and scarring were evaluated endoscopically. Inflammation, discharge, and pain during spacer removal were assessed using a visual analogue scale (VAS).

Results

Forty‐eight participants (96 nasal cavities) were recruited. Preoperatively, Lund‐Mackay computed tomography (CT) scores were similar between Silastic‐treated and GM‐treated cavities (6.38 ± 2.35 vs 6.18 ± 2.17). The incidence of synechiae and scarring did not differ significantly between spacers up to 12 weeks postoperatively. Pain during spacer removal was significantly greater for Silastic than GM spacers (2.13 ± 1.34 vs 1.51 ± 1.23, p = 0.020). Facial pain prior to removal and extent of discharge did not differ significantly between spacers.

Conclusion

Following FESS, patients report less pain during removal of GM than Silastic spacers. However, the likelihood of synechiae and scarring did not differ between either of the spacers.

     

Corticosteroid nasal irrigations are more effective than simple sprays in a randomized double‐blinded placebo‐controlled trial for chronic rhinosinusitis after sinus surgery

Background

Persistent mucosal inflammation in patients with chronic rhinosinusitis (CRS) often results in ongoing symptoms, recurrence of polypoid mucosa, infective exacerbations, and further systemic medication despite surgical intervention. Debate exists as to the most effective topical therapy in CRS.

Methods

The objective was to determine if corticosteroid delivered via a nasal irrigation or via a simple nasal spray would be more effective in controlling the symptoms and signs of CRS. A double‐blind placebo‐controlled randomized trial over 12 months was performed between 3 tertiary rhinologic clinics. After sinus surgery, all patients performed a nasal irrigation followed by a nasal spray once a day for 12 months. Groups were defined by corticosteroid (2 mg mometasone) delivered by either spray or irrigation. The primary outcomes were patient‐reported symptoms: visual analogue score (VAS) and 22‐item Sino‐Nasal Outcome Test (SNOT‐22), a global rating of sinonasal function. Secondary outcomes were also recorded from radiology (Lund‐Mackay score [LMS]) and endoscopic (Modified Lund‐Kennedy score [mLKS]) assessments.

Results

A total of 44 patients were randomized (age 50.3 ± 13.0 years; 40.9% female). Overall, patients improved significantly from either intervention. However, the corticosteroid nasal irrigation group had greater improvement in nasal blockage (?69.91 ± 29.37 vs ?36.12 ± 42.94; p = 0.029), a greater improvement on LMS (?12.07 ± 4.43 vs ?7.39 ± 6.94; p = 0.031) and less inflammation on mLKS at 12 months (7.33 ± 11.55 vs 21.78 ± 23.37; p = 0.018). One‐year posttreatment blockage, drainage, fever, and total VAS scores were all lower in the corticosteroid irrigation group.

Conclusion

In the setting of diffuse or patchy CRS disease, the use of corticosteroid delivered by nasal irrigation is superior to simple nasal spray in postsurgical patients.