How to Assess, Control, and Manage Uncontrolled CRS/Nasal Polyp Patients.

PURPOSE OF REVIEW: Chronic rhinosinusitis (CRS) is a multidimensional inflammatory disorder of the nose and paranasal sinuses. We reviewed the recent literature to identify improved methods to assess, control, and manage these difficult to control patients. RECENT FINDINGS: The role of endotyping in CRS has offered a better understanding of the underlying pathophysiology and allows for more targeted treatment. The understanding of systemic disorders and their role in CRS and the importance of topical treatment reaching the sinuses has also allowed for better control of these patients. We have provided some of the commonly identified causes for uncontrolled CRS and a sensible approach to assessing these patients. We have also focused on common areas of pitfalls in the surgery and choice of patients and the role for ongoing systemic treatment. The future of managing this difficult condition includes endotyping using inflammatory markers and individualizing the treatment to the patient by using specific monoclonal antibodies.

Topical steroids for nasal polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) represents inflammatory changes throughout the nose and sinuses from a group of disorders which all lead to swelling and overgrowth of the nasal mucosa. Topical corticosteroids have been the most widely used treatment, with each clinician using different regimes, at different doses, in different settings and with or without sinus surgery. CRSwNP requires ongoing medical management to prevent recurrence. OBJECTIVES: To assess the effects of topical corticosteroids on CRSwNP and to analyse various subgroups, including patients who had sinus surgery immediately prior to the delivery of the corticosteroids, surgery any time prior to the topical corticosteroids or patients who had never had previous surgery. Also to assess the most effective dose and delivery methods for topical corticosteroids. SEARCH METHODS: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the search was 10 April 2012. SELECTION CRITERIA: Randomised controlled trials studying topical corticosteroids for patients with CRSwNP. DATA COLLECTION AND ANALYSIS: At least two authors reviewed the search results and selected trials meeting the eligibility criteria, obtaining full texts and contacting authors. We documented our justification for the exclusion of studies. At least two authors extracted data using a pre-determined, standardised data form. MAIN RESULTS: Forty studies (3624 patients) met the inclusion criteria. The trials were at low (21 trials), medium (13 trials) and high (six trials) risk of bias. The primary outcomes were sino-nasal symptoms, polyp size and polyp recurrence after surgery. When compared to placebo, topical corticosteroids improved overall symptom scores (standardised mean difference (SMD) -0.46; 95% confidence interval (CI) -0.65 to -0.27, P < 0.00001; seven trials, n = 445) and had a higher proportion of patients whose symptoms improved (responders) (risk ratio (RR) 1.71; 95% CI 1.29 to 2.26, P = 0.0002; four trials, n = 234). Topical corticosteroids also decreased the polyp score (SMD -0.73; 95% CI -1.00 to -0.46, P < 0.00001; three trials, n = 237) and had a greater proportion of patients with a reduction in polyp size (responders) (RR 2.09; 95% CI 1.65 to 2.64, P < 0.00001; eight trials, n = 785) when compared to placebo. Topical corticosteroids also prevented polyp recurrence after surgery (RR 0.59; 95% CI 0.45 to 0.79, P = 0.0004; six trials, n = 437). Subgroup analyses by sinus surgery status revealed a greater benefit in reduction of polyp score when topical steroid was administered any time after sinus surgery (SMD -1.19; 95% CI -1.54 to -0.83) compared to patients who had never had surgery (SMD -0.13; 95% CI -0.53 to 0.28, P < 0.00001). There was no difference between groups in terms of adverse events. AUTHORS' CONCLUSIONS: Topical corticosteroids are a beneficial treatment for CRSwNP and the adverse effects are minor, with benefits outweighing the risks. They improve symptoms, reduce polyp size and prevent polyp recurrence after surgery. Patients having sinus surgery may have a greater response to topical corticosteroids but further research is required.

International assessment of inter- and intrarater reliability of the International Frontal Sinus Anatomy Classification system.

BACKGROUND: Inconsistencies in the nomenclature of structures of the frontal sinus have impeded the development of a validated "reference standard" classification system that surgeons can reliably agree upon. The International Frontal Sinus Anatomy Classification (IFAC) system was developed as a consensus document, based on expert opinion, attempting to address this issue. The purposes of this study are to: establish the reliability of the IFAC as a tool for classifying cells in the frontal recess among an international group of rhinologists; and improve communication and teaching of frontal endoscopic sinus surgery (ESS). METHODS: Forty-two computed tomography (CT) scans, each with a marked frontal cell, were reviewed by 15 international fellowship-trained rhinologists. Each marked cell was classified into 1 of 7 categories described in the IFAC, on 2 occasions separated by 2 weeks. Inter- and intrarater reliability were evaluated using Light's kappa (κ), the interclass correlation coefficient (ICC), and simple proportion of agreement. RESULTS: Interrater reliability showed pairwise κ values ranging from 0.7248 to 1.0, with a mean of 0.9162 (SD, 0.0537). The ICC was 0.98. Intrarater reliability showed κ values ranging from 0.8613 to 1.0, with a mean of 0.9407 (SD, 0.0376). The within-rater ICC was 0.98. CONCLUSION: Among a diverse sample of rhinologists (raters), there was substantial to almost perfect agreement between raters, and among individual raters at different timepoints. The IFAC is a reliable tool for classification of cells in the frontal sinus. Further outcome studies are still needed to determine the validity of the IFAC.

The microbiome and chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is a multifactorial condition in which the microbiota plays a pathogenic role. The nature of the interaction between the microbiota and the local immune system is very complex and has not been fully elucidated. Recent improvements in the microbiological techniques have greatly advanced our understanding of the complex nature of this interaction. This paper summarizes the current state of the rapidly evolving research on this subject. Defining the nature of the role of the microbiota in CRS is important because of the associated therapeutic implications.

HIV-1 and SIV Predominantly Use CCR5 Expressed on a Precursor Population to Establish Infection in T Follicular Helper Cells.

BACKGROUND: T follicular helper (Tfh) cells are increasingly recognized as a major reservoir of HIV infection that will likely need to be addressed in approaches to curing HIV. However, Tfh express minimal CCR5, the major coreceptor for HIV-1, and the mechanism by which they are infected is unclear. We have previously shown that macaque Tfh lack CCR5, but are infected in vivo with CCR5-using SIV at levels comparable to other memory CD4+ T cells. Similarly, human splenic Tfh cells are highly infected with HIV-1 DNA. Therefore, we set out to examine the mechanism of infection of Tfh cells. METHODOLOGY: Tfh and other CD4+ T cell subsets from macaque lymph nodes and spleens, splenic Tfh from HIV+ subjects, and tonsillar Tfh from HIV-uninfected subjects were isolated by cell sorting prior to cell surface and molecular characterization. HIV proviral gp120 sequences were submitted to genotypic and phenotypic tropism assays. Entry of CCR5- and CXCR4-using viruses into Tfh from uninfected tonsillar tissue was measured using a fusion assay. RESULTS: Phylogenetic analysis, genotypic, and phenotypic analysis showed that splenic Tfh cells from chronic HIV+ subjects were predominantly infected with CCR5-using viruses. In macaques, purified CCR5+PD-1intermediate(int)+ memory CD4+ T cells were shown to include pre-Tfh cells capable of differentiating in vitro to Tfh by upregulation of PD-1 and Bcl6, confirmed by qRT-PCR and single-cell multiplex PCR. Infected PD-1int cells survive, carry SIV provirus, and differentiate into PD-1hi Tfh after T cell receptor stimulation, suggesting a pathway for SIV infection of Tfh. In addition, a small subset of macaque and human PD-1hi Tfh can express low levels of CCR5, which makes them susceptible to infection. Fusion assays demonstrated CCR5-using HIV-1 entry into CCR5+ Tfh and pre-Tfh cells from human tonsils. CONCLUSION: The major route of infection of Tfh in macaques and humans appears to be via a CCR5-expressing pre-Tfh population. As the generation of Tfh are important for establishing effective immune responses during primary infections, Tfh are likely to be an early target of HIV-1 following transmission, creating an important component of the reservoir that has the potential to expand over time.

Sinus surgery and delivery method influence the effectiveness of topical corticosteroids for chronic rhinosinusitis: systematic review and meta-analysis.

BACKGROUND: Published randomized controlled trials (RCTs) on the efficacy of intranasal corticosteroid (INCS) in chronic rhinosinusitis (CRS) use either nasal delivery (nasal drop or nasal spray) or sinus delivery (sinus catheter or sinus irrigation) in patients with or without sinus surgery. This influences topical drug delivery and distribution. The effect of these factors on the published results of RCTs is assessed. This systematic review explores the strength of evidence supporting the influence of sinus surgery and delivery methods on the effectiveness of topical steroids in studies for CRS with meta-analyses. METHODS: A systematic review was conducted of RCTs comparing INCS with either placebo or no intervention for treating CRS. Data were extracted for meta-analysis and subgroup analyses by sinus surgery status and topical delivery methods. RESULTS: Forty-eight studies (3961 patients) met the inclusion criteria. INCS improved overall symptoms (standardized mean difference [SMD], -0.49; p < 0.00001) and the proportion of responders (risk ratio [RR], 0.59; p < 0.00001) compared with placebo. It decreased nasal polyp size with a greater proportion of responders (RR, 0.48; p < 0.00001) and prevented polyp recurrence (RR, 0.59; p = 0.0004) compared with placebo. Reduction of polyp size was greater in patients with sinus surgery (RR, 0.31; 95% confidence interval [CI], 0.20, 0.48) than those without (RR, 0.61; 95% CI, 0.46, 0.81; p = 0.009). Greater symptom improvement occurred when sinus delivery methods (SMD, -1.32; 95% CI, -2.26, -0.38) were compared with nasal delivery methods (SMD, -0.38; 95% CI, -0.55, -0.22; p < 0.00001). CONCLUSION: INCS is effective for CRS. Prior sinus surgery and direct sinus delivery enhance the effectiveness of INCS in CRS.