Quantitative sinonasal symptom assessment in an unselected pediatric population with cystic fibrosis.

INTRODUCTION: The aim of this study was to establish baseline sinonasal quality of life scores in an unselected pediatric population with cystic fibrosis (CF) and to test the correlation of those scores with various clinical outcome measurements. METHODS: A total of 50 consecutive children, ages 2-12 years, seen routinely in a large CF clinic were evaluated by using the Sinus and Nasal Quality of Life Survey (SN-5) tool at the time of their visit. At this time, the parent or guardian of the child was also questioned about recent episodes of sinusitis, antibiotic prescriptions for sinusitis, recent hospitalizations, and days missed from school or recreational activities due to sinonasal symptoms. CF genotype, pulmonary function, recent sinus surgeries, and computed tomography scores were established by thorough chart review. RESULTS: The average SN-5 score of this group was lower than published averages in children with baseline, preoperative, or postoperative chronic sinusitis, and demonstrated significant correlations with a visual analog scale, recent episodes of sinusitis, antibiotic prescriptions for sinusitis, and the number of days missed from school or recreational activities due to sinonasal symptoms, with a nonsignificant trend observed with previous sinus surgery. No correlations were seen with CF genotype, pulmonary function, or hospitalization days. Computed tomography results were overwhelmingly abnormal, and Lund-MacKay scores did not correlate with SN-5 scores or clinical outcome measurements. CONCLUSIONS: The SN-5 tool provides a quick, safe, and reliable qualitative metric for monitoring sinonasal symptoms in young children with CF.

Passive smoke exposure in chronic rhinosinusitis as assessed by hair nicotine.

BACKGROUND: Prevalence of passive smoke exposure is relatively unknown in chronic rhinosinusitis (CRS). Previous studies have attempted to establish this relationship using subjective, questionnaire-based methodologies to assess smoke exposure, thus introducing the potential for error bias. The purpose of this study was to accurately determine the prevalence of passive smoke exposure in CRS and control patients using hair nicotine levels as a quantitative measure of cigarette smoke exposure. METHODS: Hair samples were obtained at time of surgery from 569 patients: 404 undergoing surgery for CRS and 165 controls undergoing surgery for repair of cerebrospinal fluid leak, removal of pituitary tumors, or adenoidectomy from 2007 to 2013. Patient charts were reviewed for reported smoking status. Hair nicotine was quantified using reversed-phase high-performance liquid chromatography. Nonsmoking patients were classified as passive smoke exposed or smoke naïve according to the hair nicotine results. Statistical analysis was performed to test for differences in demographic information and smoke exposure prevalence between CRS, CRS subtypes, and controls. RESULTS: The prevalence of passive smoke exposure in CRS as documented by hair nicotine was lower than previously reported subjective estimates. Passive smoke exposure rates were equivalent between those with CRS versus controls and significantly higher in children. Severity of passive smoke exposure was also equivalent between CRS subsets and controls. Annual passive smoke exposure prevalence did not change over time. CONCLUSION: There is no clear evidence of avoidance of passive smoke exposure in the CRS population compared with controls. Passive smoke exposure also remained stable over time despite recent regional implementation of smoking bans. Given the constancy of exposure, it is critical that the impact of passive smoke on CRS exacerbation, outcomes, and pathophysiology be evaluated in large-scale clinical studies.

Cigarette smoke exposure is associated with vitamin D3 deficiencies in patients with chronic rhinosinusitis.

BACKGROUND: Cigarette smoke (CS) plays a role in the exacerbation of chronic rhinosinusitis (CRS); however, the mechanism for this is unknown. We hypothesize that CS impairs human sinonasal epithelial cell (HSNEC) conversion of 25(OH)D3 (25VD3) to 1,25-dihydroxyvitamin D3 (1,25VD3) and, furthermore, that supplementation with 1,25VD3 will reverse smoke-induced inflammatory responses by HSNECs. OBJECTIVE: We sought to determine the effect of CS on vitamin D3 (VD3) levels, conversion, and regulation of CS-induced inflammation in control subjects and patients with CRS. METHODS: Blood and sinus tissue explants were collected at the time of surgery from control subjects, patients with chronic rhinosinusitis without nasal polyps, and patients with chronic sinusitis with nasal polyps (CRSwNP). Expression of VD3 metabolizing enzymes were measured by using RT-PCR. Primary HSNECs were cultured from tissue explants. 25VD3 with and without cigarette smoke extract (CSE) was used to examine conversion of 25VD3 to 1,25VD3, as well as HSNEC production of proinflammatory cytokines. RESULTS: CS exposure was associated with reduced circulating and sinonasal 25VD3 levels in all groups compared with those seen in CS-naive, disease-matched counterparts. CS exposure decreased expression of CYP27B1 and was especially pronounced in patients with CRSwNP. CSE impairs control HSNEC conversion of 25VD3. HSNECs from patients with CRSwNP also demonstrate an intrinsic reduction in conversion of 25VD3 to 1,25VD3. Exogenous 1,25VD3 reduces CSE-induced cytokine production by HSNECs. CONCLUSIONS: Exposure to CS is associated with reduced 25VD3 levels and an impaired ability of HSNECs to convert 25VD3 to 1,25VD3. Addition of 1,25VD3 reduces the proinflammatory effects of CS on HSNECs. Impaired VD3 conversion by CS exposure represents a novel mechanism through which CS induces its proinflammatory effects.

Systematic review of immunotherapy for chronic rhinosinusitis.

BACKGROUND: Immunotherapy (IT) has been well established as an effective treatment for allergic rhinitis (AR), but little is known about the benefits of IT on clinical outcomes of comorbid chronic rhinosinusitis (CRS). The goal of this publication is to systematically review the literature regarding outcomes of IT in patients with atopic CRS. METHODS: A systematic review of the literature was conducted including studies that assessed the efficacy of IT on clinical outcome measures in CRS including without polyp, with polyp, and allergic fungal rhinosinusitis subgroups. Excluded articles were those only reporting outcomes specific to asthma or AR. RESULTS: Seven studies met the inclusion and exclusion criteria for this review, none of which were randomized controlled trials. Generally, symptom scores improved in patients treated with IT when compared with baseline data and control patients. Objective endoscopic exam measures improved with IT treatment in short-term studies. Significant improvements were observed in radiographic assessments, and there was a decreased necessity for revision surgery, interventional office visits, and intranasal and oral steroid use. CONCLUSION: Conclusions are limited by the paucity of available data on the efficacy of IT for treating CRS-specific outcome measures. There is weak evidence to support the use of IT as an adjunctive treatment in CRS patients, particularly in the postoperative period.

Balloon laryngoplasty for pediatric laryngeal stenosis: case series and systematic review.

OBJECTIVES/HYPOTHESIS: The aim of this study was to systematically review available literature on the outcomes of children treated with balloon laryngoplasty (BLP) as a primary or adjuvant treatment for subglottic or laryngeal stenosis, as well as briefly report on a new series of 60 children treated at the Medical University of South Carolina from 2007 to 2013. STUDY DESIGN: Review of published case series and retrospective chart review. METHODS: A literature search was performed in PubMed and MEDLINE to identify trials that reported clinical outcomes of BLP in human patients under the age of 18 with subglottic or laryngeal stenosis. Single case reports and series studying the dilation of tracheal or bronchial stenosis alone were excluded. Hospital billing codes were used to identify appropriate patients for retrospective chart review. A successful outcome for chart review was determined to be decannulation of previous tracheostomy or avoidance of open laryngotracheoplasty or tracheostomy. RESULTS: Seven studies published between 1991 and 2012 met inclusion criteria and reported outcomes with success defined through improvement of symptoms, decrease in Myer-Cotton level of stenosis, decannulation, or avoidance of reconstructive procedures. Including 60 children from our institution, 202 patients between 1 day and 22 years of age (average 35 months) underwent 457 dilations, with an average of 2.26 dilations per patient (2.25 in our population). The overall success rate was 64% (77% in our population). No complications were reported with subglottic or laryngeal dilations. CONCLUSIONS: BLP is a highly effective, low-risk alternative or adjunct to traditional reconstructive procedures in children with subglottic or laryngeal stenosis. LEVEL OF EVIDENCE: 4.

Systemic monocyte-derived dendritic cells and associated Th2 skewing in chronic rhinosinusitis.

INTRODUCTION: Monocyte-derived dendritic cells (moDCs) are antigen-presenting cells capable of directing immune responses toward T-helper 1 (Th1) or T-helper 2 (Th2) phenotypes. The systemic profile of moDCs and their association with Th1/Th2 skewing in chronic rhinosinusitis (CRS) is unclear. The purpose of this study is to characterize circulating moDCs in controls, CRS without nasal polyps (CRSsNP), and CRS with nasal polyps (CRSwNP) and correlate moDCs with Th1/Th2 skewing, mucosal inflammation on computed tomography (CT), and quality of life (QoL). STUDY DESIGN: Cross-sectional study. SETTING: Tertiary care hospital. SUBJECTS: Blood was drawn from control (n = 12), CRSsNP (n = 18), and CRSwNP (n = 15) patients during endoscopic sinus surgery. METHODS: Peripheral blood moDCs were analyzed with flow cytometry for expression of HLA-DR, CD209, and CD14. Th1 and Th2 cells were identified by CXCR3 and CCR8 expression, respectively. Lund-Mackay CT scores were assigned by blinded graders. Sino-Nasal Outcome Test 22 (SNOT-22) surveys were completed by patients before surgery. RESULTS: CRSsNP and CRSwNP displayed elevations in systemic moDCs compared with controls. In CRSwNP, systemic Th2 skewing was observed and circulating CD4+ Th2 cells correlated with percent moDCs. MoDCs strongly correlated with higher Lund-Mackay CT scores in CRSsNP but not in CRSwNP. No relationship between moDCs and SNOT-22 scores was observed for either subset of CRS. CONCLUSION: These data support that CRSwNP and CRSsNP display alterations in systemic immune profiles. CRSwNP is characterized by significant elevations in circulating moDCs, which is associated with systemic Th2-biased inflammation. Circulating moDCs are associated with mucosal inflammation on CT imaging in CRSsNP. No association between moDCs and QoL is evident in either CRS subset.

Leukotriene antagonists in nasal polyposis: a meta-analysis and systematic review.

BACKGROUND: Leukotriene antagonists (LTAs) provide a potential strategy for the management of chronic rhinosinusitis with nasal polyposis (CRSwNP), which is often refractory to medical and surgical treatment. The purpose of this study is to determine the impact of LTA treatment alone and in conjunction with intranasal corticosteroids (INCSs) on nasal symptoms, objective clinical outcomes, and immune parameters in CRSwNP. METHODS: A systematic review was performed including studies that assessed the effectiveness of LTAs on clinical outcome measures of CRSwNP. Exclusion criteria were trials assessing LTAs in CRS without nasal polyps or asthma symptoms only. Quantitative analysis was performed using a random effects model. RESULTS: Twelve studies fulfilled eligibility: five randomized control trials and seven case series. LTAs showed significant improvements in CRSwNP symptoms over placebo; however, these randomized trials were unable to be combined via meta-analysis. The two studies used in meta-analysis showed a standardized mean difference of pooled overall symptom scores of 0.02 (95% confidence interval, -0.39-0.44) between LTA and INCS study arms, indicating no difference between the treatment modalities. Improvement was described by all studies in symptoms, clinical outcomes, and/or immune parameters after LTA treatment, with greater improvements in a subset of symptoms beyond that observed with INCSs. Concomitant asthma, aspirin-exacerbated respiratory disease, and atopy did not significantly or consistently affect these results. CONCLUSION: LTAs are an effective tool for treating CRSwNP, with limited benefit as an adjunctive therapy. Additional study is required to determine the most beneficial strategy and patient population for their use.

Selection of a simian-human immunodeficiency virus strain resistant to a vaginal microbicide in macaques.

PSC-RANTES binds to CCR5, inhibits human immunodeficiency virus type 1 (HIV-1) entry, and has been shown as a vaginal microbicide to protect rhesus macaques from a simian-human immunodeficiency virus chimera (SHIV(SF162-p3)) infection in a dose-dependent manner. In this study, env gene sequences from SHIV(SF162-p3)-infected rhesus macaques treated with PSC-RANTES were analyzed for possible drug escape variants. Two specific mutations located in the V3 region of gp120 (K315R) and C-helical domain of gp41 (N640D) were identified in a macaque (m584) pretreated with a 100 microM dose of PSC-RANTES. These two env mutations were found throughout infection (through week 77) but were found at only low frequencies in the inoculating SHIV(SF162-p3) stock and in the other SHIV(SF162-p3)-infected macaques. HIV-1 env genes from macaque m584 (env(m584)) and from inoculating SHIV(SF162-p3) (env(p3)) were cloned into an HIV-1 backbone. Increases in 50% inhibitory concentrations to PSC-RANTES with env(m584) were modest (sevenfold) and most pronounced in cells expressing rhesus macaque CCR5 as compared to human CCR5. Nonetheless, virus harboring env(m584), unlike inoculating virus env(p3), could replicate even at the highest tissue culture PSC-RANTES concentrations (100 nM). Dual-virus competitions revealed a dramatic increase in fitness of chimeric virus containing env(m584) (K315R/N640D) over that containing env(p3), but again, only in rhesus CCR5-expressing cells. This study is the first to describe the immediate selection and infection of a drug-resistant SHIV variant in the face of a protective vaginal microbicide, PSC-RANTES. This rhesus CCR5-specific/PSC- RANTES resistance selection is particularly alarming given the relative homogeneity of the SHIV(SF162-p3) stock compared to the potential exposure to a heterogeneous HIV-1 population in human transmission.