Nasal allergen challenge (NAC) is an important tool to diagnose allergic rhinitis. In daily clinical routine, experimentally, or when measuring therapeutic success clinically, nasal allergen challenge is fundamental. It is further one of the key diagnostic tools when initiating specific allergen immunotherapy. So far, national recommendations offered guidance on its execution; however, international divergence left many questions unanswered. These differences in the literature caused EAACI to initiate a task force to answer unmet needs and find a consensus in executing nasal allergen challenge. On the basis of a systematic review containing nasal allergen challenges of the past years, task force members reviewed evidence, discussed open issues, and studied variations of several subjective and objective assessment parameters to propose a standardized way of a nasal allergen challenge procedure in clinical practice. Besides an update on indications, contraindications, and preparations for the test procedure, main recommendations are a bilaterally challenge with standardized allergens, with a spray device offering 0.1 mL per nostril. A systematic catalogue for positivity criteria is given for the variety of established subjective and objective assessment methods as well as a schedule for the challenge procedure. The task force recommends a unified protocol for NAC for daily clinical practice, aiming at eliminating the previous difficulty of comparing NAC results due to unmet needs.

Purpose: Programmed death-ligand 1 (PD-L1; also known as CD274 or B7-H1) expression represents a mechanism of immune escape for cancer. Our purpose was to characterize tumor PD-L1 expression and associated T-cell infiltration in primary laryngeal squamous cell carcinomas (SCC). Experimental Design: A well-annotated cohort of 260 operable primary laryngeal SCCs [formalin-fixed paraffin-embedded (FFPE) specimens] was morphologically characterized for stromal tumor-infiltrating lymphocytes (TIL), on hematoxylin/eosin-stained whole sections and for PD-L1 mRNA expression by qRT-PCR in FFPE specimens. For PD-L1 protein expression, automated quantitative protein analysis (AQUA) was applied on tissue microarrays consisting of two cores from these tumors. In addition, PD-L1 mRNA expression in fresh-frozen tumors and normal adjacent tissue specimens was assessed in a second independent cohort of 89 patients with primary laryngeal SCC. Results: PD-L1 mRNA levels were upregulated in tumors compared with surrounding normal tissue (P = 0.009). TILs density correlated with tumor PD-L1 AQUA levels (P = 0.021). Both high TILs density and high PD-L1 AQUA levels were significantly associated with superior disease-free survival (DFS; TILs: P = 0.009 and PD-L1: P = 0.044) and overall survival (OS; TILs: P = 0.015 and PD-L1: P = 0.059) of the patients and retained significance in multivariate analysis. Conclusions: Increased TILs density and PD-L1 levels are associated with better outcome in laryngeal squamous cell cancer. Assessment of TILs and PD-L1 expression could be useful to predict response to immune checkpoint inhibitors. Clin Cancer Res; 22(3); 704–13. ©2015 AACR.

Purpose The sino-nasal outcomes test-22 (SNOT-22) represents the reference questionnaire to assess patients with chronic rhinosinusitis (CRS). As weak correlations between objective CRS parameters and SNOT-22 total score have been observed, factor analyses have aimed to identify underlying factorial structures. However, ambiguous factor loadings and problematic item-domain assignments have resulted. Moreover, such factor analyses have mainly been performed in non-European CRS patients, while European data remain sparse. This study thus sought to address these issues. Methods Principal component analysis and confirmatory factor analysis were performed from SNOT-22 questionnaires completed by European CRS patients. Goodness of fit, internal consistencies, and factor loadings were calculated. Item-domain assignment was based on statistical grounds and clinical meaningfulness. Additionally, this study investigated correlations between SNOT-22 domains and external reference criteria, including Lund–Mackay score, Lund–Naclerio score and the brief symptom inventory 18 (BSI-18). Results One hundred and thirty-four European CRS patients were included. Principal component analysis proposed four SNOT-22 domains (“ nasal symptoms ”, “ otologic symptoms ”, “ sleep symptoms ”, “ emotional symptoms ”), which explained 63.6% of variance. Observed item-domain-assignment differed from previously proposed item-domain assignments. All factor loadings were > 0.5, except “cough” (0.42) and “facial pain or pressure” (0.49). For confirmatory factor analysis, satisfactory goodness of fit (RMSEA = 0.66; CFI = 0.92; TLI = 0.90) and internal consistencies (Cronbach-α: total score = 0.93; domains = 0.75–0.91) were observed. Significant positive correlations were found between the “ nasal symptoms ” domain and both the Lund–Mackay score ( r = 0.48; p < 0.001) and the Lund–Naclerio score ( r = 0.27, p < 0.01). Significant positive correlations were also identified between “ emotional symptoms ” and BSI-18 total score ( r = 0.64, p < 0.001). Conclusions Principal component analysis performed for SNOT-22 questionnaires completed by European CRS patients indicated a different item-domain-assignment than previously reported. Confirmatory factor analysis suggested acceptable and clinically plausible psychometric properties for the resulting factorial structure. Significant correlations between the “ nasal symptoms ” and the “ emotional symptoms ” domains were observed with objective CRS parameters. The resulting factorial structure with different item-domain assignments may ...