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26.  Local expression of interleukin-17a is correlated with nasal eosinophilia and clinical severity in allergic rhinitis 
Allergy & Rhinology  2014;5(1):e22-e27.
Interleukin (IL)-17A is a major cytokine produced by Th17 cells, which are associated with chronic inflammations. The local expression of IL-17A in allergic rhinitis (AR) remains to be characterized. We sought to determine the role of IL-17A expression in human inferior turbinate mucosa in the pathophysiology of AR. Inferior turbinate mucosa was sampled from medical treatment–resistant, surgery-required patients with perennial AR (PAR, n = 21), nonallergic rhinitis with eosinophilia syndrome (NARES, n = 7), and nonallergic hypertrophic rhinitis (HR, n = 13). IL-17A expression was determined with immunohistochemical staining. The mean number of IL-17A+ cells and eosinophils per field were counted. Total serum immunoglobulin E (IgE) levels, blood eosinophil count, and forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio were also examined in each patient. IL-17A was primarily expressed in infiltrating inflammatory cells. The number of IL-17A+ cells in nasal mucosa was significantly higher in the PAR group compared with HR (p = 0.002) and NARES (p = 0.021) groups. There was a significant and positive correlation between the number of IL-17A+ cells and total nasal symptom score (rho = 0.403; p = 0.011), especially sneezing score (rho = 0.471; p = 0.003). The number of IL-17A+ cells was significantly and positively correlated with the degree of eosinophil infiltration (rho = 0.623; p < 0.001), but not with total serum IgE levels (rho = 0.284; p = 0.098), blood eosinophil counts (rho = 0.302; p = 0.056), or FEV1/FVC ratio (rho = 0.092; p = 0.569). The present study provides evidence that IL-17A expression in the nasal mucosa is associated with the pathophysiology of AR, including disease severity and nasal eosinophilia.
doi:10.2500/ar.2014.5.0078
PMCID: PMC4019741  PMID: 24758732
Allergic rhinitis; eosinophil; IL-17A; nasal mucosa; total nasal symptom score
27.  Validation of the applicability of the traditional Chinese version of the University of Pennsylvania Smell Identification Test in patients with chronic rhinosinusitis 
Allergy & Rhinology  2014;5(1):e28-e35.
The 40-item University of Pennsylvania Smell Identification Test (UPSIT) is the most widely used smell test in the world. Presently, culturally modified versions of this test are available in multiple languages. A traditional Chinese version of the UPSIT (UPSIT-TC) has been developed for administration in Taiwan. The purpose of this study was to investigate the validity and reliability of the UPSIT-TC in Taiwanese patients with chronic rhinosinusitis (CRS). The phenylethyl alcohol (PEA) odor detection threshold test, the North American version of UPSIT (UPSIT-NA), and the UPSIT-TC were administered to 40 healthy subjects and to 100 CRS patients before and after functional endoscopic sinus surgery (FESS). The UPSIT-TC showed good internal consistency (Cronbach's alpha = 0.887, 0.886, and 0.870 at three test occasions) and test–retest reliability (p < 0.001). The scores of UPSIT-TC were significantly correlated to the PEA thresholds (p < 0.001). The UPSIT-TC scores were significantly higher than those of the UPSIT-NA (p = 0.028) when analysis was performed with logistic regression with independent variables including test occasions (before or after FESS), test methods (UPSIT-NA or UPSIT-TC), status of polyp (with or without), and PEA thresholds (improved or did not improve). In addition, there were significant between-group differences in UPSIT-TC scores including healthy versus CRS, CRS with polyps versus CRS without polyps, and PEA thresholds improved versus PEA thresholds which did not improve. The UPSIT-TC is reliable and valid for measuring olfactory function in Taiwanese patients with rhinosinusitis. In addition, the UPSIT-TC clearly resulted in better performance than that of UPSIT-NA.
doi:10.2500/ar.2014.5.0084
PMCID: PMC4019742  PMID: 25199144
Chronic rhinosinusitis; functional endoscopic sinus surgery; nasal polyp; olfactory function; phenyl ethyl alcohol odor detection threshold test; reliability; smell test; traditional Chinese version; UPSIT; validity
28.  Frontal sinus cholesterol granuloma: Case report 
Allergy & Rhinology  2014;5(1):e36-e38.
A case report of a massive cholesterol granuloma (CG) of the frontal sinus in a 15-year-old male subject treated endoscopically is reported. CGs are slowly expanding, cystic lesions that are rarely observed in the frontal sinus. Frontal sinus CGs characteristically present with proptosis, diplopia, and a unilateral painless expanding mass above the orbit. Patients frequently report a history of chronic nasal obstruction or head trauma. Although the pathogenesis is unclear, it is likely multifactorial in etiology. Surgical resection via endoscopic sinus surgery has been gaining popularity because of the minimally invasive approach and lower rates of recurrence.
doi:10.2500/ar.2014.5.0073
PMCID: PMC4019743  PMID: 24612824
Case report; cholesteatoma; cholesterol; cholesterol granuloma; endoscopic sinus surgery; frontal sinus; granuloma; surgical technique
29.  Smell sparing unilateral intracranial dermoid resection 
Allergy & Rhinology  2014;5(1):e39-e40.
Intracranial dermoid cysts are congenital ectodermal inclusion cysts that have a propensity to occur in the midline sellar, parasellar, or frontonasal regions. These cysts enlarge by means of glandular secretion and epithelial desquamation. Surgical resection has traditionally included a craniotomy, but endoscopic approaches are now used with increasing regularity. A binostril approach is normally used to access dermoid cysts due to the midline nature of the lesions. In this case report, we describe the successful surgical resection of a dermoid with 1.5-cm of intracranial extension using a unilateral endonasal endoscopic approach with no complications and with no postoperative anosmia. Although the unilateral endoscopic technique is not plausible for all epidermoid or dermoid cysts of the anterior cranial fossa, it should be considered a viable alternative technique when faced with a dermoid limited to one side of the falx cerebri.
doi:10.2500/ar.2014.5.0074
PMCID: PMC4019744  PMID: 24612984
Anosmia; dermoid cyst; endoscopic sinus surgery; hyposmia; nasoseptal flap; skull base surgery
30.  Asthma linked with rhinosinusitis: An extensive review 
Allergy & Rhinology  2014;5(1):e41-e49.
Current literature related to asthma diagnosis, epidemiology, pathogenesis, and treatment linked with rhinosinusitis is important. Asthma is very heterogeneous; new theories and treatments are emerging. It is a growing epidemic among children and adults in the United States and the severity of asthma is caused by many factors such as lack of education, poor early recognition, decreased symptom awareness, improper medications, and phenotypic changes. Genetic variation, innate immune genes, those involved in tissue remodeling and arachidonic acid metabolism, and inflammatory mediators might contribute to the pathogenesis of chronic rhinosinusitis (CRS) linked with asthma. This extensive review addresses concepts of the burden of asthma and sinusitis, altered innate immunity, adaptive immunity, asthma remodeling, the airway epithelium, the role of airway smooth muscle cells, united allergic airway, genetics, an integral part in asthma, and CRS. In addition, the role of vitamin D in both asthma and CRS in the elderly and pediatric population, various treatment options, and exhaled nitric oxide are briefly addressed.
doi:10.2500/ar.2014.5.0083
PMCID: PMC4019745  PMID: 24684837
Asthma; FeNO; genetics; phenotypes; remodeling; sinusitis; treatments; vitamin D
31.  Pathology quiz case: Plasmacytoid dendritic cell neoplasm 
Allergy & Rhinology  2014;5(1):e50-e52.
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy that possesses a heterogenous clinical and immunophenotypic presentation. The current case report describes an interesting and unique presentation of BPDCN as a primary paranasal sinus tumor without evidence of cutaneous or systemic involvement. As such, the report further contributes to the ongoing debate regarding the true putative origin of the neoplasm, as well as highlights the optimal diagnostic modalities, paramount importance of early diagnosis, and vast heterogeneity exhibited by this fascinating malignancy. The atypical presentation described here indicates the manifestations of BPDCN are more heterogenous than previously documented and thus can not be definitively ruled out in the absence of bone marrow, peripheral blood, or cutaneous involvement. Furthermore, atypical neoplastic presentations mandate flow cytometry and adjunctive immunohistochemistry for the definitive diagnosis of BPDCN, and early diagnosis of such neoplasms are critical for rapid initiation of treatment and improved outcomes.
doi:10.2500/ar.2014.5.0085
PMCID: PMC4019746  PMID: 25199145
Blastic plasmacytoid dendritic cell neoplasm; endoscopic sinus surgery; ethmoid sinus; flow cytometry; immunohistochemistry; maxillary sinus; sphenoid sinus
32.  Soluble HLA-G serum levels depend on allergy type and IgE levels 
Allergy & Rhinology  2014;5(1):e9-e11.
Allergic rhinitis (AR) is characterized by Th2 polarized immune response. Soluble HLA (sHLA) molecules play an immunomodulatory activity. Two different studies evidenced that both patients with seasonal AR (SAR) and patients with perennial AR (PAR) had higher sHLA-G levels than normal controls. The aim of this study was to compare sHLA-G serum levels in SAR and PAR patients, also considering allergen-specific IgE. One hundred sixty-eight AR patients were enrolled, 94 with SAR and 74 with PAR. A group of 116 healthy subjects was considered as control. sHLA-G and allergen-specific IgE serum levels were determined by immunoenzymatic method. SAR patients had significantly higher levels of sHLA-G than PAR patients (p = 0.0194). sHLA-G was moderately related to allergen-specific IgE both in SAR (r = 0.497) and in PAR patients (r = 0.584). The present study provides evidence that sHLA-G serum levels depend on the type of allergy and are related to allergen-specific IgE serum levels. These findings may suggest that sHLA-G could be a biomarker of allergic reaction.
doi:10.2500/ar.2014.5.0076
PMCID: PMC4019747  PMID: 24612937
Allergic rhinitis; IgE; perennial allergens; pollens; sHLA-G
33.  The anatomical and functional relationship between allergic conjunctivitis and allergic rhinitis 
Allergy & Rhinology  2013;4(3):e110-e119.
There are numerous anatomic connections between the allergic conjunctivitis and allergic rhinitis. The most obvious reason is the physical connection via the nasolacrimal apparatus. However, a closer look at innervation, circulatory, lymphatic, and neurogenic systems reveals much more than a physical connection. The eye is richly innervated by parasympathetic nerves that enter the eyes after traveling in conjunction with the parasympathetic input to the nasal cavity. Parasympathetic innervation governing the tear film and nasal secretion can intersect at the pterygopalatine ganglion. Neurogenic inflammation affects both the eye and the nose as evidenced by the presence of the same neurogenic factors. Venous flow is in the SOV area connecting the eye and the nose, once thought to be without valves. In the past, this thinking is the basis for concern about the danger triangle of the face. Recent literature has shown otherwise. Although valves are present, there are still pathways where bidirectional flow exists and a venous connection is made. The most likely area for venous communication is the pterygoid plexus and cavernous sinus. The venous flow and connections also offers a pathway for allergic shiners. Understanding the mutual connections between the nasal mucosa and the ocular surface can also affect treatment strategies.
doi:10.2500/ar.2013.4.0067
PMCID: PMC3911799  PMID: 24498515
Allergic conjunctivitis; cavernous sinus; nasolacrimal; naso-ocular reflex; neurogenic inflammation; ocular allergy; pterygoid plexus; pterygopalatine ganglion; rhinitis
34.  Efficacy of mometasone furoate and fluticasone furoate on persistent allergic rhinoconjunctivitis 
Allergy & Rhinology  2013;4(3):e120-e126.
Allergic rhinoconjunctivitis denotes both nasal and ocular manifestation of allergy, which may be solely treated with intranasal steroid. This study compares the efficacy of mometasone furoate nasal spray (NS) and fluticasone furoate NS in treatment of allergic rhinoconjunctivitis. The secondary objective is to study the severity of baseline ocular symptoms in allergic rhinoconjunctivitis. Seventy-eight patients with allergic rhinoconjunctivitis were assessed subjectively and objectively using twice-daily symptom scores for nasal (reflective total nasal symptom score [rTNSS] and instantaneous TNSS [iTNSS]) and ocular (reflective total ocular symptom score [rTOSS] and instantaneous TOSS [iTOSS]) symptoms, rhinoconjunctivitis quality-of-life questionnaires (RQOLQs), and acoustic rhinometry. All measurements were taken at baseline and at 4 and 8 weeks of treatment. Sixty-three patients who were randomized into the mometasone furoate group (n = 36) and the fluticasone furoate group (n = 27) completed the study. Seventy-six percent of patients had mild ocular symptoms, 20.5% had moderate symptoms, and only 2.6% had severe symptoms at baseline based on the iTOSS; 65.1% had mild nasal symptoms and 3% had severe nasal symptoms. There was significant reduction in the symptom scores after 1 week (p < 0.05). Both groups had significant improvement in RQOLQ scores after 1 month, which further improved at 2 months (p < 0.05). The nasal dimensions also improved in both groups (p < 0.05) but there was no statistically significant difference between groups. Both mometasone furoate and fluticasone furoate are effective as single-modality treatment of allergic rhinoconjunctivitis. The majority of patients manifest mild ocular symptoms that may be solely treated with intranasal steroids.
doi:10.2500/ar.2013.4.0065
PMCID: PMC3911800  PMID: 24498516
Allergic rhinoconjunctivitis; fluticasone furoate; intranasal steroids; mometasone furoate; ocular symptoms; perennial allergic rhinitis
35.  Retrospective cohort study of leukotriene receptor antagonist therapy for preventing upper respiratory infection-induced acute asthma exacerbations 
Allergy & Rhinology  2013;4(3):e127-e131.
Upper respiratory tract infections (URIs) represent the most frequent cause of acute asthma exacerbations. It has yet to be determined whether leukotriene receptor antagonist (LTRA) treatment prevents URI-induced acute asthma exacerbations in adults. The objective of the present study was to evaluate the preventive effects of LTRA treatment on URI-induced acute asthma exacerbations. The incidences of URI alone, acute asthma exacerbation without URI, and URI-induced acute asthma exacerbation were determined retrospectively by analyzing diary and medical records of 321 adult asthmatic patients (mean age, 56.3 ± 17.2 years; male/female ratio, 117:204) over 1 year. Results were compared between patients who had been taking an LTRA (n = 137) and those who had never taken any LTRA (n = 184) during the study periods. Significantly fewer URIs alone and acute asthma exacerbations without URI occurred in patients with than in those without prophylactic daily use of LTRA. LTRA treatment significantly reduced the durations of URIs alone and of total acute asthma exacerbations, as well as the incidence of mild exacerbations of asthma. In contrast, in patients with URI-induced acute asthma exacerbations, LTRA treatment failed to significantly reduce the interval between URI onset and acute asthma exacerbation, as well as the duration and severity of both URIs and acute asthma exacerbations. Use of an LTRA for adult asthmatic patients appears to reduce the incidences of URIs alone and acute asthma exacerbations without URI, but it failed to prevent URI-induced acute asthma exacerbations once a URI occurred.
doi:10.2500/ar.2013.4.0062
PMCID: PMC3911801  PMID: 24498517
Acute asthma exacerbation; bronchial asthma; inhaled corticosteroids; inhaled long-acting beta2-agonist; leukotriene receptor antagonist; montelukast; pranlukast; retrospective cohort study; short-acting beta2-agonist; upper respiratory tract infection
36.  Association of matrix metalloproteinase 8 genetic polymorphisms with bronchial asthma in a Japanese population 
Allergy & Rhinology  2013;4(3):e132-e139.
Asthma has a strong genetic component. The final disease phenotype results from complex interactions between environment and multiple genes of small-to-modest effects. We investigated whether the polymorphism in genes encoding inflammatory mediators and cytokines is important for solving the onset and progression of asthma. We investigated whether 31 single nucleotide polymorphisms (SNPs) in genes encoding cytokines or monokines (interleukin [IL]-5R, matrix metalloproteinase [MMP] 8, beta2 adrenergic receptor, cytotoxic T-lymphocyte–associated antigen 4, IL-3, C-reactive protein, cytochrome P450 (CYP) 2C9, CYP3A4, a disintegrin and metalloproteinase [ADAM] 33, cysteinyl leukotriene receptor [CysLTR] 1, CysLTR2, eosinophilic cationic protein, glucocorticoid receptor, and leukotriene A 4 hydrolase) are related to asthma development in 206 Japanese bronchial asthma patients and 127 healthy controls. Using multifactor dimensionality reduction (MDR), we identified rs17099451 in MMP8, using a single locus model, with a mean cross-validation of 87.0%. Using a two-locus model, combinations of MMP8 and rs44707 in ADAM33, and MMP8 and rs40401 in IL-3, were identified, with mean cross-validation consistencies reaching 45.0%. Of the SNPs selected by the MDR method, rs17099451 in MMP8 and rs40401 in IL-3 were regarded as the most significant results in a 2 × 2 dominant model analysis. The finding that an MMP8 allele was most strongly related to asthma development indicates that metalloproteinase function is crucial to the airflow limitation process involved in this disease.
doi:10.2500/ar.2013.4.0063
PMCID: PMC3911802  PMID: 24498518
Asthma; Japanese population; multifactor dimensionality reduction (MDR); rs17099451 in MMP8; rs44707 in ADAM33; rs40401 in IL-3; single nucleotide polymorphism (SNP)
37.  Piezoelectric sensing: Evaluation for clinical investigation of deviated nasal septum 
Allergy & Rhinology  2013;4(3):e140-e150.
Noninvasive objective evaluation of nasal airflow is one of the important clinical aspects. The developed polyvinylidene fluoride (PVDF) sensor enables measurement of airflow through each side of the nose using its piezoelectric property. This study was designed to evaluate the diagnostic capability of the PVDF sensor in assessing the deviated nasal septum (DNS). PVDF nasal sensor uses its piezoelectric property to measure the peak-to-peak amplitude (Vp-p) of nasal airflow in both of the nostrils: right nostril (RN) and left nostril (LN), separately and simultaneously. We have compared the results of PVDF nasal sensor, visual analog scale (VAS), and clinician scale for 34 DNS patients and 28 healthy controls. Additionally, the results were further analyzed by receiver operating characteristic curve and correlation between PVDF nasal sensor and VAS in detecting DNS. We found a significant difference in the peak-to-peak amplitude values of the test group and the control group. The correlation between the PVDF nasal sensor measurements and VAS (RN and LN combined) for test group was statistically significant (−0.807; p < 0.001). Sensitivity and specificity of the PVDF nasal sensor measurements in the detection of DNS (RN and LN combined) was 85.3 and 74.4%, respectively, with optimum cutoff value ≤0.34 Vp-p. The developed PVDF nasal sensor is noninvasive and requires less patient efforts. The sensitivity and specificity of the PVDF nasal sensor are reliable. According to our findings, we propose that the said PVDF nasal sensor can be used as a new diagnostic tool to evaluate the DNS in routine clinical practice.
doi:10.2500/ar.2013.4.0066
PMCID: PMC3911803  PMID: 24498519
Deviated nasal septum; piezoelectric property; polyvinylidene fluoride; visual analog scale
38.  Practice patterns regarding noninvasive rhinosinusitis in the immunosuppressed patient population 
Allergy & Rhinology  2013;4(3):e151-e154.
The number of immunosuppressed patients is growing remarkably. Currently, there is no guideline on how treatment of noninvasive sinusitis in these patients may differ from that of the general population, and practice patterns vary widely across the country. The purpose of this survey was to examine practice patterns and management for this patient population. A survey and literature review were performed. The survey was sent to the membership list serve of the American Rhinologic Society. Twelve questions were asked. Four demographic questions were asked about the physicians and their practices. Four questions were asked about the type of immunocompromised patients they saw. Two questions were asked about management in the setting of significant acute and chronic sinusitis. The responses were collected and analyzed using Pearson independent chi-square testing. Of 871 members on the list serve only 89 physicians responded. The majority of responders were sinus and skull base surgeons practicing in an academic setting. There was a large range of geographic location, years in practice, and patient population. Two significant findings related years in practice to management of chronic sinus immunocompromised patients (p = 0.012) and correlated the choice of management option in acute and chronic sinus immunocompromised patients (p = 0.006). There is no standardized method of treating the vulnerable patient population of immunocompromised patients with noninvasive acute and chronic sinusitis and this survey shows the wide range of practice. Clinical research is needed to standardize and optimize treatment for these patients.
doi:10.2500/ar.2013.4.0070
PMCID: PMC3911804  PMID: 24498520
Acute; chronic; immunocompromised; immunodeficiency; immunosuppressed; management; medical therapy; rhinosinusitis; sinusitis; surgical therapy; treatment
39.  Use of the Hadad-Bassagasteguy flap for repair of recurrent cerebrospinal fluid leak after prior transsphenoidal surgery 
Allergy & Rhinology  2013;4(3):e155-e161.
The Hadad-Bassagasteguy vascularized nasoseptal pedicled flap (HBF) is an effective technique for reconstruction of skull base defects with low incidence of postoperative cerebrospinal fluid (CSF) leak. Advanced planning is required as posterior septectomy during transsphenoidal surgery can preclude its use due to destruction of the vascular pedicle. We present four cases in which the HBF was successfully used to repair recurrent CSF leaks despite prior posterior septectomy and transsphenoidal surgery. A retrospective chart review was performed on all patients who developed recurrent CSF leak after transsphenoidal surgery over a 7-year period (2006–2013). Data were collected regarding demographics, clinical presentation, intraoperative findings, and surgical outcomes. Four patients who developed recurrent CSF drainage after transsphenoidal surgery were managed with HBF reconstruction during the study period. Two were men and two were women with a mean age of 37 years (range, 24–48 years). All had previously undergone resection of a pituitary macroadenoma via a transsphenoidal approach, with intraoperative CSF leaks repaired using multilayered free grafts. Recurrent CSF rhinorrhea arose 0.37–12 months (mean, 2.98 months) after the initial pituitary surgery. Active CSF drainage could be visualized intraoperatively with posterior septal perforations present. The HBF was successfully used in all cases, with no evidence of recurrent CSF leak after a mean follow-up of 2.35 years. The HBF may be salvaged for repair of recurrent CSF leaks even in the context of prior posterior septectomy and transsphenoidal surgery. However, longer follow-up is necessary to determine the long-term efficacy of this procedure in such revision cases.
doi:10.2500/ar.2013.4.0072
PMCID: PMC3911805  PMID: 24498521
Cerebrospinal fluid leak repair; nasoseptal flap; transsphenoidal surgery
40.  Stent hypersensitivity and infection in sinus cavities 
Allergy & Rhinology  2013;4(3):e162-e165.
Persistent mucosal inflammation, granulation tissue formation, hypersensitivity, and multifactorial infection are newly described complications of retained drug-eluting stents from endoscopic sinus surgery for refractory rhinosinusitis. In an important report published in Allergy and Rhinology, a 45-year-old male patient suffering from recalcitrant chronic rhinosinusitis underwent functional endoscopic sinus surgery and was found, for the first time, to have steroid-eluting catheters that were inadvertently left in the ethmoid and frontal sinuses. The retained catheters had caused persistent mucosal inflammation and formation of granulation tissue denoting hypersensitivity reaction. These consequences had induced perpetuation of symptoms of chronic rhinosinusitis. Meticulous removal of the retained stents with the nitinol wings from inflamed tissues of the frontal, ethmoidal, and sphenoethmoidal recesses in which they were completely imbedded was successfully performed without polypoid regrowth. Cultures of specimens taken from both left and right stents showed heavy growth of Stenotrophomonas maltophilia and moderate growth of Klebsiella oxytoca, coagulase negative Staphylococcus, and beta-hemolytic Streptococcus anginosus. Fungal infection was not detected. The current knowledge and experience regarding stent hypersensitivity and infection in relation with the use of stents in sinus cavities is reviewed.
doi:10.2500/ar.2013.4.0071
PMCID: PMC3911806  PMID: 24498522
Biodegradable stents; drug eluting stents; stent hypersensitivity; stent implantation; stent infection; stent retaining; stents
41.  Intracranial mucocele formation in the context of longstanding chronic rhinosinusitis: A clinicopathologic series and literature review 
Allergy & Rhinology  2013;4(3):e166-e175.
Chronic rhinosinusitis (CRS) can lead to serious long-term adverse sequelae, particularly if left untreated. The aim of this study was to describe a series of intracranial mucoceles (ICMs) that arose in the context of longstanding CRS combined with a review of the pertinent literature. A retrospective chart review was performed on all patients who developed ICMs in association with CRS between 2003 and 2012. The clinical presentation, radiographic features, surgical approach, intraoperative findings, and patient outcome were examined in the context of a literature review. Sixty-five cases of mucoceles were identified in patients with a history of CRS, of which seven (10.8%) were intracranial. Five patients were men and two were women with a mean age of 42.1 years. Headache, facial pressure, retro-orbital pain, and visual disturbances were the most common presenting symptoms. Five of the seven had previously undergone sinonasal surgery. Imaging studies showed ICMs involving the anterior cranial fossa, two of which were bilateral. Latency between onset of CRS and ICM detection ranged from 3 to 19 years (mean, 9.4 years). All patients underwent endoscopic transnasal drainage with three also requiring a concurrent, open neurosurgical procedure to access the intracranial component. There were no postoperative complications, and no recurrences were observed after a mean follow-up of 2.7 years. ICMs presenting as delayed complications of CRS are uncommon and constitute a surgical challenge. Open, external skull base approaches used in conjunction with transnasal endoscopic drainage procedures may be necessary to achieve successful management of this rare condition.
doi:10.2500/ar.2013.4.0064
PMCID: PMC3911807  PMID: 24498523
Chronic rhinosinusitis; complications; intracranial mucoceles
42.  Endoscopic transnasal eustachian tube reconstruction via light cable technique: A technical report 
Allergy & Rhinology  2013;4(3):e176-e178.
doi:10.2500/ar.2013.4.0069
PMCID: PMC3911808  PMID: 24498524
Eustachian tube; light cable; nasopharynx; rhinology
43.  Endoscopic nonembolized resection of an extensive sinonasal cavernous hemangioma: A case report and literature review 
Allergy & Rhinology  2013;4(3):e179-e183.
Sinonasal hemangiomas, although rare, must be considered in the evaluation of intranasal masses with profuse epistaxis. Although the availability of literature discussing cavernous hemangiomas in this location is limited, there have been no case reports of exclusively soft tissue sinonasal cavernous hemangiomas extending to the anterior skull base (ASB) that were resected purely endoscopically. Here, we describe the successful endoscopic resection of an extensive right sinonasal cavernous hemangioma extending to but not invading the ASB. Although highly vascular, in select cases, these tumors can be successfully resected endoscopically without embolization by experienced endoscopic sinus and skull base surgeons.
doi:10.2500/ar.2013.4.0068
PMCID: PMC3911809  PMID: 24498525
Anterior skull base; benign tumor; cavernous hemangioma; endoscopic endonasal approach; endoscopic skull base surgery; epistaxis; hemangioma; paranasal sinus; sinonasal tumor; skull base tumor
44.  Primary spontaneous cerebrospinal fluid leaks located at the clivus 
Allergy & Rhinology  2013;4(2):e100-e104.
Transclival meningoceles and primary spontaneous cerebrospinal fluid (CSF) leaks at the clivus are extremely rare lesions and only few of them have been reported in the literature. We report here six cases of transclival primary spontaneous CSF leaks through the clivus. A retrospective case study was performed. We reviewed six cases involving sinonasal CSF leaks located at the clivus treated between 1997 and 2009. Presenting symptoms, duration of symptoms, defect size, site of defect, surgical approach and technique of defect closure, intraoperative complications, postoperative complications, and recurrences are discussed. All CSF leaks were located in the upper central part of the clivus. two of six patients showed signs of increased intracranial pressure (ICP) including arachnoid pits and/or empty sella. For three patients a purely transnasal approach was used with multilayer reconstruction using a nonvascularized graft, and three patients underwent a transnasal transseptal approach with a multilayer reconstruction, with nasoseptal flap. No recurrences of CSF leaks at clivus or other sites were observed to date with a mean follow-up of 10.3 years (range, 3–15 years). Spontaneous CSF rhinorrhea located at the clivus is an extremely rare condition. To date, only eight cases have been described. Here, we report the largest group of six consecutive cases. Irrespective of the used reconstruction technique in all cases a 100% closure rate was achieved. However, identification of increased ICP is an essential aspect and this condition should be treated either medically or surgically.
doi:10.2500/ar.2013.4.0053
PMCID: PMC3793111  PMID: 24124635
Clivus; CSF leak; expanded endonasal approach; meningocele
45.  Total aplasia of the paranasal sinuses 
Allergy & Rhinology  2013;4(2):e105-e109.
Although a variety of theories have been proposed about functions of the paranasal sinuses, not one is clear today. Nonetheless, paranasal sinus–related diseases are associated with a high rate of morbidities. Therefore, it is essential to identify the structure and pathophysiology of the paranasal sinuses. Computed tomography (CT) is a valuable tool displaying anatomic variations and diseases. Because paranasal sinus development is a complex and long-lasting process, there are great structural variations between individuals. Several degrees and combinations of aplasias and hypoplasias have been reported; however, there is only one case of total paranasal sinus aplasia in the literature. Here, we present the second case of total paranasal sinus aplasia. Paranasal sinus development, functions of the paranasal sinuses, and the role of CT were evaluated.
doi:10.2500/ar.2013.4.0056
PMCID: PMC3793112  PMID: 24124636
Aplasia; computed tomography; functions of the paranasal sinuses; paranasal sinus
46.  Perceptual accuracy of upper airway compromise in children: Clinical relevance and future directions for research 
Allergy & Rhinology  2013;4(2):e54-e62.
Approximately 80% of children with asthma have coexisting allergic rhinitis. The accurate recognition and assessment of asthma and rhinitis symptoms is an integral component of guideline-based treatment for both conditions. This article describes the development and preliminary evaluation of a novel paradigm for testing the accuracy of children's assessment of their upper airway (rhinitis) symptoms. This work is guided by our previous research showing the clinical efficacy of tools to evaluate children's perceptual accuracy of asthma symptoms and linking accurate asthma symptom perception to decreased asthma morbidity (Fritz G, et al., Ethnic differences in perception of lung function: A factor in pediatric asthma disparities? Am J Respir Crit Care Med 182:12–18, 2010; Klein RB, et al., The Asthma Risk Grid: Clinical interpretation of symptom perception, Allergy Asthma Proc 251–256, 2004). The pilot study tests a paradigm that allows for the examination of the correspondence of children's assessment of their upper airway functioning with actual values of upper airway flow through the use of a portable, handheld nasal peak flowmeter. Nine children with persistent asthma were evaluated over a 4-week period. The article describes the rhinitis perceptual accuracy paradigm and reviews the results of a pilot study, showing a large proportion of inaccurate rhinitis symptoms “guesses” by the sample of children with persistent asthma. Patterns of inaccuracy, rhinitis control, and asthma morbidity are also described. Directions for future work are reviewed. The development of clinical tools to evaluate children's accuracy of rhinitis symptoms are needed, given the central role of the self-assessment of symptoms in guideline-based care. Accurate perception of the severity of rhinitis symptoms may enhance rhinitis control, lessen the burden of asthma, and prevent unnecessary emergency use among this high-risk group of children.
doi:10.2500/ar.2013.4.0060
PMCID: PMC3793113  PMID: 24124637
Allergy; asthma; children; perceptual accuracy; rhinitis; treatment; upper airway
47.  Identification of pannexins in rat nasal mucosa 
Allergy & Rhinology  2013;4(2):e63-e65.
Pannexins are a second family of gap-junction proteins in vertebrates, classified as pannexin-1, pannexin-2, and pannexin-3. Pannexin-1 is one of the candidates for channel-mediated ATP release into the extracellular space. In airway epithelia, ATP signaling modulates multiple cellular functions such as mucus/ion secretion and mucociliary clearance systems. However, the expression of pannexins in the upper airway has not been investigated. Nasal septal mucosae were collected from adult male Wistar rats aged 20–24 weeks. The expression of pannexin-1, pannexin-2, and pannexin-3 was examined by reverse transcription polymerase chain reaction (RT-PCR) and by whole-mount fluorescence immunohistochemistry. Transcripts for pannexin-1, pannexin-2, and pannexin-3 were detected in nasal septal mucosae of adult rats by RT-PCR. Distinct immunohistochemical fluorescence for pannexin-1 was observed in the epithelial layer, whereas there was no immunoreactivity for pannexin-2 or pannexin-3. This is the first article establishing the existence of pannexins (predominantly pannexin-1) in the upper airway, suggesting their possible participation in the physiological functions of ATP release and signaling in this tissue.
doi:10.2500/ar.2013.4.0052
PMCID: PMC3793114  PMID: 24124638
Immunohistochemistry; nasal mucosa; pannexin; rat; RT-PCR
48.  Validation of a grading system for lateral nasal wall insufficiency 
Allergy & Rhinology  2013;4(2):e66-e68.
This study was designed to validate a grading scheme for lateral nasal wall insufficiency with interrater and intrarater reliability measures. Representative endoscopic videos depicting varied degrees of lateral nasal wall insufficiency were collated into a 30-clip video (15 clips in duplicate). This was rated by five reviewers for a total of 150 observations. Interrater and intrarater reliability were determined using Fleiss kappa and intraclass correlation coefficient (ICC) statistics, respectively. Good agreement was established between reviewers (interrater reliability), with a Fleiss kappa of 0.7733 (p < 0.01). Analysis of intrarater variability with the ICC revealed a very strong agreement (ICC = 0.88; p < 0.01). The proposed grading system is shown to have good interrater and intrarater reliability. It provides a reliable instrument for assessing lateral wall insufficiency.
doi:10.2500/ar.2013.4.0054
PMCID: PMC3793115  PMID: 24124639
Collapse; grading; internal valve; lateral nasal wall; lateral wall; nasal valve; obstruction
49.  Immunopathology features of chronic rhinosinusitis in high-altitude dwelling Tibetans 
Allergy & Rhinology  2013;4(2):e69-e76.
Chronic rhinosinusitis (CRS) presents distinct inflammatory and remodeling patterns in different populations and environments. Tibetan ethnic groups live at high altitudes and in cold weather conditions. We sought to examine whether Tibetans exhibit distinct CRS pathology or characteristics. Sinonasal polyps and mucosal tissue were obtained from 14 Tibetan patients with CRS and nasal polyps (CRSwNPs), 13 patients with CRS without nasal polyps (CRSsNPs), and 12 Tibetan controls. Tissue homogenates and serum samples were assayed for several T-helper (TH) cell cytokines and mediators using enzyme linked immunosorbent assay profiles were measured using quantity polymerase chain reaction. Several key inflammatory cells were examined for immunohistochemical markers. CRSwNPs were characterized by increased mediator promoting eosinophilic inflammation (interleukin [IL]-5, eosinophil cationic protein, and total immunoglobulin E) and slight synergism with expression of IL-8, IL-2sRa, IL-1beta, IL-6, and myeloperoxidase, and a predominance of eosinophils, mast cells, and neutrophils. GATA-3 transcription factor was significantly increased and Foxp3 showed a tendency to be impaired in CRSwNPs compared with controls. CRSsNPs were characterized by significantly high levels of transforming growth factor beta1, increased interferon γ, and a significant enhancement of Foxp3 and T-beta compared with CRSwNPs. There were reduced numbers of inflammatory cells but increased levels of macrophages in CRSsNPs. Compared with CRSsNPs, CRSwNPs present a severe inflammatory reaction and show a TH2 milieu with apparently impaired regulatory T cells (Treg) function and increased inflammatory cells infiltration predominated by eosinophilic and mast cells. In contrast, TH1 polarization with enhanced Treg function and increased levels of macrophages appear in CRSsNPs.
doi:10.2500/ar.2013.4.0055
PMCID: PMC3793116  PMID: 24124640
Chronic rhinosinusitis; eosinophils; high altitude; interleukin-5; nasal polyps; neutrophils; T-cell subsets; Tibetan patients; transcription factor
50.  Characteristics of candidates for allergen immunotherapy 
Allergy & Rhinology  2013;4(2):e77-e81.
Allergic rhinitis (AR) may be cured by allergen immunotherapy (AIT). However, patient characteristics for prescribing AIT are not well defined. This study aimed at evaluating the patient's profile to be a candidate for AIT in a cohort of patients suffering from AR, evaluated in 20 Italian Allergy or Ear, Nose, and Throat Centers. The study has been performed on 198 patients (98 men; mean age, 26.8 years) with AR (assessed by Allergic Rhinitis and Its Impact on Asthma [ARIA] criteria). The kind and the number of prescribed allergen extracts, type of diagnosis, severity of symptoms, and patient's perception of symptoms and drug use were evaluated. Patients were subdivided in AIT-treated and without AIT (as controls) subgroups. Most of the patients (69.7%) had persistent AR with moderate–severe symptoms. The mean number of sensitization was 3.4. ARIA classification and sensitization number did not affect AIT choice, but the type of allergen was relevant. AIT-treated patients had milder symptoms than controls if assessed by doctors, but AIT patients perceived more severe symptoms and larger drug use than controls. This study shows that the choice of AIT is based on patient's perception and type of allergen, but number of sensitizations, symptom severity assessed by doctors, and ARIA classification are not relevant factors. The key message might be that it is always relevant to pay attention to the complaints referred by the patient.
doi:10.2500/ar.2013.4.0061
PMCID: PMC3793117  PMID: 24124641
Allergen immunotherapy; allergic rhinitis; patient's perception; polysensitization

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