Microgeographic factors and patterns of aeroallergen sensitisation.

OBJECTIVE: To examine patterns of airborne allergen (aeroallergen) sensitisation in the Greater Sydney area (Sydney), and their relationships with climate, coastal proximity and environment (urban v regional). DESIGN, SETTING, PARTICIPANTS: Retrospective cross-sectional study of patients who underwent aeroallergen skin prick testing at three Sydney allergy clinics, January 2001 - October 2014. MAIN OUTCOME MEASUREMENTS: Proportions of patients sensitised to specific aeroallergen types; relationships between sensitisation patterns and climate and geography. RESULTS: Of 1421 patients who met the selection criteria (mean age, 28.3 years [SD, 21.3]; 53.3% were female), 1092 (76.8%) were sensitised to at least one aeroallergen. Those living less than 15 km from the coast were less commonly sensitised to cockroach (< 15 km, 15.1%; 15-30 km, 40.0%; > 30 km, 39.7%; P < 0.001) and grass aeroallergens (< 15 km, 36.5%; 15-30 km, 52.2%; > 30 km, 58.1%; P < 0.001) than patients further inland; the same applied to mould, weed and tree aeroallergens. Subtropical grass sensitisation was more common in temperate/warm summer climates (about 50%) than in temperate/hot summer (27.1%) or subtropical climates (15%) (P < 0.001), and less common in urban (36.7%) than in regional areas (54%; P = 0.014). 72.4% of grass-sensitised patients were co-sensitised to both temperate and subtropical grasses. A selected ten-aeroallergen skin prick test panel identified 98.5% of atopic patients in this Sydney sample. CONCLUSIONS: Environmental and geographic factors are associated with different patterns of allergic sensitisation in Sydney. Extensive co-sensitisation to subtropical and temperate grasses has implications for immunotherapy in Australia, where most currently available therapies are based on formulations directed at temperate grasses only.

Topical Vitamin D May Modulate Human Sinonasal Mucosal Responses to House Dust Mite Antigen.

BACKGROUND: Respiratory epithelium is a key defense against inhaled pathogens. Vitamin D3 (VD) has been suggested to modulate airway inflammation; however, its effect on innate airway defenses, the physical barrier, mucociliary apparatus, and cytokine release remains unclear. OBJECTIVE: To investigate the outcomes of VD application prior to challenge in an in vitro model of human sinonasal epithelium, through assessment of epithelial transepithelial resistance (TER), cilia beat frequency (CBF), and interleukin (IL)-6 release, and secondarily to determine whether topical VD is beneficial to patients with inflammatory sinonasal pathology. METHODS: Primary human sinonasal epithelial cells from patients with eosinophilic chronic rhinosinusitis (eCRS) and healthy controls were cultured in air-liquid interface (ALI). Well-differentiated cultures from each patient were pretreated for 24 hours with 4 different VD doses. Toxicity was quantified at 24 hours in unchallenged ALI by lactate dehydrogenase (LDH) assay. Innate responses were assessed by measuring TER and CBF before and up to 24 hours after house dust mite Dermatophagoides pteronyssinus challenge. IL-6 release was evaluated 24-hour postchallenge. RESULTS: Fifteen patients (53 ± 13.5 years, 60% females, 53% eCRS) representing 120 ALI wells were assessed. VD (0, 25, 50, 150 IU/mL) released less LDH than vehicle, indicating noncytotoxicity (0.15 ± 0.02; 0.15 ± 0.00; 0.14 ± 0.02; 0.11 ± 0.01 vs 0.17 ± 0.03, P = .004). VD increased TER for eCRS wells at 5 minutes (50 IU/mL: Δ6.76 ± 3.93 vs Δ3.87 ± 2.46, P = .04) and 24 hours (50 IU/mL: Δ0.88 ± 0.49 vs Δ0.40 ± 0.42, P = .02; 150 IU/mL: Δ1.06 ± 0.58 vs Δ0.47 ± 0.46, P = .01). CBF increased at 1 hour for eCRS wells (50 IU/mL: Δ0.62 ± 0.14 vs Δ0.41 ± 0.13, P = .001; 150 IU/ml: Δ0.60 ± 0.13 vs Δ0.38 ± 0.11, P < .001). IL-6 release was similar between normal and eCRS wells. CONCLUSION: Topical VD supplementation in eCRS patients may be beneficial for innate epithelial defenses. VD is noncytotoxic and does not adversely affect the physical barrier, mucociliary apparatus, or IL-6 release. Further studies should clarify its potential as a therapeutic agent.

Association Between Mental Health Status and Patient Satisfaction With the Functional Outcomes of Rhinoplasty.

IMPORTANCE: Mental health can have an impact on patient satisfaction with rhinoplasty. However, the association between mental health and patient satisfaction with functional outcomes of rhinoplasty is poorly understood. OBJECTIVE: To determine whether preoperative mental health is associated with satisfaction with functional outcomes of rhinoplasty. DESIGN, SETTING, AND PARTICIPANTS: This case-control study assessed baseline nasal function and postsurgical functional outcomes for 88 consecutive patients undergoing rhinoplasty with both cosmetic and functional goals at 2 tertiary rhinologic centers in Sydney, Australia. EXPOSURES: Poor mental well-being was defined preoperatively by the Optum SF-36v2 Health Survey mental component summary. MAIN OUTCOMES AND MEASURES: Nasal function was assessed with patient-reported outcome measures, including visual analog scales, the Nasal Obstruction Symptom Evaluation Scale (NOSE), the 22-item Sinonasal Outcome Test (SNOT-22), and Likert scales. Objective outcomes included nasal peak inspiratory flow, nasal airway resistance, and minimum cross-sectional area. All outcomes were assessed preoperatively and 6 months postoperatively. The 36-item Optum SF-36v2 Health Survey mental component summary was used to assess mental well-being, with a score of less than 40 indicating poor mental well-being and a score 40 or higher indicating normal well-being. RESULTS: Mean (SD) patient age was 37.6 (12.9) years and 53 of 88 (60.2%) were women. The mental component summary defined impaired well-being in n = 24 (cases) and normal well-being in n = 64 (controls). There were improvements in the total study population across most nasal function outcomes and in both groups. After rhinoplasty, benefit was seen for both groups in visual analog scale (left side mean [SD] change, 18 [30]; P < .001 and right side mean [SD] change, 24 [30]; P < .001); NOSE (mean [SD] change, 1.35 [1.21]; P < .001); and SNOT-22 (mean [SD] change, 0.81 [0.88]; P < .001) scores. Nasal peak inspiratory flow improved for both groups (mean [SD] change, 32 [45] L/min; P < .001), while nasal airway resistance and minimum cross-sectional area remained similar (change in nasal airway resistance, 0.086 Pa/cm3/s; 95% CI, -0.007 Pa/cm3/s to 0.179 Pa/cm3/s and change in minimum cross-sectional area, -0.04 cm2; 95% CI, -0.21 cm2 to 0.13 cm2). Patients with poor mental health had similar improvements in nasal function compared with controls. CONCLUSIONS AND RELEVANCE: Rhinoplasty imparts similar benefits to nasal function assessed by patient-reported outcome measures and objective airflow measures regardless of preoperative mental health status. LEVEL OF EVIDENCE: 3.

Allergic sensitization does not predispose to sinus inflammation in externalized paranasal sinuses.

BACKGROUND: Chronic rhinosinusitis (CRS) has a multifactorial etiology, with a debate about the role of inhalant allergy in the pathogenesis of CRS. OBJECTIVE: This study assessed the impact of allergy status on externalized paranasal sinuses after tumor resection to determine if a predisposition to inhalant allergy brought about additional inflammation after sinus surgery. METHODOLOGY: A case-control study was performed on patients who had no history of CRS who underwent paranasal sinus tumor resection. Allergic sensitization was defined by a positive serum ImmunoCAP test result. Outcomes were measured at least 6 months after surgery by using the modified Lund-MacKay endoscopic score and the 22-item Sino-Nasal Outcome test, with rhinitis, sleep, psychological, ear and/or facial, and sinus subscores to assess the impact of allergy status on mucosal inflammation. RESULTS: A total of 103 patients (53.44 ± 17.46 years; 46% women) were assessed. Of these, 61.17% were allergically sensitized at the time of surgery. Postsurgery endoscopic assessment was similar [the modified Lund-Mackay endoscopic score allergic sensitized 0.5 (1.7) versus nonallergic sensitized 0.0 (0.9); p = 0.15]. Sinonasal symptoms were also similar between the groups' 22-item Sino-Nasal Outcome test scores, allergic sensitized versus allergic nonsensitized, (allergic 28.9 ± 20.8 versus nonallergic 33.5 ± 19.7; p = 0.31), rhinitis score (5.9 ± 5.5 versus 6.4 ± 4.7; p = 0.66), sleep score (6.9 ± 5.9 versus 7.7 ± 4.8; p = 0.50), ear and/or facial symptom score (3.4 ± 3.6 versus 4.3 ± 3.3; p = 0.22), psychological score (6.9 ± 6.0 versus 8.3 ± 6.7; p = 0.29), and of nasal symptom score (6.4 ± 5.2 versus 7.0 ± 5.3; p = 0.61). CONCLUSIONS: Externalization of the sinuses in patients with inhalant allergy did not bring about significant additional inflammation in patients after tumor surgery.

Acute radiology rarely confirms sinus disease in suspected recurrent acute rhinosinusitis.

BACKGROUND: Episodic or recurrent sinonasal symptoms are often suspected as "sinus" in origin. With normal sinus radiology between events, the diagnosis of recurrent acute rhinosinusitis (RecARS) is made. However, other conditions can produce episodic symptoms. In this study we analyze acutely performed computed tomography (CT) in a population with suspected or self-diagnosed "sinus" disease. METHODS: Patients referred to a tertiary clinic for suspected RecARS were assessed. Sinus changes were defined by CT (initial assessment) and during the acute event, by a semiurgent CT performed during the symptomatic episode. Mucosal thickening, ostiomeatal compromise, and severe septal deformity were recorded. Symptom profile was assessed during both time-points with the 22-item Sino-Nasal Outcome Test (SNOT-22). RESULTS: Forty-eight patients (49.5 ± 14.7 years of age, 70.8% female) were assessed. At presentation, 75% were resolute in a diagnosis of "sinus." Baseline Lund-Mackay scores were <6 (median 0 [interquartile range 1]). Ostiomeatal compromise was 6.8% left and 4.5% right at baseline. Of the patients who returned for acute CT (n = 27), SNOT-22 and subdomains were similar to baseline. Septal deviation was similar (13.6% vs 15.3%). Acutely, ostiomeatal compromise was 0% left and 7.4% right (n = 2). Of these 2 patients with ostiomeatal compromise, 1 was diagnosed with RecARS (4%) and the other with triptan-responsive migraine, with incidental sinus changes. Final diagnosis was rhinitis (47%), headache/migraine (37%), and facial pain otherwise undefined (12.5%). CONCLUSION: Patients with a history of "recurrent acute sinusitis" and normal CT scans between episodes rarely have abnormal CT findings during acute exacerbations of symptoms. Antibiotics and surgical intervention are often inappropriate in this population.

Association of Mental Health Status With Perception of Nasal Function.

IMPORTANCE: Mental health issues are thought to be overrepresented among patients undergoing rhinoplasty and may be associated with patient presentation prior to surgery. OBJECTIVE: To assess the association of poor mental health with perception of nasal function. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study of patients presenting for airway assessment was performed from December 1, 2011, to October 31, 2015, at 2 tertiary rhinoplasty centers in Sydney, Australia. Mental health was independently defined preoperatively by the Mental Component Summary of the 36-item Short Form Health Survey version 2 (a score of <40 indicated poor mental well-being), the Rosenberg Self-Esteem Scale (a score of <15 indicated low self-esteem), and the Dysmorphic Concerns Questionnaire (a score of >11 indicated above-average dysmorphic concerns). MAIN OUTCOMES AND MEASURES: Nasal function was assessed with patient-reported outcome measures, including the Nasal Obstruction Symptom Evaluation Scale, the 22-item Sinonasal Outcome Test, a visual analog scale to rate ease of breathing on the left and right sides, and Likert scales to assess overall function and nasal obstruction. Nasal airflow was assessed by nasal peak inspiratory flow, nasal airway resistance, and minimum cross-sectional area. RESULTS: Among 495 patients in the study (302 women and 193 men; mean [SD] age, 36.5 [13.6] years), compared with patients with good mental health, those with poor mental health had poorer scores in all patient-reported outcome measures, including the visual analog scale for the left side (mean [SD], 51 [25] vs 42 [25]; P = .001), visual analog scale for the right side (mean [SD], 54 [24] vs 45 [26]; P < .001), Nasal Obstruction Symptom Evaluation Scale (mean [SD], 2.64 [0.95] vs 1.96 [1.04]; P < .001), 22-item Sinonasal Outcome Test (mean [SD], 2.14 [0.84] vs 1.33 [0.83]; P < .001), nasal obstruction (58 of 145 [40.2%] vs 83 of 350 [23.7%] with severe or worse obstruction; P < .001), and nasal function (72 of 145 [49.7%] vs 111 of 350 [31.8%] with poor or worse function; P < .001). Subclinical differences in nasal peak inspiratory flow could be demonstrated, but all other nasal airflow measures were similar. Low self-esteem produced a similar pattern, but dysmorphia did not. CONCLUSIONS AND RELEVANCE: Poor mental health status is associated with a poorer self-perception of nasal function compared with those who are mentally healthy with clinically similar nasal airflow. Clinicians should be aware that patients with poor mental health reporting obstructed airflow may in part be representing an extension of their negative emotions rather than true obstruction and may require further assessment prior to surgery. LEVEL OF EVIDENCE: NA.

Middle turbinate edema as a diagnostic marker of inhalant allergy.

BACKGROUND: Middle turbinate edema could be a characteristic feature of aeroallergen sensitization. In this study we sought to determine the diagnostic characteristics of middle turbinate edema as a marker of inhalant allergy. METHODS: A cross-sectional diagnostic study was performed on patients who had undergone nasal endoscopy and allergy testing. Allergy status was determined by positive serology or epicutaneous testing. Endoscopy was reviewed by blinded assessors for middle turbinate head edema. Appearance was graded as either normal, focal, multifocal, diffuse, or polypoid edema. Receiver-operator (ROC) analysis, likelihood ratio (LR), sensitivity, specificity, and positive predictive value (PPV) were determined. RESULTS: One hundred eighty-seven patients representing 304 nasal cavities were assessed (42% female, age 39.74 ± 14.7 years, 57% allergic). Diffuse edema (PPV 91.7%/LR = 8) and polypoid edema (PPV 88.9%/LR = 6.2) demonstrated the strongest association with inhalant allergy. Multifocal edema was used as a cut-off to represent inhalant allergy from ROC analysis, which demonstrated 94.7% specificity and 23.4% sensitivity. The PPV for multifocal was 85.1% and LR = 4.4. CONCLUSION: Middle turbinate edema is a useful nasal endoscopic feature to predict presence of inhalant allergy and, although not sensitive, has excellent PPV.

Vitamin D pathway regulatory genes encoding 1α-hydroxylase and 24-hydroxylase are dysregulated in sinonasal tissue during chronic rhinosinusitis.

BACKGROUND: Vitamin D deficiency is associated with many inflammatory respiratory disease states. However, serum vitamin D concentrations may not reflect tissue-specific availability. In this study we sought to assess the local expression of genes essential in vitamin D regulation in chronic rhinosinusitis (CRS). METHODS: A cross-sectional study of adult patients undergoing endoscopic sinus surgery was performed. Patients were defined as having CRS with polyps (CRSwNP) or without polyps (CRSsNP), or normal sinus mucosa. Sinus mucosal biopsies were assessed using quantitative polymerase chain reaction to determine expression of genes encoding the vitamin D receptor (VDR), 25-hydroxylase (CYP2R1), 1α-hydroxylase (CYP27B1), and 24-hydroxylase (CYP24A1). Expression levels correlated with serum 25(OH)D [sum 25(OH)D2  and 25(OH)D3 ], the 22-item Sinonasal Outcome Test (SNOT-22), and Nasal Symptom Score (NSS). Separate analyses were performed for patients grouped by tissue eosinophilia. RESULTS: Thirty-one patients were assessed (age 49.47 ± 18.14 years, 48.4% female), including 8 CRSsNP, 10 CRSwNP, and 13 controls. CRSsNP and CRSwNP mucosa exhibited decreased CYP27B1 compared with controls (0.0437 [Interquartile range (IQR) 0.0999] vs 0.3260 [IQR 2.9384] vs 0.6557 [IQR 1.1005], p = 0.039), whereas CYP24A1 was upregulated (0.8522 [IQR 1.3170] vs 1.2239 [IQR 4.4197] vs 0.1076 [IQR 0.1791], p = 0.025). CYP24A1 was upregulated in both non-eosinophilic CRS and eosinophilic CRS (1.1337 [IQR 2.3790] vs 0.9555 [IQR 3.2811] vs 0.1076 [IQR 0.1791], p = 0.033). Significant correlations were observed between NSS and CYP2R1 (r = -0.432, p = 0.022), CYP24A1 (r = 0.420, P = 0.026), and VDR (r = 0.425, p = 0.024), although no correlations with serum 25(OH)D were observed. CONCLUSIONS: The local regulation of vitamin D in sinonasal tissue during CRS may be independent of serum 25(OH)D levels. Vitamin D may be dysregulated at multiple levels, with decreased transcription of the metabolic gene CYP27B1 and increased transcription of the catabolic gene CYP24A1 observed.

Clinical implications of mucosal remodeling from chronic rhinosinusitis.

BACKGROUND: Prognostic implications of mucosal remodeling in chronic rhinosinusitis (CRS) remain unclear. Remodeling of respiratory mucosa in asthma is associated with greater medication use and decreased function. This study investigates the implications of mucosal remodeling on long-term clinical outcomes in patients with CRS. METHODS: A case-control study of adult patients with CRS undergoing endoscopic sinus surgery (ESS) was performed. Mucosal remodeling was defined by squamous metaplasia, subepithelial fibrosis, and/or basement membrane thickening. The presence of remodeling changes were assessed relative to clinical and treatment outcomes at a minimum of 12 months postoperatively. Clinical outcomes were assessed at baseline and 12 months using a Nasal Symptom Score (NSS) and 22-item Sino-Nasal Outcome Test (SNOT-22). Treatment outcomes were assessed by oral corticosteroid usage (burst/continuous), topical corticosteroid irrigation frequency, and further surgical intervention. RESULTS: A total of 110 patients (48.73 ± 14.75 years, 48.2% female) were assessed. Significant improvements where seen for the entire population, in both NSS (2.64 ± 1.06 to 1.34 ± 1.08, p < 0.001) and SNOT-22 (2.05 ± 0.96 to 1.06 ± 0.79, p < 0.001). Patients with remodeling (n = 88) were younger (47.2 ± 14.8 vs 54.7 ± 13.5 years, p = 0.03), but had similar symptom scores. Remodeling was seen in CRS with nasal polyposis (CRSwNP) (54.5%) and eosinophilic chronic rhinosinusitis (eCRS) (59.8%). Symptom improvement at 12 months was similar between remodeled and non-remodeled groups (NSS: Δ1.34 ± 1.20 vs Δ1.12 ± 1.31, p = 0.395; SNOT-22: Δ1.05 ± 0.91 vs Δ0.73 ± 0.95, p = 0.124); however, patients with remodeling had greater corticosteroid irrigation frequency (64.0% vs 31.6% daily use, Kendall's tau-b p = 0.004). CONCLUSION: Established mucosal remodeling predicts a greater reliance on topical therapies to reach similar clinical endpoints as those without remodeling.

Topical concentrated epinephrine (1:1000) does not cause acute cardiovascular changes during endoscopic sinus surgery.

BACKGROUND: Topical epinephrine is used in endoscopic sinonasal surgery for local vasoconstriction. Potential for cardiovascular complications remains a concern for some due to the possibility of systemic absorption. Topical vs injected epinephrine was examined in a prospective analysis of perioperative cardiovascular effects, and in an audit of cardiovascular complications during endoscopic sinonasal surgery. METHODS: A prospective cohort study of patients undergoing endoscopic sinonasal surgery was performed. Topical (1:1000) and injected (1:100,000) epinephrine were assessed. Cardiovascular outcomes of heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and electrocardiogram (ECG) changes were examined at baseline and minutely post-topical application (to 10 minutes) and postinjection (to 5 minutes). A retrospective assessment of cardiovascular events associated with a standardized regimen of topical (1:2000) and injected (1:100,000) epinephrine was performed. RESULTS: Nineteen patents were assessed (43.42 ± 15.90 years, 47.4% female) in the prospective analysis. Post-topical epinephrine, no significant changes occurred in any cardiovascular parameter. However, following injected epinephrine, changes in HR (59.53 vs 64.11 bpm, p < 0.001), SBP (96.16 vs 102.95 mmHg, p = 0.015), DBP (56.53 vs 60.74 mmHg, p = 0.019), and MAP (69.74 vs 74.81 mmHg, p = 0.002) occurred. On repeated-measures analysis of variance (ANOVA) all parameters were significantly affected by injection. No ECG abnormalities were seen in either topical or injection phases. The retrospective analysis of 1260 cases identified 2 cases of cardiovascular complications (0.16%), both relating to injected epinephrine. CONCLUSION: Combination topical (1:1000 to 1:2000) and injectable (1:100,000) epinephrine is safe for use in endoscopic sinonasal surgery. Injection resulted in the cardiovascular changes and accounted for the cardiovascular events reported.

Two-dimensional assessment of the nasal valve area cannot predict minimum cross-sectional area or airflow resistance.

BACKGROUND: Clinicians who manage nasal obstruction often comment on the shape and size of the nasal valve (NV) area. However, correlation of the symptoms of obstruction, nasal airflow dynamics, and the endoscopic appearance of the anatomic cross-sectional area of the NV is poorly understood. Endoscopic imaging and calculation of the NV area is investigated as a tool for either clinical or research use. OBJECTIVE: To describe and evaluate a two-dimensional measurement of the minimum cross-sectional area (MCA) of the NV by using endoscopic imaging. METHODS: A cross-sectional study of patients with symptoms of nasal obstruction who were undergoing nasal assessment was performed. The NV was measured with digital imaging taken from the endoscopy. Adobe Photoshop was used to calculate the digital MCA of the NV based on pixel count and a reference marker placed in the image field. Airway parameters were assessed by using a nasal obstruction visual analog scale, nasal airway resistance via rhinomanometry, and acoustic rhinometry derived MCA (acoustic MCA). Correlation of the digital MCA and airway parameters was made and interobserver correlation of the MCA measures was calculated. RESULTS: Thirty-three nasal airways were assessed: mean (standard deviation) digital MCA (0.28 ± 0.13 cm(2)) and mean (standard deviation) acoustic MCA (0.51 ± 0.15 cm(2)). Correlation of the digital MCA with visual analog scale was poor (Pearson r = 0.10, p = 0.56). Similar finding between digital and acoustic MCA was poor (Pearson r = 0.50, p = 0.56, respectively) despite a moderately strong interobserver correlation for the digital MCA (Pearson r = 0.79, p < 0.001). CONCLUSION: Qualitative endoscopic assessment of the NV may help clinicians predict NV dysfunction but simple two-dimensional measures seemed to be of limited value in accurately assessing the three-dimensional NV quantitatively.