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1.  Practical recommendations for mixing allergy immunotherapy extracts 
Allergy & Rhinology  2015;6(1):e1-e7.
Critical aspects of formulating allergy immunotherapy vaccines include the selection, total number, and proportions of each allergen component in therapeutic mixtures. The immunotherapy prescription, determined by a medical provider, details the dosing and schedule for treatment as well as the specific composition of the treatment vials. Allergen extracts are composed of many components such as proteins, glycoproteins, and proteases. Some components in allergen extracts are cross-reactive, meaning that treatment with an extract from one species may confer partial protection against a triggering allergen from another species. Conversely, some allergen extracts are incompatible with other extracts when combined in a mixture for treatment, resulting in lowered therapeutic potential for the patient. Therefore, knowledge of allergen extract cross-reactivities and incompatibilities guides the preparation of subcutaneous immunotherapy prescriptions. In a clinical setting, an understanding of what can and can not be mixed is one critical element in improving treatment outcomes.
doi:10.2500/ar.2015.6.0111
PMCID: PMC4388870  PMID: 25860164
Allergen; allergy; compatibility SCIT; cross-reactivity; disease modifying; extract; immunotherapy; Joint Task Force guideline; USP 797
2.  Endoscopic dacryocystorhinostomy as treatment for lower lacrimal pathway obstructions in adults: Review article 
Allergy & Rhinology  2015;6(1):e12-e19.
Obstruction of the lacrimal pathway is manifested by epiphora, infection, and blurred vision as well as ocular and facial pain. Conservative treatments only achieve temporary relief of symptoms, thus surgery is the treatment of choice. Dacryocystorhinostomy (DCR) is recognized as the most suitable treatment for patients with obstructions of the lacrimal system at the level of the sac or in the nasolacrimal duct. The aim of this operation is to create a bypass between the lacrimal sac and the nasal cavity. During the past 2 decades, advances in rigid endoscopic equipment and other instruments have made it possible to obtain more information about the anatomic landmarks of the nasolacrimal system, which led to the development of less-invasive and safer endoscopic techniques. However, many parts of the treatment process related to endoscopic endonasal dacryocystorhinostomy (EN-DCR) still remain controversial. This article reviews the published literature about the technical issues associated with the success of EN-DCR, and clarifies the pros and cons of different pre- and postoperative procedures in adults with lower lacrimal pathway obstructions.
doi:10.2500/ar.2015.6.0116
PMCID: PMC4388871  PMID: 25860166
Dacryocystorhinostomy; endonasal; endoscopy; epiphora; lower lacrimal pathway; review
3.  A postal survey of hereditary hemorrhagic telangectasia in the northeast of England 
Allergy & Rhinology  2015;6(1):e20-e27.
The aim of this study is to identify the demographics and epistaxis burden of hereditary hemorrhagic telangiectasia (HHT). A questionnaire was sent to participants with HHT who were recruited from a prospectively maintained respiratory clinic data base in a tertiary hospital. Details on demographics, HHT symptoms, family history, epistaxis severity, and treatment received were recorded. There were 34 of 60 responses (57%). Two responses were from families of the deceased. Of the 32 evaluable patients (men, 14; women 18), the average age was 51 years (range, 23–78 years). The average age of HHT diagnosis was 31 years (range, 3–61 years). The diagnosis of HHT was made by the respiratory team in 13 patients; neurologist (2); ear, nose, and throat (ENT) specialist (4); general practitioner (5); hematologist (4); gastroenterologist (1); and not mentioned in two patients. Twenty-seven of 32 patients (84%) had a positive family history of HHT. Only 13 patients had formal genetic testing (4 endoglin, 1 activin receptor–like kinase, 8 unknown gene). All patients who presented to the respiratory clinic had a background of epistaxis, which was noted on presentation. The average age at initial epistaxis was 14 years (range, 2–50 years). The frequency of epistaxis was daily 63% (n = 20), weekly 9% (3), monthly 16% (5), and a few times a year 10% (3), and unstated in one patient. Nine of 32 patients (28%) required a transfusion. Six patients thought that they were unable to perform daily activities due to epistaxis. Only 15 of 32 patients (47%) were under the care of an ENT specialist. The treatment plan for epistaxis management was deemed good by 7 patients, adequate in 8, poor in 6, and not stated by 11 patients. In conclusion, this survey is the first to quantify the epistaxis burden within the northeast of England. The management of epistaxis needs specific education and treatment to optimize the quality of life among these patients.
doi:10.2500/ar.2015.6.0114
PMCID: PMC4388872  PMID: 25860167
Hereditary hemorrhagic telangiectasia; epistaxis
4.  Monitor height ergonomics: A comparison of operating room video display terminals 
Allergy & Rhinology  2015;6(1):e28-e32.
A surgeon's eyes should be positioned 1 meter (m) distant and no more than 15° below the top of an operating monitor (0.27 m). We sought to determine which operating room video display terminal can best accommodate ergonomically optimized gaze during surgery. Floor to eye height was measured for surgeons in seated, perched, and standing positions. These ranges were then compared to vertical displacement ranges for monitors measured from floor to top of the screen. Eye height was measured for standing (1.56–1.80 m), perched (1.40–1.65 m), and seated (1.10–1.32 m) positions. The minimum distance (min) between the floor and the top of the monitor and the vertical mobility range (VR) of the monitor were measured throughout a tertiary medical center including towers with boom arms (TcB) (min: 1.58 m, VR: 0.37 m), towers without booms (TsB) (min: 1.82 m, VR: 0.025 m), ceiling mounted booms (CMB) (min: 1.34 m:, VR: 1.04 m), and portable monitors (PM) (min: 1.73 m, VR: 0.04 m). The tangent of 15° declination was used to calculate a correction factor to determine the minimum optimal ergonomic display height. The correction factor was subtracted from the eye height at each position to determine the lowest target height and the highest target floor to eye distance for each position. Analysis of variance with least significant difference post hoc testing identified all minimum distances and vertical ranges to be statistically different (p < 0.001). Monitor vertical displacement varied between styles of carts. CMB video display terminal systems can accommodate standing, perched and the tallest seated surgeons. TcB, TsB and PM systems cannot adequately accommodate all standing, perched or seated surgeons.
doi:10.2500/ar.2015.6.0119
PMCID: PMC4388873  PMID: 25860168
Endoscopic sinus surgery; video display terminals; surgical ergonomics; fatigue; computer terminals; task performance and analysis; operating rooms; occupational health; otolaryngology; human engineering
5.  Changes of micro-RNAs in asymptomatic subjects sensitized to Japanese cedar pollen after prophylactic sublingual immunotherapy 
Allergy & Rhinology  2015;6(1):e33-e38.
Japanese cedar pollinosis is the predominant seasonal allergic rhinitis in Japan, and it has increased in prevalence during the past 10 years. Sublingual immunotherapy (SLIT) is considered a safe and effective treatment for pollinosis. Micro-RNAs (miRNAs) are a class of short single-stranded RNA molecules that posttranscriptionally silence gene expression and may mediate allergic immune responses. The aim of this study was to investigate the miRNA alteration in asymptomatic subjects sensitized to Japanese cedar pollen under prophylactic SLIT under part of a randomized, double-blind, placebo-controlled, multiple-center trial. Analysis was undertaken in 15 asymptomatic subjects sensitized to Japanese cedar pollen–specific IgE (ImmunoCAP class ≥2) who participated in 2013. The SLIT group (n = 6) received standardized Japanese cedar pollen extract and the placebo group (n = 9) received an inactive placebo for 5 months covering the cedar pollen season. Changes in serum miRNAs were measured by real-time quantitative polymerase chain reaction to determine whether SLIT had effects on profiles of circulating miRNA. Seven subjects in the placebo group developed pollinosis symptoms, whereas no subjects in the SLIT group did (p = 0.007). Serum hsa-miR-223 was significantly up-regulated in postseason compared with preseason samples. The hsa-let-7b was significantly more down-regulated in postseason than in preseason samples from the placebo group; however, no significant differences were observed in those from the SLIT group. A significant decrease in circulating let-7b was also observed in the subjects who developed symptoms. Prophylactic SLIT was effective in preventing the development of pollinosis. Alterations in miRNA expression occurred in asymptomatic, sensitized subjects during cedar pollen season.
doi:10.2500/ar.2015.6.0107
PMCID: PMC4388874  PMID: 25675113
Allergic rhinitis; biomarker; immunotherapy; micro-RNA; placebo; pollinosis; prophylaxis; sensitization; tolerance
6.  A retrospective study of peanut and tree nut allergy: Sensitization and correlations with clinical manifestations 
Allergy & Rhinology  2015;6(1):e39-e43.
Peanut (PN) and tree nut (TN) allergies are among the leading causes of fatal food-induced anaphylaxis and are increasing in prevalence, especially in children. Their cosensitization and concurrent clinical allergy have been understudied. This retrospective study investigated the correlation between PN and TN allergy, both in terms of in vitro sensitization (IVS) and clinical allergic manifestations. We conducted a retrospective medical record review at the Allergy Clinic at University Hospital of Brooklyn. Fourteen hundred six charts were reviewed, of which 76 (5.4%) had documented relevant clinical allergy: PN allergy but not TN allergy (n = 29) or TN allergy but not PN allergy (n = 11) or both (n = 30). Six patients with PN allergy but no TN exposure history were not included in the analysis. The majority of patients (67/76, 88.1%) had a concurrent history of asthma, rhinoconjunctivitis, or AD. Sensitivity of TN IVS predicting PN IVS was 38/39 (97%). Similarly, sensitivity of PN IVS predicting TN IVS was 38/42 (91%). Sensitivity of TN clinical allergy predicting PN allergy was 30/59 (51%). Sensitivity of PN clinical allergy predicting TN allergy was 30/41 (73%). The total number of organ systems involved in reported clinical reactions correlated with IVS to TN (p = 0.004) but not IVS to PN (p = 0.983). In summary, we found PN sensitization predicts TN sensitization in vitro, with lower predictability for clinical reactions.
doi:10.2500/ar.2015.6.0108
PMCID: PMC4388875  PMID: 25860169
Allergy; clinical reaction; cosensitization; cross-reactivity; peanut; sensitization; tree nut
7.  Chronic vulvovaginal Candida hypersensitivity: An underrecognized and undertreated disorder by allergists 
Allergy & Rhinology  2015;6(1):e44-e49.
Vulvovaginal candidiasis infections are estimated to occur at least once during the lifetime of 75% of the female population. It has been proposed that some women with recurrent vulvovaginal candidiasis (RVVC) develop sensitization to Candida albicans and clinically improve in response to Candida immunotherapy. Here, we report a case series of 12 women diagnosed with chronic vulvovaginal Candida hypersensitivity subsequently treated with Candida immunotherapy and review potential systemic and localized host immune defense mechanisms involved in C. albicans overgrowth and sensitization. A retrospective review of vulvovaginal Candida hypersensitivity in women who were treated with C. albicans immunotherapy over the past eight years was conducted. Twelve women who qualified for a diagnosis of vulvovaginal Candida hypersensitivity were treated with Candida immunotherapy. Eleven of the 12 (92%) women reported clinical improvement after immunotherapy. The majority of these women were not sensitized to seasonal or perennial aeroallergens and clinically responded to lower concentrations of C. albicans allergen than what has been previously reported. In general, Candida immunotherapy was well tolerated. Chronic vulvovaginal Candida hypersensitivity is an underrecognized disorder by primary care physicians and therefore an undertreated disorder by allergists. A double-blinded, placebo-controlled randomized trial is necessary to firmly establish the efficacy of treatment with Candida immunotherapy. This investigation should be designed to include mechanistic studies that would help to better understand the etiology of this disorder.
doi:10.2500/ar.2015.6.0113
PMCID: PMC4388876  PMID: 25860170
Candida albicans; hypersensitivity; immunotherapy; recurrent vulvovaginal candidiasis; cell-mediated immunity; humoral immunity; Treg cells
8.  Perioperative management for patients with hereditary angioedema 
Allergy & Rhinology  2015;6(1):e50-e55.
Hereditary angioedema (HAE) is a rare autosomal dominant disease that results from mutations in the C1-esterase inhibitor (C1-INH) gene. HAE is characterized by recurrent episodes of angioedema of the skin (face, extremities, genitalia, trunk), the gastrointestinal tract, and respiratory tract. Symptoms experienced can be debilitating, may impact quality of life, and can be life threatening. Preventing attacks particularly for patients undergoing procedures is critical. Patients with HAE may now treat acute attacks or prevent attacks with medications that have recently become available in the United States; however, these same medications can be used for perioperative management for patients undergoing medical, surgical, and dental procedures. Periprocedural planning is important for patients to reduce the incidence of acute attacks. Education is critical and increasing awareness of short-term prophylaxis options will allow providers to develop an appropriate action plan for their patients. The goal of this review is to increase awareness for HAE treating physicians, surgeons, anesthesia, and emergency room physicians by examining the available treatment options, researching the literature, and summarizing available data for periprocedural management. The availability of treatment options has increased over the past few years, expanding options for physicians and patients living with HAE and improve safety during the perioperative period and at the time of other procedures.
doi:10.2500/ar.2015.6.0112
PMCID: PMC4388877  PMID: 25860171
Anesthesia; C1-esterase inhibitor; danazol; dental; ecallantide; fresh frozen plasma; hereditary angioedema; icatibant; surgery
9.  Nickel sensitization and dietary nickel are a substantial cause of symptoms provocation in patients with chronic allergic-like dermatitis syndromes 
Allergy & Rhinology  2015;6(1):e56-e63.
Data in literature seem to show that, in patients with contact allergic dermatitis, dietary nickel might be a cause of systemic dermatitis, but little information exists in literature about the role of nickel sensitization and dietary nickel in patients with allergic-like chronic dermatitis syndromes. The prevalence of nickel sensitization in patients with chronic allergic-like, non-IgE-mediated skin diseases, and the possible impact of dietary nickel on symptom provocation and persistence has been assessed in the present retrospective study on a case series of 1726 patients referred to our allergy unit for chronic allergic-like skin diseases. IgE-mediated pathogenesis and other differential diagnoses excluded, patients were patch tested. Nickel-positive patients underwent an elimination diet and double-blind placebo-controlled nickel challenge (DBPCNC) test. A total of 339 (20%) tested nickel-positive. Fifty-two patients (15%) recovered by avoiding sources of nickel contact and 29 (10%) dropped out. Out of the remaining nickel-sensitized patients, 277 (80%) achieved complete or near complete recovery with low-nickel content diet, and 185 of them (89%) were positive to DBPCNC. We conclude that nickel sensitization and dietary nickel seem to be the chief trigger for provocation and persistence of symptoms in an important part (∼11%) of patients with chronic allergic-like dermatitis syndromes.
doi:10.2500/ar.2015.6.0109
PMCID: PMC4388878  PMID: 25747857
Nickel allergy; nickel sensitization; allergic-like chronic dermatitis; chronic urticarial; adult atopic eczema; chronic pruritus; systemic contact dermatitis; dietary nickel; nickel diet; nickel challenge test
10.  Successful desensitization of a patient with aplastic anemia to antithymocyte globulin 
Allergy & Rhinology  2015;6(1):e64-e67.
Antithymocyte globulin (ATG) is a polyclonal gamma immunoglobulin derived from either rabbit or equine serum that serves as therapy for aplastic anemia; however, ATG causes serum sickness in up to 70% and anaphylaxis in up to 5% of recipients. Intradermal (ID) skin testing has been the primary technique used to evaluate for a preexisting Gell and Coombs type I hypersensitivity reaction to ATG. There are no data reporting the predictive value of delayed reactions to ID testing on the risk of serum sickness. This study was designed to establish the importance of epicutaneous and ID skin testing before the administration of ATG through a case report and literature discussion. We report a patient with severe aplastic anemia that was successfully desensitized to ATG after a negative epicutaneous skin test and positive ID skin test. The patient had neither systemic nor localized reactions during the desensitization. Desensitization to ATG in patients with positive epicutaneous skin testing has been shown to be associated with serious and potentially life-threatening complications and should only be considered when the benefits outweigh the risks. Epicutaneous skin testing should be considered in conjunction with ID skin testing when screening for potential sensitivity to ATG. Because of the serious risk of anaphylaxis, desensitization should be performed in an intensive care unit setting in conjunction with a physician familiar with drug desensitization and the management of anaphylaxis.
doi:10.2500/ar.2015.6.0110
PMCID: PMC4388879  PMID: 25730287
Anaphylaxis; antithymocyte globulin; ATG; drug allergy
11.  In-office use of a steroid-eluting implant for maintenance of frontal ostial patency after revision sinus surgery 
Allergy & Rhinology  2015;6(1):e68-e75.
Achieving long-term, successful outcomes with endoscopic sinus surgery (ESS) can be challenging in patients with recalcitrant chronic rhinosinusitis (CRS). Local complications, including scar formation and ostial stenosis, can lead to recurrent blockage and subsequent relapse. The frontal sinus is particularly vulnerable to surgical failure given its narrow outflow and inaccessibility to topical therapies. The advent of steroid-eluting sinus implants has enhanced ESS outcomes, with significant reductions in synechiae, inflammation, and secondary postoperative interventions when placed in the ethmoid cavity. However, use of this technology in the frontal sinus has yet to be described. The purpose of this report is to present two cases, in which in-office frontal placement of a mometasone furoate (MF)-eluting implant facilitated maintenance of ostial patency after revision ESS. The clinical presentation, in-office intervention, and treatment outcomes were examined. Two patients (male, 63 and 68 years of age) with a history of multiple ESS presented with recurrent unilateral frontal headache refractory to medical therapy. Nasal endoscopy/imaging revealed frontal sinus outflow obstruction. Both declined revision ESS under general anesthesia and underwent endoscopic frontal sinustomy/ostial dilation in the clinic. A MF-eluting implant was placed in the frontal sinus at the end of the procedure, with preservation of ostial patency upon last follow-up at 3 and 11 months, respectively. In-office placement of a MF-eluting implant successfully maintained frontal ostial patency in patients with a history of multiple ESS. Additional randomized trials are necessary to determine statistical significance, cost-effectiveness analysis, and long-term efficacy of frontal sinus implantation.
doi:10.2500/ar.2015.6.0104
PMCID: PMC4388880  PMID: 25668577
Chronic; endoscopic; frontal; implant; in-office; patency; rhinosinusitis; sinus; steroid eluting
12.  Maxillary sinus manifestations of methamphetamine abuse 
Allergy & Rhinology  2015;6(1):e76-e79.
Methamphetamines are the second most commonly used illicit drug worldwide and cost the United States health-care system ∼$23.4 billion annually. Use of this drug affects multiple organ systems and causes a variety of clinical manifestations. Although there are commonly known sequelae of methamphetamine abuse such as “meth mouth,” there is limited evidence regarding maxillary sinus manifestations. The following cases highlight the initial evaluation and management of two methamphetamine abusers with loculated purulent collections within the maxillary sinus as a result of methamphetamine abuse. Our aim was to delineate the otolaryngologic symptoms associated with the patients' methamphetamine abuse. Computed tomography and magnetic resonance imaging studies revealed loculated purulent collections within the maxillary sinus of probable odontogenic origin in both patients. Methamphetamine abuse leading to rampant caries and poor oral hygiene may predispose individuals for craniofacial infections and fluid collections. These cases illustrate the development of maxillary sinusitis and maxilla mucoceles that have been associated with methamphetamine use.
doi:10.2500/ar.2015.6.0106
PMCID: PMC4388881  PMID: 25675268
Abscess; abuse; cyst; intranasal; maxillary; methamphetamine; odontogenic; route; sinus
13.  Sinus penetration of saline solution irrigation and atomizer in a cadaveric polyp and allergic fungal sinusitis model 
Allergy & Rhinology  2015;6(1):e8-e11.
Allergic fungal sinusitis (AFS) is a stubborn disease requiring surgical and medical management. Delivery of topical medication is paramount in these patients, but the most difficult to accomplish. We investigated heavy irrigation (nasal douche) and atomized medication delivery potential in a cadaveric sinus model of polypoid AFS disease. Three disease models were created: a control that involved unoperated sinuses and no simulated disease; an unoperated AFS with type II polyposis mode; and an operated model with recurrent allergic fungal sinusitis with type II polyposis. The maxillary sinus showed the best irrigation and overall the heavy irrigator was more efficient than the atomizer.
doi:10.2500/ar.2015.6.0115
PMCID: PMC4388882  PMID: 25860165
Rhinology; sinus surgery; allergic fungal sinusitis; nasal polyp; cadaver model; topical sinus penetration; nasal irrigation
14.  Eosinophilic gastroenteritis due to egg allergy presenting as acute pancreatitis 
Allergy & Rhinology  2015;6(1):e80-e81.
We describe a case of a 25-year-old female with newly diagnosed egg allergy, presenting with both peripheral and duodenal eosinophilia suspicious for eosinophilic gastroenteritis (EG). The EG was severe enough to have likely caused acute pancreatitis. Cessation of all egg products lead to resolution of all symptoms. This represents the first report of EG manifesting as pancreatitis due to egg ingestion.
doi:10.2500/ar.2015.6.0105
PMCID: PMC4388883  PMID: 25668683
Eosinophilic gastroenteritis; eosinophilia; egg allergy; acute pancreatitis; hypersensitivity; food allergy
15.  Image-guided sphenoidotomy in revision functional endoscopic sinus surgery 
Allergy & Rhinology  2014;5(3):e116-e119.
The application of image-guided systems to sinus surgery is gaining in popularity. This study tried to evaluate the efficacy of image-guided surgery (IGS) in the fenestration of the sphenoid sinus in patients with chronic rhinosinusitis (CRS) who received revision functional endoscopic sinus surgery (FESS). A total of 51 CRS patients who received revision FESS incorporating IGS between January 2010 and August 2011 by two surgeons were enrolled in this study. A group of 30 CRS patients who underwent revision FESS by the senior surgeon without incorporating IGS was chosen for comparison. The penetration rates for the sphenoid sinus were 91.2% when performed by the senior surgeon with IGS and 91.3% when done by the other surgeon with IGS. The penetration rate for the sphenoid sinus was 68.6% for revision FESS without IGS. The fenestration rate for the sphenoid sinus in revision FESS without IGS was significantly lower than that in revision FESS with IGS (p = .004). Our results showed that IGS was a beneficial procedure for opening the sphenoid sinus in the revision cases.
doi:10.2500/ar.2014.5.0093
PMCID: PMC4275455  PMID: 25565045
Chronic rhinosinusitis; fenestration rate; functional endoscopic sinus surgery; image-guided surgery; revision; sphenoid sinus; surgeon
16.  Treatment of chronic frontal sinusitis with difficult anatomy: A hybrid balloon technique in four cases 
Allergy & Rhinology  2014;5(3):e120-e124.
The presence of frontal cells poses unique challenges when using endoscopic approaches. This study describes the use of a balloon dilation system as an aid for functional endoscopic sinus surgery (FESS) to access the frontal sinus in cases that would traditionally require open approaches. We present a case series of four patients with chronic rhinosinusitis refractive to medical management who underwent FESS with the aid of a balloon dilation system at a tertiary referral center. All patients had variant forms of frontal sinus anatomy. Surgical techniques will be described and use of the balloon system will be reviewed. All patients (aged 13–68 years) successfully underwent fontal sinusotomies with the assistance of a balloon dilation system, which was used in a variety of ways: to dilate the narrow infundibulum of a high intersinus septal cell, to remove an anteriorly located type III frontal sinus cell, to expand the natural frontal ostium in the presence of excessive agger nasi pneumatization, and to remove a type IV frontal sinus cell. All patients were spared an osteoplastic flap or trephination, and there were no intraoperative complications. No postoperative bleeding, infection, or cerebral spinal fluid leaks were reported. Balloon dilation in combination with standard frontal sinus dissection techniques may be beneficial for a select group of patients with complex frontal anatomy. In this series of patients, the balloon dilation system was used as a tool during FESS and eliminated the need for open approaches.
doi:10.2500/ar.2014.5.0096
PMCID: PMC4275456  PMID: 25565046
Balloon catheter dilation; chronic rhinosinusitis (CRS); endoscopic sinus surgery; frontal recess; frontal sinus; frontal sinus cell; frontal sinus outflow tract; frontoethmoid cell; hybrid balloon; intersinus septal cell
17.  Effect of oxygen tension on tissue-engineered human nasal septal chondrocytes 
Allergy & Rhinology  2014;5(3):e125-e131.
Tissue-engineered nasal septal cartilage may provide a source of autologous tissue for repair of craniofacial defects. Although advances have been made in manipulating the chondrocyte culture environment for production of neocartilage, consensus on the best oxygen tension for in vitro growth of tissue-engineered cartilage has not been reached. The objective of this study was to determine whether in vitro oxygen tension influences chondrocyte expansion and redifferentiation. Proliferation of chondrocytes from 12 patients expanded in monolayer under hypoxic (5% or 10%) or normoxic (21%) oxygen tension was compared over 14 days of culture. The highest performing oxygen level was used for further expansion of the monolayer cultures. At confluency, chondrocytes were redifferentiated by encapsulation in alginate beads and cultured for 14 days under hypoxic (5 or 10%) or normoxic (21%) oxygen tension. Biochemical and histological properties were evaluated. Chondrocyte proliferation in monolayer and redifferentiation in alginate beads were supported by all oxygen tensions tested. Chondrocytes in monolayer culture had increased proliferation at normoxic oxygen tension (p = 0.06), as well as greater accumulation of glycosaminoglycan (GAG) during chondrocyte redifferentiation (p < 0.05). Chondrocytes released from beads cultured under all three oxygen levels showed robust accumulation of GAG and type II collagen with a lower degree of type I collagen immunoreactivity. Finally, formation of chondrocyte clusters was associated with decreasing oxygen tension (p < 0.05). Expansion of human septal chondrocytes in monolayer culture was greatest at normoxic oxygen tension. Both normoxic and hypoxic culture of human septal chondrocytes embedded in alginate beads supported robust extracellular matrix deposition. However, GAG accumulation was significantly enhanced under normoxic culture conditions. Chondrocyte cluster formation was associated with hypoxic oxygen tension.
doi:10.2500/ar.2014.5.0097
PMCID: PMC4275457  PMID: 25565047
Cartilage tissue engineering; chondrocyte; human nasal septal cartilage; hypoxia; normoxia; oxygen tension
18.  Levamisole-adulterated cocaine induced skin necrosis of nose, ears, and extremities: Case report 
Allergy & Rhinology  2014;5(3):e132-e136.
Levamisole is an immunomodulatory and antihelminthic drug, previously removed from the United States market, and now estimated to be present in the vast majority of cocaine distributed in the United States. Levamisole-adulterated cocaine (LAC) exposure can result in neutropenia, thrombocytopenia, and vasculitis with a predilection for subsites of the face. The objective of this review is to increase awareness among otolaryngologists of the manifestations of LAC exposure. We present the case of a 33-year-old woman with a history of cocaine use, consulted for purpuric, necrotic lesions of the nose, cheeks, and ears, with accompanying leukopenia, thrombocytopenia, and positive antineutrophil cytoplasmic antibodies (ANCA). The effects of levamisole are immune mediated, with antibodies directed against neutrophils causing neutropenia, and vasculitis caused by antibody deposition or secondary to induction of antiphospholipid antibodies causing thrombosis. LAC exposure can be differentiated from other similar appearing pathologies by evaluating serology for specific ANCA. The most important treatment is cessation of cocaine use, which most often results in complete resolution of symptoms. Awareness of the presentation, complications, and treatment of LAC exposure may be especially important for otolaryngologists, who may be one of the firsts to evaluate an affected patient.
doi:10.2500/ar.2014.5.0101
PMCID: PMC4275458  PMID: 25565048
Levamisole; levamisole-adulterated cocaine; vasculitis; thrombotic vasculopathy; immunomodulatory; purpura; skin necrosis
19.  Tonsil volume and allergic rhinitis in children 
Allergy & Rhinology  2014;5(3):e137-e142.
Tonsil hypertrophy (TH) is very common in children. Previously, it has been reported that an inverse relationship exists between adenoid hypertrophy (AH) and allergic rhinitis (AR). This study aimed to investigate the possible relationship between tonsil volume and AR diagnosis in a group of children complaining of upper airways obstruction. Globally, 171 children (91 boys; mean age, 6.6 years) were studied. Clinical visit, nasal endoscopy, and skin-prick test were performed in all patients. TH and anterior nasal obstruction were graded using the Friedman's classifications. Adenoid volume was graded using the Parikh's classification. Fifty-eight children (33.9%) had relevant TH (grades 3–4); 77 children (44.94%) had AR. There was a strong correlation (gamma = 0.564; p < 0.001) between TH and AH. Tonsil volume was inversely associated with AR diagnosis (odds ratio [OR], 0.314). Risk factors for TH were intense mucosal inflammation (pale mucous membranes) and AH (OR, 3.54 and 2.856, respectively). This study shows that large tonsils are negatively associated with allergy, whereas intense inflammation is a risk factor for TH; AH may be frequently associated with TH.
doi:10.2500/ar.2014.5.0095
PMCID: PMC4275459  PMID: 25565049
Allergic rhinitis; children; nasal endoscopy; tonsils hypertrophy
20.  Characterization of aeroallergen sensitivities in children with allergic rhinitis and chronic rhinosinusitis 
Allergy & Rhinology  2014;5(3):e143-e145.
Allergic rhinitis is a common comorbid condition in pediatric chronic rhinosinusitis (CRS). Testing for aeroallergen sensitization should therefore be considered in the evaluation of children with CRS. At present the aeroallergen sensitivity profile of children with CRS remains uncharacterized. In this study, we retrospectively identify a consecutive series of children with CRS and allergic rhinitis who have undergone joint otolaryngology and allergy evaluation at a single tertiary care center. We describe the aeroallergen sensitivity profiles (based upon formal skin testing) of these children, stratifying them according to co-morbidity status: 1) CRS with cystic fibrosis (CF), 2) CRS with immune deficiency and 3) uncomplicated CRS (without co-morbid CF, immune deficiency or primary ciliary dyskinesia). We identify 208 children (average age 9.3 years, standard deviation 4.8 years) with CRS and allergic rhinitis meeting inclusion criteria, 140 with uncomplicated CRS, 64 with co-morbid immune deficiency and 4 with co-morbid CF. The prevalence of indoor aeroallergen sensitivities (62.9–100.0%) was more common than that of outdoor aeroallergen sensitivities (43.8–50.0%) in all three cohorts of children. In all three cohorts, the most common indoor aeroallergen sensitivity was to dust mites (50.0–75.0%) and the most common outdoor aeroallergen sensitivity was to tree pollens (43.8–50.0%). The aeroallergen sensitivity profile of children with CRS and allergic rhinitis appears to be similar to that of the general pediatric population with allergic rhinitis, and parallels the aeroallergen sensitivities previously described for adults with CRS and allergic rhinitis. Knowledge of the aeroallergen sensitivities in children with CRS and allergic rhinitis will enhance both diagnostic and treatment strategies.
doi:10.2500/ar.2014.5.0102
PMCID: PMC4275460  PMID: 25565050
Aeroallergen; allergic rhinitis; chronic rhinosinusitis; epidemiology; pediatric; sensitivities; skin testing
21.  CD8+ T cells implicated in the pathogenesis of allergic fungal rhinosinusitis 
Allergy & Rhinology  2014;5(3):e146-e156.
Fungi in paranasal sinuses are characteristic and considered a major pathogenic factor in a subset of chronic rhinosinusitis (CRS) patients, known as allergic fungal rhinosinusitis (AFRS). CD8+ T cells are enriched in AFRS sinuses but their role in fungal-specific responses is unknown. Alternaria alternata– and Aspergillus fumigatus–specific T lymphocyte responses were investigated in 6 AFRS patients, 10 eosinophilic mucus CRS (EMCRS) patients, 10 CRS with nasal polyps (CRSwNPs) patients, 6 allergic rhinitis with fungal allergy (ARFA) patients, and five controls. Fungal-specific proliferation of human peripheral blood mononuclear cells (PBMCs) was studied prospectively. Proliferating cells were examined for CD3, CD4, CD8, and CD25 expression. Relevant clinical characteristics, fungal allergy, detection of fungi in sinuses, and CD4+ and CD8+ composition of sinus T cells were also examined. CD4+ T-cell division to fungi occurred in all samples, regardless of fungal allergy or CRS. Fungal-specific CD8+ T-cell division occurred in all ARFA and control samples and the majority of CRSwNP patients; however, CD8+ T cells failed to proliferate in AFRS and EMCRS patients. The CD8+ T cells from AFRS patients also did not up-regulate the activation marker, CD25, with fungal antigen exposure. Presence of A. alternata– and A. fumigatus–specific CD4+ and CD8+ T-cell proliferation in healthy individuals, ARFA, and CRSwNP patients suggests that both T-cell subsets may be important in immune responses to these fungi. In AFRS and EMCRS patients, only fungal-specific CD4+ T-cell proliferation occurred; hence, a lack of CD8+ T-cell proliferation and activation in the presence of sinus eosinophilic mucus in these patients, regardless of fungal allergy, is a novel finding. This raises the question whether a dysfunctional CD8+ T-cell response predisposes to ineffective clearance and accumulation of fungi in the sinuses of susceptible patients.
doi:10.2500/ar.2014.5.0103
PMCID: PMC4275461  PMID: 25565051
Allergic fungal rhinosinusitis; allergic fungal sinusitis; Alternaria; Aspergillus; chronic rhinosinusitis; CD4+; CD8+; dysfunctional; eosinophilic mucus; fungi; human; lymphocytes; mucosa; nasal polyp; proliferation; prospective; sinus; T cells; tissue
22.  Fractional exhaled nitric oxide (FeNo) in different asthma phenotypes 
Allergy & Rhinology  2014;5(3):e157-e161.
Fractioned exhaled nitric oxide (FeNO) is a noninvasive marker of inflammation in asthmatic patients. FeNO can be used to monitor airway inflammation, but individual responses make tailored interventions based on FeNO difficult. The correlation between the asthma control test (ACT), FEV1, and FeNO was evaluated in this study to ascertain the correct usage of FeNO with different asthma phenotypes regarding their control, allergy, comorbidity, obesity, age, smoking status, and severity. ACT, pulmonary function, and FeNO in 416 asthmatic patients on combined therapy were retrospective evaluated. Correlations between these parameters and the FeNO levels in different asthma phenotypes were calculated. In the study population, FeNO was 31.8 ± 28.5 parts per billion (ppb), FEV1 was 83.4 ± 19% and ACT was 19 ± 5.2. ACT scores were negatively correlated with FeNO (r = −0.31; p = 0.002). FeNO was different in patients with positive and negative skin-prick test (p < 0.05), with and without allergic rhinitis (p < 0.01), and with and without allergic conjunctivitis (p < 0.01). Significantly higher FeNO levels were found with logistic regression analysis only in patients with a history of emergency room visits (ERVs) (p = 0.024). The rate of the ERV of the patients with an ACT score more than or equal to 20 and with a FeNO value of more than 35 ppb was 22.9%, but with a FeNO value of less than 35 ppb was 6.5% (p = 0.004). Allergy and allergic comorbidities may lead to an increase in FeNO levels. Patients with a history of ERV have markedly higher FeNO levels, although they have an ACT score more than or equal to 20.
doi:10.2500/ar.2014.5.0099
PMCID: PMC4275462  PMID: 25565052
Airway markers; allergic rhinitis; asthma; asthma control; asthma control test; emergency room visit; fractional exhaled nitric oxide; noninvasive monitoring; pulmonary function; reflux.
23.  Sinonasal phosphaturic mesenchymal tumor: Case report and systematic review 
Allergy & Rhinology  2014;5(3):e162-e167.
We report a case of sinonasal phosphaturic mesenchymal tumor (PMT) and conduct a systematic review of the literature to highlight a unique paraneoplastic syndrome associated with PMT. We used English language publications from Medline and Cochrane databases (1970–2013) as data sources. A systematic review of the literature was conducted. All reported cases of head and neck PMTs were included. The presence or absence of the associated paraneoplastic syndrome was noted. We found 33 cases of PMT in the head and neck reported in the literature, 17 of which occurred in the sinonasal area. Approximately 5% of all PMTs are located in the head and neck. Just greater than half are concentrated in the sinonasal area, and the remaining involve various bony and soft tissue structures of the head and neck. PMT is sometimes associated with a paraneoplastic syndrome of tumor-induced (oncogenic) osteomalacia (TIO) causing bone pain, muscle weakness, and pathologic fractures. We present the 18th reported case of sinonasal PMT. A smooth mucosa-covered midline intraseptal mass filling the posterior nasal cavity with destruction and erosion of the skull base was found in an adult male. The patient underwent successful endoscopic resection with wide negative margins and is without recurrence at 24-month follow-up. PMT is a benign, locally aggressive tumor with rare malignant transformation. Knowledge of the bony invasion and destruction caused by this tumor is essential in planning surgical resection with wide negative margins. Familiarity with the associated TIO is essential to investigate for and manage any associated bony morbidity.
doi:10.2500/ar.2014.5.0100
PMCID: PMC4275463  PMID: 25565053
Phosphaturic mesenchymal tumor; sinonasal; oncogenic osteomalacia; tumor-induced osteomalacia; phosphaturia; mesenchymal tumors
24.  Anterior ethmoidal artery emerging anterior to bulla ethmoidalis: An abnormal anatomical variation in Waardenburg's syndrome 
Allergy & Rhinology  2014;5(3):e168-e171.
In endoscopic sinus surgery, the anterior ethmoidal artery (AEA) is usually identified as it traverses obliquely across the fovea ethmoidalis, posterior to the bulla ethmoidalis and anterior to or within the ground lamella's attachment to the skull base. Injury to the AEA may result in hemorrhage, retraction of the AEA into the orbit, and a retrobulbar hematoma. The resulting increase in intraorbital pressure may threaten vision. Waardenburg's syndrome (WS) is a rare congenital, autosomal dominantly inherited disorder, distinguished by characteristic facial features, pigmentation abnormalities, and profound, congenital, sensorineural hearing loss. We present a case of AEAs located anterior to the bulla ethmoidalis in a 36-year-old male with WS and chronic rhinosinusitis. The anatomic abnormality was not obvious on a preoperative computed tomography scan and was discovered intraoperatively when the left AEA was injured, resulting in a retrobulbar hematoma. The hematoma was immediately identified and decompressed endoscopically without lasting complications. The AEA on the right was identified intraoperatively and preserved. The characteristic craniofacial features in WS were probably associated with the abnormal vascular anatomy. Endoscopic sinus surgeons should be aware of these potential anatomic anomalies in patients with abnormal craniofacial development.
doi:10.2500/ar.2014.5.0094
PMCID: PMC4275464  PMID: 25565054
Anterior ethmoidal artery; bulla ethmoidalis; anatomical variation; Waardenburg's syndrome
25.  Novel treatment of allergic fungal sinusitis using omalizumab 
Allergy & Rhinology  2014;5(3):e172-e174.
A case report of recalcitrant allergic fungal sinusitis (AFS) refractory to systemic corticosteroids and multiple functional endoscopic sinus surgeries (FESSs) treated with anti-IgE antibody omalizumab is reported. AFS is often classified with chronic rhinosinusitis (CRS). Although similar symptoms are among the two diseases, AFS has a unique pathophysiology. Patients with AFS demonstrate type 1 hypersensitivity to fungal allergens, increased total serum IgE, increased CD8+ T-cell prevalence, and IL-4 and IL-5 response. Omalizumab should be considered in the treatment of AFS.
doi:10.2500/ar.2014.5.0098
PMCID: PMC4275465  PMID: 25565055
Allergic bronchopulmonary aspergillosis; allergic fungal rhinosinusitis; allergic fungal sinusitis; aspergillosis; Bent; CD8+; IgE; Kuhn; omalizumab; sinobronchial allergic mycosis

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