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1.  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
2.  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
3.  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
4.  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
5.  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
6.  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
7.  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
8.  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.
9.  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
10.  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
11.  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
12.  Beware of the caterpillar: Anaphylaxis to the spotted tussock moth caterpillar, Lophocampa maculata 
Allergy & Rhinology  2014;5(2):e113-e115.
We present a case report of a 5-year-old boy with presumed anaphylaxis to the caterpillar, Lophocampa maculata, manifesting as the acute development of diffuse urticaria and progressive dyspnea. This reaction required prompt treatment with antihistamines and a bronchodilator. Allergen scratch testing with a homogenized caterpillar extract suggests that immunoglobulin E–mediated type I hypersensitivity as the pathophysiological mechanism responsible for the boy's anaphylaxis. This case report represents the first documented occurrence of an anaphylactic reaction to Lophocampa maculata and adds to the rare incidence of documented hypersensitivity to the order Lepidoptera.
doi:10.2500/ar.2014.5.0086
PMCID: PMC4124577  PMID: 24988176
Anaphylaxis; caterpillar; childhood; hypersensitivity; insect; Lophocampa maculata; spotted tussock moth; tiger moth
13.  The usefulness of preoperative biopsy in unilateral nasal masses 
Allergy & Rhinology  2014;5(2):e53-e55.
Unilateral nasal masses are considered suspicious for proliferative diseases. Several tools are routinely used to investigate unilateral lesions such as imaging and nasal biopsy. This study investigated the usefulness of nasal biopsy in predicting the actual nature of unilateral lesions. Preoperative nasal biopsy pathological results were compared with the final pathology obtained during an operation. Forty-six patients with unilateral nasal masses were included in the study group. In 40 patients the final pathology was similar to the preoperative nasal biopsy. In three patients the biopsy specimen was a benign polyp and the final pathology was of an inverted papilloma in two patients and hemangiopericytoma in one patient. In two patients the biopsy specimen was suspicious for an inverted papilloma and the final pathology was a benign polyp. In one patient the biopsy specimen was chordoma and the final pathology was osteosarcoma. The total agreement was 86.9%. The kappa value was 81.2%. Preoperative nasal biopsy is important and useful in evaluating unilateral nasal masses.
doi:10.2500/ar.2014.5.0082
PMCID: PMC4124578  PMID: 24684868
Nasal biopsy; operation; pathology; polyps; preoperative nasal biopsy; proliferative disease; unilateral nasal mass
14.  Assessment of allergenicity to fungal allergens of Rohtak city, Haryana, India 
Allergy & Rhinology  2014;5(2):e56-e65.
Fungal spores are known as one of the important bioparticles causing allergic manifestation in human beings. Hence, knowledge of season and prevalence of the airborne allergens to which the patients are exposed is a prerequisite for proper diagnosis and treatment of allergic disorders in hypersensitive individuals. Keeping this in view, aerial survey was performed in the atmosphere of Rohtak city for 2 consecutive years (March 2008–February 2010), using a volumetric petri plate sampler. A total of 45 fungal spore types were recorded during the survey period. In the present study, February–April and July–November were identified as the peak seasons for Rohtak city. Cladosporium was the main contributor to the total fungal load with 25.14% followed by Alternaria (18.05%), Aspergillus niger (7.66%), Curvularia (5.31%), and Epicoccum (5.29%). Fifteen dominant viable fungal spore types were represented in the form of a fungal calendar. An attempt has also been made to assess the allergenicity of some of the fungal types recorded from the atmosphere of Rohtak city. The magnitude of variations observed in markedly positive skin reactions (2+ and above) varied from 17.3 to 2.3%. Penicillium oxalicum showed a markedly positive reaction in maximum number of patients (26; 17.3%) followed by Rhizopus nigricans (23; 15.3%). ELISA was performed with the sera of patients showing markedly positive skin reactions and the sera were classified into four groups based on percent binding. The majority of the sera showed 0–15% binding to different antigenic extracts, while sera showing >60% binding were least in number. Greater than 30% binding was observed against antigens of Rhizopus nigricans, Epicoccum purpurascens, Penicillium oxalicum, Curvularia lunata, Aspergillus flavus, Candida albicans and Neurospora sitophila. The concordance between positive skin reaction and serum-specific IgE antibodies ranged from 16.7 to 69.2%.
doi:10.2500/ar.2014.5.0088
PMCID: PMC4124579  PMID: 24988378
Aerobiology; asthma; allergens; bioassay; fungal calendar; fungus; hypersensitivity; immunoassay; immunoglobulin E; seasonal variations
15.  Modified oral metronidazole desensitization protocol 
Allergy & Rhinology  2014;5(2):e66-e69.
The Center for Disease Control guidelines recommend desensitization to metronidazole in patients with trichomoniasis and hypersensitivity to metronidazole. There is only one published oral metronidazole desensitization protocol. The purpose of this study was to design a new, more gradual oral desensitization protocol to decrease systemic reactions that may occur when using the previously published protocol. We present two patients with presumed IgE-mediated allergy to metronidazole who underwent oral desensitization using our modified protocol. Case 1 was a 65-year-old woman with trichomoniasis who presented for metronidazole desensitization with a history of intraoperative anaphylaxis and positive skin tests to metronidazole. The patient tolerated six doses of the modified desensitization but developed systemic symptoms of nasal congestion and diffuse pruritus after the 25- and 100-mg doses. Both reactions were treated with intravenous (i.v.) antihistamines. Because of gastrointestinal irritation, the desensitization was completed at a dose of 250 mg orally every 6 hours. Case 2 was a 42-year-old woman with trichomoniasis and a history of hives immediately after administration of i.v. metronidazole who presented for desensitization. The patient had negative skin-prick and intradermal testing to metronidazole. She developed lip tingling and pruritus on her arms 15 minutes after the 10-mg dose. Fexofenadine at 180 mg was given orally and symptoms resolved. She tolerated the rest of the protocol without reaction and received a total dose of 2 g of metronidazole. Our oral metronidazole desensitization for presumed IgE-mediated reactions offers a second option for physicians wishing to use a more gradual escalation in dose.
doi:10.2500/ar.2014.5.0080
PMCID: PMC4124580  PMID: 24612959
Anaphylaxis; desensitization; drug allergy; immediate-type allergy; intradermal skin test; metronidazole; nitroimidazoles; skin-prick testing; tinidazole; trichomonas
16.  Numerical investigation of the flow field in realistic nasal septal perforation geometry 
Allergy & Rhinology  2014;5(2):e70-e77.
The computational fluid dynamics (CFD) are used to evaluate the physiological function of the nose. We evaluated the aerodynamics of the nasal cavity in a patient with septal perforation (SP), pre- and postvirtual repair. Three-dimensional nasal models were reconstructed, and then a wide range of the pressure drops and flow rates were analyzed. The airflow velocity is higher in the central region and is lower around the boundary of the SP. The air velocity in the SP increases as the pressure drop increases. Furthermore, at the anterior part of the SP, the shear stress is higher in the upper part. In addition, the repair of SP does not affect the total nasal airflow rate and the velocity contour patterns. The potential usage of the CFD technique as a predictive technique to explore the details and a preoperative assessment tool to help in clinical decision making in nasal surgery is emphasized.
doi:10.2500/ar.2014.5.0090
PMCID: PMC4124581  PMID: 24988523
Aerodynamics; airflow velocity; computational fluid dynamics; geometry; nasal cavity; nasal septal perforation
17.  Azelastine and budesonide (nasal sprays): Effect of combination therapy monitored by acoustic rhinometry and clinical symptom score in the treatment of allergic rhinitis 
Allergy & Rhinology  2014;5(2):e78-e86.
The aim of this study was to objectively evaluate the effects of intranasal therapy with azelastine (AZE), budesonide (BUD), and combined AZE plus BUD (AZE/BUD) using a nasal provocation test (NPT) and acoustic rhinometry in patients with allergic rhinitis. A randomized, single-blind, crossover study with three treatment sequences was used. Thirty patients with persistent AR received the three treatments using a nasal spray twice daily for 30 days and were evaluated by an NPT with histamine before and after each period of treatment. The treatment comparison, assessed by the nasal responsiveness to histamine, was monitored based on subjective (symptom score) and objective parameters (acoustic rhinometry). The minimal cross-area 2 (MCA2) was measured by acoustic rhinometry at 1, 4, 8, and 12 minutes after NPT for each histamine concentration administered (0.5, 1, 2, 4, and 6 mg/mL) up to at least a 20% reduction in the MCA2 from baseline (NPT20). The subjects were scored regarding nasal response encompassing histamine dose and time after histamine administration that caused nasal obstruction (NPT20 score) to assess the treatments' effects. Combination therapy produced a significant increase in baseline MCA2, viz., the improvement of nasal patency (p = 0.005). The symptoms score was significantly decreased after treatment with AZE (p = 0.03), BUD (p < 0.0001), and AZE/BUD (p < 0.0001), compared with pretreatment. The NPT20 score was significantly higher (p = 0.0009) after AZE/BUD, compared with AZE and BUD on their own. Thus, AZE therapy combined with BUD might provide more therapeutic benefits than the isolated drugs for improving nasal patency.
doi:10.2500/ar.2014.5.0089
PMCID: PMC4124582  PMID: 24988550
Acoustic rhinometry; allergic rhinitis; azelastine; budesonide; histamine; intranasal drug; nasal obstruction; nasal patency; nasal provocation test
18.  Mycobacterium chelonae dacryocystitis after endoscopic dacryocystorhinostomy 
Allergy & Rhinology  2014;5(2):e87-e90.
Mycobacterium chelonae is a rapidly growing nontuberculous Mycobacterium and an uncommon cause of aggressive, treatment-resistant ocular and periocular infection. This is the first known case report of a woman who developed unilateral M. chelonae dacryocystitis after undergoing endoscopic sinus surgery and right endoscopic dacryocystorhinostomy (DCR) with Crawford stent placement. We describe our findings and effective methods to manage the infection. Three weeks after undergoing DCR, the patient acutely developed symptoms consistent with dacryocystitis. The patient was treated with broad-spectrum antibiotics followed by incision and drainage of the dacryocystocele abscess, with initial cultures showing no organisms. With continued signs of infection, the Crawford stent was later removed. Cultures eventually grew M. chelonae and the patient was treated with 4 months of antibiotic therapy. While receiving antibiotics, the patient developed three abscesses along the inferior lid requiring excision. After 21 months, the patient remains free of infection and has not experienced any other complications. This case serves as a reminder to consider M. chelonae as a potential cause of periocular infection, which may be more likely to occur postoperatively with indwelling devices, as well as in patients with sinonasal issues requiring nasal irrigations. This organism can be difficult to treat because of multidrug resistance and biofilm production. Recommended therapy includes surgical debridement, removal of any implanted devices, and a two-drug antibiotic regimen for at least 4 months.
doi:10.2500/ar.2014.5.0081
PMCID: PMC4124583  PMID: 24613068
Atypical Mycobacterium; bicanalicular stent; chronic rhinosinusitis; dacryocystitis; dacryocystorhinostomy; endoscopic dacryocystorhinostomy; endoscopic sinus surgery; Mycobacterium chelonae; nasal polyps; nontuberculous Mycobacterium
19.  Expression of surface markers on the blood cells during the delayed asthmatic response to allergen challenge 
Allergy & Rhinology  2014;5(2):e96-e109.
Patients with bronchial asthma develop various types of asthmatic response to bronchial challenge with allergen, such as immediate/early asthmatic response (IAR), late asthmatic response (LAR) or delayed asthmatic response (DYAR), because of different immunologic mechanisms. The DYAR, occurring between 24 and 56 hours after the bronchial allergen challenge (p < 0.01), differs from IAR and LAR in clinical as well as immunologic features. This study investigates the expression of CD molecules (markers) on the surface of particular cell populations in the peripheral blood and their changes during the DYAR. In 17 patients developing the DYAR (p < 0.01), the bronchial challenge with allergen was repeated 2–6 weeks later. The repeated DYAR (p < 0.001) was combined with recording of CD molecule expression on various types of blood cells by means of flow cytometry up to 72 hours after the challenge. The results were expressed in percent of the mean relative fluorescence intensity. The DYAR was accompanied by (a) increased expression of CD11b, CD11b/18, CD16,CD32, CD35, CD62E, CD62L, CD64, and CD66b on neutrophils; CD203C on basophils; CD25 and CD62L on eosinophils; CD14, CD16, CD64, and CD86 on monocytes; CD3, CD4, CD8, CD11a, CD18, and CD69 on lymphocytes; CD16, CD56, CD57, and CD94 on natural killer (NK) cells; and CD31, CD41, CD61, CD62P, and CD63 on thrombocytes and (b) decreased expression of CD18 and CD62L on eosinophils, CD15 on neutrophils, and CD40 on lymphocytes. These results suggest involvement of cell-mediated hypersensitivity mechanism, on participation of Th1- lymphocytes, neutrophils, monocytes, NK cells, and thrombocytes in the DYAR.
doi:10.2500/ar.2014.5.0087
PMCID: PMC4124585  PMID: 24988283
Bronchial provocation tests with allergen; CD molecules; delayed asthmatic response; monocytes; neutrophils; NK cells; Th1 lymphocytes; thrombocytes
20.  Egg baked in product open oral food challenges are safe in selected egg-allergic patients 
Allergy & Rhinology  2014;5(2):e110-e112.
Egg allergy is one of the most common food allergies in children. Most egg-allergic children are able to tolerate egg baked in product (EBP) and will likely outgrow his/her egg allergy. By introducing EBP in the diet of an egg-allergic child, diet can be expanded and family stress can be reduced. Recent evidence suggests that children who tolerate EBP and continue to consume it will have quicker resolution of egg allergy than those who strictly avoid EBP; therefore, we aimed to evaluate the egg-allergic children who underwent EBP oral food challenge (OFC) in our allergy clinic to help define any specific predictors to be used in predicting the outcome of such challenges. We performed a retrospective chart review and 43 egg-allergic patients underwent EBP OFC in our outpatient allergy office from January 2011 to December 2012 were excluded. Nine patients who did not have a prior history of symptomatic egg ingestion. Clinical characteristics and laboratory findings of the remaining 34 patients were all recorded and analyzed. Of the remaining 34 patients, 22 (64.7%) were boys. Average age of first reaction to egg was 12.90 months, with average age at EBP OFC of 71.32 months. The average of the most recent skin-prick test wheal size was 10.10 mm and serum-specific IgE to egg white was 3.21 kU/L. Twenty-eight of the 34 patients (82.4%) passed the EBP OFC. Of the six patients who failed, none required epinephrine. After analysis of all of the clinical characteristics and laboratory findings, no risk factors, such as skin-prick test wheal size, were identified to be associated with an increased risk of failing EBP OFC. EBP OFC is a valuable tool to assess tolerance. As seen in our group of patients, the majority of egg-allergic patients pass EBP OFC. Thus, OFC should be considered as a clinical tool to expand a patient's diet and to improve quality of life as early as possible. Because we were unable to determine any clinical or laboratory predictors helpful to select egg-allergic patients who are likely to pass EBP OFC, additional prospective studies are necessary to determine the ideal egg-allergic patient who is likely to pass EBP OFC.
doi:10.2500/ar.2014.5.0092
PMCID: PMC4124576  PMID: 25198996
Baked egg; baked egg oral food challenge; egg allergy; egg baked in product; egg baked in product oral food challenge; food allergy; oral food challenge; serum-specific IgE; skin-prick testing
21.  Very low dose bevacizumab for the treatment of epistaxis in patients with hereditary hemorrhagic telangiectasia 
Allergy & Rhinology  2014;5(2):e91-e95.
Hereditary hemorrhagic telangiectasia (HHT) is a disease characterized by mucocutaneous telangiectasias and visceral arteriovenous malformations. The genetic mutations that cause this disease result in elevated levels of vascular endothelial growth factor, which is inhibited by bevacizumab. Previous studies have shown bevacizumab treatment to be effective in reducing symptoms, but study protocols have all used oncological dosing parameters, which carry several well-described serious side effects. This study investigates whether drastically lower dosages of bevacizumab than normally used in oncological treatment could control epistaxis in patients with HHT and medically refractory epistaxis. A prospective, open-label, noncomparative study enrolled six patients receiving 0.125-mg/kg infusions of bevacizumab once every 4 weeks for a total of six infusions. Severity of epistaxis was assessed with the epistaxis severity score, and quality-of-life measures were followed with the 20-item Sino-Nasal Outcome Test and 36-item Short Form surveys. A statistically significant improvement was seen in the control of epistaxis severity and frequency, with minimal negative side effects and high patient satisfaction. Very low dose bevacizumab treatment is an effective method of controlling medically refractory epistaxis in patients with HHT and additional investigation to optimize dosing guidelines is warranted.
doi:10.2500/ar.2014.5.0091
PMCID: PMC4124584  PMID: 25199101
Angiogenesis; Avastin; bevacizumab; epistaxis; hereditary hemorrhagic telangiectasia; Osler–Weber–Rendu disease; VEGF
22.  Introducing a New Feature to Allergy and Rhinology 
Allergy & Rhinology  2014;5(1):e1.
doi:10.2500/ar.2014.5.1418
PMCID: PMC4019737  PMID: 25199143
23.  Radiofrequency inferior turbinate reduction improves smell ability of patients with chronic rhinitis and inferior turbinate hypertrophy 
Allergy & Rhinology  2014;5(1):e12-e16.
Radiofrequency inferior turbinate reduction (RFITR) of inferior turbinate hypertrophy (ITH) is an effective way to treat patients with intractable nasal mucosal obstruction. The objective of this study was to assess smell ability, nasal symptoms, inferior turbinate grading (ITG), peak nasal inspiratory flow (PNIF) of patients with chronic rhinitis (CR), and ITH before and after RFITR. Patients with CR and ITH, aged 18–60 years, who underwent RFITR, were prospectively recruited. Smell ability (measured by smell detection threshold [SDT]), visual analog scale (VAS) of nasal symptoms, ITG, and PNIF before and 6–10 weeks after RFITR were compared. Forty-eight subjects were included. All nasal symptoms were significantly decreased after RFITR. After surgery, SDT (tested by phenyl ethyl alcohol) was worsened in 7 patients (14.6%), improved in 8 patients (16.7%), and did not change in 33 patients (68.7%). SDT after RFITR of six patients in the worsened SDT group were still within normal range (> −6.5). There was only one patient whose SDT changed from normosmia to mild hyposmia (−7.25 to −5.38). In the improved SDT group, two of eight patients had obviously better SDT after RFITR, which changed from moderate hyposmia to normosmia (−3.65 to −10; −3.73 to −10), whereas six of eight patients had little better SDT after RFITR. RFITR also significantly reduced ITG and improved PNIF. In conclusion, the treatment of patients with CR and ITH with RFITR significantly improved PNIF, ITG, and nasal symptoms assessed by VAS, although SDT after RFITR could be the same or improved or worsened.
doi:10.2500/ar.2014.5.0077
PMCID: PMC4019738  PMID: 24612902
Chronic rhinitis; inferior turbinate hypertrophy; peak nasal inspiratory flow; radiofrequency inferior turbinate reduction; smell detection threshold
24.  Comparison of two nasal cell collection methods in determining cyclic adenosine monophosphate levels and its association with olfaction: A feasibility study 
Allergy & Rhinology  2014;5(1):e17-e21.
Cyclic adenosine monophosphate (cAMP) is a second messenger that may be associated with olfactory function. No known studies have compared existing collection methods for determining nasal cAMP levels. This is a prospective study comparing the comfort and reliability of the nasal curette and cytobrush. A secondary outcome collected for feasibility testing was characterizing the association between cAMP and olfactory function. We enrolled 19 normal olfaction and 10 olfactory dysfunction subjects. Olfaction was measured by the University of Pennsylvania Smell Identification Test. Two samples were obtained from each nasal cavity at the initial visit and at 1 week follow-up. Comfort was measured by a visual analog scale (VAS). cAMP levels were determined by an enzyme immunoassay. For the curette and cytobrush, mean VAS scores were 0.3 and 0.7 cm (p = 0.48). Intraclass correlation coefficients were 0.81 (curette) and 0.65 (cytobrush) for the initial visit and 0.64 and 0.54 between the initial and follow-up visit. Using the curette, mean cAMP was 537 and 480 fmol/(mg/mL) for the normal and dysfunction cohorts (p = 0.18). Using the cytobrush, cAMP was 505 and 477, respectively (p = 0.65). The curette and cytobrush are both comfortable and reliable collection methods for determining nasal cAMP levels.
doi:10.2500/ar.2014.5.0079
PMCID: PMC4019739  PMID: 24613015
Anosmia; cAMP; curette; cytobrush; olfaction; olfactory epithelium; UPSIT
25.  Evaluation on quality of life in patients with nasal polyposis managed with optimal medical therapy 
Allergy & Rhinology  2014;5(1):e2-e8.
Nasal polyposis (NP) has a great impact on quality of life (QOL) and its management involves a combination of medical therapy and surgery. To the authors' knowledge, no publication has extensively examined NP after optimal medical treatment based on subjective evaluations. The aim of this prospective study was designed to evaluate the QOL in NP patients after (1) a short course of oral steroids, (2) initial 3-month course of macrolide, and (3) long-term treatment with intranasal steroids. A total of 55 patients with grades I and II NP were consecutively treated with oral prednisolone at 25 mg in a single dose for 2 weeks, macrolide at 250 mg daily for the first 3 months, and long-term intranasal steroids. Patients were followed up and evaluated at baseline and 3, 6, and 12 months for QOL measure. At baseline, patients with grade I and grade II NP showed significantly worse QOL scores on all Rhinosinusitis Disability Index domains, particularly for physical function (4.59 ± 1.41) and were significantly higher in social function (3.16 ± 1.17). At 3, 6, and 12 months of treatment, patients showed a significant improvement in all impaired QOL domains compared with baseline after optimal medical therapy (p < 0.05). These results suggest that the optimal medical treatment to improve QOL incorporates medical polypectomy with a short course of oral steroids in addition to macrolide and this can be maintained by long-term intranasal steroid therapy.
doi:10.2500/ar.2014.5.0075
PMCID: PMC4019740  PMID: 24612853
Aspirin sensitivity; asthma; grade I and I nasal polyps; loss sense of smell; macrolide; medical polypectomy; nasal obstruction; nasal polyposis; quality of life; topical intranasal steroids

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