Evaluation of the reproducibility of responses to nasal allergen challenge and effects of inhaled nasal corticosteroids.

BACKGROUND: Similar immune responses in the nasal and bronchial mucosa implies that nasal allergen challenge (NAC) is a suitable early phase experimental model for drug development targeting allergic rhinitis (AR) and asthma. We assessed NAC reproducibility and the effects of intranasal corticosteroids (INCS) on symptoms, physiology, and inflammatory mediators. METHODS: 20 participants with mild atopic asthma and AR underwent three single blinded nasal challenges each separated by three weeks (NCT03431961). Cohort A (n = 10) underwent a control saline challenge, followed by two allergen challenges. Cohort B (n = 10) underwent a NAC with no treatment intervention, followed by NAC with 14 days pre-treatment with saline nasal spray (placebo), then NAC with 14 days pre-treatment with INCS (220 µg triamcinolone acetonide twice daily). Nasosorption, nasal lavage, blood samples, forced expiratory volume 1 (FEV1), total nasal symptom score (TNSS), peak nasal inspiratory flow (PNIF) were collected up to 24 h after NAC. Total and active tryptase were measured as early-phase allergy biomarkers (≤30 min) and IL-13 and eosinophil cell counts as late-phase allergy biomarkers (3-7 h) in serum and nasal samples. Period-period reproducibility was assessed by intraclass correlation coefficients (ICC), and sample size estimates were performed using effect sizes measured after INCS. RESULTS: NAC significantly induced acute increases in nasosorption tryptase and TNSS and reduced PNIF, and induced late increases in nasosorption IL-13 with sustained reductions in PNIF. Reproducibility across NACs varied for symptoms and biomarkers, with total tryptase 5 min post NAC having the highest reproducibility (ICC = 0.91). Treatment with INCS inhibited NAC-induced IL-13 while blunting changes in TNSS and PNIF. For a similar crossover study, 7 participants per treatment arm are needed to detect treatment effects comparable to INCS for TNSS. CONCLUSION: NAC-induced biomarkers and symptoms are reproducible and responsive to INCS. NAC is suitable for assessing pharmacodynamic activity and proof of mechanism for drugs targeting allergic inflammation.

Effect of intranasal corticosteroid treatment on allergen-induced changes in group 2 innate lymphoid cells in allergic rhinitis with mild asthma.

BACKGROUND: Allergic rhinitis is characterized by rhinorrhea, nasal congestion, sneezing and nasal pruritus. Group 2 innate lymphoid cells (ILC2s), CD4+ T cells and eosinophils in nasal mucosa are increased significantly after nasal allergen challenge (NAC). Effects of intranasal corticosteroids (INCS) on ILC2s remain to be investigated. METHODS: Subjects (n = 10) with allergic rhinitis and mild asthma were enrolled in a single-blind, placebo-controlled, sequential treatment study and treated twice daily with intranasal triamcinolone acetonide (220 µg) or placebo for 14 days, separated by a 7-day washout period. Following treatment, subjects underwent NAC and upper airway function was assessed. Cells from the nasal mucosa and blood, sampled 24 h post-NAC, underwent flow cytometric enumeration for ILC2s, CD4+ T and eosinophil progenitor (EoPs) levels. Cell differentials and cytokine levels were assessed in nasal lavage. RESULTS: Treatment with INCS significantly attenuated ILC2s, IL-5+ /IL-13+ ILC2s, HLA-DR+ ILC2s and CD4+ T cells in the nasal mucosa, 24 h post-NAC. EoP in nasal mucosa was significantly increased, while mature eosinophils were significantly decreased, 24 h post-NAC in INCS versus placebo treatment arm. Following INCS treatment, IL-2, IL-4, IL-5 and IL-13 were significantly attenuated 24 h post-NAC accompanied by significant improvement in upper airway function. CONCLUSION: Pre-treatment with INCS attenuates allergen-induced increases in ILC2s, CD4+ T cells and terminal differentiation of EoPs in the nasal mucosa of allergic rhinitis patients with mild asthma, with little systemic effect. Attenuation of HLA-DR expression by ILC2s may be an additional mechanism by which steroids modulate adaptive immune responses in the upper airways.

Pediatric pre-tonsillectomy education programs: A systematic review.

INTRODUCTION: Over 14,000 tonsillectomies are performed in Ontario annually. Challenges with home postoperative care frequently lead to Emergency Department (ED) visits. A 2013 Ontario Pediatric Health Council recommended the integration of patient education into tonsillectomy care. Understanding the existing educational services is fundamental to optimally implementing such programs into clinical settings. METHODS: Systematic review of the Ovid Medline, Cochrane, CINAHL and EMBASE Classic databases were conducted using PRISMA guidelines. RESULTS: Our search identified 335 articles. Final inclusion consisted of 10 studies. These studies included eight pre-operative booklets, one smartphone app, three text-message programs, one video program, one internet resource, and three caregiver programs. Most resources improved post-tonsillectomy ED visits, patient anxiety and pain management, while others had no effect on these factors. CONCLUSIONS: There is mixed data regarding the efficacy of pre-tonsillectomy education programs on perioperative outcomes. Further research is required to better understand the utility of such programs and their implementation into healthcare settings.

Morphine or Ibuprofen for post-tonsillectomy analgesia: a randomized trial.

BACKGROUND: Pediatric sleep disordered breathing is often caused by hypertrophy of the tonsils and is commonly managed by tonsillectomy. There is controversy regarding which postsurgical analgesic agents are safe and efficacious. METHODS: This prospective randomized clinical trial recruited children who had sleep disordered breathing who were scheduled for tonsillectomy +/- adenoid removal. Parents were provided with a pulse oximeter to measure oxygen saturation and apnea events the night before and the night after surgery. Children were randomized to receive acetaminophen with either 0.2-0.5 mg/kg oral morphine or 10 mg/kg of oral ibuprofen. The Objective Pain Scale and Faces Scale were used to assess effectiveness on postoperative day 1 and day 5. The primary endpoint was changes in respiratory parameters during sleep. RESULTS: A total of 91 children aged 1 to 10 years were randomized. On the first postoperative night, with respect to oxygen desaturations, 86% of children did not show improvement in the morphine group, whereas 68% of ibuprofen patients did show improvement (14% vs 68%; P < .01). The number of desaturation events increased substantially in the morphine group, with an average increase of 11.17 ± 15.02 desaturation events per hour (P < .01). There were no differences seen in analgesic effectiveness, tonsillar bleeding, or adverse drug reactions. CONCLUSIONS: Ibuprofen in combination with acetaminophen provides safe and effective analgesia in children undergoing tonsillectomy. Post-tonsillectomy morphine use should be limited, as it may be unsafe in certain children.

Intra-thyroidal hemangioma--a rare congenital anomaly: case presentation and literature review.

Infantile hemangiomas (IH) present and evolve in a predictable way. In certain cases, however, they can be of clinical significance. IHs in the airway can cause significant respiratory distress. We present the first reported case of an intrathyroidal hemangioma to cause significant respiratory distress, which was successfully treated with propranolol and dexamethasone. A review of the literature was also performed.

YouTube: a good source of information on pediatric tonsillectomy?

OBJECTIVE: To investigate YouTube as a patient information source on pediatric tonsillectomy. METHODS: YouTube was searched on July 31, 2012 for the search terms pediatric tonsillectomy (PT), tonsillectomy (T) and tonsil surgery (TS). Non-English videos were excluded. Two physician reviewers independently assessed the videos for characteristics, usefulness, and information source. Usefulness was assessed according to a checklist developed by the authors. Any discrepancies were resolved by consensuses. Data were analyzed with SPSS software. RESULTS: One hundred fifty-six videos were included in the analysis. Forty videos were classified as very or moderately useful (25.6%). Sources of the videos were as follows: patient experience, 103 videos (66%); physician, 30 (19%); surgical technique, 14 (9%); and news report, 9 (6%). Physician sourced information was generally at least moderately useful (58%) and patient experience videos were the predominant source of videos categorized as not useful or misleading (50%). Physician sourced information (coefficient=0.61; 95% CI: .21 to 1.00, p=0.003) and PT search term (coefficient=0.26; 95% CI: 0.05 to .47, p=0.017) were the most useful videos after adjusting for mean duration, days online, number of views and page search. CONCLUSION: YouTube has a large number of videos on pediatric tonsillectomy with a variety of content ranging from very useful to not useful, and misleading. Health care professionals must recognize the potential influence that these video Web sites may have on patient attitudes.

Thymic cyst: a fourth branchial cleft anomaly.

We report a unique case of a fourth branchial cleft cyst found within the thymus of an adult patient. In the literature to date, there have been no reports of such a finding in the adult population. These anomalies can often cause recurrent acute suppurative thyroiditis or recurrent deep neck abscesses. Delay in recognizing the underlying etiology can lead to significant complications.

Use of the external jugular vein as the sole recipient vein in head and neck free flap reconstruction.

OBJECTIVE: The selection of recipient vessels suitable for microvascular anastomosis within the head and neck region is an essential element affecting patency and outcome. Our aim was to ascertain whether the use of external jugular vein as the sole recipient vein is related to an increase in free flap failure in head and neck reconstructive surgery. METHODS: A retrospective review of all head and neck free flaps performed at an academic centre during a 3-year period was performed. Cases in which the external jugular vein was the lone recipient vein were analyzed. The same two surgeons completed all microvascular anastomosis. The outcome measure was free flap survival. RESULTS: Forty-seven of 49 flaps (96%), which used the external jugular vein as the sole recipient vein, survived. The two failures resulted from venous thrombosis but were successfully salvaged. CONCLUSION: The free flap success rate is well within the range of figures previously reported in large studies. Use of the external jugular vein as the sole recipient vein in head and neck free flap reconstruction does not increase the risk of free flap failures. This suggests that the external jugular vein is a viable option when choosing a single recipient vein in head and neck free tissue transfers.