What is the optimal outcome after endoscopic sinus surgery in the treatment of chronic rhinosinusitis? A consultation of Canadian experts.

OBJECTIVES: Many experts feel that in the absence of well-defined goals for success, they have an easier time identifying failure. As success ought to not be defined only by absence of failure, we aimed to define optimal outcomes for endoscopic sinus surgery (ESS) in chronic rhinosinusitis (CRS) by obtaining expert surgeon perspectives. METHODS: A total of 12 surgeons participated in this targeted consultation. Face to face semi-structured interviews were performed with expert surgeons in the field of CRS and ESS. General impressions and personal definitions of acceptable operative success and optimal operative outcomes were compiled and summarized. RESULTS: According to an expert survey, patients' main objectives are an improvement in their chief complain, a general improvement in quality of life (QoL), and a better overall symptomatic control. The most important aspects of endoscopy for defining a successful intervention were an adequate mucus circulation, a healthy mucosa, minimal edema, and patency of all explored cavities or ostia. In the assessment of surgical outcomes, it was determined that both objective and patient reported data must be carefully examined, with more attention given to subjective outcomes. CONCLUSIONS: According to data gathered from a Canadian expert consultation, a definition of success must be based on both subjective data and nasal endoscopy. We propose to define an acceptable outcome as either a subjective improvement of at least the minimal clinically improvement difference of a validated patient reported outcome questionnaire, along with a satisfactory endoscopic result (1) or a complete subjective resolution with a sub-optimal endoscopy (2).

Resident's preparedness for independent practice following Otorhinolaryngology-Head and Neck Surgery residency program: a cross-sectional survey.

PURPOSE: Evaluate perception of preparedness for independent practice following the Otorhinolaryngology-Head and Neck Surgery residency program of Université de Montréal. METHODS: Cross-sectional survey of graduates from the past 10 years. Participants were asked about their level of confidence at the end of their residency for various procedures using a 5-point Likert scale. RESULTS: 7 out of 27 procedures were mastered by most physicians at the end of residency. The highest confidence level was in head and neck surgery (4 out of 5 procedures with a mean confidence level of 4 or higher) and lowest in laryngology and otology (both having 3 procedures with a median confidence level of 2 or less). The lowest confidence level was seen in ossiculoplasty and thyroplasty, being the only procedures to have a mean confidence level below 2. The highest scores were seen in superficial parotidectomy, direct microlaryngoscopy and trans-oral drainage of an abscess. These latter were the only procedures in which 100% of the respondent had a confidence level of 4 or 5. DISCUSSION: It has recently been suspected that these fields were potential weaknesses, so adjustments were made. This study provides new information to improves the curriculum. Recent and incoming change's impact on resident's confidence will be assessed in the future. CONCLUSION: This study highlights procedures and Otorhinolaryngology-Head and Neck Surgery subspecialties in which more surgical exposure or curriculum changes could increase resident's confidence and skills as part of a comprehensive Otorhinolaryngology practice.

Superiorly based facial artery musculomucosal flap: A versatile pedicled flap.

BACKGROUND: The superiorly based facial artery musculomucosal (FAMM) flap is pedicled on the angular artery. This flap offers a well-vascularized mucosal surface allowing closure of medium size defects, most frequently within the oral cavity and intranasal region. METHODS: We describe a superiorly based harvest of the FAMM flap, which may be used for closure of multiple head and neck surgical defects. An operative technique video is provided, which can be viewed online. RESULTS: Our results demonstrate a fast and relatively straightforward harvest technique of the FAMM flap. This intraoral flap is a useful reconstructive tool, which also has the advantage to leave no visible external scars. CONCLUSION: The superiorly pedicled FAMM flap is a versatile and effective technique that may be integrated in the algorithm for reconstruction of head and neck defects.

Objective Assessment of Technical Skills in Otorhinolaryngology-Head and Neck Surgery Residents: A Systematic Review.

Objectives The primary goal is the indexation of validated methods used to assess surgical competency in otorhinolaryngology-head and neck surgery (ORL-HNS) residents. Secondary goals include assessment of the reliability and validity of these tools, as well as the documentation of specific procedures in ORL-HNS involved. Data Sources MEDBASE, OVID, Medline, CINAHL, and EBM, as well as the printed references, available through the Université de Montréal library. Review Methods The PRISMA method was used to review digital and printed databases. Publications were reviewed by 2 independent reviewers, and selected articles were fully analyzed to classify evaluation methods and categorize them by procedure and subspecialty of ORL-HNS involved. Reliability and validity were assessed and scored for each assessment tool. Results Through the review of 30 studies, 5 evaluation methods were described and validated to assess the surgical competency of ORL-HNS residents. The evaluation method most often described was the combined Global Rating Scale and Task-Specific Checklist tool. Reliability and validity for this tool were overall high; however, considerable data were unavailable. Eleven distinctive surgical procedures were studied, encompassing many subspecialties of ORL-HNS: facial plastics, general ear-nose-throat, laryngology, otology, pediatrics, and rhinology. Conclusions Although assessment tools have been developed for an array of surgical procedures, involving most ORL-HNS subspecialties, the use of combined checklists has been repeatedly validated in the literature and shown to be easily applicable in practice. It has been applied to many ORL-HNS procedures but not in oncologic surgery to date.

Biocompatibility and pharmacokinetics of fluticasone-eluting sinus implant in a rabbit model.

BACKGROUND: A novel, bioabsorbable, fibrinogen-based implant has been developed as a mucosal dressing after endoscopic sinus surgery (ESS). This implant can be formulated with fluticasone propionate (FP) for local elution of corticosteroid to reduce postoperative inflammation and promote mucosal healing. OBJECTIVE: This study investigated the biocompatibility and pharmacokinetics of the implant in a rabbit model. METHODS: Implants with and without FP were placed on both intact and demucosalized maxillary sinuses of 33 New Zealand White rabbits. Sinuses with either intact or denuded bone without implants acted as controls. Histopathologic assessments were carried out at 5, 15, and 28 days. Concentrations of FP in the maxillary sinus mucosa, nasal cavity mucosa, and plasma were measured for up to 44 days. RESULTS: Implants placed on intact mucosa or denuded bone were grossly integrated within 15 days. Minimal foreign body reaction was seen with negligible differences for inflammation, fibrosis, or bone remodeling among controls, sinuses with the implant, or sinuses with the implant plus FP, at all time points. All samples also showed complete or near-complete percentage reepithelialization at 28 days, although the denuded bone controls demonstrated greater percentage reepithelialization at 5 days compared with denuded bone with the implant or implant plus FP (p < 0.0001). The maxillary sinus mucosa demonstrated levels of FP of >140 ng/g up to 44 days. Plasma concentrations of FP were generally very low and were undetectable after day 7. CONCLUSIONS: The implant and the implant plus FP seemed to be biocompatible in rabbits. The implant plus FP effectively eluted steroid locally over at least 44 days, with negligible plasma concentrations. Further studies are warranted regarding potential therapeutic applications in patients undergoing ESS for chronic rhinosinusitis.

Modified Facial Artery Musculomucosal Flap for Reconstruction of Posterior Skull Base Defects.

Objectives The superiorly pedicled facial artery musculomucosal (FAMM) flap has been successfully used for reconstruction of head and neck defects since 1992. Common sites of defects include the oral cavity and oropharynx. This article presents a clinical case in which we have successfully used a newly developed modification of the FAMM flap for bulky nasopharyngeal and skull base reconstruction. Results Our patient is a 71-year-old man who presented with a large parapharyngeal and clival chordoma. After tumor removal through combined endoscopic and cervical approach, the internal carotid artery (ICA) in the nasopharyngeal portion was left exposed. A modified superiorly based FAMM flap measuring up to 10 cm in length and 2.5 cm in width was successfully harvested and used to completely cover the defect and the ICA. The flap survived local radiation therapy at the long-term follow-up. Conclusion We have developed a new modification of the FAMM flap, using the fascia of the masseter muscle. This is the first reported case in the literature using a modified FAMM flap for the reconstruction of nasopharyngeal and skull base defect.

Sustained Inner Ear Steroid Delivery via Bioabsorbable Stent: A Tolerability and Feasibility Study on Guinea Pigs.

OBJECTIVE: To determine the feasibility and tolerability of a steroid-eluting middle ear device on an animal model. STUDY DESIGN: Prospective experimental. SETTING: Experimental animal study. SUBJECTS AND METHOD: Mometasone furoate (MF)-eluting miniature sticks were implanted through a myringotomy incision into the middle ear of 10 guinea pigs. Two additional ears of 2 animals served as controls. Fourteen days after implantation, perilymphatic fluid was collected through an endaural cochleostomy. MF concentrations were measured with high-performance liquid chromatography, and the middle ear mucosal inflammation was graded with hematoxylin and eosin colorations. RESULTS: Fourteen days after implantation, all tympanic membranes had fully healed. An average of 165 ng/mL of MF was detected in the perilymphatic fluid of the experimental ears, and none was measured in control ears. Microscopic residues of the ministicks were found in 90% of the samples, confirming the bioabsorbable properties of this device. Histologic analysis of the middle ear mucosa found similar inflammation profiles in both groups, thereby suggesting middle ear tolerability. CONCLUSION: MF-coated bioabsorbable miniature stick allows for prolonged delivery over 14 days without injuring the middle ear mucosa. Middle ear-sustained steroid delivery may prove to be beneficial in numerous neurotologic conditions.

Effects of Fluticasone Furoate on Clinical and Immunological Outcomes (IL-17) for Patients With Nasal Polyposis Naive to Steroid Treatment.

OBJECTIVES: We investigated the effect of topical steroids on clinical outcomes and related immune response of chronic rhinosinusitis with nasal polyp (CRSwNP) patients and in eradicating some polyps. We want to explore a new potential mechanism linked to Th-17 cells. METHODS: Prospective, double-blind, placebo-controlled studies with 24 allergic and nonallergic patients were randomized to either placebo or fluticasone furoate for 12 weeks. Assessment of clinical response, endoscopic score with biopsies of the inferior turbinate, and polyps before and after treatment were performed. Biopsies were stained for T-cells, eosinophils, neutrophils, and IL-17A/F. RESULTS: Steroid treatment improved the mean symptoms scores from 7.12 to 4.02 (P < .01) and the polyp score from 5.13 to 3.31 (P < .05), but the comparison with placebo was not statistically significant in nonallergics due to insufficient study power. Steroid treatment decreased eosinophil counts on allergics but not neutrophils or T-cells. The IL-17A/F expression was higher in nonallergics with high neutrophil counts and was inclined by steroids. Compared to baselines, IL-17 cells were significantly less in allergic individuals and were not observed in allergics and with high neutrophil counts. CONCLUSION: Topical steroids were more effective on certain nasal polyp phenotypes. Identification of polyp phenotype might be essential to ensure a better therapeutic response to intranasal corticosteroids.

Intratympanic corticosteroids injections: a systematic review of literature.

The objective of the study was to determine the evidence of intratympanic steroids injections (ITSI) for efficacy in the management of the following inner ear diseases: Ménière's disease, tinnitus, noise-induced hearing loss (NIHL) and idiopathic sudden sensorineural hearing loss (ISSNHL). The data sources were literature review from 1946 to December 2014, PubMed and Medline. A systematic review of the existing literature was performed. Databases were searched for all human prospective randomized clinical trials using ITSI in at least one treatment group. The authors identified 29 prospective randomized clinical trials investigating the benefits of an intratympanic delivery of steroids. Six articles on Ménière's disease were identified, of which one favored ITSI over placebo in vertigo control. Of the five randomized clinical trials on tinnitus therapy, one study found better tinnitus control with ITSI. The only available trial on NIHL showed significant hearing recovery with combination therapy (ITSI and oral steroids therapy). Seventeen studies were identified on ISSNHL, of which 10 investigated ITSI as a first-line therapy and 7 as a salvage therapy. Studies analysis found benefits in hearing recovery in both settings. Due to heterogeneity in treatment protocols and follow-up, a meta-analysis was not performed. Given the low adverse effects rates of ITSI therapy and good patient tolerability, local delivery should be considered as an interesting adjunct to the therapy of the ISSNHL and NIHL. Only one article over six where ITSI therapy offers potential benefits to patients with Ménière's disease in the control of tinnitus and vertigo was found. ITSI does not seem to be effective in the treatment of tinnitus.

Steroid-eluting sinus implant for in-office treatment of recurrent nasal polyposis: a prospective, multicenter study.

BACKGROUND: Treatment options for chronic rhinosinusitis with recurrent polyposis (CRSwNP) after endoscopic sinus surgery (ESS) are limited, and include frequent use of systemic steroids and revision surgery. A bioabsorbable, steroid-eluting implant was studied for its ability to dilate sinuses obstructed by polyps and provide localized, controlled steroid delivery to reestablish sinus patency. This study assessed the initial feasibility, safety, and efficacy of steroid-eluting implants placed in the office setting in patients who were candidates for revision ESS. METHODS: Prospective, multicenter study enrolling 12 patients who had prior ESS but experienced recurrent polyposis refractory to medical therapy. Implants were placed bilaterally under topical anesthesia in-office. Follow-up through 6 months included endoscopic grading, patient-reported outcomes (22-item Sino-Nasal Outcomes Test [SNOT-22]) and need for revision ESS. RESULTS: Implants were successfully inserted in 21 of 24 (88%) ethmoid sinuses, resulting in 11 evaluable patients. No serious adverse events occurred. Within 1 month, mean bilateral polyp grade was reduced from 4.5 at baseline to 2.3 (p = 0.008) and sustained through 6 months (2.33; p = 0.008). Mean SNOT-22 score was significantly improved from 2.19 at baseline to 0.90 within 1 month (p = 0.001) and sustained to 6 months (1.03; p = 0.012). Sixty-four percent of patients were no longer revision ESS candidates at 6 months. CONCLUSION: The study provided initial clinical evidence of the feasibility, safety, and efficacy of in-office steroid-eluting implant placement in CRS patients with recurrent polyposis after ESS. Although further studies are needed, the results suggest this therapy may provide a safe and effective, office-based option for the treatment of obstructive polyposis.

3D+t brain MRI segmentation using robust 4D Hidden Markov Chain.

In recent years many automatic methods have been developed to help physicians diagnose brain disorders, but the problem remains complex. In this paper we propose a method to segment brain structures on two 3D multi-modal MR images taken at different times (longitudinal acquisition). A bias field correction is performed with an adaptation of the Hidden Markov Chain (HMC) allowing us to take into account the temporal correlation in addition to spatial neighbourhood information. To improve the robustness of the segmentation of the principal brain structures and to detect Multiple Sclerosis Lesions as outliers the Trimmed Likelihood Estimator (TLE) is used during the process. The method is validated on 3D+t brain MR images.

Facial artery musculomucosal flap for reconstruction of skull base defects: a cadaveric study.

OBJECTIVES/HYPOTHESIS: Failure in skull base defects reconstruction following tumor resection can have serious consequences such as ascending meningitis and pneumocephaly. The nasoseptal flap showed a very low incidence of cerebrospinal fluid leak but is not always available. The superiorly pedicled facial artery musculomucosal (FAMM) flap has been successfully used for reconstruction of head and neck defects. Our objective is to show that the FAMM flap can be used as a new alternative in skull base reconstruction. STUDY DESIGN: Cadaveric study. Feasibility. METHODS: Thirteen specimens underwent bilateral FAMM flap dissection. Two new modifications of the traditional FAMM flap have been developed. Feasibility in FAMM flap transfer to the skull base was investigated through endoscopic skull base dissection and maxillectomy in four specimens. Measurements were recorded for each harvested flap. RESULTS: The mean surface area of the modified FAMM flap efficient for reconstruction was 15.90 cm(2) . The flaps easily covered the simulated defects of the frontal sinus and the fovea ethmoidalis areas. Modifications of the traditional FAMM flap were necessary for a tension-free coverage of the planum sphenoidale and sella turcica. CONCLUSION: The FAMM flap holds high potential as a new alternative vascular flap in skull base reconstruction. However, it has not been used in patients yet and should be considered only when other options are not available. New modifications developed in this article can elongate the traditional FAMM flap, potentially contributing to a tighter seal of the skull base defect than FAMM flap alone.

Interrater reliability of endoscopic parameters following sinus surgery.

OBJECTIVES/HYPOTHESIS: To determine the interrater reliability of a set of postoperative endoscopic scoring parameters in patients with chronic rhinosinusitis who have undergone endoscopic sinus surgery (ESS). STUDY DESIGN: Prospective cohort with retrospective review. METHODS: One hundred twenty video-endoscopic evaluations in 20 subjects recorded at 14, 30, and 45 days after ESS were scored in real time by the clinical investigators who performed the endoscopies and recorded the videos and retrospectively by an independent panel of four sinus surgeons who were blinded to all information. The scoring parameters included categoric grading for adhesion formation and middle turbinate position and continuous grading (visual analog scale) for degree of inflammation and crusting. Interrater reliability of the panel members was assessed using the Fleiss kappa test, bias index and prevalence index for categoric data, and the Shrout-Fleiss test for continuous data. The level of agreement between the panel and the real-time clinical investigator was also assessed. RESULTS: For categoric variables, strong agreement between raters on the panel was found for both middle turbinate position (kappa=0.499, prevalence index=0.925) and adhesions (kappa=0.364, prevalence index=0.829). For continuous data, good agreement between raters was found for both inflammation (reliability coefficient=0.554) and crusting (reliability coefficient=0.620). Real-time investigator scoring and panel scoring showed strong agreement. CONCLUSIONS: These results suggest that the endoscopic scoring parameters assessed (middle turbinate position, adhesions, inflammation, and crusting) have acceptable interexaminer reproducibility and are suitable for evaluating ESS outcomes in the postsurgical period.

Effect of Th2 type cytokines on hCLCA1 and mucus expression in cystic fibrosis airways.

Correlations between expression of interleukin (IL)-9, the calcium-activated chloride channel hCLCA1 and mucus expression in cystic fibrosis (CF) airways have suggested a causal relationship. To verify this hypothesis mucosal tissue from upper airways of CF patients (N=5) was stimulated with the Th2 type cytokines IL-4, IL-9, or IL-13. Expression of hCLCA1 mRNA and protein as well as mucus and mucin (MUC5AC) gene expression was quantified using real time PCR, immunohistochemistry (hCLCA1) and PAS staining (mucus). Th2 type cytokines significantly increased hCLCA1 protein expression (P<0.05) whereas increase in hCLCA1 mRNA expression failed to reach statistical significance (P>0.05). Mucin protein and MUC5AC mRNA expression were not significantly changed (P>0.05). These data suggest that Th2 type cytokines may increase hCLCA1 expression in CF but may not have a significant effect on mucus expression. Therefore the role of hCLCA1 as a mediator of mucus overexpression in CF has to be questioned.

Extracranial complications of endoscopic transsphenoidal sellar surgery.

BACKGROUND: The endoscopic transsphenoidal approach for the resection of sellar tumours has rapidly increased in popularity. However, few studies report on the extracranial complications of this procedure. To be able to critically evaluate all of the outcomes from this approach, the occurrence of any extracranial complications that result from its performance needs to be established. OBJECTIVE: To examine specifically what extracranial complications are associated with this surgical approach to sellar lesions. METHODS: A retrospective analysis of a consecutive case series was performed to identify the extracranial complications for primary sellar lesions operated on using an endoscopic transsphenoidal approach performed during the years 2003 to 2006. Patients had a minimal postoperative follow-up of 6 months. RESULTS: A total of 135 patients were eligible for analysis, of whom 82% underwent an isolated endoscopic transsellar approach to the sellar tumour. Extracranial complications occurred in 29.6% of the operated cases. The most common complications were prolonged nasal crusting (10.4%), synechia formation (8.8%), and septal deviation (3.7%). The use of a combined transplanum and transsellar approach was not associated with a significant increase in complications (p = .354). CONCLUSIONS: It is important that the outcomes, including the complications that can arise from the endoscopic transsphenoidal approach to sellar lesions, be established if meaningful comparisons are to be drawn between it and classic microscopic approaches to the sella turcica. From this study, although considered minor, up to one-third of patients may be expected to experience an extracranial complication from this surgery.

Selective irrigation of paranasal sinuses in the treatment of recalcitrant chronic sinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) refractory to medical and surgical therapy is a challenging entity to treat. Topical antibiotics and anti-inflammatory drugs have been increasingly used in managing this disorder. The aim of this pilot study is to evaluate the role of maxillary sinus antrostomy tubes (MAST) in selectively irrigating paranasal sinuses with topical antibiotics with anti-inflammatory in treating recalcitrant CRS. A prospective clinical trial was performed at a tertiary referral center. METHODS: Thirteen patients with failed maximal medical and surgical therapies for chronic sinusitis were enrolled in the study. Endoscopic scores as well as the Sino-Nasal Outcome Test 16 (SNOT-16) scores were obtained before and 3, 8, and 16 weeks after maxillary sinus intubation with MAST. All patients received topical antibiotics with anti-inflammatory medication for 21 days. RESULTS: Statistically significant reductions in SNOT-16 and endoscopic scores were found before and after topical irrigations. Both scores continued to improve at the 8th and 16th weeks. CONCLUSION: Selective irrigation of maxillary sinuses using MAST is a viable alternative in treating recalcitrant CRS.

Local induction of a specific Th1 immune response by allergen linked immunostimulatory DNA in the nasal explants of ragweed-allergic subjects.

BACKGROUND: Allergen immunotherapy is effective in allergic individuals however efforts are being made to improve its safety, convenience, and efficacy. It has recently been demonstrated that allergen-linked immunostimulatory DNA (ISS) is effective in stimulating an allergen-specific Th1 response with decreased allergenicity. The objective of this study is to investigate whether ISS linked to purified ragweed allergen Amb-a-1 (AIC) can inhibit local allergen-specific Th2 and induce allergen-specific Th1 responses in explanted nasal mucosa of ragweed-sensitive subjects. In addition, we set out to determine whether AIC is more effective compared to stimulation with unlinked Amb a 1 and ISS. METHODS: Tissue from ragweed-sensitive patients (n = 12) was cultured with whole ragweed allergen (RW), Amb-a-1, AIC, Amb-a-1 and ISS (unlinked), or tetanus toxoid (TT) for 24 hours. IL-4, -5, -13, TNF-alpha and IFN-gamma mRNA-positive cells were visualized by in situ hybridization and T cells, B cells and neutrophils were enumerated using immunocytochemistry. RESULTS: RW or Amb-a-1 increased the number of IL-4, IL-5, and IL-13 mRNA+ cells in the tissue compared to medium alone. AIC had similar cytokine mRNA reactivity as control tissue. AIC and TT increased IFNgamma-mRNA expression. Unlinked Amb-a-1 and ISS showed similar effects to AIC, however this response was weaker. The number of TNF mRNA+ cells, T cells, B cells and neutrophils remained unchanged. CONCLUSIONS: AIC is effective in stimulating a local allergen-specific Th1- and abolishing Th2-cytokine mRNA reactivity in the nose and may be considered as a strong candidate for an improved approach to immunotherapy in ragweed-sensitive individuals.

Delayed-iatrogenic injury of the thoracic aorta by an anterior spinal instrumentation.

We present a case of a 15-year-old girl who presented to us with an unusual low back pain. About 7 years ago, this patient had corrective surgery for her idiopathic left thoracolumbar scoliosis. Recent surgery revealed a laceration of the posterior wall of the thoracic aorta by an impending screw thread. This injury was repaired by the vascular surgeons and, subsequently, the patient had full recovery without any complications.

Amb a 1-immunostimulatory oligodeoxynucleotide conjugate immunotherapy increases CD4+CD25+ T cells in the nasal mucosa of subjects with allergic rhinitis.

BACKGROUND: We have previously shown that short-course treatment with Amb a 1-immunostimulatory phosphorothioate oligonucleotide conjugate (AIC) before the ragweed season modifies the response of the nasal mucosa to allergen challenge in ragweed-sensitive patients by increasing Th1 cytokines and decreasing both Th2 cytokines and eosinophilia after the ragweed season. The effect of AIC immunotherapy on CD4+CD25+ T cell expression in the nasal mucosa is unknown. OBJECTIVE: To determine the in vivo effect of short-course AIC immunotherapy on CD4+CD25+ regulatory T cells in the nasal mucosa of ragweed-sensitive subjects. METHODS: 19 ragweed-sensitive patients with allergic rhinitis were randomly assigned to receive either 6 escalating doses of AIC (0.06-12microg; n = 12) or placebo (n = 7) at weekly intervals immediately before the 2001 ragweed season. Nasal biopsies were taken at baseline prior to immunization and again post immunization 24 hours after ragweed allergen challenge at the start and end of the ragweed season. The expression of T regulatory cells, IL-10 and TGF-beta was assessed at each time point by immunohistochemistry. RESULTS: The numbers of allergen-induced CD4+-, CD4+CD25+-, IL-10- and TGF-beta-positive cells in the nasal mucosa after AIC immunization before the ragweed season did not differ between the two groups. Repeat challenge after the ragweed season led to a significant increase in CD4+CD25+ cells in AIC-compared with placebo-treated subjects. A trend toward an increase in IL-10-positive cells in the AIC-treated group did not reach statistical significance. CONCLUSIONS: Short-course AIC immunotherapy increases CD4+CD25+ regulatory T cell infiltration in the nasal mucosa following allergen challenge after seasonal ragweed-pollen exposure.