Thomas Sanford

Contrasting the Microbiomes From Healthy Volunteers and Patients With Chronic Rhinosinusitis

IMPORTANCE Chronic rhinosinusitis (CRS) is the persistent inflammation of the sinus and nasal passages lasting over 3 months. The etiology of CRS is not well understood. OBJECTIVE To obtain insights into the disease process, we contrasted the microbiome and immune response from patients with CRS and healthy controls. DESIGN, SETTING, AND PARTICIPANTS A case vs control design was used. Samples were collected in the operating room in an institutional hospital or clinic. Thirty patients with CRS and 12 healthy controls undergoing surgery were recruited. MAIN OUTCOMES AND MEASURES The microbiome was analyzed by deep sequencing of the bacterial 16S and fungal 18S ribosomal RNA genes. Immune response was measured by quantification of 30 different cytokines by multiplexed enzyme-linked immunosorbent assay, and immune cells in the lavage were identified by flow cytometry. The immune response of peripheral blood leukocytes to the lavage microbiota was assessed by interleukin (IL)-5 enzyme-linked immunospot assay. RESULTS While quantitative increase in most bacterial and fungal species was observed in patients with CRS relative to controls, the microbiomes of patients with CRS were qualitatively similar to the controls. Because these results indicated that bacteria and fungi are not triggering CRS, we undertook a more detailed characterization of the immune response. Patients with CRS had increased levels of the following cytokines: IL-4, IL-5, IL-8, and IL-13, along with increased levels of eosinophils and basophils in the lavage. Importantly, peripheral blood leukocytes isolated from patients with CRS responded to control lavage samples (ie, to commensals) to produce IL-5. In contrast, the same lavage sample evoked no IL-5 production in leukocytes from healthy controls. CONCLUSIONS AND RELEVANCE These findings support the theory that in some cases CRS results from an immune hyperresponsiveness to commensal organisms.

Surgical Management of the Deviated Septum: Techniques in Septoplasty

This article provides a review of contemporary techniques in nasal septal surgery. Relevant anatomy and physiology of the nose and nasal septum are discussed. The essentials of a complete diagnostic evaluation are outlined. The evolution of surgical approaches to the correction of a deviated septum, including classic submucosal resection, traditional septoplasty, and open techniques, is covered. Complications of septoplasty are reviewed, with an emphasis on prevention and treatment. The recently popularized endoscopic septoplasty, a significant advance in septal surgery, is addressed elsewhere in this issue.

A systematic review of the sinonasal microbiome in chronic rhinosinusitis.

Background The interaction between the host and microorganisms in chronic rhinosinusitis (CRS) is poorly understood and is a growing area of interest. More recently, methodologies have been developed to assess the microbiome without the use of culture by analyzing the bacterial 16S ribosomal RNA gene. We reviewed the microbiome literature to better understand the role of microbes in CRS. Methods Systematic review of studies that used the 16S ribosomal RNA gene deep sequencing. Results Nine publications met the search criteria. Eight studies evaluated the microbiome in controls (total, 83 subjects; range, 3-28 per study), whereas six of the studies included patients with CRS (total, 121 patients; range, 7-43 per study). Various sequencing techniques, primers, sample sites, and extraction methods were used. Of the articles that specified the number of taxa in controls, an average of 1587 taxa were identified (range, 911-2330). Significant heterogeneity was noted among the studies; however, Firmicutes, Actinobacteria, and Bacteroides phyla were identified in every sample of control patients and patients with CRS. Three of the studies showed enrichment to some degree of Staphylococcus aureus in patients with CRS. The total bacterial burden in CRS was similar to the controls. One study demonstrated a decrease in diversity, whereas other studies did not show any changes in CRS when compared with controls. Conclusion Although there are common phyla present in both control patients and patients with CRS, no consistent enrichment of any particular taxon was identified. Our findings indicated that there was no clear single causative microbe in CRS. More studies are needed to better understand the significance of the host interaction with the microbiome and the role it plays in CRS.

Patients with Pediatric Obstructive Sleep Apnea Show Altered T-Cell Populations with a Dominant TH17 Profile

Objective To characterize the immunologic changes of the tonsil as they correlate with increasing apnea-hypopnea index (AHI) in children. Study Design Prospective immunologic analysis. Setting Tertiary care pediatric otolaryngology practice. Subjects Tonsils were collected from 24 children with obstructive sleep apnea, all of whom had undergone polysomnography at an accredited sleep center using scoring determined by the American Academy of Sleep Medicine 2007 scoring manual. Patients were excluded if they had been diagnosed with craniofacial abnormalities, neuromuscular disorders, or immunodeficiency. Methods Single-cell suspensions were isolated from tonsils of 13 individuals and stained with fluor-conjugated antibodies and analyzed using fluorescence-activated cell sorting. Single-cell suspensions from tonsils of 11 additional individuals were incubated 21 hours and subjected to multiplexed enzyme-linked immunosorbent assay cytokine analysis. Results In patients with an AHI >5 events/h, there was a statistically significant increase in the fraction of CD4+ CD45RO+ T cells (P < .01), and the percentage of CD8+ FoxP3+ T cells (TcREG) showed a statistically significant decrease (P < .005). Cytokine analysis revealed high levels of interleukin (IL)–17A, IL-1b, IL-10, and IL-12p70 production. Cytokine profiles revealed a conspicuous absence of IL-4 and IL-2. Conclusions Our results indicate the tonsils of patients with obstructive sleep apnea have an ongoing inflammatory response characterized by increased effector CD4 T cells and decreased FoxP3 CD8 T cells. The TH17 skewing suggests that local immune activation may be either autoimmune or due to an extracellular pathogen.

Extramedullary plasmacytoma in the anterior cervical region.

1. Benitz KF, Roberts GKS, Yusa A. Morphologic effects of minocycline in laboratory animals. Toxicol Appl Pharmacol 1967;11:150-70. 2. Attwood HD, Dennett X. A black thyroid and minocycline treatment. BMJ 1976;2:1109-10. 3. Onyia JN, Forrest LA, Forsthoefel K. Papillary carcinoma associated with black thyroid gland. Am J Otolaryngol 1996;17:299302. 4. Saul SH, Dekker A, Lee RE, et al. The black thyroid: its relation to minocycline use in man. Arch Pathol Lab Med 1983;107:1737. 5. Jennings TA, Sheehan CE, Chodos RB, et al. Follicular carcinoma associated with minocycline-induced black thyroid. Endocrine Pathology 1996;7:345-8. 6. Folsom DL, Gauderer MWL, Dahms WT. Nodular hyperplasia, black thyroid, and chronic minocycline ingestion in a teenager. Arch Surg 1992;127:1476-7. 7. Landas SK, Marsh WL, Schuller DE, et al. Nonpigmented papillary carcinoma in a black thyroid gland. Arch Otolaryngol Head Neck Surg 1990;116:735-7. 8. Pastolero GC, Asa SL. Drug-related pigmentation of the thyroid associated with papillary carcinoma. Arch Pathol Lab Med 1994;118:79-83. 9. Wenig BM, Heffess CS, Adair CF. Atlas of endocrine pathology. Philadelphia: WB Saunders; 1997. p. 42-3, 73-7, 108-9. 10. Enochs WS, Nilges MJ, Swartz HM. The minocycline-induced thyroid pigment and several synthetic models: identification and characterization by electron paramagnetic resonance spectroscopy. J Pharmacol Exp Ther 1993;266:1164-76. 11. Taurog A, Dorris ML, Doerge DR. Minocycline and the thyroid: antithyroid effects of the drug, and the role of thyroid peroxidase in minocycline-induced black pigmentation of the thyroid gland. Thyroid 1996;6:211-9. 12. Faddis DM, Daroca PJ, Krementz ET. Oxyphilic (Hürthle cell) adenoma arising in a black thyroid gland. South Med J 1990;83: 976-8.

Allergy Symptom Response to Intradermal Testing-Based Immunotherapy: A Retrospective Study of Clinical Practice

OBJECTIVE: Evaluate the multiple end-organ targets affected by intradermal testing (IDT)-based immunotherapy. STUDY DESIGN AND SETTING: We conducted a retrospective medical record review of 139 patients, as well as a follow-up questionnaire in a university setting. RESULTS: Statistically significant differences (t-tests, P < 0.05) were observed in the prevalence of symptoms after IDT-based immunotherapy for each category (ear, eye, nasal, and throat). When divided into treatment time groups, the reduction was less in the first group (0–6 months therapy), than the subsequent groups (6–24 months and >24 months). The reduction leveled off after 6 months of therapy, with no difference seen between the 6- to 24-month and >24-month groups. CONCLUSIONS: IDT-based immunotherapy has a broad response on otolaryngic allergy symptoms that appears to be consistent over time. SIGNIFICANCE: IDT-based immunotherapy is an effective form of treatment for allergy-induced diseases of the head and neck.

The Pediatric Allergic Nose

Allergic rhinitis (AR) is one of the most common ailments that can involve the pediatric upper airway with a prevalence of 20–40%. AR is closely related to asthma and atopic dermatitis. Along with the airway symptoms, AR also has an effect on the cognitive performance of a child. Diagnosis of AR is made by a combination of history and physical examination in combination with allergy testing. Allergy testing is done in vivo (skin testing) or in vitro (Rast testing). Treatment of AR can include allergen avoidance, pharmacotherapy, and immunotherapy. All three of these therapies are effective and safe.