Human Extrafollicular CD4+ Th Cells Help Memory B Cells Produce Igs.

Follicular helper T (Tfh) cells are necessary for germinal center B cell maturation during primary immune responses; however, the T cells that promote humoral recall responses via memory B cells are less well defined. In this article, we characterize a human tonsillar CD4+ T cell subset with this function. These cells are similar to Tfh cells in terms of expression of the chemokine receptor CXCR5 and the inhibitory receptor PD-1, IL-21 secretion, and expression of the transcription factor BCL6; however, unlike Tfh cells that are located within the B cell follicle and germinal center, they reside at the border of the T cell zone and the B cell follicle in proximity to memory B cells, a position dictated by their unique chemokine receptor expression. They promote memory B cells to produce Abs via CD40L, IL-10, and IL-21. Our results reveal a unique extrafollicular CD4+ T cell subset in human tonsils, which specialize in promoting T cell-dependent humoral recall responses.

Improvement in asthma control and inflammation in children undergoing adenotonsillectomy.

BACKGROUND: Observational studies suggest that asthma control improves after adenotonsillectomy, but longitudinal studies that correlate the effect of the procedure on the levels of biomarkers associated with airway inflammation are limited. METHODS: We conducted a longitudinal, observational study on pediatric patients, both with and without asthma, undergoing adenotonsillectomy. Asthma control test (ACT) scores and chitinase activity in the circulation were measured at time of surgery and at 6-mo follow-up. RESULTS: Sixty-six children with asthma and 64 control subjects were enrolled. Mean ACT scores improved by three points (P < 0.001) after 6 mo. 85% of children with poorly controlled asthma demonstrated an increase in ACT score of at least three points or a decrease in emergency department/urgent care visits, oral corticosteroid courses, or rescue short acting bronchodilator usage. Chitinase activity decreased significantly in asthmatics who improved (P < 0.01). Higher chitinase activity levels at baseline were associated with improved asthma control following surgery (P < 0.01). CONCLUSION: In children with high preoperative circulating chitinase activity levels, asthma control and healthcare utilization were significantly improved after adenotonsillecotmy. Chitinase activity decreased after surgery in children with improved control. This suggests that adenotonsillectomy modulates chitinase activity, affecting airway inflammation and improving airway disease.

The 3-ounce (90-cc) water swallow challenge: a screening test for children with suspected oropharyngeal dysphagia.

OBJECTIVES: To investigate the clinical utility of the 3-ounce (90-cc) water swallow challenge alone to determine both aspiration status and oral feeding recommendations in children. DESIGN: Cross-sectional evaluation of a diagnostic test with a consecutive, referral-based sample. SETTING: Urban, tertiary care, teaching hospital. PARTICIPANTS: Fifty-six children (age range 2-18 years; mean 13 years) referred for swallowing evaluations. OUTCOME MEASURES: Aspiration status during fiberoptic endoscopic evaluation of swallowing (FEES) was the objective criterion standard with which results from the 3-ounce water swallow challenge were compared. RESULTS: Twenty-two (39.3%) participants passed and 34 (60.7%) failed the 3-ounce challenge. Sensitivity for predicting aspiration status during FEES = 100.0 percent, specificity = 51.2 percent, and false-positive rate = 48.4 percent. Sensitivity for identifying individuals who were deemed safe for oral intake based on FEES results = 100.0 percent, specificity = 44.0 percent, and false-positive rate = 56.0 percent. CONCLUSIONS: If the 3-ounce water swallow challenge is passed, not only thin liquids but diet recommendations with puree and solid food consistencies can be made without the need for further instrumental dysphagia assessment. SIGNIFICANCE: The 3-ounce water swallow challenge has been shown to be a clinically useful screening test for oropharyngeal dysphagia in children.

Age at diagnosis, but not HPV type, is strongly associated with clinical course in recurrent respiratory papillomatosis.

BACKGROUND: Recurrent Respiratory Papillomatosis (RRP) is a rare disease characterized by the growth of papillomas in the airway and especially the larynx. The clinical course is highly variable among individuals and there is poor understanding of the factors that drive an aggressive vs an indolent course. METHODS: A convenience cohort of 339 affected subjects with papillomas positive for only HPV6 or HPV11 and clinical course data available for 1 year or more, from a large multicenter international study were included. Exploratory data analysis was conducted followed by inferential analyses with frequentist and Bayesian statistics. RESULTS: We examined 339 subjects: 82% were diagnosed prior to the age of 18 years, 65% were infected with HPV6, and 69% had an aggressive clinical course. When comparing age at diagnosis with clinical course, the probability of aggressiveness is high for children under five years of age then drops rapidly. For patients diagnosed after the age of 10 years, an indolent course is more common. After accounting for confounding between HPV11 and young age, HPV type was minimally associated with aggressiveness. Fast and Frugal Trees (FFTs) were utilized to determine which algorithms yield the highest accuracy to classify patients as having an indolent or aggressive clinical course and consistently created a branch for diagnostic age at ~5 years old. There was no reliable strong association between clinical course and socioeconomic or parental factors. CONCLUSION: In the largest cohort of its type, we have identified a critical age at diagnosis which demarcates a more aggressive from less aggressive clinical course.

Correlation of presentation and pathologic condition in primary ciliary dyskinesia.

OBJECTIVES: To better characterize primary ciliary dyskinesia (PCD) and improve the diagnosis of this uncommon disorder. STUDY DESIGN AND SETTING: We retrospectively reviewed the records of 118 patients with ciliary biopsy or brushing specimens examined at Yale University School of Medicine from 1991 to 2001. RESULTS: Sinonasal, middle ear, and pulmonary infections were more common in patients with PCD-positive biopsy results than in those with negative results. In addition, PCD caused by random ciliary orientation presented similarly to PCD caused by other ultrastructural defects. CONCLUSIONS: Patients who present with cough alone are highly unlikely to have PCD (chi(2 ) test, 24.85; P<.001). In contrast, patients who present with multiple manifestations are highly likely to have PCD (chi(2) test, 22.2; P<.001). This information may assist the clinician in the diagnosis of PCD.

Preoperative anxiety, postoperative pain, and behavioral recovery in young children undergoing surgery.

OBJECTIVE: Findings from published studies suggest that the postoperative recovery process is more painful, slower, and more complicated in adult patients who had high levels of preoperative anxiety. To date, no similar investigation has ever been conducted in young children. METHODS: We recruited 241 children aged 5 to 12 years scheduled to undergo elective outpatient tonsillectomy and adenoidectomy. Before surgery, we assessed child and parental situational anxiety and temperament. After surgery, all subjects were admitted to a research unit in which postoperative pain and analgesic consumption were assessed every 3 hours. After 24 hours in the hospital, children were discharged and followed up at home for the next 14 days. Pain management at home was standardized. RESULTS: Parental assessment of pain in their child showed that anxious children experienced significantly more pain both during the hospital stay and over the first 3 days at home. During home recovery, anxious children also consumed, on average, significantly more codeine and acetaminophen compared with the children who were not anxious. Anxious children also had a higher incidence of emergence delirium compared with the children who were not anxious (9.7% vs 1.5%) and had a higher incidence of postoperative anxiety and sleep problems. CONCLUSIONS: Preoperative anxiety in young children undergoing surgery is associated with a more painful postoperative recovery and a higher incidence of sleep and other problems.