Pediatric dysphonia: It's not about the nodules.

OBJECTIVE: Despite the fact that vocal nodules are the most common cause of chronic dysphonia in children, uncertainty and lack of consensus complicates practically every diagnostic and management decision. Selecting an optimal staging system is fundamental to understanding a disease process, mandatory for uniform reporting, and crucial to predicting natural history and treatment outcomes. The ideal prognostic model for vocal nodules is under intense debate. The purpose of this study was to analyze the predictive power of vocal nodule grade to severity of voice metrics in children. METHODS: Seventy-nine patients diagnosed with vocal cord nodules between 2006 and 2012 were drawn from UPMC Children's Hospital of Pittsburgh Voice, Resonance and Swallowing Center Research Registry. Subject age at time of diagnosis, nodule grade, relevant co-morbidities, scores on The Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V), parent-reported Pediatric Voice Handicap Index (pVHI), the phonotraumatic behaviors profile, habitual speaking pitch fundamental frequencies, pitch range, volume intensity, and s/z ratio were recorded and compiled into a de-identified database for analysis. RESULTS: Based on the Kruskal-Wallis H Test, there was no statistically significant correlation between nodule grade and total pitch range (p = .21), s/z ratio (p = .50), volume intensity (p = .33), overall CAPE-V Scores (p = .15), or pVHI Scores (p = .29). Chi-squared tests also revealed no significant associations between nodule grade and abnormality in habitual speaking pitch (p = .14 for fundamental frequency while sustaining a vowel sound, p = .37 for fundamental frequency while speaking structured tasks i.e. counting, or p = .76 while speaking in conversation). CONCLUSION: The current "gold-standard" for grading vocal nodule size suggests that the nodules themselves are not driving the standard dysphonic metrics that are most commonly collected and monitored in such children. This outcome is consistent with other studies reporting similar findings and was expected based on the inconsistencies in the reported literature to date. By extension, the conventional wisdom of avoiding surgical treatment of vocal nodules in children seems prudent as there is little evidence to suggest that the nodules themselves are "driving" the severity of the dysphonia. Ultimately identifying the true "drivers" of dysphonia in children will suggest alternative therapies that are more specific and directed to the pathophysiology. Most pediatric voice care professionals will welcome such discoveries as those in the front line of patient care are often rendered helpless and frustrated.

Novel rat model of tympanostomy tube otorrhea.

OBJECTIVE: Tympanostomy tube otorrhea (TTO), caused by the presence of pathogenic bacteria in the middle ear, is the most common complication of TT insertion. No studies have described a reproducible animal model of TTO. We aimed to develop a rat model of TTO which, in turn, could be used to assay the levels of TNF-α and IL-1ß through the course of the infection. METHODS: The left Eustachian tubes of 55 male Sprague-Dawley albino rats were occluded with gutta-percha (ETO=Eustachian Tube Occlusion). Middle ear (ME) effusion was ascertained by weekly otomicroscopy. At 3 weeks tympanostomy tubes were placed bilaterally and the MEs were inoculated bilaterally with Streptococcus pneumoniae through the tubes. The rats were randomly assigned to one of two daily ototopical treatments: ciprofloxacin/dexamethasone (CDX) or placebo. The animals in each of the two treatment groups were further divided to receive 1, 2, 5 or 7 days of treatment. The rats were sacrificed after treatment was finished. The rates of otorrhea, positive middle ear (ME) cultures, and levels of TNF-α and IL-1ß in the ME fluid were measured. RESULTS: Left ETO followed by ME inoculation with S. pneumoniae and treatment with placebo resulted in persistent infection (100% culture-positive ME fluid at 10 days) and otorrhea (85.7%). Persistent infection of the left ear was accompanied by significantly elevated the levels of IL-1ß and TNF-α. Ears treated with CDX had lower rates of otorrhea at all time points and lower levels of IL-1ß and TNF-α. CONCLUSIONS: This study is the first to describe a reproducible animal model of acute TTO. Surgical obstruction of the ET, followed by TT placement and ME inoculation with S. pneumoniae induced persistent otorrhea and infection. Both IL-1ß and TNF-α appear to be potential markers of persistent middle ear infection. This novel model may be used in future studies of the pathogenesis and therapy of TTO.

Differences in bacteriologic treatment failures in acute otitis externa between ciprofloxacin/dexamethasone and neomycin/polymyxin B/hydrocortisone: results of a combined analysis.

OBJECTIVE: To compare treatment failure rates for the two major acute otitis externa (AOE) pathogens, Pseudomonas aeruginosa and Staphylococcus aureus, by topical therapy with ciprofloxacin 0.3%/dexamethasone 0.1% (CDex) or neomycin 0.35%/polymyxin B 10,000 IU/mL/hydrocortisone 1% (Cort) based on clinical and microbiological failure in patients positive for these pathogens at baseline. RESEARCH DESIGN AND METHODS: A combined analysis was conducted from two similar, but non-identical clinical trials involving CDex vs. Cort. Outcomes of the combined efficacy analysis were treatment failure rates and antibiotic susceptibility values for P. aeruginosa and S. aureus. The raw data for the treatment failure rates from the two studies were combined to calculate the overall treatment failure rates of each treatment group. Chi-square tests of independence were conducted to assess differences in treatment failure rates between treatment groups. RESULTS: Of the 789 patients with culture-positive ears prior to the initiation of therapy, 61.0% (n = 481) were positive for P. aeruginosa and 8.9% (n = 70) were positive for S. aureus. While treatment failure rates for S. aureus were similar for the two therapies, CDex had a significantly lower treatment failure rate than Cort (5.1 vs. 13.0%; p = 0.0044) for P. aeruginosa. All of the persisting P. aeruginosa and S. aureus isolates were susceptible to fluoroquinolones and neomycin/polymyxin B. LIMITATIONS: The analysis strength is dependent on pooled data from similar studies. CONCLUSIONS: Ototopical ciprofloxacin 0.3%/dexamethasone 0.1% more effectively eradicates P. aeruginosa compared to Cort. Eradication of S. aureus by either drug was similar. These results favor CDex as a better first-line choice in the treatment of AOE compared to Cort.

Effects of ciprofloxacin-dexamethasone on myringotomy wound healing.

OBJECTIVE: To evaluate the effects of the ciprofloxacin-dexamethasone (CDX) combination ototopical treatment after myringotomy on tympanic membrane (TM) healing in ears with eustachian tube obstruction (ETO) and unobstructed ears. STUDY DESIGN: Prospective, randomized, masked, controlled. METHODS: ETO was created in the left ear of 30 rats to induce a model of otitis media with effusion (OME). After 3 weeks, bilateral myringotomy was performed (day 0). Animals were randomized into three groups to receive no treatment or bilateral once daily ototopical treatment with balanced salt solution (BSS, vehicle) or CDX for 13 days. Bilateral otomicroscopy was performed on days 7, 14, and 28. On day 14, five randomly selected animals per group were humanely euthanized and the TM harvested for histology. Three additional rats provided normal negative control ears for histologic comparisons. RESULTS: On day 14, TM perforation healing rates were 100% in all ears of untreated and BSS-treated animals, 89% (8/9) in CDX-treated obstructed ears, and 30% (3/10) in CDX-treated unobstructed ears (P < .05 vs. BSS). On day 28, 100% (5/5) of the CDX-treated unobstructed ears and 80% (4/5) of the CDX-treated obstructed ears were healed. Histology showed initial TM thickening postmyringotomy in all ears but no significant qualitative differences between groups on day 28. CONCLUSION: Myringotomy healing was transiently modulated by treatment with CDX but proceeded normally after CDX discontinuation. This early modulation might enhance middle ear drainage and middle ear concentrations of CDX when tympanostomy tube surgery is performed in patients with active OME and ETO, thus potentially reducing otorrhea and preventing or treating infection. It would not be expected to increase the risk of premature tube extrusion or adversely affect normal healing of the TM after usual spontaneous extrusion.

Prostaglandin E2 inhibition of keloid fibroblast migration, contraction, and transforming growth factor (TGF)-beta1-induced collagen synthesis.

Keloid formation has been linked to aberrant fibroblast activity, exacerbated by growth factors and inflammatory mediators. Prostaglandin E2 (PGE2), synthesized from arachidonic acid by cyclooxygenases (COX) and synthases (PGES), acts as both an inflammatory mediator and fibroblast modulator. Although PGE2 has known antifibrotic effects in the lower airway, its role in dermal fibrosis in general, and keloid formation in particular, remains unclear. This study focused on: (1) the effects of PGE2 on keloid fibroblast migration, contraction, and collagen synthesis and (2) endogenous PGE2 synthesis in response interleukin-1beta. PGE2 decreased keloid fibroblast migration and contraction via an EP2/EP4-cAMP mechanism that disrupted actin cytoskeletal dynamics and reversed transforming growth factor-beta1-induced collagen I and III synthesis. Impaired fibroblast PGE2 production has been linked to lower airway fibrosis and recently to keloid formation. Here, we showed that interleukin-1beta stimulation leads to nuclear factor-kappaB translocation to the nucleus, resulting in up-regulation of COX-2 and microsomal PGE2 synthase 1. Up-regulation of COX-2 in, and secretion of PGE2 by keloid fibroblasts are diminished compared with their normal fibroblast counterparts. We suggest that the antifibrotic effects of PGE2 during keloid formation are potentially diminished due to aberrant paracrine fibroblast signaling. Exogenous PGE2 may supplement decreased endogenous levels and inhibit keloid formation or progression.

Topical ciprofloxacin/dexamethasone otic suspension is superior to ofloxacin otic solution in the treatment of granulation tissue in children with acute otitis media with otorrhea through tympanostomy tubes.

OBJECTIVE: Comparison of topical ciprofloxacin/dexamethasone otic suspension (CIP/DEX) to ofloxacin otic solution (OFL) for treatment of granulation tissue in children with AOMT. STUDY DESIGN: 599 children aged >/=6 months to 12 years with AOMT of up to 3 weeks' duration were enrolled. Patients received either CIP/DEX 4 drops twice daily for 7 days or OFL 5 drops twice daily for 10 days. Granulation tissue severity was graded at clinic visits on days 1, 3, 11, and 18. RESULTS: Granulation tissue was present in 90 of 599 AOMT patients (15.0%) at baseline. CIP/DEX treatment was superior to OFL for reduction of granulation tissue at the day 11 visit (81.3% compared with 56.1%, P = 0.0067) and the day 18 visit (91.7% compared with 73.2%, P = 0.0223). Both topical otic preparations are safe and well tolerated in pediatric patients. CONCLUSION: CIP/DEX was superior to OFL in the treatment of granulation tissue in children with AOMT.