Martyn Barnes

Treatment of Chronic Rhinosinusitis With Nasal Polyposis With Oral Steroids Followed by Topical Steroids: A Randomized Trial

BACKGROUND Chronic rhinosinusitis (CRS) with nasal polyposis is common. The long-term efficacy and safety of approaches to medical management are not well-known. OBJECTIVE To evaluate the efficacy and safety of a 2-week regimen of oral steroid therapy followed by 26 weeks of sequential topical steroid maintenance therapy. DESIGN Parallel randomized trial with computer-generated block randomization and central allocation. Patients and investigators were blinded to group assignment. (ClinicalTrials.gov registration number: NCT00788749) SETTING A specialty rhinology clinic in Tayside, Scotland. PATIENTS 60 adults with CRS and moderate-sized or larger nasal polyps who were referred by their primary physicians for specialty care. INTERVENTIONS Patients were randomly assigned in a 1:1 ratio to receive oral prednisolone, 25 mg/d, or placebo for 2 weeks, followed in both groups by fluticasone propionate nasal drops, 400 µg twice daily, for 8 weeks and then fluticasone propionate nasal spray, 200 µg twice daily, for 18 weeks. MEASUREMENTS Polyp grading (primary outcome), hyposmia score, quality of life, symptoms, nasal patency, adrenal function, and bone turnover. RESULTS The mean decrease in polyp grade from baseline to 2 weeks was 2.1 units (SD, 1.1) in the prednisolone group and 0.1 unit (SD, 1.0) in the placebo group (mean difference between groups, -1.8 units [95% CI, -2.4 to -1.2 units]; P < 0.001). The difference between groups was -1.08 units (CI, -1.74 to -0.42 unit; P = 0.001) at 10 weeks and -0.8 unit (CI, -1.8 to 0.2 unit; P = 0.11) at 28 weeks. The mean decrease in hyposmia score from baseline to 2 weeks was 31.12 mm (SD, 30.1) in the prednisolone group and 1.41 mm (SD, 30.6) in the placebo group (mean difference between groups, -28.33 mm [CI, -42.71 to -13.96 mm]; P = 0.002). The difference between groups was -16.06 mm (CI, -30.99 to -1.13 mm; P = 0.03) at 10 weeks and -12.13 mm (CI, -30.55 to 6.29 mm; P = 0.19) at 28 weeks. Prednisolone therapy resulted in transient suppression of adrenal function and increase in bone turnover after 2 weeks, with a return to baseline at 10 and 28 weeks. LIMITATIONS Patients were referred from primary care to a single-center rhinology clinic, which limits the generalizability of results. Serial measurements of surrogates of nasal inflammation (such as nitric oxide or cytokine levels) were not performed. CONCLUSION Initial oral steroid therapy followed by topical steroid therapy seems to be more effective over 6 months than topical steroid therapy alone in decreasing polyp size and improving olfaction in patients referred for specialty care of CRS with at least moderate nasal polyposis. PRIMARY FUNDING SOURCE Chief Scientist Office, Scotland; National Health Service Tayside Small Grants Scheme; and an Anonymous Trust grant from University of Dundee.

Effects of levocetirizine as add‐on therapy to fluticasone in seasonal allergic rhinitis

Background Addition of H1 antagonists to intranasal corticosteroid treatment of allergic rhinitis (AR) is common in clinical practice and recommended by guidelines, despite some evidence that the additive benefits are negligible.

The minimal clinically important difference in allergic rhinitis

Background When presented with results from clinical measurements or research findings, clinicians must first make an interpretation of their importance, not only in statistical terms, but also the ‘clinical importance’ given the size of the change observed. To do this, they require an understanding of the relationship between their outcome measures, and the patients perception of change. The minimal clinically important difference (MCID) illustrates this relationship by calculating the smallest change in a given outcome that is meaningful to a patient. There are few reports of calculated MCIDs in the Rhinology literature.

Airway dysfunction in nasal polyposis: a spectrum of asthmatic disease?

Background Chronic rhinosinusitis with nasal polyposis (CRSwNP) represents an interesting model to investigate the existence of a non‐allergic unified airway. The factors associated with airway dysfunction in CRSwNP are not fully understood.

Respirable dose delivery of fluticasone propionate from a small valved holding chamber, a compact breath actuated integrated vortex device and a metered dose inhaler

AIMS To compare the respirable dose delivery of the hydrofluroalkane fluticasone propionate (HFA-FP) via an optimally prepared Aerochamber Plus spacer (AP), via a Synchro-Breathe (SB) device, and pMDI Evohaler (EH). METHODS Seventeen mild to moderate asthmatics completed the study using a randomized, double-blind, double-dummy, three way crossover design. Single doses of placebo or HFA-FP 2.0 mg were administered via the EH, AP, and SB devices. The overnight urinary cortisol : creatinine ratio (OUCC) was measured at baseline and after each dose. RESULTS Significant suppression of OUCC occurred from baseline with AP and SB but not EH devices (geometric mean fold suppression, 95% CI): AP: 3.18 (2.29, 4.36), P < 0.001; SB: 1.79 (1.31, 2.40), P = 0.001; EH: 1.12 (0.69, 1.44), p = 0.37 (equating to 68%, 45% and 9% falls, respectively). Significant differences in OUCC between devices were as follows: (geometric mean fold difference, 95% CI): AP vs. EH. 2.83 (2.09, 3.82), P < 0.001; AP vs. SB: 1.78 fold (1.21, 2.60), P = 0.003; SB vs. EH: 1.59 (1.09, 2.31), P = 0.013 (equating to 65%, 44% and 37% differences, respectively). CONCLUSIONS The use of an optimally prepared AP spacer and breath actuated SB device, when compared with pMDI, significantly increased the respirable dose of HFA-FP.

Effects of intranasal corticosteroid on nasal adenosine monophosphate challenge in persistent allergic rhinitis

Background:  Response to a single dose nasal adenosine monophosphate challenge has been used as a surrogate inflammatory marker for allergic rhinitis. Attenuation of response following intranasal corticosteroid would further validate the challenge.

Comparative safety and efficacy of 2 formulations of fluticasone aqueous nasal spray in persistent allergic rhinitis.

BACKGROUND There are few data on the clinical equivalence of different nasal corticosteroids in persistent allergic rhinitis (AR). Studies measuring plasma concentrations after a single dose may not predict relative systemic bioactivity at steady state. OBJECTIVE To compare a test formulation of fluticasone propionate with the innovator using a noninferiority design. METHODS Twenty-three patients with persistent AR were randomized to completion in a double-blind, placebo-controlled, crossover manner to receive the formulations at 200 microg/d for 4 weeks, with baselines measured after 2-week run-in and washout periods. The primary outcome measure was the Mini Rhinoconjunctivitis Quality of Life Questionnaire (MiniRQLQ) score. RESULTS Both formulations produced significant improvements in MiniRQLQ scores as change from baseline (P < .001), with a nonsignificant mean difference (test vs innovator) of -0.06 U (95% confidence interval [CI], -0.41 to 0.52 U) and the lower bound of the 95% CI being above the predefined noninferiority limit of -0.7 U. Both formulations produced significant improvements in peak nasal inspiratory flow rates as change from baseline (P < .01), with a nonsignificant mean difference of 0.5 L x min(-1) (95% CI, 9.8 to 10.8 L x min(-1)). There were also significant reductions in total nasal symptom scores (P < .01), with a nonsignificant mean difference of 0.4 U (95% CI, 0.3 to 1.1 U). No significant suppression of the 10-hour overnight urinary cortisol to creatinine ratio was seen with either formulation. CONCLUSIONS The test formulation was noninferior to the innovator for the primary outcome of MiniRQLQ score. The secondary efficacy and safety end points also support the interchangeability of the 2 formulations.

Effect of levocetirizine on nasal provocation testing with adenosine monophosphate compared with allergen challenge in allergic rhinitis

Background End‐organ hyperreactivity is an important feature of the allergic airway. There are no data directly comparing the responsiveness to treatment of different nasal provocation tests (NPT).

R159: Minimal Clinically Important Differences in Rhinology

PROBLEM: For chronic diseases, common in rhinology, adapting medical research to guidelines and decisions requires an interpretation of the patient’s perception of the importance of treatment effects. To guide such interpretation, previous researchers have defined cut-offs (minimally clinically important differences or MCIDs) beyond which a change in a particular outcome can be expected to be of perceptible benefit to a patient. METHODS: Seven years of data from research studies of the Asthma and Allergy Research group, University of Dundee, were analyzed to determine MCIDs for common outcomes in rhinology. Well-established, as well as novel approaches, were used: anchor and distribution-based approaches, with regression and meta-analysis techniques. RESULTS: Estimates were obtained for the MCID for the Mini Rhinoconjunctivitis Quality of Life Questionnaire (miniRQLQ), Peak Nasal Inspiratory Flow (PNIF) and Total Nasal Symptoms scores (TNS). Nasal nitric oxide had no correlation with patient perceptions of benefit. Heterogeneity was demonstrated–associated with rhinitis and treatment types–but the size of these effects was small, and useful MCIDs were obtained. Uncertainty of the estimates and the variability between subjects were quantified. CONCLUSION: MCIDs approximated 0.42 units for miniRQLQ, 5 L/min for PNIF, and 0.55 units for TNS. The estimates were transferable within the breadth of studies included. Previous MCID research has failed to quantify uncertainty and within-subject variability, and this has limited any utility in the interpretation of research findings. SIGNIFICANCE: If studies are large enough and outcomes sensitive, even the smallest treatment effects are demonstrable (“p 0.05”) for an intervention. MCIDs put these into perspective by determining the clinical significance and illustrating the likely perceived benefit to the patient. SUPPORT: The study was funded by a departmental grant from the asthma and allergy research group and received no financial support from the pharmaceutical or other industries. R160 Short-Term Tolerance of Intranasal Hypertonic Saline Aerosol Ashley Norris Weigand (presenter); Norman H Tiffin, RRT; Lisa Cambridge, MD

S108 – Close Margin Excision Outcomes in Head and Neck Skin Cancer

Objectives 1) Determine clinical and histological outcomes for patients following close margin excisions of head and neck skin cancer. 2) Guide decisions regarding further intervention and follow-up. Methods Retrospective review of Otolaryngology department skin excisions from 1991 to 2008. Pathology reports and casenotes were reviewed to identify lesions excised with less than 1mm margins and determine their further management and outcome. Kaplan-Meier survival analysis was used to obtain the number needed to follow up for 2 years (NNFU) to detect a recurrence. Results Of 1223 skin cancers, 1207 histology reports were obtained-24% were squamous cell carcinomas, 76% were basal cell carcinomas. 1060 had histological (lateral and deep) margin assessments. Of these, 72.4% were complete, 16.1% close (<1mm) and 11.5% incomplete. 112 closely excised lesions were identified and 107 casenotes were obtained. 2 underwent ‘immediate’ further excision, both demonstrating no residual tumour. Of the remaining 105 subjects, 8 developed clinically suspected recurrence, but 5 were disproved histologically. During follow-up, 10 subjects had a new lesion diagnosed (9 malignant). 12 patients had new lesions diagnosed beyond follow-up; 6 were malignant. 104 (97%) of the original closely excised lesions did not require further excision within the studys 4.1 years of observation (mean) following the initial procedure (range 1.5–12.1). The NNFU following close margin excisions was 34 (95% CI 16 to infinity). Conclusions In similar cases, close surgical margins will rarely indicate a need for further surgery or follow-up. Good quality patient advice leaflets and self-monitoring is advised.