A comparison of men and women undergoing septoplasty-the Swedish national septoplasty register.

Objective: Men represent more than two-thirds of septoplasty patients in many studies, but differences between men and women in terms of patient selection or outcome are seldom reported. This study aims to investigate whether women undergoing septoplasty differ from men in critical variables before and after surgery, in a large national sample of septoplasties. Design: Cross-sectional register study. Participants: The study includes 2,532 patients from the National Swedish Septoplasty Register undergoing septoplasty with or without additional turbinoplasty on the indication of nasal obstruction in 2014-2019. Patients in the register have not been preselected. Main outcome measures: Preoperative variables and postoperative outcome were compared between men and women. Results: Men accounted for 1,829 (72%) of the patients. There was no significant difference between men and women in severity of self-reported nasal obstruction or type of surgery performed (septoplasty with or without turbinoplasty). Mean postoperative nasal obstruction 12 months after surgery and overall satisfaction with the result were similar. Women, however, reported more complications 12 months postoperatively, while men reported more problems with snoring and obstructive sleep apnea preoperatively. Conclusion: In this large national patient cohort undergoing septoplasty, we found no differences in preoperative nasal obstruction or postoperative patient-rated outcome in men and women undergoing septoplasty, despite the fact that 72% of the patients were men. It thus remains unclear why women are under-represented in septoplasty surgery in this and many other cohorts.

HealthSWEDE: costs with sublingual immunotherapy-a Swedish questionnaire study.

BACKGROUND: The aim of this cross-sectional survey was to compare the health-economic consequences for allergic rhinitis (AR) patients treated with sublingual Immunotherapy (SLIT) in terms of direct and indirect costs with a reference population of patients receiving standard of care pharmacological therapy. METHODS: Primary objective was to analyse the health-economic consequences of SLIT for grass pollen allergy in Sweden vs reference group waiting for subcutaneous immunotherapy (SCIT). A questionnaire was mailed to two groups of AR patients. RESULTS: The questionnaire was distributed to 548 patients, 307 with SLIT and 241 in reference group (waiting for SCIT). Response rate was 53.8%. Mean annual costs were higher for reference patients than SLIT group; € 3907 (SD 4268) vs € 2084 (SD 1623) p < 0.001. Mean annual direct cost was higher for SLIT-patients, € 1191 (SD 465) than for reference, € 751 (SD 589) p < 0.001. Mean annual indirect costs for combined absenteeism and presenteeism were lower for patients treated with SLIT, € 912 (SD 1530), than for reference, € 3346 (SD 4120) p < 0.001, with presenteeism as main driver. CONCLUSIONS: SLIT seems to be a cost-beneficial way to treat seasonal AR. This information might be used to guide future recommendations.

Age and Unplanned Postoperative Visits Predict Outcome after Septoplasty: A National Swedish Register Study.

OBJECTIVE: To study predictors of symptom relief six months after septoplasty using data from the Swedish National Septoplasty Register. PARTICIPANTS: This is a retrospective register study of adult patients undergoing septoplasty in Sweden in 2003-2012. OUTCOME: Relief of nasal symptoms was analysed in relation to age, gender, size of hospital performing the surgery, addition of turbinoplasty, and unplanned postoperative visits to the hospital due to pain, bleeding, or infection. RESULTS: In all, 76% of the patients (n = 5,865) rated their symptoms as "almost gone" or "gone" six months after septoplasty. With every 10-year increase in the age of the patients, the OR was 1.19, 95% CI 1.15-1.23, for a better result and 1.54, 95% CI 1.38-1.71, if the septoplasty was performed at a county hospital versus a university hospital. If there was no unplanned postoperative visit due to pain, bleeding, or infection, the OR for a better result was 1.6, 95% CI 1.39-1.85. CONCLUSION: In this large national cohort of septoplasties, most of the patients felt that their symptoms had gone or almost gone six months after septoplasty. Higher age, surgery at smaller hospitals, and no unplanned visits to the hospital postoperatively predicted a better outcome.

Treatment of idiopathic rhinitis with kinetic oscillations - a multi-centre randomized controlled study.

CONCLUSIONS: The potential effects of KOS are still uncertain regarding the most effective air pressure to be used as well as the physiological effects on the nasal mucosa. The results of the study do not support a convincing treatment effect by KOS on IR. OBJECTIVES: Idiopathic rhinitis (IR) is a common disorder, affecting ∼10-20% of the population. A new method for treating IR, Kinetic Oscillation Stimulation (KOS), has been reported to have beneficial effects on total vasomotor symptom scores (TVRSS). The primary objective with this study was to evaluate if a mean pressure of 65 mbar, pressure amplitude of 100 mbar, and 68 Hz treatment with KOS had a positive effect on total vasomotor symptom scores (TVRSS), as compared with a mean pressure of 65 mbar, pressure amplitude of 4 mbar, and 68 Hz treatment in patients with idiopathic rhinitis. METHODS: Two hundred and seven patients were randomized (Full Analysis Set, FAS) in the study, including five visits and lasting for ∼25 weeks. All patients had two treatment episodes, and all patients had at least one treatment, meant as active, with high amplitude pressure for 10 min in each nostril. Group 1 had two such treatments, and Group 2 had one treatment with low amplitude pressure, initially meant as placebo, on one occasion. Because of numerical improvements in these two groups, a new control group, Group 3, was introduced. They had one new control treatment where the balloon was inserted into the nose, without any air inflation and without oscillations. RESULTS: KOS treatment with high amplitude pressure did not have significant beneficial effects as compared to low amplitude pressure on TVRSS. Numerical improvements in TVRSS and SNOT 22 were found when comparing high and low amplitude pressure treatments with uninflated balloon treatment. However, this part of the study was initially single-blinded, and these results were secondary objectives.

Biological effects and clinical efficacy of a topical Toll-like receptor 7 agonist in seasonal allergic rhinitis: a parallel group controlled phase IIa study.

OBJECTIVE AND DESIGN: The purpose of the study was to examine effects of pre-treatment with a Toll-like receptor 7 (TLR7) agonist (AZD8848) in allergic rhinitis and to evaluate clinical effects of two dosing regimens. SUBJECTS: The study involved 83 patients with allergic rhinitis. Data on effects of AZD8848 on symptoms were analysed with data from a previous study (n = 68) of identical double blind, parallel group design (NCT00770003). TREATMENT: The treatment involved intranasal AZD8848 20 µg three times weekly, 60 µg once weekly, or placebo for 5 weeks. METHODS: Nasal lavage and plasma were analysed for proof-of-mechanism markers. Daily nasal allergen challenges were given for 7 days, starting 24 h after the final AZD8848 dose. Symptoms were monitored after each challenge and every morning and evening. RESULTS: Markers of TLR-activation increased following AZD8848 administration (CXCL10, TNFα, IL-6, IFNγ). Symptoms recorded soon after allergen challenge were reduced up to eight days after the final dose of AZD8848. Morning and evening symptoms were also reduced, and these changes reached statistical significance for morning observations. Adverse effects were more frequent in the 20 µg three times weekly group. CONCLUSIONS: Repeated administration of AZD8848 activated TLR7 and produced IFN-induced effects. This was associated with a sustained reduction in allergen responsiveness.

Repeated intranasal TLR7 stimulation reduces allergen responsiveness in allergic rhinitis.

BACKGROUND: Interactions between Th1 and Th2 immune responses are of importance to the onset and development of allergic disorders. A Toll-like receptor 7 agonist such as AZD8848 may have potential as a treatment for allergic airway disease by skewing the immune system away from a Th2 profile. OBJECTIVE: To evaluate the efficacy and safety of intranasal AZD8848. METHODS: In a placebo-controlled single ascending dose study, AZD8848 (0.3-600 µg) was given intranasally to 48 healthy subjects and 12 patients with allergic rhinitis (NCT00688779). In a placebo-controlled repeat challenge/treatment study, AZD8848 (30 and 60 µg) was given once weekly for five weeks to 74 patients with allergic rhinitis out of season: starting 24 hours after the final dose, daily allergen challenges were given for seven days (NCT00770003). Safety, tolerability, pharmacokinetics, and biomarkers were monitored. During the allergen challenge series, nasal symptoms and lavage fluid levels of tryptase and α2-macroglobulin, reflecting mast cell activity and plasma exudation, were monitored. RESULTS: AZD8848 produced reversible blood lymphocyte reductions and dose-dependent flu-like symptoms: 30-100 µg produced consistent yet tolerable effects. Plasma interleukin-1 receptor antagonist was elevated after administration of AZD8848, reflecting interferon production secondary to TLR7 stimulation. At repeat challenge/treatment, AZD8848 reduced nasal symptoms recorded ten minutes after allergen challenge up to eight days after the final dose. Tryptase and α2-macroglobulin were also reduced by AZD8848. CONCLUSIONS: Repeated intranasal stimulation of Toll-like receptor 7 by AZD8848 was safe and produced a sustained reduction in the responsiveness to allergen in allergic rhinitis. TRIAL REGISTRATION: NCT00688779 and NCT00770003 as indicated above.

Effects of a dual CCR3 and H1-antagonist on symptoms and eosinophilic inflammation in allergic rhinitis.

BACKGROUND: The CC-chemokine receptor-3 (CCR3) has emerged as a target molecule for pharmacological intervention in allergic inflammation. OBJECTIVE: To examine whether a dual CCR3 and H1-receptor antagonist (AZD3778) affects allergic inflammation and symptoms in allergic rhinitis. METHODS: Patients with seasonal allergic rhinitis were subjected to three seven days' allergen challenge series. Treatment with AZD3778 was given in a placebo and antihistamine-controlled design. Symptoms and nasal peak inspiratory flow (PIF) were monitored in the morning, ten minutes post challenge, and in the evening. Nasal lavages were carried out at the end of each challenge series and alpha2-macroglobulin, ECP, and tryptase were monitored as indices of allergic inflammation. RESULTS: Plasma levels of AZD3778 were stable throughout the treatment series. AZD3778 and the antihistamine (loratadine) reduced rhinitis symptoms recorded ten minutes post challenge during this period. AZD3778, but not the anti-histamine, also improved nasal PIF ten minutes post challenge. Furthermore, scores for morning and evening nasal symptoms from the last five days of the allergen challenge series showed statistically significant reductions for AZD3778, but not for loratadine. ECP was reduced by AZD3778, but not by loratadine. CONCLUSIONS: AZD3778 exerts anti-eosinophil and symptom-reducing effects in allergic rhinitis and part of this effect can likely be attributed to CCR3-antagonism. The present data are of interest with regard to the potential use of AZD3778 in allergic rhinitis and to the relative importance of eosinophil actions to the symptomatology of allergic rhinitis. TRIAL REGISTRATION: EudraCT No: 2005-002805-21.

Effects of topical formoterol alone and in combination with budesonide in a pollen season model of allergic rhinitis.

BACKGROUND: beta(2)-Agonists may exert mast cell stabilizing and anti-plasma exudation effects. While available data suggest no or only marginal effects of beta(2)-agonists on symptoms of allergic rhinitis, little is known about whether these drugs may add to the efficacy of anti-rhinitis drugs. OBJECTIVE: To examine effects of a beta(2)-agonist, alone and in combination with an intranasal glucocorticosteroid, on symptoms and signs of allergic rhinitis. METHODS: Patients were examined in a pollen season model. Budesonide 64 microg, alone and in combination with formoterol 9 microg, as well as formoterol 9 microg alone was given in a placebo-controlled and crossover design. After 7 days of treatment, the patients received allergen challenges for 7 days. Symptoms and nasal peak inspiratory flow (PIF) were recorded. Nasal lavages with and without histamine were carried out at the end of each challenge series. These lavages were analysed for tryptase, eosinophil cationic protein (ECP), and alpha(2)-macroglobulin as indices of mast cell activity, eosinophil activity, and plasma exudation, respectively. RESULTS: Budesonide reduced symptoms of allergic rhinitis and improved nasal PIF in the morning, in the evening as well as post allergen challenge. Formoterol alone did not affect symptoms or nasal PIF and did not affect the efficacy of budesonide. Tryptase, ECP, and alpha(2)-macroglobulin were significantly reduced by budesonide. Formoterol alone did not affect these indices and did not affect the anti-inflammatory effect of budesonide. CONCLUSION: The present dose of formoterol does not affect symptoms and inflammatory signs of allergic rhinitis and does not add to the efficacy of topical budesonide.

Establishing a model of seasonal allergic rhinitis and demonstrating dose-response to a topical glucocorticosteroid.

BACKGROUND: Symptoms of seasonal allergic rhinitis may vary greatly. Hence, for research purposes, there is a need for disease-like models of allergic rhinitis. In a preliminary study, involving 7 days' challenge with allergen, promising symptom consistency was obtained and dose-response to a glucocorticosteroid could, in part, be demonstrated. OBJECTIVE: To establish this model of seasonal allergic rhinitis and test the hypothesis that mometasone furoate is more potent than budesonide as an antirhinitis drug. METHODS: Thirty-eight patients with seasonal allergic rhinitis received treatment with spray-formulations of placebo, budesonide 64 microg, budesonide 256 microg, and mometasone furoate 200 microg in a double-blind, crossover design. After 3 days' treatment, individualized nasal allergen-challenges were administered daily for 7 days while the treatment continued. Nasal symptoms and peak inspiratory flow (PIF) were recorded. RESULTS: During the last 3 days of allergen challenge without active treatment, consistent around-the-clock symptoms were recorded and recordings during these days were used in the analysis. With few exceptions the active treatments reduced nasal symptoms and improved nasal PIF (P values <0.001 to 0.05). Budesonide caused dose-dependent improvements in evening symptoms, morning nasal PIF, and nasal PIF recorded 10 minutes after allergen-challenge (P values <0.05). Budesonide 256 microg produced greater improvement than mometasone furoate 200 microg for nasal PIF 10 minutes after allergen-challenge (P < 0.05). CONCLUSION: The present allergen challenge method, producing consistent symptoms and nasal PIF data, emerges as a model of seasonal allergic rhinitis well suited for exploring potency and efficacy of drug intervention. The present data do not support the view that mometasone furoate is a more potent antirhinitis drug than budesonide.