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Introduction: The role of microbial profiles in Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) pathogenesis is increasingly recognised, with microbial imbalances perpetuating inflammation. We performed this study to associate the different nasal microbiological profile changes with the response to surgical or monoclonal treatment., Methods: This prospective observational study evaluated changes in the nasal microbial profiles of 44 patients (22 dupilumab, 22 surgery) over 6 months. Clinical assessments were performed at baseline and follow-ups, including Sino-Nasal Outcome Test-22 (SNOT-22) scores and Sniffin Sticks-Identification (SS-I) olfactory testing. Microbial profiling of nasal swabs was carried out by microbial culture and subsequent molecular identification by Polymerase chain reaction (PCR) and sequencing., Results: Baseline characteristics of 44 patients (22 dupilumab, 22 surgery) enrolled in this study were similar between groups. In the dupilumab group, Staphylococcus epidermidis prevalence rose from 37.03% to 59.25%, while Pseudomonas aeruginosa was eradicated. Moreover, dupilumab stabilised Staphylococcus aureus at 63.64%, while its prevalence increased in the surgery group (from 22.72% to 50%). When bacterial groups were associated with clinical scores, P. aeruginosa carriers had worse SNOT-22 (21.00 ± 1.41) and SS-I (5.50 ± 0.71) scores. Instead, S. epidermidis-colonised patients exhibited significantly lower mean SNOT-22 (15.39 ± 8.54) and greater SS-I scores (8.39 ± 3.77). The best outcomes were found in the subgroup of S. epidermidis carriers undergoing the dupilumab treatment., Conclusion: The two treatments modulated the microbial profiles differently, and, most importantly, clinical responses might depend on the association between treatment and the dominant bacterial species colonising the nasal cavity. Further investigation into microbial-restorative strategies could enhance outcomes for better treatment of CRS., (© 2024 John Wiley & Sons Ltd.)

Introduction: Management of severe chronic rhinosinusitis with nasal polyps (CRSwNP) has changed significantly in recent years, with different treatments now available including biologics and endoscopic sinus surgery (ESS), although there are still few comparative studies. We aimed to compare 1-year outcomes of patients with severe CRSwNP treated with dupilumab or ESS plus intranasal corticosteroids (INCS)., Methods: In this retrospective, real-life, observational, cohort study, we enrolled 101 patients with severe CRSwNP who were treated with INCS and either ESS (n = 49) or dupilumab (n = 52). The following outcomes were considered: nasal polyp score (NPS), Sino Nasal Outcome Test-22 (SNOT-22), visual analogue scale (VAS) for specific symptoms, Sniffin' Sticks identification test (SSIT), need for oral corticosteroids (OCS) and local eosinophilia detected by nasal cytology., Results: ΔNPS was significantly higher in the surgery group up to 12 months when the difference with dupilumab group was no longer significant (ΔNPS: 4 vs. 4.1). ΔVAS rhinorrhoea, ΔVAS smell and ΔSNOT-22 were significantly higher in the dupilumab group at 12 months (p < .05). SSIT scores were significantly better in the dupilumab group starting from the first month of follow-up (p < .05). In the dupilumab group, only 6.1% of patients had detectable local eosinophilia compared to 57% in the surgery group alongside with a lower need for OCS (16.3% vs. 61%)., Conclusions: Both dupilumab and ESS were effective in improving outcomes in patients with severe CRSwNP over 12 months. Nevertheless, patients treated with dupilumab had greater improvement in terms of SNOT-22, VAS rhinorrhoea, VAS smell and SSIT scores, with better control of local inflammation and less need for OCS., (© 2024 John Wiley & Sons Ltd.)

Objectives: To explore the effect of intranasal administration of recombinant human basic fibroblast growth factor (rh-bFGF) on postoperative chronic rhinosinusitis with nasal polyps (CRSwNP) patients., Design: A prospective, randomised, controlled, single-blinded trial., Setting and Participants: Seventy-five hospitalised patients who met the criteria of primary bilateral CRSwNP were enrolled from March 2020 to January 2021., Main Outcome Measures: Visual analogue scale, 22-item Sino-Nasal Outcome Test, Lund-Kennedy (L-K) system and scanning electron microscopy and quantitative real-time polymerase chain reaction., Results: Seventy-five patients with CRSwNP were randomly assigned to three groups, and 72 patients completed the 1-month medication regimen and 1-year follow-up. Rh-bFGF nasal-spray and drop application reduced general nasal VAS scores within 2 weeks after endoscopic sinus surgery (ESS) compared to the control group. In contrast, only rh-bFGF nasal-drops reduced SNOT-22 scores at 2 weeks and 1 year compared with the control group. A significant reduction in the endoscopic L-K score was observed in the rh-bFGF nasal-spray and drop group compared with the control group. This is primarily because rh-bFGF promotes cilia growth in the nasal mucosal epithelium after the operation, as illustrated by scanning electron microscopy and expression of CP110, Tap73 and Foxj1 mRNA. For eosinophilic CRSwNP, the general VAS score of rh-bFGF nasal-drops was more obviously reduced compared to the control group after ESS. A similar trend was observed for L-K score., Conclusions: Rh-bFGF nasal-drops and sprays can quickly and effectively relieve postoperative symptoms and improve long-term prognosis of patients with CRSwNP. Moreover, rh-bFGF nasal-drops is also an effective method for postoperative patients with eosinophilic CRSwNP., (© 2022 The Authors. Clinical Otolaryngology published by John Wiley & Sons Ltd.)

Background: Rhinitis affects up to 40% of the population worldwide and can significantly reduce quality of life. Some patients remain symptomatic despite maximal medical therapy. In refractory cases, posterior nasal neurectomy (PNN-the endoscopic division of the intranasal nerve branches containing postganglionic parasympathetic fibres) is postulated to reduce symptom burden., Objectives of Review: To establish whether PNN is effective and safe in the management of allergic and non-allergic rhinitis., Type of Review: Systematic review., Methods: A comprehensive literature search was undertaken using PubMed, EMBASE, MEDLINE, and Cochrane. The inclusion criteria were: studies published in English, studies where PNN was performed either with or without additional procedures, and where measures of objective/subjective outcomes and/or complications were reported. Extracted data included study type, sample size, surgical technique, study population characteristics, follow-up period, outcome measures, complications of surgery, and symptom outcomes., Results: A total of 23 articles satisfied the inclusion criteria studying in total 2282 patients. Sample size ranged from 8 to 1056. There were 3 randomised controlled trials, 3 case-control studies, and the remaining 17 were case series using both objective and subjective outcome measures. All but one study found improved patient-reported outcomes following PNN. Complications were reported in 14 studies-epistaxis was the most common complication and was observed in 30 patients (1.5% of subjects)., Conclusions: PNN had a low rate of complications. Although most studies reported significant symptomatic improvement, their heterogeneity, level of evidence, study design, and/or quality was not sufficient to draw any firm conclusions on the effectiveness of the procedure. Larger, well-designed studies are needed to clarify its role in the management of difficult-to-treat rhinitis., (© 2022 John Wiley & Sons Ltd.)

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease of the upper airways. AZD1981 is a selective antagonist of chemoattractant receptor-homologous molecule expressed on T helper type 2 and other type 2 cells, including innate lymphoid cells type 2, eosinophils, and basophils., Objective: To evaluate the efficacy of AZD1981 in reducing nasal polyp size when added to intranasal corticosteroids in adult patients with CRSwNP., Methods: Eighty-one subjects (18-70 years of age) with CRSwNP were recruited and screened for trial eligibility from allergy and otolaryngology clinics from a single tertiary care site between June 2016 and August 2019. Eligible patients were randomized in a double-blind fashion to receive either AZD1981 (n = 22) or placebo (n = 21) orally three times a day for 12 weeks, added to intranasal corticosteroids. The primary endpoint was a change in nasal polyp score (NPS) at 12 weeks. Secondary endpoints included improvement in sinus computed tomography using Lund Mackay scoring, symptoms using visual analog scale, quality of life using Sino Nasal Outcome Test-22, and the Brief Smell Identification Test., Results: Forty-three patients met the inclusion criteria and were enrolled. At 12 weeks, there was no difference in NPS change in the AZD1981 arm (mean 0, standard error 0.34, n = 15) compared with placebo (mean 0.20, standard error 0.36, n = 17); mean difference -0.20 (95% confidence interval: -1.21, 0.81; p = .69). No significant differences were observed for Lund Mackay score, symptoms, quality of life, or smell test. AZD1981 was well tolerated except for one case of hypersensitivity reaction., Conclusion: In patients with CRSwNP, the addition of AZD1981 to intranasal corticosteroids did not change nasal polyp size, radiographic scores, symptoms, or disease-specific quality of life., (© 2022 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.)

Chronic rhinosinusitis (CRS) is a highly heterogeneous disorder exhibiting considerable epidemiological, clinical and immunopathological variations across patients with distinct ethnic backgrounds and in different geographic locations. Asian CRS patients present less eosinophilic and type 2 (T2) inflammation, but more prominent neutrophilic inflammation compared with patients in Western countries. Although several biologics targeting important elements of T2 inflammation, such as IL-4, IL-5, IL-13 and IgE, demonstrate promising benefit for Caucasian patients with recurrent nasal polyps, their efficacy in Asian patients remains poorly defined. The distinct endotypes in Asian patients warrant the identification and selection of patients who would benefit from T2 biologics in Asian countries. Additionally, developing novel treatments targeting neutrophilic, type 1, and type 3 inflammation may benefit approximately 50% of Asian CRS patients with non-T2 inflammation. In this review, we summarized and discussed recent progress in the study of Asian CRS endotypes in comparison with those in patients in Western countries, and the methods of identifying Asian patients with eosinophilic or T2 inflammation. T2 biologic treatment of Asian CRS patients, potential therapeutic candidates targeting non-T2 inflammation in Asian CRS patients and the progress on developing other T2 biologics were discussed., (© 2021 John Wiley & Sons Ltd.)

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) can be a severe and debilitating disease associated with significant morbidity, loss of smell, sinus pressure and asthma exacerbations. Eosinophils play a role in the majority (85%) of patients. Benralizumab, an afucosylated monoclonal antibody directed against the IL-5 receptor, has powerful apoptotic effects on eosinophils., Objective: We sought to investigate the therapeutic benefit of inhibiting the IL-5 receptor using benralizumab to treat severe rhinosinusitis with nasal polyps., Methods: Patients with severe NP (defined by endoscopic grade 5 or more out of 8) with elevated eosinophils and a history of previous surgical or endoscopic polypectomy met entry criteria and were randomized in a double-blind fashion to receive 30 mg benralizumab SC or placebo. Endoscopic NP score was assessed at baseline and at treatment week 20. CT scan, SNOT-22 survey and UPSIT smell test score changes were also evaluated., Results: Thirty-three patients were screened, and twenty-four (n = 24) were enrolled in the study. Compared with baseline, benralizumab significantly improved NP score (-0.9 ± 0.2, P = 0.004) whereas placebo did not (-0.3 ± 0.3, P = 0.166). Benralizumab induced polyp size reduction compared with placebo did not reach statistical significance (P = 0.103). Five of 12 benralizumab-treated patients (42%) had improvements in all major outcomes (polyp score, CT, SNOT-22 and smell test) versus 2 out of 12 placebo (17%). The ratio of blood eosinophil count to allergen skin test positivity correlated with polyp reduction., Conclusion: Benralizumab was well-tolerated and compared with baseline achieved a statistically significant reduction in nasal polyp size, sinus occupancy, symptoms and improved sensation of smell for most patients (83%)., (© 2021 John Wiley & Sons Ltd.)

Objectives: We aimed to investigate the bone mineral density (BMD) in a group of Swedish patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) with or without asthma, as well as to evaluate whether the treatment of this patient group is in accordance with the EPOS recommendations., Design, Settings and Participants: Adult patients with a diagnosis of CRSwNP, and a history of at least two courses of oral corticosteroids (OCS) during the last year, were consecutively included in this study at five centres., Main Outcome Measures: The BMD of the patients was measured by Dual-energy X-ray absorptiometry (DXA), which is the only technology for classifying BMD according to the criteria established by WHO., Results: A total of 51 patients, with an average number of 7 years with OCS treatment, were enrolled. During the last 12 months, the mean number of OCS courses was 2.76, and the total mean intake was 891 mg of Prednisone equivalents. According to the T-scores, 17 patients were measured to have ≤-1 SD T-score lumbar spine, which is considered to be osteopenia, and five patients had <-2.5 SD T-score, considered as osteoporosis. However, when taking age and gender into account and analysing the Z-scores, only 2 patients had a reduced density of the spine and none in the hip, which is no difference compared to a matched Swedish population., Conclusions: This prospective study shows that 2-3 moderate courses of OCS annually may be used without high risk of causing osteopenia/osteoporosis in patients with CRSwNP., (© 2019 John Wiley & Sons Ltd.)

Objectives: Gastroesophageal reflux recommended treatment (dose and duration) with proton-pump inhibitor (PPI) compared to placebo significantly reduces the signs and symptoms of laryngopharyngeal reflux (LPR) and comorbid chronic rhinosinusitis (CRS)., Design: Double-blind randomised placebo-controlled trial., Setting: Eight weeks of treatment with omeprazole 20 mg once daily (OD)., Participants: Sixty patients (28 women, aged 19-87 years) with diagnosed LPR and comorbid CRS., Main Outcome Measures: Significant reduction in signs and symptoms (reflux symptom index (RSI) score as subjective, and reflux finding score (RFS) as objective measure) of LPR after 8 weeks of treatment with omeprazole 20 mg OD when compared to placebo. Secondary objectives were significant reduction in signs and symptoms of comorbid CRS after 8 weeks of treatment with omeprazole 20 mg OD when compared to placebo and the association of the severity of signs and symptoms of LPR with the ones of CRS., Results: RSI and RFS decreased significantly more in the active treatment group after 8 weeks compared to placebo (P < .001 for both). CRS and endoscopy scoring decreased both significantly more in the active group after 8 weeks compared to placebo (P < .001 for both). CRS scoring significantly correlated with RSI (R = 0.312, P = .015) but not with RFS (R = 0.199, P = .127)., Conclusions: The results of our trial suggest that omeprazole 20 mg OD for 8 weeks was effective in reducing signs and symptoms of both LPR and CRS, although in most patients still present at the end of the trial., (© 2017 John Wiley & Sons Ltd.)

Background: Chronic rhinosinusitis is a very common inflammatory disease that impairs quality of life and is associated with high healthcare spending. Chronic rhinosinusitis treatment commonly involves the use of intranasal corticosteroids, oral antibiotics, and surgery. Macrolides have been identified as a potential treatment option for chronic rhinosinusitis due to their immunomodulatory effects; however, the evidence supporting their use is still conflicting., Objective: The purpose of this systematic review was to evaluate new evidence along with previously reported studies of the use of macrolides in the treatment of chronic rhinosinusitis., Search Strategy: Medline, EMBASE, Cochrane CENTRAL, LILACS, clinicaltrials.gov, and the International Clinical Trials Registry Platform were all searched (until June 2015 Medline and EMBASE searches were updated January 2016). Randomised controlled trials comparing low-dose macrolide antibiotics versus placebo, as an adjunct to other therapies, or low-dose macrolide therapy alone versus other therapies were included in this review., Evaluation Method: Quality of the evidence was evaluated using the Cochrane risk of bias tool. Continuous outcomes were expressed as mean differences or standardised mean differences with 95% confidence interval. Data were pooled using fixed-effects models., Results: Nine randomised controlled trials met the inclusion criteria. Studies were classified into three distinct comparisons: Low-dose macrolide therapy vs. placebo, low-dose macrolide +/- nasal steroids vs. nasal steroid and low-dose macrolides vs. other therapies. The overall quality of the evidence is low due to limitations in study design, imprecision, and indirectness., Conclusions: Positive results were seen with the use of macrolide therapy in the postoperative period in patients with nasal polyps. A firm conclusion with respect to the effectiveness of the use of macrolides for the treatment of chronic rhinosinusitis cannot be reached based on the available evidence. Further study using a placebo-controlled design evaluating the use of macrolides in clearly defined chronic rhinosinusitis populations is needed., (© 2016 John Wiley & Sons Ltd.)

Objectives: There is currently conflicting level 1 evidence in the use of long-term antibiotics for chronic rhinosinusitis without nasal polyps. The primary aim of this feasibility study was to optimise future randomised trial design by assessing recruitment and retention of patients alongside providing preliminary data on symptomatic control., Design: Prospective, multicentre feasibility (cohort) study with all patients receiving macrolide therapy for 12 weeks and a further subsequent 12-week follow-up. Participants received a 12-week course of clarithromycin 250 mg alongside twice daily topical mometasone and nasal douching. Primary outcomes focused on recruitment, retention and compliance. Clinical and quality-of-life outcomes measures were also recorded., Setting: Patients were prospectively recruited from six UK outpatient clinics., Participants: Adult patients with chronic rhinosinusitis without nasal polyps and no prior endoscopic sinus surgery underwent baseline assessment and then follow-up at 3 and 6 months., Main Outcome Measures: Six-month recruitment and retention data., Results: Over 13 months, 55 adults were recruited from five centres. Four patients declined participation. 75% of patients were retained within the study. Dropouts included one medication contraindication, three unable to tolerate medication and 10 not attending full follow-up. Sino Nasal Outcome Test-22 and endoscopic scores showed statistically significant improvement. No other clinical or quality-of-life assessment improvements were seen., Conclusion: Retention and recruitment to a trial using long-term clarithromycin to treat chronic rhinosinusitis without nasal polyps is achievable and this data will support a future randomised controlled trial. The study provides vital insight into trial design, thus informing UK research networks and rhinology researchers internationally., (© 2016 John Wiley & Sons Ltd.)

Background: The incidence of sleep-related breathing disorders is correlated with lower and upper airway inflammatory diseases, such as asthma and allergic rhinitis. We hypothesized that corticosteroids treatment would lead to a greater reduction in disease severity in obstructive sleep apnoea syndrome (OSAS) patients with concomitant allergic rhinitis vs. non-allergic OSAS patients by reducing the level of inflammation in upper airway tissues., Objective: This study was performed to determine whether treatment with intranasal corticosteroids could reduce upper airway inflammation and improve sleep parameters in obstructive sleep apnoea syndrome patients with or without concomitant allergic rhinitis., Methods: Obstructive sleep apnoea syndrome patients with (n = 34) or without (n = 21) documented allergic rhinitis voluntarily enrolled in the study and were assessed at baseline and after corticosteroids treatment for 10-12 weeks. Sleep studies were performed and biopsies were obtained from the inferior turbinate, nasopharynx, and uvula. The apnoea-hypopnoea index, sleep quality, and level of daytime alertness were determined, and immunocytochemistry was used to phenotype tissue inflammation., Results: Standard sleep indices improved following treatment in the entire cohort of obstructive sleep apnoea syndrome patients, with greater improvement seen in the allergic rhinitis group. Allergic rhinitis patients demonstrated significantly improved O2 saturation and a lower supine apnoea-hypopnoea index score after corticosteroid treatment; similar improvements were not seen in the non-allergic rhinitis group. Eosinophilia was detected at all three sites in the allergic rhinitis group, but not in the non-allergic rhinitis group. Following treatment, fewer eosinophils and CD4 lymphocytes were documented at all three biopsy sites in the allergic group; the reduction in inflammation was less apparent in the non-allergic rhinitis group., Conclusion: This study has provided important molecular and clinical evidence regarding the ability of corticosteroids to reduce upper airway inflammation and improve obstructive sleep apnoea syndrome morbidity patients with concomitant allergic rhinitis., (© 2013 John Wiley & Sons Ltd.)

In 2010 over 200 articles were published in Clinical and Experimental Allergy including editorials, reviews, opinion articles, letters, book reviews and of course at the heart of the journal, papers containing original data which have moved the field of allergy forward on a number of fronts. For the third year running the editors felt it would be of value to summarize the key messages contained in these papers as a snapshot of where the cutting edge of research into allergic disease is leading. We have broadly followed the sections of the journal, although this year the mechanistic articles are grouped together and the studies involving experimental models of disease are discussed throughout the paper. In the field of asthma and rhinitis phenotypes and biomarkers continue to a major pre-occupation of our authors. There is continued interest in mechanisms of inflammation and disordered lung function with the mouse model of asthma continuing to offer new insights. There is also a steady flow of papers investigating new therapies, including those derived from plants and herbs, although many are mechanistic with too few high quality clinical trials. The mechanisms involved in allergic disease are well covered with many strong papers using clinical material to ask relevant questions. Pro-pre and snybiotics continue to be of major interest to our authors and this remains a controversial and complicated field. The discipline of epidemiology has retained its interest in risk factors for the development of allergic disease with a view to refining and debating the reasons for the allergy epidemic. There is continued interest in the relationship between helminthic disease and allergy with a new twist in 2010 involving studies using infection with helminths as a potential treatment. The genetics of allergic disease continues to be very productive, although the field has moved on from only investigating single nucleotide polymorphisms of candidate genes to Genome Wide Association Studies and an increasing and welcome emphasis on gene-environment interactions. In the field of clinical allergy there is steady flow of papers describing patterns of drug allergy with renewed interest in reactions to contrast media, but food allergy is the major area of interest in this section of the journal. Lastly in the field of allergens there is a growing interest in the role of component resolved diagnosis in improving the diagnosis and management of allergic disease. Another excellent year, full of fascinating and high quality work, which the journal has been proud to bring to the allergy community., (© 2011 Blackwell Publishing Ltd.)

Objectives: To retrospectively review the first treatment response of dogs with mycotic rhinosinusitis to commonly utilised treatment techniques., Methods: Medical records of dogs treated for mycotic rhinosinusitis were obtained retrospectively via a manual review of the clinical databases of six veterinary referral centres for the period of January 1998 to June 2008, and first treatment outcome was evaluated. Historical and clinicopathological findings were also reviewed to evaluate their impact on treatment success or failure., Results: There was no significant difference in first treatment outcome between treatment groups (P=0.21). When all topical treatments were considered together (n=85), 39 dogs (45.8%) had a successful first treatment. Initial treatment success was associated with a younger age (56.3 versus 75.8 months; P=0.02) and was 2.7 times more likely in dogs with unilateral disease, although this was not significant (P=0.07). Adjunctive therapy with systemic antifungal agents was associated with treatment failure (P< or =0.01). Fifty-nine dogs (69.4%) responded successfully following multiple treatments., Clinical Significance: Treatment of mycotic rhinosinusitis remains challenging, and multiple treatments are frequently required for adequate treatment. Reasons for first treatment failure are likely multifactorial in origin, making it difficult to predict those dogs that are likely to have a superior prognosis, regardless of the treatment type used.

This guidance for the management of patients with rhinosinusitis and nasal polyposis has been prepared by the Standards of Care Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI). The recommendations are based on evidence and expert opinion and are evidence graded. These guidelines are for the benefit of both adult physicians and paediatricians treating allergic conditions. Rhinosinusitis implies inflammation of the nose and sinuses which may or may not have an infective component and includes nasal polyposis. Acute rhinosinusitis lasts up to 12 weeks and resolves completely. Chronic rhinosinusitis persists over 12 weeks and may involve acute exacerbations. Rhinosinusitis is common, affecting around 15% of the population and causes significant reduction in quality of life. The diagnosis is based largely on symptoms with confirmation by nasendoscopy. Computerized tomography scans and magnetic resonance imaging are abnormal in approximately one third of the population so are not recommended for routine diagnosis but should be reserved for those with acute complications, diagnostic uncertainty or failed medical therapy. Underlying conditions such as immune deficiency, Wegener's granulomatosis, Churg-Strauss syndrome, aspirin hypersensitivity and allergic fungal sinusitis may present as rhinosinusitis. There are few good quality trials in this area but the available evidence suggests that treatment is primarily medical, involving douching, corticosteroids, antibiotics, anti-leukotrienes, and anti-histamines. Endoscopic sinus surgery should be considered for complications, anatomical variations causing local obstruction, allergic fungal disease or patients who remain very symptomatic despite medical treatment. Further well conducted trials in clearly defined patient groups are needed to improve management.

The mainstay of treatment of chronic rhinosinusitis is through the administration of topical nasal drugs. The delivery and intranasal distribution of these is therefore of potential clinical significance. Until there is progress in the nasal drug distribution assessment methodology, it will be difficult to improve topical nasal drug delivery, which is known to be suboptimal in many ways. This study reviews intranasal drug delivery assessment methods, the present knowledge and explores future directions for research.

Background: Leukotrienes (LTs) appear to be crucial mediators of aspirin (ASA)-induced lower respiratory tract reactions. Therefore, it is logical to assume that leukotriene-modifier drugs (LTMDs) might block these reactions., Objective: The aim of this study was to determine whether concomitant treatment with LTMDs was associated with a reduction of ASA-provoked lower respiratory tract reactions in patients with aspirin-exacerbated respiratory disease (AERD), when compared to AERD patients who were not treated with LTMDs. Secondly, if ASA-induced lower respiratory tract reactions were prevented in LTMD-treated patients, was there then a higher prevalence of upper respiratory reactors or, alternatively, a higher prevalence of blocked reactions ('non-reactors') in this group., Methods: Of 271 patients suspected by history of having AERD, 96 were taking cys-LT receptor antagonists (cys-LTRAs) and 12 were taking zileuton at the time of oral ASA challenges. A matched control group of 163 patients was not receiving LTMDs. All subjects underwent standard oral ASA challenges. Reactions were classified as follows: classic [naso-ocular combined with a 20% or > decline in forced expiratory volume of 1 s (FEV1)]; pure lower (20% or > decline in FEV1 without naso-ocular); partial asthma (naso-ocular + 15-20% decline in FEV1); upper only (naso-ocular with < 15% decline in FEV1); negative (no reactions)., Results: In patients treated with cys-LTRAs, there were significant reductions in numbers of patients with ASA-induced bronchospastic reactions and a concomitant increase in upper respiratory reactors. There were no significant differences in mean provoking doses of ASA or the percent changes in FEV1 values in both groups. In the 12 patients receiving zileuton, no reactions to ASA (16%) were similar to the cys-LTRA-treated group (11%) and the control group (15%)., Conclusion: During oral ASA challenges, LTMD treatment appeared to shift target organ responses from both upper and lower respiratory tracts to upper tract alone. LTMD blocking of the entire respiratory tract did not appear to occur.

Steroid nose drops are used frequently to treat rhinosinusitis and nasal polyposis. The middle meatal area is of key importance in the pathophysiology of these conditions. This study assesses which of three head positions commonly used to instil nose drops resulted in the highest coverage of this area. Discomfort levels were also studied using a visual analogue scale for each position. Five volunteers were studied in: (i) head back (HB); (ii) head forward and down (HFD); and (iii) lying head back (LHB) positions. Betamethasone nose drops, dyed with fluorescein, were instilled into each nostril and the distribution was studied endoscopically. The middle meatus area distribution was highest in the LHB position (55.51%), followed by HFD (31.55%) and HB (6.87%) positions. Comparison of distribution between HB and LHB (P = 0.002) and between HB and HFD (P = 0.045) was statistically significant. The HFD position was most uncomfortable (mean discomfort score 8.8) whereas the HB (2.4) and LHB (2.6) were similar. The LHB would, therefore, appear to be the most suitable position for instillation of steroid nose drops.

Pregnancy rhinitis is a common condition with longstanding nasal congestion; troublesome for the mother, possibly also affecting the fetus. There is need for a safe, effective treatment. Nasal corticosteroids, indisputable in other types of rhinitis, have not been evaluated in pregnancy rhinitis. In this placebo-controlled, randomized, double-blind study with parallel groups, we evaluated the effect of 8 weeks of treatment with fluticasone propionate aqueous nasal spray in 53 women with pregnancy rhinitis. Daily symptom scores and nasal peak expiratory flow, as well as acoustic rhinometry before and after treatment, did not show any difference between the groups. Placebo resulted in 6/27 responders, compared with 5/26 for active treatment. There was no detectable influence on maternal cortisol as measured by morning S-cortisol and overnight 12-h-U-cortisol, or any difference in ultrasound measures of fetal growth or pregnancy outcome. Altogether, our study indicates no significant effects of the treatment described here.

Background: Specific immunotherapy is the only currently available allergen-orientated treatment able to modify the natural history of respiratory allergic diseases. Safety and clinical efficacy of this treatment are well documented, but evidence about the ability to reduce new sensitizations is still poor., Objective: We report a retrospective study conducted in order to assess the prevention of new sensitizations in monosensitized subjects treated with specific immunotherapy vs. monosensitized patients treated with anti-allergic drugs., Methods: 8396 monosensitized patients with respiratory symptoms were selected according to an open, retrospective design. Group A included 7182 patients submitted to specific immunotherapy (and anti-allergic drugs when needed) for 4 years and then treated with drugs for at least 3 years. Group B included 1214 patients treated only with drugs for at least 7 years. All patients underwent prick test with a standard panel of allergens and total and specific IgE determination before and after 4 years of treatment and again 3 years later., Results: Groups were well balanced. Polysensitized subjects were 23.75% in Group A and 68.03% in Group B after 4 years (P < 0.0001) and 26.95% and 76.77%, respectively, after 7 years (P < 0.0001). Asthmatic subjects were more prone to develop polysensitization in comparison to subjects suffering only from rhinitis (32.14% instead of 27.29% after 4 years, 36.5% instead of 31.33% after 7 years; P < 0.0001). Specific IgE decreased by 24.11% in Group A and increased by 23.87% in Group B (P < 0.0001). Total IgE decreased by 17.53% in Group A and increased by 13.71% in Group B (P < 0.0001)., Conclusions: Specific immunotherapy was observed retrospectively to reduce new sensitizations in monosensitized subjects suffering from respiratory allergic diseases.

Adrenocortical suppression is a well-known risk of systemic steroids, but is thought less likely to occur with topical intranasal corticosteroids. However, the UK Committee on the Safety of Medicines (UKCSM) has expressed concern about the possibility of this complication. We assessed the prevalence of adrenal suppression in patients with rhinitis using intranasal beclomethasone and betamethasone; and the potential value of salivary cortisol as a tool for detecting this complication. Sixty-six patients (38 men: 28 women; mean age 49.6[SD 16.0] years) were prospectively screened for adrenal insufficiency using clinical assessment and salivary cortisol measurements. Abnormalities at this initial screening were confirmed with a Short Synacthen Test (SST). No patient was clinically Cushingoid. All 22 beclomethasone users had normal salivary cortisols. Eleven (25%) of 44 patients using betamethasone had subnormal salivary cortisol levels (mean morning cortisol 2.8[SD 0.9]nmol/l) suggesting adrenal suppression, which was confirmed by an impaired SST in each case. The positive predictive value of salivary cortisol measurements was 100%. Only patients with abnormal salivary cortisols had a SST, so no comment can be made about sensitivity/specificity. Topical betamethasone may produce occult adrenal insufficiency and assessment of adrenal function is recommended in these patients. Measurement of salivary cortisol is a useful, non-invasive and economical test for monitoring patients using intranasal corticosteroids.

Background: Nonallergic rhinitis with eosinophilia (NARES), accounting for some 15% of perennial rhinitis, is a nasal disorder whose main features are eosinophil counts in nasal smear higher than 10% and negative IgE tests. The mainstay of treatment is topical corticosteroids., Objective: To evaluate the adjunctive effect of loratadine, a non-sedating antihistamine with anti-allergic activity, on nasal symptoms and eosinophil counts in nasal secretions in patients with NARES., Methods: Thirty patients with NARES were divided in two groups, half receiving flunisolide two 25 microg puffs per nostril morning and night plus loratadine 10 mg u.i.d. and half the same doses of flunisolide plus placebo, according to a double-blind fashion, for 3 weeks. The effectiveness of the treatment in the two groups was evaluated by comparing symptom scores and eosinophil counts, and safety was assessed by comparing the adverse effects., Results: The loratadine treated group had better results both in nasal symptoms, with a decrease in sneezing (P < 0.000001) and rhinorrhoea (P < 0.006), respectively, corresponding with 73.4% and 66.7% with respect to 46.6% and 26.7% in the control group, and in eosinophil counts which decreased by 20% compared with 14.3% in patients treated with placebo and flunisolide. As to safety, only nasal irritation in two patients, one in each group, was reported., Conclusion: Loratadine improves the effectiveness of flunisolide in treatment of NARES with no change in safety, and with no sedation.

H1 antihistamines are widely used in the treatment of conditions such as seasonal and perennial allergic rhinitis, urticaria and angioedema, as well as being an adjunct therapy for anaphylaxis. The development of new compounds within this class of pharmacological agents is based on preclinical and clinical assessments prior to registration. Preclinical assessment of novel compounds has been advanced both by the definition of the molecular structure of the H1 receptor and by high throughput screening, which allows the definition of potent and selective candidate compounds. The elimination, in subsequent evaluations, of those compounds with potential for central nervous system and cardiotoxic effects and those with inappropriate pharmacokinetics restricts the subsequent toxicological and clinical evaluation of novel H1 antihistamines. Clinical evaluation is based initially on human volunteer studies to define pharmacodynamic, pharmacokinetic and safety parameters. Local challenge models such as in the skin or nose for oral therapy or nose and conjunctiva for topical drug development allow definition of potential dose for administration, speed of onset of activity and duration of effect, both in comparison to placebo and to reference compounds. While a range of laboratory allergen challenge models, pollen chamber challenge studies and acute 'day in the park' study designs have been used in the early clinical evaluation of H1 antihistaminic activity, ultimately it is the efficacy of novel compounds in naturally occurring disease that is of importance. The assessment of the magnitude and profile of clinical disease improvement in specific disease areas is thus the crucial evaluation. The appropriate selection and characterization of patients, the optimization of the trial design, dependent upon the nature of the disease, and the appropriate selection of endpoints for analysis are thus critical considerations, as well as evaluation of appropriate safety criteria.

Background: Capsaicin has been shown previously to reduce nasal complaints in patients with a non-allergic non-infectious perennial rhinitis. Proposed pathophysiological mechanisms for non-allergic non-infectious perennial rhinitis include a chronic inflammatory disorder of an antigenic or neurogenic nature as well as the possibility of a functional neuronal disorder. We hypothesized that the beneficial effect of capsaicin might be the result of a down-regulation of inflammation (by a reduction of inflammatory cells) or through modulation of neural tissue density., Methods: Patients were treated with either a placebo or capsaicin spray solution delivering 0.15 mg of capsaicin per nostril once every second or third day for a total of seven treatments. Both sides were treated each visit. Biopsies were taken before and 2 weeks, 3 months and 9 months after the treatment period. Immunohistochemical staining of the biopsy specimen was performed to ascertain the effect of treatment on immunocompetent cell densities (quantitative) and neural tissue densities (semi-quantitative) in the nasal mucosa., Results: Nasal complaints were significantly reduced in the capsaicin-treated group. The number of CD1+, CD25+, CD3+, CD68+, BMK13+, IgE+, tryptase+, and chymase+ cells did not significantly differ between capsaicin and placebo group. No significant differences between both groups were found in pan-neurogenic staining of nasal mucosa using neurofilament and synaptophysine., Conclusion: Capsaicin aqueous nasal spray has previously been shown to reduce nasal complaints without affecting cellular homeostasis or overall neurogenic staining up to 9 months after treatment. Immunocompetent cells are not involved in non-allergic non-infectious perennial rhinitis.

The association of rhinitis and asthma in the same patient is frequent and requires an appropriate treatment strategy. Several studies have investigated the effect of antirhinitis treatment on concurrent asthma symptoms and pathophysiology. Most of these studies have been performed in patients with seasonal allergic rhinitis and asthma. Treatment with intranasal corticosteroids during the pollen season decreases asthma symptoms and prevents the increase in non-allergic bronchial hyperresponsiveness in patients with a combination of rhinitis and asthma symptoms. This treatment also inhibits the increase in bronchial hyperresponsiveness in patients with rhinitis symptoms alone. The observation that treatment with intranasal corticosteroids reduces non-allergic bronchial hyperresponsiveness in patients with rhinitis is remarkable and will stimulate thought about the mode of action of these drugs. Intranasal sodium cromoglycate has also been studied and, although effective, has been shown to be less effective than intranasal corticosteroids in controlling the accompanying asthma symptoms in patients with seasonal allergic rhinitis and asthma. Treatment with antihistamines also reduced the symptoms of rhinitis and asthma during the pollen season. However, the optimal therapy for patients with a history of seasonal allergic rhinitis and asthma remains to be established. Few data are available on the effect of treatment for perennial allergic rhinitis on perennial asthma. The rather frequent combination of rhinitis and asthma therefore warrants further study.

The inflammatory response that results in allergic rhinitis and asthma is complex and involves numerous cell types, such as lymphocytes, mast cells, and eosinophils, and mediators, such as histamine, arachidonic acid metabolites, toxic proteins, and cytokines. Therefore, many different classes of pharmacological agents, acting at various discrete points, can influence the symptoms induced by this process. The various classes of agents include antihistamines, decongestants, anticholinergics, leukotriene antagonists, beta-adrenoceptor agonists, theophylline, sodium cromoglycate and corticosteroids. In this article the mechanism of action of each of these classes is discussed, together with their use in allergic rhinitis and asthma.

Background: The risk of suppression of hypothalamic-pituitary-adrenal (HPA) function in children on topical glucocorticosteroids is currently much debated., Objective: To review data on HPA function in children with asthma and rhinitis on topical glucocorticosteroids, and to discuss the value of HPA function measures in clinical practice and research., Method: A review of peer refereed data., Results/conclusions: There is no evidence that insufflated or inhaled glucocorticosteroids in recommended doses have ever caused clinically significant HPA insufficiency in any child. Using sensitive measures of basal adrenal activity, however, several studies have found suppressive effects with specific drugs, high doses and application systems. These observations may represent homeostatic diminution in endogenous cortisol. Such measures have no place in the management of children on topical glucocorticosteroids, but may be useful in clinical trials assessing systemic activity of administration regimens and application devices. In children growth suppression seems to the most important adverse effect of topical glucocorticosteroids.

Background: Several authors described capsaicin, the pungent substance in red pepper, as an efficacious therapy for non-allergic non-infectious perennial rhinitis (NANIPER). Repeated capsaicin application induces peptide depletion and specific degeneration of the unmyelinated sensory C-fibres in the nasal mucosa., Methods: We performed a placebo-controlled (NaCl 0.9%) study with 25 NANIPER patients. Daily record charts and visual analogue scales (VAS) were used for clinical evaluation. Nasal lavages were obtained before, during, and after treatment., Results: There was a significant and long-term reduction in the VAS scores in the capsaicin group. No significant difference was found between the placebo and capsaicin treated groups for the mean group concentrations of leukotriene (LT) C4/D4/E4, prostaglandin D2 (PGD2), and tryptase. The levels of mast cell mediators, tryptase and PGD2, and leukotrienes, mediators derived from a variety of inflammatory cells, were low at baseline and comparable with levels observed in nasal lavages obtained from normals., Conclusion: As involvement of inflammation could not be demonstrated, it is not surprising that capsaicin has no effect on inflammatory mediators. This suggests that inflammatory cells do not play a major part in the pathogenesis of NANIPER.

Background: Controversy still exists about the treatment of rhinitis medicamentosa and treatment has never been objectively evaluated., Objective: To study the effect of fluticasone propionate aqueous nasal spray compared to placebo nasal spray in the treatment of rhinitis medicamentosa., Methods: A parallel randomized, double-blind study was conducted to evaluate the treatment of rhinitis medicamentosa. Two groups containing 10 patients with rhinitis medicamentosa in each group stopped their overuse of nasal vasoconstrictor spray immediately and were treated with either fluticasone propionate nasal spray once daily 200 micrograms, or placebo nasal spray for 14 days. The nasal mucosal swelling was recorded with rhinostereometry, acoustic rhinometry and a peak inspiratory flow meter. Nasal stuffiness was estimated on a visual analogue scale in the morning and in the evening of each day., Results: The mucosal swelling decreased after 7 and 14 days of treatment with fluticasone propionate as well as placebo, but the reduction was significantly greater after treatment with fluticasone propionate. The symptom scores for nasal stuffiness showed a marked reduction during the treatment period in both groups, but there was a faster onset of symptom reduction after treatment with fluticasone propionate., Conclusion: Fluticasone propionate is more effective and has a faster onset of action than placebo in the treatment of rhinitis medicamentosa. An adequate treatment of these patients consists of a combination of vasoconstrictor withdrawal and a topical corticosteroid to alleviate the withdrawal process.

Objective: Chronic middle ear disease is common in Aboriginal children, and may be linked to nasal inflammation and Eustachian tube dysfunction. The pattern of nasal inflammation is unknown. The study reported here was performed to define the role of allergy and infection in causing nasal inflammation in Aboriginal children with chronic middle ear disease., Methodology: Thirty-one Aboriginal children aged between 3 and 7 years underwent clinical assessment, audiometry and allergy skin tests. Nasal swabs for bacterial culture and cytology were performed during the winter and again in spring to identify any seasonal variation. A randomized trial of nasal beclomethasone for 8 weeks was conducted in children with abnormal tympanometry to identify the effect of therapy upon nasal cytology., Results: Twenty-six of the 31 children had abnormal tympanograms. Average hearing levels were reduced in nine children. Pathogenic organisms were isolated from most children: Streptococcus pneumoniae (82%), Haemophilus influenzae (79%), Moraxella catarrhalis (39%) and Staphylococcus aureus (29%). Eight of the 31 children (26%) were atopic. Nasal cytology disclosed a marked neutrophil infiltrate (80% of cells) during the winter, which fell significantly in spring to 52% of cells. Only two subjects had nasal eosinophilia of >10%. There was no effect of beclomethasone on nasal cytology., Conclusions: Chronic ear disease in Aboriginal children is associated with nasal inflammation, neutrophil infiltration and the presence of bacteria. These features suggest respiratory infection as the main cause of chronic nasal inflammation in Aboriginal children with middle ear disease. There is a seasonal variation in the severity of the nasal infiltrate, consistent with increased infections during winter. Despite a high prevalence of atopy, allergic nasal disease was uncommon.

Background: Fluticasone propionate is a new potent, topically active corticosteroid with negligable oral bioavailability. Data on its comparative efficacy in perennial allergic and non-allergic rhinitis are limited., Objective: To compare the efficacy and safety of fluticasone propionate aqueous nasal spray (FPANS) 200 micrograms once or twice daily with beclomethasone dipropionate aqueous nasal spray (BPD) 200 micrograms twice daily and placebo in patients with allergic and non-allergic perennial rhinitis., Methods: The 12-week study had a multicentre, double-blind, randomized, parallel group design. Efficacy was assessed from symptom scores recorded on daily diary cards., Results: FPANS 200 micrograms once or twice daily was significantly better than placebo but not better than BDP in relieving the nasal symptoms of rhinitis. FPANS at either dose was equally effective in the treatment of allergic and non-allergic perennial rhinitis. There were few adverse events and no treatment-related abnormalities in laboratory measurements in either FPANS-treated group. Comparison between treatment groups indicated that FPANS was as well tolerated as placebo and BDP at the doses studied., Conclusions: In the majority of patients FPANS 200 micrograms once daily in as effective as BDP 200 micrograms twice daily in the relief of perennial allergic rhinitis.

Intranasal budesonide and beclomethasone dipropionate (BDP), each administered as aqueous, aerosol formulations at dosages of 200 micrograms twice a day, morning and evening, were compared over a 3-week period in a randomized, parallel group study of 88 adults with seasonal allergic rhinitis. Budesonide treatment produced significantly lower mean symptom scores for the whole study compared with BDP for runny nose, itchy nose and sneezing (P < 0.05). The difference in nasal symptom scores produced by budesonide in comparison with BDP was particularly great towards the end of the treatment period. The budesonide-treated group also had lower scores for nasal blockage and two eye symptoms (runny and sore eyes), but the differences noted were not significant. Adverse events recorded by both groups were mild and transient. In conclusion, aqueously administered budesonide is likely to be of more clinical value than BDP for the control of seasonal allergic rhinitis.

Intranasal fluorocarbon anticholinergic agents have been used to treat the nasal hypersecretion of perennial non-allergic rhinitis, but chronic use has been restricted either due to the potential for systemic anticholinergic adverse events or due to the irritating properties of the fluorocarbon metered dose formulations. This study evaluates a new aqueous nasal formulation of ipratropium bromide (Atrovent Nasal Spray 0.03%) in subjects with perennial non-allergic rhinitis in a double-blind, placebo-controlled trial. Two hundred and twenty-eight patients were randomized to receive two sprays per nostril of either ipratropium bromide (42 micrograms/nostril) or placebo-administered three times a day as an aqueous nasal spray over an 8-week interval. Patients were evaluated bi-weekly and maintained daily diaries for duration and severity of nasal symptoms. Ipratropium bromide reduced the mean severity and duration of rhinorrhoea within the first week and throughout the 8 weeks of active treatment compared with placebo (P < 0.05). Secondary endpoints of efficacy (patient and physician global assessments and a quality of life assessment) also supported the use of ipratropium bromide nasal spray for rhinitis symptom control. With the reduction in rhinorrhoea by the ipratropium bromide nasal spray, patients reported a marked improvement in daily moods vs placebo (P < 0.01). Both placebo and ipratropium bromide nasal spray induced a modest reduction of nasal congestion, sneezing and postnasal drip. This improvement in these other nasal symptoms was consistent with the known soothing effects of a nasal saline vehicle. There were no drug-related serious or systemic anticholinergic adverse events.(ABSTRACT TRUNCATED AT 250 WORDS)

Nasal instillation of bradykinin elicits many of the characteristic features of rhinitis. To assess the relevance of histamine release from metachromatic cells and the activation of cholinergic pathways, we investigated the effects of terfenadine, a histamine H1-receptor antagonist, and ipratroprium bromide, a selective antimuscarinic agent, on bradykinin induced rhinorrhoea, nasal airways resistance (NAR), nasal pain and plasma protein leakage. Oral terfenadine (120 mg) or matched placebo and nasal ipratropium bromide (80 micrograms) or matched placebo were administered at 4 hr and 30 min respectively prior to bradykinin nasal challenge in two randomized, double-blind and cross-over studies on eight non-rhinitic subjects. Thus subjects received either double-placebo, oral terfenadine and nasal placebo, oral placebo and nasal ipratopium bromide or oral terfenadine and nasal ipratropium bromide, as pretreatment. Bradykinin challenge induced mean maximal increases of 57%, 59%, 77% and 72% in NAR on the placebo, terfenadine, ipratropium bromide and terfenadine plus ipratropium bromide pretreatment days respectively. These increments were not significantly different. Similarly rhinorrhoea and nasal pain induced by bradykinin nasal challenge were not significantly different on the four challenge days. Bradykinin nasal challenge caused a mean maximal increase in albumin levels in recovered nasal lavages of 11.5, 13.0, 12.2 and 12.3 times of baseline levels on the placebo, terfenadine, ipratropium bromide and terfenadine plus ipratroprium bromide pretreatment days respectively. Similarly total protein levels achieved a mean maximal increase of 8.0, 8.2, 7.9 and 8.8 times of baseline levels on these challenge days. The increments in both albumin and total protein did not significantly differ on the 4 challenge days.(ABSTRACT TRUNCATED AT 250 WORDS)