Fluticasone Proprionate Research Articles

FLUTICASONE FUROATE AND VILANTEROL (FF/VI) VERSUS FLUTICASONE PROPRIONATE AND FORMOTEROL (FP/FM) AS MAINTENANCE THERAPY IN STABLE ASTHMATIC PATIENTS- A COMPARATIVE STUDY

Background: Fluticasone furoate (FF) is a novel long-acting inhaled corticosteroid (ICS). Vilanterol (VI) is a long‐acting beta2‐agonist (LABA) that binds to the beta2‐adrenoceptor on the airway smooth muscle, producing bronchodilation. The corticosteroid fluticasone propionate (FP)and the long-acting β₂-adrenoceptor agonist (LABA) formoterol fumarate (FM) have been combined in a single, pressurized, metered-dose, aerosol inhaler for the maintenance treatment of patients aged ≥12 years with persistent asthma.This study evaluated the efficacy and safety of Fluticasone furoate 100 mcgandVilanterol 6 mcg versus Fluticasone proprionate 250 mcg and Formoterol 25 mcg for 12 weeks in patients with persistent asthma as maintenance therapy. Methods and Materials: A hospital based comparative study was conducted among stable asthmatic patients attended to Santhiram Medical College and General Hospital, Nandyal during January 2024 to June 2024(6months) by using convenient sampling method with sample size 60. Study tool was pre-designed, pre-tested, asthma control questionnaire5 (ACQ5),asthma control test (ACT) and Ask 12 adherence barrier survey. Results: Among 60 patients, 30 patients (Group1) were given Fluticasone furoate and Vilanterol and another 30 patients (Group 2) were given Fluticasone proprionate and Formoterol. All the patients (both the treatment groups) completed the 12 weeks treatment period. Improvements from baseline in 0- to 24-h wmFEV1 were observed with both FF/VI (376 mL) and FP/FM (353 mL) the adjusted mean treatment difference was not statistically significant. There were no differences between 0- to 4-h serial wmFEV1, asthma control test, ACQ5 and Ask 12 adherence barrier survey. There was no difference in reported exacerbations between treatments. Adverse events reported in the present study were not significant. Both treatments were well tolerated. Conclusion: The present study shows that the efficacy of once daily Fluticasone furoate and Vilanterol was not inferior as compared to the efficacy of twice daily Fluticasone proprionate and Formoterol as maintenance therapy in stable asthmatic patients. Howevertreatment with once daily FF/VI has the advantage of forgetfulness and inconvenience of inhalation.Henceonce daily FF/VI can be also useful for stable asthmatic patients as maintenance therapy as FF/VI DPI treatment.

Effects of Fluticasone Propionate on Klebsiella pneumoniae and Gram-Negative Bacteria Associated with Chronic Airway Disease.

Inhaled corticosteroids (ICS) are commonly prescribed first-line treatments for asthma and chronic obstructive pulmonary disease (COPD). Recent evidence has shown that ICS use is associated with changes in the airway microbiome, which may impact clinical outcomes such as potential increased risk for pneumonia in COPD. Although the immunomodulatory effects of corticosteroids are well appreciated, whether ICS could directly influence the behavior of respiratory tract bacteria has been unknown. In this pilot study we explored the effects of fluticasone proprionate, a commonly prescribed inhaled corticosteroid, on respiratory bacteria with an expanded focus on Klebsiella pneumoniae, a species previously implicated in fluticasone-associated pneumonia in COPD. We observed significant effects of fluticasone proprionate on growth responses of K. pneumoniae, as well as other bacterial species isolated from asthmatic patients. Fluticasone-exposed K. pneumoniae displayed altered expression of several bacterial genes and reduced the metabolic activity of bronchial epithelial cells and their expression of human β-defensin 2. Targeted assays identified a fluticasone metabolite from fluticasone-exposed K. pneumoniae cells, suggesting this species may be capable of metabolizing fluticasone proprionate. Collectively, these observations support the hypothesis that specific members of the airway microbiota possess the functional repertoire to respond to or potentially utilize corticosteroids in their microenvironment. These findings lay a foundation for novel research directions into the potential direct effects of ICS, often prescribed long term to patients, on the broader airway microbial community and on the behavior of specific microbial species implicated in asthma and COPD outcomes. IMPORTANCE Inhaled corticosteroids are widely prescribed for many respiratory diseases, including asthma and COPD. While they benefit many patients, corticosteroids can also have negative effects. Some patients do not improve with treatment and even experience adverse side effects. Recent studies have shown that inhaled corticosteroids can change the make-up of bacteria in the human respiratory tract. However, whether these medications can directly impact the behavior of such bacteria has been unknown. Here, we explored the effects of fluticasone propionate, a commonly prescribed inhaled corticosteroid, on Klebsiella pneumoniae and other airway bacteria of interest, including primary species isolated from adult asthma patients. We provide evidence of growth responses to direct fluticasone exposure in culture and further examined fluticasone's effects on K. pneumoniae, including gene expression changes and effects of fluticasone-exposed bacteria on airway cells. These findings indicate that members of the human airway bacterial community possess the functional ability to respond to corticosteroids, which may have implications for the heterogeneity of treatment response observed clinically.

Paediatric in vitro models showed significant variations in fluticasone proprionate output from valved holding chambers.

We compared potential differences in drug delivery between different valved holding chambers (VHCs) used by asthma patients, with and without facemasks. An in vitro study design was created using a fluticasone propionate (FP) pressurised metered dose inhaler (pMDI) connected to a VHC. VHCs without facemasks and with sealed and unsealed facemasks were placed against face models that mimicked the features of a 1-year-old infant and a 4-year-old child. We analysed the amount of FP deposited on the filter in the face model after five breaths with a tidal volume of 75mL. Our measurements showed significant differences in the amounts of FP deposited on the filters, even without facemasks. The amount of FP delivered through the VHC and facemask combinations differed significantly, depending on the degree of the lack of facemask to face seal. All the tested VHCs showed significantly better drug output without a facemask. The VHC and facemasks chosen had a considerable and significant impact on FP delivery. The facemask seal should be checked whenever a VHC facemask combination is used. Young children should be taught to use the VHC mouthpiece as early as possible to optimise FP delivery and achieve more effective asthma therapy.

Use of PBPK Modeling To Evaluate the Performance of Dissolv It, a Biorelevant Dissolution Assay for Orally Inhaled Drug Products.

The dissolution of inhaled drug particles in the lungs is a challenge to model using biorelevant methods in terms of (i) collecting a respirable emitted aerosol fraction and dose, (ii) presenting this to a small volume of medium that is representative of lung lining fluid, and (iii) measuring the low concentrations of drug released. We report developments in methodology for each of these steps and utilize mechanistic in silico modeling to evaluate the in vitro dissolution profiles in the context of plasma concentration–time profiles. The PreciseInhale aerosol delivery system was used to deliver Flixotide aerosol particles to DissolvIt apparatus for measurement of dissolution. Different media were used in the DissolvIt chamber to investigate their effect on dissolution profiles, these were (i) 1.5% poly(ethylene oxide) with 0.4% l-alphaphosphatidyl choline, (ii) Survanta, and (iii) a synthetic simulated lung lining fluid (SLF) based on human lung fluid composition. For fluticasone proprionate (FP) quantification, solid phase extraction was used for sample preparation with LC–MS/MS analysis to provide an assay that was fit for purpose with a limit of quantification for FP of 312 pg/mL. FP concentration–time profiles in the flow-past perfusate were similar irrespective of the medium used in the DissolvIt chamber (∼0.04–0.07%/min), but these were significantly lower than transfer of drug from air-to-perfusate in isolated perfused lungs (0.12%/min). This difference was attributed to the DissolvIt system representing slower dissolution in the central region of the lungs (which feature nonsink conditions) compared to the peripheral regions that are represented in the isolated lung preparation. Pharmacokinetic parameters (Cmax, Tmax, and AUC0-∞) were estimated from the profiles for dissolution in the different lung fluid simulants and were predicted by the simulation within 2-fold of the values reported for inhaled FP (1000 μg dose) administered via Flixotide Evohaler 250 μg strength inhaler in man. In conclusion, we report methods for performing biorelevant dissolution studies for orally inhaled products and illustrate how they can provide inputs parameters for physiologically based pharmacokinetic (PBPK) modeling of inhaled medicines.

Inhaled Corticosteroid use and the Risk of Pneumonia and COPD Exacerbations in the UPLIFT Study

RationaleUnlike many other COPD studies, the 4-year UPLIFT trial permitted inhaled corticosteroid (ICS) use during run-in and treatment phases. This provided the opportunity to prospectively observe the continuing effects of ICS on respiratory events in closely observed COPD population.ObjectivesWe aimed to determine rate and number of episodes of pneumonia and exacerbations of COPD in patients entering the study on no ICS, fluticasone proprionate (FP), and other ICS.MethodsThe UPLIFT dataset was examined retrospectively, and patients were divided into three groups based on their medications at entry: no ICS, FP and other ICS. Poisson regression was used to compare the frequency of respiratory adverse events.Measurements and Main ResultsAt entry, the groups were well matched apart from a higher FEV1% predicted (38 vs. 41%; ICS vs. no ICS, respectively) and prevalence of current smoking (26 vs. 36%; ICS vs. no ICS, respectively). Incidence rates of pneumonia were significantly higher in patients taking ICS compared to no ICS (0.068 vs. 0.056 respectively; p = 0.012). When the FP group was compared to the other ICS, the event rate was even higher (0.077 vs. 0.058, respectively; p < 0.001). COPD exacerbations were more frequent in patients taking ICS, with significantly greater rate in the FP group compared to that seen with other ICS (0.93 vs. 0.84 respectively; p = 0.013).ConclusionsICS use was associated an increase in respiratory adverse event rates, but whether this was due to more severe illness at entry is unknown. In subgroup analysis, the excess of morbidity in the ICS group appeared to be mainly associated with those receiving FP at randomisation.

Serum cortisol concentration in horses with heaves treated with fluticasone proprionate over a 1 year period

The purpose of this study is to measure the effect of long-term administration of inhaled fluticasone proprionate on cortisol concentrations in heaves-affected horses. Eleven horses with heaves were treated with fluticasone at least once daily at dosages required to improve lung function or with antigen avoidance alone for 1 year. Morning serum cortisol was measured before and after 10, 30, 110, 190, 230, 280, and 320 days of treatment. Cortisol was also measured in the afternoon of day 330. Cortisol was significantly lower in the Fluticasone group on days 30, 110, and 190 when compared with the Antigen avoidance group. Cortisol measured on day 330 was also significantly lower in the Fluticasone group. Results indicate that inhaled fluticasone, when administered at therapeutic dosages, can significantly suppress serum cortisol concentrations for 8–24 h. The clinical significance of this finding remains to be ascertained, as no clinical signs were associated with this cortisol suppression.

Making A World Of Difference For Patients With Multiple Medications

When Janine Mansour, PharmD, reviewed Jack's medication profile at Ralphs Pharmacy in Culver City, CA, she was surprised to learn that none of his seven medications was an ACE inhibitor or a statin. He managed his type 2 diabetes with metformin and glipizide and occasionally took a low-dose aspirin. And he used fluticasone proprionate (Flonase—GlaxoSmithKline) for his allergies.

Effect of delivery device on systemic exposure to inhaled fluticasone propionate in children with asthma

Effect of delivery device on systemic exposure to inhaled fluticasone propionate in children with asthma

Sir David Jack: an extraordinary drug discoverer and developer

Sir David Jack, FRS, was a remarkable man, driven by altruistic intent, a passionate and exceptional scientist, who was able to apply the full power of his impressive intellect to the discovery of new and important medicines for the benefit of patients in need. This involved not only a critical focus on basic discovery, but also the proper application of drug development sciences (pharmacology, drug metabolism, toxicology, analytical chemistry, chemical manufacturing, pharmaceutics and clinical medicine) to ensure that a sound scientific idea at the bench could be turned into the reality of a useful medicine for patients. His broad, applied and integrated approach to drug discovery is what makes David Jack stand out, even among others highly regarded and acknowledged for their contributions to medical research and drug discovery. In addition he was a great leader and commanded the respect of all who worked for him, no matter where they worked in the organization. All he asked was that each and every employee focused on the task in hand, namely to find ‘better medicines for the treatment of poorly-treated common diseases’. He repeatedly espoused the idea that if you did not know ‘how in general terms’ what you were doing might eventually lead to this end then you should not be doing it. If such focused efforts proved to be successful, patients would benefit and so would the company and the resulting revenue generated would provide yet more opportunity to find different or further improved medicines. With David’s vision and leadership an amazingly impressive number of important new medicines materialized from the Allen and Hanburys site at Ware, including inhaled beclamethasone diproprionate (Becotide®), fluticasone proprionate (Flixotide®), salbutamol/albuterol (Ventolin®) and salmeterol (Serevent®) for asthma therapy, labetalol (Trandate®) for hypertension, ranitidine (Zantac®) for gastric acid diseases, ondansetron (Zofran®) for the treatment of emesis associated with cancer chemotherapy and sumatriptan (Imigran®/Imitrex®) for the treatment of

Steroid-insensitive tobacco smoke-induced lung inflammation models in the mouse

Methods Female mice were exposed daily to TS for 4 or 11 days. Control animals were exposed to air. Mice were killed 24hrs after the last TS-exposure, lungs lavaged and prepared for histological assessment. Steroids were given orally (dexamethasone (DEX) 300ug/kg; budesonide (BUD) 10mg/kg, 1hr prior to, and 6hrs after each TS exposure) or intra-nasally (fluticasone proprionate (FP), DEX , BUD, beclomethasone, mometasone and ciclesonide dosed at 100-500ug/kg 1hr prior to each TS-exposure). Steroid efficacy was also investigated in a mouse LPS lung inflammation model.

Resveratrol has salutary effects on mucociliary transport and inflammation in sinonasal epithelium.

Therapeutic agents that enhance mucociliary transport (via stimulation of transepithelial Cl- secretion) and inhibit inflammation could provide considerable advantages over conventional treatments for chronic rhinosinusitis (CRS). The objectives of the present study were to investigate whether the polyphenolic compound resveratrol promotes transepithelial Cl- transport and inhibits KC/IL-8 secretion in sinonasal epithelium. In vitro and in vivo study. Transepithelial Cl- transport was investigated in primary murine nasal septal (MNSE) and human sinonasal epithelial (HSNE) cultures. In vivo activity was also measured using the murine nasal potential difference assay. CFTR R-domain phosphorylation and cAMP levels were examined as a test of cAMP/PKA-dependent activation. In vitro LPS-induced KC/IL-8 secretion was quantified and compared to a panel of intranasal steroids. Resveratrol(100 μM) significantly increased CFTR-mediated Cl- transport (change in short-circuit current, ΔI(SC) ) in both MNSE (13.51 ± 0.77 vs. 4.4 ± 0.66 [control]; P < .05) and HSNE (12.28 ± 1.08 vs. 0.69 ± 0.32 [control]; P < .05). Cl- secretion across in vivo murine nasal epithelium was also enhanced (-4 ± 1.8 vs. -0.8 ± 1.7mV [control], P < .05). There was no increase in cellular cAMP or CFTR R-domain phosphorylation detected. Resveratrol also significantly inhibited KC/IL-8 secretion in a dose-dependent fashion (pg/mL) in MNSE (181 ± 39[100 μM) vs. 94 ± 16 [200 μM] vs. 16 ± 22 [500 μM] vs. 1195 ± 355 [LPS control]; P < .001). The compound robustly abrogated KC/IL-8 secretion when compared to ciclesonide (765 ± 139), triamcinolone (561 ± 124), and budesonide (742 ± 428), but had similar activity to fluticasone proprionate (65 ± 47). Similar effects were demonstrated in HSNE (975 ± 244 [100 μM] vs. 1825 ± 144 [LPS control]; P < .001) with inhibition comparable to fluticasone proprionate (785 ± 277). These in vitro and in vivo findings indicate resveratrol is a potent Cl- secretagogue and anti-inflammatory agent. Future clinical trials for CRS are warranted.

Prolonged protection of the new inhaled corticosteroid fluticasone furoate against AMP hyperresponsiveness in patients with asthma

Single-dose inhaled corticosteroids (ICS) induce direct anti-inflammatory effects in asthma thereby improving airway hyperresponsiveness (AHR). A novel enhanced-affinity ICS, fluticasone furoate (FF), demonstrated a prolonged duration of action in vitro. The aim of this study was to evaluate the efficacy and duration of action of a single dose of FF by studying protection against AHR to adenosine 5'-monophosphate (AMP) and effects on exhaled nitric oxide (eNO). A randomized, double-blind, placebo-controlled, 6-way crossover study (FFA10026) was performed in 24 patients with allergic asthma (mean age 32.8 years, FEV(1) ≥ 70% predicted and PC(20) AMP ≤ 50 mg/ml). Each subject received a single dose of FF 1000 μg, fluticasone proprionate (FP) 1000 μg, or placebo at 2 (FF only), 14 or 26 h prior to AMP challenge and eNO measurement. FF significantly improved PC(20) AMP compared to placebo, the difference in doubling concentrations being 2.18 (95% confidence interval: 1.13-3.23), 1.54 (0.48-2.59), and 1.30 (0.26-2.34) at 2, 14 and 26 h. FP improved PC(20) AMP significantly at 14 h compared to placebo, but not at the 26-hour time point, the difference in doubling concentrations being 1.72 (0.70-2.75) and 0.33 (-0.69-1.34). There was no significant effect on eNO after either FF or FP at all time points. FF was well tolerated and there were no serious adverse events. The new inhaled corticosteroid FF, but not FP, demonstrates prolonged protection up to 26 h against AHR to AMP in asthma patients.

Fluticasone propionate for treatment of esophageal lichen planus. A case series

Esophageal lichen planus is a rare condition, and although the majority of cases occur in conjunction with lichen planus at other sites, the endoscopic features are often misinterpreted resulting in a delay in diagnosis. We report a series of five patients presenting to our unit between 2005 and 2009. All five patients were female and presented with dysphagia. Endoscopy demonstrated proximal esophageal stricturing in four patients. Characteristic histological findings were found in four patients. Lichen planus was diagnosed at other sites, and preceded gastrointestinal symptoms, in all patients; five had oral involvement, two had genital involvement, and one had dermal involvement. All patients received proton pump inhibitor therapy without demonstrable benefit. Administration of oral fluticasone proprionate resulted in symptomatic improvement in three patients.

Inhaled Fluticasone and the Hormonal and Inflammatory Response to Brief Exercise

Inhaled corticosteroids (ICS) improve symptoms in lung diseases, such as asthma. Initial data suggest that the effects of ICS remain localized in the lung; however, recent studies demonstrate alteration to the peripheral immune system in patients with asthma. We sought to evaluate the effect of ICS on peripheral immune mediators and hypothalamic-pituitary-adrenal axis and their response to exercise in healthy men. Eleven healthy males (18-30 yr old) were placed on 2 wk of fluticasone proprionate (440 μg) twice daily. A 30-min bout of exercise was performed on a cycle ergometer at approximately 70% of peak work rate before and after the start of ICS. Blood was sampled before and after exercise. Cytokines and hypothalamic-pituitary-adrenal axis mediators were measured by ELISA, and fluticasone was measured by liquid chromatography/tandem mass spectrometry. After ICS treatment, cortisol and adrenocorticotropin were decreased, and a blunted exercise response was observed for cortisol, adrenocorticotropin, and growth hormone. Peripheral leukocytes and neutrophils were significantly increased in response to exercise in both the untreated and the ICS-treated conditions and at baseline after ICS treatment. Interleukin-6 was elevated with ICS treatment, but the exercise response was blunted. Circulating median fluticasone levels were 0.15 ng·mL(-1) and were increased to 0.20 ng·mL(-1) in response to exercise. Exercise revealed deficits in growth hormone production after ICS treatment not identified by static markers. Neutrophils were shown to be surrogate markers of the systemic effect of ICS. Exercise significantly increased circulating levels of fluticasone. Exercise challenge tests can be used to assess the physiological effect of exogenous corticosteroids.

Effect of Two Weeks of Inhaled Fluticasone on the Hormonal and Inflammatory Response to Brief Exercise in Healthy Young Men

RATIONALE: Inhaled corticosteroids (ICS) improve lung disorders, such as asthma, by altering the immune system. Initial data suggest ICS effects remain localized to the lung; however, recent studies demonstrate alteration to the peripheral immune system in patients with asthma. We evaluated the effect of ICS on peripheral immune mediators and HPA axis, and their response to exercise, in healthy adult males.METHODS: Eleven healthy males (age 18-30 years old) were placed on 2 weeks of Fluticasone proprionate (440 mcg) twice daily. A 30 minute bout of exercise was performed on a cycle ergometer at about 70% peak work rate before and after the start of ICS. Blood was sampled pre- and end-exercise. Cytokines and HPA axis mediators were measured by ELISA and fluticasone by liquid chromatography/tandem mass spectrometry.RESULTS: After ICS-treatment, cortisol and ACTH were decreased and a blunted exercise response observed for cortisol, ACTH, and GH. Peripheral leukocytes and neutrophils were significantly increased in response to exercise in both the untreated and ICS-treated conditions, and at baseline after ICS-treatment. IL-6 was elevated with ICS-treatment but the exercise response blunted. Circulating mean fluticasone levels were 0.15 ng/mL and increased to 0.22 ng/mL in response to exercise.CONCLUSIONS: Exercise revealed deficits of the HPA axis and GH production after ICS-treatment not identified by static markers. Neutrophils were shown to be sensitive surrogate markers of the systemic effect of ICS. Exercise significantly increased circulating levels of fluticasone. Exercise challenge tests can be used to assess subtle, physiological impacts of exogenous corticosteroids. RATIONALE: Inhaled corticosteroids (ICS) improve lung disorders, such as asthma, by altering the immune system. Initial data suggest ICS effects remain localized to the lung; however, recent studies demonstrate alteration to the peripheral immune system in patients with asthma. We evaluated the effect of ICS on peripheral immune mediators and HPA axis, and their response to exercise, in healthy adult males. METHODS: Eleven healthy males (age 18-30 years old) were placed on 2 weeks of Fluticasone proprionate (440 mcg) twice daily. A 30 minute bout of exercise was performed on a cycle ergometer at about 70% peak work rate before and after the start of ICS. Blood was sampled pre- and end-exercise. Cytokines and HPA axis mediators were measured by ELISA and fluticasone by liquid chromatography/tandem mass spectrometry. RESULTS: After ICS-treatment, cortisol and ACTH were decreased and a blunted exercise response observed for cortisol, ACTH, and GH. Peripheral leukocytes and neutrophils were significantly increased in response to exercise in both the untreated and ICS-treated conditions, and at baseline after ICS-treatment. IL-6 was elevated with ICS-treatment but the exercise response blunted. Circulating mean fluticasone levels were 0.15 ng/mL and increased to 0.22 ng/mL in response to exercise. CONCLUSIONS: Exercise revealed deficits of the HPA axis and GH production after ICS-treatment not identified by static markers. Neutrophils were shown to be sensitive surrogate markers of the systemic effect of ICS. Exercise significantly increased circulating levels of fluticasone. Exercise challenge tests can be used to assess subtle, physiological impacts of exogenous corticosteroids.

Acute Adrenal Crisis in an Asthmatic Child Treated with Inhaled Fluticasone Proprionate

Adrenal suppression secondary to prolonged inhaled corticosteroid use is usually limited to biochemical abnormalities, with no obvious clinical effects. Acute adrenal crisis is much rarer event but has been reported with increasing frequency. We report a case of a 7-year-old asthmatic child who presented with an acute history of lethargy after a respiratory infection. He was maintained on 220 μg/day of fluticasone propionate for several years. Initial evaluation revealed severe adrenal suppression, with undetectable cortisol levels and minimal response after stimulation with ACTH. After fluticasone was discontinued, a gradual recovery of the adrenal axis was seen. This case shows that acute adrenal crisis may be a consequence even at the usual prescribed doses, stressing the importance of using the lowest dose of inhaled steroids needed to control symptoms and having an increased awareness of this complication.

Acute Adrenal Crisis in an Asthmatic Child Treated with Inhaled Fluticasone Proprionate

Acute Adrenal Crisis in an Asthmatic Child Treated with Inhaled Fluticasone Proprionate

Add‐on salmeterol compared to double dose fluticasone in pediatric asthma: A double‐blind, randomized trial (VIAPAED)

In asthmatic children whose symptoms are uncontrolled on standard doses of inhaled corticosteroids (ICS), guidelines recommend to either increase the ICS dose or to add further controller medication, e.g. a long acting ss2-agonist (LABA). The aim of this study was to compare the efficacy and safety of doubling the dose of ICS (fluticasone proprionate FP 200 microg twice daily) with adding a long-acting beta-2 agonist to the ICS (SFC, salmeterol 50 microg/ FP 100 microg twice daily) in children with uncontrolled asthma. Children between 4 and 16 years of age were eligible for this multicenter, randomized, double blind, double dummy, parallel-group study. During a 14-day run-in phase, all children inhaled FP 100 microg b.i.d. Patients with persistent symptoms on > or =7 of 14 days were randomized to 8 weeks treatment with a Diskus(R) containing either SFC 50 microg/100 microg b.i.d. or FP 200 microg b.i.d.. The primary endpoint was the mean change in morning (a.m.) PEF from baseline. The initial statistical hypothesis of non-inferiority of SFC vs. FP was confirmed in an adaptive interim analysis, so that the study was terminated prematurely. 441 patients from 39 centers entered the run-in phase, and 64% of these were randomized to treatment (N = 138 to SFC and N = 145 to FP). After 8 weeks, patients on SFC had significantly better results for primary and secondary endpoints: The mean increase in morning PEF was 30.4 +/- 34.1 L/min in the SFC group and 16.7 +/- 35.8 L/min in the fluticasone group, and the mean (95% CI) improvement from baseline a.m. PEF in the ITT group was significantly larger after SFC (+8.6 L/min, CI: [1.3; infinity]). Patients in the SFC group experienced 8.7% (CI: [1.2;16.3]) more days without asthma symptoms and 8.0% (CI: [0.6;15.3]) more days without salbutamol than patients receiving FP. Good asthma control was achieved for a longer period in the SFC (3.4 +/- 2.7 weeks) group than in the FP group (2.7 +/- 2.7, P = 0.02). Both treatments were generally well tolerated. Asthma exacerbations were recorded in 3 and 6 and SAEs in 2 and 1 patients from the SFC and FP groups, respectively. In children with persistent asthma inadequately controlled on low dose ICS alone, adding a long acting beta-2-agonist to ICS in a single inhaler was more effective than doubling the ICS dose. These results support recommendations of adding LABA to low-dose ICS as the preferred controller option for children older than 4 years with symptomatic asthma.

Nasal endothelial interleukin‐10 expression is negatively correlated with nasal symptoms after allergen provocation

Despite major efforts, factors that predict or correspond to the level of allergic symptoms remain elusive. Given our previous observations of mucosal interleukin-10 (IL-10) expression by local tissue cells and its described role as immune modulator, we hypothesized that, in allergic rhinitis, nasal mucosal IL-10 expression could influence the severity of symptoms. In this study, we investigated endothelial IL-10 expression in nasal mucosa of healthy- and house dust mite allergic patients, both before and after provocation, and under nasal steroid therapy. Nasal turbinate biopsies were taken from healthy individuals as well as from house dust mite allergic patients, both before and after provocation. Allergic patients received fluticasone proprionate aqueous nasal spray or control treatment. In the allergic patients, endothelial IL-10 scores based on immunohistochemical stainings were correlated with allergic symptoms, measured by visual analog scores. At baseline, variable levels of endothelial IL-10 were detected in nasal biopsies. After nasal provocation, but not at baseline, endothelial IL-10 expression corresponded very closely to the allergic symptoms after allergen provocation. Low symptom scores were correlated with high endothelial IL-10 scores. This correlation disappeared after fluticason propionate treatment. There is a large variation in the level of endothelial IL-10 expression both in healthy individuals and in house dust mite allergic patients. Endothelial IL-10 expression may affect local immune reactions resulting in reduced levels of allergic symptoms.

Functional endoscopic sinus surgery improved asthma symptoms as well as PEFR and olfaction in patients with nasal polyposis

Nasal polyposis is a disease known to be associated with asthma. The management is anti-inflammatory, with topical and oral corticosteroids as the first-line treatment. The effect of surgical treatment on lower airway inflammation has not been sufficiently studied. The aim of this study is to investigate the effects of functional endoscopic sinus surgery (FESS) as well as fluticasone proprionate nasal drops (FPND) 400 microg b.i.d. on nasal and lower airway parameters in asthmatics with nasal polyposis. This was a prospective 21-week study of 68 patients with asthma and nasal polyposis, on the benefits of FESS on nasal '(butanol test, subjective olfaction, peak nasal inspiratory flow, congestion, rhinorrhoea, and polyp score)', and on the lower airway parameters (dyspnea, cough, mean daily peak expiratory flow rate (PEFR), and lung function tests). It also included a randomized, double-blind, placebo-controlled 14 weeks phase on FPND. Functional endoscopic sinus surgery significantly improved mean asthma symptom scores and daily PEFR and all nasal parameters including subjective and objective olfaction tests. This is the first study that shows the benefits of FESS on butanol tests in patients with nasal polyposis. We found no significant difference between topical treatment with FPND or placebo in the nasal or lower airway variables. Functional endoscopic sinus surgery improved nasal and asthma symptoms in patients with nasal polyposis. Functional endoscopic sinus surgery could be considered early in the natural course of nasal polyposis with concomitant asthma, as well as a second-line treatment in nasal polyposis patients with a reduced sense of smell. The potential benefits of FPND 400 microg b.i.d. were probably overshadowed by FESS.