Fluticasone Treatment Research Articles

Microbiome modifications by steroids during viral exacerbation of asthma and in healthy mice.

In the present studies the assessment of how viral exacerbation of asthmatic responses with and without pulmonary steroid treatment altered the microbiome in conjunction with immune responses presents striking data. The overall findings identify that while steroid treatment of allergic animals diminished the severity of the respiratory syncytial virus (RSV)-induced exacerbation of airway function and mucus hypersecretion, there were local increases in IL-17A expression. Analysis of lung and gut microbiome suggested that there are differences in the RSV exacerbation that are further altered by fluticasone (FLUT) treatment. Using metagenomic inference software, PICRUSt2, we were able to predict that the metabolite profile that the changed gut microbiome produced was significantly different with multiple metabolic pathways and associated with specific treatments with or without FLUT. Importantly, measuring plasma metabolites, our data indicate that there are significant changes associated with chronic allergen exposure, RSV exacerbation, and with FLUT treatment. The changes to the metabolites have contributions from both host and microbial pathways. To understand if airway steroids on their own altered lung and gut microbiome along with host responses to RSV infection, naïve animals were treated with FLUT prior to RSV infection. The naïve animals with FLUT prior to RSV infection demonstrated enhanced disease corresponding to altered microbiome and the PICRUSt2 metagenomic inference analysis. Altogether, these findings set the foundation for identifying important correlations of severe viral exacerbated allergic disease with microbiome changes a potential for early life pulmonary steroid influence on subsequent viral induced disease.

A steroid-resistant cockroach allergen model is associated with lung and cecal microbiome changes.

The pathogenesis of asthma has been partially linked to lung and gut microbiome. We utilized a steroid-resistant chronic model of cockroach antigen-induced (CRA) asthma with corticosteroid (fluticasone) treatment to examine lung and gut microbiome during disease. The pathophysiology assessment demonstrated that mucus and airway hyperresponsiveness were increased in the chronic CRA with no alteration in the fluticasone (Flut)-treated group, demonstrating steroid resistance. Analysis of mRNA from lungs showed no decrease of MUC5AC or Gob5 in the Flut-treated group. Furthermore, flow-cytometry in lung tissue showed eosinophils and neutrophils were not significantly reduced in the Flut-treated group compared to the chronic CRA group. When the microbiome profiles were assessed, data showed that only the Flut-treated animals were significantly different in the gut microbiome. Finally, a functional analysis of cecal microbiome metabolites using PiCRUSt showed several biosynthetic pathways were significantly enriched in the Flut-treated group, with tryptophan pathway verified by ELISA with increased kynurenine in homogenized cecum samples. While the implications of these data are unclear, they may suggest a significant impact of steroid treatment on future disease pathogenesis through microbiome and associated metabolite pathway changes.

The clinical efficacy of fluticasone propionate combined with ACEI/ARB in the treatment of immunoglobulin A nephropathy

BackgroundImmunoglobulin A nephropathy (IgAN) is the most common primary glomerulopathy worldwide, and lacks the effective treatment. The study was aimed to investigate the clinical efficacy of fluticasone propionate aerosol combined with angiotensin converting enzyme inhibitor / angiotensin receptor blocker (ACEI/ARB) in the treatment of IgAN.Methods142 patients with biopsy-proven IgAN at Shenzhen People?s hospital from June 2018 to June 2020 were enrolled. The patients were randomly divided into the supportive care plus fluticasone group and the supportive care group. The patients of the supportive care plus fluticasone group were treated with fluticasone propionate aerosol (250 ?g Bid) combined with ACEI/ARB, while the supportive care group was merely treated with ACEI/ARB. The patients were followed up at 3, 6 and 9 months after enrollment. Primary outcomes include changes in proteinuria and estimated glomerular filtration rate (eGFR).ResultsThe level of proteinuria in the supportive care plus fluticasone group was significantly lower compared with the supportive care group at 0, 3, 6 and 9 months. Meanwhile, during the follow-up period, no serious adverse events were recorded during the study in either group. However, fluticasone treatment did not alleviate the decline in eGFR.ConclusionFluticasone propionate aerosol combined with ACEI/ARB can reduce the level of proteinuria in thetreatment of IgAN, and has no significant effects on renal function.

Integrated basic lung and heart ultrasound with X-ray (TUSX) for the diagnosis of asthma, chronic bronchitis and laryngeal paralysis, and treatment with inhaled fluticasone using home-made mask in dogs and cats.

Basic lung and heart ultrasound examination combined with chest X-ray (TUSX) is currently considered to be very useful for differentiation of asthma, chronic bronchitis and laryngeal paralysis from other diseases with dyspnea/coughing. Among 252 client-owned animals with persistent dyspnea/cough/noisy breathing, in 197 of them: pulmonary edema, pneumonia, lung cancer, free pleural fluid, pneumothorax, lung contusion or heart disease were diagnosed. The remaining 55 animals (42 dogs and 13 cats) were diagnosed with asthma (in 13 cats), chronic bronchitis (in 37 dogs) and laryngeal paralysis (in 5 dogs) using TUSX. These animals were qualified for inhaled fluticasone treatment using 3 types of spacers - two commercial and a home- -made mask. 36 animals (65.5%) completed the trail. In 26 of them (72.2%) the owners observed complete, long lasting relief of the symptoms, and the owners of 7 animals (19.5%) declared a considerable clinical improvement, regardless of the type of spacer used. The owners of 3 animals (8.3%) did not see any improvement. The proposed diagnostic and therapeutic management improved long-term clinical status of the vast majority (91.7%) of animals. Therefore, it seems justified to include the TUSX diagnostic protocol in daily veterinary practice and to encourage owners to prepare home-made face masks for inhaled fluticasone treatment.

Cyclo-VEGI inhibits bronchial artery remodeling in a murine model of chronic asthma

Purpose/Aim: In the context of asthma, airway bronchial remodeling and angiogenesis in the bronchial mucosa are well established. Cyclopeptidic-vascular endothelial growth inhibitor (cyclo-VEGI) is an inhibitor of the vascular endothelial growth factor (VEGF) receptor that increases the proliferation of endothelial cells and the formation of new vessels. However, changes in the bronchial arteries of patients with asthma have not been clearly elucidated. We investigated whether structural changes occurred in bronchial arteries, as well as the effects of cyclo-VEGI in a mouse model of chronic asthma (in vivo) and human fibroblasts (in vitro). Materials and Methods: A validated mouse model of allergic airway inflammation with ovalbumin (OVA) as the causative allergen was used for the study. Mice were treated with cyclo-VEGI or fluticasone during OVA challenge. In vitro experiments were conducted to determine whether fibroblasts proliferated following elastin exposure and the effects of cyclo-VEGI on them. Results: OVA sensitization and challenge led to greater perivascular smooth muscle area, more elastic fibers, and elevated expression of vascular cell adhesion molecule (VCAM)-1 antigen. These phenomena indicated changes to bronchial arteries. Cyclo-VEGI and fluticasone treatment both inhibited airway hyper-responsiveness and inflammation. Cyclo-VEGI-treated mice exhibited decreased perivascular smooth muscle area, elastin fibers, and VCAM-1 expression. Fluticasone-treated mice exhibited reductions in perivascular smooth muscle but not in perivascular elastin or VCAM-1 expression. In vitro, fibroblast proliferation was enhanced by elastin treatment, which was inhibited by cyclo-VEGI treatment. Eotaxin expression was elevated in elastin-treated fibroblasts and decreased with cyclo-VEGI treatment. Conclusions: Vascular remodeling occurred in our mouse model of chronic asthma. Cyclo-VEGI could reduce airway inflammation and hyper-responsiveness by inhibiting VCAM-1 expression and elastin deposition around the bronchial arteries.

Sarsasapogenin and fluticasone combination improves DNFB induced atopic dermatitis lesions in BALB/c mice

Objective Atopic dermatitis (AD) is a pruritic, chronic, relapsing inflammatory skin disease. The research aims to study the effects of Sarsasapogenin and its combination with Fluticasone in 2, 4-Dinitrofluorobenzene (DNFB) induced atopic dermatitis in BALB/c mice. Material and Methods Thirty male Balb/c mice were divided into 5 groups: (i) Normal control (NC), (ii) Disease control (DNFB), (iii) Sarsasapogenin (SG) (50 µg/mice), (iv) Fluticasone (FC) (50 µg/mice), (v) Sarsasapogenin + Fluticasone (SG + FC) combination (25 µg/mice). Dermatitis was induced by repeated application of DNFB in Balb/c mice. On topical application of SG, FC, and SG + FC combination on the ear and skin lesions, body weight, ear weight, ear thickness, erythema score, spleen weight, cytokines, immunoglobulin E (IgE) levels, nitric oxide (NO) level, hematological parameters, and oxidative stress markers were evaluated. Histological analysis of the ear tissue was also done. Results The results stated that SG and SG + FC treatment to mice considerably decrease the ear weight, ear thickness, spleen weight, serum IgE, cytokines, NO levels, and restoration of antioxidant stress markers with elevation in the hematological parameters. The observations were further confirmed by histopathological analysis of ear tissue. Conclusion These data specify that SG has been demonstrated as a probable therapy for the treatment of allergic skin diseases in combination with FC by decreasing its dose from 50 to 25 µg/mice to avoid the chronic side effects of FC. Hence, it can be concluded that SG and SG + FC combination significantly improved the AD-like symptoms in the DNFB sensitized mice through mitigating the production of proinflammatory mediators and restoration of oxidative stress markers.

Protective effect of sarsasapogenin in TNBS induced ulcerative colitis in rats associated with downregulation of pro-inflammatory mediators and oxidative stress

Background Ulcerative colitis (UC) is a chronic inflammatory bowel condition considered by oxido-nitrosative stress and the release of pro-inflammatory cytokines that affects the mucosal lining of the colon. Sarsasapogenin (SG), as an active component, has been found in many plants, and it exhibits potential protective effects, such as anti-inflammatory, antioxidant, anti-psoriasis, anti-arthritis, anti-asthma, anti-depressant and anti-cancer. However, the effects of SG on UC remain unknown. Objective The purpose of this study was to investigate the effects of SG on 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced UC in rats. Method Thirty Wistar rats were randomized into five groups: (i) Normal control, (ii) Disease control (TNBS), (iii) Sarsasapogenin (SG) (50 µg/rat), (iv) Fluticasone (FC) (50 µg/rat), (v) Sarsasapogenin + Fluticasone (SG + FC) (25 µg/rat). UC was induced in rats by trans-rectal instillation of TNBS (10 mg/kg). SG, FC and SG + FC were administered for 11 days and on the 8th day colitis was induced. Several molecular, biochemical and histological alterations were evaluated in the colon tissue. All treatment group results were compared to the TNBS group results. Result The study results revealed that treatment of rats with SG and SG + FC combination significantly decreased the colon weight/length ratio, macroscopic inflammation score, lesions score, diarrhea score and adhesion score. Combination treatment in rats significantly reduced the production of biochemical parameters, proinflammatory cytokines, haematological parameters, serum IgE levels and restored the oxidative stress markers. SG and SG + FC treatment also considerably restored the histopathological changes induced by TNBS. Conclusion Thus, SG and SG + FC combination could alter the disease progression and could be a hopeful therapeutic target for the management of UC by reducing its dose in combination with FC to elude the long term adverse effects of FC.

Relevance of Plasma Matrix Metalloproteinase-9 for Bronchiolitis Obliterans Syndrome after Allogeneic Hematopoietic Cell Transplantation

Bronchiolitis obliterans syndrome (BOS) is a highly morbid form of chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT). Several plasma proteins have been identified as biomarkers for BOS after lung transplantation. The relevance of these biomarkers in BOS patients after allogeneic HCT has not been examined. We hypothesized that biomarkers associated with BOS after lung transplantation are also associated with BOS after allogeneic HCT. We tested plasma samples from 33 adult HCT patients who participated in a phase II multicenter study of fluticasone, azithromycin, and montelukast (FAM) treatment for new-onset BOS (NCT01307462), and matched control samples of HCT patients who had non-BOS chronic GVHD (n=31) and those who never experienced chronic GVHD (n=29) (NCT00637689 and NCT01902576). Candidate biomarkers included matrix metalloproteinase-9 (MMP-9), MMP-3, and chitinase-3-like-1 glycoprotein (YKL-40). MMP-9 concentrations were higher in the patients with BOS compared with those with non-BOS chronic GVHD (P=.04) or no chronic GVHD (P < .001). MMP-3 concentrations were higher in patients with BOS (P < .001) or non-BOS chronic GVHD (P < .001) compared with those with no chronic GVHD. YKL-40 concentrations did not differ statistically among the 3 groups. MMP-9 concentrations before starting FAM therapy were higher in patients who experienced treatment failure within 6 months compared with those with treatment success (P=.006), whereas MMP-3 or YKL-40 concentrations did not differ statistically between these 2 groups. Patients with an MMP-9 concentration ≥200,000 pg/mL before starting FAM therapy had worse overall survival compared with those with lower MMP-9 concentrations. Our data suggest that plasma MMP-9 concentration could serve as a relevant biomarker at diagnosis of BOS after allogeneic HCT for prognostication of survival and for prediction of treatment response. Further validation is needed to confirm our findings.

Prevention of middle ear barotrauma with oxymetazoline/fluticasone treatment

Prevention of middle ear barotrauma with oxymetazoline/fluticasone treatment Middle ear barotrauma (MEB) is a common complication of hyperbaric oxygen (HBO2) therapy. It has been reported in more than 40% of HBO2 treatments and can interrupt the sequence of HBO2. MEB may lead to pain, tympanic membrane rupture, and even hearing loss.The aim of this study was to determine if pretreatment with intranasal fluticasone and oxymetazoline affected the incidence of MEB. We conducted a retrospective chart review of subjects undergoing HBO2 at our institution between February 1, 2014, and May 31, 2019. Subjects in the fluticasone/oxymetazoline (FOT) treatment group used intranasal fluticasone 50 mcg two times per day and oxymetazoline 0.05% one spray two times per day beginning 48 hours prior to initial HBO2. Oxymetazoline was discontinued after four days. Fluticasone was continued for the duration of HBO2 therapy. A total of 154 unique subjects underwent 5,683 HBO2 treatments: 39 unique subjects in the FOT group underwent 1,501 HBO2; 115 unique subjects in the nFOT (no oxymetazoline or fluticasone treatment) group underwent 4,182 HBO2 treatments. The incidence of MEB was 15.4% in the FOT group and 16.2% in the nFOT group. This was not a statistically significant difference (OR = 0.77; p = 0.636). Treatment pressure, age over 65 years, male sex, and BMI were not associated with a difference in MEB incidence. In summary, pretreatment with intranasal oxymetazoline and fluticasone in patients undergoing HBO2 did not significantly reduce MEB. More investigation with larger numbers of participants and prospective studies could further clarify this issue.

Treatment with compounded fluticasone suspension improves the clinical, endoscopic, and histologic features of eosinophilic esophagitis.

No approved medication exists for the treatment of eosinophilic esophagitis (EoE) in the United States, which forces patients to utilize off-label drugs and/or create their own formulations. We assessed the efficacy of a standardized compounded fluticasone suspension. To do this, we performed a retrospective cohort study identifying all EoE patients treated with compounded fluticasone. Compounded fluticasone was prescribed during routine clinical care and dispensed by a specialty compounding pharmacy. Clinical data were extracted from medical records. Outcomes (symptomatic, endoscopic, and histologic) were assessed after the initial and last compounded fluticasone treatment in our system. There were 27 included patients (mean age 34.2; 67% male; 96% white) treated for a mean length of 5.4 ± 4.4months. The majority (89%) previously utilized dietary elimination or topical corticosteroids, and many (75%) had primary non-response or secondary loss of response to these treatments. After starting compounded fluticasone, symptoms and endoscopic findings improved [dysphagia (89 vs. 56%, P = 0.005), food impaction (59 vs. 4%, P = 0.003), heartburn (26 vs. 4%, P = 0.01), chest pain (26 vs. 8%, P = 0.05), white plaques (63 vs. 32%; P = 0.005), furrows (81 vs. 60%; P = 0.06), and edema (15 vs. 4%; P = 0.16)]. The median of the peak eosinophil counts decreased from 52 to 37 eos/hpf (P = 0.10) and 35% of patients achieved <15 eos/hpf. In conclusion, compounded fluticasone provided a significant improvement in symptoms and endoscopic findings, with more than a third achieving histologic response in a treatment refractory EoE population. Compounded fluticasone should be considered as an EoE management option.

Inhaled corticosteroids and risk of influenza in patients with asthma: a meta-analysis of randomized controlled trials.

It was reported that inhaled corticosteroids (ICS) treatment may affect local immunity and microbial community of the airway. However, whether ICS treatment increases the risk of influenza in patients with asthma remains unclear. This meta-analysis aimed to compare the risk of influenza between ICS and non-ICS treatment in patients with asthma. PubMed, Embase, Cochrane Library and Clinical Trials.gov were searched from inception until November 2019. Randomized controlled trials (RCTs) were included that compared ICS treatment with non-ICS treatment on the risk of influenza in patients with asthma. Meta-analyses were conducted by the Peto approach and Mantel-Haenszel approach with corresponding 95% CIs. Nine trials involving 6486 patients were included in this meta-analysis. The risk of influenza was not different between ICS treatment and the control groups (Peto OR: 1.01, 95% CI 0.74-1.37, P = 0.95). The results of subgroup analyses based on durations (long-term and short-term treatment), doses (high-, medium- and low-dose treatment) and types (fluticasone and budesonide treatment) of ICS were consistent with the above pooled results. Moreover, subgroup analysis based on patients' age also revealed that use of ICS did not increase the risk of influenza. Results of the two meta-analysis approaches were similar. Use of ICS does not increase the risk of influenza in patients with asthma. This study adds to safety evidence of ICS as a regular controller treatment for patients with asthma.

Distinct associations of sputum and oral microbiota with atopic, immunologic, and clinical features in mild asthma

Whether microbiome characteristics of induced sputum or oral samples demonstrate unique relationships to features of atopy or mild asthma in adults is unknown. We sought to determine sputum and oral microbiota relationships to clinical or immunologic features in mild atopic asthma and the impact on the microbiota of inhaled corticosteroid (ICS) treatment administered to ICS-naive subjects with asthma. Bacterial microbiota profiles were analyzed in induced sputum and oral wash samples from 32 subjects with mild atopic asthma before and after inhaled fluticasone treatment, 18 atopic subjects without asthma, and 16 nonatopic healthy subjects in a multicenter study (NCT01537133). Associations with clinical and immunologic features were examined, including markers of atopy, type 2 inflammation, immune cell populations, and cytokines. Sputum bacterial burden inversely associated with bronchial expression of type 2 (T2)-related genes. Differences in specific sputum microbiota also associated with T2-low asthma phenotype, a subgroup of whom displayed elevations in lung inflammatory mediators and reduced sputum bacterial diversity. Differences in specific oral microbiota were more reflective of atopic status. After ICS treatment of patients with asthma, the compositional structure of sputum microbiota showed greater deviation from baseline in ICS nonresponders than in ICS responders. Novel associations of sputum and oral microbiota to immunologic features were observed in this cohort of subjects with or without ICS-naive mild asthma. These findings confirm and extend our previous report of reduced bronchial bacterial burden and compositional complexity in subjects with T2-high asthma, with additional identification of a T2-low subgroup with a distinct microbiota-immunologic relationship.

Effects of inhaled fluticasone propionate on extrinsic tongue muscles in rats.

Obstructive sleep apnea (OSA) is more common in patients with asthma, and inhaled corticosteroids may contribute to OSA pathogenesis in these patients. This study tested the effects of orally inhaled fluticasone propionate (FP) on extrinsic tongue muscles. Unanesthetized rats were treated with FP or placebo for 28 days. On day 29, tongue retrusive and protrusive functions were tested via hypoglossal nerve stimulation under a state of anesthesia, followed by genioglossus (GG), styloglossus (SG) and hyoglossus (HG) muscle extraction, after euthanasia, for histology [myosin heavy chain (MHC) fibers and laminin content reflecting extracellular matrix (ECM)]. On protrusive testing, FP increased percent maximum tetanic force at 40 Hz (P = 0.03 vs. placebo) and endurance index (P = 0.029 vs. placebo). On retrusive testing, FP increased maximum twitch (P = 0.026 vs. placebo) and tetanic forces (P = 0.02 vs. placebo) with no effect on endurance index. On histology, FP increased GG cross-sectional area of MHC type IIa (P = 0.036 vs. placebo) and tended to increase type IIb (P = 0.057 vs. placebo) fibers and HG MHC IIx fibers (P = 0.065). The FP group had significantly increased laminin-stained areas, of greatest magnitude in the HG muscle. FP affects tongue protrusive and retrusive functions differently, concurrent with a shift in MHC fibers and increased ECM accumulation. These differential alterations may destabilize the tongue's "muscle hydrostat" during sleep and promote collapse.NEW & NOTEWORTHY The effects of inhaled corticosteroid on upper airway may contribute to OSA pathogenesis in asthma. In this study, we tested the effects of orally inhaled fluticasone propionate on tongue protrusive and retrusive functions and on tongue extrinsic muscle fiber composition and molecular properties. We found that fluticasone treatment: 1) increased protrusive endurance and retrusive maximum twitch and tetanic force; and 2) on histology, increased cross-sectional area of myosin heavy chain (MHC) type IIa fibers and tended to increase cross-sectional area of MHC type IIb fibers in the protrusive muscle and of MHC IIx fibers in the retrusors. It also increased laminin-stained areas, across extrinsic tongue muscles, of greatest magnitude in the retrusors; and 3) reduced protein degradation and activated pathways associated with increased protein synthesis in the protrusor. These differential effects on the protrusors and retrusors may destabilize the tongue's "muscle hydrostat" properties during sleep and promote collapse.

Nebulized step-down budesonide vs. fluticasone in infantile asthma: A retrospective cohort study.

The United States Food and Drug Administration has approved budesonide in infantile asthma but nebulization of infants under budesonide has the risk of relapse of asthma. The objective of the present study was to compare the effectiveness and safety of fluticasone step-down treatment with budesonide step-down treatment in infantile asthma. The data of 778 infants with confirmed asthma were included in the analysis. Infants who had received nebulized 500 µg budesonide twice daily for 6 weeks followed by 250 µg budesonide twice daily for 6 weeks were included in the BS group (n=389), while infants who had received nebulized 250 µg fluticasone twice daily for 6 weeks followed by 125 µg fluticasone twice daily for 6 weeks were included in the FC group (n=389). The data of lung function tests and a safety study were collected and analyzed. Budesonide treatment achieved a reduced specific airway resistance (sRaw; 1.28±0.11 vs. 1.21±0.10 kPa/sec; P<0.0001, q=13.45) and improved forced expiratory volume in 1 sec (FEV1; 0.977±0.068 vs. 0.997±0.085 l/sec; P<0.0001, q=5.54). In addition, fluticasone treatment achieved a reduced sRaw (1.27±0.1 vs. 1.23±0.11 kPa/sec, P<0.0001, q=7.39) and improved FEV1 (0.971±0.069 vs. 0.992±0.085 l/sec; P=0.0003, q=5.46). Of note, the efficacy of budesonide to reduce sRaw (P=0.008, q=3.69) and improve FEV1 (P<0.0001, q=6.93) was greater than that of fluticasone. The budesonide treatment group had more post-treatment symptom-free days than the fluticasone treatment group (165.56±23.15 vs. 112.21±9.45 days; P<0.0001). The step-down approach of budesonide nebulization may better support the functional and clinical outcomes with an increased number of post-treatment symptom-free days compared with fluticasone in infantile asthma (level of evidence, 3).

The impact of intranasal fluticasone on patients with obstructive sleep apnea: a prospective study

IntroductionObstructive sleep apnea is the most common type of sleep apnea, which is caused by complete or partial obstructions of the upper airway. Nasal obstruction is also considered as one of the independent risk factors of obstructive sleep apnea. ObjectivePatients with obstructive sleep apnea. MethodsWe enrolled patients with obstructive sleep apnea from June to December 2015 and treated them with intranasal corticosteroid spray for four weeks. Several parameters were obtained before and after the treatment, including Nasal Obstruction Symptom Evaluation scores, Pittsburgh Sleep Quality Index questionnaire and Epworth Sleepiness Scale questionnaire. ResultsFifty patients completed questionnaires prior to and following the intranasal fluticasone treatments. The average age was 39.7 ± 15.6 y, with a male to female ratio of 3:2. The post-treatment Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, and Nasal Obstruction Symptom Evaluation scores all indicated a decrease compared to pre-treatment scores, from 10.4 to 8.74, 7.86 to 6.66 and 9.08 to 6.48, respectively. A significant decrease was observed in the Nasal Obstruction Symptom Evaluation ≥10 group in all three categories, but not in the Nasal Obstruction Symptom Evaluation <10 group. ConclusionsIntranasal fluticasone treatment may be useful for patients with nasal obstruction-related obstructive sleep apnea to improve sleep quality and limit daytime dysfunction.

Inhaled corticosteroids and risk of upper respiratory tract infection in patients with asthma: a meta-analysis.

Recent studies have suggested a possible association between respiratory infection and the use of inhaled corticosteroids (ICS). We aimed to ascertain the risk of upper respiratory tract infection (URTI) with long-term inhaled corticosteroid use among patients with asthma. Through a comprehensive literature search of PubMed, Cochrane Library, EMBASE, and Google Scholar from inception to May 2018, we included randomized controlled trials of any ICS vs. a control treatment for asthma, with reporting of URTI as an adverse event. We conducted meta-analyses by the Peto approaches to generate summary estimates comparing ICS with non-ICS treatment on the risk of URTI. Seventeen trials (15,336 subjects) were included. Compared with non-ICS treatment, ICSs were associated with a significantly increased risk of URTI (Peto OR, 1.24; 95% CI 1.08-1.42; I2 = 5%, p = 0.002). Subgroup analyses were performed for different dose, both high- and low-dose ICSs were associated with a significantly increased risk of URTI (high dose: Peto OR, 1.46; 95% CI 1.05-2.03; I2 = 0%; p = 0.03) (low dose: Peto OR, 1.20; 95% CI 1.04-1.39; I2 = 25%; p = 0.01). Moreover, fluticasone was observed with an increased risk of URTI (Peto OR, 1.18; 95% CI 1.02-1.38; p = 0.03; heterogeneity: I2 = 21%) but not budesonide, low-dose fluticasone treatment was associated with a significantly higher risk of URTI but not high dose. This study raises safety concerns about the risk of URTI associated with ICS use in patients with asthma, but it should be further investigated.

Effect of Dexamethasone and Fluticasone on Airway Hyperresponsiveness in Horses With Inflammatory Airway Disease.

BackgroundAirway hyperresponsiveness (AWHR), expressed as hypersensitivity (PC 75 RL) or hyperreactivity (slope of the histamine dose‐response curve), is a feature of inflammatory airway disease (IAD) or mild equine asthma in horses. Glucocorticoids are used empirically to treat IAD.ObjectivesTo determine whether dexamethasone (DEX) (0.05 mg/kg IM q24h) and inhaled fluticasone (FLUT) (3,000 μg q12h) administered by inhalation are effective in decreasing AWHR, lung inflammation, and clinical signs in horses with IAD.MethodsA randomized crossover study design was used. Eight horses with IAD were assigned to a treatment group with either DEX or FLUT. Measured outcomes included lung mechanics during bronchoprovocative challenges, bronchoalveolar lavage fluid (BALF) cytology, and scoring of clinical signs during exercise.ResultsDexamethasone and FLUT abolished the increase in RL by 75% at any histamine bronchoprovocative dose in all horses after the first week of treatment. However, after 2 weeks of FLUT treatment, 1 horse redeveloped hypersensitivity. There was a significant decrease in the number of lymphocytes after treatment with both DEX and FLUT (P = .039 for both) but no significant differences in other BALF cell types or total cell counts (P > .05). There was no difference in the scoring of the clinical signs during each treatment and washout period (P > .05).Conclusions and Clinical ImportanceBoth DEX and FLUT treatments significantly inhibit airway hypersensitivity and hyperreactivity in horses with IAD. There are no significant effects on the clinical signs or the number of inflammatory cells (except lymphocytes) in BALF. The treatments have no residual effect 3 weeks after discontinuation.

Disease activity in eosinophilic esophagitis is associated with impaired esophageal barrier integrity.

In eosinophilic esophagitis (EoE), the esophageal barrier integrity is impaired. Integrity can be assessed with different techniques. To assess the correlations between esophageal eosinophilia and various measures of mucosal integrity and to evaluate whether endoscopic impedance measurements can predict disease activity, endoscopies and mucosal integrity measurements were performed in adult EoE patients with active disease (≥15 eosinophils/high-power field) at baseline (n = 32) and after fluticasone (n = 15) and elemental dietary treatment (n = 14) and in controls (n = 19). Mucosal integrity was evaluated during endoscopy using electrical tissue spectroscopy (ETIS) measuring mucosal impedance and transepithelial electrical resistance (TER) and transepithelial molecule-flux through biopsy specimens in Ussing chambers. We included 61 measurements; 32 of patients at baseline and 29 after treatment, 3 patients dropped out. After treatment, 20 patients were in remission (≤15 eosinophils/high-power field) and these measurements were compared with 41 measurements of patients with active disease (at baseline or after failed treatment). All four mucosal integrity measures showed significant impairment in active EoE compared with remission. Eosinophilia was negatively correlated with ETIS and TER and positively with transepithelial molecule flux (P ≤ 0.001). The optimal ETIS cutoff to predict disease activity was 6,000 Ω·m with a sensitivity of 79% [95% confidence interval (CI) 54-94%], specificity of 84% (95% CI 69-94%), positive predictive values of 89% (95% CI 77-95%) and negative predictive values of 71% (95% CI 54-84%). In EoE patients, markers of mucosal integrity correlate with esophageal eosinophilia. Additionally, endoscopic mucosal impedance measurements can predict disease activity.NEW & NOTEWORTHY In adult patients with eosinophilic esophagitis (EoE), the mucosal integrity, measured by making use of four different parameters, correlates strongly with esophageal eosinophilia. The accuracy of endoscopically measured mucosal impedance to distinguish active disease from remission was acceptable with moderate specificity and sensitivity. Mucosal impedance measurements can predict disease activity in adult EoE patients.

Long-term use of inhaled corticosteroids and risk of upper respiratory tract infection in chronic obstructive pulmonary disease: a meta-analysis

Recent studies have suggested that inhaled corticosteroids (ICS) may be associated with higher risks of tuberculosis and pneumonia in patients with COPD. However, it is not known whether ICS increases the risk of upper respiratory tract infection (URTI). Aim of this study was to explore the relationship between ICS and URTI. Through a comprehensive literature search of PubMed, EMBASE, Cochrane Library, and Google Scholar from inception to March 2016, we identified randomized controlled trials of ICS therapy lasting at least 6 months. A meta-analysis by the Peto approach was also conducted to generate summary estimates comparing ICS with non-ICS treatment on the risk of URTI. A total of 14 studies involving 19,777 subjects were considered in the meta-analysis. Compared with non-ICS treatment, ICS were associated with a significantly increased risk of URTI (Peto OR: 1.16; 95% CI: 1.05–1.29; I2 = 9%; p = .004). Subgroup analyzes were performed for different dose, high-dose ICS was associated with a significantly increased risk of URTI (Peto OR: 1.19; 95% CI: 1.05–1.34; I2 = 0%; p = .005), whereas low-dose ICS showed a non-significant increased risk of URTI (Peto OR: 1.10; 95% CI: 0.91–1.33; I2 = 0%; p = .32). Moreover, fluticasone was observed with an increased risk of URTI but not mometasone; high-dose fluticasone treatment was associated with a significantly higher risk of URTI but not low-dose. These results suggested to us that ICS use may increase the risk of URTI in patients with COPD, but it should be further investigated.

Fluticasone furoate induced iatrogenic Cushing syndrome in a pediatric patient receiving anti-retroviral therapy.

SummaryWe present a case of iatrogenic Cushing’s syndrome, induced by treatment with fluticasone furoate (1–2 dd, 27.5 µg in each nostril) in a pediatric patient treated for congenital HIV. The pediatric patient described in this case report is a young girl of African descent, treated for congenital HIV with a combination therapy of Lopinavir/Ritonavir (1 dd 320/80 mg), Lamivudine (1 dd 160 mg) and Abacavir (1 dd 320 mg). Our pediatric patient presented with typical Cushingoid features (i.e. striae of the upper legs, full moon face, increased body and facial hair) within weeks after starting fluticasone furoate therapy, which was exacerbated after increasing the dose to 2 dd because of complaints of unresolved rhinitis. Biochemical analysis fitted iatrogenic Cushing’s syndrome, with a repeatedly low cortisol (<0.03 µM, ref 0.14–0.60 µM) and low ACTH (9 pg/mL, ref 9–52 pg/mL) without signs of adrenal insufficiency. No other biochemical abnormalities that could point to adrenal or pituitary dysfunction were detected; electrolytes, thyroid and gonadal function, and IGF-1 were within the normal range. Pharmacogenetic analysis revealed that the pediatric patient carried the CYP3A4 *1B/*1G and CYP3A5 *3/*3 genotype (associated with a partial and complete loss of enzyme activity, respectively) which is associated with the development of iatrogenic Cushing’s syndrome in patients treated for HIV due to the strong inhibition of CYP3 enzymes by Ritonavir. Upon discontinuation of fluticasone treatment, the pediatric patient improved both clinically and biochemically with normalisation of cortisol and ACTH within a couple of weeks.Learning points:Fluticasone therapy may induce iatrogenic Cushing’s syndrome in a patient treated with anti-retroviral therapy.Pharmacogenetic analysis, in particular CYP3A genotyping, provides useful information in patients treated for HIV with respect to possible future steroid treatment.Fluticasone furoate is not detected in the Siemens Immulite cortisol binding assay.