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Gastroenterology & Hepatology Apr 2022Eosinophilic esophagitis (EoE) is a chronic immune-mediated condition identified by eosinophilic infiltration of the esophageal mucosa. Historically, pharmacologic...
Eosinophilic esophagitis (EoE) is a chronic immune-mediated condition identified by eosinophilic infiltration of the esophageal mucosa. Historically, pharmacologic options have been limited to proton pump inhibitors and swallowed topical corticosteroids, neither of which have been approved by the US Food and Drug Administration for the treatment of EoE. The goal of therapy is ultimately to avoid irreversible stricturing disease. Despite the rising prevalence of EoE, there have been few therapeutic advancements until recently. Some newer topical corticosteroid preparations are being studied, including a budesonide suspension (TAK-721), orodispersible tablet formulations of budesonide and fluticasone (APT-1011), and mometasone and ciclesonide preparations. Also in various stages of clinical trials are potential disease-modifying biologics such as dupilumab, cendakimab, lirentelimab, benralizumab, and mepolizumab. Some of these medications have proven efficacious for other atopic conditions and show incredible promise for the treatment of eosinophilic gastrointestinal diseases. Further studies will be needed to determine long-term treatment outcomes for each of these drugs.
PubMed: 35505944
DOI: No ID Found -
Iranian Journal of Basic Medical... Jan 2023A new binary mixture containing mometasone furoate (MF) and calcipotriol (CP) is suggested to manage psoriasis; since the combined stability profile of these drugs is...
Simultaneous determination of mometasone furoate and calcipotriol in a binary mixture by validated HPLC and chemometric-assisted UV spectrophotometric methods and identification of degradation products by LC-MS.
OBJECTIVES
A new binary mixture containing mometasone furoate (MF) and calcipotriol (CP) is suggested to manage psoriasis; since the combined stability profile of these drugs is poorly understood.
MATERIALS AND METHODS
Herein MF, CP, and their mixtures were subjected to various stress conditions. Also, stability-indicating HPLC was developed and validated according to ICH guidelines with Box-Behnken design. The degradation products (DPs) were predicted and identified using LC-MS. The bioactivity and toxicity of DPs were studied using molecular docking and alamarBlue assay, respectively. Spectroscopic techniques of the first derivative, first-derivative ratio, and the mean-centering of ratio spectra were also used to determine MF and CP in the mixture because of spectra overlapping.
RESULTS
The major degradants for MF in alkaline conditions were DP1, DP2, and DP3, while in thermal and UV conditions, only DP1 was generated. CP gave one degradant in all conditions. No new impurity was observed in the MF and CP mixtures. The results of spectrophotometry showed good linearity in the range of 4-50 and 2-20 µg/ml, while linearity for HPLC was in the range of 4-50 and 0.5-2.5 µg/ml for MF and CP, respectively. Recovery was 99.61-100.38% for UV and 100.4% for HPLC methods of MF and 100.6-101.4% for UV and 99.5% for HPLC methods of CP.
CONCLUSION
The developed methods can be used as simple, accurate, precise, and rapid techniques for routine quality control of MF and CP mixtures.
PubMed: 36594065
DOI: 10.22038/IJBMS.2022.65436.14396 -
Allergy & Rhinology (Providence, R.I.) 2013Allergic rhinoconjunctivitis denotes both nasal and ocular manifestation of allergy, which may be solely treated with intranasal steroid. This study compares the...
Allergic rhinoconjunctivitis denotes both nasal and ocular manifestation of allergy, which may be solely treated with intranasal steroid. This study compares the efficacy of mometasone furoate nasal spray (NS) and fluticasone furoate NS in treatment of allergic rhinoconjunctivitis. The secondary objective is to study the severity of baseline ocular symptoms in allergic rhinoconjunctivitis. Seventy-eight patients with allergic rhinoconjunctivitis were assessed subjectively and objectively using twice-daily symptom scores for nasal (reflective total nasal symptom score [rTNSS] and instantaneous TNSS [iTNSS]) and ocular (reflective total ocular symptom score [rTOSS] and instantaneous TOSS [iTOSS]) symptoms, rhinoconjunctivitis quality-of-life questionnaires (RQOLQs), and acoustic rhinometry. All measurements were taken at baseline and at 4 and 8 weeks of treatment. Sixty-three patients who were randomized into the mometasone furoate group (n = 36) and the fluticasone furoate group (n = 27) completed the study. Seventy-six percent of patients had mild ocular symptoms, 20.5% had moderate symptoms, and only 2.6% had severe symptoms at baseline based on the iTOSS; 65.1% had mild nasal symptoms and 3% had severe nasal symptoms. There was significant reduction in the symptom scores after 1 week (p < 0.05). Both groups had significant improvement in RQOLQ scores after 1 month, which further improved at 2 months (p < 0.05). The nasal dimensions also improved in both groups (p < 0.05) but there was no statistically significant difference between groups. Both mometasone furoate and fluticasone furoate are effective as single-modality treatment of allergic rhinoconjunctivitis. The majority of patients manifest mild ocular symptoms that may be solely treated with intranasal steroids.
PubMed: 24498516
DOI: 10.2500/ar.2013.4.0065 -
The Cochrane Database of Systematic... Dec 2011Lichen sclerosus is a chronic, inflammatory skin condition that most commonly occurs in adult women, although it may also be seen in men and children. It primarily... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Lichen sclerosus is a chronic, inflammatory skin condition that most commonly occurs in adult women, although it may also be seen in men and children. It primarily affects the genital area and around the anus, where it causes persistent itching and soreness. Scarring after inflammation may lead to severe damage by fusion of the vulval lips (labia); narrowing of the vaginal opening; and burying of the clitoris in women and girls, as well as tightening of the foreskin in men and boys, if treatments are not started early. Affected people have an increased risk of genital cancers.
OBJECTIVES
To assess the effects of topical interventions for genital lichen sclerosus and adverse effects reported in included trials.
SEARCH METHODS
We searched the following databases up to 16 September 2011: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE (from 2005), EMBASE (from 2007), LILACS (from 1982), CINAHL (from 1981), British Nursing Index and Archive (from 1985), Science Citation Index Expanded (from 1945), BIOSIS Previews (from 1926), Conference Papers Index (from 1982), and Conference Proceedings Citation Index - Science (from 1990). We also searched ongoing trial registries and scanned the bibliographies of included studies, published reviews, and papers that had cited the included studies.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of topical interventions in genital lichen sclerosus.
DATA COLLECTION AND ANALYSIS
Two authors independently selected trials, extracted data, and assessed the risk of bias. A third author was available for resolving differences of opinion.
MAIN RESULTS
We included 7 RCTs, with a total of 249 participants, covering 6 treatments. Six of these RCTs tested the efficacy of one active intervention against placebo or another active intervention, while the other trial tested three active interventions against placebo.When compared to placebo in one trial, clobetasol propionate 0.05% was effective in treating genital lichen sclerosus in relation to the following outcomes: 'participant-rated improvement or remission of symptoms' (risk ratio (RR) 2.85, 95% confidence interval (CI) 1.45 to 5.61) and 'investigator-rated global degree of improvement' (standardised mean difference (SMD) 5.74, 95% CI 4.26 to 7.23).When mometasone furoate 0.05% was compared to placebo in another trial, there was a significant improvement in the 'investigator-rated change in clinical grade of phimosis' (SMD -1.04, 95% CI -1.77 to -0.31).Both trials found no significant differences in reported adverse drug reactions between the corticosteroid and placebo groups. The data from four trials found no significant benefit for topical testosterone, dihydrotestosterone, and progesterone. When used as maintenance therapy after an initial treatment with topical clobetasol propionate in another trial, topical testosterone worsened the symptoms (P < 0.05), but the placebo did not.One trial found no differences between pimecrolimus and clobetasol propionate in relieving symptoms through change in pruritus (itching) (SMD -0.33, 95% CI -0.99 to 0.33) and burning/pain (SMD 0.03, 95% CI -0.62 to 0.69). However, pimecrolimus was less effective than clobetasol propionate with regard to the 'investigator-rated global degree of improvement' (SMD -1.64, 95% CI -2.40 to -0.87). This trial found no significant differences in reported adverse drug reactions between the pimecrolimus and placebo groups.
AUTHORS' CONCLUSIONS
The current limited evidence demonstrates the efficacy of clobetasol propionate, mometasone furoate, and pimecrolimus in treating genital lichen sclerosus. Further RCTs are needed to determine the optimal potency and regimen of topical corticosteroids, examine other topical interventions, assess the duration of remission or prevention of flares, evaluate the reduction in the risk of genital squamous cell carcinoma or genital intraepithelial neoplasia, and examine the efficacy in improving the quality of the sex lives of people with this condition.
Topics: Adult; Anti-Inflammatory Agents; Child; Clobetasol; Dermatologic Agents; Dihydrotestosterone; Female; Genital Diseases, Male; Humans; Lichen Sclerosus et Atrophicus; Male; Mometasone Furoate; Pregnadienediols; Randomized Controlled Trials as Topic; Tacrolimus; Testosterone Propionate; Vulvar Lichen Sclerosus
PubMed: 22161424
DOI: 10.1002/14651858.CD008240.pub2 -
Pulmonary Pharmacology & Therapeutics Oct 2021QMF149 is an inhaled fixed-dose combination of indacaterol acetate and mometasone furoate (MF) delivered via Breezhaler®, under development for once-daily treatment of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
QMF149 is an inhaled fixed-dose combination of indacaterol acetate and mometasone furoate (MF) delivered via Breezhaler®, under development for once-daily treatment of asthma. MF delivered via Twisthaler® is approved as Asmanex® Twisthaler® for the treatment of asthma. Bridging of MF delivered via Twisthaler® to MF delivered via Breezhaler® was undertaken as part of QMF149 development to enable dose comparisons between the devices. Pharmacokinetics (PK) of MF were characterized in two studies; a single dose PK study in healthy volunteers and a pharmacokinetic/pharmacodynamic (PK/PD) study in asthma patients.
OBJECTIVES
The PK study in healthy volunteers evaluated the PK of single doses of MF via Breezhaler® (50-400 μg) and compared systemic exposure of MF following administration via Breezhaler® and Twisthaler® 400 μg (2 inhalations of 200 μg). The study in patients with asthma characterized the MF PK profile following once-daily inhalation of MF via Breezhaler® and Twisthaler® devices for 4 weeks.
METHODS
In the open-label, single-dose, crossover study, healthy subjects sequentially received MF via Twisthaler® (400 μg, medium-dose inhaled corticosteroid [ICS]) and escalating doses via Breezhaler® (50, 100, 200, 400 μg). PK data were obtained up to 72 h post-dose. In the double-blind, double-dummy, parallel-group study, asthma patients were randomised to receive either MF 80 μg (low-dose ICS) or 320 μg (high-dose ICS) via Breezhaler®, or 200 μg (low-dose ICS) or 800 μg (2 inhalations of 400 μg; high-dose ICS) via Twisthaler® once daily for 4 weeks. PK sampling was performed on Days 1 and 28 at pre-dose and up to 24 h post-dose.
RESULTS
In the healthy volunteer PK study, 20 healthy subjects completed all treatments. Dose-normalised AUC of MF was 1.8-1.9-fold higher when delivered via Breezhaler® versus Twisthaler®. AUC and C of MF increased in a dose-proportional manner over the range of 50-400 μg via Breezhaler®. Results from this study guided dose selection of MF via Breezhaler® for the asthma study. In the asthma study, in a subset of 96 patients, mean systemic exposure (AUC and C) for MF 80 and 320 μg via Breezhaler® was comparable with MF 200 and 800 μg via Twisthaler®, respectively, on Day 28.
CONCLUSION
PK characterization in a healthy volunteer PK study and subsequently an asthma study enabled selection of 80 μg (low), 160 μg (medium), and 320 μg (high) delivered via Breezhaler® as MF doses comparable to the 200 μg, 400 μg and 800 μg doses delivered by Twisthaler®, respectively, as part of QMF149 formulation development.
Topics: Administration, Inhalation; Asthma; Cross-Over Studies; Double-Blind Method; Dry Powder Inhalers; Humans; Mometasone Furoate; Pregnadienediols
PubMed: 33771722
DOI: 10.1016/j.pupt.2021.102019 -
PloS One 2023The life quality of about two-thirds of patients with COVID-19 is affected by related olfactory dysfunctions. The negative impact of olfactory dysfunction ranged from...
Effect of any form of steroids in comparison with that of other medications on the duration of olfactory dysfunction in patients with COVID-19: A systematic review of randomized trials and quasi-experimental studies.
BACKGROUND
The life quality of about two-thirds of patients with COVID-19 is affected by related olfactory dysfunctions. The negative impact of olfactory dysfunction ranged from the decreased pleasure of eating to impaired quality of life. This research aimed to provide a comprehensive understanding of the effects of corticosteroid treatments by comparing that to other currently available treatments and interventions.
METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist's 27-point checklist was used to conduct this review. PubMed (Public/Publisher MEDLINE), PubMed Central and EMBASE (Excerpta Medica Database) databases were conveniently selected and Boolean search commands were used for a comprehensive literature search. Five core search terms were "effects of treatments", " COVID-19-related olfactory dysfunction", "corticosteroids", "treatments" and "interventions". The reporting qualities of the included studies were appraised using JBI (Joanna Briggs Institute) appraisal tools. The characteristics of the 21 experimental studies with a total sample (of 130,550) were aggregated using frequencies and percentages and presented descriptively. The main interventions and their effects on the duration of the COVID-19-related olfactory dysfunction were narratively analyzed.
RESULTS
Among patients with COVID-19, the normal functions of the olfactory lobe were about 23 days earlier to gain with the treatments of fluticasone and triamcinolone acetonide nasal spray compared with that of mometasone furoate nasal spray and oral corticosteroid. The smell loss duration was reduced by fluticasone and triamcinolone acetonide nasal spray 9 days earlier than the inflawell syrup and 16 days earlier than the lavender syrup. The nasal spray of corticosteroids ended the COVID-19-related smell loss symptoms 2 days earlier than the zinc supplementation, about 47 days earlier than carbamazepine treatment and was more effective than palmitoylethanolamide (PEA) and luteolin and omega-3 supplementations and olfactory training. Treatment with oral corticosteroid plus olfactory training significantly improved Threshold, Discrimination and Identification (TDI) scores compared with olfactory training alone. A full dose of the COVID-19 vaccination was not uncertain to reduce the COVID-19-related smell loss duration.
CONCLUSION
Corticosteroid treatment is effective in reducing the duration of COVID-19-related smell loss and olfactory training, the basic, essential and effective intervention, should be used as a combination therapy.
Topics: Humans; Nasal Sprays; Anosmia; Quality of Life; Triamcinolone Acetonide; COVID-19; Randomized Controlled Trials as Topic; Steroids; Adrenal Cortex Hormones; Fluticasone
PubMed: 37531338
DOI: 10.1371/journal.pone.0288285 -
BMC Pulmonary Medicine Jan 2021A once-daily (o.d.) fixed-dose combination of indacaterol acetate (IND), glycopyrronium bromide (GLY), and mometasone furoate (MF) delivered via the Breezhaler device...
BACKGROUND
A once-daily (o.d.) fixed-dose combination of indacaterol acetate (IND), glycopyrronium bromide (GLY), and mometasone furoate (MF) delivered via the Breezhaler device (IND/GLY/MF) is being developed for treatment of asthma. This study compared steady-state pharmacokinetics of IND, GLY and MF between Japanese and Caucasian male subjects after multiple inhalations of IND/GLY/MF o.d.
METHODS
This was a single-center, open-label, 2-treatment crossover study with a 21-day washout period. Japanese and Caucasian subjects received IND/GLY/MF 150/50/80 μg (inhaled corticosteroid [ICS] medium-dose) or 150/50/160 μg o.d. (ICS high-dose) for 14 days in each period. Pharmacokinetics were characterized up to 24 h post-dose on Days 1 and 14.
RESULTS
In total, 16 Japanese (median age 31 years [range 20-40 years], mean weight 68.3 kg) and 17 Caucasian subjects (median age 27 years [range 21-43 years], mean weight 75.0 kg) were randomized. Geometric mean ratios (Japanese/Caucasian) [90% confidence interval (CI)] for C for IND, GLY and MF at the high ICS dose on Day 14 were 1.31 [1.13, 1.51] 1.38 [1.13, 1.69] and 1.07 [0.969, 1.18], respectively. Geometric mean ratios (Japanese/Caucasian) [90% CI] for AUC on Day 14 for IND, GLY and MF at the high ICS dose were 1.17 [1.01, 1.35], 1.05 [0.920, 1.20] and 1.15 [1.05, 1.27] respectively. Similar trends were noted for all components for the medium ICS dose treatment. IND/GLY/MF was safe and well tolerated; no AEs suspected to be study drug-related were observed.
CONCLUSION
Pharmacokinetics of IND, GLY and MF (high and medium dose) when delivered as a fixed-dose combination were comparable between Japanese and Caucasian subjects. The IND/GLY/MF combination at the administrated doses was safe and well tolerated in both ethnic groups.
TRIAL REGISTRATION
Japan Registry of Clinical Trial: jRCT2031200227, retrospectively registered on 04, December, 2020.
Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Asian People; Cross-Over Studies; Drug Combinations; Female; Glycopyrrolate; Healthy Volunteers; Humans; Indans; Male; Mometasone Furoate; Quinolones; White People; Young Adult
PubMed: 33413291
DOI: 10.1186/s12890-020-01382-6 -
The Cochrane Database of Systematic... Apr 2019Hand eczema is an inflammation of the skin of the hands that tends to run a chronic, relapsing course. This common condition is often associated with itch, social... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hand eczema is an inflammation of the skin of the hands that tends to run a chronic, relapsing course. This common condition is often associated with itch, social stigma, and impairment in employment. Many different interventions of unknown effectiveness are used to treat hand eczema.
OBJECTIVES
To assess the effects of topical and systemic interventions for hand eczema in adults and children.
SEARCH METHODS
We searched the following up to April 2018: Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, AMED, LILACS, GREAT, and four trials registries. We checked the reference lists of included studies for further references to relevant trials.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that compared interventions for hand eczema, regardless of hand eczema type and other affected sites, versus no treatment, placebo, vehicle, or active treatments.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Primary outcomes were participant- and investigator-rated good/excellent control of symptoms, and adverse events.
MAIN RESULTS
We included 60 RCTs, conducted in secondary care (5469 participants with mild to severe chronic hand eczema). Most participants were over 18 years old. The duration of treatment was short, generally up to four months. Only 24 studies included a follow-up period. Clinical heterogeneity in treatments and outcome measures was evident. Few studies performed head-to-head comparisons of different interventions. Risk of bias varied considerably, with only five studies at low risk in all domains. Twenty-two studies were industry-funded.Eighteen trials studied topical corticosteroids or calcineurin inhibitors; 10 studies, phototherapy; three studies, systemic immunosuppressives; and five studies, oral retinoids. Most studies compared an active intervention against no treatment, variants of the same medication, or placebo (or vehicle). Below, we present results from the main comparisons.Corticosteroid creams/ointments: when assessed 15 days after the start of treatment, clobetasol propionate 0.05% foam probably improves participant-rated control of symptoms compared to vehicle (risk ratio (RR) 2.32, 95% confidence interval (CI) 1.38 to 3.91; number needed to treat for an additional beneficial outcome (NNTB) 3, 95% CI 2 to 8; 1 study, 125 participants); the effect of clobetasol compared to vehicle for investigator-rated improvement is less clear (RR 1.43, 95% CI 0.86 to 2.40). More participants had at least one adverse event with clobetasol (11/62 versus 5/63; RR 2.24, 95% CI 0.82 to 6.06), including application site burning/pruritus. This evidence was rated as moderate certainty.When assessed 36 weeks after the start of treatment, mometasone furoate cream used thrice weekly may slightly improve investigator-rated symptom control compared to twice weekly (RR 1.23, 95% CI 0.94 to 1.61; 1 study, 72 participants) after remission is reached. Participant-rated symptoms were not measured. Some mild atrophy was reported in both groups (RR 1.76, 95% CI 0.45 to 6.83; 5/35 versus 3/37). This evidence was rated as low certainty.Irradiation with ultraviolet (UV) light: local combination ultraviolet light therapy (PUVA) may lead to improvement in investigator-rated symptom control when compared to local narrow-band UVB after 12 weeks of treatment (RR 0.50, 95% CI 0.22 to 1.16; 1 study, 60 participants). However, the 95% CI indicates that PUVA might make little or no difference. Participant-rated symptoms were not measured. Adverse events (mainly erythema) were reported by 9/30 participants in the narrow-band UVB group versus none in the PUVA group. This evidence was rated as moderate certainty.Topical calcineurin inhibitors: tacrolimus 0.1% over two weeks probably improves investigator-rated symptom control measured after three weeks compared to vehicle (14/14 tacrolimus versus 0/14 vehicle; 1 study). Participant-rated symptoms were not measured. Four of 14 people in the tacrolimus group versus zero in the vehicle group had well-tolerated application site burning/itching.A within-participant study in 16 participants compared 0.1% tacrolimus to 0.1% mometasone furoate but did not measure investigator- or participant-rated symptoms. Both treatments were well tolerated when assessed at two weeks during four weeks of treatment.Evidence from these studies was rated as moderate certainty.Oral interventions: oral cyclosporin 3 mg/kg/d probably slightly improves investigator-rated (RR 1.88, 95% CI 0.88 to 3.99; 1 study, 34 participants) or participant-rated (RR 1.25, 95% CI 0.69 to 2.27) control of symptoms compared to topical betamethasone dipropionate 0.05% after six weeks of treatment. The risk of adverse events such as dizziness was similar between groups (up to 36 weeks; RR 1.22, 95% CI 0.80 to 1.86, n = 55; 15/27 betamethasone versus 19/28 cyclosporin). The evidence was rated as moderate certainty.Alitretinoin 10 mg improves investigator-rated symptom control compared with placebo (RR 1.58, 95% CI 1.20 to 2.07; NNTB 11, 95% CI 6.3 to 26.5; 2 studies, n = 781) and alitretinoin 30 mg also improves this outcome compared with placebo (RR 2.75, 95% CI 2.20 to 3.43; NNTB 4, 95% CI 3 to 5; 2 studies, n = 1210). Similar results were found for participant-rated symptom control: alitretinoin 10 mg RR 1.73 (95% CI 1.25 to 2.40) and 30 mg RR 2.75 (95% CI 2.18 to 3.48). Evidence was rated as high certainty. The number of adverse events (including headache) probably did not differ between alitretinoin 10 mg and placebo (RR 1.01, 95% CI 0.66 to 1.55; 1 study, n = 158; moderate-certainty evidence), but the risk of headache increased with alitretinoin 30 mg (RR 3.43, 95% CI 2.45 to 4.81; 2 studies, n = 1210; high-certainty evidence). Outcomes were assessed between 48 and 72 weeks.
AUTHORS' CONCLUSIONS
Most findings were from single studies with low precision, so they should be interpreted with caution. Topical corticosteroids and UV phototherapy were two of the major standard treatments, but evidence is insufficient to support one specific treatment over another. The effect of topical calcineurin inhibitors is not certain. Alitretinoin is more effective than placebo in controlling symptoms, but advantages over other treatments need evaluating.Well-designed and well-reported, long-term (more than three months), head-to-head studies comparing different treatments are needed. Consensus is required regarding the definition of hand eczema and its subtypes, and a standard severity scale should be established.The main limitation was heterogeneity between studies. Small sample size impacted our ability to detect differences between treatments.
Topics: Calcineurin Inhibitors; Eczema; Emollients; Humans; Immunosuppressive Agents; Odds Ratio; Pruritus; Randomized Controlled Trials as Topic; Severity of Illness Index; Treatment Outcome
PubMed: 31025714
DOI: 10.1002/14651858.CD004055.pub2 -
Journal of Otolaryngology - Head & Neck... Apr 2023Chronic rhinosinusitis (CRS) is a complex inflammatory disease of the sinonasal tract. To understand this disease entity and develop targeted treatments, a reproducible...
BACKGROUND
Chronic rhinosinusitis (CRS) is a complex inflammatory disease of the sinonasal tract. To understand this disease entity and develop targeted treatments, a reproducible animal model is paramount.
AIMS/OBJECTIVES
To optimize a murine model of eosinophilic CRS by establishing benchmark histological markers and validate its fidelity in evaluating intranasal treatments.
MATERIAL AND METHODS
Forty-five Balb/c mice were included in the 7-week protocol. Experimental animals (n = 20) were induced a CRS disease state upon receiving intraperitoneal sensitization with ovalbumin (OVA), followed by intranasal OVA with Aspergillus oryzae protease. Analysis of complete blood count with differential, peripheral blood smear, and histological markers from the nasal cavity mucosa were performed. CRS mice were additionally treated with intranasal saline (n = 5) or mometasone (n = 10) and compared with control groups of untreated CRS (n = 5) and healthy (n = 5) mice after week 7.
RESULTS
Histological analysis of experimental animal nasal mucosa revealed significantly higher levels of eosinophilic tissue infiltration/degranulation, hyaline droplets, Charcot-Leyden crystals, and respiratory epithelial thickness compared to healthy controls. Treatment with mometasone significantly reversed the histopathological changes observed in CRS mice.
CONCLUSION AND SIGNIFICANCE
This murine model induced substantial local eosinophilic inflammation within sinonasal mucosa, that was reversible with mometasone. This model may be used to evaluate the efficacy of therapeutics designed to target CRS.
Topics: Animals; Mice; Rhinitis; Disease Models, Animal; Sinusitis; Nasal Mucosa; Chronic Disease; Eosinophilia; Nasal Polyps; Mometasone Furoate
PubMed: 37098626
DOI: 10.1186/s40463-023-00637-6 -
Journal of Personalized Medicine Nov 2023The nasal microbiome represents the main environmental factor of the inflammatory process in chronic rhinosinusitis (CRS). Antibiotics and steroids constitute the... (Review)
Review
BACKGROUND
The nasal microbiome represents the main environmental factor of the inflammatory process in chronic rhinosinusitis (CRS). Antibiotics and steroids constitute the mainstay of CRS therapies. However, their impact on microbial communities needs to be better understood. This systematic review summarizes the evidence about antibiotics' and steroids' impact on the nasal microbiota in patients with CRS.
METHODS
The search strategy was conducted in accordance with the PRISMA guidelines for systematic reviews. The authors searched all papers in the three major medical databases (PubMed, Scopus, and Cochrane Library) using the PICO tool (population, intervention, comparison, and outcomes). The search was carried out using a combination of the key terms "Microbiota" or "Microbiome" and "Chronic Rhinosinusitis".
RESULTS
Overall, 402 papers were identified, and after duplicate removal (127 papers), excluding papers off-topic (154) and for other structural reasons (110), papers were assessed for eligibility; finally, only 11 papers were included and summarized in the present systematic review. Some authors used only steroids, other researchers used only antibiotics, and others used both antibiotics and steroids. With regard to the use of steroids as exclusive medical treatment, topical mometasone and budesonide were investigated. With regard to the use of antibiotics as exclusive medical treatments, clarithromycin, doxycycline, roxithromycin, and amoxicillin clavulanate were investigated. Regarding the use of both antibiotics and steroids, two associations were investigated: systemic prednisone combined with amoxicillin clavulanate and topical budesonide combined with azithromycin.
CONCLUSIONS
The impact that therapies can have on the nasal microbiome of CRS patients is very varied. Further studies are needed to understand the role of the nasal microbiome, prevent CRS, and improve therapeutic tools for personalized medicine tailored to the individual patient.
PubMed: 38003898
DOI: 10.3390/jpm13111583