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Clinical Otolaryngology : Official... Jul 2024Leukotrienes play a significant role in the pathogenesis of adenoid hypertrophy (A.H.). Therefore, we aimed to analyse the role of montelukast, a leukotriene receptor... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Leukotrienes play a significant role in the pathogenesis of adenoid hypertrophy (A.H.). Therefore, we aimed to analyse the role of montelukast, a leukotriene receptor antagonist, alone or in combination with mometasone, a potent local intranasal steroid, for the treatment of A.H.
METHODS
Participants were children with A.H. were treated with montelukast alone or montelukast and mometasone furoate. The main outcome measures were effect of montelukast on clinical symptoms of A.H. A literature review was conducted using online search engines, Cochrane Library, PubMed, Web of Science and Scopus, for randomized clinical trials assessing children with A.H. treated with montelukast alone or montelukast and mometasone furoate. Seven randomized clinical trials (RCTs) were included with 742 children.
RESULTS
Our study reveals that montelukast alone or in combination with intranasal mometasone furoate significantly improves clinical symptoms of adenoid hypertrophy such as snoring, sleeping disturbance, mouth breathing and A/N ratio. Montelukast was superior to placebo in decreasing snoring (SMD = -1.00, 95% CI [-1.52, -0.49]), sleep discomfort (SMD = -1.26, 95% CI [-1.60, -0.93]), A/N ratio (MD = -0.11, 95% CI [-0.14, -0.09]) and mouth breathing (SMD = -1.36, 95% CI [-1.70, -1.02]). No difference was detected between montelukast and mometasone versus mometasone alone in snoring (SMD = -0.21, 95%CI [-0.69, 0.27]); however, the combination group was superior to the mometasone alone in mouth breathing (SMD = -0.46, 95% CI [-0.73, -0.19]).
CONCLUSIONS
The limitation of studies included a small sample size, with an overall low to medium quality. Thus, further larger, higher-quality RCTs are recommended to provide more substantial evidence.
Topics: Humans; Adenoids; Cyclopropanes; Quinolines; Acetates; Sulfides; Hypertrophy; Child; Mometasone Furoate; Leukotriene Antagonists; Administration, Intranasal; Drug Therapy, Combination; Treatment Outcome
PubMed: 38700144
DOI: 10.1111/coa.14169 -
Cureus Mar 2024Lichen planus (LP) is a common T-cell-mediated autoimmune skin disease, and its exact etiology is unknown. Typically, it affects the trunk, flexural surfaces, and the...
Lichen planus (LP) is a common T-cell-mediated autoimmune skin disease, and its exact etiology is unknown. Typically, it affects the trunk, flexural surfaces, and the mucosa.We report a rare finding of LP involving both eyelids in a 67-year-old female. A 67-year-old Saudi female with a medical history of diabetes mellitus, hypothyroidism and rheumatoid arthritis presented with a three-month history of pruritic skin eruptions in both eyelids. She had no associated musculoskeletal symptoms or fatigue and no medical or family history of atopy. The patient had violaceous, thin, scaly plaques confined to both eyelids. Oral mucosa, genitalia, scalp, and nails were not affected. Histopathology from the right lower eyelid confirmed the diagnosis of LP. Hepatitis C virus serology was negative. Patient was examined by ophthalmology to rule out conjunctival involvement of LP. She had dry eyes only. She was initially managed by topical tacrolimus 0.1% ointment and didn't tolerate it due to severe reaction. She tolerated mometasone propionate 0.1% cream, which relieved the itch and partially improved the lesions. Although rare, LP of the eyelids must be considered among differential diagnoses of eyelid dermatitis. It can be confined, or it may concomitantly involve other parts of the body. LP of the eyelid may also extend to the conjunctiva, so it's important to screen patients by ophthalmology to rule out possible ocular involvement. This is the first case report of a Saudi patient with LP confined to the eyelid. The management of LP involving the eyelids is challenging. Treatment options include topical steroids, tacrolimus ointment, phototherapy and oral retinoids (etretinate).
PubMed: 38690479
DOI: 10.7759/cureus.57299 -
International Journal of Clinical... Apr 2024Inhalational corticosteroids (ICS) were observed to increase the pneumonia risk in chronic obstructive pulmonary airway disorder (COPD). However, it is unknown whether... (Review)
Review
BACKGROUND
Inhalational corticosteroids (ICS) were observed to increase the pneumonia risk in chronic obstructive pulmonary airway disorder (COPD). However, it is unknown whether any differences exist between the drugs within the ICS class.
AIM
This study aimed to evaluate the risk of pneumonia associated with different ICS and identify factors that predict pneumonia in patients with moderate-to-severe COPD using a network meta-analysis.
METHOD
Electronic databases (Medline, Cochrane CENTRAL and Google Scholar) were searched for trials comparing ICS in COPD patients. The outcomes were pneumonia and serious pneumonia. Odds ratios (OR) with 95% confidence interval (95% CI) were estimated. Meta-regression was used to identify the predictors. The strength of evidence was graded using the Grading of Recommendations, Assessment, Development, and Evaluations approach.
RESULTS
Sixty-six studies (103,347 participants) were included. Fluticasone (OR: 1.46; 95% CI: 1.26, 1.7), mometasone (OR: 2.2; 95% CI: 1.05, 4.6), and beclometasone (OR: 1.7; 95% CI: 1.1, 2.6) were observed with an increased pneumonia risk compared to placebo. Fluticasone (OR: 1.5; 95% CI: 1.3, 1.7) was observed with an increased risk of serious pneumonia. High doses (OR: 1.2; 95% CI: 1.03, 1.4), BMI ≥ 25 kg/m (OR: 1.6; 95% CI: 1.1, 2.2), and history of exacerbations in the preceding year predicted the pneumonia risk. Evidence strength was moderate.
CONCLUSION
ICS class differences in pneumonia risk were observed in terms of pooled effect estimates but it is unlikely that any clinically relevant differences exist. Risk-benefit analysis supports ICS use in moderate-severe COPD.
PubMed: 38664319
DOI: 10.1007/s11096-024-01736-8 -
Journal of Clinical Medicine Mar 2024: Mometasone furoate nasal spray is efficacious in relieving allergic rhinitis symptoms. The objectives of this study were, firstly, to compare the efficacy of Elonide...
: Mometasone furoate nasal spray is efficacious in relieving allergic rhinitis symptoms. The objectives of this study were, firstly, to compare the efficacy of Elonide to Nasonex and a placebo and secondly, to investigate the side effects of Elonide. : This was a prospective, single-centered, double blinded, randomized, placebo-controlled, non-inferiority trial. A total of 163 participants from the Otorhinolaryngology Clinic, Hospital Canselor Tuanku Muhriz (HCTM), were randomized into three treatment groups receiving Elonide (n = 56), Nasonex (n = 54), and placebo (n = 53) nasal sprays using an online randomizer (Random.org). Treatment was administered for 4 weeks. The primary outcome measure was the Total Nasal Resistance (TNR), and the secondary outcomes were the Visual Analogue Score (VAS) and the Rhinoconjunctivitis Quality of Life Questionnaire (RQOLQ) score. Side effects were recorded. : There were significant improvements for all groups from baseline. The Elonide group had the greatest mean difference for all primary and secondary outcomes compared to Nasonex and the placebo (0.77 ± 2.44 vs. 0.35 ± 1.16, = 1.00 vs. 0.17 ± 0.82, = 0.01). Elonide is non-inferior to Nasonex ( = 1.00) and superior to the placebo ( < 0.05). The highest side effects reported were for Nasonex (n = 14, 26%), followed by the placebo (n = 8, 16%) and Elonide (n = 6, 12%); headaches (n = 9, 17%) and sore throat (n = 9, 17%) were the most common. : Elonide has similar efficacy to Nasonex when compared to a placebo in the treatment of AR in adults. Elonide is safe and tolerable, with fewer side effects and no adverse side effects.
PubMed: 38610648
DOI: 10.3390/jcm13071883 -
Biomedical Chromatography : BMC Jul 2024We report the development and the validation of a sensitive liquid chromatography-mass spectrometry (LC-MS/MS) method for mometasone furoate (MF) analysis in human...
Highly sensitive liquid chromatography-mass spectrometry method for the quantitative analysis of mometasone furoate in human plasma: Method validation and application to clinical pharmacokinetic studies.
We report the development and the validation of a sensitive liquid chromatography-mass spectrometry (LC-MS/MS) method for mometasone furoate (MF) analysis in human plasma. Plasma samples were processed through liquid-liquid extraction and analyzed using LC-MS/MS operating in positive mode using multiple reaction monitoring of transitions m/z 520.9 → 355.0 and m/z 525.8 → 355.0 for MF and the internal standard (IS), respectively. Separation was achieved at 1.0 mL/min on a C column using a gradient elution of mobile phase of 0.05% ammonia in water (phase A) and acetonitrile (phase B). The assay range was 0.250-100 pg/mL and proved to be accurate and precise MF. Normalized recoveries were consistent and reproducible with a coefficient of variation (CV%) value of 6.0. The CV (%) of the IS normalized matrix factor was not observed in normal, lipemic, and hemolyzed plasmas. Dilutions of 1:10 were accurately quantified. A cycle of three freeze and thaw and stabilities at room temperature and on the autosampler were demonstrated. In addition, MF in the presence of indacaterol and glycopyrronium was proven to be stable at -70°C for at least 157 days. The present method was successfully applied to quantify MF in patients receiving MF, indacaterol, and glycopyrronium as a fixed-dose combination.
Topics: Humans; Mometasone Furoate; Tandem Mass Spectrometry; Reproducibility of Results; Chromatography, Liquid; Linear Models; Sensitivity and Specificity; Drug Stability; Liquid-Liquid Extraction; Limit of Detection; Liquid Chromatography-Mass Spectrometry
PubMed: 38599686
DOI: 10.1002/bmc.5871 -
Leukemia Research May 2024Over the years, the overall survival of older patients diagnosed with acute myeloid leukemia (AML) has not significantly increased. Although standard cytotoxic therapies...
Over the years, the overall survival of older patients diagnosed with acute myeloid leukemia (AML) has not significantly increased. Although standard cytotoxic therapies that rapidly eliminate dividing myeloblasts are used to induce remission, relapse can occur due to surviving therapy-resistant leukemic stem cells (LSCs). Hence, anti-LSC strategies have become a key target to cure AML. We have recently shown that previously approved cardiac glycosides and glucocorticoids target LSC-enriched CD34 cells in the primary human AML 8227 model with more efficacy than normal hematopoietic stem cells (HSCs). To translate these in vitro findings into humans, we developed a mathematical model of stem cell dynamics that describes the stochastic evolution of LSCs in AML post-standard-of-care. To this, we integrated population pharmacokinetic-pharmacodynamic (PKPD) models to investigate the clonal reduction potential of several promising candidate drugs in comparison to cytarabine, which is commonly used in high doses for consolidation therapy in AML patients. Our results suggest that cardiac glycosides (proscillaridin A, digoxin and ouabain) and glucocorticoids (budesonide and mometasone) reduce the expansion of LSCs through a decrease in their viability. While our model predicts that effective doses of cardiac glycosides are potentially too toxic to use in patients, simulations show the possibility of mometasone to prevent relapse through the glucocorticoid's ability to drastically reduce LSC population size. This work therefore highlights the prospect of these treatments for anti-LSC strategies and underlines the use of quantitative approaches to preclinical drug translation in AML.
Topics: Humans; Leukemia, Myeloid, Acute; Neoplastic Stem Cells; Models, Theoretical; Cytarabine
PubMed: 38579483
DOI: 10.1016/j.leukres.2024.107485 -
Animal Models and Experimental Medicine Apr 2024Adenoid hypertrophy (AH) is a common pediatric disease that significantly impacts the growth and quality of life of children. However, there is no replicable and valid...
BACKGROUND
Adenoid hypertrophy (AH) is a common pediatric disease that significantly impacts the growth and quality of life of children. However, there is no replicable and valid model for AH.
METHODS
An AH rat model was developed via comprehensive allergic sensitization, chronic inflammation induction, and chronic intermittent hypoxia (CIH). The modeling process involved three steps: female Sprague-Dawley rats (aged 4-5 weeks) were used for modeling. Allergen sensitization was induced via intraperitoneal administration and intranasal provocation using ovalbumin (OVA); chronic nasal inflammation was induced through intranasal lipopolysaccharide (LPS) administration for sustained nasal irritation; CIH akin to obstructive sleep apnea/hypopnea syndrome was induced using an animal hypoxia chamber. Postmodel establishment, behaviors, and histological changes in nasopharynx-associated lymphoid tissue (NALT) and nasal mucosa were assessed. Arterial blood gas analysis and quantification of serum and tissue levels of (interleukin) IL-4 and IL-13, OVA-specific immunoglobulin E (sIgE), eosinophil cationic protein (ECP), tumor necrosis factor (TNF-α), IL-17, and transforming growth factor (TGF)-β were conducted for assessment. The treatment group received a combination of mometasone furoate and montelukast sodium for a week and then was evaluated.
RESULTS
Rats exhibited notable nasal symptoms and hypoxia after modeling. Histopathological analysis revealed NALT follicle hypertrophy and nasal mucosa inflammatory cell infiltration. Elevated IL-4, IL-13, IL-17, OVA-sIgE, ECP, and TNF-α levels and reduced TGF-β levels were observed in the serum and tissue of model-group rats. After a week of treatment, the treatment group exhibited symptom and inflammatory factor improvement.
CONCLUSION
The model effectively simulates AH symptoms and pathological changes. But it should be further validated for genetic, immunological, and hormonal backgrounds in the currently used and other strains and species.
PubMed: 38572767
DOI: 10.1002/ame2.12396 -
Skin Appendage Disorders Apr 2024Psoriasis is an autoimmune papulosquamous disorder characterized by erythematous plaques. There are various subtypes, of which follicular psoriasis (FP) is an...
INTRODUCTION
Psoriasis is an autoimmune papulosquamous disorder characterized by erythematous plaques. There are various subtypes, of which follicular psoriasis (FP) is an underreported entity, presenting as scaly follicular papules. Only a few cases have been reported, with limited dermoscopy findings having been described. This report aims to review the literature and emphasize the role of dermoscopy in the diagnosis of this rare variant.
CASE REPORT
A 31-year-old diabetic and obese male presented with symmetrical, itchy, scaly follicular lesions on his axillae, elbows, and knees for 6 months. Clinical differentials included follicular pityriasis rosea, pityriasis versicolor, or eczema. Dermoscopy revealed white scales and erythematous areas with multiple red dots present around hair follicles. Histopathology showed distended follicular infundibula with parakeratotic scales and psoriasiform changes, leading to a diagnosis of FP. Treatment with topical mometasone furoate and oral levocetirizine led to complete resolution within a month.
DISCUSSION
FP is a relatively uncommon subtype of psoriasis, manifesting differently in adults and juveniles. Although its exact cause remains unknown, hair follicle immune cells and/or keratin 17 (K17) may be involved. Dermoscopy can help distinguish it by revealing typical features including perifollicular white scales and vascular structures. Further epidemiological studies and long-term follow-up are needed for a comprehensive understanding of FP.
PubMed: 38572197
DOI: 10.1159/000536049 -
Drug Metabolism and Disposition: the... Apr 2024Drug-induced liver injury (DILI) is a frequent cause of clinical trial failures during drug development. While inhibiting bile salt export pump (BSEP) is a...
Drug-induced liver injury (DILI) is a frequent cause of clinical trial failures during drug development. While inhibiting bile salt export pump (BSEP) is a well-documented DILI mechanism, interference with genes related to bile acid (BA) metabolism and transport can further complicate DILI development. Here, the effects of twenty-eight compounds on genes associated with BA metabolism and transport were evaluated, including those with discontinued development or use, boxed warnings, and clean labels for DILI. The study also included rifampicin and omeprazole, pregnane X receptor and aryl hydrocarbon receptor ligands, and four mitogen-activated protein kinase kinase (MEK1/2) inhibitors. BSEP inhibitors with more severe DILI, notably pazopanib and CP-724714, significantly upregulated the expression of 7 alpha-hydroxylase (CYP7A1), independent of small heterodimer partner (SHP) expression. CYP7A1 expression was marginally induced by omeprazole. In contrast, its expression was suppressed by mometasone (10-fold), vinblastine (18-fold), hexachlorophene (2-fold), bosentan (2.1-fold), and rifampin (2-fold). All four MEK1/2 inhibitors that show clinical DILI were not potent BSEP inhibitors but significantly induced CYP7A1 expression, accompanied by a significant SHP gene suppression. Sulfotransferase 2A1 and BSEP were marginally upregulated, but no other genes were altered by the drugs tested. Protein levels of CYP7A1 were increased with the treatment of CYP7A1 inducers and decreased with obeticholic acid, an farnesoid X receptor ligand. CYP7A1 inducers significantly increased bile acid (BA) production in hepatocytes, indicating the overall regulatory effects of BA metabolism. This study demonstrates that CYP7A1 induction via various mechanisms can pose a risk for DILI, independently or in synergy with BSEP inhibition, and it should be evaluated early in drug discovery. SIGNIFICANCE STATEMENT: Kinase inhibitors, pazopanib and CP-724714, inhibit BSEP and induce CYP7A1 expression independent of small heterodimer partner (SHP) expression, leading to increased bile acid (BA) production and demonstrating clinically elevated drug-induced liver toxicity. MEK1/2 inhibitors that show BSEP-independent drug-induced liver injury (DILI) induced the CYP7A1 gene accompanied by SHP suppression. CYP7A1 induction via SHP-dependent or independent mechanisms can pose a risk for DILI, independently or in synergy with BSEP inhibition. Monitoring BA production in hepatocytes can reliably detect the total effects of BA-related gene regulation for de-risking.
Topics: Humans; ATP Binding Cassette Transporter, Subfamily B, Member 11; Indazoles; Chemical and Drug Induced Liver Injury; Omeprazole; Bile Acids and Salts; Cholesterol 7-alpha-Hydroxylase; Pyrimidines; Sulfonamides
PubMed: 38485279
DOI: 10.1124/dmd.124.001675 -
Iranian Journal of Otorhinolaryngology Mar 2024Adenoid hypertrophy is a common childhood disease; its standard treatment is adenoidectomy. The desire for medical management is increasing due to fewer complications...
INTRODUCTION
Adenoid hypertrophy is a common childhood disease; its standard treatment is adenoidectomy. The desire for medical management is increasing due to fewer complications and more convenience. The present study investigated the effect of adding oral montelukast to mometasone nasal spray in treating adenoid hypertrophy.
MATERIALS AND METHODS
This was a randomized, double-blind, placebo-controlled study conducted at a referral teaching hospital (Tehran, Iran) from September 2020 to September 2021. Children aged 2 to 14 years with clinical and radiological findings of adenoid hypertrophy were enrolled. Patients were randomly divided into two groups: mometasone nasal spray with oral montelukast (case group) or mometasone with placebo (control group). Then, the clinical scores were compared before and two months after the intervention.
RESULTS
Ninety-six patients completed the study [62.5% male (n=60)]. Of these, 51 were in the case and 45 in the control group. The clinical score in each group decreased significantly after the intervention (P<0.001), but the decrease in clinical score in the case group was not significantly different from the control (p=0.576).
CONCLUSION
The results showed that the combination therapy with mometasone and montelukast has the same efficacy as mometasone and placebo in treating adenoid hypertrophy. Adding montelukast to mometasone has no additional effect.
PubMed: 38476566
DOI: 10.22038/IJORL.2024.73906.3490