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Journal of Personalized Medicine Jun 2022Pharmacogenetics research on leukotriene modifiers (LTMs) for asthma has been developing rapidly, although pharmacogenetic testing for LTMs is not yet used in clinical...
Pharmacogenetics research on leukotriene modifiers (LTMs) for asthma has been developing rapidly, although pharmacogenetic testing for LTMs is not yet used in clinical practice. We performed a systematic review and meta-analysis on the impact of pharmacogenomics on LTMs response. Studies published until May 2022 were searched using PubMed, EMBASE, and Cochrane databases. Pharmacogenomics/genetics studies of patients with asthma using LTMs with or without other anti-asthmatic drugs were included. Statistical tests of the meta-analysis were performed with Review Manager (Revman, version 5.4, The Cochrane Collaboration, Copenhagen, Denmark) and R language and environment for statistical computing (version 4.1.0 for Windows, R Core Team, Vienna, Austria) software. In total, 31 studies with 8084 participants were included in the systematic review and five studies were also used to perform the meta-analysis. Two included studies were genome-wide association studies (GWAS), which showed different results. Furthermore, none of the SNPs investigated in candidate gene studies were identified in GWAS. In candidate gene studies, the most widely studied SNPs were ALOX5 (tandem repeats of the Sp1-binding domain and rs2115819), LTC4S-444A/C (rs730012), and SLCO2B1 (rs12422149), with relatively inconsistent conclusions. LTC4S-444A/C polymorphism did not show a significant effect in our meta-analysis (AA vs. AC (or AC + CC): −0.06, 95%CI: −0.16 to 0.05, p = 0.31). AA homozygotes had smaller improvements in parameters pertaining to lung functions (−0.14, 95%CI: −0.23 to −0.05, p = 0.002) in a subgroup of patients with non-selective CysLT receptor antagonists and patients without inhaled corticosteroids (ICS) (−0.11, 95%CI: −0.14 to −0.08, p < 0.00001), but not in other subgroups. Variability exists in the pharmacogenomics of LTMs treatment response. Our meta-analysis and systematic review found that LTC4S-444A/C may influence the treatment response of patients taking non-selective CysLT receptor antagonists for asthma, and patients taking LTMs not in combination with ICS for asthma. Future studies are needed to validate the pharmacogenomic influence on LTMs response.
PubMed: 35887565
DOI: 10.3390/jpm12071068 -
Seminars in Cancer Biology May 2022The oleogum resins of Boswellia species known as frankincense have been used for ages in traditional medicine in India, China and the Arabian world independent of its... (Review)
Review
The oleogum resins of Boswellia species known as frankincense have been used for ages in traditional medicine in India, China and the Arabian world independent of its use for cultural and religious rituals in Europe. During the past two decades, scientific investigations provided mounting evidence for the therapeutic potential of frankincense. We conducted a systematic review on the anti-inflammatory and anti-cancer activities of Boswellia species and their chemical ingredients (e.g. 3-O-acetyl-11-keto-β boswellic acid, α- and β-boswellic acids, 11-keto-β-boswellic acid and other boswellic acids, lupeolic acids, incensole, cembrenes, triterpenediol, tirucallic acids, and olibanumols). Frankincense acts by multiple mechanisms, e.g. by the inhibition of leukotriene synthesis, of cyclooxygenase 1/2 and 5-lipoxygenase, of oxidative stress, and by regulation of immune cells from the innate and acquired immune systems. Furthermore, frankincense modulates signaling transduction responsible for cell cycle arrest and inhibition of proliferation, angiogenesis, invasion and metastasis. Clinical trials showed the efficacy of frankincense and its phytochemicals against osteoarthritis, multiple sclerosis, asthma, psoriasis and erythematous eczema, plaque-induced gingivitis and pain. Frankincense revealed beneficial effects towards brain tumor-related edema, but did not reduce glioma size. Even if there is no treatment effect on brain tumors itself, the management of glioma-associated edema may represent a desirable improvement. The therapeutic potential against other tumor types is still speculative. Experimental toxicology and clinical trials revealed only mild adverse side effects. More randomized clinical trials are required to estimate the full clinical potential of frankincense for cancer therapy.
Topics: Anti-Inflammatory Agents; Boswellia; Frankincense; Glioma; Humans; Immunologic Factors; Resins, Plant
PubMed: 32027979
DOI: 10.1016/j.semcancer.2020.01.015 -
Clinical and Experimental Allergy :... Feb 2017Pharmacogenetics studies of anti-inflammatory medication of asthma have expanded rapidly in recent decades, but the clinical value of their findings remains limited. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pharmacogenetics studies of anti-inflammatory medication of asthma have expanded rapidly in recent decades, but the clinical value of their findings remains limited.
OBJECTIVE
To perform a systematic review of pharmacogenomics and pharmacogenetics of inhaled corticosteroids (ICS) and leukotriene modifiers (LTMs) in patients with asthma.
METHODS
Articles published between 1999 and June 2015 were searched using PubMed and EMBASE. Pharmacogenomics/genetics studies of patients with asthma using ICS or LTMs were included if ≥1 of the following outcomes were studied: lung function, exacerbation rates or asthma symptoms. The studies of Single Nucleotide Polymorphisms (SNPs) that had been replicated at least once were assessed in more detail.
RESULTS
In total, 59 publications were included in the systematic review: 26 addressed LTMs (including two genomewide Genome-Wide association studies [GWAS]) and 33 addressed ICS (including four GWAS). None of the GWAS reported similar results. Furthermore, none of the SNPs assessed in candidate gene studies were identified in a GWAS. No consistent reports were found for candidate gene studies of LTMs. In candidate gene studies of ICS, the most consistent results were found for rs28364072 in FCER2. This SNP was associated with all three outcomes of poor response, and the largest effect was reported with the risk of exacerbations (hazard ratio, 3.95; 95% CI, 1.64-9.51).
CONCLUSION AND CLINICAL RELEVANCE
There is a lack of replication of genetic variants associated with poor ICS or LTM response. The most consistent results were found for the FCER2 gene [encoding for a low-affinity IgE receptor (CD23)] and poor ICS response. Larger studies with well-phenotyped patients are needed to assess the clinical applicability of ICS and LTM pharmacogenomics/genetics.
Topics: Adrenal Cortex Hormones; Alleles; Animals; Anti-Asthmatic Agents; Asthma; Genetic Variation; Humans; Leukotriene Antagonists; Pharmacogenetics; Pharmacogenomic Variants; Treatment Outcome
PubMed: 27790783
DOI: 10.1111/cea.12844 -
American Journal of Rhinology & Allergy 2013Leukotriene antagonists (LTAs) provide a potential strategy for the management of chronic rhinosinusitis with nasal polyposis (CRSwNP), which is often refractory to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Leukotriene antagonists (LTAs) provide a potential strategy for the management of chronic rhinosinusitis with nasal polyposis (CRSwNP), which is often refractory to medical and surgical treatment. The purpose of this study is to determine the impact of LTA treatment alone and in conjunction with intranasal corticosteroids (INCSs) on nasal symptoms, objective clinical outcomes, and immune parameters in CRSwNP.
METHODS
A systematic review was performed including studies that assessed the effectiveness of LTAs on clinical outcome measures of CRSwNP. Exclusion criteria were trials assessing LTAs in CRS without nasal polyps or asthma symptoms only. Quantitative analysis was performed using a random effects model.
RESULTS
Twelve studies fulfilled eligibility: five randomized control trials and seven case series. LTAs showed significant improvements in CRSwNP symptoms over placebo; however, these randomized trials were unable to be combined via meta-analysis. The two studies used in meta-analysis showed a standardized mean difference of pooled overall symptom scores of 0.02 (95% confidence interval, -0.39-0.44) between LTA and INCS study arms, indicating no difference between the treatment modalities. Improvement was described by all studies in symptoms, clinical outcomes, and/or immune parameters after LTA treatment, with greater improvements in a subset of symptoms beyond that observed with INCSs. Concomitant asthma, aspirin-exacerbated respiratory disease, and atopy did not significantly or consistently affect these results.
CONCLUSION
LTAs are an effective tool for treating CRSwNP, with limited benefit as an adjunctive therapy. Additional study is required to determine the most beneficial strategy and patient population for their use.
Topics: Adrenal Cortex Hormones; Chronic Disease; Humans; Leukotriene Antagonists; Nasal Polyps; Randomized Controlled Trials as Topic; Recurrence; Rhinitis; Sinusitis
PubMed: 24274224
DOI: 10.2500/ajra.2013.27.3976 -
Clinical Reviews in Allergy & Immunology Oct 2023Taxanes in the treatment of cancer are associated with a significant incidence of hypersensitivity reactions, which may preclude their use in patients in need of first... (Review)
Review
Taxanes in the treatment of cancer are associated with a significant incidence of hypersensitivity reactions, which may preclude their use in patients in need of first line therapy. Drug desensitization induces transient immunological tolerance and has allowed the reintroduction of taxanes in highly allergic patients. Increase the knowledge of hypersensitivity reactions (HSR) during the administration of taxanes. A systematic review regarding the safety and efficacy of rapid drug desensitization (RDD) for taxanes HSR. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, was registered in PROSPERO(CRD42021242324) and a comprehensive search was conducted in Medline, Embase, Web of Science and Scopus databases. 25 studies encompassing 10 countries were identified and 976 patients with initial HSR to paclitaxel (n = 707) and docetaxel (n = 284), that underwent a total of 2,396 desensitizations. The most common symptoms were cutaneous (74.6%) with paclitaxel and respiratory (72.6%) with docetaxel. Severe initial hypersensitivity reactions including anaphylaxis occurred in 39.6% and 13% of paclitaxel and docetaxel cases respectively and during the first (87.4%) or second exposure (81.5%). Patients tolerated well RDD and breakthrough reactions (BTR) occurred in 32.2% of paclitaxel-treated patients and in 20.6% of docetaxel treated patients. Premedications included corticosteroids, antihistamines and leukotriene receptor antagonists. The most commonly used protocol was the BWH 3 bags 12 steps, all protocols showed a success rate between 95-100%, with no reported deaths. RDD is a safe and effective procedure in patients with HSR to taxanes and protocols should be standardized for wide range implementation.
PubMed: 37589840
DOI: 10.1007/s12016-023-08968-y -
Leukotriene receptor antagonist addition to intranasal steroid: systematic review and meta-analysis.Rhinology Feb 2021Intranasal corticosteroids (INCS) and leukotriene receptor antagonist (LTRA) have different mechanisms of action. The combination of INCS and LTRA (INCS+LTRA) are... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Intranasal corticosteroids (INCS) and leukotriene receptor antagonist (LTRA) have different mechanisms of action. The combination of INCS and LTRA (INCS+LTRA) are utilized to control the allergic rhinitis (AR) symptoms. The effects of this com- bination have not been made evident yet.
METHODOLOGY
Randomized controlled trials studying the effects of INCS+LTRA vs INCS in monotherapy on rhinoconjunctivitis symptoms in patients with AR were included. Data were pooled for meta-analysis. The outcomes were nasal symptoms, ocular symptoms, disease-specific quality of life (QOL), and adverse events.
RESULTS
Six studies (358 participants) met the inclusion criteria. There were no differences between INCS+LTRA and INCS mono- therapy on composite nasal symptom score, total daytime symptom score, total night time symptom score, disease-specific QOL and adverse events. The results favoured the effects of INCS-LTRA on ocular symptoms.
CONCLUSIONS
The effects of the INCS+LTRA combination are not different from INCS in monotherapy in the improvement of both nasal symptoms and patient's QOL. The combination may, however, be better on improving ocular symptoms.
Topics: Administration, Intranasal; Adrenal Cortex Hormones; Humans; Leukotriene Antagonists; Quality of Life; Rhinitis, Allergic; Steroids
PubMed: 32692787
DOI: 10.4193/Rhin20.126 -
The American Journal of Medicine Mar 2004To compare the clinical efficacy of leukotriene receptor antagonists with that of placebo, antihistamines, and nasal corticosteroids in patients with allergic rhinitis... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To compare the clinical efficacy of leukotriene receptor antagonists with that of placebo, antihistamines, and nasal corticosteroids in patients with allergic rhinitis or nasal polyposis.
METHODS
We performed a systematic review and meta-analysis of randomized controlled trials of the effectiveness of leukotriene receptor antagonists in patients with rhinitis. Composite daily rhinitis symptom scores (as a percentage of the maximum score) and rhinitis-specific quality of life (unit scores ranging from 0 to 6) were pooled after assessing heterogeneity among studies. The pooled estimates were expressed as weighted mean differences between treatments in a random-effects model. We considered a difference of 10% in nasal score and 0.6 units in quality-of-life score to be clinically relevant.
RESULTS
Of the 196 citations, 11 studies on seasonal allergic rhinitis were used in the analysis: eight evaluating leukotriene receptor antagonists alone or in combination with other treatments versus placebo or other treatments (n = 3924) and three evaluating leukotriene receptor antagonists plus an antihistamine (n = 80). Leukotriene receptor antagonists reduced mean daily rhinitis symptom scores (in absolute terms) 5% (95% confidence interval [CI]: 3% to 7%) more than did placebo. However, antihistamines improved the nasal symptoms score 2% (95% CI: 0% to 4%) more than did leukotriene receptor antagonists, and nasal corticosteroids improved the score 12% (95% CI: 5% to 18%) more than did leukotriene antagonists. Leukotriene receptor antagonists significantly improved rhinoconjunctivitis quality of life by 0.3 units (95% CI: 0.24 to 0.36 units) when compared with placebo. There were no randomized controlled trials evaluating the effect of leukotriene receptor antagonists on perennial allergic rhinitis or polyposis.
CONCLUSION
Leukotriene receptor antagonists are modestly better than placebo, as effective as antihistamines, but less effective than nasal corticosteroids in improving symptoms and quality of life in patients with seasonal allergic rhinitis.
Topics: Drug Therapy, Combination; Histamine H1 Antagonists; Humans; Leukotriene Antagonists; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal
PubMed: 14984820
DOI: 10.1016/j.amjmed.2003.10.030 -
Current Allergy and Asthma Reports Dec 2022Non-steroidal exacerbated respiratory disease (N-ERD) currently requires aspirin challenge testing for diagnosis. Urinary leukotriene E4 (uLTE) has been extensively... (Meta-Analysis)
Meta-Analysis Review
PURPOSE OF REVIEW
Non-steroidal exacerbated respiratory disease (N-ERD) currently requires aspirin challenge testing for diagnosis. Urinary leukotriene E4 (uLTE) has been extensively investigated as potential biomarker in N-ERD. We aimed to assess the usefulness of uLTE as a biomarker in the diagnosis of N-ERD.
RECENT FINDINGS
N-ERD, formerly known as aspirin-intolerant asthma (AIA), is characterised by increased leukotriene production. uLTE indicates cysteinyl leukotriene production, and a potential biomarker in N-ERD. Although several studies and have examined the relationship between uLTE and N-ERD, the usefulness of uLTE as a biomarker in a clinical setting remains unclear.
FINDINGS
Our literature search identified 38 unique eligible studies, 35 were included in the meta-analysis. Meta-analysis was performed (i.e. pooled standardised mean difference (SMD) with 95% confidence intervals (95% CI)) and risk of bias assessed (implementing Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy (Cochrane DTA)). Data from 3376 subjects was analysed (1354 N-ERD, 1420 ATA, and 602 HC). uLTE was higher in N-ERD vs ATA (n = 35, SMD 0.80; 95% CI 0.72-0.89). uLTE4 increased following aspirin challenge in N-ERD (n = 12, SMD 0.56; 95% CI 0.26-0.85) but not ATA (n = 8, SMD 0.12; CI - 0.08-0.33). This systematic review and meta-analysis showed that uLTE is higher in N-ERD than ATA or HC. Likewise, people with N-ERD have greater increases in uLTE following aspirin challenge. However, due to the varied uLTE measurement and result reporting practice, clinical utility of these findings is limited. Future studies should be standardised to increase clinical significance and interpretability of the results.
Topics: Humans; Leukotriene E4; Anti-Inflammatory Agents, Non-Steroidal; Aspirin
PubMed: 36374376
DOI: 10.1007/s11882-022-01049-8 -
BMJ Clinical Evidence Aug 2011Bronchiectasis is usually a complication of previous lower respiratory infection, and causes chronic cough and copious production of sputum, which is often purulent.... (Review)
Review
INTRODUCTION
Bronchiectasis is usually a complication of previous lower respiratory infection, and causes chronic cough and copious production of sputum, which is often purulent. Bronchiectasis may cause signs of chronic obstructive pulmonary disease. It can also be associated with cystic fibrosis and other congenital disorders, foreign body inhalation, and other causes of lung damage.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments in people with bronchiectasis but without cystic fibrosis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We performed a GRADE evaluation of the quality of evidence for interventions.
RESULTS
We found 19 systematic reviews, RCTs, or observational studies that met our inclusion criteria.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: anticholinergic therapy, beta(2) agonists, bronchopulmonary hygiene physical therapy, corticosteroids (inhaled, oral), exercise or physical training, hyperosmolar agents (inhaled), leukotriene receptor antagonists, methyl-xanthines (oral), mucolytics (bromhexine or deoxyribonuclease), prolonged-use antibiotics, and surgery.
Topics: Administration, Inhalation; Administration, Oral; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Bronchiectasis; Cystic Fibrosis; Humans; Leukotriene Antagonists; Lung
PubMed: 21846412
DOI: No ID Found -
The Journal of Allergy and Clinical... 2017Urinary leukotriene E4 (ULTE4) may be a biomarker that distinguishes aspirin-intolerant asthma from other asthma subtypes. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Urinary leukotriene E4 (ULTE4) may be a biomarker that distinguishes aspirin-intolerant asthma from other asthma subtypes.
OBJECTIVE
To estimate the diagnostic testing accuracy of ULTE4 as a marker of aspirin intolerance in patients with asthma using previously published studies.
METHODS
We identified relevant clinical studies from a systematic review of English and non-English articles using MEDLINE, EMBASE, and CENTRAL (inception to February 10, 2015). Articles were screened at the abstract and full-text level by 2 independent reviewers. We included previously published studies that analyzed ULTE4 in human subjects with asthma characterized as having or not having aspirin intolerance on the basis of a specified definition: convincing history of aspirin intolerance, positive aspirin challenge, or both as the criterion standard. Individual-level data points from all included studies were obtained and analyzed.
RESULTS
The search strategy identified 867 potential articles, of which 86 were reviewed at the full-text level and 10 met criteria for inclusion. The sensitivity, specificity, positive predictive value, and negative predictive values of ULTE4 to determine aspirin intolerance in subjects with asthma were 0.55, 0.82, 0.75, and 0.66 (Amersham-enzyme immunoassay); 0.76, 0.77, 0.70, and 0.78 (Cayman-enzyme immunoassay); 0.70, 0.81, 0.86, and 0.79 (mass spectrometry); and 0.81,0.79, 0.65, and 0.88 (radioimmunoassay) at optimal thresholds of 192, 510, 167 to 173, and 66 to 69 pg/mg Cr, respectively. The diagnostic odds ratio for each methodology was 6.0, 11.9, 10.5, and 19.1, respectively.
CONCLUSIONS
ULTE4 is a marker for aspirin-intolerant asthma and could potentially be used as a clinical test to identify the risk of aspirin intolerance in subjects with asthma.
Topics: Aspirin; Asthma; Biomarkers; Cyclooxygenase Inhibitors; Drug Hypersensitivity; Humans; Leukotriene E4
PubMed: 28202405
DOI: 10.1016/j.jaip.2016.11.004