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European Respiratory Review : An... Dec 2023We aim to assess the impact of montelukast on paediatric patients with asthma/allergic rhinitis, measured using patient-reported outcome measures, compared with other... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
We aim to assess the impact of montelukast on paediatric patients with asthma/allergic rhinitis, measured using patient-reported outcome measures, compared with other treatments or placebo.
METHODS
Protocol registration CRD42020216098 (www.crd.york.ac.uk/PROSPERO). MEDLINE and Embase databases were used to conduct the search. Two authors independently selected studies and extracted data, and a third reviewer resolved discrepancies. Meta-analyses were constructed to estimate the standardised mean difference (SMD) using a random-effects model.
RESULTS
Out of 3937 articles identified, 49 studies met the inclusion criteria, mostly randomised clinical trials (sample sizes: 21-689 patients). The SMD of change pooled estimators for the global, mental and physical domains of health-related quality of life were not statistically significant. For daytime and night-time symptoms scores, the SMD (95% CI) was in favour of inhaled corticosteroids (-0.12, -0.20- -0.05 and -0.23, -0.41- -0.06, respectively). The pooled estimator for global asthma symptoms was better for montelukast when compared with placebo (0.90, 0.44-1.36).
CONCLUSIONS
The synthesis of the available evidence suggests that, in children and adolescents, montelukast was effective in controlling asthma symptoms when compared with placebo, but inhaled corticosteroids were superior in controlling symptoms, especially at night-time. These findings of our systematic review concur with current guidelines for asthma treatment.
Topics: Adolescent; Humans; Child; Quality of Life; Asthma; Rhinitis, Allergic; Adrenal Cortex Hormones
PubMed: 37852659
DOI: 10.1183/16000617.0124-2023 -
The Journal of Allergy and Clinical... Dec 2023Atopic dermatitis (AD) is a common skin condition with multiple topical treatment options, but uncertain comparative effects. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Atopic dermatitis (AD) is a common skin condition with multiple topical treatment options, but uncertain comparative effects.
OBJECTIVE
We sought to systematically synthesize the benefits and harms of AD prescription topical treatments.
METHODS
For the 2023 American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters AD guidelines, we searched MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, ICTRP, and GREAT databases to September 5, 2022, for randomized trials addressing AD topical treatments. Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects network meta-analyses addressed AD severity, itch, sleep, AD-related quality of life, flares, and harms. The Grading of Recommendations Assessment, Development and Evaluation approach informed certainty of evidence ratings. We classified topical corticosteroids (TCS) using 7 groups-group 1 being most potent. This review is registered in the Open Science Framework (https://osf.io/q5m6s).
RESULTS
The 219 included trials (43,123 patients) evaluated 68 interventions. With high-certainty evidence, pimecrolimus improved 6 of 7 outcomes-among the best for 2; high-dose tacrolimus (0.1%) improved 5-among the best for 2; low-dose tacrolimus (0.03%) improved 5-among the best for 1. With moderate- to high-certainty evidence, group 5 TCS improved 6-among the best for 3; group 4 TCS and delgocitinib improved 4-among the best for 2; ruxolitinib improved 4-among the best for 1; group 1 TCS improved 3-among the best for 2. These interventions did not increase harm. Crisaborole and difamilast were intermediately effective, but with uncertain harm. Topical antibiotics alone or in combination may be among the least effective. To maintain AD control, group 5 TCS were among the most effective, followed by tacrolimus and pimecrolimus.
CONCLUSIONS
For individuals with AD, pimecrolimus, tacrolimus, and moderate-potency TCS are among the most effective in improving and maintaining multiple AD outcomes. Topical antibiotics may be among the least effective.
Topics: Humans; Dermatitis, Atopic; Tacrolimus; Network Meta-Analysis; Quality of Life; Randomized Controlled Trials as Topic; Dermatologic Agents; Asthma; Eczema; Anti-Bacterial Agents
PubMed: 37678572
DOI: 10.1016/j.jaci.2023.08.030 -
The Journal of Allergy and Clinical... Dec 2023Atopic dermatitis (AD) is an inflammatory skin condition with multiple systemic treatments and uncertainty regarding their comparative impact on AD outcomes. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Atopic dermatitis (AD) is an inflammatory skin condition with multiple systemic treatments and uncertainty regarding their comparative impact on AD outcomes.
OBJECTIVE
We sought to systematically synthesize the benefits and harms of AD systemic treatments.
METHODS
For the 2023 American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters AD guidelines, we searched MEDLINE, EMBASE, CENTRAL, Web of Science, and GREAT databases from inception to November 29, 2022, for randomized trials addressing systemic treatments and phototherapy for AD. Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects network meta-analyses addressed AD severity, itch, sleep, AD-related quality of life, flares, and harms. The Grading of Recommendations Assessment, Development and Evaluation approach informed certainty of evidence ratings. This review is registered in the Open Science Framework (https://osf.io/e5sna).
RESULTS
The 149 included trials (28,686 patients with moderate-to-severe AD) evaluated 75 interventions. With high-certainty evidence, high-dose upadacitinib was among the most effective for 5 of 6 patient-important outcomes; high-dose abrocitinib and low-dose upadacitinib were among the most effective for 2 outcomes. These Janus kinase inhibitors were among the most harmful in increasing adverse events. With high-certainty evidence, dupilumab, lebrikizumab, and tralokinumab were of intermediate effectiveness and among the safest, modestly increasing conjunctivitis. Low-dose baricitinib was among the least effective. Efficacy and safety of azathioprine, oral corticosteroids, cyclosporine, methotrexate, mycophenolate, phototherapy, and many novel agents are less certain.
CONCLUSIONS
Among individuals with moderate-to-severe AD, high-certainty evidence demonstrates that high-dose upadacitinib is among the most effective in addressing multiple patient-important outcomes, but also is among the most harmful. High-dose abrocitinib and low-dose upadacitinib are effective, but also among the most harmful. Dupilumab, lebrikizumab, and tralokinumab are of intermediate effectiveness and have favorable safety.
Topics: Humans; Dermatitis, Atopic; Network Meta-Analysis; Quality of Life; Randomized Controlled Trials as Topic; Eczema; Asthma; Treatment Outcome
PubMed: 37678577
DOI: 10.1016/j.jaci.2023.08.029 -
European Respiratory Review : An... Sep 2023The United States Food and Drug Administration issued a black box warning on the mental health adverse effects of montelukast in 2020. Age-related effects on the risk of... (Review)
Review
BACKGROUND
The United States Food and Drug Administration issued a black box warning on the mental health adverse effects of montelukast in 2020. Age-related effects on the risk of developing specific neuropsychiatric events in montelukast users remain largely unknown.
OBJECTIVE
To describe the risk of neuropsychiatric events associated with montelukast in adults and children with asthma.
METHODS
A systematic search of all studies investigating neuropsychiatric events in montelukast users was performed in PubMed, the Cochrane Library and Embase from inception to 7 September 2022. Animal studies and conference abstracts were excluded.
RESULTS
59 studies (21 pharmacovigilance studies, four reviews from 172 randomised controlled trials, 20 observational studies, 10 case reports and four case series) evaluating neuropsychiatric events in patients with asthma on montelukast were reviewed. No significant association was shown between montelukast and suicide-related events in six of the observational studies. No association was found for depression as defined by the International Classification of Diseases 10 revision codes in three observational studies and a review of randomised clinical trials. However, findings from four studies using antidepressant prescriptions as the outcome identified significant associations. Consistent with nine pharmacovigilance studies, two large-scale observational studies revealed possible associations of montelukast with anxiety and sleeping disorders in adult patients with asthma, respectively. However, the results were not replicated in two observational studies on children.
CONCLUSION
Montelukast is not associated with suicide- and depression-related events in asthma patients. Older adults may be particularly susceptible to anxiety and sleeping disorders.
Topics: Child; Animals; Humans; Aged; Asthma; Acetates; Quinolines; Cyclopropanes; Anti-Asthmatic Agents
PubMed: 37758273
DOI: 10.1183/16000617.0079-2023 -
Journal of Asthma and Allergy 2023Airway hyperresponsiveness (AHR) is a key feature of asthma. Biologic therapies used to treat asthma target specific components of the inflammatory pathway, and their... (Review)
Review
BACKGROUND
Airway hyperresponsiveness (AHR) is a key feature of asthma. Biologic therapies used to treat asthma target specific components of the inflammatory pathway, and their effects on AHR can provide valuable information about the underlying disease pathophysiology. This review summarizes the available evidence regarding the effects of biologics on allergen-specific and non-allergen-specific airway responses in patients with asthma.
METHODS
We conducted a systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, including risk-of-bias assessment. PubMed and Ovid were searched for studies published between January 1997 and December 2021. Eligible studies were randomized, placebo-controlled trials that assessed the effects of biologics on AHR, early allergic response (EAR) and/or late allergic response (LAR) in patients with asthma.
RESULTS
Thirty studies were identified for inclusion. Bronchoprovocation testing was allergen-specific in 18 studies and non-allergen-specific in 12 studies. Omalizumab reduced AHR to methacholine, acetylcholine or adenosine monophosphate (3/9 studies), and reduced EAR (4/5 studies) and LAR (2/3 studies). Mepolizumab had no effect on AHR (3/3 studies), EAR or LAR (1/1 study). Tezepelumab reduced AHR to methacholine or mannitol (3/3 studies), and reduced EAR and LAR (1/1 study). Pitrakinra reduced LAR, with no effect on AHR (1/1 study). Etanercept reduced AHR to methacholine (1/2 studies). No effects were observed for lebrikizumab, tocilizumab, efalizumab, IMA-638 and anti-OX40 ligand on AHR, EAR or LAR; benralizumab on LAR; tralokinumab on AHR; and Ro-24-7472 on AHR or LAR (all 1/1 study each). No dupilumab or reslizumab studies were identified.
CONCLUSION
Omalizumab and tezepelumab reduced EAR and LAR to allergens. Tezepelumab consistently reduced AHR to methacholine or mannitol. These findings provide insights into AHR mechanisms and the precise effects of asthma biologics. Furthermore, findings suggest that tezepelumab broadly targets allergen-specific and non-allergic forms of AHR, and the underlying cells and mediators involved in asthma.
PubMed: 37496824
DOI: 10.2147/JAA.S410592 -
The Journal of Allergy and Clinical... Feb 2024A maintenance oral corticosteroid (OCS) in addition to high-dose inhaled corticosteroids plus long-acting β-agonists in patients with severe asthma leads to long-term... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A maintenance oral corticosteroid (OCS) in addition to high-dose inhaled corticosteroids plus long-acting β-agonists in patients with severe asthma leads to long-term adverse events. Oral corticosteroid-sparing agents are of high priority.
OBJECTIVE
This network meta-analysis assessed biologics' comparative efficacy and safety in OCS-dependent patients with asthma.
METHODS
We performed a systematic search through PubMed, Scopus, Embase, the Cochrane Center of Controlled Trials, and Google Scholar for randomized controlled trials that addressed the efficacy and safety of biologics compared with placebo in OCS-dependent patients with asthma from inception to July 2023. The primary outcome was an overall reduction in the OCS dose while asthma control was maintained.
RESULTS
We included seven randomized controlled trials involving 1,052 OCS-dependent patients with asthma. Compared with placebo, benralizumab every 8 weeks, benralizumab every 4 weeks, dupilumab, and mepolizumab were efficacious in achieving a reduction in the OCS dose with low to moderate confidence (odds ratio [95% CI]: 4.12 [2.22-7.64]; 4.09 [2.22-7.55]; 3.25 [1.90-5.55]; and 2.39 [1.25-4.57], respectively) whereas tralokinumab, tezepelumab, and subcutaneous reslizumab were ineffective. An indirect comparison found no significant differences among benralizumab, dupilumab, and mepolizumab. Efficacy in reducing exacerbations was consistent with the primary analysis. High baseline blood eosinophil counts benefit from anti-IL-5 therapies, whereas high FeNO levels favor dupilumab regardless of blood eosinophil counts. Adverse events between biologics and placebo were comparable, except for eosinophilia with dupilumab.
CONCLUSIONS
In OCS-dependent patients with asthma, benralizumab, dupilumab, and mepolizumab were superior to placebo in reducing the OCS dose. Evaluating baseline biomarkers helps in choosing the proper biologics to maximize treatment effects.
Topics: Humans; Anti-Asthmatic Agents; Biological Products; Network Meta-Analysis; Asthma; Adrenal Cortex Hormones; Eosinophilia
PubMed: 37972921
DOI: 10.1016/j.jaip.2023.11.007 -
The Journal of Allergy and Clinical... Aug 2023Allergic rhinitis (AR) is associated with significant clinical and socioeconomic burdens. It is a frequent risk factor for other atopic diseases, such as asthma. Thus, a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Allergic rhinitis (AR) is associated with significant clinical and socioeconomic burdens. It is a frequent risk factor for other atopic diseases, such as asthma. Thus, a comprehensive updated description of the epidemiology of AR in the pediatric population is needed to understand its implications better.
OBJECTIVE
To determine the incidence, prevalence, and epidemiology of AR among children over the past 10 years.
METHODS
We conducted a systematic review and meta-analysis using a protocol registered and published with the International Prospective Register of Systematic Reviews (Register No. CRD42022332667). We searched databases, registers, and Web sites for cohort or cross-sectional studies published between 2012 and 2022, evaluating the epidemiology (incidence or prevalence) of AR in the pediatric population. We assessed study quality of and risk for bias using items derived from the Strengthening the Reporting of Observational Studies in Epidemiology statement.
RESULTS
Twenty-two studies were included in the analysis. The overall prevalence of physician-diagnosed AR was 10.48%, the overall prevalence of self-reported current (past 12 months) AR was 18.12%, and the overall prevalence of self-reported lifetime AR was 19.93%. The incidence could not be determined. The analysis of prevalence of AR over time showed a rising trend in physician-diagnosed AR over the years (8.39% in 2012 to 2015 vs 19.87% in 2016 to 2022).
CONCLUSIONS
Allergic rhinitis has significant impacts on the pediatric population, with an increasing trend for diagnosed AR over the years. Further investigations concerning the incidence, comorbidities, diagnosis, and treatment are needed to provide a complete overview of the disease as well as its burden and management.
Topics: Humans; Child; Cross-Sectional Studies; Rhinitis, Allergic; Asthma; Comorbidity; Risk Factors; Prevalence
PubMed: 37236349
DOI: 10.1016/j.jaip.2023.05.016 -
Chest Nov 2023Nontuberculous mycobacterial pulmonary disease (NTM-PD) is widely underdiagnosed, and certain patient groups, such as those with underlying respiratory diseases, are at... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Nontuberculous mycobacterial pulmonary disease (NTM-PD) is widely underdiagnosed, and certain patient groups, such as those with underlying respiratory diseases, are at increased risk of developing the disease. Understanding patients at risk is essential to allow for prompt testing and diagnosis and appropriate management to prevent disease progression.
RESEARCH QUESTION
What are the risk factors for NTM-PD that should prompt a physician to consider NTM testing and diagnosis?
STUDY DESIGN AND METHODS
Electronic searches of PubMed and EMBASE were conducted in July 2021 for the period 2011-2021. Inclusion criteria were studies of patients with NTM-PD with associated risk factors. Data were extracted and assessed using the Newcastle-Ottawa Scale. Data analysis was conducted using the R-based "meta" package. Only studies that reported association outcomes for cases with NTM-PD compared with control participants (healthy populations or participants without NTM-PD) were considered for the meta-analysis.
RESULTS
Of the 9,530 searched publications, 99 met the criteria for the study. Of these, 24 formally reported an association between possible risk factors and the presence of NTM-PD against a control population and were included in the meta-analysis. Comorbid respiratory disease was associated with a significant increase in the OR for NTM-PD (bronchiectasis [OR, 21.43; 95% CI, 5.90-77.82], history of TB [OR, 12.69; 95% CI, 2.39-67.26], interstitial lung disease [OR, 6.39; 95% CI, 2.65-15.37], COPD [OR, 6.63; 95% CI, 4.57-9.63], and asthma [OR, 4.15; 95% CI, 2.81-6.14]). Other factors noted to be associated with an increased risk of NTM-PD were the use of inhaled corticosteroids (OR 4.46; 95% CI, 2.13-9.35), solid tumors (OR, 4.66; 95% CI, 1.04-20.94) and the presence of pneumonia (OR, 5.54; 95% CI, 2.72-11.26).
INTERPRETATION
The greatest risk for NTM-PD is conferred by comorbid respiratory diseases such as bronchiectasis. These findings could help with identification of patient populations at risk for NTM-PD to drive prompt testing and appropriate initiation of therapy.
Topics: Humans; Mycobacterium Infections, Nontuberculous; Risk Factors; Bronchiectasis; Asthma; Respiratory Tract Diseases; Nontuberculous Mycobacteria; Lung Diseases; Retrospective Studies
PubMed: 37429481
DOI: 10.1016/j.chest.2023.06.014 -
Allergy Sep 2023In 2014, the European Academy of Allergy and Clinical Immunology published prevalence estimates for food allergy (FA) and food sensitization (FS) to the so-called eight... (Meta-Analysis)
Meta-Analysis Review
In 2014, the European Academy of Allergy and Clinical Immunology published prevalence estimates for food allergy (FA) and food sensitization (FS) to the so-called eight big food allergens (i.e. cow's milk, egg, wheat, soy, peanut, tree nuts, fish and shellfish) in Europe for studies published between 2000 and 2012. The current work provides 10-year updated prevalence estimates for these food allergens. A protocol was registered on PROSPERO before starting the research (reference number CRD42021266657). Six databases were searched for studies published 2012-2021, added to studies published up to 2012, resulting in a total of 93 studies. Most studies were graded as at moderate risk of bias. The overall pooled estimates for all age groups of self-reported lifetime prevalence were as follows: cow's milk (5.7%, 95% confidence interval 4.4-6.9), egg (2.4%, 1.8-3.0), wheat (1.6%, 0.9-2.3), soy (0.5%, 0.3-0.7), peanut (1.5%, 1.0-2.1), tree nuts (0.9%, 0.6-1.2), fish (1.4%, 0.8-2.0) and shellfish (0.4%, 0.3-0.6). The point prevalence of food challenge-verified allergy were as follows: cow's milk (0.3%, 0.1-0.5), egg (0.8%, 0.5-1.2), wheat (0.1%, 0.01-0.2), soy (0.3%, 0.1-0.4), peanut (0.1%, 0.0-0.2), tree nuts (0.04%, 0.02-0.1), fish (0.02%, 0.0-0.1) and shellfish (0.1%, 0.0-0.2). With some exceptions, the prevalence of allergy to common foods did not substantially change during the last decade; variations by European regions were observed.
Topics: Humans; Food Hypersensitivity; Prevalence; Europe; Clinical Protocols; Incidence; Clinical Studies as Topic; Age Factors; Child; Infant, Newborn; Infant; Child, Preschool; Adolescent
PubMed: 37405695
DOI: 10.1111/all.15801 -
Frontiers in Psychology 2023Growing evidence from scientific research elucidates the important role of alexithymia in chronic immune diseases. This Review aims to explore the presence of... (Review)
Review
Growing evidence from scientific research elucidates the important role of alexithymia in chronic immune diseases. This Review aims to explore the presence of alexithymia in patients affected by asthma and clarify its associations with other involved psychological and physical factors. In January 2023, according to PRISMA guidelines, a systematic search using PubMed and Scopus was conducted. Twenty-six studies were eligible based on inclusion criteria. Alexithymia was significantly present in asthma patients, with most studies reporting a higher prevalence (from 9 to 62.8%) than in control groups (approximately 10%). The coexistence of asthma and alexithymia was associated with a worse quality of life, psychiatric comorbidity, poor symptom control, and difficulty in recognizing exacerbations of the disease. These results suggest that alexithymia can negatively impact the management of asthma. For this reason, we recommend an accuracy assessment in clinical settings and the implementation of psychological interventions to promote the emotional and physical wellbeing of asthmatic patients.
PubMed: 37609491
DOI: 10.3389/fpsyg.2023.1221648