-
European Journal of Neurology Nov 2023The role of the gut microbiome in the pathogenesis of Parkinson disease (PD) is under intense investigation, and the results presented are still very heterogeneous.... (Review)
Review
BACKGROUND AND PURPOSE
The role of the gut microbiome in the pathogenesis of Parkinson disease (PD) is under intense investigation, and the results presented are still very heterogeneous. These discrepancies arise not only from the highly heterogeneous pathology of PD, but also from widely varying methodologies at all stages of the workflow, from sampling to final statistical analysis. The aim of the present work is to harmonize the workflow across studies to reduce the methodological heterogeneity and to perform a pooled analysis to account for other sources of heterogeneity.
METHODS
We performed a systematic review to identify studies comparing the gut microbiota of PD patients to healthy controls. A workflow was designed to harmonize processing across all studies from bioinformatics processing to final statistical analysis using a Bayesian random-effects meta-analysis based on individual patient-level data.
RESULTS
The results show that harmonizing workflows minimizes differences between statistical methods and reveals only a small set of taxa being associated with the pathogenesis of PD. Increased shares of the genera Akkermansia and Bifidobacterium and decreased shares of the genera Roseburia and Faecalibacterium were most characteristic for PD-associated microbiota.
CONCLUSIONS
Our study summarizes evidence that reduced levels of butyrate-producing taxa in combination with possible degradation of the mucus layer by Akkermansia may promote intestinal inflammation and reduced permeability of the gut mucosal layer. This may allow potentially pathogenic metabolites to transit and enter the enteric nervous system.
PubMed: 36593694
DOI: 10.1111/ene.15671 -
The Cochrane Database of Systematic... Aug 2017Heated, humidified air has long been used by people with the common cold. The theoretical basis is that steam may help congested mucus drain better and that heat may... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Heated, humidified air has long been used by people with the common cold. The theoretical basis is that steam may help congested mucus drain better and that heat may destroy the cold virus as it does in vitro. This is an update of a review last published in 2013.
OBJECTIVES
To assess the effects of inhaling heated water vapour (steam) in the treatment of the common cold by comparing symptoms, viral shedding, and nasal resistance.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (to February 2017), MEDLINE (1966 to 24 February 2017), Embase (1990 to 24 February 2017), and Current Contents (1998 to 24 February 2017). We also searched World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) (8 March 2017) and ClinicalTrials.gov (8 March 2017) as well as reference lists of included studies.
SELECTION CRITERIA
Randomised controlled trials using heated water vapour in participants with the common cold or experimentally induced common cold were eligible for inclusion.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Three review authors independently screened titles and abstracts for inclusion of potential studies identified from the search. We recorded the selection process in sufficient detail to complete a PRISMA flow diagram. We used a data collection form for study characteristics and outcome data that was developed and used for previous versions of this review. Two review authors independently extracted data, and a third review author resolved any disagreements. We used Review Manager 5 software to analyse data.
MAIN RESULTS
We included six trials from five publications involving a total of 387 participants. We included no new studies in this 2017 update. The 'Risk of bias' assessment suggested an unclear risk of bias in the domain of randomisation and a low risk of bias in performance, detection, attrition, and reporting.It was uncertain whether heated, humidified air provides symptomatic relief for the common cold, as the fixed-effect analysis showed evidence of an effect (odds ratio (OR) 0.30, 95% confidence interval (CI) 0.16 to 0.56; 2 studies, 149 participants), but the random-effects analysis showed no significant difference in the results (OR 0.22, 95% CI 0.03 to 1.95). There is an argument for using either form of analysis. No studies demonstrated an exacerbation of clinical symptom scores. One study conducted in the USA demonstrated worsened nasal resistance, but an earlier Israeli study showed improvement. One study examined viral shedding in nasal washings, finding no significant difference between treatment and placebo groups (OR 0.47, 95% CI 0.04 to 5.19). As judged by the subjective response to therapy (i.e. therapy did not help), the number of participants reporting resolution of symptoms was not significantly higher in the heated humidified group (OR 0.58, 95% CI 0.28 to 1.18; 2 studies, 124 participants). There was significant heterogeneity in the effects of heated, humidified air on different outcomes, therefore we graded the quality of the evidence as low. Some studies reported minor adverse events (including discomfort or irritation of the nose).
AUTHORS' CONCLUSIONS
The current evidence does not show any benefits or harms from the use of heated, humidified air delivered via the RhinoTherm device for the treatment of the common cold. There is a need for more double-blind, randomised trials that include standardised treatment modalities.
Topics: Air; Common Cold; Heating; Humans; Humidity; Picornaviridae Infections; Randomized Controlled Trials as Topic; Respiratory Therapy; Rhinovirus; Steam; Virus Shedding
PubMed: 28849871
DOI: 10.1002/14651858.CD001728.pub6 -
The Cochrane Database of Systematic... Jun 2022Respiratory disease is the main cause of morbidity and mortality in cystic fibrosis (CF), and many different therapies are used by people with CF in the management of... (Review)
Review
BACKGROUND
Respiratory disease is the main cause of morbidity and mortality in cystic fibrosis (CF), and many different therapies are used by people with CF in the management of respiratory problems. Bronchodilator therapy is used to relieve symptoms of shortness of breath and to open the airways to allow clearance of mucus. Despite the widespread use of inhaled bronchodilators in CF, there is little objective evidence of their efficacy. A Cochrane Review looking at both short- and long-acting inhaled bronchodilators for CF was withdrawn from the Cochrane Library in 2016. That review has been replaced by two separate Cochrane Reviews: one on long-acting inhaled bronchodilators for CF, and this review on short-acting inhaled bronchodilators for CF. For this review 'inhaled' includes the use of pressurised metered dose inhalers (MDIs), with or without a spacer, dry powder devices and nebulisers.
OBJECTIVES
To evaluate short-acting inhaled bronchodilators in children and adults with CF in terms of clinical outcomes and safety.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books on 28 March 2022 and searched trial registries for any new or ongoing trials on 12 April 2022. We also searched the reference lists of relevant articles and reviews.
SELECTION CRITERIA
We searched for randomised controlled trials (RCTs) or quasi-RCTs that looked at the effect of any short-acting inhaled bronchodilator delivered by any device, at any dose, at any frequency and for any duration compared to either placebo or another short-acting inhaled bronchodilator in people with CF. We screened references as per standard Cochrane methodology.
DATA COLLECTION AND ANALYSIS
Two review authors extracted data and assessed risk of bias using the Cochrane RoB 1 tool. Where we were not able to enter data into our analyses we reported results directly from the papers. We assessed the certainty of evidence using GRADE.
MAIN RESULTS
We included 11 trials from our systematic search, with 191 participants meeting our inclusion criteria; three of these trials had three treatment arms. Eight trials compared short-acting inhaled beta-2 agonists to placebo and four trials compared short-acting inhaled muscarinic antagonists to placebo. Three trials compared short-acting inhaled beta-2 agonists to short-acting inhaled muscarinic antagonists. All were cross-over trials with only small numbers of participants. We were only able to enter data into the analysis from three trials comparing short-acting inhaled beta-2 agonists to placebo. Short-acting inhaled beta-2 agonists versus placebo All eight trials (six single-dose trials and two longer-term trials) reporting on this comparison reported on forced expiratory volume in 1 second (FEV), either as per cent predicted (% predicted) or L. We were able to combine the data from two trials in a meta-analysis which showed a greater per cent change from baseline in FEV L after beta-2 agonists compared to placebo (mean difference (MD) 6.95%, 95% confidence interval (CI) 1.88 to 12.02; 2 trials, 82 participants). Only one of the longer-term trials reported on exacerbations, as measured by hospitalisations and courses of antibiotics. Only the second longer-term trial presented results for participant-reported outcomes. Three trials narratively reported adverse events, and these were all mild. Three single-dose trials and the two longer trials reported on forced vital capacity (FVC), and five trials reported on peak expiratory flow, i.e. forced expiratory flow between 25% and 75% (FEF). One trial reported on airway clearance in terms of sputum weight. We judged the certainty of evidence for each of these outcomes to be very low, meaning we are very uncertain about the effect of short-acting inhaled beta-2 agonists on any of the outcomes we assessed. Short-acting inhaled muscarinic antagonists versus placebo All four trials reporting on this comparison looked at the effects of ipratropium bromide, but in different doses and via different delivery methods. One trial reported FEV % predicted; three trials measured this in L. Two trials reported adverse events, but these were few and mild. One trial reported FVC and three trials reported FEF. None of the trials reported on quality of life, exacerbations or airway clearance. We judged the certainty of evidence for each of these outcomes to be very low, meaning we are very uncertain about the effect of short-acting inhaled muscarinic antagonists on any of the outcomes we assessed. Short-acting inhaled beta-2 agonists versus short-acting inhaled muscarinic antagonists None of the three single-dose trials reporting on this comparison provided data we could analyse. The original papers from three trials report that both treatments lead to an improvement in FEV L. Only one trial reported on adverse events; but none were experienced by any participant. No trial reported on any of our other outcomes. We judged the certainty of evidence to be very low, meaning we are very uncertain about the effect of short-acting inhaled beta-2 agonists compared to short-acting inhaled muscarinic antagonists on any of the outcomes we assessed.
AUTHORS' CONCLUSIONS
All included trials in this review are small and of a cross-over design. Most trials looked at very short-term effects of inhaled bronchodilators, and therefore did not measure longer-term outcomes. The certainty of evidence across all outcomes was very low, and therefore we have been unable to describe any effects with certainty.
Topics: Administration, Inhalation; Adult; Bronchodilator Agents; Child; Cystic Fibrosis; Forced Expiratory Volume; Humans; Muscarinic Antagonists
PubMed: 35749226
DOI: 10.1002/14651858.CD013666.pub2 -
The Cochrane Database of Systematic... Sep 2018Dornase alfa is currently used as a mucolytic to treat pulmonary disease (the major cause of morbidity and mortality) in cystic fibrosis. It reduces mucus viscosity in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Dornase alfa is currently used as a mucolytic to treat pulmonary disease (the major cause of morbidity and mortality) in cystic fibrosis. It reduces mucus viscosity in the lungs, promoting improved clearance of secretions. This is an update of a previously published review.
OBJECTIVES
To determine whether the use of dornase alfa in cystic fibrosis is associated with improved mortality and morbidity compared to placebo or other medications that improve airway clearance, and to identify any adverse events associated with its use.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and abstracts from conferences. Date of the most recent search of the Group's Cystic Fibrosis Register: 23 April 2018.Clinicaltrials.gov and the International Clinical Trials Registry Platform were also searched to identify unpublished or ongoing trials. Date of most recent search: 07 June 2018.
SELECTION CRITERIA
All randomised and quasi-randomised controlled trials comparing dornase alfa to placebo, standard therapy or other medications that improve airway clearance.
DATA COLLECTION AND ANALYSIS
Authors independently assessed trials against the inclusion criteria; two authors carried out analysis of methodological quality and data extraction. GRADE was used to assess the level of evidence.
MAIN RESULTS
The searches identified 69 trials, of which 19 (2565 participants) met our inclusion criteria. Fifteen trials compared dornase alfa to placebo or no dornase alfa (2447 participants); two compared daily dornase to hypertonic saline (32 participants); one compared daily dornase alfa to hypertonic saline and alternate day dornase alfa (48 participants); one compared dornase alfa to mannitol and the combination of both drugs (38 participants). Trial duration varied from six days to three years.Dornase alfa compared to placebo or no treatmentDornase alfa improved forced expiratory volume at one second at one month (four trials, 248 participants), three months (one trial, 320 participants; moderate-quality evidence), six months (one trial, 647 participants; high-quality evidence) and two years (one trial, 410 participants). Limited low-quality evidence showed no difference between groups for changes in quality of life. There was a decrease in pulmonary exacerbations with dornase alfa in trials of up to two years (moderate-quality evidence). One trial that examined the cost of care, including the cost of dornase alfa, found that the cost savings from dornase alfa offset 18% to 38% of the medication costs.Dornase alfa: daily versus alternate dayOne cross-over trial (43 children) found no differences between treatment regimens for lung function, quality of life or pulmonary exacerbations (low-quality evidence).Dornase alfa compared to other medications that improve airway clearanceResults for these comparisons were mixed. One trial (43 children) showed a greater improvement in forced expiratory volume at one second for dornase alfa compared to hypertonic saline (low-quality evidence), and one trial (23 participants) reported no difference in lung function between dornase alfa and mannitol or dornase alfa and dornase alfa plus mannitol (low-quality evidence). One trial (23 participants) found a difference in quality of life favouring dornase alfa when compared to dornase alfa plus mannitol (low-quality evidence); other comparisons found no difference in this outcome (low-quality evidence). No trials in any comparison reported any difference between groups in the number of pulmonary exacerbations (low-quality evidence).When all comparisons are assessed, dornase alfa did not cause significantly more adverse effects than other treatments, except voice alteration and rash.
AUTHORS' CONCLUSIONS
There is evidence to show that, compared with placebo, therapy with dornase alfa improves lung function in people with cystic fibrosis in trials lasting from one month to two years. There was a decrease in pulmonary exacerbations in trials of six months or longer. Voice alteration and rash appear to be the only adverse events reported with increased frequency in randomised controlled trials. There is not enough evidence to firmly conclude if dornase alfa is superior to other hyperosmolar agents in improving lung function.
Topics: Adolescent; Child; Child, Preschool; Cystic Fibrosis; Deoxyribonuclease I; Expectorants; Forced Expiratory Volume; Humans; Infant; Mannitol; Randomized Controlled Trials as Topic; Recombinant Proteins; Saline Solution, Hypertonic; Vital Capacity
PubMed: 30187450
DOI: 10.1002/14651858.CD001127.pub4 -
Chronic Respiratory Disease 2021Rheumatoid arthritis (RA) is a chronic autoimmune disease primarily affecting joints but often also associated with lung involvement such as bronchiectasis (BE). The aim... (Meta-Analysis)
Meta-Analysis
Rheumatoid arthritis (RA) is a chronic autoimmune disease primarily affecting joints but often also associated with lung involvement such as bronchiectasis (BE). The aim of the present systematic review and meta-analysis is to provide an update on the current evidence regarding the prevalence and association between RA and BE. This systematic review and meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines with literature search using the terms 'Bronchiectasis AND Rheumatoid Arthritis' without a date limitation on PubMed during May 2020. A total of 28 studies fulfilled the predefined criteria and were included in the present review, with 19 being cross-sectional studies. Twenty-three studies were included in the meta-analysis. The pooled prevalence estimate was 2.69% (95% CI 1.63-4.42) in clinically defined BE, and 24.9% (95% CI 19.21-31.67) in radiologic disease. Many inconsistencies exist regarding potential risk factors for BE in RA patients such as gender, RA duration and severity, as both negative and positive associations have been reported. Although very little is known about possible causative mechanisms between RA and BE, potential pathways might be antigenic stimulation from pulmonary mucus and/or systemic inflammation from joint disease affecting the lungs. At present, the available evidence of bronchiectasis in patients with RA is insufficient to identify RA-associated risk factors for the development of BE, possibly apart from duration of RA, and, consequently, also to fully explore a possible causal relationship between the two disease. However, the increased prevalence of BE in RA patients warrants further studies to explore the association between RA and BE.
Topics: Arthritis, Rheumatoid; Bronchiectasis; Cross-Sectional Studies; Humans; Risk Factors
PubMed: 33590765
DOI: 10.1177/1479973121994565 -
Respiratory Medicine Aug 2018Familial dysautonomia (Riley-Day syndrome, hereditary sensory autonomic neuropathy type-III) is a rare genetic disease caused by impaired development of sensory and... (Review)
Review
BACKGROUND
Familial dysautonomia (Riley-Day syndrome, hereditary sensory autonomic neuropathy type-III) is a rare genetic disease caused by impaired development of sensory and afferent autonomic nerves. As a consequence, patients develop neurogenic dysphagia with frequent aspiration, chronic lung disease, and chemoreflex failure leading to severe sleep disordered breathing. The purpose of these guidelines is to provide recommendations for the diagnosis and treatment of respiratory disorders in familial dysautonomia.
METHODS
We performed a systematic review to summarize the evidence related to our questions. When evidence was not sufficient, we used data from the New York University Familial Dysautonomia Patient Registry, a database containing ongoing prospective comprehensive clinical data from 670 cases. The evidence was summarized and discussed by a multidisciplinary panel of experts. Evidence-based and expert recommendations were then formulated, written, and graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system.
RESULTS
Recommendations were formulated for or against specific diagnostic tests and clinical interventions. Diagnostic tests reviewed included radiological evaluation, dysphagia evaluation, gastroesophageal evaluation, bronchoscopy and bronchoalveolar lavage, pulmonary function tests, laryngoscopy and polysomnography. Clinical interventions and therapies reviewed included prevention and management of aspiration, airway mucus clearance and chest physical therapy, viral respiratory infections, precautions during high altitude or air-flight travel, non-invasive ventilation during sleep, antibiotic therapy, steroid therapy, oxygen therapy, gastrostomy tube placement, Nissen fundoplication surgery, scoliosis surgery, tracheostomy and lung lobectomy.
CONCLUSIONS
Expert recommendations for the diagnosis and management of respiratory disease in patients with familial dysautonomia are provided. Frequent reassessment and updating will be needed.
Topics: Bronchoalveolar Lavage; Bronchoscopy; Brugada Syndrome; Consensus; Deglutition Disorders; Dysautonomia, Familial; Evidence-Based Practice; Humans; New York; Pneumonia, Aspiration; Polysomnography; Prospective Studies; Respiration Disorders; Respiratory Function Tests
PubMed: 30053970
DOI: 10.1016/j.rmed.2018.06.017 -
Digestive Diseases (Basel, Switzerland) 2021Mucus protects the epithelium against invaders and toxic materials. Sticky and thick mucus is characteristic of CF.
BACKGROUND
Mucus protects the epithelium against invaders and toxic materials. Sticky and thick mucus is characteristic of CF.
OBJECTIVE
The aim of this systematic review is to characterize the specific mucins secreted in the lung and intestinal tract of CF patients.
METHODS
A systematic literature search was conducted up to December 31, 2019. The following terms were used: "cystic fibrosis" AND "mucin." Case-control studies comparing mucin expression in CF patients to healthy controls were included.
RESULTS
We found 741 eligible studies, 694 studies were rejected because they were performed in animals and not in full text, and 32 studies were excluded being editorials, duplications, review articles, meta-analysis, or not in English. Fifteen studies were eligible for our study, including 150 CF patients compared to 82 healthy controls, all fulfilled the inclusion criteria. The main mucin types expressed in the sinus submucosal glands, sputum, tracheobronchial surface epithelium, and lung submucosal glands were MUC5AC and MUC5B. Increase in the number of sinusoidal submucosal glands and expression of MUC5B was found in CF patients, but no such difference from healthy controls was found for the number of goblet cells in the surface epithelium nor in the expression of -MUC5AC. The opposite was found in the tracheobronchial surface epithelium and in the lungs.
CONCLUSIONS
Increased expression of MUC5AC in the surface epithelium and of MUC5B in the subepithelial glands may be the result of higher secretion rate of mucin into the lumen of the respiratory tract, causing mucus plaque, infection, and inflammation.
Topics: Animals; Bodily Secretions; Case-Control Studies; Cystic Fibrosis; Gastrointestinal Tract; Humans; Lung; Mucin 5AC; Mucin-5B; Mucins
PubMed: 33049746
DOI: 10.1159/000512268 -
The Cochrane Database of Systematic... Feb 2016Cystic fibrosis is the most common, life-threatening, recessively inherited disease of Caucasian populations. It is a multisystem disorder caused by a mutation in the... (Review)
Review
BACKGROUND
Cystic fibrosis is the most common, life-threatening, recessively inherited disease of Caucasian populations. It is a multisystem disorder caused by a mutation in the gene encoding the cystic fibrosis transmembrane conductance regulator protein which is important in producing sweat, digestive juices and mucus.The impaired or absent function of this protein results in the production of viscous mucus within the lungs and an environment that is susceptible to chronic airway obstruction and pulmonary colonization by a range of pathogenic bacteria. Morbidity and mortality of cystic fibrosis is related to chronic pulmonary sepsis and its complications by these bacteria.Influenza can worsen the course of the disease in cystic fibrosis by increasing the risk of pneumonia and secondary respiratory complications. Antiviral agents form an important part of influenza management and include the neuraminidase inhibitors zanamivir and oseltamivir. These inhibitors can limit the infection and prevent the spread of the virus.
OBJECTIVES
To assess the effects of neuraminidase inhibitors for the treatment of influenza infection in people with cystic fibrosis.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Most recent search: 02 November 2015.
SELECTION CRITERIA
Randomised controlled trials and quasi-randomised controlled trials comparing neuraminidase inhibitors with placebo or other antiviral drugs.
DATA COLLECTION AND ANALYSIS
Two review authors had planned to independently screen studies, extract data and assess risk of bias using standard Cochrane methodologies. No studies were identified for inclusion.
MAIN RESULTS
No relevant studies were retrieved after a comprehensive search of the literature.
AUTHORS' CONCLUSIONS
We were unable to identify any randomised controlled studies or quasi-randomised controlled studies on the efficacy of neuraminidase inhibitors for the treatment of influenza infection in people with cystic fibrosis. The absence of high level evidence for the effectiveness of these interventions emphasises the need for well-designed, adequately powered, randomised controlled clinical studies.
Topics: Cystic Fibrosis; Enzyme Inhibitors; Humans; Influenza, Human; Neuraminidase
PubMed: 26905631
DOI: 10.1002/14651858.CD008139.pub4 -
The Cochrane Database of Systematic... Nov 2015Bronchiectasis is characterised by a widening of the airways, leading to excess mucus production and recurrent infection. It is more prevalent in women and those in... (Review)
Review
BACKGROUND
Bronchiectasis is characterised by a widening of the airways, leading to excess mucus production and recurrent infection. It is more prevalent in women and those in middle age. Many patients with bronchiectasis do not adhere to treatments (medications, exercise and airway clearance) prescribed for their condition. The best methods to change these adherence behaviours have not been identified.
OBJECTIVES
To assess the effects of interventions to enhance adherence to any aspect of treatment in adults with bronchiectasis in terms of adherence and health outcomes, such as pulmonary exacerbations, health-related quality of life and healthcare costs.
SEARCH METHODS
We searched the Cochrane Airways Group Specialised Register (CAGR), which contains trial reports identified through systematic searches of CENTRAL, MEDLINE, EMBASE, CINAHL, AMED and PsycINFO, from inception to October 2015.
SELECTION CRITERIA
We planned to include randomised controlled trials (RCTs) of adults with bronchiectasis that compared any intervention aimed at enhancing adherence versus no intervention, usual care or another adherence intervention. We excluded studies of those who had bronchiectasis due to cystic fibrosis.
DATA COLLECTION AND ANALYSIS
Two review authors (AMcC and ET) independently screened titles, abstracts and full-texts of identified studies.
MAIN RESULTS
Searches retrieved 36 studies reported in 37 articles; no eligible studies were identified.
AUTHORS' CONCLUSIONS
We did not identify any studies that assessed the effect of interventions to enhance adherence to treatment in bronchiectasis. Adequately powered, well-designed trials of adherence interventions for bronchiectasis are needed.
Topics: Adult; Bronchiectasis; Humans; Patient Compliance
PubMed: 26576499
DOI: 10.1002/14651858.CD011023.pub2 -
Reproductive Biology and Endocrinology... Feb 2024Biomarker identification could help in deciphering endometriosis pathophysiology in addition to their use in the development of non invasive diagnostic and prognostic... (Review)
Review
Biomarker identification could help in deciphering endometriosis pathophysiology in addition to their use in the development of non invasive diagnostic and prognostic approaches, that are essential to greatly improve patient care. Despite extensive efforts, no single potential biomarker or combination has been clinically validated for endometriosis.Many studies have investigated endometriosis-associated biological markers in specific tissues, but an integrative approach across tissues is lacking. The aim of this review is to propose a comprehensive overview of identified biomarkers based on tissue or biological compartment, while taking into account endometriosis phenotypes (superficial, ovarian or deep, or rASRM stages), menstrual cycle phases, treatments and symptoms.We searched PubMed and Embase databases for articles matching the following criteria: 'endometriosis' present in the title and the associated term 'biomarkers' found as Medical Subject Headings (MeSH) terms or in all fields. We restricted to publications in English and on human populations. Relevant articles published between 01 January 2005 (when endometriosis phenotypes start to be described in papers) and 01 September 2022 were critically analysed and discussed.Four hundred forty seven articles on endometriosis biomarkers that included a control group without endometriosis and provided specific information on endometriosis phenotypes are included in this review. Presence of information or adjustment controlling for menstrual cycle phase, symptoms and treatments is highlighted, and the results are further summarized by biological compartment. The 9 biological compartments studied for endometriosis biomarker research are in order of frequency: peripheral blood, eutopic endometrium, peritoneal fluid, ovaries, urine, menstrual blood, saliva, feces and cervical mucus. Adjustments of results on disease phenotypes, cycle phases, treatments and symptoms are present in 70%, 29%, 3% and 6% of selected articles, respectively. A total of 1107 biomarkers were identified in these biological compartments. Of these, 74 were found in several biological compartments by at least two independent research teams and only 4 (TNF-a, MMP-9, TIMP-1 and miR-451) are detected in at least 3 tissues with cohorts of 30 women or more.Integrative analysis is a crucial step to highlight potential pitfalls behind the lack of success in the search for clinically relevant endometriosis biomarkers, and to illuminate the physiopathology of this disease.
Topics: Humans; Female; Endometriosis; Biomarkers; Endometrium; Prognosis
PubMed: 38341605
DOI: 10.1186/s12958-023-01181-8