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BMC Pulmonary Medicine Nov 2023Numerous studies have demonstrated the potential of pirfenidone to enhance the prognosis of patients afflicted with idiopathic pulmonary fibrosis (IPF). Although... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Numerous studies have demonstrated the potential of pirfenidone to enhance the prognosis of patients afflicted with idiopathic pulmonary fibrosis (IPF). Although N-acetylcysteine (NAC) is utilized as an antioxidant in IPF treatment, the combination of NAC and pirfenidone has produced inconsistent outcomes in certain studies. To assess the clinical effectiveness and safety of NAC plus pirfenidone (designated as the treatment group) versus pirfenidone monotherapy (designated as the control group), we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs).
METHODS
RCTs of NAC plus pirfenidone were reviewed searching from databases and networks of unpublished and published studies in any language. Using pair-wise meta-analysis, changes in pulmonary function test (PFT) parameters and safety were evaluated.
RESULTS
Two independent reviewers selected and obtained data from 5 RCTs (n = 398), comprising 1 study from Japan, 1 from Europe, and 3 from China. NAS plus pirfenidone as compared to pirfenidone monotherapy for IPF may not reduce the incidence of skin effects(RR 1.26 [95%CI 0.64 to 2.45]) and mortality(RR 0.35 [95%CI 0.07 to 1.68])(both moderate certainty). NAS plus pirfenidone as compared to pirfenidone monotherapy for IPF may not reduce the incidence of at least one side effects(RR 1.00 [95%CI 0.84 to 1.19]; low certainty),severe side effects(RR 0.67 [95%CI 0.30 to 1.47]; low certainty) and gastrointestinal effects(RR 0.67 [95%CI 0.41 to 1.09]; low certainty) with possibly no effect in Δ%DLco(SMD -0.17 [95%CI -0.15 to 0.48]; low certainty). Meanwhile, the effect of NAS plus pirfenidone as compared to pirfenidone monotherapy on ΔFVC(SMD 0.18 [95%CI -0.68 to 1.05]), Δ%FVC(SMD -2.62 [95%CI -5.82 to 0.59]) and Δ6MWT(SMD -0.35 [95%CI -0.98 to 0.28]) is uncertain(extremely low certainty).
CONCLUSION
Moderate certainty evidence suggests that NAS plus pirfenidone, compared to pirfenidone monotherapy for IPF, does not reduce the incidence of skin effects and mortality.
Topics: Humans; Acetylcysteine; Pyridones; Treatment Outcome; Idiopathic Pulmonary Fibrosis
PubMed: 38031002
DOI: 10.1186/s12890-023-02778-w -
European Respiratory Review : An... Jun 2017Lung fibrosis can be observed in systemic sclerosis and in idiopathic pulmonary fibrosis, two disorders where lung involvement carries a poor prognosis. Although much... (Review)
Review
Lung fibrosis can be observed in systemic sclerosis and in idiopathic pulmonary fibrosis, two disorders where lung involvement carries a poor prognosis. Although much has been learned about the pathogenesis of these conditions, interventions capable of reversing or, at the very least, halting disease progression are not available. Recent studies point to the potential role of micro messenger RNAs (microRNAs) in cancer and tissue fibrogenesis. MicroRNAs are short non-coding RNA sequences (20-23 nucleotides) that are endogenous, evolutionarily conserved and encoded in the genome. By acting on several genes, microRNAs control protein expression. Considering the above, we engaged in a systematic review of the literature in search of overlapping observations implicating microRNAs in the pathogenesis of both idiopathic pulmonary fibrosis (IPF) and systemic sclerosis (SSc). Our objective was to uncover top microRNA candidates for further investigation based on their mechanisms of action and their potential for serving as targets for intervention against lung fibrosis. Our review points to microRNAs of the -29 family, -21-5p and -92a-3p, -26a-5p and let-7d-5p as having distinct and counter-balancing actions related to lung fibrosis. Based on this, we speculate that readjusting the disrupted balance between these microRNAs in lung fibrosis related to SSc and IPF may have therapeutic potential.
Topics: Fibroblasts; Gene Expression Regulation; Genetic Markers; Humans; Idiopathic Pulmonary Fibrosis; Lung; MicroRNAs; Scleroderma, Systemic; Skin
PubMed: 28515040
DOI: 10.1183/16000617.0125-2016 -
Archives of Environmental &... 2022Air pollution is a big ecumenical problem associated with public health around the world. The rapid development of nanotechnology worldwide resulted in a significant... (Meta-Analysis)
Meta-Analysis
Air pollution is a big ecumenical problem associated with public health around the world. The rapid development of nanotechnology worldwide resulted in a significant increase in human exposure with unknown particles, and ultimately leading to an increase in acute and chronic diseases. The effect of nanoparticles on pulmonary fibrosis has been reported in vivo and in vitro studies; however, the results are inconsistent. The present systematic review and meta-analysis of animal preclinical studies was conducted to assess the effect of nanoparticles on pulmonary fibrosis. A systematic search of online databases and gray literature as well as reference lists of retrieved studies was performed up to February 2019 to identify preclinical animal studies. Studies were assessed for methodological quality using the SYstematic Review Center for Laboratory animal Experimentation bias risk tool (SYRCLE's ROB tool). Pooled standardized mean difference (SMD) estimate with corresponding 95% CI was calculated using inverse-variance weights method while random effects meta-analysis was used, taking into account conceptual heterogeneity. To assess the robustness of pooled estimates as well as heterogeneity across studies, sensitivity analysis and Cochran statistic (with statistic) was carried out using Stata 11.0. Of 6494 retrieved studies, 85 were reviewed in depth for eligibility. 16 studies met the criteria for inclusion in this systematic review. The meta-analysis was conducted on 10 studies which had reported the mean of TGF-β in 7 days after exposure by nanoparticles jointly (exposure compared to no exposure). Findings showed that exposure to nanoparticles significantly induced pulmonary fibrosis (SMD: 4.12, 95% CI: 2.57-5.67). A statistical heterogeneity was found [ < 0.001 (Q statistics), = 83.0%] across studies. Nanoparticles were the most influencing in inducing pulmonary fibrosis in animal models. Sensitivity analysis demonstrated consistency of the results, indicating that the meta-analysis model was robust. Publication bias (using visual inspection and statistical tests) was unlikely in the association between nanoparticles and pulmonary fibrosis. We found that the nanoparticles significantly induce pulmonary fibrosis through increasing proinflammatory cytokine TGF-β and histopathological changes.
Topics: Air Pollution; Animals; Nanoparticles; Pulmonary Fibrosis; Research Design; Transforming Growth Factor beta
PubMed: 35244528
DOI: 10.1080/19338244.2021.2001637 -
Cells Nov 2023There is an increasing recognition of the crucial role of the right ventricle (RV) in determining the functional status and prognosis in multiple conditions. In the past... (Review)
Review
There is an increasing recognition of the crucial role of the right ventricle (RV) in determining the functional status and prognosis in multiple conditions. In the past decade, the epigenetic regulation (DNA methylation, histone modification, and non-coding RNAs) of gene expression has been raised as a critical determinant of RV development, RV physiological function, and RV pathological dysfunction. We thus aimed to perform an up-to-date review of the literature, gathering knowledge on the epigenetic modifications associated with RV function/dysfunction. Therefore, we conducted a systematic review of studies assessing the contribution of epigenetic modifications to RV development and/or the progression of RV dysfunction regardless of the causal pathology. English literature published on PubMed, between the inception of the study and 1 January 2023, was evaluated. Two authors independently evaluated whether studies met eligibility criteria before study results were extracted. Amongst the 817 studies screened, 109 studies were included in this review, including 69 that used human samples (e.g., RV myocardium, blood). While 37 proposed an epigenetic-based therapeutic intervention to improve RV function, none involved a clinical trial and 70 are descriptive. Surprisingly, we observed a substantial discrepancy between studies investigating the expression (up or down) and/or the contribution of the same epigenetic modifications on RV function or development. This exhaustive review of the literature summarizes the relevant epigenetic studies focusing on RV in human or preclinical setting.
Topics: Humans; Heart Ventricles; Epigenesis, Genetic; Ventricular Dysfunction, Right; Myocardium; Ventricular Function, Right
PubMed: 38067121
DOI: 10.3390/cells12232693 -
Pediatric Health, Medicine and... 2021Limited information and literature exist examining pulmonary infections caused by nontuberculous mycobacterial specifically in an infant population. The objective of our... (Review)
Review
Limited information and literature exist examining pulmonary infections caused by nontuberculous mycobacterial specifically in an infant population. The objective of our study was to summarize clinical characteristics and outcomes of infant patients with nontuberculous mycobacterial pulmonary infection via systematic literature review to identify common diagnostic and treatment regimens for this infection in infants. A search of MEDLINE and PubMed databases in October 2019 using MeSH search terms "infant," "NTM," "pulmonary," and "Mycobacterium abscessus" yielded 139 articles. Inclusion criteria were i) English-language studies including cases and case series with ii) established nontuberculous mycobacterial pulmonary infection in iii) a patient population of infants no older than 24 months. Patients with cystic fibrosis and any study which did not contain relevant information such as infection and age were excluded. This yielded data on 37 patients extracted from 28 studies analyzed. The most common strain was complex, isolated in 56.8% of patient diagnoses. Bronchoscopy/thoracoscopy with a subsequent culture were the most common diagnostic techniques, utilized in 64.9% of cases. Drug therapeutic treatment was utilized in 86% of cases, with a median of three drugs administered. Notable limitations of this study are the small sample size and its retrospective nature, which relies on information reported in previous case studies. Although there is limited formal clinician consensus on the treatment of NTM pulmonary infection and how it may differ in an infant population, our findings indicate an informal consensus typically involving diagnostic lung specimen culture and antibiotic therapy.
PubMed: 35002357
DOI: 10.2147/PHMT.S332434 -
Frontiers in Pediatrics 2022Metabolomics is an emerging area of research and has the potential to identify clinical biomarkers for predicting or diagnosing cystic fibrosis (CF) pulmonary...
INTRODUCTION
Metabolomics is an emerging area of research and has the potential to identify clinical biomarkers for predicting or diagnosing cystic fibrosis (CF) pulmonary exacerbations (PEx).
OBJECTIVE
To identify clinically promising metabolites across different sample sources that can be used to predict or diagnose PEx in CF.
EVIDENCE REVIEW
Searches for original literature were completed through EMBASE, MEDLINE, and all databases on the Web of Science with no restrictions on language or publication date. Gray literature was collected through Google Scholar. Additional studies were obtained by contacting authors and searching reference lists of candidate papers. The patient population included individuals with CF. Studies involving patients who underwent lung transplantation were excluded. The outcome was the prediction or diagnosis of pulmonary exacerbations from metabolites directly measured from biological samples. Search results were downloaded and imported into Covidence and duplicates were removed automatically. Any remaining duplicates were manually tagged and excluded. Two independent reviewers screened each abstract for eligibility and repeated this process for full texts. Risk of bias was conducted using QUADAS-2 by two independent reviewers. A third author resolved any remaining conflicts.
RESULTS
A combined 3974 relevant abstracts were identified and 115 full texts were assessed for eligibility. The final 25 studies underwent data extraction for study design, patient demographics, studied metabolites, concentration values, and diagnostic accuracy values. Included studies differed considerably in methodologies, sample specimen types (exhaled breath condensate [EBC], sputum, saliva, plasma, urine), and disease states. We identified 19 unique metabolites that were measured by two or more studies of which 2 have the potential to predict PEx (EBC 4-hydroxycyclohexylcarboxylic acid [4-HCHC] and lactic acid) and 6 to diagnose PEx (EBC 4-HCHC and lactic acid, sputum lactic acid and nitrate, and plasma arginine and methionine).
CONCLUSION AND RELEVANCE
This systematic review has identified promising metabolites for further study in CF. Certain metabolites may provide clinical potential in predicting or diagnosing PEx, but further validation studies are required. With better tools to aid in the earlier identification of PEx, clinicians can implement preventative measures to mitigate airway damage. https://www.crd.york.ac.uk/prospero/.
PubMed: 35712620
DOI: 10.3389/fped.2022.896439 -
The Cochrane Database of Systematic... Sep 2014Self-management education may help patients with cystic fibrosis and their families to choose, monitor and adjust treatment requirements for their illness, and also to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Self-management education may help patients with cystic fibrosis and their families to choose, monitor and adjust treatment requirements for their illness, and also to manage the effects of illness on their lives. Although self-management education interventions have been developed for cystic fibrosis, no previous systematic review of the evidence of effectiveness of these interventions has been conducted.
OBJECTIVES
To assess the effects of self-management education interventions on improving health outcomes for patients with cystic fibrosis and their caregivers
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register (date of the last search: 22 August 2013).We also searched databases through EBSCO (CINAHL; Psychological and Behavioural Sciences Collection; PsychInfo; SocINDEX) and Elsevier (Embase) and handsearched relevant journals and conference proceedings (date of the last searches: 01 February 2014 ).
SELECTION CRITERIA
Randomised controlled trials, quasi-randomised controlled trials or controlled clinical trials comparing different types of self-management education for cystic fibrosis or comparing self-management education with standard care or no intervention.
DATA COLLECTION AND ANALYSIS
Two authors assessed trial eligibility and risk of bias. Three authors extracted data.
MAIN RESULTS
Four trials (involving a total of 269 participants) were included. The participants were children with cystic fibrosis and their parents or caregivers in three trials and adults with cystic fibrosis in one trial. The trials compared four different self-management education interventions versus standard treatment: (1) a training programme for managing cystic fibrosis in general; (2) education specific to aerosol and airway clearance treatments; (3) disease-specific nutrition education; and (4) general and disease-specific nutrition education. Training children to manage cystic fibrosis in general had no statistically significant effects on weight after six to eight weeks, mean difference -7.74 lb (i.e. 3.51 kg) (95% confidence interval -35.18 to 19.70). General and disease-specific nutrition education for adults had no statistically significant effects on: pulmonary function (forced expiratory volume at one second), mean difference -5.00 % (95% confidence interval -18.10 to 8.10) at six months and mean difference -5.50 % (95% confidence interval -18.46 to 7.46) at 12 months; or weight, mean difference - 0.70 kg (95% confidence interval -6.58 to 5.18) at six months and mean difference -0.70 kg (95% confidence interval -6.62 to 5.22) at 12 months; or dietary fat intake scores, mean difference 1.60 (85% confidence interval -2.90 to 6.10) at six months and mean difference 0.20 (95% confidence interval -4.08 to 4.48) at 12 months. There is some limited evidence to suggest that self-management education may improve knowledge in patients with cystic fibrosis but not in parents or caregivers. There is also some limited evidence to suggest that self-management education may result in positively changing a small number of behaviours in both patients and caregivers.
AUTHORS' CONCLUSIONS
The available evidence from this review is of insufficient quantity and quality to draw any firm conclusions about the effects of self-management education for cystic fibrosis. Further trials are needed to investigate the effects of self-management education on a range of clinical and behavioural outcomes in children, adolescents and adults with cystic fibrosis and their caregivers.
Topics: Adolescent; Adult; Caregivers; Child; Cystic Fibrosis; Humans; Nutrition Therapy; Parents; Patient Education as Topic; Randomized Controlled Trials as Topic; Self Care; Young Adult
PubMed: 25198249
DOI: 10.1002/14651858.CD007641.pub3 -
Radiology Jul 2023Background Radiological lung may explain the persistence of respiratory complaints in post-COVID-19 condition (long-COVID). Purpose To perform a systematic review and... (Meta-Analysis)
Meta-Analysis
Background Radiological lung may explain the persistence of respiratory complaints in post-COVID-19 condition (long-COVID). Purpose To perform a systematic review and meta-analysis of the prevalence and type of COVID-19 residual lung abnormalities at 1-year chest CT. Materials and Methods A literature search of PubMed, Web of Science, Embase, and Medline databases was performed from January 2020 to January 2023. Full-text reports of CT lung in adults (≥18 years) with confirmed COVID-19 at 1-year follow-up were included. The prevalence of any residual lung abnormality and type (fibrotic or not) was analyzed according to the Fleischner Glossary. The meta-analysis included studies with chest CT data assessable in no less than 80% of individuals. A random-effects model was used to estimate pooled prevalence. Multiple sub-group (country, journal category, methodological quality, study setting, outcomes) and meta-regression analyses were performed to identify potential sources of heterogeneity. I statistics estimated low (25%), moderate (26-50%) and high (>50%) heterogeneity. 95% Prediction Intervals (95% PIs) were computed to describe the expected estimates range. Results Of 22 709 records, 21 studies were reviewed (20 prospective, 9 from China, and 7 in radiology journals). The meta-analysis included 14 studies with chest CT data in 1854 of 2043 individuals (M/F: 1109/934). Estimates of lung were highly heterogeneous (7.1-96.7%), with a pooled frequency of 43.5% (I=94%; 95% PI: 5.9%, 90.4%). This also applied to single non-fibrotic changes, including ground glass opacity, consolidations, nodules/masses, parenchymal bands, and reticulations. The prevalence range of fibrotic traction bronchiectasis/bronchiolectasis was 1.6-25.7% (I=93%; 95% PI: 0.0%, 98.6%;); honeycombing was unremarkable (0-1.1%; I=58%; 95% PI: 0%, 60%). Lung were unrelated to any characteristics of interest. Conclusion The prevalence of COVID-19 lung at 1-year chest CT is highly heterogeneous among studies. Heterogeneity determinants remain unknown suggesting caution in data interpretation with no convincing evidence. PROSPERO (CRD42022341258) COVID-19 pneumonia, pulmonary fibrosis, chest CT, long-COVID, systematic review, metaanalysis See also the editorial by Parraga and Svenningsen in this issue.
Topics: Adult; Humans; COVID-19; SARS-CoV-2; Post-Acute COVID-19 Syndrome; Prospective Studies; Lung; Tomography, X-Ray Computed; Bronchiectasis; Pulmonary Fibrosis; Disease Progression
PubMed: 37404150
DOI: 10.1148/radiol.230535 -
Journal of Thoracic Disease Nov 2023The role of combination treatments with two antifibrotic agents, pirfenidone and nintedanib, has been not established in idiopathic pulmonary fibrosis (IPF). This study...
BACKGROUND
The role of combination treatments with two antifibrotic agents, pirfenidone and nintedanib, has been not established in idiopathic pulmonary fibrosis (IPF). This study was performed to investigate the safety and tolerability of combination antifibrotic treatment in patients with IPF.
METHODS
We conducted a proportional meta-analysis and searched PubMed, EMBASE, and the Cochrane Central Register for relevant clinical trials. The primary outcome was the proportion of discontinuation of combination treatment over the treatment period. We also examined the pooled proportions of serious and any adverse drug reactions (ADRs).
RESULTS
Four clinical trials involving 191 patients were analyzed. In pooled estimates, 29% of patients discontinued treatment during the study period [95% confidence interval (CI): 17-41%, I=65.42%]. The pooled proportions of serious and any ADRs were 10% (95% CI: 1-19%; I=79.13%) and 82% (95% CI: 75-90%; I=39.20%), respectively. During the follow-up period, gastrointestinal symptoms were the most frequent ADR. Acute exacerbation (AE) of IPF was reported in 7.0% of patients.
CONCLUSIONS
Our findings showed relatively frequent incidence of discontinuation and ADRs for combination therapy in IPF. Further large-scale, randomized, controlled trials are needed to support our results because of the methodological limitations of the included trials and a scarcity of trials for analysis.
PubMed: 38090320
DOI: 10.21037/jtd-23-946 -
The Cochrane Database of Systematic... Dec 2023Cystic fibrosis (CF) is a life-shortening, autosomal recessive disease that leads to abnormal electrolyte concentration in exocrine secretions. Secretion stasis in... (Review)
Review
BACKGROUND
Cystic fibrosis (CF) is a life-shortening, autosomal recessive disease that leads to abnormal electrolyte concentration in exocrine secretions. Secretion stasis in paranasal sinuses determines chronic rhinosinusitis (CRS) and nasal polyposis. Endoscopic sinus surgery is used to open the sinuses and allow medical treatment to work properly.
OBJECTIVES
To determine the effects of sinus surgery alone or in combination with medical treatment (non-surgical) compared to medical treatment (non-surgical) alone on both nasal and pulmonary function in people with CF diagnosed with CRS with nasal polyposis. Further, to evaluate the impact of sinus surgery (with or without medical treatment) on hospitalization rates, use of antibiotics and pulmonary exacerbation rates.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and hand searching of journals and conference abstract books. Date of last search: 4 July 2022. We also searched other databases (Pubmed, Embase, World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), Virtual Health Library and ClinicalTrials.gov). Date of last search: 18 September 2022.
SELECTION CRITERIA
Randomized controlled trials (RCTs) comparing groups who underwent endoscopic sinus surgery and groups with medical treatment alone.
DATA COLLECTION AND ANALYSIS
The review authors independently selected studies, extracted data, assessed the risk of bias and evaluated the certainty of the evidence using GRADE. They contacted the authors of the included study for additional information.
MAIN RESULTS
We identified 66 publications relating to 50 studies from electronic searches. Only one study fulfilled the inclusion criteria, and only limited information was available. In this study, 28 participants aged 19 to 28 years were randomized in equal numbers to either nasal irrigation alone or nasal irrigation with surgery (endoscopic polypectomy with extended sinusotomy). The certainty of the evidence was very low according to the GRADE approach. We are uncertain whether, compared to medical treatment alone, the addition of surgical intervention improves nasal symptoms, or reduces bacterial colonization, the use of antibiotics and pulmonary exacerbations. We are also uncertain whether the addition of surgery to medical treatment leads to changes in pulmonary function. There was one episode of bleeding during surgery that was corrected during the procedure with no further consequences. The study did not report on survival.
AUTHORS' CONCLUSIONS
Very low-certainty evidence means we are not certain if endoscopic sinus surgery to treat chronic rhinosinusitis with nasal polyposis in cystic fibrosis is effective. Future research should be multicentric to increase the number of participants and increase statistical power. Adequate randomization and allocation concealment are important to guarantee that the groups are similar. Blinding, however, may not be possible in an ethical trial; even without blinding, results can achieve high-level evidence if the outcomes used are objective parameters. Future research should follow participants of all ages for at least 12 months to evaluate the evolution of nasal polyposis, its recurrence and how symptoms may return. We also consider mortality an important outcome to be assessed. Future clinical research should consider the effects of cystic fibrosis transmembrane conductance regulators, a new group of drugs that may affect the development of nasal polyps.
Topics: Humans; Cystic Fibrosis; Nasal Polyps; Anti-Bacterial Agents; Sinusitis; Chronic Disease; Randomized Controlled Trials as Topic
PubMed: 38063253
DOI: 10.1002/14651858.CD014084.pub2