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Pediatric Gastroenterology, Hepatology... Jan 2022Inflammation plays an important role in the outcome of patients with cystic fibrosis (CF). It may develop due to cystic fibrosis transmembrane conductance regulator... (Review)
Review
Inflammation plays an important role in the outcome of patients with cystic fibrosis (CF). It may develop due to cystic fibrosis transmembrane conductance regulator protein dysfunction, pancreatic insufficiency, or prolonged pulmonary infection. Fecal calprotectin (FC) has been used as a noninvasive method to detect inflammation. Therefore, the aim of the current meta-analysis was to investigate the relationship between FC and phenotype severity in patients with CF. In this study, searches were conducted in PubMed, Science Direct, Scopus, and Embase databases up to August 2021 using terms such as "cystic fibrosis," "intestine," "calprotectin," and "inflammation." Only articles published in English and human studies were selected. The primary outcome was the level of FC in patients with CF. The secondary outcome was the relationship between FC and clinical severity. Statistical analysis was performed using Comprehensive Meta-Analysis software. Of the initial 303 references, only six articles met the inclusion criteria. The mean (95% confidence interval [CI]) level of FC was 256.5 mg/dL (114.1-398.9). FC levels were significantly associated with pancreatic insufficiency (mean, 243.02; 95% CI, 74.3 to 411.6; =0.005; I=0), pulmonary function (r=-0.39; 95% CI, -0.58 to -0.15; =0.002; I=60%), body mass index (r=-0.514; 95% CI, 0.26 to 0.69; <0.001; I=0%), and Pseudomonas colonization (mean, 174.77; 95% CI, 12.5 to 337.02; =0.035; I=71%). While FC is a reliable noninvasive marker for detecting gastrointestinal inflammation, it is also correlated with the severity of the disease in patients with CF.
PubMed: 35087728
DOI: 10.5223/pghn.2022.25.1.1 -
BioMed Research International 2022The novel coronavirus first emerged in Wuhan, China, and quickly spread across the globe, spanning various countries and resulting in a worldwide pandemic by the end of... (Review)
Review
BACKGROUND
The novel coronavirus first emerged in Wuhan, China, and quickly spread across the globe, spanning various countries and resulting in a worldwide pandemic by the end of December 2019. Given the current advances in treatments available for COVID-19, mesenchymal stem cell (MSC) therapy seems to be a prospective option for management of ARDS observed in COVID-19 patients. This present study is aimed at exploring the therapeutic potential and safety of using MSC obtained by isolation from health cord tissues in the treatment of patients with COVID-19.
METHODS
A systematic search was done based on the guidelines of the PRISMA 2020 statement. A literature search was executed using controlled vocabulary and indexing of trials to evaluate all the relevant studies involving the use of medical subject headings (MeSH) in electronic databases like PubMed, Embase, Scopus, Register of Controlled Trials (CENTRAL), and clinicaltrials.gov up to 31 December 2021. The protocol was registered in the PROSPERO register with ID CRD42022301666. . After screening finally, 22 remaining articles were included in this systematic review. The studies revealed that MSC exosomes are found to be superior to MSC alone in terms of safety owing to being smaller with a lesser immunological response which leads to free movement in blood capillaries without clumping and also cannot further divide, thus reducing the oncogenic potential of MSC-derived exosomes as compared to MSC only. The studies demonstrated that the lungs healed with the use of exosomes compared to how they presented initially at the hospital. MSCs are found to increase the angiogenesis process and alveolar reepithelization, reducing markers like TNF alpha, TGF beta, and COL I and III, reducing the growth of myofibroblasts and increasing survivability of endothelium leading to attenuated pulmonary fibrosis and even reversing them. . We can conclude that the use of mesenchymal stem cells or their derived exosomes is safe and well-tolerated in patients with COVID-19. It improves different parameters of oxygenation and helps in the healing of the lungs. The viral load along with different inflammatory cells and biomarkers of inflammation tend to decrease. Chest X-ray, CT scan, and different radiological tools are used to show improvement and reduced ongoing destructive processes.
Topics: COVID-19; Exosomes; Humans; Mesenchymal Stem Cells; Prospective Studies; Pulmonary Fibrosis
PubMed: 35782071
DOI: 10.1155/2022/9346939 -
Transplantation Reviews (Orlando, Fla.) Dec 2023There is lack of consensus on non-tuberculous mycobacteria pulmonary disease (NTM-PD) treatment regimen and duration in patient listed for lung transplantation (LTx). We... (Review)
Review
BACKGROUND
There is lack of consensus on non-tuberculous mycobacteria pulmonary disease (NTM-PD) treatment regimen and duration in patient listed for lung transplantation (LTx). We conducted a systematic review on treatment regimen and duration pre- and directly post-LTx, for patients with known NTM-PD pre-LTx. Additionally, we searched for risk factors for NTM disease development post-LTx and for mortality.
METHODS
Literature was reviewed on PubMed, Embase and the Cochrane Library, for articles published from inception to January 2022. Individual patient data were sought.
RESULTS
Sixteen studies were included reporting 92 patients. Most frequent used agents were aminoglycosides and macrolides for Mycobacterium abscessus (M. abscessus) and macrolides and tuberculostatic agents for Mycobacterium avium complex (M. avium complex). The median treatment duration pre-LTx was 10 months (IQR 6-17) and 2 months (IQR 2-8) directly post-LTx. Longer treatment duration pre-LTx was observed in children and in patients with M. abscessus. 46% of the patients with NTM-PD pre-LTx developed NTM disease post-LTx, related mortality rate was 10%. Longer treatment duration pre-LTx (p < 0.001) and sputum non-conversion pre-LTx (p = 0.003) were significantly associated with development of NTM-disease post-LTx. Longer treatment duration pre-LTx (p = 0.004), younger age (p < 0.001) and sputum non-conversion (p = 0.044) were risk factors for NTM related death.
CONCLUSIONS
The median treatment duration pre-LTx was 10 months (IQR 6-17) and 2 months (IQR 2-8) directly post-LTx. Patients with longer treatment duration for NTM-PD pre-LTx and with sputum non-conversion are at risk for NTM disease post-LTx and for NTM-related death. Children were particularly at risk for NTM related death.
Topics: Child; Humans; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous; Lung Diseases; Lung Transplantation; Anti-Bacterial Agents; Macrolides
PubMed: 37832509
DOI: 10.1016/j.trre.2023.100800 -
The Cochrane Database of Systematic... Mar 2021Dornase 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
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: 12 October 2020. Clinicaltrials.gov and the International Clinical Trials Registry Platform were also searched to identify unpublished or ongoing trials. Date of most recent search: 08 February 2021.
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 74 trials, of which 19 (2565 participants) met our inclusion criteria. 15 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 treatment Dornase alfa probably improved forced expiratory volume at one second (FEV) 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 treatment may make little or no difference in quality of life. Dornase alfa probably reduced the number of pulmonary exacerbations 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 day One cross-over trial (43 children) found little or no difference between treatment regimens for lung function, quality of life or pulmonary exacerbations (low-quality evidence). Dornase alfa compared to other medications that improve airway clearance Results for these comparisons were mixed. One trial (43 children) showed dornase alfa may lead to a greater improvement in FEV compared to hypertonic saline (low-quality evidence), and one trial (23 participants) reported little or no differences in lung function between dornase alfa and mannitol or dornase alfa and dornase alfa plus mannitol (low-quality evidence). One trial (23 participants) found dornase alfa may improve quality of life compared to dornase alfa plus mannitol (low-quality evidence); other comparisons found little or 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 may improve 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, probably due to treatment. 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; Adult; Child; Child, Preschool; Cystic Fibrosis; Deoxyribonuclease I; Disease Progression; Expectorants; Forced Expiratory Volume; Humans; Infant; Mannitol; Placebos; Randomized Controlled Trials as Topic; Recombinant Proteins; Saline Solution, Hypertonic; Vital Capacity
PubMed: 33735508
DOI: 10.1002/14651858.CD001127.pub5 -
Cureus Sep 2022A cystic fibrosis (CF) transmembrane conductor regulator (CFTR) gene modulating triple therapy combining elexacaftor-tezacaftor-ivacaftor (Trikafta) has been recently... (Review)
Review
A cystic fibrosis (CF) transmembrane conductor regulator (CFTR) gene modulating triple therapy combining elexacaftor-tezacaftor-ivacaftor (Trikafta) has been recently discovered. Its approval by the Food and Drug Administration (FDA) in 2019 has expanded the target therapy group to individuals aged twelve and up with at least one Phe508del (phenylalanine 508 deletion) mutation in the CFTR gene. This systematic review aims to assess this combination therapy's safety and efficacy. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, an in-depth search was performed. The search was done by utilizing databases such as PubMed Central (PMC), Google Scholar, and Science Direct for articles related to this topic. Studies published in the last five years in the English language were chosen preliminarily. Further eligibility criteria and quality assessment tools were employed to assess the risk of bias and finalize ten articles to be used in this review. The chosen articles constituted four randomized control trials (RCTs), four systematic reviews, and two narrative reviews. The last date for data collection was April 24, 2022. Based on the findings of this review, we concluded that by combining three CFTR modulators, this therapy had outperformed all the currently available medications in terms of improving pulmonary function, reducing exacerbations, and enhancing the quality of life of CF patients. In clinical trials, headache and rash were the most common side effects, and laboratory testing to assess liver function is suggested. Long-term safety and effectiveness must be confirmed by the continued review of real-life patient data. Studies done on triple therapy thus far have been promising. Unfortunately, a small proportion of the CF population remains ineligible for any form of CFTR modulator therapy owing to their type of genetic mutation, and this provides ground for further research in this field.
PubMed: 36284811
DOI: 10.7759/cureus.29359 -
Frontiers in Pharmacology 2023Elexacaftor-Tezacaftor-Ivacaftor (ELE/TEZ/IVA) is believed to be an effective and well-tolerated treatment for cystic fibrosis (CF), but the exact efficacy and safety...
Elexacaftor-Tezacaftor-Ivacaftor (ELE/TEZ/IVA) is believed to be an effective and well-tolerated treatment for cystic fibrosis (CF), but the exact efficacy and safety profile are still unknown. This study aimed to clarify the extent of functional restoration when patients are given with triple combination treatment and demonstrate the prevalence of adverse events, to evaluate the overall profile of ELE/TEZ/IVA on CF. A literature search was conducted in PubMed, Web of Science and Cochrane Library. Random effects single-arm meta-analysis was performed to decipher the basal characteristics of CF, the improvement and safety profile after ELE/TEZ/IVA treatment. A total 53 studies were included in this analysis. For all the patients in included studies. 4 weeks after ELE/TEZ/IVA treatment, the increasement of percentage of predicted Forced Expiratory Volume in the first second (ppFEV) was 9.23% (95%CI, 7.77%-10.70%), the change of percentage of predicted Forced Vital Capacity (ppFVC) was 7.67% (95%CI, 2.15%-13.20%), and the absolute change of Cystic Fibrosis Questionnaire-Revised (CFQ-R) score was 21.46 points (95%CI, 18.26-24.67 points). The Sweat chloride (SwCl) was significantly decreased with the absolute change of -41.82 mmol/L (95%CI, -44.38 to -39.25 mmol/L). 24 weeks after treatment, the increasement of ppFEV was 12.57% (95%CI, 11.24%-13.90%), the increasement of ppFVC was 10.44% (95%CI, 7.26%-13.63%), and the absolute change of CFQ-R score was 19.29 points (95%CI, 17.19-21.39 points). The SwCl was significantly decreased with the absolute change of -51.53 mmol/L (95%CI, -56.12 to -46.94 mmol/L). The lung clearance index (LCI) was also decreased by 1.74 units (95%CI, -2.42 to -1.07 units). The body mass index increased by 1.23 kg/m (95%CI, 0.89-1.57 kg/m). As for adverse events, 0.824 (95%CI, 0.769-0.879) occurred during ELE/TEZ/IVA period, while the incidence of severe adverse events was 0.066 (95%CI, 0.028-0.104). ELE/TEZ/IVA is a highly effective strategy and relatively safe for CF patients and needs to be sustained to achieve better efficacy. Identifier: CRD42023441840.
PubMed: 38186649
DOI: 10.3389/fphar.2023.1275470 -
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 -
BMJ Open Respiratory Research Dec 2023We aimed to assess the available evidence for corticosteroids in fibrotic interstitial lung disease (fILD) to inform the randomised embedded multifactorial adaptive... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
We aimed to assess the available evidence for corticosteroids in fibrotic interstitial lung disease (fILD) to inform the randomised embedded multifactorial adaptive platform ILD.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
We searched Embase, Medline, Cochrane CENTRAL and Web of Science databases from inception to April 17 2023.
ELIGIBILITY CRITERIA
We included studies that compared corticosteroids with standard care, placebo or no treatment in adult patients with fILD.
DATA EXTRACTION AND SYNTHESIS
We report on the change in forced vital capacity (FVC) and mortality. We used random-effects meta-analysis to estimate relative risk (RR) for dichotomous outcomes, and mean difference (MD) and standardised MDs for continuous outcomes, with 95% CIs.
RESULTS
Of the 13 229 unique citations identified, we included 10 observational studies comprising 1639 patients. Corticosteroids had an uncertain effect on mortality compared with no treatment (RR 1.03 (95% CI 0.85 to 1.25); very low certainty evidence). The effect of corticosteroids on the rate of decline in FVC (% predicted) was uncertain when compared with no treatment (MD 4.29% (95% CI -8.26% to 16.83%); very low certainty evidence). However, corticosteroids might reduce the rate of decline in FVC in patients with non-idiopathic pulmonary fibrosis (IPF) fILD (MD 10.89% (95% CI 5.25% to 16.53%); low certainty evidence), while an uncertain effect was observed in patients with IPF (MD -3.80% (95% CI -8.94% to 1.34%); very low certainty evidence).
CONCLUSIONS
The current evidence on the efficacy and safety of corticosteroids in fILD is limited and of low certainty. Randomised trials are needed to address this significant research gap.
Topics: Adult; Humans; Adrenal Cortex Hormones; Lung Diseases, Interstitial; Vital Capacity
PubMed: 38160015
DOI: 10.1136/bmjresp-2023-002008 -
RMD Open Oct 2023We conducted a systematic review and meta-analysis to determine the efficacy of non-conventional synthetic disease-modifying antirheumatic drug (ncs-DMARD) strategies on... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
We conducted a systematic review and meta-analysis to determine the efficacy of non-conventional synthetic disease-modifying antirheumatic drug (ncs-DMARD) strategies on patients with rheumatoid arthritis (RA)-associated interstitial lung disease (ILD).
METHODS
PubMed, EMBASE, the Cochrane Library and Web of Science were searched for relevant articles from inception to 1 June 2022. The results obtained from the analysis were expressed as mean difference (MD), effect size and 95% CI.
RESULTS
A total of 17 studies, including 1315 patients with RA-ILD, were eligible. The ncs-DMARDs included abatacept, rituximab, tocilizumab, tumour necrosis factor and Janus kinase inhibitors. Compared with the baseline, there were no significant changes in forced vital capacity (FVC), forced expiratory volume in the first second (FEV) and diffusion lung capacity for carbon monoxide (DLCO) values in the pooled data after ncs-DMARD treatment (alone or combined with conventional therapy) (p=0.36 for FVC; p=0.96 for FEV and p=0.46 for DLCO). Of note, FVC was obviously increased in rituximab subgroup (MD=-4.62, 95% CI -8.90 to -0.33, p=0.03). Also, high-resolution CT non-progression rate and fatality rate due to ILD progression in patients with RA-ILD were 0.792 (95% CI 0.746 to 0.834, p=0.015) and 0.049 (95% CI 0.035 to 0.065, p=0.000), respectively.
CONCLUSION
ncs-DMARDs alone or combined with conventional therapy might be an optimal and promising treatment for stabilising or improving ILD in patients with RA-ILD.
PROSPERO REGISTRATION NUMBER
CRD42022356816.
Topics: Humans; Rituximab; Antirheumatic Agents; Arthritis, Rheumatoid; Lung Diseases, Interstitial; Abatacept
PubMed: 37899093
DOI: 10.1136/rmdopen-2023-003487 -
Healthcare (Basel, Switzerland) Mar 2022Since the onset of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, various potential targeted therapies for SARS-CoV-2 infection have been... (Review)
Review
Since the onset of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, various potential targeted therapies for SARS-CoV-2 infection have been proposed. The protective effects of mineralocorticoid receptor antagonists (MRA) against tissue fibrosis, pulmonary and systemic vasoconstriction, and inflammation have been implicated in potentially attenuating the severity of SARS-CoV-2 infection by inhibiting the deleterious effects of aldosterone. Furthermore, spironolactone, a type of MRA, has been suggested to have a beneficial effect on SARS-CoV-2 outcomes through its dual action as an MRA and antiandrogen, resulting in reduced transmembrane protease receptor serine type 2 (TMPRSS2)-related viral entry to host cells. In this study, we sought to investigate the association between MRA antagonist therapy and mortality in SARS-CoV-2 patients via systematic review and meta-analysis. The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE and EMBASE databases were searched for studies that reported the incidence of mortality in patients on MRA with SARS-CoV-2 infection. Pooled odds ratio (OR) and 95% confidence interval (CI) of the outcome were obtained using the random-effects model. Five studies with a total of 1,388,178 subjects (80,903 subjects receiving MRA therapy) met the inclusion criteria. We included studies with all types of MRA therapy including spironolactone and canrenone and found no association between MRA therapy and mortality in SARS-CoV-2 infection (OR = 0.387, 95% CI: 0.134-1.117, = 0.079).
PubMed: 35455823
DOI: 10.3390/healthcare10040645