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Cureus Mar 2021Cystic fibrosis is an autosomal recessive disorder caused by a mutation in genes for cystic fibrosis transmembrane conductance regulator (CFTR) protein. CFTR gene is... (Review)
Review
Cystic fibrosis is an autosomal recessive disorder caused by a mutation in genes for cystic fibrosis transmembrane conductance regulator (CFTR) protein. CFTR gene is responsible for the production of sweat, digestive fluids, and mucus, and any mutation in this would lead to the thickening of these secretions. Cystic fibrosis is a multi-organ disorder, but 80% of patients suffer from respiratory problems due to chronic infections most commonly caused by . Eradication of these infections has become a challenge as has developed resistance to multiple antibiotics. In several studies, iron has been shown to play an integral role in biofilm formation which is the predominant resistance mechanism used by to combat antibiotics. The increased iron content in cystic fibrosis patients' sputum samples explains their increased susceptibility to infections. Hence in this review article, we have used the research data available on therapeutic agents that target iron as an adjuvant treatment for chronic infection. We systematically screened three databases using focused words and Medical Subject Headings (MeSH) terms for relevant articles. Further, we applied the inclusion and exclusion criteria and performed a thorough quality appraisal. Thirty shortlisted relevant studies were meticulously reviewed. In our opinion, novel therapeutic approaches targeting iron such as iron chelators, gallium, and cefiderocol have potent anti-biofilm properties. Future studies and clinical trials using these approaches in the management of chronic infection might help in decreasing morbidity and mortality in patients with cystic fibrosis. Exploring these approaches might also help to combat other resistant organisms whose survival is dependent on iron.
PubMed: 33833927
DOI: 10.7759/cureus.13716 -
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 -
International Journal of Environmental... Feb 2021Titanium dioxide (TiO) is used as a food additive in pastries, sweets, and sauces. It is recognized as safe by food safety authorities, but in recent years, governments... (Review)
Review
BACKGROUND
Titanium dioxide (TiO) is used as a food additive in pastries, sweets, and sauces. It is recognized as safe by food safety authorities, but in recent years, governments and scientists have raised concerns about its genotoxicity. This systematic review aims to assess the potential associations between food TiO exposure and microbiota composition and functions.
METHODS
A systematic literature search was performed up to December 2020 in PubMed, Web of Science, and Scopus databases. The PRISMA guidelines followed. The risk of bias was assessed from ARRIVE and SYRCLE tools.
RESULTS
A total of 18 animal studies were included (n = 10 mice, n = 5 rats, n = 2 fruit flies, n = 1 silkworm). Studies varied significantly in protocols and outcomes assessment. TiO exposure might cause variations in abundance in specific bacterial species and lead to gut dysfunctions such as a reduction in SCFAs levels, goblet cells and crypts, mucus production, and increased biomarkers of intestinal inflammation.
CONCLUSIONS
Although the extrapolation of these results from animals to humans remains difficult, this review highlights the key role of gut microbiota in gut nanotoxicology and stimulates discussions on the safe TiO use in food and dietary supplements. This systematic review was registered at PROSPERO as CRD42020223968.
Topics: Animals; Food Additives; Gastrointestinal Microbiome; Mice; Microbiota; Rats; Titanium
PubMed: 33669592
DOI: 10.3390/ijerph18042008 -
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 -
Surgery Research and Practice 2021Gastric Cancer (GC) is the fourth most common malignancy worldwide and the second leading cause of cancer-related mortality for both sexes. The gold standard for... (Review)
Review
INTRODUCTION
Gastric Cancer (GC) is the fourth most common malignancy worldwide and the second leading cause of cancer-related mortality for both sexes. The gold standard for diagnosing GC is oesophagogastroduodenoscopy (OGD). Excess mucus on the gastric mucosa impairs the detection of early GC.
AIM
To synthesize available evidence of the effect of premedication with a mucolytic agent among adults undergoing elective nontherapeutic OGD, compared to placebo or other mucolytic agents, on mucosal visibility during OGD.
METHODS
A systematic review was conducted. PubMed, EMBASE, CINAHL, Cochrane central register of controlled trials (CENTRAL), and Web of Science were searched for relevant studies. A random-effects meta-analysis was performed to determine the mean difference in total mucosal visibility score (TMVS) between the pooled mucolytic agents and control. Subgroup analyses were performed to determine the mean TMVS difference for simethicone versus control and the impact of different timings and doses of mucolytic premedication.
RESULTS
13 studies, involving 11,086 patients, including 6178 females (55.7%), with a mean age of 53.4 were identified and 6 of these were brought forward to meta-analysis. This revealed a mean difference of -2.69 (95% CI -3.5, -1.88) in total mucosal visibility scores (TMVS) between the pooled mucolytic agents and control. For simethicone, the mean difference was -2.68 (95% CI -4.94, -0.43). A simethicone dose of 133 mg was most effective with a mean difference of -4.22 (95% CI -5.11, -3.33). Assessing timing of administration across all mucolytic agents revealed a mean difference for the >20 minutes group of -3.68 (95% CI -4.77, -2.59). No adverse events were reported in any included trials.
CONCLUSIONS
Regular use of premedication with mucolytic agents prior to routine OGD is associated with improved TMVS with no reported adverse events.
PubMed: 33553573
DOI: 10.1155/2021/1570121 -
Journal of Traditional Chinese Medicine... Feb 2021To evaluate the effectiveness and safety of Xuanbai Chengqi decoction (, XBCQD) plus Western Medicine (WM) in treatment of severe pneumonia with symptom pattern of... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the effectiveness and safety of Xuanbai Chengqi decoction (, XBCQD) plus Western Medicine (WM) in treatment of severe pneumonia with symptom pattern of phlegm-heat obstructing lung.
METHODS
Randomized controlled trials (RCTs) investigating the effect of XBCQD on severe pneumonia with symptom pattern of phlegm-heat obstructing lung, were included in this study. Seven electronic databases were searched up to March 2019. Meta-analysis was conducted by Review Manager 5.3 software. Risk ratio (RR) and mean difference (MD) with 95% confidence interval (CI) were used as effect estimation.
RESULTS
Eleven RCTs were included, involving 992 participants. Meta-analysis showed that XBCQD combined with WM achieved better effectiveness than WM alone in terms of total effective rate [RR = 1.23, 95%CI (1.16, 1.30)], clinical pulmonary infection score [CPIS, MD = -2.02, 95%CI (-2.42, -1.63)], acute physiology and chronic health evaluation Ⅱ [APACHEⅡ, MD = -6.81, 95% CI (-8.26, 5.37)], mechanical ventilation time [MD = -101.41, 95%CI (-140.47, -62.34)], and lactic acid content in arterial blood [MD = -2.41, 95%CI (-2.64, -2.18)].
CONCLUSION
XBCQD combined with WM had better benefit than WM alone to the patients of severe pneumonia with the symptom pattern of phlegm-heat obstructing lung. However, due to low quality of the included studies, more rigorously designed studies were required to further evaluate the effectiveness and safety of XBCQD in the treatment of severe pneumonia with symptom pattern of phlegm-heat obstructing lung.
Topics: Drug Therapy, Combination; Drugs, Chinese Herbal; Hot Temperature; Humans; Lung; Mucus; Pneumonia; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 33522193
DOI: 10.19852/j.cnki.jtcm.2021.01.003 -
Research Square Jan 2021The unprecedented outbreak of a contagious respiratory disease caused by a novel coronavirus has led to a pandemic since December 2019, claiming millions of lives. The...
BACKGROUND
The unprecedented outbreak of a contagious respiratory disease caused by a novel coronavirus has led to a pandemic since December 2019, claiming millions of lives. The study systematically reviews and summarizes COVID-19's impact based on symptoms, demographics, comorbidities, and demonstrates the association of demographics in cases and mortality in the United States.
METHODS
PubMed and Google Scholar were searched from December 2019- August 2020, and articles restricted to the English language were collected following PRISMA guidelines. US CDC data was used for establishing statistical significance of age, sex, and race.
RESULTS
Among 3745 patients in China, mean age is 50.63 (95% CI: 36.84, 64.42) years, and 55.7 % (95% CI: 52.2, 59.2) were males. Symptoms included fever 86.5% (82.7, 90.0), fatigue 41.9% (32.7, 51.4), dyspnea 29.0% (21.2, 37.5), cough 66.0% (61.3, 70.6), mucus 66% (61.3, 70.6), lymphopenia 18.9% (5.2, 38.0). Prevalent comorbidities were hypertension 16.4% (12.5, 20.8), diabetes 8.9% (7.0, 11.1), CVD 10.9% (6.1, 16.7), ARDS 14.6% (4.9, 27.8), malignancy 1.5 (0.05, 2.8), 1.3% (0.08, 1.9), COPD 1.3 (0.08, 1.9). 63.5 % (33.5, 88.7) received oxygen therapy, 20.8% (8.9, 35.7) were in ventilation, 23.5% (5.9, 47.8) were at the ICU. 86.5% (76.8, 94) had antiviral, 73.9% (55.3, 89.0) had antibiotics, 30% (20.6, 40.2) corticosteroids treatment.In the US, the odds ratio of infection in males to females is 0.873 (CI: 0.052,14.791), while the odds of dying from infection is 1.378 (CI: 0.081, 23.528) for males. The prevalence of infection is higher in females; case and death rates are higher in whites and Hispanics than other races; the death rate is higher in males irrespective of race and age; death rate per 100,000 population increases monotonically with age.
CONCLUSION
Results showed that metabolic diseases comprising CVD, diabetes, hypertension, and respiratory diseases, including COPD, ARDS, are the most common comorbidities to severe condition and poor prognosis in covid-19 patients. Following the recent FDA's guidance for designing Covid-19 vaccine trials, stratification factors of age, race, sex, and comorbidities need consideration in allocation. This study aimed to provide clinical researchers, health policy planners a detailed insight into the coronavirus disease.
PubMed: 33469575
DOI: 10.21203/rs.3.rs-144684/v1 -
The Journal of Allergy and Clinical... May 2021Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to Aspergillus fumigatus and impacts 10% of individuals with cystic fibrosis (CF). A... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to Aspergillus fumigatus and impacts 10% of individuals with cystic fibrosis (CF). A diagnosis of ABPA is challenging to establish in CF owing to overlapping clinical and radiologic features with CF lung disease. Recent studies have identified blood tests, imaging, and other biomarkers that may be useful for diagnosis.
OBJECTIVE
To summarize biomarkers that can aid in the diagnosis of ABPA in CF patients and to quantify their diagnostic accuracy through meta-analysis.
METHODS
We searched MEDLINE, EMBASE, and the Cochrane Controlled Register of Trials and included studies that used a laboratory technique or imaging modality in CF patients diagnosed with ABPA. Pooled sensitivity and specificity were calculated using a hierarchical summary receiver operating characteristic model.
RESULTS
We identified 791 articles, of which 29 met our eligibility criteria and 9 were included in the meta-analysis. Hyperattenuating mucus on computed tomography (CT) scan (n = 3 studies; pooled sensitivity 62% and specificity 92%) and serum specific immunoglobulin E against recombinant Aspergillus funigatus antigens f4 (n = 6; 69%, 89%) and f6 (n = 6; 39%, 97%) demonstrated high specificity. Based on single studies, serum thymus and activation regulated chemokine (92%, 94%), stimulated basophil expression of CD203c (94%, 74%), the inverted mucoid impaction signal on magnetic resonance imaging (94%, 100%), and skin prick test with recombinant Aspergillus fumigatus f4 and/or f6 (100%, 100%) showed high sensitivity and specificity.
CONCLUSIONS
Recent studies have found promising biomarkers for diagnosing ABPA in CF. Further research is needed to improve our understanding of their utility in diagnosis and disease monitoring.
Topics: Aspergillosis, Allergic Bronchopulmonary; Aspergillus fumigatus; Biomarkers; Cystic Fibrosis; Humans; Immunoglobulin E
PubMed: 33454395
DOI: 10.1016/j.jaip.2020.12.064 -
Journal of Investigative Medicine : the... Mar 2021Overproduction of mucus and impaired clearance play important roles in the pathogenesis of muco-obstructive lung diseases (MOLDs). This study aims to evaluate the... (Meta-Analysis)
Meta-Analysis
Overproduction of mucus and impaired clearance play important roles in the pathogenesis of muco-obstructive lung diseases (MOLDs). This study aims to evaluate the therapeutic effect and safety of nebulized hypertonic saline (HS) on MOLDs. Five electronic databases including PubMed, Excerpt Medica Database (EMBASE), Cochrane Central Register of Controlled Trials, ClinicalTrials.gov and International Standard Randomized Controlled Trial Number Register were searched until June 2019. Randomized controlled trials or randomized controlled crossover trials which investigated the therapeutic effect of HS versus non-HS for MOLDs were included. Twenty-one studies met the eligibility criteria. For cystic fibrosis (CF), although the forced expiratory volume in the first second and forced vital capacity did not improve significantly (mean difference (MD) -0.48, 95% CI -3.72 to 2.76), (MD 1.85, 95% CI -4.31 to 8.01), respectively), the clearance capability of lung and quality of life (QOL) improved significantly in the HS group ((standard mean difference 0.44, 95% CI 0.02 to 0.87), (MD -0.64, 95% CI -)1.14, to 0.13), respectively). However, the results of trial sequential analysis showed the evidence needed more researches to support. The effect of nebulized HS on non-CF bronchiectasis, chronic obstructive pulmonary disease, and primary ciliary dyskinesia also need more evidence to conclude, since current studies are limited and results are inconsistent. Most adverse events of nebulized HS were mild and transient. In summary, the current available evidence suggests that nebulized HS may increase the QOL in CF, but there was no significant improvement in lung function. However, it is not possible to draw firm conclusions for other MOLDs due to limited data.
Topics: Cystic Fibrosis; Forced Expiratory Volume; Humans; Lung Diseases, Obstructive; Quality of Life; Saline Solution, Hypertonic
PubMed: 33272932
DOI: 10.1136/jim-2020-001479 -
PLoS Pathogens Oct 2020Since SARS-CoV-2 appeared in the human population, the scientific community has scrambled to gather as much information as possible to find good strategies for the...
Since SARS-CoV-2 appeared in the human population, the scientific community has scrambled to gather as much information as possible to find good strategies for the containment and treatment of this pandemic virus. Here, we performed a systematic review of the current (pre)published SARS-CoV-2 literature with a focus on the evidence concerning SARS-CoV-2 distribution in human tissues and viral shedding in body fluids. In addition, this evidence is aligned with published ACE2 entry-receptor (single cell) expression data across the human body to construct a viral distribution and ACE2 receptor body map. We highlight the broad organotropism of SARS-CoV-2, as many studies identified viral components (RNA, proteins) in multiple organs, including the pharynx, trachea, lungs, blood, heart, vessels, intestines, brain, male genitals and kidneys. This also implicates the presence of viral components in various body fluids such as mucus, saliva, urine, cerebrospinal fluid, semen and breast milk. The main SARS-CoV-2 entry receptor, ACE2, is expressed at different levels in multiple tissues throughout the human body, but its expression levels do not always correspond with SARS-CoV-2 detection, indicating that there is a complex interplay between virus and host. Together, these data shed new light on the current view of SARS-CoV-2 pathogenesis and lay the foundation for better diagnosis and treatment of COVID-19 patients.
Topics: Antiviral Agents; Betacoronavirus; COVID-19; Coronavirus Infections; Female; Humans; Lung; Male; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; Receptors, Virus; SARS-CoV-2
PubMed: 33125439
DOI: 10.1371/journal.ppat.1009037