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Pulmonary Pharmacology & Therapeutics Oct 2023Invasive fungal infections potentially result in fatal outcomes in immunocompromised hosts. Compared to intravenous administration, a nebulization therapy can achieve a...
PURPOSE
Invasive fungal infections potentially result in fatal outcomes in immunocompromised hosts. Compared to intravenous administration, a nebulization therapy can achieve a high concentration of drug delivered in the respiratory tract, without a systematic absorption. We herein summarized the study findings on the safety and clinical utility of nebulized liposomal amphotericin B therapy.
METHODS
According to the PRISMA Extension for Scoping Reviews, we performed a search on MEDLINE and EMBASE for articles with relevant keywords, including "inhaled liposomal amphotericin B″, "nebulized liposomal amphotericin B″, or "aerosolized liposomal amphotericin B″, from the inception of these databases to August 31, 2022.
RESULTS
Of the 172 articles found, 27 articles, including 13 case reports, 11 observational studies, and 3 clinical trials, were selected. Generally, findings showed that nebulized liposomal amphotericin B treatment appeared to be safe and without severe adverse effects. We found an accumulated evidence for the safety, tolerability, and effectiveness of nebulized liposomal amphotericin B prophylaxis among lung transplantation recipients; however, a randomized controlled study has yet to be reported. Data on hemato-oncological patients are relatively scarce; however, a randomized controlled study suggested the prophylactic effect of nebulized liposomal amphotericin B on invasive pulmonary aspergillosis. Observational and randomized controlled studies to evaluate therapeutic efficacy of the nebulized liposomal amphotericin B therapy have not been performed.
CONCLUSION
In conclusion, we found increasing evidence for the effectiveness of the inhalation therapy among patients after lung transplantation and with hemato-oncological diseases.
Topics: Humans; Antifungal Agents; Amphotericin B; Infusions, Intravenous; Randomized Controlled Trials as Topic
PubMed: 37414132
DOI: 10.1016/j.pupt.2023.102233 -
Diagnostics (Basel, Switzerland) Mar 2023: The prevalence of aspergillus sensitization (AS) and allergic bronchopulmonary aspergillosis (ABPA) in asthmatic children remains unclear. : To systematically review... (Review)
Review
: The prevalence of aspergillus sensitization (AS) and allergic bronchopulmonary aspergillosis (ABPA) in asthmatic children remains unclear. : To systematically review the literature to estimate the prevalence of AS and ABPA in children with bronchial asthma. : We searched the PubMed and Embase databases for studies reporting the prevalence of AS or ABPA in pediatric asthma. The primary outcome was to assess the prevalence of AS, while the secondary outcome was to evaluate the prevalence of ABPA. We pooled the prevalence estimates using a random effects model. We also calculated the heterogeneity and publication bias. : Of the 11,695 records retrieved, 16 studies with 2468 asthmatic children met the inclusion criteria. Most studies were published from tertiary centers. The pooled prevalence of AS in asthma (15 studies; 2361 subjects) was 16.1% (95% confidence intervals [CI], 9.3-24.3). The prevalence of AS was significantly higher in prospective studies, studies from India, and those from developing countries. The pooled prevalence of ABPA in asthma (5 studies; 505 children) was 9.9% (95% CI, 0.81-27.6). There was significant heterogeneity and publication bias for both outcomes. : We found a high prevalence of AS and ABPA in asthmatic children. There is a need for community-based studies from different ethnicities using a standard methodology to ascertain the true prevalence of AS and ABPA in pediatric asthma.
PubMed: 36900068
DOI: 10.3390/diagnostics13050922 -
Journal de Mycologie Medicale Mar 2023Invasive aspergillosis (IA) affects more than 300,000 people annually worldwide with a case fatality rate reaching 80%. However, in Africa despite the presence of risk... (Review)
Review
Invasive aspergillosis (IA) affects more than 300,000 people annually worldwide with a case fatality rate reaching 80%. However, in Africa despite the presence of risk factors for the development of IA, the burden of these fungal infections remained unknown. This systematic review aimed to update the available information on the epidemiology and the therapeutic management of IA in Africa. The published papers were systematically searched on major medical databases from September 20 to October 10, 2021. The list of references of eligible articles and the Google scholar database were also checked in order to search for possible eligible articles. Results were reported following the Preferred Reporting Items for Systematic and Meta-analyses (PRISMA) guidelines. The search yielded 1864 articles of which 29 met the inclusion criteria. This systematic review showed the existence of IA in Africa. The prevalence of IA can reach 27% with a fatality rate of more than 60%. The most common clinical form of IA found was invasive pulmonary aspergillosis. The main predisposing conditions identified were neutropenia, HIV/AIDS, renal transplant recipients, and renal failure. Aspergillus section Flavi and Nigri were the main Aspergillus species identified and Aspergillus section Fumigati was uncommon. The main management strategy for IA cases was to start antifungal therapy only after a failure of broad-spectrum antibiotic therapy. This review provided evidence of the existence of invasive aspergillosis in Africa and especially a high rate of undiagnosed invasive aspergillosis cases.
Topics: Humans; Antifungal Agents; Aspergillosis; Invasive Pulmonary Aspergillosis; Aspergillus; Invasive Fungal Infections; Risk Factors; Africa
PubMed: 36265260
DOI: 10.1016/j.mycmed.2022.101328 -
Clinical Imaging Oct 2022Common CT abnormalities of pulmonary aspergillosis represent a cavity with air-meniscus sign, nodule, mass, and consolidation having an angio-invasive pattern. This...
PURPOSE
Common CT abnormalities of pulmonary aspergillosis represent a cavity with air-meniscus sign, nodule, mass, and consolidation having an angio-invasive pattern. This study aims to conduct a systematic review and an individual patient-level image analysis of CT findings of COVID-19-associated pulmonary aspergillosis (CAPA).
METHODS
A systematic literature search was conducted to identify studies reporting CT findings of CAPA as of January 7, 2021. We summarized study-level clinical and CT findings of CAPA and collected individual patient CT images by inviting corresponding authors. The CT findings were categorized into four groups: group 1, typical appearance of COVID-19; group 2, indeterminate appearance of COVID-19; group 3, atypical for COVID-19 without cavities; and group 4, atypical for COVID-19 with cavities. In group 2, cases had only minor discrepant findings including solid nodules, isolated airspace consolidation with negligible ground-glass opacities, centrilobular micronodules, bronchial abnormalities, and cavities.
RESULTS
The literature search identified 89 patients from 25 studies, and we collected CT images from 35 CAPA patients (mean age 62.4 ± 14.6 years; 21 men): group 1, thirteen patients (37.1%); group 2, eight patients (22.9%); group 3, six patients (17.1%); and group 4, eight patients (22.9%). Eight of the 14 patients (57.1%) with an atypical appearance had bronchial abnormalities, whereas only one (7.1%) had an angio-invasive fungal pattern. In the study-level analysis, cavities were reported in 12 of 54 patients (22.2%).
CONCLUSION
CAPA can frequently manifest as COVID-19 pneumonia without common CT abnormalities of pulmonary aspergillosis. If abnormalities exist on CT images, CAPA may frequently accompany bronchial abnormalities.
Topics: Aged; COVID-19; Data Analysis; Humans; Lung; Male; Middle Aged; Pulmonary Aspergillosis; Tomography, X-Ray Computed
PubMed: 35908455
DOI: 10.1016/j.clinimag.2022.07.003 -
PloS One 2012Bronchoalveolar lavage (BAL) galactomannan (GM) assay has been used for diagnosing invasive aspergillosis (IA). We aimed to derive a definitive estimate of the overall... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Bronchoalveolar lavage (BAL) galactomannan (GM) assay has been used for diagnosing invasive aspergillosis (IA). We aimed to derive a definitive estimate of the overall accuracy of BAL-GM for diagnosing IA.
METHODS AND RESULTS
We undertook a systematic review of thirty diagnostic studies that evaluated the BAL-GM assay for diagnosing IA. PubMed and CBM (China Biological Medicine Database) databases were searched for relevant studies published in all languages up until Feb 2012. The pooled diagnostic odds ratio (DOR) and summary receiver operating characteristic (SROC) were constructed for each cutoff value. Additionally, pooled sensitivity (SEN), specificity (SPE), and positive and negative likelihood ratios (PLR and NLR, respectively) were calculated for summarizing overall test performance. Thirty studies were included in this meta-analysis. The summary estimates of pooled DOR, SEN, SPE, PLR, and NLR of the BAL-GM assay (cutoff value 0.5) for proven or probable IA were 52.7 (95% confidence interval (CI) 31.8-87.3), 0.87 (95% CI 0.79-0.92), 0.89 (95% CI 0.85-0.92), 8.0 (95% CI 5.7-11.1) and 0.15 (95% CI 0.10-0.23) respectively. The SROC was 0.94 (95% CI 0.92-0.96). Compared with cutoff value of 0.5, it has higher DOR, SPE and PLR, and similar SEN and NLR with cutoff value of 1.0, which indicated the optimal cutoff value might be 1.0. Compared with BAL-GM, serum GM has a lower SEN and higher SPE, while PCR displays a lower SEN and a similar SPE.
CONCLUSION
With the optimal cutoff value of 1.0, the BAL-GM assay has higher SEN compared to PCR and serum GM test. It is a useful adjunct in the diagnosis of proven and probable IA.
Topics: Bronchoalveolar Lavage Fluid; Case-Control Studies; Diagnostic Tests, Routine; Galactose; Humans; Invasive Pulmonary Aspergillosis; Mannans; Odds Ratio; Predictive Value of Tests; Probability; ROC Curve; Reproducibility of Results; Sensitivity and Specificity
PubMed: 22905261
DOI: 10.1371/journal.pone.0043347 -
Journal of the Intensive Care Society Aug 2021Non-valvular cardiac aspergillosis is a rare infection of the pericardium, myocardium or endocardium and is associated with a high mortality. There is a paucity of... (Review)
Review
INTRODUCTION
Non-valvular cardiac aspergillosis is a rare infection of the pericardium, myocardium or endocardium and is associated with a high mortality. There is a paucity of reports of non-valvular cardiac aspergillosis in critically ill and solid organ transplant (SOT) patients. The majority of cases have been reported in haemato-oncology patients, some of whom have undergone a bone marrow transplant.
OBJECTIVES
We describe four cases affected by non-valvular cardiac aspergillosis in the intensive care setting including a systematic review of this extremely rare infection which is associated with high mortality.
RESULTS
All four-patients died but presented with varying clinical, radiological and microbiological evidence of the disease. Three patients presented following complications after solid organ transplantation, two in the context of acute liver failure and emergency liver transplant and one several years after a double lung transplant. The last patient presented with necrotising gall stone pancreatitis, multi-organ failure and subsequently a prolonged intensive care unit (ICU) stay. On review of the literature, January 1955 to July 2019, 45 cases were identified, with different risk factors, clinical and radiological manifestations, treatment regimen and outcome.
CONCLUSION
Antemortem diagnosis of cardiac aspergillosis is difficult and rare, with no cases reporting positive blood culture results. Galactomannan serology has poor sensitivity in solid organ transplant patients, further reduced by prophylactic antimicrobial treatment, which is common in the ICU setting especially post-transplant patients. Due to the scarcity of cases, treatment is extrapolated from invasive aspergillosis management, with emphasis on early treatment with combination therapy.
PubMed: 34422107
DOI: 10.1177/1751143720936821 -
Pulmonary Pharmacology & Therapeutics Aug 2023Allergic bronchopulmonary aspergillosis (ABPA) is complicated by exacerbations in more than one-third of the subjects. Whether nebulized amphotericin B (NAB) therapy... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Allergic bronchopulmonary aspergillosis (ABPA) is complicated by exacerbations in more than one-third of the subjects. Whether nebulized amphotericin B (NAB) therapy prevents ABPA exacerbations remains unclear.
OBJECTIVES
The primary objective of this systematic review and meta-analysis was to determine the frequency of subjects remaining exacerbation-free, one year after initiating NAB. The key secondary objectives were the time to first exacerbation and the safety of NAB therapy.
METHODS
We searched the PubMed and Embase databases for studies evaluating ≥5 subjects of ABPA managed with NAB. We report the pooled proportion of ABPA subjects remaining exacerbation free after one year. For the randomized controlled trials (RCTs), we estimate the pooled risk difference (RD) of exacerbation-free status at one year with NAB versus the control arm.
RESULTS
We included five studies for our analysis; three were observational (n = 28) and two RCTs (n = 160). The pooled proportion (95% confidence interval [CI]) of subjects remaining exacerbation free with NAB at one year was 76% (62-88). The pooled RD (95% CI) of an exacerbation-free status at one year was 0.33 (-0.12 to 0.78) and was not significantly different between the NAB and control arms. The time to first exacerbation was longer with NAB than with the standard therapy. No serious adverse events were reported with NAB.
CONCLUSION
NAB does not improve exacerbation-free status at one year; however, weak evidence suggests it delays ABPA exacerbations. More research using different dosing regimens is required.
Topics: Humans; Amphotericin B; Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Databases, Factual; Observational Studies as Topic
PubMed: 37230237
DOI: 10.1016/j.pupt.2023.102226 -
Clinical Microbiology and Infection :... May 2024Cerebrospinal fluid (CSF) galactomannan is an adjunctive test for central nervous system (CNS) aspergillosis diagnosis with unclear diagnostic test characteristics. (Review)
Review
BACKGROUND
Cerebrospinal fluid (CSF) galactomannan is an adjunctive test for central nervous system (CNS) aspergillosis diagnosis with unclear diagnostic test characteristics.
OBJECTIVES
To evaluate the diagnostic test characteristics of CSF galactomannan in CNS aspergillosis.
METHODS
Systematic review and meta-analysis.
DATA SOURCES
MEDLINE, Embase, Web of Science, and Scopus, from inception to 24 February 2023.
STUDY ELIGIBILITY CRITERIA
Prospective and retrospective studies with 1-group and 2-group designs using any galactomannan assay on CSF to diagnose CNS aspergillosis.
PARTICIPANTS
Adult and/or paediatric patients with CNS aspergillosis.
TEST(S)
Galactomannan testing on CSF specimens.
REFERENCE STANDARD
European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORTC/MSGERC) diagnostic criteria, or equivalent.
ASSESSMENT OF RISK OF BIAS
QUADAS-2 assessment in duplicate.
METHODS OF DATA SYNTHESIS
Bivariate restricted maximum likelihood estimation random-effects meta-analysis, summarized using forest and summary receiver operating characteristic plots; bivariate meta-regression models to investigate heterogeneity; and subgroup and sensitivity analyses to explore subgroup effects and methodologic choices (PROSPERO registration: CRD42022296331; funding: none).
RESULTS
We included eight studies (n = 342 participants). The summary estimates of CSF galactomannan sensitivity and specificity were 69.0% (95% CI, 57.2-78.7%) and 94.4% (95% CI, 82.8-98.3%), respectively. Using meta-regression, galactomannan cut-off (p = 0.38), EORTC/MSGERC criteria version (p = 0.48), or whether the reference standard was defined as both proven and probable or only proven aspergillosis (p = 0.48) did not explain observed heterogeneity. No subgroup effects were demonstrated by analysing the EORTC/MSGERC criteria reference standard used (e.g. 2002 vs. 2008 definitions) or whether paediatric patients were included. Diagnostic sensitivity was improved using a galactomannan cut-off of 1.0, and by excluding high risk of bias and 1-group design studies.
DISCUSSION
CSF galactomannan is a highly specific but insensitive test for use as a component of CNS aspergillosis diagnosis. Few included studies, no prospective studies, and a high risk of bias are study limitations.
PubMed: 38810927
DOI: 10.1016/j.cmi.2024.05.013 -
The International Journal of... Aug 2009The prevalence of Aspergillus hypersensitivity (AH) and allergic bronchopulmonary aspergillosis (ABPA) in bronchial asthma is reported differently in various studies. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The prevalence of Aspergillus hypersensitivity (AH) and allergic bronchopulmonary aspergillosis (ABPA) in bronchial asthma is reported differently in various studies.
OBJECTIVE
To determine the prevalence of AH and ABPA in asthma using a systematic review.
METHODS
We searched the MEDLINE and EMBASE databases for studies published from 1965 to 2008 and included studies that report the prevalence of AH/ABPA in asthma. We calculated the proportions with 95% confidence interval (CI) to assess the prevalence of AH/ABPA in the individual studies and pooled the results using a random effects model.
RESULTS
Our search yielded 21 eligible studies. The prevalence of AH in bronchial asthma was 28% (95%CI 24-34), and was higher with an intradermal test vs. a prick test (28.7% vs. 24.8%, P = 0.002), but did not vary with the type of antigen used (indigenous or commercial). The prevalence of ABPA in bronchial asthma and Aspergillus-hypersensitive bronchial asthma was respectively 12.9% (95%CI 7.9-18.9) and 40% (95%CI 27-53). There was a wide variation in the criteria used for the diagnosis of ABPA. There was significant statistical heterogeneity assessed by the I(2) test and Cochran Q statistic in all the outcomes.
CONCLUSIONS
There is a high prevalence of AH and ABPA in patients with bronchial asthma. Careful screening should therefore be performed in all patients with bronchial asthma. Intradermal tests are more sensitive than prick tests for the diagnosis of AH. Finally, there is a need to adopt a uniform methodology and criteria for the diagnosis of AH/ABPA.
Topics: Antigens, Fungal; Aspergillosis, Allergic Bronchopulmonary; Asthma; Comorbidity; Humans; Intradermal Tests; Prevalence
PubMed: 19723372
DOI: No ID Found -
Clinical and Experimental Allergy :... Dec 2015The prevalence of Aspergillus sensitization (AS) and allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis (CF) has been varyingly reported. The aim of this... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The prevalence of Aspergillus sensitization (AS) and allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis (CF) has been varyingly reported. The aim of this systematic review was to estimate the overall prevalence of AS/ABPA in CF.
METHODS
We searched the PubMed and EmBase databases for studies reporting the prevalence of AS/ABPA in CF. We calculated the proportion with 95% confidence interval (CI) to assess the prevalence of AS and ABPA in the individual studies and then pooled the results using a random effects model. Statistical heterogeneity was assessed using the I2 test while publication bias was assessed using both graphical and statistical methods.
RESULTS
Our search yielded 64 eligible studies. The pooled prevalence of AS was 39.1% (95% CI: 33.3-45.1) and was higher with skin test compared to specific IgE (43.8% vs. 32.8%, P = 0.002); however, the prevalence did not vary with the type of skin test used (intradermal or percutaneous). The prevalence of ABPA was 8.9% (95% CI: 7.4-10.7) and was higher in adults as compared to children (10.1% vs. 8.9%, P < 0.0001). There was a wide variation in the criteria used for diagnosing ABPA. Almost 50% (12/23) of the publications after 2004 used criteria other than the CF foundation criteria for diagnosing ABPA. There was significant statistical heterogeneity and evidence of publication bias.
CONCLUSIONS
There is a high prevalence of AS and ABPA in patients with CF. Despite six decades of research, there is still a need to adopt uniform methodology and criteria for the diagnosis of AS/ABPA.
Topics: Aspergillosis, Allergic Bronchopulmonary; Aspergillus; Cystic Fibrosis; Humans; Immunization; Prevalence
PubMed: 26177981
DOI: 10.1111/cea.12595