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Clinical and Experimental Allergy :... Oct 2014Allergic bronchopulmonary aspergillosis (ABPA) is a rare disease that affects patients with asthma or cystic fibrosis. Its debilitating course has led to the search for... (Review)
Review
Allergic bronchopulmonary aspergillosis (ABPA) is a rare disease that affects patients with asthma or cystic fibrosis. Its debilitating course has led to the search for new treatments, including antifungals and monoclonal antibodies. To evaluate the efficacy and safety of antifungal treatments in patients with ABPA and either asthma or cystic fibrosis, we performed a systematic review of the literature on the effects of antifungal agents in ABPA using three biomedical databases. Quality assessment was performed using the GRADE methodology and, where appropriate, studies with comparable outcomes were pooled for meta-analysis. Thirty-eight studies - four randomized controlled trials and 34 observational studies - met the eligibility criteria. The antifungal interventions described were itraconazole, voriconazole, posaconazole, ketoconazole, natamycin, nystatin and amphotericin B. An improvement in symptoms, frequency of exacerbations and lung function was reported in most of the studies and was more common with oral azoles. Antifungals also had a positive impact on biomarkers and radiological pulmonary infiltrates, but adverse effects were also common. The quality of the evidence supporting these results was low or very low due to a shortage of controlled studies, heterogeneity between studies and potential bias. Antifungal interventions in ABPA improved patient and disease outcomes in both asthma and cystic fibrosis. However, the recommendation for their use is weak and clinicians should therefore weigh up desirable and undesirable effects on a case-by-case basis. More studies with a better methodology are needed, especially in cystic fibrosis, to increase confidence in the effects of antifungal treatments in ABPA.
Topics: Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Biomarkers; Cystic Fibrosis; Forced Expiratory Volume; Humans; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 24809846
DOI: 10.1111/cea.12333 -
The Journal of Hospital Infection Jul 2021COVID-19-associated pulmonary aspergillosis (CAPA) is defined as invasive pulmonary aspergillosis occurring in COVID-19 patients. The purpose of this review was to...
COVID-19-associated pulmonary aspergillosis (CAPA) is defined as invasive pulmonary aspergillosis occurring in COVID-19 patients. The purpose of this review was to discuss the incidence, characteristics, diagnostic criteria, biomarkers, and outcomes of hospitalized patients diagnosed with CAPA. A literature search was performed through Pubmed and Web of Science databases for articles published up to 20 March 2021. In 1421 COVID-19 patients, the overall CAPA incidence was 13.5% (range 2.5-35.0%). The majority required invasive mechanical ventilation (IMV). The time to CAPA diagnosis from illness onset varied between 8.0 and 16.0 days. However, the time to CAPA diagnosis from intensive care unit (ICU) admission and IMV initiation ranged between 4.0-15.0 days and 3.0-8.0 days. The most common diagnostic criteria were the modified AspICU-Dutch/Belgian Mycosis Study Group and IAPA-Verweij et al. A total of 77.6% of patients had positive lower respiratory tract cultures, other fungal biomarkers of bronchoalveolar lavage and serum galactomannan were positive in 45.3% and 18.2% of patients. The CAPA mortality rate was high at 48.4%, despite the widespread use of antifungals. Lengthy hospital and ICU stays ranging between 16.0-37.5 days and 10.5-37.0 days were observed. CAPA patients had prolonged IMV duration of 13.0-20.0 days. The true incidence of CAPA likely remains unknown as the diagnosis is limited by the lack of standardized diagnostic criteria that rely solely on microbiological data with direct or indirect detection of Aspergillus in respiratory specimens, particularly in clinical conditions with a low pretest probability. A well-designed, multi-centre study to determine the optimal diagnostic approach for CAPA is required.
Topics: Antifungal Agents; COVID-19; Humans; Incidence; Invasive Pulmonary Aspergillosis; Observational Studies as Topic; Respiration, Artificial
PubMed: 33891985
DOI: 10.1016/j.jhin.2021.04.012 -
Infection Feb 2022Invasive pulmonary aspergillosis has been increasingly recognized in COVID-19 patients, termed COVID-19-associate pulmonary aspergillosis (CAPA). Our meta-analysis aims... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Invasive pulmonary aspergillosis has been increasingly recognized in COVID-19 patients, termed COVID-19-associate pulmonary aspergillosis (CAPA). Our meta-analysis aims to assess the clinical characteristics and outcomes of patients diagnosed with CAPA compared to those without CAPA.
METHODS
We searched the Pubmed, Cochrane Library, SCOPUS, and Web of Science databases for studies published between January 1, 2020 and August 1, 2021, containing comparative data of patients diagnosed with CAPA and those without CAPA.
RESULTS
Eight cohort studies involving 729 critically ill COVID-19 patients with comparative data were included. CAPA patients were older (mean age 66.58 vs. 59.25 years; P = 0.007) and had underlying chronic obstructive pulmonary disease (COPD) (13.7 vs. 6.1%; OR 2.75; P = 0.05). No differences in gender, body mass index (BMI), and comorbidities of diabetes and cancer were observed. CAPA patients were more likely to receive long-term corticosteroid treatment (15.0 vs. 5.3%; OR 3.53; P = 0.03). CAPA patients had greater severity of illness based on sequential organ failure assessment (SOFA) score with a higher all-cause in-hospital mortality rate (42.6 vs. 26.5%; OR 3.39; P < 0.001) and earlier ICU admission from illness onset (mean 11.00 vs. 12.00 days; P = 0.003). ICU length of stay (LOS), invasive mechanical ventilation (IMV) duration, the requirement of inotropic support and renal replacement therapy were comparable between the two groups.
CONCLUSIONS
CAPA patients are typically older with underlying COPD and received long-term corticosteroid treatment. Furthermore, CAPA is associated with higher SOFA scores, mortality, and earlier onset of ICU admission from illness onset.
Topics: Aged; COVID-19; Critical Illness; Humans; Intensive Care Units; Invasive Pulmonary Aspergillosis; Pulmonary Aspergillosis; Respiration, Artificial; SARS-CoV-2
PubMed: 34570355
DOI: 10.1007/s15010-021-01701-x -
Infectious Diseases Now Nov 2021Aspergillus is a ubiquitous ascomycete that can cause a variety of clinical presentations depending on immune status. Central nervous system aspergillosis is a fatal...
Aspergillus is a ubiquitous ascomycete that can cause a variety of clinical presentations depending on immune status. Central nervous system aspergillosis is a fatal disease with non-specific clinical features. The aim of this systematic review was to evaluate the epidemiology, clinical features, diagnosis and therapeutic interventions in CNS aspergillosis patients. We also aimed to examine the possible predictors of mortality in neuroaspergillosis. Literature search was performed in Medline, PubMed, and Google scholar and all patients≥18 years with proven CNS aspergillosis were included. A total of 175 articles (235 patients) were included in the final analysis. Their mean age was 51 years and the majority were male (57.4%). Overall case-fatality was 45.1%. Aspergillus fumigatus was the most common species (70.8%) followed by A. flavus (18.6%). Corticosteroids (22.6%), malignancy (19.1%) and diabetes mellitus (14%) were the most common risk factors. Neuroimaging findings included cerebral abscess (70.2%), meningitis (14%), infarction (13.2%) and mycotic aneurysm (8.9%). Disseminated disease (29.2% vs 17.8%, p 0.03), CSF hypoglycorrhachia (48.1% vs 22.2%, P: 0.001) and heightened CSF galactomannan (3.62 vs 2.0ng/ml, p 0.05), were the factors associated with poor outcome in neuroaspergillosis. Persons infected with Aspergillus flavus (13.1% vs 3.1%, P: 0.01), and having been treated with Voriconazole (51.9% vs 29.2%, P: 0.004) were more likely to survive. Our review will provide insight into the different spectrums of CNS aspergillosis. Notwithstanding the promising role of Voriconazole, future work is required to ascertain the role of combination antifungal therapy.
Topics: Aspergillosis; Central Nervous System; Female; Humans; Male; Middle Aged; Neuroaspergillosis; Treatment Outcome; Voriconazole
PubMed: 33964485
DOI: 10.1016/j.idnow.2021.04.002 -
Chest Mar 2024Influenza-associated pulmonary aspergillosis (IAPA) increasingly is being reported in critically ill patients. We conducted this systematic review and meta-analysis to... (Meta-Analysis)
Meta-Analysis
Prevalence, Risk Factors, Clinical Features, and Outcome of Influenza-Associated Pulmonary Aspergillosis in Critically Ill Patients: A Systematic Review and Meta-Analysis.
BACKGROUND
Influenza-associated pulmonary aspergillosis (IAPA) increasingly is being reported in critically ill patients. We conducted this systematic review and meta-analysis to examine the prevalence, risk factors, clinical features, and outcomes of IAPA.
STUDY QUESTION
What are the prevalence, risk factors, clinical features, and outcomes of IAPA in critically ill patients?
STUDY DESIGN AND METHODS
Studies reporting IAPA were searched in the following databases: PubMed MEDLINE, CINAHL, Cochrane Library, Embase, Scopus, Cochrane Trials, and ClinicalTrials.gov. We performed one-group meta-analysis on risk factors, clinical features, morbidity, and mortality using random effects models.
RESULTS
We included 10 observational studies with 1,720 critically ill patients with influenza, resulting in an IAPA prevalence of 19.2% (331 of 1,720). Patients who had undergone organ transplantation (OR, 4.8; 95% CI, 1.7-13.8; I = 45%), harbored a hematogenous malignancy (OR, 2.5; 95% CI, 1.5-4.1; I = 0%), were immunocompromised (OR, 2.2; 95% CI, 1.6-3.1; I = 0%), and underwent prolonged corticosteroid use before admission (OR, 2.4; 95% CI, 1.4-4.3; I = 51%) were found to be at a higher risk of IAPA developing. Commonly reported clinical and imaging features were not particularly associated with IAPA. However, IAPA was associated with more severe disease progression, a higher complication rate, and longer ICU stays and required more organ supports. Overall, IAPA was associated with a significantly elevated ICU mortality rate (OR, 2.6; 95% CI, 1.8-3.8; I = 0%).
INTERPRETATION
IAPA is a common complication of severe influenza and is associated with increased mortality. Early diagnosis of IAPA and initiation of antifungal treatment are essential, and future research should focus on developing a clinical algorithm.
TRIAL REGISTRY
International Prospective Register of Systematic Reviews; No.: CRD42022284536; URL: https://www.crd.york.ac.uk/prospero/.
Topics: Humans; Critical Illness; Influenza, Human; Prevalence; Pulmonary Aspergillosis; Risk Factors
PubMed: 37742914
DOI: 10.1016/j.chest.2023.09.019 -
The Journal of Hospital Infection Feb 2022Invasive pulmonary aspergillosis is increasingly identified as a complication of influenza, termed 'influenza-associated pulmonary aspergillosis' (IAPA). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Invasive pulmonary aspergillosis is increasingly identified as a complication of influenza, termed 'influenza-associated pulmonary aspergillosis' (IAPA).
AIMS
To assess the morbidity and mortality of critically ill influenza patients with and without IAPA.
METHODS
PubMed, Cochrane Library, Scopus and Embase databases were searched for studies containing comparative data of critically ill influenza patients with IAPA. Primary outcomes were all-cause in-hospital and intensive care unit (ICU) mortality. Secondary outcomes were clinical characteristics; duration of invasive mechanical ventilation (IMV); ICU and hospital length of stay (LOS); and requirement for vasopressor, renal replacement therapy (RRT) and extracorporeal membrane oxygenation (ECMO).
FINDINGS
The incidence of IAPA was 28.8% in 853 critically ill influenza patients, with an overall mortality rate of 33.4%. No differences in age and comorbidities were observed. Patients with IAPA were predominantly male and received chronic corticosteroids. In-hospital (49.2% vs 27.0%; P=0.002) and ICU (46.8% vs 20.8%; P<0.001) mortality rates were higher among patients with IAPA than in patients without IAPA. A greater proportion of patients with IAPA required IMV, and had a prolonged IMV duration (mean 17.3 vs 10.5 days; P<0.001), ICU LOS (mean 26.8 vs 12.8 days; P=0.001) and hospital LOS (mean 38.7 vs 27.0 days; P=0.003). Patients with IAPA had greater disease severity and were significantly more likely to require vasopressor (76.4% vs 57.9%; P<0.001), RRT (45.7% vs 19.1%; P<0.001) and ECMO (25.9% vs 12.8%; P=0.004) support compared with patients without IAPA.
CONCLUSIONS
A diagnosis of IAPA in critically ill patients is associated with greater morbidity and mortality. Early recognition and more research are needed to determine better diagnostic and treatment strategies.
Topics: Critical Illness; Humans; Influenza, Human; Intensive Care Units; Invasive Pulmonary Aspergillosis; Male; Pulmonary Aspergillosis
PubMed: 34843812
DOI: 10.1016/j.jhin.2021.11.016 -
Journal of Fungi (Basel, Switzerland) Jul 2022Disseminated disease following invasive pulmonary aspergillosis (IPA) remains a significant contributor to mortality amongst patients with hematologic malignancies... (Review)
Review
Disseminated disease following invasive pulmonary aspergillosis (IPA) remains a significant contributor to mortality amongst patients with hematologic malignancies (HMs). At the highest risk of mortality are those with disseminated disease to the central nervous system, known as cerebral aspergillosis (CA). However, little is known about the risk factors contributing to disease amongst HM patients. A systematic review using PRISMA guidelines was undertaken to define HM patient subgroups, preventative measures, therapeutic interventions, and outcomes of patients with disseminated CA following IPA. The review resulted in the identification of 761 records, of which 596 articles were screened, with the final inclusion of 47 studies and 76 total patients. From included articles, the proportion of CA was assessed amongst HM patient subgroups. Further, pre-and post-infection characteristics, fungal species, and mortality were evaluated for the total population included and HM patient subgroups. Patients with acute myeloid leukemia and acute lymphoid lymphoma, patients receiving corticosteroids as a part of their HM therapeutic regimen, and anti-fungal prophylaxis constitute the top identified patient populations at risk for disseminated CA. Overall, information presented here indicates that measures for the prevention of IPA should be taken in higher-risk HM patient subgroups. Specifically, the type of anti-fungal therapy used should be carefully considered for those patients with IPA and increased risk for cerebral dissemination. Additional reports detailing patient characteristics are needed to define further the risk of developing disseminated CA from IPA in patients with HMs.
PubMed: 35887477
DOI: 10.3390/jof8070722 -
Neurosurgical Review Jun 2022The clinical features and prognostic factors of intracranial aspergillosis in immunocompetent patients without risk factors are not well known. PubMed, Scopus, Google... (Review)
Review
The clinical features and prognostic factors of intracranial aspergillosis in immunocompetent patients without risk factors are not well known. PubMed, Scopus, Google Scholar, and Web of Science were searched for all relevant case reports/series on adult patient (≥ 18 years) with aspergillosis published from 1976 to 2018. One hundred eighty-two patients (median age, 40 years; range, 18-83 years; male:female, 115:67) were identified. Types of intracranial aspergillosis included intracranial mass from the skull base (54.9%), pure intraparenchymal disease (23.6%), meningoencephalitis (13.2%), and dural-based mass (8.2%). Vascular complications occurred in 44 patients (26.3%). Eighty-one patients (44.5%) had favourable final clinical outcomes without any deficits, whereas 58 (31.9%) died. Disease-related mortality improved significantly over time (43.1% [28/65] before 2000, 25.9% [30/116] after 2001; p = 0.021). Patients with meningoencephalitis demonstrated the highest mortality rate (79.2%, 19/24). Medical non-responders (patients whose disease course worsened after receiving the initial medication regimen) and vascular complications (the presentation of subarachnoid haemorrhage, intracerebral haemorrhage, or infarction related to the rupture or occlusion of intracranial vessels) were significantly associated with mortality (p < 0.001). Findings from the current review may help predict patient prognosis at the initial assessment and determine potential prognostic factors.
Topics: Adult; Aspergillosis; Female; Humans; Male; Meningoencephalitis; Skull Base; Subarachnoid Hemorrhage
PubMed: 35278148
DOI: 10.1007/s10143-022-01738-y -
The Lancet. Infectious Diseases Feb 2009A systematic review and meta-analysis was done on the use of PCR tests for the diagnosis of invasive aspergillosis. Data from more than 10000 blood, serum, or plasma... (Meta-Analysis)
Meta-Analysis Review
A systematic review and meta-analysis was done on the use of PCR tests for the diagnosis of invasive aspergillosis. Data from more than 10000 blood, serum, or plasma samples obtained from 1618 patients at risk for invasive aspergillosis were retrieved from 16 studies. Overall, the mean diagnostic odds ratios (DORs) of PCR for proven and probable cases were similar whether two consecutive positive samples were required to define positivity (DOR 15.97 [95% CI 6.83-37.34]) or a single positive PCR test was required (DOR 16.41 [95% CI 6.43-41.88]). Sensitivity and specificity of PCR for two consecutive positive samples were 0.75 (95% CI 0.54-0.88) and 0.87 (95% CI 0.78-0.93), respectively, and if only a single positive sample was required, these values were 0.88 (95% CI 0.75-0.94) and 0.75 (95% CI 0.63-0.84), respectively. Whereas specificity based on a single positive test was significantly lower (p=0.027) than two positive tests, the sensitivity and DOR did not differ significantly. A single PCR-negative result is thus sufficient to exclude a diagnosis of proven or probable invasive aspergillosis. However, two positive tests are required to confirm the diagnosis because the specificity is higher than that attained from a single positive test. Populations at risk varied and there was a lack of homogeneity of the PCR methods used. Efforts are underway to devise a standard for Aspergillus sp PCR for screening, which will help enable formal validation of PCR and estimate its use in patients most likely to benefit.
Topics: Aspergillosis; Aspergillus; DNA, Fungal; Humans; Polymerase Chain Reaction; ROC Curve; Sensitivity and Specificity
PubMed: 19179225
DOI: 10.1016/S1473-3099(09)70019-2 -
Lung Jun 2024Treatment of allergic bronchopulmonary aspergillosis (ABPA) is challenging. Biological therapies have been reported as adjunctive treatments for ABPA, primarily in case... (Review)
Review
BACKGROUND
Treatment of allergic bronchopulmonary aspergillosis (ABPA) is challenging. Biological therapies have been reported as adjunctive treatments for ABPA, primarily in case series or case reports. This study aimed to analyze the efficacy of biologics for managing ABPA both qualitatively and quantitatively.
METHODS
All articles on APBA published in October 2023 were searched in PubMed, Web of Science, ClinicalTrials.gov, and Embase databases. The effects of interest were the mean changes from baseline for outcomes, including exacerbation rates, oral corticosteroids usage (OCS), and total immunoglobulin E (IgE) levels. Reported outcomes were quantitatively synthesized by usual or individual patient data (IPD) meta-analyses. PROSPERO registration number: CRD42022373396.
RESULTS
A total of 86 studies were included in the systematic review including 346 patients. Sixteen studies on omalizumab were pooled for the usual meta-analysis. Omalizumab therapy significantly reduced exacerbation rates (- 2.29 [95%CI - 3.32, - 1.26]), OCS dosage (- 10.91 mg [95%CI - 18.98, - 2.85]), and total IgE levels (- 273.07 IU/mL [95%CI - 379.30, - 166.84]), meanwhile improving FEV1% predicted (10.09% [95%CI 6.62, 13.55]). Thirty-one studies on dupilumab, mepolizumab, or benralizumab were pooled to perform an IPD meta-analysis, retrospectively. Both dupilumab and mepolizumab significantly reduced exacerbation rates, OCS, and total IgE levels. Benralizumab showed a similar trend, but it was not statistically significant. Tezepelumab showed weak evidence of its effects on ABPA. All five biologics led to milder clinical symptoms (e.g., cough, wheezing) with serious adverse effects that happened once in omalizumab treatment.
CONCLUSION
These results indicate the clinical benefit of omalizumab, dupilumab, and mepolizumab in patients with ABPA. Further randomized, controlled studies with a larger sample size and longer follow-up are needed to confirm these findings.
PubMed: 38898129
DOI: 10.1007/s00408-024-00717-y