Reduction of apoptosis and preservation of mitochondrial integrity under ischemia/reperfusion injury is mediated by estrogen receptor β

Background

Estrogen improves cardiac recovery after ischemia/reperfusion (I/R) by yet incompletely understood mechanisms. Mitochondria play a crucial role in I/R injury through cytochrome c-dependent apoptosis activation. We tested the hypothesis that 17β-estradiol (E2) as well as a specific ERβ agonist improve cardiac recovery through estrogen receptor (ER)β-mediated mechanisms by reducing mitochondria-induced apoptosis and preserving mitochondrial integrity.

Methods

We randomized ovariectomized C57BL/6N mice 24h before I/R to pre-treatment with E2 or a specific ERβ agonist (ERβA). Isolated hearts were perfused for 20min prior to 30min global ischemia followed by 40min reperfusion.

Results

Compared with controls, ERβA and E2 treated groups showed a significant improvement in cardiac recovery, i.e. an increase in left ventricular developed pressure, dP/dtmax and dP/dtmin. ERβA and E2 pre-treatment led to a significant reduction in apoptosis with decreased cytochrome c release from the mitochondria and increased mitochondrial levels of anti-apoptotic Bcl2 and ACAA2. Protein levels of mitochondrial translocase inner membrane (TIM23) and mitochondrial complex I of respiratory chain were increased by ERβA and E2 pre-treatment. Furthermore, we found a significant increase of myosin light chain 2 (MLC2) phosphorylation together with ERK1/2 activation in E2, but not in ERβA treated groups.

Conclusions

Activation of ERβ is essential for the improvement of cardiac recovery after I/R through the inhibition of apoptosis and preservation of mitochondrial integrity and can be a achieved by a specific ERβ agonist. Furthermore, E2 modulates MLC2 activation after I/R independent of ERβ.

     

Maternal-fetal hepatic and placental metabolome profiles are associated with reduced fetal growth in a rat model of maternal obesity

Introduction

Maternal obesity is associated with a range of pregnancy complications, including fetal growth restriction (FGR), whereby a fetus fails to reach its genetically determined growth. Placental insufficiency and reduced nutrient transport play a role in the onset of FGR.

Objectives

Metabolomic profiling was used to reveal altered maternal and fetal metabolic pathways in a model of diet induced obesity during pregnancy, leading to reduced fetal growth.

Methods

We examined the metabolome of maternal and fetal livers, and placenta following a high fat and salt intake. Sprague–Dawley rats were assigned to (a) control diet (CD; 1 % salt, 10 % kcal from fat), (b) high salt diet (SD; 4 % salt, 10 % kcal from fat), (c) high fat diet (HF; 1 % salt, 45 % kcal from fat) or (d) high-fat high-salt diet (HFSD; 4 % salt, 45 % kcal from fat) 21 days prior to pregnancy and during gestation. Metabolites from maternal and fetal livers, and placenta were identified using gas and liquid chromatography combined with mass spectrometry.

Results

Maternal HF intake resulted in reduced fetal weight. Altered metabolite profiles were observed in the HF maternal and fetal liver, and placenta. Polyunsaturated fatty acid metabolism was significantly altered in maternal and fetal liver by maternal fat intake.

Conclusion

Excess of linoleic and α-linoleic acid (essential fatty acids) may be detrimental during placentation and associated with a reduction in fetal weight. Additionally, maternal, placental and fetal response to increased fat consumption seems likely to involve palmitoleic acid utilization as an adaptive response during maternal obesity.

     

Complement C4 induces regulatory T cells differentiation through dendritic cell in systemic lupus erythematosus

Background

Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease. Complement component 4 (C4) has be proved to play a role in pathogenesis of SLE. In the present study, we investigated the effect of C4 on T cells differentiation.

Methods

Thirty SLE patients were included in this study. CD4+ T cells were isolated from healthy subjects, and dendritic cells (DCs) were isolated from healthy subjects or SLE patients. C4 was supplemented to co-incubate with T cells and DCs.

Results

Serum C4 concentration was positively correlated with regulatory T cell (Treg) percentage (R² = 0.5907, p < 0.001) and TGFβ concentration (R² = 0.5641, p < 0.001) in SLE patients. Different concentrations of C4 had no effect on T cells differentiation. Co-incubated T cells with DCs and C4 for 7 days, the Treg percentage and TGF-β concentration were significantly elevated. In addition, pre-treated DCs (from healthy subjects or SLE patients) with C4 and then co-incubated with T cells, the increases of Treg percentage and TGF-β concentration were also observed.

Conclusion

C4 takes part in T cells differentiation to Treg cells via DCs.

     

Lung injury-induced skeletal muscle wasting in aged mice is linked to alterations in long chain fatty acid metabolism

Introduction

Older patients are more likely to acquire and die from acute respiratory distress syndrome (ARDS) and muscle weakness may be more clinically significant in older persons. Recent data implicate muscle ring finger protein 1 (MuRF1) in lung injury-induced skeletal muscle atrophy in young mice and identify an alternative role for MuRF1 in cardiac metabolism regulation through inhibition of fatty acid oxidation.

Objectives

To develop a model of lung injury-induced muscle wasting in old mice and to evaluate the skeletal muscle metabolomic profile of adult and old acute lung injury (ALI) mice.

Methods

Young (2 month), adult (6 month) and old (20 month) male C57Bl6 J mice underwent Sham (intratracheal H₂O) or ALI [intratracheal E. coli lipopolysaccharide (i.t. LPS)] conditions and muscle functional testing. Metabolomic analysis on gastrocnemius muscle was performed using gas chromatography-mass spectrometry (GC–MS).

Results

Old ALI mice had increased mortality and failed to recover skeletal muscle function compared to adult ALI mice. Muscle MuRF1 expression was increased in old ALI mice at day 3. Non-targeted muscle metabolomics revealed alterations in amino acid biosynthesis and fatty acid metabolism in old ALI mice. Targeted metabolomics of fatty acid intermediates (acyl-carnitines) and amino acids revealed a reduction in long chain acyl-carnitines in old ALI mice.

Conclusion

This study demonstrates age-associated susceptibility to ALI-induced muscle wasting which parallels a metabolomic profile suggestive of altered muscle fatty acid metabolism. MuRF1 activation may contribute to both atrophy and impaired fatty acid oxidation, which may synergistically impair muscle function in old ALI mice.

     

Inhibition of inflammation using diacerein markedly improved renal function in endotoxemic acute kidney injured mice

Background

Inflammation is an important pathogenic component of endotoxemia-induced acute kidney injury (AKI), finally resulting in renal failure. Diacerein is an interleukin-1β (IL-1β) inhibitor used for osteoarthritis treatment by exerting anti-inflammatory effects. This study aims to investigate the effects of diacerein on endotoxemia-induced AKI.

Methods

Male C57BL/6 mice were intraperitoneally injected with lipopolysaccharide (LPS, 10 mg/kg) for 24 h prior to diacerein treatment (15 mg/kg/day) for another 48 h. Mice were examined by histological, molecular and biochemical approaches.

Results

LPS administration showed a time-dependent increase of IL-1β expression and secretion in kidney tissues. Diacerein treatment normalized urine volume and osmolarity, reduced blood urea nitrogen (BUN), fractional excretion of sodium (FENa), serum creatinine and osmolarity, and protected renal function in an endotoxemic AKI mice model. In the histopathologic study, diacerein also improved renal tubular damage such as necrosis of the tubular segment. Moreover, diacerein inhibited LPS-induced increase of inflammatory cytokines, such as IL-1β, tumor necrosis factor-α, monocyte chemoattractant protein-1 and nitric oxide synthase 2. In addition, LPS administration markedly decreased aquaporin 1 (AQP1), AQP2, AQP3, Na,K-ATPase α1, apical type 3 Na/H exchanger and Na-K-2Cl cotransporter expression in the kidney, which was reversed by diacerein treatment. We also found that diacerein or IL-1β inhibition prevented the secretion of inflammatory cytokines and the decrease of AQP and sodium transporter expression induced by LPS in HK-2 cells.

Conclusion

Our study demonstrates for the first time that diacerein improves renal function efficiently in endotoxemic AKI mice by suppressing inflammation and altering tubular water and sodium handing. These results suggest that diacerein may be a novel therapeutic agent for the treatment of endotoxemic AKI.

     

Heart rate variability after radiofrequency ablation of epicardial ganglionated plexuses on the ovine left atrium

Background

Ganglionated plexuses (GP) are terminal parts of cardiac autonomous nervous system (ANS). Radiofrequency ablation (RFA) for atrial fibrillation (AF) possibly affects GP. Changes in heart rate variability (HRV) after RFA can reflect ANS modulation.

Methods

Epicardial RFA of GP on the left atrium (LA) was performed under the general anesthesia in 15 mature Romanov sheep. HRV was used to assess the alterations in autonomic regulation of the heart. A 24???hour ECG monitoring was performed before the ablation, 2 days after it and at each of the 12 following months. Ablation sites were evaluated histologically.

Results

There was an instant change in HRV parameters after the ablation. A standard deviation of all intervals between normal QRS (SDNN), a square root of the mean of the squared differences between successive normal QRS intervals (RMSSD) along with HRV triangular index (TI), low frequency (LF) power and high frequency (HF) power decreased, while LF/HF ratio increased. Both the SDNN, LF power and the HF power changes persisted throughout the 12???month follow???up. Significant decrease in RMSSD persisted only for 3 months, HRV TI for 6 months and increase in LF/HF ratio for 7 months of the follow???up. Afterwards these three parameters were not different from the preprocedural values.

Conclusions

Epicardial RFA of GP’s on the ovine left atrium has lasting effect on the main HRV parameters (SDNN, HF power and LF power). The normalization of RMSSD, HRV TI and LF/HF suggests that HRV after epicardial RFA of GPs on the left atrium might restore over time.

     

Corneal Collagen Cross-Linking for the Management of Mycotic Keratitis

Purpose

To evaluate the efficiency of corneal collagen cross-linking (CXL) in addition to topical voriconazole in cases with mycotic keratitis.

Design

Retrospective case series in a tertiary university hospital.

Participants

CXL was performed on 13 patients with mycotic keratitis who presented poor or no response to topical voriconazole treatment.

Methods

The clinical features, symptoms, treatment results and complications were recorded retrospectively. The corneal infection was graded according to the depth of infection into the stroma (from grade 1 to grade 3). The visual analogue scale was used to calculate the pain score before and 2 days after surgery.

Main Outcome Measures

Grade of the corneal infection.

Results

Mean age of 13 patients (6 female and 7 male) was 42.4 ± 17.7 years (20–74 years). Fungus was demonstrated in culture (eight patients) or cytological examination (five patients). Seven of the 13 patients (54%) were healed with topical voriconazole and CXL adjuvant treatment in 26 ± 10 days (15–40 days). The remaining six patients did not respond to CXL treatment; they initially presented with higher grade ulcers. Pre- and post-operative pain score values were 8 ± 0.8 and 3.5 ± 1, respectively (p < 0.05).

Conclusions

The current study suggests that adjunctive CXL treatment is effective in patients with small and superficial mycotic ulcers. These observations require further research by large randomized clinical trials.

     

End stage renal disease patients have a skewed T cell receptor Vβ repertoire

Background

End stage renal disease (ESRD) is associated with defective T-cell mediated immunity. A diverse T-cell receptor (TCR) Vβ repertoire is central to effective T-cell mediated immune responses to foreign antigens. In this study, the effect of ESRD on TCR Vβ repertoire was assessed.

Results

A higher proportion of ESRD patients (68.9 %) had a skewed TCR Vβ repertoire compared to age and cytomegalovirus (CMV) – IgG serostatus matched healthy individuals (31.4 %, P?<?0.001). Age, CMV serostatus and ESRD were independently associated with an increase in shifting of the TCR Vβ repertoire. More differentiated CD8⁺ T cells were observed in young ESRD patients with a shifted TCR Vβ repertoire. CD31-expressing naive T cells and relative telomere length of T cells were not significantly related to TCR Vβ skewing.

Conclusions

ESRD significantly skewed the TCR Vβ repertoire particularly in the elderly population, which may contribute to the uremia-associated defect in T-cell mediated immunity.

     

Optimization of fecal sample preparation for untargeted LC-HRMS based metabolomics

Introduction

Collecting feces is easy. It offers direct outcome to endogenous and microbial metabolites.

Objectives

In a context of lack of consensus about fecal sample preparation, especially in animal species, we developed a robust protocol allowing untargeted LC-HRMS fingerprinting.

Methods

The conditions of extraction (quantity, preparation, solvents, dilutions) were investigated in bovine feces.

Results

A rapid and simple protocol involving feces extraction with methanol (1/3, M/V) followed by centrifugation and a step filtration (10 kDa) was developed.

Conclusion

The workflow generated repeatable and informative fingerprints for robust metabolome characterization.

     

Defective pro-IL-1β responses in macrophages from aged mice

Background

Cytokines regulated by the inflammasome pathway have been extensively implicated in various age-related immune pathologies. We set out to elucidate the contribution of the nod-like receptor protein 3 (NLRP3) inflammasome pathway to the previously described deficiencies in IL-1β production by macrophages from aged mice. We examined the production of pro-IL-1β and its conversion into IL-1β as two separate steps and compared these cytokine responses in bone marrow derived macrophages from young (6–8 weeks) and aged (18–24 months) C57BL/6 mice.

Findings

Relative to macrophages from young mice, macrophages from aged mice produced less pro-IL-1β after TLR4 stimulation with LPS. However upon activation of the NLRP3 inflammasome with ATP, macrophages from young and aged mice were able to efficiently convert and secrete intracellular pro-cytokines as functional cytokines.

Conclusions

Lower levels of IL-1β production are a result of slower and lower overall production of pro-IL-1β in macrophages from aged mice.

     

Perioperative Duloxetine and Etoricoxibto improve postoperative pain after lumbar Laminectomy: a randomized,double-blind,controlled study

Background

Duloxetine, Etoricoxib and opioid are of the commonly administered drugs in Lumbar laminectomy. The aim of this study is to assess the effect of perioperative use of Duloxetine in combination with Etoricoxib on postoperative pain and opioid requirements.

Methods

One hundred twenty patients with ASA physical status were enrolled with age between 18 and 70 years. Patients were divided randomly into four groups of 30 patients: group P received placebo, group E received etoricoxib 120 mg, group D received duloxetine 60 mg and group D/E received duloxetine 60 mg capsules and etoricoxib 120 mg; 1 h before surgery and 24 h after.

Results

Neither Duloxetine nor etoricoxib individually had effect on pain with movement, while their combination revealed a significant reduction in pain scores over the entire postoperative period at rest and on movement. Etoricoxib showed a significant decrease in pain at all times at rest when compared with group P, while it showed significant pain decrease only at 0, 2 and 4 h when compared with group D. On the other hand duloxetine alone showed significant decrease in pain at rest at 24 h and 48 h when compared with group P. ConcerningMorphine requirement after 24 h.; it wassignificantly lower in the D/E group in comparison with groups P, E and D. It should be noted also that there was a significant decrease morphine requirement in both groups E and D.

Conclusion

The perioperative administration of the combination of etoricoxib and duloxetine improved analgesia and reduced opioid consumption without significant side effects.

Trial registration

ISRCTN48329522. 17 June 2017

     

Minimal variation of the plasma lipidome after delayed processing of neonatal cord blood

Background

Cord blood lipids are potential disease biomarkers. We aimed to determine if their concentrations were affected by delayed blood processing.

Method

Refrigerated cord blood from six healthy newborns was centrifuged every 12 h for 4 days. Plasma lipids were analysed by liquid chromatography/mass spectroscopy.

Results

Of 262 lipids identified, only eight varied significantly over time. These comprised three dihexosylceramides, two phosphatidylserines and two phosphatidylethanolamines whose relative concentrations increased and one sphingomyelin that decreased.

Conclusion

Delay in separation of plasma from refrigerated cord blood has minimal effect overall on the plasma lipidome.

     

Ligand-dependent differences in estrogen receptor beta-interacting proteins identified in lung adenocarcinoma cells corresponds to estrogenic responses

Background

A recent epidemiological study demonstrated a reduced risk of lung cancer mortality in breast cancer patients using antiestrogens. These and other data implicate a role for estrogens in lung cancer, particularly nonsmall cell lung cancer (NSCLC). Approximately 61% of human NSCLC tumors express nuclear estrogen receptor β (ERβ); however, the role of ERβ and estrogens in NSCLC is likely to be multifactorial. Here we tested the hypothesis that proteins interacting with ERβ in human lung adenocarcinoma cells that respond proliferatively to estradiol (E₂) are distinct from those in non-E₂-responsive cells.

Methods

FLAG affinity purification of FLAG-ERβ-interacting proteins was used to isolate ERβ-interacting proteins in whole cell extracts from E₂ proliferative H1793 and non-E₂-proliferative A549 lung adenocarcinoma cell lines. Following trypsin digestion, proteins were identified using liquid chromatography electrospray ionization tandem mass spectrometry (LC-MS/MS). Proteomic data were analyzed using Ingenuity Pathway Analysis. Select results were confirmed by coimmunoprecipitation.

Results

LC-MS/MS identified 27 non-redundant ERβ-interacting proteins. ERβ-interacting proteins included hsp70, hsp60, vimentin, histones and calmodulin. Ingenuity Pathway Analysis of the ERβ-interacting proteins revealed differences in molecular and functional networks between H1793 and A549 lung adenocarcinoma cells. Coimmunoprecipitation experiments in these and other lung adenocarcinoma cells confirmed that ERβ and EGFR interact in a gender-dependent manner and in response to E₂ or EGF. BRCA1 interacted with ERβ in A549 cell lines and in human lung adenocarcinoma tumors, but not normal lung tissue.

Conclusion

Our results identify specific differences in ERβ-interacting proteins in lung adenocarcinoma cells corresponding to ligand-dependent differences in estrogenic responses.

     

Increased riboflavin production by knockout of 6-phosphofructokinase I and blocking the Entner–Doudoroff pathway in <Emphasis Type="Italic">Escherichia coli</Emphasis>

Objectives

To construct an Escherichia coli strain capable of producing riboflavin with high titer and yield.

Results

A low copy number plasmid pLS01 containing a riboflavin operon under the control of a constitutive promoter was constructed and introduced into Escherichia coli MG1655. Subsequently, the pfkA, edd and ead genes were disrupted, and the resulting strain LS02T produced 667 mg riboflavin/l in MSY medium supplied with 10 g glucose/l in flask cultivation. In a fed-batch process, riboflavin production of the strain reached 10.4 g/l with a yield of 56.8 mg riboflavin/g glucose.

Conclusion

To our knowledge, this is the first report of engineered E. coli strains that can produce more than 10 g riboflavin/l in fed-batch cultivation, indicating that E. coli has potential for riboflavin production.

     

A relative quantitative positive/negative ion switching method for untargeted lipidomics via high resolution LC-MS/MS from any biological source

Introduction

Advances in high-resolution mass spectrometry have created renewed interest for studying global lipid biochemistry in disease and biological systems.

Objectives

Here, we present an untargeted 30 min. LC-MS/MS platform that utilizes positive/negative polarity switching to perform unbiased data dependent acquisitions (DDA) via higher energy collisional dissociation (HCD) fragmentation to profile more than 1000–1500 lipid ions mainly from methyl-tert-butyl ether (MTBE) or chloroform:methanol extractions.

Methods

The platform uses C₁₈ reversed-phase chromatography coupled to a hybrid QExactive Plus/HF Orbitrap mass spectrometer and the entire procedure takes?~10 h from lipid extraction to identification/quantification for a data set containing 12 samples (~4 h for a single sample). Lipids are identified by both accurate precursor ion mass and fragmentation features and quantified using LipidSearch and Elements software.

Results

Using this approach, we are able to profile intact lipid ions from up to 18 different main lipid classes and 66 subclasses. We show several studies from different biological sources, including cultured cancer cells, resected tissues from mice such as lung and breast tumors and biological fluids such as plasma and urine.

Conclusions

Using mouse embryonic fibroblasts, we showed that TSC2^?/? KD significantly abrogates lipid biosynthesis and that rapamycin can rescue triglyceride (TG) lipids and we show that SREBP^?/? shuts down lipid biosynthesis significantly via mTORC1 signaling pathways. We show that in mouse EGFR driven lung tumors, a large number of TGs and phosphatidylmethanol (PMe) lipids are elevated while some phospholipids (PLs) show some of the largest decrease in lipid levels from ~?2000 identified lipid ions. In addition, we identified more than 1500 unique lipid species from human blood plasma.

     

Catesbeianin-1, a novel antimicrobial peptide isolated from the skin of <Emphasis Type="Italic">Lithobates catesbeianus</Emphasis> (American bullfrog)

Objectives

To identify and characterize a novel antimicrobial peptide, catesbeianin-1.

Results

Catesbeianin-1 is 25 amino acids long and is α-helical, cationic and amphipathic. It had antimicrobial activity against Gram-positive and Gram-negative bacteria. It was resistant against trypsin and pepsin. Catesbeianin-1 exhibited moderate hemolytic activity (approx 8%) at 100 μg/ml, and its HC₅₀ (50% hemolytic concentration) was 300 μg/ml. Its cytotoxicity was approx 10–20% at 100 μg/ml, and its CC₅₀ (50% cytotoxic concentration) was >100 μg/ml. The LD₅₀ of catesbeianin-1 in mice was 80 mg/kg. At 3.1 µg/ml, catesbeianin-1 significantly inhibited the growth of methicillin-resistant Staphylococcus aureus.

Conclusions

A new antimicrobial peptide from the skin of Lithobates catesbeianus (American bullfrog) may represent a template for the development of novel antimicrobial agents.

     

Proteomic identification of moesin upon exposure to acrolein

Background

Acrolein (allyl Aldehyde) as one of smoke irritant exacerbates chronic airway diseases and increased in sputum of patients with asthma and chronic obstructive lung disease. But underlying mechanism remains unresolved. The aim of study was to identify protein expression in human lung microvascular endothelial cells (HMVEC-L) exposed to acrolein.

Methods

A proteomic approach was used to determine the different expression of proteins at 8 h and 24 h after treatment of acrolein 30 nM and 300 nM to HMVEC-L. Treatment of HMVEC-L with acrolein 30 nM and 300 nM altered 21 protein spots on the two-dimensional gel, and these were then analyzed by MALDI-TOF MS.

Results

These proteins included antioxidant, signal transduction, cytoskeleton, protein transduction, catalytic reduction. The proteins were classified into four groups according to the time course of their expression patterns such as continually increasing, transient increasing, transient decreasing, and continually decreasing. For validation immunohistochemical staining and Western blotting was performed on lung tissues from acrolein exposed mice. Moesin was expressed in endothelium, epithelium, and inflammatory cells and increased in lung tissues of acrolein exposed mice compared with sham treated mice.

Conclusions

These results indicate that some of proteins may be an important role for airway disease exacerbation caused by acrolein exposure.

     

Impact of airflow limitation in chronic heart failure

Background

Comorbidities are common in chronic heart failure (HF) patients, but diagnoses are often not based on objective testing. Chronic obstructive pulmonary disease (COPD) is an important comorbidity and often neglected because of shared symptoms and risk factors. Precise prevalence and consequences are not well known. Therefore, we investigated prevalence, pulmonary treatment, symptoms and quality of life (QOL) of COPD in patients with chronic HF.

Methods

205 patients with stable HF for at least 1 month, aged above 50 years, were included from our outpatient cardiology clinic, irrespective of left ventricular ejection fraction. Patients performed post-bronchodilator spirometry, a six-minute walk test (6-MWT) and completed the Kansas City Cardiomyopathy Questionnaire (KCCQ). COPD was diagnosed according to GOLD criteria. Restrictive lung function was defined as FEV₁/FVC ≥0.70 and FVC <80% of predicted value. The BODE and ADO index, risk scores in COPD patients, were calculated.

Results

Almost 40% fulfilled the criteria of COPD and 7% had restrictive lung disease, the latter being excluded from further analysis. Noteworthy, 63% of the COPD patients were undiagnosed and 8% of those without COPD used inhalation therapy. Patients with COPD had more shortness of breath despite little difference in HF severity and similar other comorbidities. KCCQ was significantly worse in COPD patients. The ADO and BODE indices were significantly different.

Conclusion

COPD is very common in unselected HF patients. It was often not diagnosed and many patients received treatment without being diagnosed with COPD. Presence of COPD worsens symptoms and negatively effects cardiac specific QOL.

     

Pulmonary Aspergillus Overlap Syndromes

Background

Broadly, there are three main categories in pulmonary aspergillosis: chronic forms of aspergillosis; allergic bronchopulmonary aspergillosis; and invasive aspergillosis (IPA). IPA has been further subdivided into angioinvasive and airway-invasive aspergillosis. Aspergillus overlap syndromes is defined as the occurrence of more than one form aspergillus disease in a single individual.

Objectives

To help clinicians correctly deal with AOS.

Methods

Retrospectively study the clinical findings of nine patients presenting with AOS.

Results

Four cases were diagnosed as angioinvasive aspergillosis complicated with ABPA, three cases as IPA overlap aspergilloma, and two cases as ABPA with AWIA. All the patients presented with cough and expectoration. In three patients with IPA overlap aspergilloma, two had hemoptysis, two had wheezing and fever. All of patients with IPA overlap ABPA had wheezing, dyspnea, and fever, three had sputum plugs, two had hemoptysis, and five patients had mucopurulent discharge and rhonchi in auscultation. Their total IgE ranged from 129 to 2124 IU/ml (676.5 ± 557.33 IU/ml). Fungal culture in sputum showed A. Fumigatus in three patients. All the six patients with IPA overlap ABPA applied steroid therapy and antifungal therapy. Three of them received two or more antifungal drugs successively, and three received combinational therapy. All the patients improved except one diagnosed ABPA overlap IPA.

Conclusions

Clinical manifestation of AOS is not typical. Poor first-line therapeutic effects and complicated diagnosis criteria require clinicians to be aware of AOS when facing patients with aspergillosis.