Pulmonary Aspergillus Infection Research Articles

Successful treatment of mixed pulmonary Aspergillus and Mucor infection using intrabronchial amphotericin B infusion: a case report and literature review

BackgroundReports of pulmonary aspergillosis and mucormycosis co-infections are rare; thus, limited guidance is available on early diagnosis and treatment. We present a case of mixed pulmonary Aspergillus and Mucor infection and review the literature regarding this co-infection. The diagnosis and treatment methods are summarized to improve clinicians’ understanding of the disease and to facilitate early diagnosis and treatment.Case presentationA 60-year-old male farmer with poorly controlled diabetes mellitus was admitted to hospital with a fever of unknown origin that had been present for 15 days and pulmonary aspergillosis complicated by Mucor spp. infection. Because multiple lobes were involved, the infection worsened despite surgical resection and antifungal therapy. Finally, we treated this patient with a bronchoscopic infusion of amphotericin B. After four courses of bronchoscopic amphotericin B infusion, we observed rapid clinical improvement and subsequent resolution of pulmonary infiltrates.ConclusionOur case highlights the use of bronchoscopy in the successful clinical treatment of invasive fungal diseases of the lung.

IFN Receptor 2 Regulates TNF-α-Mediated Damaging Inflammation during Aspergillus Pulmonary Infection.

The increased incidence of invasive pulmonary aspergillosis, caused by Aspergillus fumigatus, occurring in patients infected with severe influenza or SARS-CoV-2, suggests that antiviral immune responses create an environment permissive to fungal infection. Our recent evidence suggests that absence of the type I IFN receptor 2 subunit (IFNAR2) of the heterodimeric IFNAR1/2 receptor is allowing for this permissive immune environment of the lung through regulation of damage responses. Because damage is associated with poor outcome to invasive pulmonary aspergillosis, this suggested that IFNAR2 may be involved in A. fumigatus susceptibility. In this study, we determined that absence of IFNAR2 resulted in increased inflammation, morbidity, and damage in the lungs in response to A. fumigatus challenge, whereas absence of IFNAR1 did not. Although the Ifnar2-/- mice had increased morbidity, we found that the Ifnar2-/- mice cleared more conidia compared with both wild-type and Ifnar1-/- mice. However, this early clearance did not prevent invasive disease from developing in the Ifnar2-/- mice as infection progressed. Importantly, by altering the inflamed environment of the Ifnar2-/- mice early during A. fumigatus infection, by neutralizing TNF-α, we were able to reduce the morbidity and fungal clearance in these mice back to wild-type levels. Together, our results establish a distinct role for IFNAR2 in regulating host damage responses to A. fumigatus and contributing to an A. fumigatus-permissive environment through regulation of inflammation. Specifically, our data reveal a role for IFNAR2 in regulating TNF-α-mediated damage and morbidity during A. fumigatus infection.

Clinical performance of metagenomic next-generation sequencing for diagnosis of pulmonary Aspergillus infection and colonization.

Investigations assessing the value of metagenomic next-generation sequencing (mNGS) for distinguish Aspergillus infection from colonization are currently insufficient. The performance of mNGS in distinguishing Aspergillus infection from colonization, along with the differences in patients' characteristics, antibiotic adjustment, and lung microbiota, were analyzed. The abundance of Aspergillus significantly differed between patients with Aspergillus infection (n=36) and colonization (n=32) (P < 0.0001). Receiver operating characteristic (ROC) curve result for bronchoalveolar lavage fluid (BALF) mNGS indicated an area under the curve of 0.894 (95%CI: 0.811-0.976), with an optimal threshold value of 23 for discriminating between Aspergillus infection and colonization. The infection group exhibited a higher proportion of antibiotic adjustments in comparison to the colonization group (50% vs. 12.5%, P = 0.001), with antibiotic escalation being more dominant. Age, length of hospital stay, hemoglobin, cough and chest distress were significantly positively correlated with Aspergillus infection. The abundance of A. fumigatus and Epstein-Barr virus (EBV) significantly increased in the infection group, whereas the colonization group exhibited higher abundance of A. niger. BALF mNGS is a valuable tool for differentiating between colonization and infection of Aspergillus. Variations in patients' age, length of hospital stay, hemoglobin, cough and chest distress are observable between patients with Aspergillus infection and colonization.

Concomitant or sequential pulmonary infection with non-tuberculous mycobacteria and Aspergillus.

Non-tuberculous mycobacteria (NTM) and Aspergillus are ubiquitous organisms that have the potential to cause significant pulmonary disease in certain clinical contexts. An association is known to exist between NTM and Aspergillus lung infections. However, it is unclear if NTM infection predisposes to Aspergillus infection or vice versa. It is also unclear whether treatment for one results in a favourable ecological niche that facilitates the growth of the other and promotes subsequent clinical disease. An improved understanding of the link between these two pulmonary pathogens is critical to guide improvements in clinical practice, and ultimately, enhance outcomes among patients who are at risk of experiencing these infections, either concomitantly or sequentially. Here, we discuss the association between pulmonary NTM and Aspergillus infections. We address the frequency with which coinfection or sequential infections are reported to occur, predisposing risk factors that have been identified and the impact on clinical outcomes. Current data on the mechanistic links between NTM and Aspergillus lung infections are also considered. The potential implications for routine clinical practice are explored.

BI01 Disseminated Nannizziopsis fungal infection in a kidney transplant recipient: iguanas, immunosuppression or international travel?

Abstract Transplant waiting list demographics are changing profoundly in some parts of the UK, partly due to trends in global migration. This has significant implications for the spectrum of post-transplant skin malignancies and skin infections presenting to dermatologists. We present a kidney transplant recipient born in Nigeria who developed disseminated infection with Nannizziopsis spp., an emerging pathogenic fungus in humans and reptiles. A 64-year-old man from Nigeria who received a kidney transplant 10 months earlier was referred to our 2-week-wait skin cancer clinic with a 4-cm tender, ulcerated nodule on his left thigh that had been present for 2 months. He was being investigated for possible pulmonary Aspergillus infection and also had a fluctuant subcutaneous mass over the right tibia with suspected osteomyelitis. On examination, he had a similar plaque on his right hand, fluctuant subcutaneous nodules of his left flank and left upper arm, a 20-cm fluctuant swelling over his right tibia and a 2-cm plaque of his hard palate. Skin biopsy from the left flank and thigh showed suppurative granulomatous inflammation and fungal hyphae in the dermis and macrophages with septation and 45° branching. β-D-Glucan was positive and molecular identification revealed Nannizziopsis spp. Magnetic resonance imaging of the head did not show evidence of central nervous system infection. He was treated with intravenous amphotericin B for 2 months and subsequent oral posaconazole with resolution of skin and lung infection. Nannizziopsis is a genus of fungi that usually infects reptiles such as iguanas, geckos and chameleons, snakes, turtles and crocodiles. It causes cutaneous and musculoskeletal granulomatous infections which can be rapidly fatal. Fewer than 20 human cases have been reported, mostly related to travel to West Africa. Almost all infections are in immunocompromised individuals and species of Nannizziopsis reported to affect humans are generally different from those identified in animals. Our patient denied contact with reptiles, but he had travelled to Nigeria before his transplant where he probably acquired a latent infection that reactivated post-transplant. This case illustrates the importance of biopsy and culture of atypical skin lesions, particularly in immunocompromised patients. With the rising global migration and travel, such infections are likely to be seen more frequently in the UK, and both residential and travel history may be relevant. Finally, zoonotic infections are increasing globally as interspecies barriers break down. Although there is not enough evidence to caution against ownership of exotic pets in immunocompromised individuals, animal sources of rare infections should always be considered in this patient group.

A case of pulmonary aspergillus infection in underground coal mine workers

The underground environment is dark and humid, and it is easy to breed pathogenic microorganisms. A lump in the right lung of a coal mine underground transport worker was found druing occupational health examination. CT examination showed that the lump was located in the posterior segment of the upper lobe of the right lung, with point strip calcification, liquefaction necrosis, and proximal bronchial stenosis and occlusion. MRI examination FS-T(2)WI and DWI showed "target sign", annular low signal around the central high signal, and low mixed signal around the periphery, and annular high signal in the isosignal lesions on T(1)WI. Then the pulmonary aspergillus infection was confirmed by pathology.

Orca-Q Demonstrates Favorable GvHD-and-Relapse-Free Survival in Haploidentical Transplants without Post-Transplant Cyclophosphamide

^Salhotra, Srour, Lowsky and Abedi contributed equally Background: Allogeneic hematopoietic stem cell transplantation (alloHSCT) can be curative for a variety of malignant and nonmalignant disorders, but until recent years, access has been limited to patients with HLA-matched donors. The increased utilization of post-transplant cyclophosphamide (PTCy) has enabled patients to receive alloHSCT with haploidentical (haplo) related donors; however, high rates of cGVHD following myeloablative conditioning (MAC) regimens and high rates of relapse following reduced intensity conditioning regimens have been observed with this approach. Thus, GVHD-and-relapse free survival (GRFS) rates in this population at 1-year post-transplant remain low. Haplo alloHSCT with PTCy is also associated with high incidence of cytokine release syndrome (CRS) and infections. Orca-Q -an investigational precision engineered cell therapy- represents an alternative strategy which may be administered with single agent prophylaxis and does not require PTCy. The cellular composition of Orca-Q consists of enriched CD34+ stem cells combined with specific T- cell subsets and is intended to reconstitute the blood and immune systems. Orca-Q is hypothesized to reduce GVHD, relapse, and serious infections. Methods: Adult patients (18 to 65 years) with high-risk hematologic malignancies undergoing myeloablative conditioning (MAC) alloHSCT were enrolled between January 2019 to July 2022 on the haplo donor dose expansion arm of a multicenter phase 1 study of Orca-Q (NCT03802695). Haplo was defined as ≥ 4/8 but < 7/8 matched related donor at HLA-A, -B, -C, and -DRB1 typed using DNA-based high-resolution. Patients received only single agent tacrolimus (starting on day -1 and taper day +60 if no GVHD) as GVHD prophylaxis. PTCy was not permitted. The Orca-Q drug product was manufactured centrally at Orca Bio Manufacturing Site in Sacramento, CA from G-CSF mobilized peripheral blood apheresis. Results: The Orca-Q drug product was successfully manufactured and delivered to all subjects with a vein-to-vein time of less than 72 hours. A total of 21 patients (11 AML, 8 ALL, 2 CML in blast crisis) with > 30 days of follow up were included in this analysis. All were 4/8 HLA match at HLA-A, -B, C, and DRB1. Median age of subjects was 44 years (range 21 - 63) and median follow-up was 333 days (range 39 - 1020). Disease risk index (DRI) score was available in 20 showing 2 very high, 3 high, 13 intermediate, and 2 low risk categories. The M:F ratio was 12:9. Patients received either TBI (n=13) or non-TBI (n=8) based MAC regimens. 2 patients had Gr 1 CRS (CTCAE v5). Median neutrophil and platelet engraftment times were 13 days (range 8 - 25) and 16 days (range 12 - 25), respectively. 1 secondary engraftment failure was observed. The estimated incidence of BMT CTN MOP3 infections was 27% at 1 year. The estimated incidence of gr 2-4 aGVHD at 6 months was 14% which compares favorably with literature reports of 21% to 63% for gr 2-4 aGVHD in patients undergoing haplo transplant with PTCy-based prophylaxis.[1-5] Likewise, gr 3-4 aGVHD was rare with Orca-Q with only 1 case of gr 3 aGVHD and no gr 4 aGVHD. Of the 16 patients who had at least 3 months follow up, only 1 developed mild cGVHD. No patients had moderate-to-severe cGVHD, a notable improvement compared to historic rates of 24% to 31% for moderate-to-severe cGVHD with PTCy, despite the fact that Orca-Q patients receive only single agent GVHD prophylaxis.[1-4] 2 patients experienced disease relapse and there was a total of 5 deaths (2 due to relapse, 1 Aspergillus pulmonary infection, 1 respiratory failure associated with renal failure, and 1 COVID infection). GVHD-and-relapse free survival (GRFS) was 71% at 1 year with Orca-Q (Figure 1) which compares favorably to a GRFS of 46% reported by Sanz in the context of MAC haplo alloHSCT with PTCy.[2] Conclusions: Initial Orca-Q data demonstrates good clinical outcomes with single agent tacrolimus and no PTCy or MMF. Patients treated with Orca-Q experienced a low adverse event profile, low incidence and severity of both aGVHD and cGVHD, and improved GRFS rates, offering a potential new treatment option for patients undergoing haplo alloHSCT. This phase 1 study of Orca-Q continues to enroll patients with haplo donors across the US. References (1) Gooptu, M., et al. (2) Sanz, J., et al. (3) Wagner, J.E., et al. (4) Baker, M., et al. (5) Bashey, A., et al. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Chronic Cavitary Pulmonary Aspergillosis: An Unusual Cause of Chronic Cough, Pleuritic Chest Pain, and Hemoptysis in a 24-Year-Old Coal Mine Worker

Pulmonary Aspergillus infections are caused by the ubiquitous fungus mold when spores found in compost, dust, and plant material are inhaled. Manifestation of the disease is represented by a delicate balance between host and pathogen interactions, making Aspergillus infection more commonly observed in immunocompromised individuals. Chronic cavitary pulmonary aspergillosis (CCPA) is a subtype of pulmonary Aspergillosis associated with history of chronic or prior lung disease. Here we present the case of a non-immunocompromised 24-year-old male with a history of intermittent asthma with chronic pulmonary symptoms and finding of a lung mass on imaging. We describe the diagnostic challenge and surgical treatment of CCPA in medically refractory disease.

Supplementary benefits of CT-guided transthoracic lung aspiration biopsy for core needle biopsy.

ObjectiveThis study aimed to investigate the diagnostic efficacy of computed tomography (CT)-guided transthoracic lung core needle biopsy combined with aspiration biopsy and the clinical value of this combined routine microbial detection.Materials and methodsWe retrospectively collected the electronic medical records, CT images, pathology, and other data of 1085 patients with sequential core needle biopsy and aspiration biopsy of the same lung lesion under CT guidance in the First Affiliated Hospital of Wenzhou Medical University from January 2016 to January 2021. GenXpert MTB/RIF detection and BD BACTEC™ Mycobacterium/fungus culture were applied to identifying the microbiological results of these patients. We then compared the positive diagnostic rate, false negative rate, and diagnostic sensitivity rate of three methods including core needle biopsy alone, aspiration biopsy alone, and both core needle biopsy and aspiration biopsy.ResultsThe pathological results of cutting histopathology and aspiration of cell wax were examined for 1085 patients. The diagnostic rates of cutting and aspiration pathology were 90.1% (978/1085) and 86.3% (937/1085), respectively, with no significant difference (P > 0.05). Considering both cutting and aspiration pathologies, the diagnostic rate was significantly improved, up to 98% (1063/1085) (P < 0.001). A total of 803 malignant lesions were finally diagnosed (803/1085, 74.0%). The false negative rate by cutting pathology was 11.8% (95/803), which was significantly lower than that by aspiration biopsy [31.1% (250/803), P < 0.001]. Compared with core needle biopsy alone, the false negative rate of malignant lesions decreased to 5.6% (45/803) (P < 0.05). Next, the aspirates of the malignant lesions highly suspected of corresponding infection were cultured. The results showed that 16 cases (3.1%, 16/511) were infected with Mycobacterium tuberculosis complex, Aspergillus niger, and Acinetobacter baumannii, which required clinical treatment. 803 malignant tumors were excluded and 282 cases of benign lesions were diagnosed, including 232 cases of infectious lesions (82.3%, 232/282). The diagnostic rate of Mycobacterium/fungus culture for infectious lesions by aspiration biopsy (47.4%) was significantly higher than that by lung core needle biopsy (22.8%; P < 0.001). The diagnostic rate of aspiration biopsy combined with core needle biopsy was 56% (130/232). The parallel diagnostic rate of aspirated biopsy for GenXpert detection and Mycobacterium/fungal culture combined with core needle biopsy was 64.7% (150/232), which was significantly higher than that of lung core needle biopsy alone (P < 0.001). Finally, pulmonary tuberculosis was diagnosed in 90 cases (38.8%) of infectious lesions. Compared with the sensitivity of core needle biopsy to detect tuberculosis (27.8%, 25/90), the sensitivity of aspirating biopsy for GenXpert detection and Mycobacterium/fungal culture was significantly higher, at 70% (63/90) and 56.7% (51/90), respectively. Although there was no significant difference in the sensitivity of aspirated biopsy for GenXpert and Mycobacterium/fungal culture to detect pulmonary tuberculosis, the sensitivity was significantly increased to 83.3% (P < 0.05) when the two tests were combined. Moreover, when aspirated biopsies were combined with GenXpert detection, Mycobacterium/fungus culture, and core needle biopsy, the sensitivity was as high as 90% (81/90).ConclusionCT-guided lung aspiration biopsy has a significant supplementary effect on core needle biopsies, which is indispensable in clinical application. Additionally, the combination of aspiration biopsy and core needle biopsy can significantly improve the diagnostic rate of benign and malignant lesions. Aspiration biopsy showed that pulmonary malignant lesions are complicated with pulmonary tuberculosis, aspergillus, and other infections. Finally, the diagnostic ability of lung puncture core needle biopsy and aspiration biopsy combined with routine microbial detection under CT positioning in the diagnosis of pulmonary infectious diseases was significantly improved.

Aspergillus Infection of the Thoracolumbar Vertebral Body in a Chronic Hepatitis B-Related Hepatocellular Carcinoma Patient: A Case Report

This study reports a rare case of an Aspergillus infection of the thoracolumbar vertebral body in a chronic hepatitis B-related hepatocellular carcinoma patient. We report a hepatocellular carcinoma patient who presented with a 3-month history of lumbago after liver transcatheter arterial chemoembolization, and was finally diagnosed with a pulmonary and thoracolumbar vertebral body Aspergillus infection after diagnostic antifungal treatment for 1 year. This case suggests that diagnostic antifungal therapy is of great significance for patients with clinically suspected Aspergillus infections when it is difficult to obtain tissue specimens for determined diagnosis.

Clinical features and early diagnostic clues of chronic granulomatous disease

Objective: To explore the early clinical clues for diagnosis of chronic granulomatous disease (CGD). Methods: One hundred and thirty-nine children with CGD seen in Beijing Children's Hospital from January 2007 to October 2020 were included in this study. The clinical features including age of onset, first presentations, reason for being hospitalized, etiology, imaging features, clues for early diagnosis of all patients were evaluated retrospectively. According to the time of diagnosis, the patients were divided into two groups, cases diagnosed before 2015 and after 2015 and 2015. The time of diagnosis, the length of stay and the hospital charges were compared between the two groups. T test and χ2 test were used for statistical analyses. Results: One hundred and nineteen of the cases were males and 20 were females. The age of onset was 4 months (8 d to 14 years), and 103 cases (74.1%) had onset before 1 year of age. The age at diagnosis was 1.8 years (21 d to 14.7 years), and the time of diagnosis delay was 1 year (7 d to 13.7 years). One hundred and thirty-five cases (97.1%) had pulmonary infection as the main reason for hospitalization, of whom 76 cases (56.3%) had positive pulmonary etiology. One hundred and thirty-six patients (97.8%) were referred cases, of whom 5 were suspected of CGD before referral, and the misdiagnosis rate was as high as 96.3% (131/136). Eight early clues for diagnosis were found, the frequency from high to low, large bacillus Callmette-Guer scar in 99 cases (70.5%), left axillary lymphadenopathy or calcification in 73 cases (52.5%), skin or other lymph node infections in 58 cases (41.7%), skin scars in 50 cases (36.0%), multiple lung nodules in 42 cases (30.2%), perianal abscess in 35 cases (25.2%), pulmonary Aspergillus infection in 26 cases (18.7%) and pulmonary Burkholderia infection in 15 cases (10.8%). A total of 120 cases of CGD were diagnosed by respiratory burst test during hospitalization, including 55 cases diagnosed before 2015 and 65 cases diagnosed after 2015. After using these 8 early diagnosis clues, the cases diagnosed after 2015 had shorter time of diagnosis and the length of stay and lower hospitalization charge than cases diagnosed before 2014, and the difference was statistically significant ((25±7) vs. (10±5) d, (29±7) vs. (18±6) d, (3.7×104±1.2×104) vs. (3.2×104±1.2×104) Yuan, t=13.763, 9.262, 2.381, all P<0.05). Conclusions: Patients with CGD are younger at onset and the diagnosis is delayed. Pulmonary infections are the most common. Large BCG scar, left axillary lymphadenopathy or calcification, skin or other lymph node infections, skin scars, multiple lung nodules, perianal abscesses, pulmonary Aspergillus infection and Burkholderia infection can help early diagnosis of CGD.

Radiological CT Patterns and Distribution of Invasive Pulmonary Aspergillus, Non-Aspergillus, Cryptococcus and Pneumocystis Jirovecii Mold Infections - A Multicenter Study.

Clinical signs and symptoms related to invasive fungal disease are nonspecific and need to be followed up by appropriate diagnostic procedures. The goal of this study was to analyze CT imaging patterns in invasive fungal infections and their correlation with the immune status and clinical outcome. We performed a retrospective multicenter study including 85 consecutive patients with invasive pulmonary fungal infection (2011-2014). Lung patterns on computed tomography (CT) scans were classified according to the Fleischner Society glossary. The patients were grouped according to immune status (neutropenia, steroid therapy, organ transplant recipient, and other cause) and outcome (positive outcome, progressive disease, and death). The Chi square test or Fisher exact test was used. Bonferroni correction was applied. The total number of patients with invasive Aspergillus and non-Aspergillus infection (IANA), Pneumocystis jirovecii pneumonia (PCP), and Cryptococcus (CRY) was 60, 22, and 3, respectively. Patients with IANA demonstrated significantly more nodules (93 % vs. 59 %, p = 0.001), significantly fewer ground glass opacities (58 % vs. 96 %, p = 0.005), and significantly fewer positive lymph nodes (5 % vs. 41 %, p < 0.001) than patients with PCP. All patients with PCP and CRY had a favorable outcome. Patients with IANA and an adverse outcome demonstrated significantly more nodules with halo sign than patients with IANA and a favorable outcome (42.5 % vs. 15.9 %, p < 0.0001). Interestingly, patients with IANA and a favorable outcome had a higher prevalence of pulmonary infarction than patients with an adverse outcome (8 % vs. 1 %, p = 0.047). Patients with neutropenia showed significantly more consolidations (66 %) than organ transplant recipients (27 %, p = 0.045). Patients with IANA showed a higher prevalence of nodules and a lower prevalence of ground glass opacities than patients with PCP. In patients with IANA, nodules with halo sign were associated with an adverse outcome. Patients with neutropenia showed generally more consolidations, but the consolidations were not associated with an adverse outcome. · Nodules, ground glass opacities, and consolidations are common CT findings in all invasive pulmonary fungal infections.. · There is no pattern that is unique for one specific pathogen, although nodules are more predominant in IANA and Cryptococcus, and ground glass opacities are more predominant in PCP patients.. · Immune status had an impact on CT findings in fungal pneumonia with less consolidation in patients after organ transplantation compared to patients with neutropenia.. · Nodules with a halo sign are associated with a worse outcome.. · Obmann VC, Bickel F, Hosek N et al. Radiological CT Patterns and Distribution of Invasive Pulmonary Aspergillus, Non-Aspergillus, Cryptococcus and Pneumocystis Jirovecii Mold Infections - A Multicenter Study. Fortschr Röntgenstr 2021; 193: 1304 - 1314.

Epidemiological Correlation of Pulmonary Aspergillus Infections with Ambient Pollutions and Influenza A (H1N1) in Southern Taiwan.

An increase in fungal spores in ambient air is reported during a spike in particulate matter (PM2.5 and PM10) aerosols generated during dust or smog events. However, little is known about the impact of ambient bioaerosols on fungal infections in humans. To identify the correlation between the incidence of pulmonary aspergillosis and PM-associated bioaerosols (PM2.5 and PM10), we retrospectively analyzed data between 2015 and 2018 (first stage) and prospectively analyzed data in 2019 (second stage). Patient data were collected from patients in three medical institutions in Tainan, a city with a population of 1.88 million, located in southern Taiwan. PM data were obtained from the Taiwan Air Quality Monitoring Network. Overall, 544 non-repeated aspergillosis patients (first stage, n = 340; second stage, n = 204) were identified and enrolled for analysis. The trend of aspergillosis significantly increased from 2015 to 2019. Influenza A (H1N1) and ambient PMs (PM2.5 and PM10) levels had significant effects on aspergillosis from 2015 to 2018. However, ambient PMs and influenza A (H1N1) in Tainan were correlated with the occurrence of aspergillosis in 2018 and 2019, respectively. Overall (2015–2019), aspergillosis was significantly correlated with influenza (p = 0.002), influenza A (H1N1) (p < 0.001), and PM2.5 (p = 0.040) in Tainan City. Using a stepwise regression model, influenza A (H1N1) (p < 0.0001) and Tainan PM10 (p = 0.016) could significantly predict the occurrence of aspergillosis in Tainan. PM-related bioaerosols and influenza A (H1N1) contribute to the incidence of pulmonary aspergillosis.

PC945, a Novel Inhaled Antifungal Agent, for the Treatment of Respiratory Fungal Infections.

Disease due to pulmonary Aspergillus infection remains a significant unmet need, particularly in immunocompromised patients, patients in critical care and those with underlying chronic lung diseases. To date, treatment using inhaled antifungal agents has been limited to repurposing available systemic medicines. PC945 is a novel triazole antifungal agent, a potent inhibitor of CYP51, purpose-designed to be administered via inhalation for high local lung concentrations and limited systemic exposure. In preclinical testing, PC945 is potent versus Aspergillus spp. and Candida spp. and showed two remarkable properties in preclinical studies, in vitro and in vivo. The antifungal effects against Aspergillus fumigatus accumulate on repeat dosing and improved efficacy has been demonstrated when PC945 is dosed in combination with systemic anti-fungal agents of multiple classes. Resistance to PC945 has been induced in Aspergillus fumigatus in vitro, resulting in a strain which remained susceptible to other antifungal triazoles. In healthy volunteers and asthmatics, nebulised PC945 was well tolerated, with limited systemic exposure and an apparently long lung residency time. In two lung transplant patients, PC945 treated an invasive pulmonary Aspergillus infection that had been unresponsive to multiple antifungal agents (systemic ± inhaled) without systemic side effects or detected drug–drug interactions.

Hemoptysis after Lung Transplantation Caused by Bronchial Arterial Neovascularization: Angiographic Analysis and Successful Embolization

This report discusses 3 bilateral lung transplant recipients (2 female, 1 male) who presented with late hemoptysis (10 y, 18 y, and 19 y after transplantation). All patients had a history of pulmonary infections, bronchiectasis, and/or Aspergillus infection. Arteriography, through catherization of the common femoral artery, demonstrated spontaneous bronchial and systemic neovascularization arising from the thyrocervical trunk, internal thoracic artery, intercostal arteries, and dorsal scapular artery. Embolization was performed with microspheres, polyvinyl alcohol microparticles, and/or glue and effectively terminated hemoptysis. One patient died 10 d later as a result of fungal infection, and the 2 others remained in stable condition (18- and 26-mo postembolization follow-up available).

Acute lung injury and repair induced by single exposure of Aspergillus fumigatus in immunocompetent mice.

Aim: Characterize the course of acute Aspergillus fumigatus lung infection in immunocompetent mice, investigating the immunological, pathological and tissue functional modifications. Materials & methods: C57BL/6 mice were intranasally infected with A. fumigatus conidia and euthanized to access inflammatory parameters. Results: Mice infected with A. fumigatus showed an inoculum-dependent lethality and body weight loss. An intense proinflammatory cytokine release, neutrophil infiltrate and pulmonary dysfunction was also observed in the early phase of infection. In the late phase of infection, proresolving mediators release, apoptosis and efferocytosis increased and lung tissue architecture is restored. Conclusion: Our study characterized an immunocompetent model of acute pulmonary Aspergillus infection in mice and opened an array of possibilities for investigations on interactions of A. fumigatus with host-immune system.

PULMONARY ASPERGILLOMA WITH SUBCUTANEOUS FISTULA RESULTING IN MASSIVE HEMOPTYSIS & SUBCUTANEOUS EMPHYSEMA

SESSION TITLE: Monday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Aspergillomas growing in pre-existing lung cavities can lead to presentations of hemoptysis. We present a case of a 73-year-old male with NSCLC and known 4 cm left cavitary lesion presenting with cough and hemoptysis. This lead to the diagnosis of a pulmonary aspergilloma with chest wall subcutaneous emphysema due to cavitary-subcuteanous fistula. CASE PRESENTATION: A 73-year-old male with severe COPD, CAD, and NSCLC in the left upper lobe treated with chemoradiation and known cavitation arrived with cough and hemoptysis. Vitals were pertinent for tachypnea and hypoxia at 75% room air requiring BiPAP. His physical exam was notable for rales and rhonchi bilaterally. He was stabilized and treated for presumed pneumonia and COPD exacerbation. His hemoptysis was initially attributed to his known lung malignancy and anti-platelet agents. A CT Angiogram was negative for pulmonary embolism, but the cavitary lesion increased to 7 cm with a new increase in soft tissue density. Labs of note were WBC 21.1 x10 3/uL, hemoglobin 7.0 mg/dL, platelets of 304 k/uL. Beta-1,3-D-Glucan levels were < 31 pg/mL, and galactomannan EIA test index < 0.5. Blood cultures were negative. Sputum cultures were obtained with pending results. The patient continued to experience excessive cough and hemoptysis. Given the evolution of the left cavitary lesion, and the potential for infection occupying that space, he underwent CT-guided aspiration. In the preprocedural scan, an interval of two days from prior imaging, the amount of hyperdense material contained within the cavity had significantly decreased with an air-fluid level present. Furthermore, moderate subcutaneous emphysema in the left chest wall and axilla were noted, raising the question of a pleuro/broncho-cutaneous fistula between the air-filled cavity and tissues. Aspirate cultures returned with heavy growth of Aspergillus species, along with Aspergillus in the fungal cultures. He was started on voriconazole therapy and transferred to an outside facility for IR embolization due to continued massive hemoptysis. DISCUSSION: Aspergillomas can occur in patients with COPD and a history of a cavitary lesions. They can be asymptomatic. Rarely, aspergillomas can progress to invasive aspergillosis via mechanical friction or invasion of blood vessels leading to massive hemoptysis. Here, we present a case of a pulmonary aspergilloma which was complicated by chest wall subcutaneous emphysema. As far as we are aware, in a review a literature, this complication has not arisen. CONCLUSIONS: We present a case of an aspergilloma within a previous pulmonary cavity causing a cavitary-subcutaneous fistula without evidence of invasive aspergillosis resulting in subcutaneous emphysema. This shows that pulmonary aspergilloma could rarely invade the chest wall and sheds light on subcutaneous emphysema as a potential rare complication of aspergillomas without prior trauma. Reference #1: Warris, A. (2014). The biology of pulmonary aspergillus infections. Journal of Infection, 69, S36-S41. DISCLOSURES: No relevant relationships by Anthony Bekasiak, source=Web Response No relevant relationships by Aya Shnawa, source=Web Response No relevant relationships by John Tedrow, source=Web Response

SUBACUTE INVASIVE ASPERGILLOSIS: A DIAGNOSIS BASED ON EVERYTHING IT'S NOT

SESSION TITLE: Monday Fellow Case Report Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Daily exposure to Aspergillus is common, but illness typically only develops in those with an altered immune system or underlying lung pathology. Whether a patient develops allergic bronchopulmonary aspergillosis (ABPA), chronic pulmonary aspergillosis (CPA), or invasive pulmonary aspergillosis (IPA) is dependent on the host immune response and interaction with the fungus. CASE PRESENTATION: A 64 year old female with no significant medical history and 10 months of cough presented with three weeks of chest tightness and progressive dyspnea. Due to severe symptoms and diffuse expiratory wheezing she was admitted for treatment and observation. Given her exam, history of atopy and allergic rhinitis and subsequent pulmonary function tests demonstrating severe obstruction, she was diagnosed and treated for an asthma exacerbation. Her symptoms did not improve and she progressed to requiring supplemental oxygen at rest despite being on high dose steroids. A CT Chest was obtained and she revealed groundglass opacification isolated to the right upper lobe with associated mucus plugging. A wide differential was considered to include CEP/AEP, HP, atypical infections, MR, PAP or a vasculitis. Following an acute decompensation the patient was transferred to the ICU and intubated. A bronchoscopy was conducted showing mucus plugging of the left main bronchus. During her extensive evaluation IgE levels were within normal limits and Aspergillus galactomannan was negative, however respiratory cultures grew Aspergillus fumigatus. Based on the respiratory culture and clinical presentation, the patient was diagnosed with subacute invasive aspergillosis and started on voriconazole. The patient’s clinical symptoms and radiographic findings rapidly improved with antifungal treatment. Immunologic evaluation following diagnosis was unrevealing. DISCUSSION: Subacute invasive aspergillus is a rare, but increasingly recognized infectious presentation of an otherwise common mold. This case highlights the spectrum of disease seen with pulmonary aspergillosis. Although subacute invasive aspergillosis primarily occurs in the immunocompromised, our patient had no history of immunosuppression and subsequent evaluation showed no defects. Because aspergillus was not considered early in our evaluation, the patient progressed to hypoxia and ICU admission. CONCLUSIONS: Clinicians should not discard the possibility of pulmonary aspergillosis in the immunocompetent. Reference #1: Kanj A, et al. The spectrum of pulmonary aspergillosis. Respiratory Medicine 2018; 141: 121-131. Reference #2: Kosmidis C and Denning D. The clinical spectrum of pulmonary aspergillosis. Thorax 2015; 70: 270-277. Reference #3: Riscili BP and Wood KL. Noninvasive Pulmonary Aspergillus Infections. Clin Chest Medicine 2009; 30: 315-335. DISCLOSURES: No relevant relationships by Tara Brown, source=Web Response Consultant relationship with MedicalConsultant to CSA Medical Please note: $5001 - $20000 Added 03/11/2019 by Robert Browning, source=Web Response, value=Consulting fee Consultant relationship with Inovital Medical Please note: $1001 - $5000 Added 03/11/2019 by Robert Browning, source=Web Response, value=Consulting fee My spouse/partner as a Employee No relevant relationships by Nikhil Huprikar, source=Web Response

In vivo investigation of antimicrobial effects of cinnamaldehyde using immunosuppressed ICR mice with invasive pulmonary aspergillosis

ObjectiveInvasive pulmonary Aspergillus infection has the characteristics of high morbidity, difficult to be treated, poor prognosis and high mortality. This study aims to investigate the effects of cinnamaldehyde on 1,3-β-D-glucans in the pulmonary Aspergillus fumigatus cell wall to provide a basis for developing novel antifungal drugs. MethodsImmunosuppressed ICR mice were intranasally inoculated with 50 µL of A. fumigatus suspension (1 × 107 CFU/mL) and then separated into two groups, for the experimental group cinnamaldehyde was orally administered at 240 mg/kg/d consecutively for 14 d. While for the control group, voriconazole was used to treat the fungus infection. Pulmonary tissues were then extracted for 1,3-β-D-glucans assay and electron microscopy. ResultsThe concentration of 1,3-β-D-glucans was significantly different between the cinnamaldehyde and voriconazole groups, which was (1160.89 ± 364.96) pg/mL and (3885.94 ± 845.45) pg/mL, respectively (P < 0.01). Electron microscopy showed that 2−3 outer layers (1,3-β-D-glucan layer) of A. fumigatus cell wall were damaged and fell off, resulting in serious defect of the cell wall, but the cell membrane was clear and intact. ConclusionCinnamaldehyde has a significant influence on the integrity of 1,3-β-D-glucans in the pulmonary A. fumigatus cell wall, but the cell membrane is unaffected, suggesting that cinnamaldehyde has unique antifungal properties depending on its action against the 1,3-β-D-glucans on the pulmonary A. fumigatus cell wall.

Community-acquired Pneumonia with Concurrent Multi-infections of Influenza A, Staphylococcus aureus, Streptococcus pneumoniae, Legionella and Invasive Pulmonary Aspergillosis in a Diabetic Patient

Invasive pulmonary Aspergillus infection during or after severe influenza infection in an immunocompromised patient or a previously healthy person has been reported in the literature [1-2]. In addition, coinfections of Staphylococcus aureus or Streptococcus pneumoniae with influenza are common, whereas simultaneous infections of legionellosis with aspergillosis are unusual in patients with influenza [2]. We herein report a diabetic patient who presented with a community-acquired pneumonia (CAP). The initial sputum culture yielded Aspergillus species and S. aureus, which were coinfected with influenza A, Pneumococcus and Legionella, with a deteriorated fatal course.