Aspergillus Exposure Research Articles

Air Sampling for Fungus around Hospitalized Patients with Coronavirus Disease 2019.

The risk of developing coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) depends on factors related to the host, virus, and treatment. However, many hospitals have modified their existing rooms and adjusted airflow to protect healthcare workers from aerosolization, which may increase the risk of Aspergillus exposure. This study aimed to quantitatively investigate airborne fungal levels in negative and slightly negative pressure rooms for COVID-19 patients. The air in neutral pressure rooms in ordinary wards and a liver intensive care unit with high-efficiency particulate air filter was also assessed for comparison. We found the highest airborne fungal burden in recently renovated slightly negative air pressure rooms, and a higher airborne fungal concentration in both areas used to treat COVID-19 patients. The result provided evidence of the potential environmental risk of CAPA by quantitative microbiologic air sampling, which was scarcely addressed in the literature. Enhancing environmental infection control measures to minimize exposure to fungal spores should be considered. However, the clinical implications of a periodic basis to determine indoor airborne fungal levels and further air sterilization in these areas remain to be defined.

18S rRNA gene sequencing for environmental aflatoxigenic fungi and risk of hepatic carcinoma among exposed workers

Aspergillus exposure causes an increase in aflatoxin (AF) levels among exposed workers thereby increasing their risk of developing hepatocellular carcinoma (HCC). This study attempted to determine the presence of airborne aflatoxigenic fungi in environment of waste water treatment plant (WWTP); and study the hepatic cancer risks among exposed workers, emphasizing the role of glutathione S-transferases (GST) gene polymorphism protecting against the risk of hepatic cancer development due to exposure to AFs. The study isolated and identified different Aspergillus species producing AFs in air samples from WWTP sites using 18S ribosomal ribonucleic acid (18S rRNA) gene sequencing technique. GST gene polymorphisms were genotyped using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). A significant increase in blood AF levels was found among WWTP exposed workers. The occurrence of GSTT1& M1 gene polymorphism in 6% of the workers was accompanied by significant decrease in the levels of AFs and alpha fetoprotein (AFP). In conclusion, Aspergillus-producing AFs were found in air of WWTP. Continuous exposure to AF-producing fungi caused elevated AF-levels in exposed workers. However only workers with heterozygous GSTT1& M1 genotypes can detoxify AFs, thereby decreasing the risk of HCC development among exposed workers.

MicroRNA regulation and host interaction in response to Aspergillus exposure

Aspergillus is a group of conidial fungi, isolated from soil and litter, cause serious diseases in humans and animals. This ubiquitous fungus is prevalent in the air and inhalation of fungal spores is common. Fungal diseases from Aspergillus became a major health problem and are difficult to manage because they tend to be chronic and invasive, hard to diagnose and difficult to exterminate with antifungal drugs. Although, immune responses play vital roles in monitoring the fate of fungal infections and regulation of the immune responses against fungal infections might be an effective approach for controlling and reducing the pathological damages. Recent studies have shown that microRNAs (miRNAs) are assembly of regulators which modulates the immune responses during fungal infections through diversified cellular mechanisms. These small non-coding RNA sequences regulate gene expression, mostly at the post-transcriptional level and have emerged as the controller of gene expression of at least 30% human genes. Therefore, miRNAs might be considered as one of the potential goals in immunotherapy for fungal infections. The objective of this review is to explore the role of miRNAs in host recognition processes and understanding the modulation of regulatory pathways in response to Aspergillus exposure.

Aspergillus-related diseases in a cohort of patients with severe asthma: A SANI single-center report

Aspergillus fumigatus is a ubiquitous fungus growing in many environments including the human body, where it can be deposited throughout the lung. Normally, conidia are cleared by immune defenses, although saprophytic noninvasive colonization often occurs in immunocompetent subjects. Strong evidence links Aspergillus exposure with severe asthma (SA), in which defective clearance of spores allows their germination into hyphae that damage airways by producing proteases and inducing inflammatory cytokines release.

The role of occupational Aspergillus exposure in the development of diseases.

Aspergillus spp. have a high nutritional versatility and good growth on a large variety of construction materials. They also colonize soil or food, but decaying vegetation is their primary ecological niche. Therefore, exposure to fungi may occur at home, during hospitalization, during specific leisure activities, or at the workplace. The development of Aspergillus infections depends on the interplay between host susceptibility and the organism. Environments with high counts of fungal elements (conidia, hyphal fragments and others), high levels of bioarerosols, and elevated concentrations of mycotoxins or other volatile organic compounds should be considered as potential hazards, since they may present a risk to the exposed person. Rural tasks as well as work related to wood and food industries, poultries, swineries, waste handling plants, and other occupational environments involving contaminated organic material are among the ones posing higher respiratory risks to the workers. This paper presents a review of several studies related to occupational and indoor exposure to Aspergillus, potential health effects related to that exposure, and associated exposure assessment procedures.

Superoxide dismutase reduces the inflammatory response to Aspergillus and Alternaria in human sinonasal epithelial cells derived from patients with chronic rhinosinusitis.

Aspergillus fumigatus and Alternaria alternata are ubiquitous environmental fungal allergens that can exacerbate airway inflammation and contribute to the disease process in patients with chronic rhinosinusitis (CRS). These antigens have been shown to induce human sinonasal epithelial cells (HSNECs) to promote a proinflammatory response, but what is unclear is a means by which to reduce these effects. Inhaled pathogens can induce HSNECs to produce reactive oxygen species (ROS) that trigger cytokine production. This study aimed to determine whether the free radical scavenger superoxide dismutase (SOD) could reduce HSNEC-derived inflammation, as measured by interleukin (IL)-6 and IL-8 production, in response to Aspergillus or Alternaria exposure. Sinus tissue explants were collected at the time of surgery from control patients (n = 7) and patients with CRS with nasal polyps (CRSwNP) (n = 9). HSNECs were cultured from the explants and treated with Aspergillus, Alternaria, and SOD for 24 hours. Cell supernatants and lysates were collected, and IL-6 and IL-8 concentrations were measured using enzyme-linked immunosorbent assay. In control and CRSwNP HSNECs, Aspergillus and Alternaria both increased cytokine production (p < 0.05), as measured by IL-6 and IL-8 concentration. SOD treatment reduced the inflammatory response to fungal antigen exposure from CRSwNP HSNECs but not control HSNECs. In CRSwNP patients, SOD significantly decreased IL-6 and IL-8 production after Alternaria exposure and IL-8 after Aspergillus exposure (p < 0.05). When HSNECs from CRSwNP patients are treated with SOD concurrently with Aspergillus or Alternaria, SOD treatment decreases the fungal antigen-induced inflammatory response. The ability to attenuate inflammation induced by common fungal allergens with SOD treatment could provide a novel therapeutic or preventative approach for patients with CRS or other allergic inflammatory airway diseases.

Aspergillus-associated airway disease, inflammation, and the innate immune response.

Aspergillus moulds exist ubiquitously as spores that are inhaled in large numbers daily. Whilst most are removed by anatomical barriers, disease may occur in certain circumstances. Depending on the underlying state of the human immune system, clinical consequences can ensue ranging from an excessive immune response during allergic bronchopulmonary aspergillosis to the formation of an aspergilloma in the immunocompetent state. The severest infections occur in those who are immunocompromised where invasive pulmonary aspergillosis results in high mortality rates. The diagnosis of Aspergillus-associated pulmonary disease is based on clinical, radiological, and immunological testing. An understanding of the innate and inflammatory consequences of exposure to Aspergillus species is critical in accounting for disease manifestations and preventing sequelae. The major components of the innate immune system involved in recognition and removal of the fungus include phagocytosis, antimicrobial peptide production, and recognition by pattern recognition receptors. The cytokine response is also critical facilitating cell-to-cell communication and promoting the initiation, maintenance, and resolution of the host response. In the following review, we discuss the above areas with a focus on the innate and inflammatory response to airway Aspergillus exposure and how these responses may be modulated for therapeutic benefit.

Human sinonasal epithelial cells direct dendritic function and T‐cell T helper 1/T helper 2 skewing following Aspergillus exposure

In lower airway disease such as asthma, epithelial cells have been shown to be potent regulators of dendritic cell (DC) functions. However, it is unclear how human sinonasal epithelial cells (HSNECs) from patients with sinusitis regulate DC functions. Therefore, in these studies we investigated the ability of Aspergillus fumigatus exposed HSNECs to regulate DC antigen uptake, maturation, and direction of T-cell T helper 1 (Th1)/Th2 skewing. Primary HSNECs were cultured from control (n = 8), chronic sinusitis without nasal polyps (CRSsNP) (n = 9), and chronic sinusitis with nasal polyps (CRSwNP) (n = 7) patients and exposed to Aspergillus. Conditioned media was placed upon monocyte-derived DCs from healthy controls. DC antigen uptake was assessed by dextran-fluorescein isothiocyanate (FITC) uptake. DC differentiation and maturation was assessed by immunostaining for CD209, CD80, and CD86 followed by flow cytometric analysis. DC direction of T-cell Th1/Th2 skewing was evaluated by immunostaining followed by intracellular flow cytometric analysis for interferon (IFN)-γ and interleukin (IL)-5. Control and CRSsNP HSNECs have the capacity to stimulate DC antigen uptake, differentiation, and maturation following Aspergillus exposure. CRSwNP HSNECs stimulate DC activation independent of Aspergillus exposure. Furthermore, Aspergillus-exposed CRSwNP HSNECs skew T-cells toward a Th2 phenotype. CRSwNP-derived HSNECs stimulate DC maturation and Th2 skewing independent of Aspergillus exposure. However, control and CRSsNP HSNECs induce DC maturation and Th2 skewing after Aspergillus exposure. These in vitro studies demonstrate that HSNECs are key regulators of DC functions in the sinus microenvironment.

Managing building-related Aspergillus exposure.

Aspergillus exposure is difficult to avoid. Indoor dust contains spores and thermotolerant molds may colonize damp or water-damaged building materials or components. Dust control should be part of diligent maintenance since disturbing dusts, especially during building renovation, can expose occupants to spores. Colonization of HVAC systems can shed spores into a building and expose occupants. Mold colonization warrants prompt and effective remediation, including removal of the colonization with associated debris and dusts without unduly exposing remediation workers, and while controlling fugitive dusts. Cleaning may suffice for non-porous surfaces, but colonized porous materials typically must be removed. Determining successful remediation can be challenging; the objective is not to sanitize, but a building in a 'normal and typical' state, a state that is often poorly defined. This is even more troublesome for colonized HVAC components and for health care facilities. Practical remediation assessment emphasizes inspection and then environmental monitoring. Air sampling may prove useful after inspection and monitoring, assuming prior consensus on the purposeof sampling and interpretation of results. Thoughtful design, careful construction and renovation, and diligent operation and maintenance of a building are all needed to minimize the exposure of building occupants to mold.

Increased incidence of allergic sensitisation and respiratory diseases due to mould exposure: Results of the Leipzig Allergy Risk children Study (LARS)

AbstractTo investigate mould effects on health, the concentration of mould spores in air and dust was determined during a prospective cohort study. Clinical outcome was estimated by questionnaires and determination of specific IgE antibodies and intracellular cytokine production of T cells.A significant association was observed between the incidence of respiratory tract infections and exposure to Penicillium spores. Moreover, Aspergillus exposure was found to be associated with allergic rhinitis or related symptoms. In addition, T cells of children exposed to Aspergillus showed a significantly lower content of TH1 cytokines (IFN-γ, TNF-α, IL-2) producing cells. Our data suggest that mould exposure is associated with several effects on health, depending on the species involved.

Role of increased environmental Aspergillus exposure for patients with chronic obstructive pulmonary disease (COPD) treated with corticosteroids in an intensive care unit

AbstractWe report about a 75-year-old woman and a 62-year-old man hospitalised for infection-related exacerbation of chronic obstructive pulmonary disease (COPD). In both patients, respiratory function worsened after initial stabilisation and the disease took a fatal course. A careful inspection of the intensive care unit (ICU) revealed several circumstances known to be risk factors for invasive aspergillosis (reconstruction activities near to the ICU, contamination of the window sills with pigeon droppings, moist building materials due to water leakage). The case reports suggest that both critically ill patients receiving high dose corticosteroid medication possibly have acquired aspergillosis on account of increased environmental exposure to Aspergillus conidia (>102CFU/m3 air). However, due to the severity of the disease confirmation by invasive diagnostic procedures was not possible. The role of high dose corticosteroid treatment as a risk factor for invasive aspergillosis should be taken into consideration, and increased exposure to fungi consequently be reduced in health care environments, especially for patients at risk.

Indoor airborne fungal spores, house dampness and associations with environmental factors and respiratory health in children.

Children living in a damp house are more likely to suffer from respiratory symptoms and it has been suggested that exposure to fungi is an important contributing factor. However, more knowledge about underlying mechanisms for the association are needed. To identify associations between measures of house dampness, levels of airborne fungal spores, housing factors and health outcomes in children. Eighty households with 148 children between 7 and 14 years of age were recruited in the Latrobe Valley, Victoria, Australia. Some 36% of participating children were asthmatic. Six sampling visits were made to each house between March 1994 and February 1995 on a 2-monthly cycle. Samples for airborne total and viable fungal spores were collected from bedrooms, living rooms, kitchens and outdoors. A detailed dwelling characterization, using a questionnaire and inspection surveys, was carried out. Skin-prick tests were performed with extracts of common aeroallergens and a respiratory questionnaire was completed for each child. Large airborne fungal spore concentrations were recorded in association with: musty odour, water intrusion, high indoor humidity, limited ventilation through open windows, few extractor fans and failure to remove indoor mould growth. Visible mould growth or condensation evidence was associated with large concentrations of Cladosporium spores, but not with large total spore concentrations. Penicillium exposure was a risk factor for asthma, while Aspergillus exposure was a risk factor for atopy. Fungal allergies were more common among children exposed to Cladosporium or Penicillium in winter or to musty odour. Respiratory symptoms were marginally more common with exposure to Cladosporium or total spores in winter. Indoor exposure to certain fungal genera in winter was a risk factor for asthma, atopy and respiratory symptoms in children. On the other hand, no significant associations were seen between average viable or total spore concentrations and child health. Actual measurements of fungal spores predict health outcomes better than reported dampness.