Aspergillus fumigatus isolated in two-thirds of hospitalized patients with invasive aspergillosis.

A. fumigatus is mostly responsible for invasive infection followed by A. flatus, A. Niger, and A. terreus.

Aspergillus conidia (spores) are ubiquitous and thus unavoidable.

A ubiquitous mold that most commonly affects immunocompromised hosts.

The number of aspergillosis cases increases yearly as the immunosuppressed population grows, largely the result of improvements in cancer therapy the prolonged duration of risk, and development of new immunotherapeutic agents that increase susceptibility to infection, and also due to improve diagnostics.

An increase risk is associated with hematopoietic stem cell transplantation, particularly in the early period of neutropenia and during treatment of graft versus host disease, and among solid organ transplant recipients treated with glucocorticoids or other immunosuppressive drugs.

Maybe associated with Bruton’s tyrosine kinase inhibitors, CAR-T therapy.

Hospitalizations in an ICU increase predisposition to aspergillosis and include the presence of lung disease, malignancy, corticosteroids for the treatment of COPD or acute respiratory distress syndrome, and impaired mucociliary clearance.

Patients with severe respiratory viral infection or at increased risk for aspergillosis and include Covid-19.

In soil and other vegetative with most materials aspergillus species exist as saprobes, digesting dead or dying organic material.

Because of a highly competitive environment aspergillus species is required to survive in the variable temperatures, pH, water, and nutrient conditions.

The vast majority of exposure to inhaled conidia does not result in measurable colonization and people.

For individuals who require and retain conidia, there is a spectrum of clinically significant outcomes that range from asymptomatic colonization to invasive infection.

A hypersensitivity to inhaled airborne conidia causes allergic bronchopulmonary aspergillosis or asthma with fungal sensitization, whereas aspergillus fungus balls or chronic pulmonary aspergillosis develops more frequently in persons with structural lung disease.

Invasive aspergillosis is the most severe entity and is characterized by invasion of lung tissue byAspergillus hyphae in mostly severe immunocompromised hosts.

Aspergillus hyphae may invade the pulmonary arterioles, lead to ischemic necrosis, intravascular thrombosis and hemorrhagic pulmonary infarct due to hyphae growth.

The incidence of invasive pulmonary aspergillosis is increasing due to increased use of immunosuppressants, increased numbers of stem cell and solid organ transplants, and more aggressive chemotherapy regimen for hematologic malignancies.

Aspergillosis can be seen in patients receiving long-term glucocorticoid therapy, but the presence of prolonged neutropenia confirms the highest risk of invasive disease.

In individuals with invasive infection, the most devastating form of disease is primarily observed in patients with clinically significant immunosuppression.

Patients  with invasive pulmonary aspergillosis present with dry cough, shortness of breath, pleuritic chest pain, and hemoptysis: fever may be present or not.

Patients are typically ill with tachypnea, tachycardia, and hypoxia.

In such immunosuppressed patients foci of growth are unchecked, and vegetative hyphae penetrate tissue planes in blood vessels, increasing the possibility for hematogenous spread and dissemination to multiple organs.

The lungs are exposed to  Aspergillus conidia daily, and an immune response for rapid pathogen elimination is present.

The proximal airways remove conidia by mucociliary clearance and if this is impaired, colonization or infection may ensue.

The airway’s epithelial cells and alveolar  macrophages are the first line of defense against aspergillus infection and they must phagocytize conidia while minimizing inflammatory reactions and maintaining immune homeostasis.

After phagocytosis, killing occurs through the generation of reactive oxygen species, and patients with defects in this pathway such as with chronic granulomatous disease have invasive infection with aspergillosis.

Neutrophils are an important immune cell with activity against aspergillus and neutrophil recruitment depends on chemokine release from lung epithelial cells.

T cells are essential in the host defense, with both CD4 and CD8 cells providing protective immunity, and in chronic aspergillosis there is aberrant T cell responses.

For diagnosis of pulmonary aspergillosis histopathological examination and culture of the surgical lung biopsy would be the gold standard: patients are however usually severely ill and this is not feasible.

Sputum or bronchoalveolar lavage fungal stain are positive in around 30% of cases.

Radiographic images aid in the diagnosis and CT of the chest is preferred: it can identify nodules, consolidative lesions,  wedge shaped infarcts and a characteristic radiologic feature of the halo sign which is a central nodule  with greater than 1 cm surrounded by ground glass opacity.

Noninvasive by chemical markers including serum, fungal cell wall antigens, including galactomannan,  beta-D-glucagon and aspergillus PCR.

A definitive diagnosis of aspergillosis is established by culturing the organism or by direct visualization of the mold in a biopsy specimen or a respiratory specimen.

Testing BAL fluid or blood for the presence of galactmanan a component of the fungal cell wall is a useful surrogate marker at aspergillus infection.

Aspergillus spp. Is a ubiquitous saprophytic mold commonly found in soil, water, and building materials that can cause illness illness is particularly in immunocompromised or immunocompetent individuals with underlying lung pathology.
Spores from this mold have a surface charge, hydrophobicity, and the size of 2 to 5. µm to propagate by transferring air, colonizing airways in the pulmonary tree and sinuses or leading to cutaneous or ocular lesions
Contracted through the respiratory tract.

After the inhalation of airborne fungal conidia subsequent manifestation of disease depend on the host’s immune response.

Most common life threatening invasive mold infection worldwide.

The genus comprises several 100 species, but poses little threat to people with healthy immune systems.

The inhaled conidia evade the innate immune system and trigger CD 4 positive T cell responses, an immunoglobulin E mediated type I hypersensitivity and an IgG mediated type III hypersensitivity reaction.
These changes activate a cascade of inflammatory cytokines resulting in aspergillus sensitization.
This is the first step in developing allergic bronchopulmonary aspergillosis.
Progression to severe asthma with fungal sensitization or allergic bronchopulmonary aspergillosis is based on clinical worsening and specific laboratory findings.

Patients with hematologic diseases and transplant recipients make up the vast majority of invasive pulmonary aspergillosis cases.

The allergic bronchopulmonary aspergillosis is non-specific and includes a differential diagnosis with poorly controlled asthma and cystic fibrosis in patients with worsening pulmonary function or new infiltrates.
Diagnosis is confirmed when testing establishes sensitization to aspergillus antigens with compatible clinical and radiographic findings.
Non-specific lab findings include a total eosinophil count of more than 500 cells per microliter and total serum IgE level of more than 1000 international units per milliliter.
Specific tests includes serum aspergillus specific IgE andIgG levels, serum precipitating antibodies, and skin testing for aspergillus sensitivity.

Common symptoms include: dyspnea, chronic cough, productive cough and wheezing, low-grade fever, weight loss, night sweats, chest pain, brownish mucous plugs, and hemoptysis.

The severity of invasive infection correlates inversely with the immune status of the host.

Risk factors include acute leukemias, advanced chronic lymphocytic leukemia, chronic myelogenous leukemia, lymphoma, refractory myelodysplasia, aplastic anemia, transplantation, prolonged neutropenia, corticosteroid therapy, infliximab treatment, immunodeficiency diseases, covid-19, and Chimeric antigen receptor T cell therapy.

Invasive aspergillosis occurs in 3-5% of patients given lung transplants.

Invasive aspergillosis increasingly seen with recipients of allergenic hematopoietic cell transplants with an incidence rate of up to 12% (Marr KA).

Invasive aspergillosis outcome poor with 1 year mortality 50-80%.

Prognostic factors include the severity and dissemination of disease and the degree of post immunosuppression.

Persistent neutropenia, steroid use and the need for ICU care is associated with failure to respond to antifungal treatment (Ramos ER et al).

Allergic bronchopulmonary aspergillosis is an inflammatory pulmonary disease secondary to hypersensitivity reaction to aspergillus species colonizing the airway.
Allergic bronchopulmonary aspergillosis is most exclusively seen in asthma and cystic fibrosis patients.
The hypersensitivity reaction causes a spectrum of diseases with severe asthma and fungal sensitization.
Azoles, voriconazole and posaconazole, improved the outcome in both primary and salvage therapy.

Most infections occur within the first three months after a lung transplant, with a mortality rate of 52% in infected lung transplant patients.

The greater the degree of immunosuppression the greater the likelihood of presentation with disseminated disease.

Activate immune cells via toll-like receptor 2 and toll-like receptor 4.

TLR4 haplotypes in donors associated with increased risks of invasive aspergillosis among recipients of allogeneic hematopoietic cell transplants.

Pneumonia increasingly common disease with a mortality rate greater than 50% in severely immunocompromised patients.

Amphotericin B has been standard treatment for invasive aspergillosis, but superior response rate and survival advantage noted for patients treated with voriconazole making it the primary therapy for invasive pulmonary aspergillosis.

Treatment for invasive pulmonary aspergillosis should be started immediately and not delayed for establishment of a diagnosis and should be treated with antifungal agents.

The drug of choice for pulmonary aspergillosis is voriconazole due to its improve survival in comparison with amphotericin B.

Caspofungin is a second line therapy for patients in whom first line treatment when other agents has failed.

A combination of voriconazole and caspofungin for invasive pulmonary aspergillosis result in improved survival rate at 3 months compared to monotherapy, and should be considered inpatients in whom primary therapy has failed.

In patients with asthma or cystic fibrosis aspergillus species colonize the airway, invade the immune system, germinate, cause mucous plugs, can lead to bronchiectatic changes and if the left untreated pulmonary fibrosis.
Plane chest x-ray films with demonstrate transient or permanent parenchymal opacities.
 CT chest reveals features of central bronchiectasis with peripheral tapering, central lobularnodules  and mucous plugs.
Allergic bronchopulmonary aspergillosis presents with non-specific findings and variations in presentation.
Aspergillus specific IgE is the best screening test with sensitivity of 100% for levels of greater than 0.35 KUA/L.
IgE levels are elevated usually greater than 1000 IU/ML.
Diagnostic testing includes PCR, serum galactomannan testing on serum and bronchoalveolar lavage.
Treatment options include systemic glucocorticoids and antifungal regimen.
Systemic glucocorticoids is the mainstay of treatment for allergic bronchopulmonary aspergillosis and a more efficacious than antifungal therapy in inducing a response after six weeks of treatment.
The goal of therapy used to suppress the inflammatory hypersensitivity response of allergic bronchopulmonary aspergillosis.
High dose steroids along with antifungal agents such as itraconazole may be beneficial.
An anti-IgE recombinant humanized monoclonal antibody omalizumab may be efficacious.
Chronic pulmonary aspergillosis typically present in immunocompetent individuals with underlying lung disease, most commonly cavitary lesions in patients with a history of tuberculosis or non-tuberculosis mycobacterium, COPD, sarcoidosis, pneumoconiosis, lung cancer, and radiation to the lung.
Chronic pulmonary aspergillosis Is typically indolent, with the most common symptom being cough, fatigue, weight loss, night sweats, shortness of breath, and fever.
Hemoptysis they develop and 50% of patients with chronic aspergillosis.
Aspergillomas typically have stable radiographic appearance for months, but chronic cavitary pulmonary aspergillosis tends to progress overtime, cavitate, and leads to volume loss involving one or multiple lung lobes and progresses to chronic fibrosing pulmonary aspergillosis.
Treatment of chronic pulmonary aspergillosis is to prevent or reduce hemoptysis, halting disease progression or pulmonary fibrosis.
The five-year mortality rate for chronic pulmonary aspergillosis ranges between 50 and 60%.
Aspergillus nodules can be observed on repeat CT scans.
Aspergillus management depends on clinical symptoms, as asymptomatic patients can babies served as noted.
In symptomatic patients a surgical resection is curative in selected patients, with near 100% five-year survival and low rates of occurrence.
Hemoptysis is a potentially life-threatening complication and supportive measures are used for mild hemoptysis.
Oral tranexamic acid may be considered in patients with severe or life-threatening hemoptysis, and bronchial artery embolization may be required.
Chronic cavitary pulmonary aspergillosis and chronic fibrosing pulmonary aspergillosis require antifungal therapy: itraconazole or voriconazole.

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