Is Aspergillus isolated from respiratory cultures clinically significant?

THREE MAJOR GROUPS OF DISEASE

Aspergillus is an environmentally ubiquitous and easily aerosolized mold encountered through daily exposure.¹ Broadly, Aspergillus-related lung diseases can be categorized into 3 major groups (Figure 1).

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Figure 1

Pulmonary aspergillosis types, based on the patient’s medical history.

Allergic bronchopulmonary aspergillosis (ABPA) is an inflammatory lung condition caused by hypersensitivity reaction to Aspergillus antigens that almost exclusively occurs in patients with asthma or cystic fibrosis.² Allergic reactions that do not fulfill the criteria for ABPA include Aspergillus sensitization and severe asthma with fungal sensitization.

WHEN IS A POSITIVE CULTURE CLINICALLY SIGNIFICANT?

Aspergillus infections, most commonly with A fumigatus and A flavus, account for approximately 15,000 hospitalizations and an estimated $1.2 billion in hospital costs annually across the United States.⁵ Therefore, it is not uncommon for physicians to encounter an Aspergillus-positive respiratory culture in the clinical setting. This begets the question, Is the finding clinically significant?

In an adult patient without significant medical history, isolation of Aspergillus species in respiratory culture is likely a false-positive finding due to contamination or colonization of the respiratory flora by these ubiquitous fungal organisms. In hospitalized patients who undergo routine respiratory cultures, 80% to 90% of those with positive Aspergillus findings do not have significant aspergillosis lung disease.^6,7 Even in patients with proven Aspergillus pulmonary infection, respiratory cultures are positive in 20% to 50% of patients, and as such the isolation of Aspergillus in respiratory cultures is neither sensitive nor specific in the diagnosis of most fungal respiratory infections and is not an integral part of the diagnostic criteria for Aspergillus-related lung diseases.⁸ Under these circumstances, in a patient who has no underlying lung disease and no immunocompromised state, we recommend observation and no further diagnostic or therapeutic intervention.

On the other hand, in a patient with respiratory symptoms, critical illness, underlying chronic lung disease, or an immunocompromising condition, detection of Aspergillus in respiratory culture may indicate underlying Aspergillus lung disease.³ In these situations, we recommend additional workup, and if the Aspergillus is proven to be the causative agent, then appropriate treatment should be started.

THE HISTORY AND PHYSICAL

It is imperative to assess the patient’s history to quickly identify risk factors for pulmonary aspergillosis. We recommend first obtaining a thorough history and physical examination for all patients.

Key factors to consider include symptoms such as hemoptysis, chest pain, fever, and recent respiratory illness. Carefully assess for underlying chronic lung conditions including asthma, cystic fibrosis, chronic obstructive pulmonary disease, tuberculosis, lung surgery, radiation, pneumoconiosis, or sarcoidosis. In addition, a thorough evaluation should be done for conditions that may affect the immune system including leukemia, hematopoietic stem cell or solid-organ transplant, immunosuppressive therapy, and chronic corticosteroid therapy.^3,5–10 In immunocompromised patients who present with sepsis and demonstrate tachypnea, tachycardia, fever, hypotension, and hypoxia, IPA should be considered, and rapid identification and treatment of the causative agent are crucial, as the mortality rate is high.

LABORATORY TESTS AND IMAGING

In patients with clinical presentations suggestive of aspergillosis, we suggest pairing a basic laboratory assessment (ie, a complete blood cell count) with radiographic imaging. Initial laboratory findings may narrow the differential diagnosis by identifying eosinophilia, which suggests ABPA, or severe neutropenia, which suggests IPA.

For imaging, we recommend high-resolution computed tomography (CT) of the chest rather than chest radiography to evaluate for Aspergillus-related lung disease, as it has superior ability to identify nodules, consolidation, cavitary lesions, and bronchiectasis. The finding of a cavitary lesion with or without intracavitary radiopacity suggests chronic aspergillosis, whereas the “halo” sign or “air crescent” sign suggests IPA (Figure 2), and bronchiectasis is seen in patients with ABPA.¹¹ In evaluating chest CT findings, it is always useful to compare against previous imaging results and to consider other conditions that may coexist with positive Aspergillus in the respiratory sample.

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Figure 2

Computed tomography shows multiple pulmonary nodules, some surrounded by ground-glass changes consistent with the “halo” sign (arrow) in a patient with invasive pulmonary aspergillosis.

MANAGEMENT

Management depends on the Aspergillus-related diagnosis and the patient’s clinical status. When considering conditions such as ABPA or chronic aspergillosis, we suggest waiting until the diagnosis is confirmed before initiating treatment.

However, IPA is more rapidly progressive and has a high mortality rate. Therefore, if clinical suspicion is high, therapy should not be delayed for the establishment of the diagnosis of proven or probable disease. In these situations, we suggest starting empiric therapy with a triazole agent while waiting for the results of cultures and biomarkers.

ALWAYS CONSIDER THE CLINICAL PICTURE

Due to the ubiquity of Aspergillus, many patients have false-positive findings on respiratory culture and require no additional workup or treatment. However, Aspergillus-positive respiratory cultures may be an indication of underlying serious Aspergillus lung disease. A thorough history to detect symptoms, underlying chronic lung disease, or immunocompromising state, followed by targeted laboratory tests and radiologic evaluation, is adequate to ascertain the significance of this finding in most patients.

DISCLOSURES

The authors report no relevant financial relationships which, in the context of their contributions, could be perceived as a potential conflict of interest.