Chronic Cavitary Pulmonary Aspergillosis: A Case Report and Review of the Literature

Background

Aspergillus species are a significant cause of morbidity in both immunocompetent and immunocompromised patients. Disease involvement ranges from a spectrum of allergic bronchopulmonary aspergillosis to chronic (saprophytic) forms and can have an invasive component to its disease process.

The chronic form of pulmonary aspergillosis favors those individuals with none or minimally suppressed immune systems or those with minimal alterations of pulmonary parenchyma due to underlying disease. Diagnosis ideally consists of tissue and fluid samples, though because these samples are not always obtainable (1–>3) beta-D-glucan and galactomannan antigen assays continue to play a pivotal role achieving this diagnosis.

Despite Aspergillus spores being pervasive in nature and inhalation common, the clinical suspicion for this disease remains low as tissue invasion is uncommon. Because of this, the disease is often overlooked as holding a strong place on a differential diagnosis for cavitary lung lesions, which can delay diagnosis and treatment. Once diagnosed, chronic pulmonary Aspergillus treatment is straight forward; outside of monitoring liver function tests, long term treatment with a triazole is recommended as first-line treatment.

Case Report

OUTCOME AND FOLLOW-UP:

Once the patient’s sputum culture identified aspergillus, voriconazole was started, with a baseline level being obtained prior to hospital discharge. Liver function tests were measured as well, as the patient will require antifungal therapy for at least 6 months.

Unfortunately, the patient was lost to outpatient pulmonary clinic follow-up; it is unknown what her follow-up scans indicated or whether she successfully cleared her disease burden.

Discussion

Pulmonary cavities are gas filled pockets whose nidus for formation is an inflammatory consolidation within the pulmonary parenchyma [1]. Most cavities can be visualized with plain films and because of their broad etiology, it is often difficult to predict which pathology will result in a cavitation. Infections, malignancy, rheumatologic disorders, aspiration, pulmonary infarction, and displacement of pulmonary parenchyma within the thorax are just some of the pathology on the differential diagnosis list when a cavitation is discovered. One cause that is often forgot is aspergillus, a ubiquitous spore that is often indolent in the general population.

Bronchopulmonary aspergillosis, while an infrequent condition in the immunocompetent population, is spread by the inhalation of mycotic spores from the Aspergillus species. The exact extent of involvement in the United States is currently unknown as this is not a reportable disease, though A. fumigatus appears to be the most virulent [1,2]. The spores are inherent in the environment and most often are indolent in those individuals lacking structural lung disease or individuals who are immunocompromised [2]. For those patients with structural lung disease and/or an immunocompromised status, such as the case presented in this report, the Aspergillus spores can lead to a spectrum of pulmonary involvement, which are classified into 4 different forms.

The acute forms of this disease comprise allergic broncho-pulmonary aspergillosis and invasive aspergillosis. Allergic broncho-pulmonary aspergillosis has a predilection for those with asthma or cystic fibrosis, while invasive aspergillosis (angioinvasive or broncho-invasive forms) tends to occur in severely immuno-compromised patients. The chronic forms of Aspergillus infection are composed of 2 syndromes (aspergilloma and chronic cavitary pulmonary aspergillosis [CCPA]) that can be crippling to those with established pulmonary parenchymal damage [3–6]. The incidence of the acute and chronic manifestations outlined aforementioned is dependent on the immunologic status of the host and the existence of an underlying lung disease.

Specific to this case is CCPA; CCPA most often favors middle-aged patients with abnormal lung structure (chronic obstructive pulmonary disease, bronchiectasis, cystic fibrosis or chronic lung cavities) [5] versus those patients who are immunocompromised. The disease process consists of a slowly progressive course that has the ability to last for years. The frequent, though vague, constitutional symptoms of fever, malaise, fatigue, and weight loss can accompany CCPA, which make it difficult to place at the top of a differential diagnosis list and makes the diagnosis one of high suspicion. Non-specific pulmonary symptoms can range in severity from a chronic productive cough to hemoptysis [5]. Further difficulty in a diagnosis is hindered by non-specific parenchymal structural changes that can be seen on imaging, these changes can range from pleural thickening to an empyema and anything in between [7]. Mycobacterium infection and obstructive lung diseases (sans asthma) are the most frequent pulmonary diseases that are associated with CCPA. The patient presentation in this case report was not different: vague constitutional symptoms coupled with non-specific radiographic findings, made it difficult to have a high index of suspicion.

The diagnosis of CCPA was formulated by Godet et al. [3] in 2014: the constellation of immunosuppression, constitutional symptoms, the formation of a single/multiple lung cavitation, a positive serum Aspergillus percipitins test, increased biological inflammatory markers and the absence of other pathology that could mimic the aforementioned symptoms (malignancy, tuberculosis, atypical mycobacterium) help comprise the diagnostic criteria. Unfortunately, none of the aforementioned criteria in singularity is able to diagnose CCPA, though the combination of the criteria with patient specific factors often strongly argues for the diagnosis. This combination of clinical and diagnostic manifestations was chosen to help aid in the diagnosis of this disease by the updated 2016 IDSA guidelines for Aspergillus [8].

Confirmative diagnosis can be aided by the combination of histopathologic/cytologic and culture specimens. The “gold standard” procedure for obtaining a tissue sample and bronchioalveolar lavage is via bronchoscopy [6,8]. Complicating matters is the fact that the yield from obtaining an adequate specimen via bronchioalveolar lavage is low for lesions in the periphery of the pulmonary parenchyma; because of this, a lung biopsy, achieved either percutaneous or via navigational bronchial technique, should be considered in this population [9].

In the case that histopathologic specimens are unable to be obtained, such as this case, a serum assay for (1–>3) beta-D-glucan (Fungitell) should be ordered. A Fungitell assay helps in diagnosis of a fungal organism, but is not specific for Aspergillus as it is present in all fungi cell walls. Obtaining a serum and bronchioalveolar lavage galactomannan can help aid in the diagnosis as this assay is a more accurate marker for Aspergillus in both the pediatric and adult patient populations [8]. The primary laboratory test for making a diagnosis of chronic pulmonary aspergillosis is a positive serum Aspergillus immunoglobulin (Ig)G antibody level [10].

First-line treatment encompasses oral medications from the triazoles anti-fungal group. When triazoles cannot be administered, amphotericin B (AmB) deoxycholate and echinocandins serve as useful second-line therapy options for Aspergillus infections. Six months of treatment is the desired duration for patients with CCPA and radiographic progression of disease, or for patients who experience either pulmonary or general symptoms. Six months is also an acceptable treatment duration for those patients who are unfortunate to experience a progressive loss of lung function. Obtaining trough drug levels for those patients who are on prolonged azole therapy is recommended [10,11].

After 2 weeks of treatment, a non-contrast CT scan of the chest to evaluate the patient’s response to treatment is recommended for those that are diagnosed with CCPA.

Conclusions

In an immunocompromised patient with rapidly progressing radiologic findings concerning of pulmonary cavitation, Aspergillus should not be forgotten when formulating a differential diagnosis list. Diagnosis by the combination of serum and tissue specimens is easily made and the treatment consists of a prolonged duration of triazole administration.