COMMENTARY

Quandary about treatment of aspergillomas persists

Aspergillus fumigatus is an opportunistic pathogen and ubiquitous in the environment. In humans, A. fumigatus can cause a wide range of infections whose symptoms are directly determined by the immunological status of the host. Invasive aspergillosis (IA), is a systemic infection that affects immunosuppressed patients but other forms of aspergillosis includes superficial infections, allergic bronchopulmonary aspergillosis (ABPA) and aspergilloma. Development of aspergillosis is governed by a mutual dependency between host-related factors and fungal virulence. The later can be attributed to multiple aspects associated to the cell structure, morphogenetic reprogramming, stress response, secretion of enzymes and secondary metabolites, nutrient acquisition and synthesis, and adaptation to the host conditions. In this review, we describe the types of diseases caused by A. fumigatus and its symptoms according to the site of infection and the host health condition. In addition, the molecular bases of A. fumigatus pathogenesis are discussed.

The incidence of invasive aspergillosis (IA) has dramatically increased during the last decade. This infection is associated with high morbidity and mortality, ranging from 30% to 70%, especially in immunocompromised patients. Delay in diagnosis and treatment is usually associated with high mortality rates. This study was aimed to assess the diagnostic value of Galactomannan EIA (GM) for early diagnosis of aspergillosis in hospitalized patients with underlying conditions. Also, the antifungal drug susceptibility profiles of causative agents were investigated. In this descriptive cross-sectional study, during the period of 18 months starting from September 2017 until February 2019, 22 bronchoalveolar lavage (BAL) and 13 biopsies from infected sinuses were obtained from a total of 150 patients suffering from different types of hematologic malignancies. All the samples were subjected to microscopic examination and fungal culture. Also, serum specimens were obtained from all patients (n = 135). 22 serum and 17 BAL specimens were tested for the GM level. Fungal identified were confirmed through the PCR-sequencing of the β-tubulin gene. The susceptibility to amphotericin B, itraconazole, voriconazole, posaconazole, ravuconazole, and caspofungin was evaluated according to the Clinical and Laboratory Standards Institute document M38-A2 (CLSI M38-A2) broth microdilution protocol. The results showed that the incident rate of IA was 23.33% and 35 patients with IA (12 proven cases and 23 probable cases) were diagnosed according to the European Organization for Research and Treatment of Cancer and Mycoses Study Group criteria. The 35 patients with IA in the current study comprised 19 men (54.29%) and 16 women (45.71%) with the median age of 42 years. AML (31.5%) was documented as the most prevalent risk factor among our subjects with IA and Aspergillus flavus (65.7%) was the most prevailing causal agent in this study. Among patients with IA, ague (71%) and cough (60%) were the most common symptoms. In the present study, a sensitivity of 94% and a specificity of 98% was reported for GM ELISA in BAL specimens. Also, a sensitivity of 58% and a specificity of 98% was reported for GM ELISA in serum samples. Among 6 tested antifungal drugs, the lowest minimum inhibitory concentration (MIC) values were observed for posaconazole and ravuconazole which showed the range of 0.008–0.0062 $\raisebox{1ex}{$\mu g$}\!\left/ \!\raisebox{-1ex}{$ml$}\right.$ and 0.031–0.125 $\raisebox{1ex}{$\mu g$}\!\left/ \!\raisebox{-1ex}{$ml$}\right.$, respectively. The current study has demonstrated that determining the value of GM investigation in BAL and serum specimens can be promising in early diagnosis of IA, also molecular identification of the agents causing IA and their antifungal susceptibility patterns are essential issues for the targeted antifungal therapy and outcome improvement of patients with this life-threatening disease.

Aspergilloma, also known as mycetoma or fungus ball, is the most common manifestation of pulmonary involvement by Aspergillus species. The fungal ball typically forms within preexisting cavities of the lungs. Diagnosis requires both radiographic evidence along with serologic or microbiologic evidence of Aspergillus species involvement. While clinical features such as hemoptysis, chest pain, shortness of breath, cough, and fever are helpful in diagnosis, they are non-specific symptoms. Surgery is currently the mainstay of treatment for aspergilloma but is associated with considerable mortality and morbidity. Alternative options exist for patients who are poor surgical candidates and for those who prefer a less invasive treatment modality. Systemic treatment with amphotericin B is ineffective and is not recommended as a monotherapy, but systemic azoles is effective in approximately 50–80% of patients. Potential alternatives to surgery include intracavitary instillation or endobronchial administration of antifungal medication, as well as direct transbronchial aspergilloma removal. Bronchial artery embolization and radiotherapy are options to manage hemoptysis until definite eradication of the aspergilloma. More rigorous studies are needed to better establish non-surgical treatment paradigm for inoperable patients.

Aspergillomas growing in pre-existing lung cavities can lead to presentations of hemoptysis. We present a case of a 73-year-old male with non-small cell lung carcinoma (NSCLC) and known 4 cm left cavitary lesion in the left upper lobe presenting with cough and hemoptysis, leading to the diagnosis of a pulmonary aspergilloma complicated by chest wall subcutaneous emphysema due to cavitary-subcutaneous fistula in the setting of excessive cough. This case sheds light on subcutaneous emphysema as a potential rare complication of aspergillomas in patients without prior trauma.

Alors que les sinusites affectent environ 20 % de la population, les sinusites fongiques sont rares. Les champignons du genre Aspergillus sont les champignons les plus fréquemment impliqués. Les sinusites fongiques représentent un large spectre de maladies, incluant des formes invasives et non invasives, aiguës et chroniques. Une sinusite fongique invasive peut survenir chez un patient immunodéprimé ou diabétique, alors que les sinusites fongiques non invasives doivent être évoquées devant un tableau chronique réfractaire aux antibiotiques chez des patients immunocompétents, notamment la sinusite fongique allergique liée à une hypersensibilité de l’hôte vis-à-vis du champignon. Le diagnostic de ces infections nécessite des examens radiologiques, endoscopiques avec des biopsies de muqueuse sinusienne étudiées en histologie et mycologie, qui permettront de distinguer les différentes entités. Dans les formes non invasives, le traitement chirurgical est indispensable, parfois en association avec un traitement antifongique et anti-inflammatoire. Les formes invasives nécessitent un traitement antifongique associé à la chirurgie dans certaines formes, en particulier dans la mucormycose.

Although sinusitis affects about 20 % of the population, fungal sinusitis is rare. Aspergillus sp. are most frequently implicated. Fungal sinusitis represents a wide spectrum of disorders, including acute or chronic and invasive or non-invasive forms. Invasive fungal sinusitis may develop in an immunocompromised or diabetic patient, whereas non-invasive fungal sinusitis should be considered in a chronic situation, resistant to antibiotics in immunocompetent patients. Allergic fungal sinusitis is related to hypersensitivity of the host to the fungus. The diagnosis of these infections requires radiological examination and endoscopy with mucosal biopsies examined histologically and mycologically in order to distinguish the different types of sinusitis. In the non-invasive forms, surgical treatment is essential, sometimes combined with antifungal and anti-inflammatory treatment. The invasive forms require antifungal treatment, combined with surgery in some forms, particularly mucormycosis.

Intracavitary pulmonary aspergilloma is a chronic, debilitating fungal infection. Without definitive therapy, death can occur from massive hemoptysis, cachexia, or secondary infection. Although surgical resection is the standard therapy, it is not possible for many patients owing to poor pulmonary function or medical comorbidities. Aspergilloma removal through bronchoscopy is an important alternative therapy that may be available in select cases.

We retrospectively reviewed all cases referred to the University of Calgary Interventional Pulmonary Service for transbronchial removal of intracavitary aspergilloma from January 1, 2009, to January 1, 2014.

Ten patients with intracavitary pulmonary aspergilloma were identified. In 3 patients, the aspergilloma cavity was not accessible by bronchoscopy. Successful removal of the aspergilloma with symptom improvement or resolution was achieved in 6 of 7 cases. One of the patients was lost to follow-up. Minor hypoxia lasting 12 to 72 hours was observed in 5 cases. Severe sepsis requiring an extended critical care unit stay occurred in 1 case. Follow-up ranged from 9 months to 5 years.

Although not without risk of minor hypoxia and possible sepsis, for carefully selected patients, bronchoscopic removal of symptomatic intracavitary pulmonary aspergilloma may be an alternative therapy to surgical resection for this life-threatening disease.