Evaluation of the airway microbiome in non-tuberculous mycobacteria
Background: Aspiration is associated with non-tuberculous mycobacterial (NTM) pulmonary disease and airway dysbiosis is associated with increased inflammation. We examined whether NTM disease was associated with a distinct airway microbiota and immune profile.Methods: 297 oral wash and induced sputum samples were collected from 106 participants with respiratory symptoms and imaging abnormalities compatible with NTM. Lower airway samples were obtained in 20 participants undergoing bronchoscopy. 16S rRNA gene and a nested mycobacteriome sequencing approaches characterised microbiota composition. Inflammatory profiles of lower airway samples were also examined.Results: The prevalence of NTM+ cultures was 58%. Few changes were noted in microbiota characteristic or composition in oral wash and sputum samples among groups. Among NTM+ samples, 27% of the lower airway samples were enriched with Mycobacterium A mycobacteriome approach identified Mycobacterium in a greater percentage of samples, including some non-pathogenic strains. In NTM+ lower airway samples, taxa identified as oral commensals were associated with increased inflammatory biomarkers.Conclusions: The 16S rRNA gene sequencing approach is not sensitive in identifying NTM among airway samples which are culture positive. However, associations between lower airway inflammation and microbiota signatures suggest a potential role for these microbes in the inflammatory process in NTM disease.
The syndrome behind the aspergilloma [Meeting Abstract]
INTRODUCTION: Our case demonstrates a rare immunodeficiency as the cause of Aspergilloma and describes the medical and surgical management. CASE PRESENTATION: A 29 year old woman with a history of hyper-IgE syndrome with recurrent skin and lung infections presents with shortness of breath and wheezing. Three months prior, she was diagnosed with a pneumonia based upon right upper lobe consolidation on chest x-ray and treated with multiple antibiotics. Despite management, her cough with tenacious secretions and shortness of breath persisted. Physical exam showed inspiratory wheezing and restricted chest wall motion. A 4 by 7 centimeter septated, thick-walled cavity in the superior segment of the right lower lobe with dependent debris suggestive of an Aspergilloma was seen on Chest CT (image 1). Immunoglobin E level was 11,667, positive Galactomannan assay, and peripheral eosinophilia was 16% (1.17 K/uL). She was treated with Posaconazole and referred to thoracic surgery. A right lower lobectomy and partial resection of the posterior segment of the right upper lobe was performed (image 2). The patient had an uncomplicated recovery, reduced symptoms, and returned to work and exercise. Pathology was consistent with an Aspergilloma with cultures growing A. fumigatus. DISCUSSION: Hyper-IgE Syndrome, known as Job's Syndrome is associated with a dominant STAT3 mutation, a regulator of the immune response.1 Hyper-IgE syndrome subjects develop pneumatoceles, likely due to aggressive and dysregulated inflammation.1 The mortality rate of patients with fungal disease is estimated at 16.7% and in a review, four of six deaths were due to A. fumigatus lung infections.2,3 Surgical complications include air leaks and poor lung expansion.1 Our patient was referred for surgical resection based upon the large Aspergilloma size and the likelihood of worsening with conservative therapy. Post-procedure, the patient was continued on Posaconazole; while there is little data to support prophylactic anti-fungals our patient may have benefited from its use.1 CONCLUSIONS: Invasive fungal infections are a major cause of mortality in Job's Syndrome