Non-fumigatus Aspergillus species cause treatable lung disease but current diagnostics miss most cases

Original abstract

UNLABELLED: Diagnosing pulmonary diseases caused by non-fumigatus Aspergillus species remains challenging. We conducted a single-center, retrospective observational study in a French Respiratory Medicine Department. Patients with at least one respiratory sample positive for a non-fumigatus Aspergillus species, without concurrent A. fumigatus isolation over a 12-month period, were included. The primary objective was to determine the prevalence of pulmonary events (colonization or pulmonary diseases) associated with non-fumigatus Aspergillus species. Secondary objectives included species characterization and assessment of positive results for available diagnostic tests, including direct examination and fungal culture from respiratory samples, galactomannan in bronchoalveolar lavage, and serum A. fumigatus-specific IgG. Between April 2017 and January 2022, 497 patients (39.6%) had cultures positive for non-fumigatus Aspergillus species. Among them, 52 (10.5%) experienced pulmonary events: 36 were colonized, and 16 had a documented pulmonary disease. Aspergillus niger was the most frequently isolated species (41%), followed by Aspergillus flavus (27%) and Aspergillus nidulans (10%). Positive results were observed in 10/437 (2.3%) samples for direct examination, 75/808 (9.3%) for fungal culture, 7/94 (7.4%) for galactomannan in bronchoalveolar lavage, and 12/49 (24.5%) for serum Aspergillus fumigatus-specific IgG. Among patients with non-fumigatus Aspergillus positive respiratory samples, most were colonized, while nearly one-third had clinically significant pulmonary diseases, underscoring the clinical relevance of these species. Low positivity rates across diagnostic tests underscore the need for repeated respiratory sampling and fungal culture and suggest that assays primarily designed for A. fumigatus may under-detect these pulmonary events. IMPORTANCE: Non-fumigatus Aspergillus species are recognized as pulmonary pathogens, but their diagnosis is poorly documented. In this 5-year, single-center study, 497 of 1,256 patients had at least one positive respiratory culture for a non-fumigatus species, with 36 considered colonized and 16 with documented lung disease. A. niger, A. flavus, and A. nidulans accounted for almost four-fifths of the isolates. Routine tests produced poor results, with positivity rates of 2.3% for microscopy, 9.3% for repeat culture, 7.4% for bronchoalveolar galactomannan, and 24.5% for Aspergillus fumigatus serum IgG. Overall, the study shows that non-fumigatus species can cause treatable chronic lung disease, but that current diagnostics miss most cases. Until more sensitive tests are available, clinicians must rely on repeated respiratory sampling and culture to identify these infections.