Serum Cytokines Usefulness for Understanding the Pathology in Allergic Bronchopulmonary Aspergillosis and Chronic Pulmonary Aspergillosis

Abstract

Allergic bronchopulmonary aspergillosis (ABPA) and chronic pulmonary aspergillosis (CPA) are important fungal infections caused by Aspergillus species. An overlap of ABPA and CPA has been reported; therefore, it is critical to determine whether the main pathology is ABPA or CPA and whether antifungals are required. In this study, we investigated whether the serum cytokine profile is useful for understanding the pathology and for differentiating between these diseases. We compared the various serum cytokine levels among healthy subjects and patients diagnosed with asthma, ABPA, or CPA at Nagasaki University Hospital between January 2003 and December 2018. In total, 14 healthy subjects, 19 patients with asthma, 11 with ABPA, and 10 with CPA were enrolled. Interleukin (IL) -5 levels were significantly higher in patients with ABPA than in those with CPA, and IL-33 and tumor necrosis factor (TNF) levels were significantly higher in patients with CPA than in those with asthma (p < 0.05, Dunn’s multiple comparison test). The sensitivity and specificity of the IL-10/IL-5 ratio (cutoff index 2.47) for diagnosing CPA were 70% and 100%, respectively. The serum cytokine profile is useful in understanding the pathology of ABPA and CPA, and the IL-10/IL-5 ratio may be a novel supplemental biomarker for indicating the pathology of CPA.

Impact of Ascaris lumbricoides infection on the development of chronic pulmonary aspergillosis in patients with COPD

“…21 The high levels of TNF-α and IL-6 in patients with COPD with ascariasis and CPA in our study are similar to other data. 22,23 Rise in both IL-1 and IL-6 have been associated with negative health outcomes, mortality and a pro-inflammatory phenotype in COPD. IL-6 in COPD was shown to correlate negatively with lung function, and IL-1β induces airway inflammation.…”

“…21 The high levels of TNF-α and IL-6 in patients with COPD with ascariasis and CPA in our study are similar to other data. 22,23…”

Aspergillus and the Lung

“…67,68 Recently, the exposure of the respiratory epithelium to Aspergillus has been associated with the release of IL-33. [69][70][71] This is an epithelial alarmin, that activates ILC2s via the ST2 receptor, which in turn, release IL-5 and IL-13. Severe allergic inflammation is known to induce exhausted-like ILC2s with high expression of the inhibitory signal IL-10 and low expression of IL-5 and IL-13 66,69 .…”

“…The high IL-10 expression may give rise to uncontrolled Aspergillus infection and may clarify why ABPA occasionally evolves to CPA. 66,69 Noninvasive Tracheobronchial Aspergillus Disease…”

“…[69][70][71] This is an epithelial alarmin, that activates ILC2s via the ST2 receptor, which in turn, release IL-5 and IL-13. Severe allergic inflammation is known to induce exhausted-like ILC2s with high expression of the inhibitory signal IL-10 and low expression of IL-5 and IL-13 66,69 . The high IL-10 expression may give rise to uncontrolled Aspergillus infection and may clarify why ABPA occasionally evolves to CPA.…”