Increased mitochondrial metabolism in neutrophils revealed by single-cell RNA sequencing (scRNAseq) of bronchoalveolar lavage fluid (BALF) predicts remission in a fatal case of neutrophilic asthma

We present a case of lethal neutrophilic asthma, in which the patient required mechanical ventilation due to hypoxia and hypercapnia. After receiving high-dose steroid treatment, the patient eventually recovered and was successfully weaned off mechanical ventilation. To investigate the underlying mechanisms, we performed single-cell RNA sequencing (scRNAseq) analysis on the patient's bronchoalveolar lavage fluid (BALF) both before and during the remission phase. During the remission phase, we discovered a cluster of hybrid recovery-specific neutrophils (rs-Neus) that exhibited significantly higher levels of oxidative phosphorylation (OxPhos) and Tricarboxylic Acid Cycle (TCA) compared to pathological neutrophils (pNeus). Moreover, we observed a significant decrease in the inflammatory response in rs-Neus, which was found to be negatively correlated with their mitochondrial metabolic activity. Pathway analysis suggested that the hypoxia signaling pathway played a key role in the observed metabolic changes. Our fins highlight the changes in the metabolic landscape of neutrophils in BALF during the development of severe neutrophilic asthma. Furthermore, our study suggests that neutrophil mitochondrial metabolism may serve as an essential indicator of remission and underscores the potential of targeting neutrophil metabolism as a therapeutic strategy for severe neutrophilic asthma. We collected bronchoalveolar lavage fluid (BALF) of a patient with lethal neutrophilic asthma both before and during the remission phase, then analyzed the two BALF samples using scRNA-seq.