Novel Therapies for Pneumonia-Associated Severe Asthma Phenotypes

Distinct asthma phenotypes are emerging from well-defined cohort studies and appear to be associated with a history of pneumonia. Asthmatics are more susceptible to infections caused by Streptococcus pneumoniae; however, the mechanisms that underlie defective immunity to this pathogen are still being elucidated. Here, we discuss how alternatively activated macrophages (AAMs) in asthmatics are defective in bacterial phagocytosis and how respiratory viruses disrupt essential host immunity to cause bacterial dispersion deeper into the lungs. We also describe how respiratory pathogens instigate neutrophilic inflammation and amplify type-2 inflammation in asthmatics. Finally, we propose novel dual-acting strategies including granulocyte-colony-stimulating factor receptor (G-CSFR) antagonism and specialised pro-resolving mediators (SPMs) to suppress type-2 and neutrophilic inflammation without compromising pathogen clearance.