Table 3.

Future directions for research to advance understanding of persistent NTHi infection in COPD.

Area of study	Goals of future work
Adhesins	• Identify host cell receptors of NTHi adhesins
Biofilm formation	• Investigate COPD airways for NTHi biofilms
	• Simulate in vivo conditions in current in vitro models
	• Establish animal model of persistent NTHi infection
Intracellular survival	• Assess the impact of host cell invasion and intracellular survival on duration of persistence
IgA proteases	• Characterize role of IgA protease variants in NTHi persistence
Genetic variation	• Comprehensively identify targets of epigenetic regulation
	• Assess role of DNA repair mechanisms on genetic variation
	• Assess vaccine candidates based on genetic variation
Nutrient acquisition	• Characterize NTHi nutritional virulence factors
Toxin-antitoxin (TA) systems	• Elucidate the role of TA systems in NTHi persistence in the context of COPD
Outer membrane vesicles (OMVs)	• Characterize role of OMV during persistence
Immune response	• Define protective immune responses to NTHi in COPD
	• Identify vaccine formulations that elicit protective immune responses