title: Oral non-typable Haemophilus influenzae enhances physiological mechanism of airways protection.
abstract: Oral immunotherapy with inactivated non-typeable Haemophilus influenzae (NTHi) prevents exacerbations of chronic obstructive pulmonary disease, but the mechanism is unclear. The aim of this study was to determine the mechanism of protection. This was a placebo versus active prospective study over 3 months in 64 smokers. The active treatment was three courses of oral NTHi given at monthly intervals, followed by measurement of bacteriological and immunological parameters. The results can be summarized: (i) NTHi-specific T cells increased in the placebo treatment group over time (P<0.05); (ii) the T cell response in the oral NTHi group started earlier than that in the placebo group (P<0.05); and (iii) serum NTHi-specific immunoglobulin (Ig)G had significantly greater variation in the placebo group (P<0.0001). The increase in antibody in placebos over time correlated with exposure to live H. influenzae (P<0.05) determined from culture of gargles; (iv) reduction in saliva lysozyme over time (P<0.05) was detected only in the oral NTHi treatment group. These data are consistent with T cell priming of gut lymphoid tissue by aspiration of bronchus content into the gut, with oral immunotherapy augmenting this process leading to enhanced bronchus protection. The evidence for protection was a stable IgG antibody level through the study in the oral NTHi treatment group, contrasting with an increase in antibody correlating with exposure of the airways to H. influenzae in the placebo group. Saliva lysozyme was a useful biomarker of mucosal inflammation, falling after oral NTHi consistent with a reduction in the level of intralumenal inflammation.
authors.affiliation: School of Biomedical Sciences, Faculty of Health, University of Newcastle, Immunology, Hunter Area Pathology Service, HNEHS, John Hunter Hospital, Newcastle, NSW, Australia. robert.clancy@newcastle.edu.au
authors.forename: R L
authors.initials: RL
authors.lastname: Clancy
authors.forename: M L
authors.initials: ML
authors.lastname: Dunkley
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood*; D001991:Bronchitis / Q000276:immunology / Q000517:prevention & control*; D002352:Carrier Proteins / Q000032:analysis; D018450:Disease Progression; D005260:Female; D018073:Haemophilus Vaccines / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D006193:Haemophilus influenzae / Q000145:classification / Q000276:immunology*; D006801:Humans; D018928:Immunity, Mucosal; D007074:Immunoglobulin G / Q000097:blood*; D007371:Interferon-gamma / Q000032:analysis; D007781:Lactoferrin; D008297:Male; D008875:Middle Aged; D009113:Muramidase / Q000032:analysis; D009569:Nitric Oxide / Q000032:analysis; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000503:physiopathology / Q000628:therapy*; D012463:Saliva / Q000201:enzymology / Q000276:immunology; D012907:Smoking / Q000009:adverse effects; D013183:Sputum / Q000276:immunology / Q000382:microbiology; D013601:T-Lymphocytes / Q000276:immunology; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D002352:Carrier Proteins; D018073:Haemophilus Vaccines; D007074:Immunoglobulin G; C490098:LTF protein, human; D015164:Vaccines, Inactivated; D009569:Nitric Oxide; D007371:Interferon-gamma; D009113:Muramidase; D007781:Lactoferrin
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