title: Relationships between Mucosal Antibodies, Non-Typeable Haemophilus influenzae (NTHi) Infection and Airway Inflammation in COPD.
abstract: Non-typeable Haemophilus influenzae (NTHi) is a key pathogen in COPD, being associated with airway inflammation and risk of exacerbation. Why some patients are susceptible to colonisation is not understood. We hypothesised that this susceptibility may be due to a deficiency in mucosal humoral immunity. The aim of our study (NCT01701869) was to quantify the amount and specificity of antibodies against NTHi in the lungs and the associated risk of infection and inflammation in health and COPD. Phlebotomy, sputum induction and bronchoscopy were performed on 24 mild-to-moderate COPD patients and 8 age and smoking-matched controls. BAL (Bronchoalveolar lavage) total IgG1, IgG2, IgG3, IgM and IgA concentrations were significantly increased in COPD patients compared to controls. NTHi was detected in the lungs of 7 of the COPD patients (NTHi+ve-29%) and these patients had a higher median number of previous exacerbations than NTHi-ve patients as well as evidence of increased systemic inflammation. When comparing NTHi+ve versus NTHi-ve patients we observed a decrease in the amount of both total IgG1 (p = 0.0068) and NTHi-specific IgG1 (p = 0.0433) in the BAL of NTHi+ve patients, but no differences in total IgA or IgM. We observed no evidence of decreased IgG1 in the serum of NTHi+ve patients, suggesting this phenomenon is restricted to the airway. Furthermore, the NTHi+ve patients had significantly greater levels of IL-1β (p = 0.0003), in BAL than NTHi-ve COPD patients.This study indicates that the presence of NTHi is associated with reduced levels and function of IgG1 in the airway of NTHi-colonised COPD patients. This decrease in total and NTHI-specific IgG1 was associated with greater systemic and airway inflammation and a history of more frequent exacerbations and may explain the susceptibility of some COPD patients to the impacts of NTHi.
authors.affiliation: Clinical & Experimental Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Tremona Road, Southampton, United Kingdom.|Wessex Investigational Sciences Hub, University of Southampton Faculty of Medicine, Southampton General Hospital, Tremona Road, Southampton, United Kingdom.
authors.forename: Karl J
authors.identifier: http://orcid.org/0000-0003-3844-6457
authors.initials: KJ
authors.lastname: Staples
authors.affiliation: Public Health England, Porton Down, Salisbury, United Kingdom.
authors.forename: Stephen
authors.initials: S
authors.lastname: Taylor
authors.affiliation: Public Health England, Porton Down, Salisbury, United Kingdom.
authors.forename: Steve
authors.initials: S
authors.lastname: Thomas
authors.affiliation: Public Health England, Porton Down, Salisbury, United Kingdom.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Leung
authors.affiliation: Clinical & Experimental Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Tremona Road, Southampton, United Kingdom.
authors.forename: Karen
authors.initials: K
authors.lastname: Cox
authors.affiliation: GSK Vaccines, Wavre, Belgium.
authors.forename: Thierry G
authors.initials: TG
authors.lastname: Pascal
authors.affiliation: Southampton NIHR Respiratory Biomedical Research Unit, Southampton General Hospital, Tremona Road, Southampton, United Kingdom.
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Ostridge
authors.affiliation: Southampton NIHR Respiratory Biomedical Research Unit, Southampton General Hospital, Tremona Road, Southampton, United Kingdom.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Welch
authors.affiliation: Clinical & Experimental Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Tremona Road, Southampton, United Kingdom.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Tuck
authors.affiliation: Clinical & Experimental Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Tremona Road, Southampton, United Kingdom.|Wessex Investigational Sciences Hub, University of Southampton Faculty of Medicine, Southampton General Hospital, Tremona Road, Southampton, United Kingdom.|Southampton NIHR Respiratory Biomedical Research Unit, Southampton General Hospital, Tremona Road, Southampton, United Kingdom.
authors.forename: Stuart C
authors.initials: SC
authors.lastname: Clarke
authors.affiliation: Public Health England, Porton Down, Salisbury, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Gorringe
authors.affiliation: Clinical & Experimental Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Tremona Road, Southampton, United Kingdom.|Wessex Investigational Sciences Hub, University of Southampton Faculty of Medicine, Southampton General Hospital, Tremona Road, Southampton, United Kingdom.|Southampton NIHR Respiratory Biomedical Research Unit, Southampton General Hospital, Tremona Road, Southampton, United Kingdom.
authors.forename: Tom M A
authors.initials: TM
authors.lastname: Wilkinson
mesh_terms: D000368:Aged; D000907:Antibodies, Bacterial / Q000276:immunology / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016022:Case-Control Studies; D016207:Cytokines / Q000032:analysis; D004269:DNA, Bacterial / Q000302:isolation & purification / Q000378:metabolism; D005260:Female; D006192:Haemophilus Infections / Q000150:complications* / Q000382:microbiology; D006193:Haemophilus influenzae / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology / Q000378:metabolism; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007249:Inflammation / Q000209:etiology*; D053583:Interleukin-1beta / Q000032:analysis; D008168:Lung / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000276:immunology / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D012720:Severity of Illness Index; D012907:Smoking; D013183:Sputum / Q000382:microbiology
chemical_list: D000907:Antibodies, Bacterial; D016207:Cytokines; D004269:DNA, Bacterial; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D053583:Interleukin-1beta