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.

Macrophages and neutrophils: dynamic duo or partners in crime?

“…Severe infections are often associated with chronic lung diseases, like severe asthma and chronic obstructive pulmonary disease (COPD), both of which are not only associated with neutrophilia and increased LL-3716 17 but also a dysbiosis of the lung microbiome,18 with increased abundance of Proteobacteria spp and non-typeable Haemophilus influenzae (NTHi) in particular. IL-1β is already increased in the lungs of patients with COPD who are colonised with NTHi,19 and compellingly in a longitudinal cohort of patients with COPD, we observed that NTHi colonisation increased the risk of a viral infection being associated with an exacerbation compared with the presence of virus alone 20. NTHi is also frequently detected in the sputum of hospitalised patients with pneumonia 21.…”

Primary immune deficiency diseases as unrecognized causes of chronic respiratory disease

“…At the level of the target tissue, it seems intuitive that specific antibodies are an important contributor to local host defense and that their absence might contribute to chronic infection. A study of specific antibodies against non-typeable Haemophilus influenzae in COPD patients with frequent exacerbations and positive cultures for this organism showed decreased total IgG (p = 0.0068) and specific antibodies in bronchoalveolar lavage (p = 0.043) [45]. However, we do not know how often antibody deficiency contributes to COPD in clinical practice.…”

The role of Th1/Th2 cytokines played in regulation of specific CD4 + Th1 cell conversion and activation during inflammatory reaction of chronic obstructive pulmonary disease

“…Respiratory infections are associated with the majority of COPD exacerbations and their severity, especially for those with viral/bacterial coinfection . In the AECOPD patients' airway, a large number of pathogen‐specific antibodies can be found, indicating the activity of immune reaction . Because of the immune response, the level of Th1 was reduced, but the level of Th2 occupied dominant position in delayed allergy.…”

“…16 In the AECOPD patients' airway, a large number of pathogen-specific antibodies can be found, indicating the activity of immune reaction. 17 Because of the immune response, the level of Th1 was reduced, but the level of Th2 occupied dominant position in delayed allergy. Oppositely, the level of Th2 cells in remission was decreased because of the treatment, while Th1 cells were increased in cellular immunity.…”