- Title
- An oral whole-cell killed nontypeable haemophilus influenzae immunotherapeutic for the prevention of acute exacerbations of chronic airway disease
- Creator
- Clancy, Robert L.; Cripps, Allan W.
- Relation
- International Journal of Chronic Obstructive Pulonary Disease Vol. 14, p. 2423-2431
- Publisher Link
- http://dx.doi.org/10.2147/COPD.S217317
- Publisher
- Dove Medical Press
- Resource Type
- journal article
- Date
- 2019
- Description
- In subjects with chronic bronchitis, protection against acute bronchitis following oral administration of a whole-cell killed nontypeable Haemophilus influenzae (NTHi) preparation was demonstrated in the mid-1980s. Subsequently, studies aiming to validate clinical efficacy of this oral treatment were complicated by a number of factors, including the modification of clinical definitions, the implications of which were not recognized at that time. The objective of this review is to integrate our pre-clinical and clinical research in this field conducted over the past 30 years to demonstrate the evolution of the idea of communication between mucosal surfaces through the common mucosal immune system and the development of an effective oral NTHi immunotherapy. Our earliest studies recruited subjects with chronic sputum production and high levels of culture-positive sputum for Gram-negative bacteria but by 2000, the clinical diagnostic focus had switched from "chronic bronchitis" to "chronic obstructive pulmonary disease" (COPD), which was functionally defined using spirometry. This change led to variable clinical trial results, confirming the importance of chronic sputum production and culture-positive sputum. Additional conditioning factors such as patient age and gender were influential in study populations with low culture-positive sputum production. Through this period, studies in human and in rodent models provided new insights into airway protection mechanisms and the pathogenesis of airway inflammation. Key findings were the importance of a dysbiosis within the airway microbiome, and the critical role of an interdependence between the bronchus and the gut, with a Peyer's patch-dependent extra-bronchus "loop" controlling the composition of the bronchus microbiome. Within this context, intercurrent virus infections initiate a microbiome-dependant hypersensitivity reaction involving Peyer's patch-derived Th17 cells. We conclude that whole-cell killed NTHi immunotherapy has consistent and significant benefits when examined in the context of changing clinical disease definitions, age and gender, and has the potential to change the natural history of chronic airway disease.
- Subject
- lung infection; airway inflammation; oral immunotherapy; lung immunity; nontypeable Haemophilus influenzae; COPD; chronic obstructive pulmonary disease
- Identifier
- http://hdl.handle.net/1959.13/1413622
- Identifier
- uon:36651
- Identifier
- ISSN:1176-9106
- Rights
- This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.
- Language
- eng
- Full Text
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