Cargando…

An Oral Whole-Cell Killed Nontypeable Haemophilus influenzae Immunotherapeutic For The Prevention Of Acute Exacerbations Of Chronic Airway Disease

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 wer...

Descripción completa

Detalles Bibliográficos
Autores principales: Clancy, Robert L, Cripps, Allan W
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821045/
https://www.ncbi.nlm.nih.gov/pubmed/31695359
http://dx.doi.org/10.2147/COPD.S217317
_version_ 1783464074800005120
author Clancy, Robert L
Cripps, Allan W
author_facet Clancy, Robert L
Cripps, Allan W
author_sort Clancy, Robert L
collection PubMed
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.
format Online
Article
Text
id pubmed-6821045
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Dove
record_format MEDLINE/PubMed
spelling pubmed-68210452019-11-06 An Oral Whole-Cell Killed Nontypeable Haemophilus influenzae Immunotherapeutic For The Prevention Of Acute Exacerbations Of Chronic Airway Disease Clancy, Robert L Cripps, Allan W Int J Chron Obstruct Pulmon Dis Review 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. Dove 2019-10-25 /pmc/articles/PMC6821045/ /pubmed/31695359 http://dx.doi.org/10.2147/COPD.S217317 Text en © 2019 Clancy and Cripps. http://creativecommons.org/licenses/by-nc/3.0/ 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 (http://creativecommons.org/licenses/by-nc/3.0/). 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 (https://www.dovepress.com/terms.php).
spellingShingle Review
Clancy, Robert L
Cripps, Allan W
An Oral Whole-Cell Killed Nontypeable Haemophilus influenzae Immunotherapeutic For The Prevention Of Acute Exacerbations Of Chronic Airway Disease
title An Oral Whole-Cell Killed Nontypeable Haemophilus influenzae Immunotherapeutic For The Prevention Of Acute Exacerbations Of Chronic Airway Disease
title_full An Oral Whole-Cell Killed Nontypeable Haemophilus influenzae Immunotherapeutic For The Prevention Of Acute Exacerbations Of Chronic Airway Disease
title_fullStr An Oral Whole-Cell Killed Nontypeable Haemophilus influenzae Immunotherapeutic For The Prevention Of Acute Exacerbations Of Chronic Airway Disease
title_full_unstemmed An Oral Whole-Cell Killed Nontypeable Haemophilus influenzae Immunotherapeutic For The Prevention Of Acute Exacerbations Of Chronic Airway Disease
title_short An Oral Whole-Cell Killed Nontypeable Haemophilus influenzae Immunotherapeutic For The Prevention Of Acute Exacerbations Of Chronic Airway Disease
title_sort oral whole-cell killed nontypeable haemophilus influenzae immunotherapeutic for the prevention of acute exacerbations of chronic airway disease
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821045/
https://www.ncbi.nlm.nih.gov/pubmed/31695359
http://dx.doi.org/10.2147/COPD.S217317
work_keys_str_mv AT clancyrobertl anoralwholecellkillednontypeablehaemophilusinfluenzaeimmunotherapeuticforthepreventionofacuteexacerbationsofchronicairwaydisease
AT crippsallanw anoralwholecellkillednontypeablehaemophilusinfluenzaeimmunotherapeuticforthepreventionofacuteexacerbationsofchronicairwaydisease
AT clancyrobertl oralwholecellkillednontypeablehaemophilusinfluenzaeimmunotherapeuticforthepreventionofacuteexacerbationsofchronicairwaydisease
AT crippsallanw oralwholecellkillednontypeablehaemophilusinfluenzaeimmunotherapeuticforthepreventionofacuteexacerbationsofchronicairwaydisease