Dear editor
Acute exacerbations of COPD (AECOPD) are markers of disease progression and severity, andfrequently are used as an outcome variable in interventional studies.Citation1 AECOPD results in increased severity of symptoms andinduces disease progression with accelerated decline in lung function and decreased qualityof life. The risk of morbidity and mortality is also significantly increased. Most AECOPD(~85%) have an infectious etiology, induced by bacteria and viruses, often rhinovirus(~50%).Citation1
The paper by Johnston et alCitation2 againemphasized the importance of the common cold and rhinoviruses in AECOPD. They found thatcold-like symptoms are a reliable predictor of exacerbations in patients with COPD,occurring in over 80%, although actual viral detection occurred in less than half of these.Notably, the group with virus positivity exhibited more severe symptoms than other groups.They emphasized the need to better understand the relationship between rhinovirus andCOPD.
Approximately 60% of human rhinoviruses serotypes adhere to the intercellular adhesionmolecule-1 (ICAM-1). Recently, we showed that airway epithelial ICAM-1 expression isupregulated throughout the respiratory tract in smokers, and is further increased insubjects with chronic airflow obstruction (including frank COPD), even when mild.Interestingly, ICAM-1 expression in goblet cells and submucosal glands in the airway wallwas also markedly increased. Furthermore, cultured bronchial epithelial cells exposed tocigarette smoke extract exhibited significantly increased levels of ICAM-1, both at mRNAand protein levels.Citation3 We suggest thatsuch changes in pathogen adhesion sites may explain the increased vulnerability of COPDpatients to virally induced exacerbations, which is otherwise essentially unexplained.
The issue of the potential importance of the upregulation of respiratory epithelialadhesion sites as a cause of certain specific bacteria and viruses being able to gain aserendipitous special niche in the airways in COPD needs much more attention, as it mayopen a potentially new nonantibiotic mode of prevention and treatment.Citation4Haemophilus influenzae and Streptococcus pneumoniae areprominent in respiratory tract infection in smokers/COPD and are also associated withexacerbations. This may well relate to hyper-upregulation of their co-opted major airwayepithelial adhesion molecule, the platelet-activating factor receptor. Platelet-activatingfactor receptor blockers were developed over 20 years ago for the anti-inflammatorytreatment of asthma, and proved safe but ineffective; they should now be trialed for thisdifferent indication.Citation5
Moreover, the data provided by Johnston et alCitation2 suggest that an anti-ICAM-1 molecule given at an early stage of a common coldin frequent exacerbations of COPD could potentially have a prophylactic effect againstthese devastating and expensive events.
Disclosure
The authors report no conflicts of interest in this communication.
References
- KuraiDSarayaTIshiiHTakizawaHVirus-induced exacerbations in asthma andCOPDFrontMicrobiol2013411223346082
- JohnstonNWOlssonMEdsbäckerSColds as predictors of the onset and severity of COPDexacerbationsInt J Chron Obstruct PulmonDis20171283984828331305
- ShuklaSDMahmoodMQWestonSThe main rhinovirus respiratory tract adhesion site(ICAM-1) is upregulated in smokers and patients with chronic airflow limitation(CAL)RespirRes201718611028049526
- O’TooleRFShuklaSDWaltersEHDoes upregulated host cell receptor expression providea link between bacterial adhesion and chronic respiratorydisease?J TranslMed201614130427782846
- ShuklaSDSohalSSO’TooleRFEapenMSWaltersEHPlatelet activating factor receptor: gateway forbacterial chronic airway infection in chronic obstructive pulmonary disease andpotential therapeutic targetExpert Rev RespirMed20159447348526207607