Viruses exacerbating chronic pulmonary disease: the role of immune modulation

Singanayagam, Aran; Joshi, Priya V; Mallia, Patrick; Johnston, Sebastian L.

doi:10.1186/1741-7015-10-27

Cited by 74 publications

(78 citation statements)

References 117 publications

(123 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is an inflammatory condition caused by an abnormal response to particles and noxious gases, mainly cigarette smoke, in patients with a susceptible genetic background [2]. Episodes of worsening respiratory symptoms are termed acute exacerbations of COPD.…”

Section: Introductionmentioning

confidence: 99%

Human rhinovirus infection during naturally occurring COPD exacerbations

George

Garcha

Mackay

et al. 2014

European Respiratory Journal

152

119

View full text Add to dashboard Cite

Human rhinovirus (HRV) infection is an important trigger of exacerbations of chronic obstructive pulmonary disease (COPD) but its role in determining exacerbation frequency phenotype or the time-course of HRV infection in naturally occurring exacerbations is unknown.Sputum samples from 77 patients were analysed by real-time quantitative PCR for both HRV (388 samples), and Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis (89 samples). Patients recorded worsening of respiratory symptoms on daily diary cards, from which exacerbations were identified.HRV prevalence and load at exacerbation presentation were significantly higher than in the stable state (prevalence 53.3% versus 17.2%, respectively; p,0.001) but 0% by day 35 post-exacerbation. HRV load was higher in patients with cold symptoms (p50.046) or sore throats (p50.006) than those without. 73% of bacterium-negative but HRV-positive exacerbations were bacterium-positive by day 14. Patients with HRV detected at exacerbation had a higher exacerbation frequency (interquartile range) of 3.01 (2.02-5.30) per year compared with patients without HRV (2.51 (2.00-3.51)) (p50.038).HRV prevalence and load increased at COPD exacerbation, and resolved during recovery. Frequent exacerbators were more likely to experience HRV infection. Secondary bacterial infection is common after HRV infection, and provides a possible mechanism for exacerbation recurrence and a potential target for novel therapies. @ERSpublications Increased HRV prevalence and load are aetiological factors in natural COPD exacerbations and frequent exacerbations

show abstract

Section: Introductionmentioning

confidence: 99%

Human rhinovirus infection during naturally occurring COPD exacerbations

George

Garcha

Mackay

et al. 2014

European Respiratory Journal

152

119

View full text Add to dashboard Cite

show abstract

“…Paradoxically, despite ongoing inflammation, patients with both acute and chronic disease associated with mucous metaplasia exhibit heightened susceptibility to microbial colonization and infection of the airway. Likewise, secondary or mixed viral and bacterial infections are common complications in chronic lung diseases (11)(12)(13). The present study demonstrates that the Ets family transcription factor SPDEF, a transcriptional regulator required for airway mucous metaplasia, plays an unexpected role in suppressing innate immune signaling, suggesting a molecular mechanism that could inhibit inflammation while contributing to susceptibility to infection associated with chronic airway disease.…”

mentioning

confidence: 63%

SAM-pointed domain ETS factor mediates epithelial cell–intrinsic innate immune signaling during airway mucous metaplasia

Korfhagen

Kitzmiller

Chen

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Airway mucus plays a critical role in clearing inhaled toxins, particles, and pathogens. Diverse toxic, inflammatory, and infectious insults induce airway mucus secretion and goblet cell metaplasia to preserve airway sterility and homeostasis. However, goblet cell metaplasia, mucus hypersecretion, and airway obstruction are integral features of inflammatory lung diseases, including asthma, chronic obstructive lung disease, and cystic fibrosis, which cause an immense burden of morbidity and mortality. These chronic lung diseases are united by susceptibility to microbial colonization and recurrent airway infections. Whether these twinned phenomena (mucous metaplasia, compromised host defenses) are causally related has been unclear. Here, we demonstrate that SAM pointed domain ETS factor (SPDEF) was induced by rhinoviral infection of primary human airway cells and that cytoplasmic activities of SPDEF, a transcriptional regulator of airway goblet cell metaplasia, inhibited Toll-like receptor (TLR) activation of epithelial cells. SPDEF bound to and inhibited activities of TLR signaling adapters, MyD88 and TRIF, inhibiting MyD88-induced cytokine production and TRIF-induced interferon β production. Conditional expression of SPDEF in airway epithelial cells in vivo inhibited LPSinduced neutrophilic infiltration and bacterial clearance. SPDEFmediated inhibition of both TLR and type I interferon signaling likely protects the lung against inflammatory damage when inciting stimuli are not eradicated. Present findings provide, at least in part, a molecular explanation for increased susceptibility to infection in lung diseases associated with mucous metaplasia and a mechanism by which patients with florid mucous metaplasia may tolerate microbial burdens that are usually associated with fulminant inflammatory disease in normal hosts.airway epithelium | innate immunity

show abstract

“…В работах, проведенных в 70-80-е годы прошлого века, в которых для верификации возбудителей ОРВИ использовали серологические и клеточные культуральные тесты, РВ выявлялись в 10-20% случаев обострений ХОБЛ. В ис-следованиях, выполненных в последние 10-15 лет с применени-ем молекулярных методов определения патогенов, установлено, что вирусы присутствуют в респираторном тракте у 47-56% больных с обострением ХОБЛ [15].…”

Section: терапевтический архив 3 2015unclassified

“…В ряде исследований установ-лено угнетение продукции ИФН 1, 2 и 3-го типов у больных БА, муковисцидозом и ХОБЛ. Недостаточность выработки этих ци-токинов, с одной стороны, ведет к преобладанию зависимых от Т-хелперов 2-го типа (Тh2) иммунных реакций, а с другой сторо-ны -к дефициту врожденной противовирусной защиты и кле-точных иммунных реакций, направленных на инфицированную вирусом клетку [15,32].…”

Section: терапевтический архив 3 2015unclassified