Viruses and bacteria in acute asthma exacerbations - A GA 2LEN-DARE* systematic review

Allergy Department, 2nd Pediatric Clinic, National and Kapodistrian University, Athens, Greece.
Allergy (Impact Factor: 6.03). 11/2010; 66(4):458-68. DOI: 10.1111/j.1398-9995.2010.02505.x
Source: PubMed


A major part of the burden of asthma is caused by acute exacerbations. Exacerbations have been strongly and consistently associated with respiratory infections. Respiratory viruses and bacteria are therefore possible treatment targets. To have a reasonable estimate of the burden of disease induced by such infectious agents on asthmatic patients, it is necessary to understand their nature and be able to identify them in clinical samples by employing accurate and sensitive methodologies. This systematic review summarizes current knowledge and developments in infection epidemiology of acute asthma in children and adults, describing the known impact for each individual agent and highlighting knowledge gaps. Among infectious agents, human rhinoviruses are the most prevalent in regard to asthma exacerbations. The newly identified type-C rhinoviruses may prove to be particularly relevant. Respiratory syncytial virus and metapneumovirus are important in infants, while influenza viruses seem to induce severe exacerbations mostly in adults. Other agents are relatively less or not clearly associated. Mycoplasma and Chlamydophila pneumoniae seem to be involved more with asthma persistence rather than with disease exacerbations. Recent data suggest that common bacteria may also be involved, but this should be confirmed. Although current information is considerable, improvements in detection methodologies, as well as the wide variation in respect to location, time and populations, underline the need for additional studies that should also take into account interacting factors.

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Available from: Ioannis Christodoulou
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    • "It is a well-established clinical phenomenon that viral and bacterial infections are primary risk factors for acute asthma exacerbations [1], [2]. Viral infections, such as respiratory syncytial virus (RSV) and human rhinovirus (HRV), are the most predominant forms of asthma exacerbation, believed to cause almost 50% of exacerbations in adults [3]. "
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    ABSTRACT: It is well-established that bacterial and viral infections have an exacerbating effect on allergic asthma, particularly aggravating respiratory symptoms, such as airway hyperresponsiveness (AHR). The mechanism by which these infections alter AHR is unclear, but some studies suggest that Toll-like receptors (TLRs) play a role. In this study, we investigated the impact of TLR3 and TLR4 ligands on AHR and airway inflammation in a model of pre-established allergic inflammation. Female BALB/c mice were sensitised and challenged intranasally (i.n.) with either PBS or ovalbumin (OVA) and subsequently i.n. challenged with poly (I:C) (TLR3) or LPS (TLR4) for four consecutive days. The response to methacholine was measured in vivo; cellular and inflammatory mediators were measured in blood, lung tissue and broncheoalveolar lavage fluid (BALF). OVA challenge resulted in an increase in AHR to methacholine, as well as increased airway eosinophilia and TH2 cytokine production. Subsequent challenge with TLR agonists resulted in a significant increase in AHR, but decreased TLR-specific cellular inflammation and production of immune mediators. Particularly evident was a decline in LPS-induced neutrophilia and neutrophil-associated cytokines following LPS and poly (I:C) treatment. The present data indicates that TLRs may play a pivotal role in AHR in response to microbial infection in allergic lung inflammation. These data also demonstrate that aggravated AHR occurs in the absence of an exacerbation in airway inflammation and that allergic inflammation impedes a subsequent inflammatory response to TLRs. These results may parallel clinical signs of microbial asthma exacerbation, including an extended duration of illness and increased respiratory symptoms.
    Full-text · Article · Aug 2014 · PLoS ONE
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    • "A long-term impairment of lung function and structure after chlamydial infection was also shown for naturally Chlamydia-infected calves [15] and experimentally challenged mice [52]. In human medicine, asthma is a common chronic inflammatory disease of the airways, and the involvement of C. pneumoniae in asthma pathogenesis is still largely discussed [53,54]. "
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    ABSTRACT: Backround Chlamydia psittaci (Cp) is a respiratory pathogen capable of inducing acute pulmonary zoonotic disease (psittacosis) or persistent infection. To elucidate the pathogenesis of this infection, a translational large animal model was recently introduced by our group. This study aimed at quantifying and differentiating pulmonary dysfunction and acid base imbalances induced by Cp. Forty two calves were grouped in (i) animals inoculated with Cp (n = 21) and (ii) controls sham-inoculated with uninfected cell culture (n = 21). For pulmonary function testing, impulse oscillometry, capnography, and measurement of FRC (functional residual capacity) were applied to spontaneously breathing animals. Variables of acid base status were assessed in venous blood and using both (i) traditional Henderson-Hasselbalch and (ii) strong ion approach. Both obstructive and restrictive pulmonary disorders were induced in calves experimentally inoculated with Cp. While disorders in respiratory mechanics lasted for 8 to 11 days, the pattern of spontaneous breathing was mainly altered in the period of acute illness (until 4 days post inoculation, dpi). Expiration was more impaired than inspiration, resulting in elevated FRC. Ventilation was characterised by a reduction in tidal volume ( 25 %) combined with an increased percentage of dead space volume and a significant reduction of alveolar volume by 10 %. Minute ventilation increased significantly (+50 %) due to a compensatory doubling of respiratory rate. Hyperventilatory hypocapnia at 2 - 3 dpi resulted in slightly increased blood pH at 2 dpi. However, the acid base equilibrium was additionally influenced by metabolic components, i.e. the systemic inflammatory response, all of which were detected with help of the strong ion theory. Decreased concentrations of albumin (2 to 10 dpi), a negative acute phase marker, resulted in a decrease of the sum of non volatile weak acids (Atot), revealing an alkalotic effect. This was counterbalanced by acidic effects of decreased strong ion difference (SID), mediated by the interplay between hypochloraemia (alkalotic effect) and hyponatriaemia (acidic effect). This bovine model was found to be suitable for studying pathophysiology of respiratory Cp infection and may help elucidating functional host-pathogen interactions in the mammalian lung.
    Full-text · Article · Feb 2014 · Multidisciplinary respiratory medicine
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    • "Links between viruses and allergy are clinically well documented. It is clear that viral infections induce asthma/allergic exacerbations [11], [12] and viral clearance and symptoms are prolonged in allergic individuals [13]. Additionally, Rochlitzer and colleagues have recently demonstrated that chronic allergic inflammation may impair anti-viral response to acute rhinovirus infection as indicated by suppressed induction of IFN-α, IFN-γ, and IL-12 [14]. "
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    ABSTRACT: Airway epithelium is widely considered to play an active role in immune responses through its ability to detect changes in the environment and to generate a microenvironment for immune competent cells. Therefore, besides its role as a physical barrier, epithelium affects the outcome of the immune response by the production of various pro-inflammatory mediators. We stimulated airway epithelial cells with viral double stranded RNA analogue poly(I:C) or with house dust mite in a time course of 24 hours. In order to determine cytokines production by stimulated cells, we performed multiplex enzyme linked immunosorbant assay (ELISA). We demonstrate that the temporal pattern of the genes that respond to virus exposure in airway epithelium resembles to a significant degree their pattern of response to HDM. The gene expression pattern of EGR1, DUSP1, FOSL1, JUN, MYC, and IL6 is rather similar after viral (poly(I:C)) and HDM exposure. However, both triggers also induce a specific response (e.g. ATF3, FOS, and NFKB1). We confirmed these data by showing that epithelial cells produce a variety of similar mediators in response to both poly(I:C) and HDM challenge (IL1-RA, IL-17, IFN-α and MIP1-α), sometimes with a quantitative difference in response (IL2-R, IL-6, IL-8, MCP-1, MIG, and HGF). Interestingly, only four mediators (IL-12, IP-10, RANTES and VEGF) where up-regulated specifically by poly(I:C) and not by HDM. Additionally, we report that pre-exposure to HDM deregulates production of cytokines and mediators in response to poly(I:C). Epithelial cells responses to the HDM-allergen and a virus strongly resemble both in gene expression and in protein level explaining why these two responses may affect each other.
    Full-text · Article · Feb 2014 · PLoS ONE
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