Respiratory syncytial virus prevention and asthma in healthy preterm infants: a randomised controlled trial

Scheltema, Nienke M.; Nibbelke, Elisabeth E.; Pouw, Juliëtte N; Blanken, Maarten O; Rovers, Maroeska M.; Naaktgeboren, Christiana A.; Mazur, Natalie I; Wildenbeest, Joanne G; Ent, Cornelis K. van der; Bont, Louis

doi:10.1016/s2213-2600(18)30055-9

Cited by 132 publications

(78 citation statements)

References 36 publications

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“…Two recent randomized controlled trials showed that in preterm infants, palivizumab, an anti-RSV monoclonal antibody, decreased the parent-reported recurrent wheeze, but similar incidence of physician-diagnosed asthma at age 6 years was found. 82,83 Long-term effects of RSV prophylaxis appear less likely in infants with atopic family history. 60 These results clearly indicate that RSV-infection is not causal to the asthma or atopy development.…”

Section: Long-term Sequelamentioning

confidence: 99%

“…RSV immunoprophylaxis with palivizumab has also been shown to reduce recurrent wheezing (see section 7 and 8). 60,70,82,83 In the development of RV vaccine, promising results have been seen with a cross-reactive recombinant capsid protein in a mouse model. 14 Non-specific antiviral approaches to reduce asthma include strategies aiming at enhancing the patient's resistance to multiple respiratory viruses through the administration of interferons or other immunostimulatory molecules.…”

Section: Prevention Strategies Of Asthmamentioning

confidence: 99%

See 1 more Smart Citation

Bronchiolitis needs a revisit: Distinguishing between virus entities and their treatments

Jartti

Smits

Bønnelykke

et al. 2018

Allergy

113

181

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Current data indicate that the “bronchiolitis” diagnosis comprises more than one condition. Clinically, pathophysiologically, and even genetically three main clusters of patients can be identified among children suffering from severe bronchiolitis (or first wheezing episode): (a) respiratory syncytial virus (RSV)‐induced bronchiolitis, characterized by young age of the patient, mechanical obstruction of the airways due to mucus and cell debris, and increased risk of recurrent wheezing. For this illness, an effective prophylactic RSV‐specific monoclonal antibody is available; (b) rhinovirus‐induced wheezing, associated with atopic predisposition of the patient and high risk of subsequent asthma development, which may, however, be reversed with systemic corticosteroids in those with severe illness; and (c) wheeze due to other viruses, characteristically likely to be less frequent and severe. Clinically, it is important to distinguish between these partially overlapping patient groups as they are likely to respond to different treatments. It appears that the first episode of severe bronchiolitis in under 2‐year‐old children is a critical event and an important opportunity for designing secondary prevention strategies for asthma. As data have shown bronchiolitis cannot simply be diagnosed using a certain cutoff age, but instead, as we suggest, using the viral etiology as the differentiating factor.

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Section: Long-term Sequelamentioning

confidence: 99%

Section: Prevention Strategies Of Asthmamentioning

confidence: 99%

Bronchiolitis needs a revisit: Distinguishing between virus entities and their treatments

Jartti

Smits

Bønnelykke

et al. 2018

Allergy

113

181

View full text Add to dashboard Cite

show abstract

“…Subsequently, two prospective studies with RSV immunoprophylaxis have been performed to address the potential causality between RSV infection and subsequent asthma. In these recent randomized controlled trials, pre-term infants who received palivizumab demonstrated a decreased number of recurrent wheezing episodes, but the incidence of physician-diagnosed asthma at age 6 remained intact [74,75]. These effects, however, were less noticeable in infants with atopic family history, indicating that RSV infection is not causal to asthma or atopy development.…”

Section: Long-term Sequelamentioning

confidence: 99%

Role of viruses in asthma

et al. 2020

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Respiratory viral infections are the most important triggers of asthma exacerbations. Rhinovirus (RV), the common cold virus, is clearly the most prevalent pathogen constantly circulating in the community. This virus also stands out from other viral factors due to its large diversity (about 170 genotypes), very effective replication, a tendency to create Th2-biased inflammatory environment and association with specific risk genes in people predisposed to asthma development (CDHR3). Decreased interferon responses, disrupted airway epithelial barrier, environmental exposures (including biased airway microbiome), and nutritional deficiencies (low in vitamin D and fish oil) increase risk to RV and other virus infections. It is intensively debated whether viral illnesses actually cause asthma. Respiratory syncytial virus (RSV) is the leading causative agent of bronchiolitis, whereas RV starts to dominate after 1 year of age. Breathing difficulty induced by either of these viruses is associated with later asthma, but the risk is higher for those who suffer from severe RV-induced wheezing. The asthma development associated with these viruses has unique mechanisms, but in general, RV is a risk factor for later atopic asthma, whereas RSV is more likely associated with later non-atopic asthma. Treatments that inhibit inflammation (corticosteroids, omalizumab) effectively decrease RV-induced wheezing and asthma exacerbations. The anti-RSV monoclonal antibody, palivizumab, decreases the risk of severe RSV illness and subsequent recurrent wheeze. A better understanding of personal and environmental risk factors and inflammatory mechanisms leading to asthma is crucial in developing new strategies for the prevention and treatment of asthma.

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“…Respiratory syncytial virus (RSV) is a leading cause of acute, severe lower respiratory tract disease in young children with an estimated 3.2 million cases of severe lower respiratory tract illness and 48,000-74,500 in-hospital deaths in children younger than 5 years of age [1][2][3]. It is also estimated to cause 14,000 deaths each year in adults in the United States and associated with later development of reactive airway disease or asthma [4,5]. Its substantial disease burden has made RSV a priority for vaccine development for over 50 years but, unfortunately, no vaccine is yet available.…”

Section: Introductionmentioning

confidence: 99%

In vitro model for the assessment of human immune responses to subunit RSV vaccines

Chirkova

Rimawi

et al. 2020

PLoS ONE

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Respiratory syncytial virus (RSV) is the single most important cause of serious lower respiratory tract disease in infants and young children worldwide and a high priority for vaccine development. Despite over 50 years of research, however, no vaccine is yet available. One block to vaccine development is an incomplete understanding of the aberrant memory response to the formalin-inactivated RSV vaccine (FI-RSV) given to children in the 1960s. This vaccine caused enhanced respiratory disease (ERD) with later natural RSV infection. Concern that any non-live virus vaccine may also cause ERD has blocked development of subunit vaccines for young children. A number of animal FI-RSV studies suggest various immune mechanisms behind ERD. However, other than limited data from the original FI-RSV trial, there is no information on the human ERD-associated responses. An in vitro model with human blood specimens may shed light on the immune memory responses likely responsible for ERD. Memory T cell responses to an antigen are guided by the innate responses, particularly dendritic cells that present an antigen in conjunction with co-stimulatory molecules and cytokine signaling. Our in vitro model involves human monocyte derived dendritic cells (moDC) and allogenic T cell cultures to assess innate responses that direct T cell responses. Using this model, we evaluated human responses to live RSV, FI-RSV, and subunit RSV G vaccines (G-containing virus-like particles, G-VLP). Similar to findings in animal studies, FI-RSV induced prominent Th2/Th17-biased responses with deficient type-1 responses compared to live virus. Responses to G-VLPs were similar to live virus, i.e. biased towards a Th1 and not a Th2/Th17. Also mutating CX3C motif in G gave a more pronounced moDC responses associated with type-1 T cell responses. This in vitro model identifies human immune responses likely associated with ERD and provides another preclinical tool to assess the safety of RSV vaccines.

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Respiratory syncytial virus prevention and asthma in healthy preterm infants: a randomised controlled trial

Cited by 132 publications

References 36 publications

Bronchiolitis needs a revisit: Distinguishing between virus entities and their treatments

Bronchiolitis needs a revisit: Distinguishing between virus entities and their treatments

Role of viruses in asthma

In vitro model for the assessment of human immune responses to subunit RSV vaccines

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