Evidence for a causal relationship between respiratory syncytial virus infection and asthma

Rationale: Risk of subsequent asthma-like symptoms after early-life lower respiratory illness (LRI) caused by respiratory syncytial virus (RSV) is increased during the first decade of childhood and diminished thereafter by adolescence.Objectives: To determine the relation of early-life RSV-LRI on adult asthma-like symptoms and its interactive role with adult smoking.Methods: A total of 1,246 nonselected infants were enrolled at birth and prospectively followed. Virologically confirmed RSV-LRIs were assessed during the first 3 years of life. At age 22, 24, 26, and 29 years, current asthma and smoking behavior were evaluated by questionnaire. Peak flow variability was assessed at age 26 and expressed as amplitude % mean. A longitudinal analysis was used to investigate the relation of RSV-LRI and active smoking to adult outcomes.Measurements and Main Results: Neither RSV-LRI nor active smoking were directly associated with increased current adult asthma or peak flow variability. However, there was a significant interaction between RSV-LRI and active smoking in relation to current asthma (P for interaction = 0.004) and peak flow variability (P for interaction = 0.04). Among subjects with early RSV-LRI, those who actively smoked were 1.7 times more likely to have current asthma (95% confidence interval, 1.2-2.3; P = 0.003) and had greater amplitude % mean (10.0% vs. 6.4%; P = 0.02) than nonsmokers. Among subjects without early RSV-LRI, there was no difference in asthma risk or peak flow variability between active smokers and nonsmokers.Conclusions: Smoking is associated with increased risk of having asthma in young adults who had RSV-LRI in early life but not among subjects without these illnesses.

Section: Discussionmentioning

confidence: 88%

Risk of Current Asthma among Adult Smokers with Respiratory Syncytial Virus Illnesses in Early Life

Voraphani

Stern

Wright

et al. 2014

“…We and others have previously compiled the genes that have been demonstrated to be associated with RSV and asthma. Among these are polymorphisms in a number of immune response genes, suggesting immune perturbations common to both diseases : CX3CR1, TLR-4, SP-A, SP-D, IL-10, CCR5, TLR-10, IL-4, IL-13, IL-10, IL-8, IL-18, tumor necrosis factor, TLR-4, MS4A2, VDR, IL-4Ra, RANTES, TGF-b1, and ADAM33 (14,15). In addition, a recent clinical multicenter cohort study found that human IL1RL1 gene variants and nasopharyngeal IL1RL1-a levels were associated with severe RSV bronchiolitis.…”

Section: Host Genetic and Familial Determinants Linking Infant Rsv Anmentioning

confidence: 99%

“…The GA3 clade has been associated with greater severity of illness compared with clades GA2 and GA4 (41). Differential pathogenesis of RSV A subgroup strains has been reported in an animal model of infection of BALB/cJ mice with RSV A2001/2-20 (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). A subgroup strain resulted in greater disease severity, higher lung IL-13 levels, and higher lung gob-5 levels and induced airway mucin expression, supporting differential pathogenicity dependent on strain in these genetically identical mice (42).…”

Section: Viral Strain Determinants Of Infant Infection Severity and Amentioning

confidence: 99%

Toward Primary Prevention of Asthma. Reviewing the Evidence for Early-Life Respiratory Viral Infections as Modifiable Risk Factors to Prevent Childhood Asthma

Feldman

Moore

et al. 2015

171

172

A first step in primary disease prevention is identifying common, modifiable risk factors that contribute to a significant proportion of disease development. Infant respiratory viral infection and childhood asthma are the most common acute and chronic diseases of childhood, respectively. Common clinical features and links between these diseases have long been recognized, with early-life respiratory syncytial virus (RSV) and rhinovirus (RV) lower respiratory tract infections (LRTIs) being strongly associated with increased asthma risk. However, there has long been debate over the role of these respiratory viruses in asthma inception. In this article, we systematically review the evidence linking early-life RSV and RV LRTIs with asthma inception and whether they could therefore be targets for primary prevention efforts.

“…In addition to genetic factors, however, it is clear that early-life exposure to pathogens such as respiratory syncytial virus can contribute to the development of asthma (10,11). A variety of other airborne exposures can exacerbate asthma, such as house dust mite (HDM), cigarette smoke, and fungal species (12).…”

mentioning

confidence: 99%

A Novel CD4⁺ T Cell–Dependent Murine Model of Pneumocystis-driven Asthma-like Pathology

Eddens

Campfield

Serody

et al. 2016

Rationale: Infection with Pneumocystis, an opportunistic fungal pathogen, can result in fulminant pneumonia in the clinical setting of patients with immunosuppression. In murine models, Pneumocystis has previously been shown to induce a CD4 1 T cell-dependent eosinophilic response in the lung capable of providing protection.Objectives: We sought to explore the role of Pneumocystis in generating asthma-like lung pathology, given the natural eosinophilic response to infection.Methods: Pneumocystis infection or antigen treatment was used to induce asthma-like pathology in wild-type mice. The roles of CD4 1 T cells and eosinophils were examined using antibody depletion and knockout mice, respectively. The presence of anti-Pneumocystis antibodies in human serum samples was detected by ELISA and Western blotting.Measurements and Main Results: Pneumocystis infection generates a strong type II response in the lung that requires CD4 1 T cells. Pneumocystis infection was capable of priming a Th2 response similar to that of a commonly studied airway allergen, the house dust mite. Pneumocystis antigen treatment was also capable of inducing allergic inflammation in the lung, resulting in anti-Pneumocystis IgE production, goblet cell hyperplasia, and increased airway resistance. In the human population, patients with severe asthma had increased levels of anti-Pneumocystis IgG and IgE compared with healthy control subjects. Patients with severe asthma with elevated antiPneumocystis IgG levels had worsened symptom scores and lung parameters such as decreased forced expiratory volume and increased residual volume compared with patients with severe asthma who had low anti-Pneumocystis IgG.Conclusions: The present study demonstrates for the first time, to our knowledge, that Pneumocystis is an airway allergen capable of inducing asthma-like lung pathology.