Cytokine Response Patterns, Exposure to Viruses, and Respiratory Infections in the First Year of Life

Copenhaver, Christopher C.; Gern, James E.; Li, Zhanhai; Shult, Peter; Rosenthal, Louis A.; Mikus, Lance D.; Kirk, Carol J.; Roberg, K.A.; Anderson, Elizabeth; Tisler, C.J.; DaSilva, D.F.; Hiemke, H.; Gentile, Kevin; Gangnon, Ronald E.; Lemanske, Robert F.

doi:10.1164/rccm.200312-1647oc

Cited by 184 publications

(150 citation statements)

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“…The importance of Th1 responses in limiting viral respiratory infection is further confirmed by the inverse correlation between RVinduced IFN-␥ secretion from peripheral blood mononuclear cells (PBMCs) ex vivo and peak RV shedding after experimental RV inoculation of allergic adults (34). Closer to the heart of the argument is the finding that, in infants, a decrease in phytohemagglutinin-induced IFN-␥ secretion from cord blood mononuclear cells was associated with increased number of viral illnesses in the first year of life (35).…”

Section: Defense Against Viral Respiratory Infectionmentioning

confidence: 91%

Microbial Manipulation of Immune Function for Asthma Prevention: Inferences from Clinical Trials

Yoo

Tcheurekdjian

Lynch

et al. 2007

Proceedings of the American Thoracic Society

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The "hygiene hypothesis" proposes that the increase in allergic diseases in developing countries reflects a decrease in infections during childhood. Cohort studies suggest, however, that the risks of asthma are increased in children who suffer severe illness from a viral respiratory infection in infancy. This apparent inconsistency can be reconciled through consideration of epidemiologic, clinical, and animal studies. The elements of this line of reasoning are that viral infections can predispose to organ-specific expression of allergic sensitization, and that the severity of illness is shaped by the maturity of immune function, which in turn is influenced by previous contact with bacteria and viruses, whether pathogenic or not. Clinical studies of children and interventional studies of animals indeed suggest that the exposure to microbes through the gastrointestinal tract powerfully shapes immune function. Intestinal microbiota differ in infants who later develop allergic diseases, and feeding Lactobacillus casei to infants at risk has been shown to reduce their rate of developing eczema. This has prompted studies of feeding probiotics as a primary prevention strategy for asthma. We propose that the efficacy of this approach depends on its success in inducing maturation of immune function important in defense against viral infection, rather than on its effectiveness in preventing allergic sensitization. It follows that the endpoints of studies of feeding probiotics to infants at risk for asthma should include not simply tests of responsiveness to allergens, but also assessment of intestinal flora, immune function, and the clinical response to respiratory viral infection.Keywords: asthma; gastrointestinal; lactobacilli; microbes; prevention The purpose of this review is to sketch the rationale for a theory of asthma's pathogenesis. The proposed theory is that asthma is caused, at least in part, by infection, especially in infancy, by a respiratory virus, most likely a human rhinovirus (HRV). The development of asthma may thus be a function of the "asthmagenic" pathogenicity of the strains of RV causing asthma in infancy and of the efficacy of antiviral immune function at the time of infection. This review notes how the validity of this theory might be examined by adding additional outcomes to ongoing trials of feeding a "probiotic," like Lactobacillus casei, to infants as a primary prevention strategy for allergic disease. Space constraint does not permit more than a brief, partial review

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Section: Defense Against Viral Respiratory Infectionmentioning

confidence: 91%

Microbial Manipulation of Immune Function for Asthma Prevention: Inferences from Clinical Trials

Yoo

Tcheurekdjian

Lynch

et al. 2007

Proceedings of the American Thoracic Society

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“…Peripheral blood mononuclear cell cytokine responses (IFN-a, IFN-g, tumor necrosis factor-a, and IL-10) to respiratory syncytial virus (RSV) and HRV were measured as previously described, using blood collected at study enrollment (16).…”

Section: Procedures and Definitionsmentioning

confidence: 99%

Increased H1N1 Infection Rate in Children with Asthma

Kloepfer¹,

Olenec²,

Lee³

et al. 2012

Am J Respir Crit Care Med

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Rationale: The 2009 H1N1 flu appeared to cause more severe cold symptoms during the 2009-2010 flu season. Objectives: We evaluated H1N1 infections during peak viral season in children with and without asthma to determine whether the H1N1 infectivity rate and illness severity were greater in subjects with asthma. Methods: One hundred and eighty children, 4-12 years of age, provided eight consecutive weekly nasal mucus samples from September 5 through October 24, 2009, and scored cold and asthma symptoms daily. Viral diagnostics were performed for all nasal samples. Measurements and Main Results: One hundred and sixty-one children (95 with asthma, 66 without asthma) completed at least 6 of the 8 nasal samples. The incidence of H1N1 infection was significantly higher in children with asthma (41%) than in children without asthma (24%; odds ratio, 4; 95% confidence interval, 1.8-9; P , 0.001), but rates of human rhinovirus infection (90% each) and other viral infections (47 vs. 41%) were similar. In children with asthma, there was a nonsignificant trend for increased loss of asthma control during H1N1 infections compared with human rhinovirus infections (38 vs. 21%; odds ratio, 2.6; 95% confidence interval, 0.9-7.2; P ¼ 0.07). Conclusions: During peak 2009 H1N1 flu season, children with asthma were infected almost twice as often with H1N1 compared with other respiratory viruses. H1N1 infection also caused increased severity of cold symptoms compared with other viral infections. Given the increased susceptibility of children with asthma to infection, these findings reinforce the need for yearly influenza vaccination to prevent infection, and raise new questions about the mechanism for enhanced susceptibility to influenza infection in asthma.Keywords: asthma; viral infection; influenza 2009 H1N1 Flu was first reported in the United States in the spring of 2009, and eventually affected 61 million people (1), one-third of them children. Morbidity was high, with 87,000 children requiring hospitalization. The most common comorbidity for patients hospitalized as a result of H1N1 infection was asthma (2), and the percentage of children with asthma hospitalized because of the 2009 H1N1 virus was two-to fivefold higher than previous reports of hospitalization due to seasonal influenza (3, 4). Despite the observation that subjects with asthma suffer H1N1 illness with increased severity, it remains unclear at what rate they are infected and whether their symptom severity is greater than those of their nonasthmatic counterparts. Previous studies of H1N1 infectivity reflect symptomatic infections with limited reporting of mild or asymptomatic infection (5-7).A study by our group demonstrated that 90% of children with asthma are infected with human rhinoviruses (HRVs) during the month of September, and that the severity of clinical illness varies from no symptoms to severe wheezing illnesses (8). This study provided the foundation on which we designed a larger cohort to prospectively examine the relationship between illness symptom...

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“…Interferon responses in early life are inversely associated with the severity of viral respiratory illnesses [26]. In addition, infants with low ex vivo IFN-c responses in early life are more likely to have frequent viral respiratory illnesses, including those associated with wheezing [27]. In this study, we performed skin prick tests on the infants, despite our experience being that parents of prematurely born infants frequently refuse skin prick testing in a research setting, as do prematurely born children [1].…”

mentioning

confidence: 99%

Rhinovirus infection and healthcare utilisation in prematurely born infants

et al. 2013

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Our aim was to determine whether rhinovirus (RV) lower respiratory tract infections (LRTIs) in prematurely born infants increase health-related cost of care during infancy.153 infants born at ,36 weeks of gestation were prospectively followed to 1 year. Cost of care was calculated from the National Health Service reference costing scheme and healthcare utilisation determined by examining hospital/general practitioner records. 20 infants developed RV LRTIs (RV group), 17 respiratory syncytial virus (RSV) LRTIs (RSV group), 12 both RV and RSV LRTIs (RV/RSV group) and 74 had no LRTI (no LRTI group). Compared with the no LRTI group, the RV/RSV LRTI group had the greatest increase in adjusted mean cost (difference GBP 5769), followed by the RV LRTI group (difference GBP 278) and, finally, the RSV LRTI group (difference GBP 172) (p50.045). The RV group had more outpatient (p,0.05) and respiratory-related general practitioner (p,0.05) attendances, more wheezed at follow-up (p,0.001) than the no LRTI group and more had respiratory-related outpatient attendances than the RSV LRTI group (p,0.05).We conclude that RV LRTIs were associated with increased health-related cost of care during infancy; our results suggest that the RV group compared with the RSV group suffered greater chronic respiratory morbidity. @ERSpublications Rhinovirus LRTIs in prematurely born infants increases health-related cost of care during infancy

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Cytokine Response Patterns, Exposure to Viruses, and Respiratory Infections in the First Year of Life

Cited by 184 publications

References 30 publications

Microbial Manipulation of Immune Function for Asthma Prevention: Inferences from Clinical Trials

Microbial Manipulation of Immune Function for Asthma Prevention: Inferences from Clinical Trials

Increased H1N1 Infection Rate in Children with Asthma

Rhinovirus infection and healthcare utilisation in prematurely born infants

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