Serum cathelicidin, nasopharyngeal microbiota, and disease severity among infants hospitalized with bronchiolitis

Hasegawa, Kohei; Mansbach, Jonathan M.; Ajami, Nadim J.; Petrosino, Joseph F.; Freishtat, Robert J.; Teach, Stephen J.; Piedra, Pedro A.; Camargo, Carlos A.

doi:10.1016/j.jaci.2016.09.037

Cited by 32 publications

(42 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Human cathelicidin is an innate immunity host defense peptide with immunomodulatory properties. 17,38 Although vitamin D is one of the factors regulating cathelicidin production and activation, 38 the profiles did not differ with regard to 25(OH)D levels. Direct antiviral activity of cathelicidin against both RSV and rhinovirus has been reported in experimental studies 39 ; however, lower cathelicidin levels were found in children with RSV infection compared with those with rhinovirus or other non-RSV infection in 2 cohorts of children hospitalized for severe bronchiolitis, including MARC-35.…”

Section: Discussionmentioning

confidence: 90%

“…Serum allergy (total and allergen-specific IgE), 25-hydroxyvitamin D (25[OH]D), and innate immune response (cathelicidin [LL-37]) biomarkers were measured from blood samples. 17 We dichotomized total IgE levels, eosinophil counts, and 25(OH)D levels according to standard cutoffs (100 kU/L, 300 cells/mL, and 30 ng/mL, respectively) and LL-37 levels according to median values (46 ng/mL). 17 To examine nasopharyngeal microbiota, we identified 4 distinct microbiota profiles (Moraxella-dominant, Haemophilus-dominant, Streptococcus-dominant, and mixed profiles), as previously described, 18 by using partitioning around medoids with weighted UniFrac distance.…”

Section: Biomarkers and Nasopharyngeal Microbiota Profiles At Baselinmentioning

confidence: 99%

“…10 There is increasing evidence for a complex interplay between viral pathogens, host immune response, and respiratory microbiota in the pathogenesis and severity of acute respiratory tract infections, as well as their link with asthma-related outcomes. [16][17][18][19] Thus examining the heterogeneity of bronchiolitis in relation to allergy markers, immune response parameters, nasopharyngeal microbiota, and long-term respiratory outcomes might provide insight into asthma susceptibility pathways. However, to date, no study has investigated the association of severe bronchiolitis profiles defined by using a clustering approach with objectively measured biomarkers and long-term respiratory outcomes.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Severe bronchiolitis profiles and risk of recurrent wheeze by age 3 years

Dumas

Hasegawa

Mansbach

et al. 2019

Journal of Allergy and Clinical Immunology

Self Cite

106

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 90%

Section: Biomarkers and Nasopharyngeal Microbiota Profiles At Baselinmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Severe bronchiolitis profiles and risk of recurrent wheeze by age 3 years

Dumas

Hasegawa

Mansbach

et al. 2019

Journal of Allergy and Clinical Immunology

Self Cite

106

View full text Add to dashboard Cite

show abstract

“…Antimicrobial proteins are a first line of defense at barrier sites and are produced primarily by epithelial cells and innate leukocytes, particularly neutrophils (97,98). In the lung, they include surfactants as well as S100s, β-defensins, and cathelicidin and they may provide protection against important infant respiratory infections, including RSV (99)(100)(101)(102).…”

Section: Respiratory Epithelial Cellsmentioning

confidence: 99%

“…In the lung, they include surfactants as well as S100s, β-defensins, and cathelicidin and they may provide protection against important infant respiratory infections, including RSV (99)(100)(101)(102). Cathelicidin has direct antiviral activity against RSV, can prevent infection in vitro and in vivo and in children hospitalized with bronchiolitis, those with low serum cathelicidin were significantly more likely to have RSV infection and a longer hospital stay (97,(103)(104)(105)(106)(107).…”

Section: Respiratory Epithelial Cellsmentioning

confidence: 99%

Innate Immunity to Respiratory Infection in Early Life

Lambert

Culley

2017

Front. Immunol.

View full text Add to dashboard Cite

Early life is a period of particular susceptibility to respiratory infections and symptoms are frequently more severe in infants than in adults. The neonatal immune system is generally held to be deficient in most compartments; responses to innate stimuli are weak, antigen-presenting cells have poor immunostimulatory activity and adaptive lymphocyte responses are limited, leading to poor immune memory and ineffective vaccine responses. For mucosal surfaces such as the lung, which is continuously exposed to airborne antigen and to potential pathogenic invasion, the ability to discriminate between harmless and potentially dangerous antigens is essential, to prevent inflammation that could lead to loss of gaseous exchange and damage to the developing lung tissue. We have only recently begun to define the differences in respiratory immunity in early life and its environmental and developmental influences. The innate immune system may be of relatively greater importance than the adaptive immune system in the neonatal and infant period than later in life, as it does not require specific antigenic experience. A better understanding of what constitutes protective innate immunity in the respiratory tract in this age group and the factors that influence its development should allow us to predict why certain infants are vulnerable to severe respiratory infections, design treatments to accelerate the development of protective immunity, and design age specific adjuvants to better boost immunity to infection in the lung.

show abstract

Association of Rhinovirus C Bronchiolitis and Immunoglobulin E Sensitization During Infancy With Development of Recurrent Wheeze

et al. 2019

Self Cite

View full text Add to dashboard Cite

IMPORTANCE Rhinovirus infection in early life, particularly with allergic sensitization, is associated with higher risks of developing recurrent wheeze and asthma. While emerging evidence links different rhinovirus species (eg, rhinovirus C) to a higher severity of infection and asthma exacerbation, to our knowledge, little is known about longitudinal associations of rhinovirus C infection during infancy with subsequent morbidities.OBJECTIVE To examine the association of different viruses (respiratory syncytial virus [RSV], rhinovirus species) in bronchiolitis with risks of developing recurrent wheeze. DESIGN, SETTING, AND PARTICIPANTSThis multicenter prospective cohort study of infants younger than 1 year who were hospitalized for bronchiolitis was conducted at 17 hospitals across 14 US states during 3 consecutive fall to winter seasons (2011)(2012)(2013)(2014).EXPOSURES Major causative viruses of bronchiolitis, including RSV (reference group) and 3 rhinovirus species (rhinovirus A, B, and C). MAIN OUTCOMES AND MEASURES Development of recurrent wheeze (as defined in national asthma guidelines) by age 3 years.RESULTS This analytic cohort comprised 716 infants who were hospitalized for RSV-only or rhinovirus bronchiolitis. The median age was 2.9 months (interquartile range, 1.6-3.8 months), 541 (76%) had bronchiolitis with RSV only, 85 (12%) had rhinovirus A, 12 (2%) had rhinovirus B, and 78 (11%) had rhinovirus C infection. Overall, 231 (32%) developed recurrent wheeze by age 3 years. In the multivariable Cox model, compared with infants with RSV-only infection, the risk of recurrent wheeze was not significantly different in those with rhinovirus A or B (rhinovirus A: hazard ratio [HR], 1.27; 95% CI, 0.86-1.88; rhinovirus B: HR, 1.39; 95% CI, 0.51-3.77; both P > .10). By contrast, infants with rhinovirus C had a significantly higher risk (HR, 1.58; 95% CI, 1.08-2.32). There was a significant interaction between virus groups and IgE sensitization on the risk of recurrent wheeze (P for interaction < .01). Only infants with both rhinovirus C infection and IgE sensitization (to food or aeroallergens) during infancy had significantly higher risks of recurrent wheeze (HR, 3.03; 95% CI, 1.20-7.61). Furthermore, compared with RSV-only, rhinovirus C infection with IgE sensitization was associated with significantly higher risks of recurrent wheeze with subsequent development of asthma at age 4 years (HR, 4.06; 95% CI, 1.17-14.1). CONCLUSIONS AND RELEVANCEThis multicenter cohort study of infants hospitalized for bronchiolitis demonstrated between-virus differences in the risk of developing recurrent wheeze. Infants with rhinovirus C infection, along with IgE sensitization, had the highest risk. This finding was driven by the association with a subtype of recurrent wheeze: children with subsequent development of asthma.

show abstract

Serum cathelicidin, nasopharyngeal microbiota, and disease severity among infants hospitalized with bronchiolitis

Cited by 32 publications

References 30 publications

Severe bronchiolitis profiles and risk of recurrent wheeze by age 3 years

Severe bronchiolitis profiles and risk of recurrent wheeze by age 3 years

Innate Immunity to Respiratory Infection in Early Life

Association of Rhinovirus C Bronchiolitis and Immunoglobulin E Sensitization During Infancy With Development of Recurrent Wheeze

Contact Info

Product

Resources

About