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Noninvasive Sampling of Mucosal Lining Fluid for the Quantification of In Vivo Upper Airway Immune-mediator Levels
Published on: August 7, 2017
Mannose-binding lectin insufficiency is associated with airway Haemophilus colonization and a higher risk of post-RSV
Xiaoyan Zhang1, Xiang Zhang1, Xinglan Wang2
1Department of Respiratory Medicine, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, China National Clinical Research Center of Respiratory Disease, Beijing, China.
Objective:
To investigate whether mannose-binding lectin (MBL) insufficiency influences the airway microbiota composition and development of subsequent recurrent wheezing in infants with severe respiratory syncytial virus (RSV) bronchiolitis.
Methods:
Sixty-seven infants who were hospitalized during an initial episode of severe RSV bronchiolitis at 6 months of age or less were included in the study and followed up until the age of 3 years. Serum and sputum samples were collected. The serum MBL concentrations were determined by ELISA; the sputum microbiota and cytokines were analyzed by 16S rRNA-based sequencing and multiplex immunoassay, respectively.
Results:
Twenty-six infants developed recurrent wheezing by the age of 3 years, and 41 did not. The rate of MBL insufficiency was significantly higher among infants who developed recurrent wheezing compared to those who did not [50.0% (13/26) vs. 24.4% (10/41), (p = .031)]. MBL insufficiency was independently associated with a higher risk of subsequent development of recurrent wheezing (adjusted Odds Ratio: 3.5, 95% CI 1.1-12.3, p = .035). Haemophilus was found to be the most discriminative genus between infants with and without MBL insufficiency (LDA >4.0). The level of INF-γ (p = .019) in infants with MBL insufficiency was significantly lower than that among infants with normal MBL.
Conclusion:
During the first episode of severe RSV bronchiolitis in infants <6 months of age, MBL insufficiency was associated with a higher risk of developing subsequent recurrent wheezing by age three. Infants with MBL insufficiency were more likely to be colonized with Haemophilus and have weaker airway IFN-γ response.
Insights
Mannose-binding lectin (MBL) insufficiency in infants with severe respiratory syncytial virus (RSV) bronchiolitis is linked to recurrent wheezing. MBL insufficiency is associated with Haemophilus colonization and weaker airway interferon-gamma (IFN-γ) response.
Area of Science:
- Immunology
- Pediatric Respiratory Medicine
- Microbiome Research
Background:
- Severe respiratory syncytial virus (RSV) bronchiolitis in infants can lead to long-term respiratory issues.
- Mannose-binding lectin (MBL) plays a crucial role in the innate immune system.
- MBL insufficiency may impact host defense against respiratory infections and subsequent airway inflammation.
Purpose of the Study:
- To determine if MBL insufficiency affects airway microbiota composition in infants with severe RSV bronchiolitis.
- To investigate the association between MBL insufficiency and the development of recurrent wheezing in these infants.
- To explore the relationship between MBL levels, airway microbiota, and immune responses.
Main Methods:
- Study included 67 infants hospitalized with severe RSV bronchiolitis at <=6 months of age, followed until 3 years.
- Serum MBL concentrations were measured using ELISA.
- Sputum microbiota and cytokines were analyzed via 16S rRNA sequencing and multiplex immunoassay.
Main Results:
- Infants with MBL insufficiency had a significantly higher rate of recurrent wheezing (50.0% vs. 24.4%, p=0.031).
- MBL insufficiency was independently associated with increased risk of recurrent wheezing (aOR: 3.5, p=0.035).
- Haemophilus was the most discriminative bacterial genus; lower INF-γ levels were observed in infants with MBL insufficiency.
Conclusions:
- MBL insufficiency during the first RSV bronchiolitis episode increases the risk of recurrent wheezing by age three.
- Infants with MBL insufficiency show altered airway microbiota, particularly increased Haemophilus colonization.
- Weaker airway IFN-γ response is characteristic of MBL insufficiency in this cohort.
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