Babies with More LL-37 in Their Noses Had Less Severe Bronchiolitis | Research

The takeaway

Higher LL-37 antimicrobial peptide levels in nasal secretions were strongly associated with milder bronchiolitis in hospitalized infants, independent of vitamin D status.

Higher LL-37 = shorter hospital stay
Nasal LL-37 levels inversely correlated with hospitalization length (rho=-0.340, p=0.001) and oxygen duration (rho=-0.339, p=0.001) in 153 infants with bronchiolitis

What the researchers found

LL-37 levels in nasal secretions were inversely associated with multiple measures of bronchiolitis severity. Higher LL-37 meant:

- Shorter hospitalization (rho = -0.340, p = 0.001)

- Less medication use (p = 0.001)

- Shorter oxygen supplementation (rho = -0.339, p = 0.001)

- Shorter IV fluid administration (rho = -0.323, p = 0.001)

These associations remained significant after adjusting for confounding factors like age and other variables.

Notably, serum vitamin D levels were not associated with nasal LL-37 levels, challenging the assumption that vitamin D drives LL-37 production in the airways. Beta-defensin-2 nasal levels also showed no connection to disease severity.

Why it matters

Bronchiolitis is the leading cause of hospitalization in infants. There is no specific treatment. If LL-37 plays a protective role, it could become a target for prevention or treatment strategies. The lack of connection between vitamin D and nasal LL-37 challenges a common assumption in the field.

The numbers in context

N=153; median age 3.1 months; LL-37 vs hospitalization rho=-0.340; vs O2 rho=-0.339; all p=0.001

How the study worked

This was a prospective cohort study at a single pediatric center from November 2014 to April 2017. Researchers enrolled 153 infants (aged 0-18 months) with their first episode of acute bronchiolitis. They measured serum 25(OH)D (vitamin D), nasal LL-37, and nasal beta-defensin-2 levels. Disease severity was measured by length of hospitalization, oxygen duration, medication use, and IV fluid duration. Statistical analysis used non-parametric tests and multiple regression.

Who was studied

Hospitalized infants aged 0-18 months with first-episode bronchiolitis (human)

What this study cannot tell us

This is an observational study and cannot prove LL-37 caused less severe disease. Higher LL-37 might simply reflect a stronger immune system. The study was at a single center, limiting generalizability. Viral types causing bronchiolitis were not reported, and different viruses may trigger different LL-37 responses. The correlation coefficients (rho around -0.34) are moderate.

How to read the evidence

This is a well-designed prospective cohort study with appropriate statistical analysis including adjustment for confounders. The sample size of 153 is adequate and the correlations are consistent across multiple severity measures. However, as an observational study, it cannot establish causation — higher LL-37 might reflect a stronger immune system rather than causing better outcomes.

When this study was published

Published in 2021 with data collected from 2014-2017, this is recent and relevant. The field of antimicrobial peptides in pediatric respiratory disease continues to grow.

The bigger picture

LL-37 is the only cathelicidin antimicrobial peptide in humans and is increasingly recognized as a key player in innate immune defense. This study adds infant bronchiolitis to the growing list of conditions where LL-37 levels correlate with outcomes. If the relationship is causal, it could lead to novel interventions — inhaled or nasal LL-37 formulations might help protect vulnerable infants, particularly since no specific bronchiolitis treatment currently exists.

Questions still open

Could intranasal LL-37 administration prevent or reduce bronchiolitis severity in high-risk infants?
Why did vitamin D levels not correlate with nasal LL-37 — is airway LL-37 production regulated by different signals than systemic LL-37?
Does the specific virus causing bronchiolitis (RSV vs rhinovirus vs others) affect the LL-37 response?

Common questions

What is LL-37 and why does it matter for babies with bronchiolitis?

LL-37 is a natural antimicrobial peptide — a tiny protein your immune system produces to fight infections. It's found in airway secretions, skin, and other barrier tissues. This study found that infants with higher LL-37 levels in their nasal secretions had less severe bronchiolitis: shorter hospital stays, less need for oxygen, and fewer medications. This suggests LL-37 helps protect young lungs from respiratory viral infections.

Can vitamin D boost LL-37 to protect against bronchiolitis?

That was a reasonable hypothesis — vitamin D is known to stimulate LL-37 production in some tissues. But this study found no connection between blood vitamin D levels and nasal LL-37 levels in infants. This suggests that airway LL-37 production may be regulated differently than LL-37 elsewhere in the body. Simply giving vitamin D supplements may not boost nasal LL-37 where it's needed to fight bronchiolitis.

Read the original research

Cathelicidin levels in nasal secretions are associated with the severity of acute bronchiolitis.

Pediatric pulmonology, 56(6), 1673-1680

View on PubMed ↗Publisher’s paper ↗

Citation

Papadaki, Maria; Marmarinos, Antonios; Tsolia, Maria; Gourgiotis, Dimitrios; Soldatou, Alexandra. (2021). Cathelicidin levels in nasal secretions are associated with the severity of acute bronchiolitis.. Pediatric pulmonology, 56(6), 1673-1680. https://doi.org/10.1002/ppul.25349