In a new study entitled “Increased Peripheral Blood Pro-Inflammatory/Cytotoxic Lymphocytes in Children with Bronchiectasis,” researchers investigated the potential role of pro-inflammatory and cytotoxic cells, including T-cells, natural killer (NK) cells and NKT-like cells, in children with bronchiectasis. The study was published in the open access journal PLOS One.

Bronchiectasis is a disease of the airways characterized by chronic infection and inflammation and associated with enlargement of the lungs’ airways, leading to a build-up of excess mucus. While this condition is considered uncommon in children living in developed countries, the reverse is often observed in indigenous children in Alaska and Australia. However, the causes underlying systemic inflammation in these children, as well as the contribution of specific immune cells, are currently poorly characterized.

The study authors hypothesized that several cells of the immune system, including T, NKT-like and NK cells from children with bronchiectasis express higher levels of pro-inflammatory cytokines and the cytotoxic mediators granzyme b and perforin when compared to children without bronchiectasis. This hypothesis is based on the profile observed by the same team in adults with other lung diseases, such as chronic obstructive pulmonary disease (COPD), severe asthma and bronchiolitis obliterans syndrome following lung transplantation.

In order to test their hypothesis, the team recruited children diagnosed with bronchiectasis from the Royal Children’s Hospital in Brisbane and the Royal Darwin Hospital, Australia. They measured markers of systemic inflammation, including perforin and granzyme b and pro-inflammatory cytokines (IFN-γ and TNF-α), in T cell subsets, NKT-like and NK cells from blood and bronchoalveolar samples from children with bronchiectasis (n=10) and control children without bronchiectasis (n=10).

The researchers observed a significant increase in the percentage of cytotoxic T cells (CD8+ T) and T and NKT-like subsets expressing perforin and granzyme, and IFN-γ and TNF-α in the blood samples from bronchiectasis children, when compared with control children. Despite the high rate of generational cultural diversity, the group of children with bronchiectasis, identified as having Indigenous Australian ancestry, exhibited a higher increase in cytotoxic pro-inflammatory T cells (detected in the blood) when compared with non-Indigenous children with bronchiectasis. The assessed parameters showed no differences in the bronchoalveolar samples.

This study is the first study showing that bronchiectasis in children is associated with increased cytotoxic and pro-inflammatory T, NKT-like and NK cells levels in the peripheral blood. Authors highlight that future studies need to address the causes for this increase and whether therapeutics targeting these pro-inflammatory/cytotoxic cells might reduce co-morbidities in bronchiectasis patients.