Article
Fawcett, LK, Chew, ZA, Schneider-Futschik, EK et al. 2025, ‘Predictive capacity of paediatric nasal epithelial cells in sequential CFTR modulator therapy’, Thorax, vol. 81, pp. 548–559. https://thorax.bmj.com/content/81/6/548
Funding
- Sydney Children’s Hospitals Foundation
- NHMRC
- Rebecca L. Cooper Foundation
- Cystic Fibrosis Australia
- David Miller Giles Innovation Grant
- Luminesce Alliance
Key terms
- Cystic fibrosis (CF): Genetic condition that causes the body to produce abnormally thick, sticky mucus.
- F508del-CFTR: The most common genetic mutation that causes CF.
- CFTR modulators: Medications that help fix the faulty protein responsible for CF.
- Human nasal epithelial cells (HNECs): Cells collected from the nose that can be grown in a lab to mimic the lining of a patient’s airways.
- Forced expiratory volume (FEV1pp): A common lung function test that measures how much air a person can forcefully blow out in one second.
- Sweat chloride (SC): A test that measures the saltiness of sweat; it is used to track how well CF drugs are working at a cellular level.
- Precision medicine: Tailoring medical treatment to the individual characteristics of each patient.
Aim
Researchers wanted to see if they could use a child’s own nasal cells to accurately predict how they would respond to CF drugs. Because every child reacts differently—even those with the same genetic mutation—doctors need a way to choose the best treatment without relying on trial and error.
Methods
- Researchers took simple nasal brushings from 24 children and adolescents with CF.
- These human cells were grown and matured in the lab until they formed a functional model of the patient’s own airway.
- The researchers then tested different drugs on these living cell cultures and measured how well the cells could transport salt and fluids (the main problem in CF).
- The lab results were compared against the actual clinical improvements (lung function and sweat tests) seen in the children.
Results
The study found that the human cell models closely matched how children actually responded to their medication. In children with significant lung disease, the models were especially accurate at predicting who would benefit from the therapy.
Even after carrying out detailed genetic testing, researchers could not identify any genetic factors that explained why some children responded better than others. This suggests that testing human cells may provide important insights that DNA testing alone can miss.
Conclusion
The study found that the human cell models closely matched how children actually responded to their medication. In children with significant lung disease, the models were especially accurate at predicting who would benefit from the therapy.
Even after carrying out detailed genetic testing, researchers could not identify any genetic factors that explained why some children responded better than others. This suggests that testing human cells may provide important insights that DNA testing alone can miss.
Relevance
This research highlights why human-specific models are often superior to animal testing in modern medicine:
- More predictive science: Animal models frequently fail to replicate the complex biology of human CF, whereas patient-derived models provide data that is directly relevant to human disease.
- Personalised, efficient care: Models grown from a patient’s own cells can help identify the most effective treatment for that individual, using a simple nasal swab rather than costly and invasive animal experiments.
Want to learn more?
The human cell models used in the study are part of a revolution in organ-on-a-chip technology. You can explore how these tools are replacing animal models in respiratory research at Emulate Bio.