Beyond the Lungs: New Drug Brings Hope for the "Nasal" Troubles of Children with Cystic Fibrosis

Introduction: "Locked" Breathing, Not Just in the Lungs

Cystic Fibrosis (CF) is a rare genetic disease. It stems from a mutation in a gene called CFTR, which leads to the dysfunction of a key protein—the CFTR protein—in the body. This protein acts like a cell's 'gatekeeper,' controlling the flow of chloride ions and water in and out of the cell. When the 'gatekeeper' is dysfunctional, the mucus in many organs of the body becomes abnormally viscous and dry, like glue. We commonly know that this thick mucus can block the lungs, leading to severe breathing difficulties and recurrent infections. However, many people are unaware that this 'traffic jam' also occurs in the upper respiratory tract, especially in the nasal cavity and sinuses, causing patients long-term nasal congestion, sinusitis, and a reduced quality of life. These symptoms are collectively known as sinonasal disease.

In recent years, a triple combination drug called Elexacaftor/Tezacaftor/Ivacaftor (ETI), as a CFTR modulator, has brought revolutionary breakthroughs in CF treatment. It can 'repair' defective CFTR proteins, especially for the most common F508del mutation, significantly improving patients' lung function. But can it also alleviate the equally bothersome sinus problems outside the lungs? Recently, a study published in the International Forum of Allergy & Rhinology focused on this, revealing the positive impact of ETI therapy on sinonasal health in children and adolescents with CF.

Key Findings: New Drug Significantly Improves Nasal Symptoms and Quality of Life

This multi-center prospective study conducted in France included 391 CF children and adolescents (6-17 years old) carrying at least one F508del mutation. The research team systematically evaluated their sinonasal health status before starting ETI treatment and at 1, 3, 6, and 12 months after treatment, using questionnaires and CT imaging.

• Significant Relief of Nasal Symptoms: Before treatment, approximately 16.4% of children reported nasal congestion. After 12 months of ETI treatment, this proportion decreased to 9.5%. More than half (53.1%) of the children who initially had nasal congestion reported improvement.
• Improved Quality of Life: The study used the SN-5 Sinonasal Quality of Life Survey, covering five aspects: sinonasal infection, nasal congestion, emotional distress, etc. The results showed that just one month after starting treatment, the children's total SN-5 score and sub-scores for sinonasal infection, nasal congestion, and emotional distress all significantly improved, and this improvement lasted for a full year. This means that the children not only felt their noses were clearer but also experienced relief from related negative emotions.
• Objective Evidence from CT Imaging: For a subset of children who underwent sinus CT scans, imaging results provided more intuitive evidence. Using the Lund–Mackay (LMKS) scoring system (a standardized method for assessing sinus opacification), researchers found that after 12 months of treatment, the children's sinus CT scores significantly decreased from an average of 11.3 to 4.2 (lower scores indicate better conditions), indicating effective clearance of mucus blockage and inflammation in the sinuses.

Research Methods Overview: Combination of Subjective Questionnaires and Objective Imaging

The study design was scientifically rigorous. On one hand, researchers used standardized questionnaires (such as SN-5) to allow children to report their symptoms and feelings, which directly reflected the impact of treatment on their daily lives. On the other hand, low-dose sinus CT scans objectively quantified the extent of lesions in the sinuses. This evaluation method, combining subjective feelings with objective imaging, made the study's conclusions more reliable and comprehensive. The follow-up period of one year also effectively demonstrated the durability of the efficacy.

Limitations and Considerations of the Study

The research team also candidly pointed out some limitations of the study. Firstly, not all participants completed all questionnaires, which may have affected data completeness. Secondly, only a small number of patients underwent CT scans, which limited the generalizability of the imaging results. In addition, the study found an interesting phenomenon: before treatment, although CT showed many children had significant sinus problems, they reported relatively mild symptoms in the questionnaires, even similar to healthy children. This may indicate that, due to long-term adaptation, CF children may "underestimate" or become accustomed to their nasal discomfort, suggesting that doctors need to be more meticulous when taking medical histories.

Future Prospects: Beyond the Lungs, a New Perspective on Systemic Treatment

The significance of this study is profound. It clearly demonstrates that ETI, as a systemic treatment drug targeting the root cause of CF, offers benefits far beyond the lungs. It can systematically improve systemic problems caused by CFTR dysfunction, including sinonasal disease in the upper respiratory tract. This finding not only brings a better quality of life to children with CF but also provides doctors with a new, non-invasive window for observing treatment efficacy. In the future, improvements in sinus CT imaging may serve as one of the objective biomarkers for evaluating the efficacy of CFTR modulators.

Summary

In summary, this study confirms that ETI triple therapy can safely and effectively improve sinonasal disease in CF children and adolescents. The effects are significant and lasting, both from the patients' subjective feelings and objective imaging evidence. It reminds us that while focusing on the lung health of CF patients, we should not neglect nasal problems that also affect their quality of life. With the continuous development of such targeted drugs, we have reason to believe that CF patients will usher in a healthier and more comprehensive future.

References

• Petitjean, M., Letierce, A., Bonnel, A. S., Reix, P., Deneuville, E., Stremler, N., ... & Simon, F. (2025). Beyond the Lung. Impact of Elexacaftor/Tezacaftor/Ivacaftor on Sinonasal Disease in Children With Cystic Fibrosis. International Forum of Allergy & Rhinology.