Future Testing for People with Cystic Fibrosis

This article was produced by guest contributor Dr. Silke van Koningsbruggen-Rietschel and members of the Vitalograph Clinical Trials Insights Team.

Discover emerging cystic fibrosis diagnostics like LCI and oscillometry, and their role in advancing CF care and treatment monitoring.

Cystic fibrosis (CF) treatment has dramatically improved, transforming the quality and longevity of life for people with CF. However, despite these advancements, there remains a critical need for effective diagnostic tools that can optimise care and accurately monitor disease progression, especially in the small airways. As CF therapies continue to evolve, so must our methods for detecting and monitoring this complex condition.

Traditional Diagnostics

For decades, the sweat chloride test and spirometry have been central to CF diagnostics. Spirometry, which measures lung function by assessing airflow, particularly in the larger airways, has been effective but comes with limitations. It often fails to detect early changes in the smaller airways, which are critical in CF management since undetected damage can lead to significant lung complications if not addressed in time.

The sweat chloride test, which measures elevated chloride levels in sweat, remains a key diagnostic tool for identifying CF. However, while it is essential for diagnosis, it does not provide ongoing information on disease progression. This highlights the need for more sophisticated tools that can offer continuous monitoring.

Patient-Reported Outcome Measures (PROMs) offering direct insights into a patient's health and quality of life are widely available and increasingly integrated into routine clinical practice. They are well-established as secondary outcome parameters in clinical trials and are also being incorporated into patient registries for future use. Their importance lies in their ability to provide a holistic view of health outcomes, ensuring that clinical decisions and treatment evaluations are aligned with patient experiences and needs. However, they are open to potential bias in self-reporting, and require validation.

Developments in CF

The remarkable improvements in cystic fibrosis (CF) treatments over recent decades have introduced new challenges in evaluating drug efficacy. With the proportion of people with CF exhibiting normal or mild lung disease rising from 41% in 1990 to 87.4% by 2020, and severe lung disease cases falling from 23.6% to just 1.8%, the task of detecting meaningful changes in lung function during clinical trials has become more complex. For instance, median FEV1 values for critical age groups in clinical trials—such as 6-11 years and 12-17 years—are approaching 98.6% and 96.8%, respectively, with adults aged 18 and older nearing a median FEV1 of 77.1%. This high baseline lung function underscores the need for alternative outcome measures that are more sensitive to subtle changes in lung health.

Emerging Diagnostics

Lung Clearance Index (LCI) has become a widely established technology that offers new insights into CF management. LCI measures how effectively gases are cleared from the lungs and provides detailed information about both large and small airways.

Research shows that LCI can detect early lung function changes before spirometry detects any abnormalities. In one study, 65% of children with normal FEV1 had an abnormal LCI and LCI increased significantly in people with early CF, indicating early lung changes before traditional spirometry could. This ability to catch early signs of lung function deterioration is crucial, as it allows for earlier interventions and potentially reduces long-term lung damage.

LCI has become routine in many CF centres with standardised procedures. However, LCI is not without its challenges. It requires specialised equipment which can be costly and may not be available to be performed in all healthcare settings, this could limit its accessibility. Theprocedure can be complex and requires additional training for healthcare professionals.

Oscillometry is emerging as a promising diagnostic tool. It measures the mechanical properties of the lungs, particularly in the small airways, by evaluating how airwaves travel through the respiratory system. Oscillometry provides insights into small airway function that spirometry often misses. This is particularly important because small airway damage often precedes broader lung function decline, and early detection can lead to more timely interventions that may prevent long-term lung damage.

One of the significant advantages of oscillometry is its ease of use, especially for younger people with CF or those who struggle with the effort-dependent nature of spirometry. Oscillometry is less intrusive and can be performed relatively easily, making it a valuable tool for both routine monitoring and clinical trials. Studies have demonstrated that oscillometry can detect changes in lung function even when FEV1 remains normal, providing an early warning system for clinicians.

Both LCI and oscillometry offer the ability to identify early lung damage, which is crucial in tailoring treatments to individuals and preventing further lung deterioration. LCI is currently more accessible than oscillometry with access in many CF centres, standardised operating procedures and centralised overreading available for clinical trials. Furthermore, while FEV1 is still the primary outcome measure for clinical trials, LCI has been accepted as a secondary outcomes . Regulatory authorities like the European Medicines Agency have begun to accept LCI as a primary outcome in paediatric trials, but discussions continue regarding the broader adoption of these technologies .

In some clinical trials, particularly in phase two, authorities may request imaging studies, such as chest CT scans. Chest CT is widely available and has the advantage of being validated and standardised across different centres, making it a reliable tool for assessing lung structure and disease progression. However, there's the significant consideration of exposing patients to radiation.

Given these challenges, there has been growing interest in functional MRI, which is highly sensitive in monitoring disease progression by capturing changes also in lung ventilation. However, functional MRI requires very specialised equipment and is not yet fully validated, meaning more clinical trials are needed to determine its potential as a standard clinical outcome parameter in CF care.

Breakthroughs in CF Drug Development

The development of CFTR modulators has revolutionized CF treatment by targeting the underlying causes of the disease, leading to dramatically improved outcomes. The success of these therapies highlights the importance of having advanced diagnostic tools to accurately monitor disease progression and treatment efficacy. At Vitalograph, we’re proud to have played a pivotal role in advancing CF care particularly through our involvement in clinical trials for the development of Trikafta, a breakthrough drug for CF.

Future Directions

Looking ahead, innovations such as artificial intelligence hold great promise for further advancing CF diagnostics. Emerging technologies aim to provide even more precise and comprehensive assessments of disease activity and progression, potentially transforming the way CF is monitored and managed. However, ensuring the accessibility of these technologies and providing adequate training for healthcare providers will be crucial in maximizing their impact and ensuring that all people with CF benefit from these advancements.

Conclusion

The landscape of cystic fibrosis care is rapidly evolving, with significant advancements in both diagnostics and treatment. While traditional methods like spirometry and the sweat chloride test remain vital, tools like LCI and oscillometry are setting new benchmarks in care. The integration of these advanced diagnostics with innovative therapies promises to enhance outcomes and improve the quality of life for those living with CF.

Learn more:

• Webinar featuring Dr Silke van Koningsbruggen-Rietschel, https://vitalograph.com/resources/clinical-library/webinars/clinical-research-considerations-for-cystic-fibrosis-studies/  

• Impulse Oscillometry in Cystic Fibrosis, Pediatr Allergy Immunol Pulmonol. 2021 Mar; 34(1):15-22. 

• A systematic review of patient-reported outcome measures (PROMs) in cystic fibrosis, BMJ Open, 2020 Oct; 10(10): e033867v. 

• Advances in Cystic Fibrosis Diagnostics, ATS Virtual Network, 2020. 

To learn more about our cystic fibrosis expertise and clinical trial services click here.