Poor Sleep, a "Signal" of a Rare Disease? – Unveiling the Sleep Dilemmas of Patients with Cystic Fibrosis and Primary Ciliary Dyskinesia

Introduction: When Breathing is No Longer Smooth, Sleep Also Flashes Red

For most of us, a good night's sleep is the guarantee of energy for the next day. But have you ever thought that for some people with rare respiratory diseases, peaceful sleep might be a luxury? Recently, a study published in the "Journal of Clinical Medicine" focused on two types of rare disease patients – children and adults with Cystic Fibrosis (CF) and Primary Ciliary Dyskinesia (PCD) – systematically tracking changes in their sleep quality and exploring the potential impact of new targeted drugs. This study not only reveals their increasingly severe sleep problems but also points out the inseparable link between sleep quality and quality of life.

Background: Two "Intertwined" Rare Diseases

To understand this study, we first need to understand these two diseases.

Cystic Fibrosis (CF) is a genetic disease, with the main problem lying in a gene called CFTR. This gene is responsible for producing a protein channel that controls the balance of chloride ions and water inside and outside cells. When this channel "malfunctions," mucus throughout the body becomes abnormally thick and sticky, especially in the lungs and digestive system. This leads to recurrent respiratory infections, breathing difficulties, indigestion, and a series of other problems.

Primary Ciliary Dyskinesia (PCD) is another genetic disease, with the problem lying in the tiny "scavengers" of the body – cilia. The inner lining of our respiratory tract is covered with countless cilia, which continuously beat like brushes, sweeping away inhaled dust, germs, and mucus. In PCD patients, the cilia cannot beat normally, leading to the "cleaning system" being paralyzed, with consequences similar to CF: mucus accumulation, chronic cough, and recurrent lung infections.

Due to similar symptoms, patients with both diseases often face difficulties such as shortness of breath, coughing, and hypoxia, all of which can severely interfere with sleep. In recent years, CFTR modulators for CF have emerged, and these drugs can directly repair or enhance the function of "malfunctioning" CFTR proteins, greatly improving patients' lung function and quality of life. However, the impact of this revolutionary therapy on sleep, and how sleep problems in patients with these two diseases evolve over time, remain unsolved mysteries.

Key Findings: Sleep Quality Declines Over Time, Mixed Results for New Drugs

This study conducted a 4-year follow-up of 67 patients (including CF and PCD patients, children and adults), and through professional sleep and quality of life questionnaires, drew several key conclusions:

1. Overall Decline in Sleep Quality in Adult Patients: The study found that after 4 years, the overall sleep quality of adult patients significantly deteriorated, especially difficulty falling asleep.

2. More Prominent Problems in CF Patients with "Normal Pancreatic Function": Among CF patients, there is a subtype with relatively normal pancreatic function (CF-PS). Surprisingly, this group of patients experienced the most significant decline in sleep quality, especially among adults. This reminds us that even CF patients with relatively mild conditions should not overlook their sleep problems.

3. Complex Impact of CFTR Modulators on Sleep: The study compared CF patients using and not using CFTR modulators. The results showed that adult patients' sleep quality tended to decline regardless of medication use. However, in some details, the drugs seemed to play some role. For example, in children, children in the medication group seemed to have slightly worsened problems with "falling asleep and maintaining sleep." This indicates that although CFTR modulators can greatly improve lung function, their impact on sleep is not entirely positive, and may even bring new challenges, with results being "mixed."

4. Sleep and Quality of Life are Closely Related: The study confirmed an important point – the deterioration of sleep quality is closely related to the decline in quality of life. The worse the sleep, the lower the patient's perceived well-being and functional status.

Introduction to Research Methods: Combining Questionnaires and Clinical Data

Researchers used a longitudinal study design, conducting two assessments of the same group of patients over a 4-year period. They used internationally standardized questionnaires, such as the Pittsburgh Sleep Quality Index (PSQI) and the Sleep Disorders Scale for Children (SDSC), to quantitatively assess patients' sleep status. At the same time, they also collected clinical data such as patients' lung function, body mass index (BMI), infection status, and whether they used CFTR modulators, and analyzed the association between these factors and changes in sleep using statistical methods.

Limitations of the Study

The research team also frankly admitted that this study has some limitations. Firstly, the sample size was small (only 67 people), which means that some observed trends did not reach statistical significance, and conclusions need to be interpreted more cautiously. Secondly, the study relied on subjective questionnaires rather than objective sleep monitoring (such as polysomnography), which may have recall bias. Finally, regarding the impact of CFTR modulators, due to the small and complex patient population using the drugs, it is difficult to draw definitive causal conclusions.

Application Prospects and Implications: Focusing on Sleep, Improving Quality of Life for Rare Disease Patients

Despite its limitations, this study is still significant. It is the first to long-term track the evolution of sleep in CF and PCD patients and provides important observations on CFTR modulators, a new therapy. The study results remind clinicians and patients:

• Sleep problems are part of chronic disease management: For CF and PCD patients, doctors should not only focus on traditional indicators such as lung function but also routinely inquire about and assess their sleep status.
• New therapies also need to pay attention to side effects: CFTR modulators are groundbreaking, but their potential side effects (including effects on sleep and mental state) also need more research and attention to provide patients with more comprehensive guidance.
• Improving sleep means improving life: Given the strong correlation between sleep and quality of life, developing targeted sleep interventions (such as behavioral therapy, respiratory support, etc.) in the future may become a key part of improving the well-being of these rare disease patients.

Summary

This study paints a picture of the long-term sleep difficulties faced by patients with rare respiratory diseases. It tells us that over time, the sleep quality of these patients may naturally decline, and even revolutionary new drugs may not have an immediate impact on sleep, and the effects may be more complex. Future research needs larger samples and more objective measurement methods to deeply explore the complex interaction between disease, treatment, and sleep, ultimately helping every patient battling rare diseases not only breathe better but also have sweeter dreams.

References

1. Cohen-Cymberknoh, M., Lehavi, M., Gileles-Hillel, A., Atia, O., Breuer, O., & Reiter, J. (2023). Changes in Sleep in Children and Adults with Cystic Fibrosis and Primary Ciliary Dyskinesia over Time and after CFTR Modulator Therapy. Journal of Clinical Medicine, 13(1), 116.