Sleep-disordered breathing (SDB) is common, albeit underrecognized, in patients with cystic fibrosis (CF). The underdiagnosis and consequent undertreatment of SDB in the CF population can compromise patient outcomes, as conditions such as nocturnal hypoxemia, obstructive sleep apnea (OSA), and nocturnal hypoventilation can have a negative impact on patients’ quality of life.

People with CF commonly complain about poor sleep quality. Estimates indicate that 40% of children with CF have sleep complaints, with most (70%) referring to daytime sleepiness. Even clinically stable pediatric patients with CF show a high prevalence of SDB, changes in sleep architecture, and oxygen desaturation during sleep.

These conditions can affect patients in multiple ways. For instance, SDB can have deleterious neurocognitive effects that compromise the development of children with CF. It can also result in fragmented sleep which, in turn, can cause fatigue. Fatigue is highly prevalent in CF patients and has a negative impact on their well-being and emotional health.

SDB in Children With CF

Childhood SDB is characterized by increased work of breathing, restless night sleep, and excessive daytime sleepiness. These alterations can lead to cognitive impairment, behavioral disturbances, and early cardiovascular changes.

Children with CF experience frequent episodes of nocturnal hypoxemia, hypercapnia, and cough. Nocturnal hypoxemia and hypercapnia can precede daytime gas‐exchange abnormalities, while cough can contribute to increased awakening from sleep.

OSA is particularly frequent among children with CF. Estimates indicate that the prevalence of OSA and nocturnal hypoxemia in children and adolescents with CF is close to 30%. Children with CF who suffer from SDB have lower nocturnal oxygen saturation than those who do not suffer from SDB.

Reiling and Patel analyzed self-reported questionnaires from 28 children with CF to better understand their perception of sleep importance and identify barriers to sleep. A great proportion of participants indicated that sleep was very important for health (92%), overall (82%), and for lung function (75%). Participants identified technology, bedtime resistance, homework, excitability, and vest/airway treatments as frequent barriers to sleep.

SDB in Adults With CF

As the longevity of CF patients increases, the risk of developing SDB also increases, as age is a major risk factor for the development of SDB and other medical conditions associated with it (eg, obesity, diabetes, and cardiovascular diseases).

The prevalence of OSA in adults with CF is higher than that of hypoxemia and hypoventilation, though these conditions should not be neglected. In fact, lung disease severity in adult CF patients has been associated with nocturnal oxygen saturation and rapid eye movement sleep hypoventilation.

“Although adults with CF have apnea hypopnea index (AHI)/respiratory distress index in the normal range, it does not preclude SDB; this raises concern about conventional screening strategies,” Jagpal et al wrote in a review article published in Pediatric Pulmonology.

Diagnosing SDB in the CF Population

There are several diagnostic approaches to SDB, with particularities that make them more or less adequate for certain situations. For instance, oximetry may underestimate the severity of SDB and fails to diagnose nocturnal hypoventilation. Actigraphy fails to diagnose nocturnal hypoxemia, OSA, and nocturnal hypoventilation.

Home sleep testing has been used to diagnose OSA, particularly in adults. However, its use in pediatric patients is questionable and it is also not recommended in individuals with underlying lung disease, such as CF, and cardiovascular disease.

Hence, the American Academy of Sleep Medicine (AASM) recommends the use of in‐laboratory overnight polysomnography (PSG) for the diagnosis of SDB, as it can detect nocturnal hypoxemia, OSA, and nocturnal hypoventilation. Moreover, it can be used in patients with underlying cardiopulmonary disease, respiratory muscle weakness, hypoventilation, and/or chronic opioid use.

Treatment of SDB in Patients With CF

Oxygen therapy and noninvasive positive pressure ventilation (NIPPV) are the gold-standard options for the treatment of SDB. However, there are no clear guidelines for their use in CF patients.

Studies evaluating oxygen therapy for the treatment of isolated nocturnal hypoxemia are scarce and somewhat controversial. Most studies suggest the use of oxygen therapy alone at night could worsen hypercarbia and, therefore, its use should be carefully considered. On the other hand, NIPPV with or without oxygen could increase event-free (ie, hypoventilation, lung transplantation, or death) survival in adults with CF when compared to oxygen alone.

NIPPV has also been used to treat nocturnal hypoventilation in CF patients, either alone or in combination with airway clearance techniques. According to Jagpal et al, NIPPV treatment could have several benefits including improved airway clearance, increased peak exercise capacity, and slower decline in lung function. However, additional studies are needed to confirm such outcomes.

Additionally, there are several therapeutic options to manage OSA in pediatric and adult populations. Early adenotonsillectomy reduces OSA-associated symptoms in children and improves their behavior, quality of life, and PSG findings. Oral mandibular advancement devices, hypoglossal nerve stimulation, myofunctional therapy, and positional devices are common treatment options for adults. Pharmacological approaches with montelukast or nasal steroids have also been investigated, though with mixed results in pediatric and adult populations.

Experts’ Recommendations

Specialists from Rutgers Robert Wood Johnson Medical School in New Brunswick, New Jersey, “strongly encourage the CF community to incorporate evaluation for SDB in CF clinical care so that outcomes for the subset of the CF patients with comorbid SDB improve.”

To that end, they have some suggestions for clinicians:

  • Ask pediatric patients about snoring during routine visits.
  • Recognize that SDB in the CF population is not limited to OSA. It also includes other conditions, such as nocturnal hypoxemia and hypoventilation.
  • Prefer in‐laboratory overnight PSG over home sleep apnea tests for an objective SBD diagnosis.
  • Adopt a cautious posture when prescribing oxygen therapy for isolated nocturnal hypoxemia.
  • Become more aware of NIPPV as a therapeutic option for patients with SBD.
  • Seek further guidance from sleep specialists if needed.

Reference

Jagpal SK, Jobanputra AM, Ahmed OH, Santiago TV, Ramagopal M. Sleep‐disordered breathing in cystic fibrosis. Pediatr Pulmonol. 2021;56(S1):S23-S31. doi:10.1002/ppul.25028

Reiling K, Patel A. Perception of sleep importance in children with cystic fibrosis. Sleep. 2020;43(Supplement_1):A364-A365. doi:10.1093/sleep/zsaa056.956