Positive airway pressure in pediatric obstructive sleep apnea

Paediatric Respiratory Reviews 31 (2019) 43–51

Contents lists available at ScienceDirect

Paediatric Respiratory Reviews

Sleep frequently asked questions

Positive airway pressure in pediatric obstructive sleep apnea Arpita Parmar a,b,1, Adele Baker a,1, Indra Narang a,b,1,⇑ a b

Division of Respiratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada University of Toronto, Toronto, ON, Canada

Educational Aims The reader will be able to appreciate:    

The severity of obstructive sleep apnea warranting the use of positive airway pressure [PAP] treatment. The types of the devices used to deliver PAP in children. Facilitators and barriers to PAP adherence and interventions to improve PAP adherence. The challenges involved when transitioning from pediatric to adult care for patients receiving PAP.

a r t i c l e

i n f o

Keywords: Positive airway pressure Obstructive sleep apnea Children Pediatrics

a b s t r a c t Obstructive sleep apnea (OSA) is characterized by snoring, recurrent obstruction (apneas) of the upper airway which disrupts normal ventilation during sleep. In the last decade, there has been a increase in children diagnosed with persistent, severe OSA attributed to (1) the obesity epidemic as 25–60% of obese children will have obesity related OSA (2) advances in medical technology that have increased life expectancy of medically complex children (3) improved diagnostics and (4) increased awareness. Positive airway pressure (PAP) is commonly used to treat persistent, severe OSA. PAP devices deliver pressurized air via nasal or oronasal interfaces to distend the upper airway and ameliorate OSA. Although effective in treating OSA, PAP adherence is suboptimal. This review article provides an overview of (1) PAP use in pediatric OSA (2) PAP devices (3) PAP adherence, (4) strategies and interventions to improve adherence and (5) Optimizing PAP delivery during pediatric to adult transition. Ó 2019 Elsevier Ltd. All rights reserved.

A BRIEF OVERVIEW OF PREVALENCE OF PAP USE IN THE PEDIATRIC POPULATION Obstructive Sleep Apnea (OSA) is characterized by snoring, recurrent partial or complete obstruction of the upper airway, frequent oxyhemoglobin desaturations, and sleep fragmentation [1]. Pediatric OSA occurs in approximately 1–4% of otherwise healthy children [2]. The pathophysiology of OSA is attributed to by both functional and anatomical factors, which increase upper airway collapsibility [3]. Anatomical factors include adenoidal and/or tonsillar hypertrophy [4], craniofacial abnormalities [5] and functional factors include neurological changes in upper airway muscle tone ⇑ Corresponding author at: Division of Respiratory Medicine, Hospital for Sick Children, 555 University Ave, Toronto, ON M5G 1X8, Canada. E-mail address: [email protected] (I. Narang). 1 Institutional Address for all authors: The Hospital for Sick Children, 555 University Ave, Toronto, Ontario M5G 1X8, Canada. https://doi.org/10.1016/j.prrv.2019.04.006 1526-0542/Ó 2019 Elsevier Ltd. All rights reserved.

[3], poor muscle responsiveness, low arousal threshold and high loop gain [6]. In the last 10 years, there has been a paradigm shift in pediatric OSA with a marked increase in youth diagnosed with persistent, severe OSA [7]. This increase can be attributed to (1) the current obesity epidemic as 16% of youth are obese worldwide and 25– 60% of obese youth will have obesity related OSA [8], (2) advances in medical therapies and technology that have increased life expectancy of children with medical complexity (e.g. congenital heart disease, craniofacial disorders, neuromuscular conditions) as well as the increased awareness of children at high risk of persistent OSA [7,9]. Underlying pathophysiology of OSA the pediatric obese population includes soft tissues restricting the upper airway size such as fat pads in the soft palate, lateral pharyngeal wall and at the base of the tongue [10]. Functional factors predisposing to OSA include an elevated waist circumference impacting the tethering effect on

44

A. Parmar et al. / Paediatric Respiratory Reviews 31 (2019) 43–51

pharyngeal airway, impaired neuromuscular control and increased mechanical load that affect chest wall mechanics and reduce lung compliance [11]. Untreated OSA is an independent risk factor for cardiovascular and metabolic risk, increased anxiety and depression and poor quality of life (QOL) [12–14]. Pediatric OSA is also associated with poor neurocognitive outcomes including behavioral disturbances, learning deficits and poor school performance [15]. OSA also results in a 226% increase in health care utilization compared to children without OSA [16]. Adenotonsillectomy (AT) is recommended as the first-line treatment for pediatric OSA [17]. However AT is not always effective, especially in children with associated comorbidities such as obesity, trisomy 21 and neuromuscular disease [4,18,19]. Positive airway pressure (PAP) is the most efficacious treatment for persistent OSA after AT [20]. It is also increasingly used as a first line therapy for OSA when adenoids and tonsils are not thought to be contributing to upper airway obstruction during sleep. PAP therapy is associated with significant improvements in OSA symptoms/indices and daytime sleepiness [4]. PAP use is also associated with improvements in cardiovascular and metabolic risk, QOL, and academic performance [21–23]. PAP has been used in pediatric OSA for over 30 years and has a worldwide prevalence ranging from 2.1 to 13.7/100 000 children [24]. In the pediatric population, there has also been a 3 fold increase for in home PAP use in the past decade [25].

Finally, prolonged use of PAP at higher pressures can impede maxillary and mandibular bone growth in children depending on the pressure points of the interface used [27]. Regular assessment and alternating interface types is recommended. Comfort features There are two distinct trademark comfort features in CPAP and APAP: ramp/delay and pressure reduction during exhalation. Ramp or delay is a feature whereby the device automatically starts PAP at a sub-therapeutic level, increasing to prescription pressure during the transition from wake to sleep. The goal is to prevent delayed sleep onset and PAP intolerance related to initiation of therapy at a high prescription pressure. Ramp starting pressure and ramp duration can be set as fixed values, or set to automatically adjust based on patient data collected by the device. In some devices, ramp can be automatically re-initiated at night upon detection of a nighttime awakening. The ramp time typically runs over fifteen to twenty minutes. Pressure reduction during exhalation is an option to ease discomfort related to exhaling against high pressure. The PAP device detects the beginning of exhalation and either diverts some airflow from the patient or reduces the motor speed to drop the treatment pressure according to the reduction level selected. In either case, the pressure reduction is never greater than 3 cmH2O below set pressure.

AN OVERVIEW OF PAP DEVICES The two types of PAP therapy prescribed in children to treat obstructive sleep apnea (OSA) are Continuous Positive Airway Pressure (CPAP) and Bi-level Positive Airway Pressure (BPAP). A wide variety of CPAP and BPAP devices are commercially available, each with unique capabilities and proprietary algorithms used to measure the phases of the respiratory cycle and airflow resistance. Modes of PAP therapy Differing modes of CPAP and BPAP therapy are available according to patient need. See Table 1 for a summary of the modes, their indications, functionality, prescription parameters and humidification options. Interfaces Historically, a dearth of commercially available pediatric sized PAP interfaces made effective treatment challenging; however, this has improved with mask options available for all ages. There are four types of mask interfaces: (1) nasal; (2) nasal pillow; (3) oronasal; and (4) total face. For infants and young children, nasal masks, which cover only the nose, are most commonly used due to their low anatomic dead space. Excessive mouth leak can adversely affect therapy efficacy; this can be resolved by use of a pacifier for infants and chin strap for children. Nasal pillows, which insert into the nares, are a comfortable option for adolescents, but are not designed for young children. Oronasal masks, which cover mouth and nose, and total face masks, which cover mouth, nose and eyes, are less common in pediatrics due to risks which present when a young child cannot remove the mask: aspiration with emesis, or asphyxia with loss of airflow. Further, there is the risk of hypercapnia related to the anatomic dead space of the mask. Yet these interfaces are required for some pediatric patients with facial deformity [26], or with excessive mouth breathing for whom a nasal mask with chin strap is ineffective. Appropriate assessment of mask size, pressure and airflow are necessary to ensure adequate mask flushing, mitigating the risk of hypercapnea.

Data management software Many devices have the ability to wirelessly transfer data via cellular or Wi-Fi, from the device to a cloud-based software program on a daily basis. This allows the patient to view therapy data online, via smartphone applications or on the device itself. Data acquisition capabilities for the clinician include remote monitoring of cloud-based data, or manually downloading data from the device via data card, USB, or data cable. Download data reports The PAP data available to the clinician varies by manufacturer and device sophistication. Most devices collect both usage and efficacy data; however, some basic models collect only usage data. A usage and efficacy data report of an adolescent with OSA and coexisting obesity can be found in Fig. 1. Bar graphs summarizing these data are shown in Fig. 2. Caution should be exercised when reviewing AHI data from PAP devices in pediatrics, as the algorithms for AHI on current PAP devices are derived from adult criteria. A review of leak data in relation to AHI is important as a high leak can adversely affect the reliability of AHI measurement. PAP ADHERENCE IN PEDIATRIC OSA Although PAP is increasingly prescribed for pediatric OSA there is no defined threshold to measure PAP adherence. It is also difficult to extrapolate a definition of adherence from adults, because children have greater recommended and actual sleep durations which vary substantially with age and development [28]. In adults, PAP usage for greater than 4 h per night is associated with improvements in OSA indices (e.g., reduced apnea-hypopnea index) and self-reported daytime sleepiness (Epworth sleepiness scale score) [29,30]. In adults, there is also a linear relationship between hours of nightly PAP usage and improvements in OSA symptoms, which levels off at approximately 7 h of use, with no further benefits thereafter [29,30].

Table 1 Positive airway pressure devices used in pediatric patients. Mode

Primary Indication and Clinical Utility

Functionality

CPAP: Fixed pressure CPAP Mode

OSA

Distends upper airway preventing pharyngeal collapse

 Single fixed pressure (cmH2O)  Range: 4–25 cmH2O (device dependent)

Auto-CPAP: Auto-titrating CPAP Mode

1. OSA 2. Positional or REM-related OSA 3. PAP therapy acclimatization prior to PSG 4. CPAP patients with sudden change in OSA severity due to surgery or rapid weight change Patients with OSA who are intolerant to CPAP at high pressures due to discomfort exhaling, not mitigated by comfort features

Auto-adjusting CPAP pressure, within a prescribed range, upon detection of upper airway resistance/airflow limitation. Provide higher pressures only when required during varying sleep stages or positions.

 Minimum CPAP pressure (cmH2O)  Maximum CPAP pressure (cmH2O)  Range: 4-25 cmH2O (device dependent)

Two pressures prescribed: higher inspiratory pressure and lower expiratory pressure to provide cycling levels of pressure which is synchronized with the patient breath Auto-adjusting EPAP level as in Auto-CPAP with a fixed pressure support level allowing for higher pressures upon inhalation. Cycling pressure is synchronized with patient effort.

    

Inspiratory Time (device specific) Rise Time Trigger Sensitivity Cycle Sensitivity Pressure Range: 4-40 cmH2O

Water chamber with temperature control for heated humidity or cool passive humidity

                         

Min-Max EPAP Pressure Support Inspiratory Time (device specific) Rise Time Trigger Sensitivity Cycle Sensitivity Pressures range: 4-40 cmH2O (device dependent EPAP and IPAP Back Up Rate Inspiratory Time Rise Time Trigger Sensitivity Cycle Sensitivity Pressure range: 4-40 cmH2O (device dependent) Target Alveolar Ventilation OR Target Tidal Volume EPAP (fixed or Min/Max) Pressure Support (Min/Max) Back up rate Inspiratory Time (fixed or Min/Max) Rise Time Trigger Sensitivity Cycle Sensitivity Pressure range: from 4-40 cmH2O

Water chamber with temperature control for heated humidity or cool passive humidity

Auto-BPAP:Auto-titrating Spontaneous BPAP Mode

1. Positional or REM-related OSA where patient is intolerant to high Auto-PAP pressures 2. BPAP therapy acclimatization prior to PSG

BPAP-ST: Spontaneous- Timed BPAP Mode

Children with OSA who present with mixed apnea, CPAP emergent central apneas, or persistent hypoventilation following resolution of OSA with CPAP.

Similar to BPAP-S with the addition of a back-up respiratory rate setting to ensure a minimum number of breaths per minute are delivered.

VAPS:Volume Assured Pressure Support BPAP Mode

Obesity Hypoventilation Syndrome Congenital central hypoventilation syndrome

Auto-titrating pressure support allows delivery of a constant target volume in the presence of changing lung mechanics and patient effort resulting from changes in sleep position or sleep stage.

Humidification In-line heat and moisture exchanger device Water chamber with temperature control for heated humidity or cool passive humidity Water chamber with temperature control for heated humidity or cool passive humidity

Water chamber with temperature control for heated humidity or cool passive humidity

A. Parmar et al. / Paediatric Respiratory Reviews 31 (2019) 43–51

BPAP-S: Spontaneous BPAP Mode

Prescription/Settings

Water chamber with temperature control for heated humidity or cool passive humidity

Auto-CPAP = Auto-titrating Continuous Positive Airway Pressure; Auto-BPAP = Auto-titrating Bilevel Positive Airway Pressure; BPAP = Bi-level Positive Airway Pressure; CPAP = Continuous Positive Airway Pressure; EPAP = Exhaled Positive Airway Pressure; IPAP = Inhaled Positive Airway Pressure; OSA = Obstructive Sleep Apnea; PSG = Polysomnography; VAPS = Volume Assured Pressure Support Mode.

45

46

A. Parmar et al. / Paediatric Respiratory Reviews 31 (2019) 43–51

There are sufficient data which together conclude that adherence to PAP therapy for the management of OSA is suboptimal in the adult and pediatric population. Alarmingly, low adherence rates to PAP have not improved in decades [31]. In the past 30 years, thousands of children and adolescents have been prescribed PAP therapy for OSA, but there are limited data (22 studies) on adherence with a small sample size of (median n = 50; range 13–140) (See Table 2). In the pediatric population, objective data within the last 10 years, show PAP adherence rates to be between 3 and 4 hours a night in the majority of studies [21,32–40] as shown in Table 2. However, in one study, Ramirez et al, observed high levels of PAP usage (greater than 8 h per night) when PAP was initiated in a dedicated pediatric non-invasive ventilation unit where patients and their caregivers have ample clinical and behavioral support and guidance readily available [37]. Similarly, Machaalani et al also reported high adherence rates at approximately 7 hours per night for CPAP users and 9 hours per night for BPAP users [41]. Higher adherence rates were related to (1) multidisciplinary support at initiation of PAP with close and early follow up of patients, and (2) the diagnostic profile of the pediatric patients on BPAP (e.g., neuromuscular disease), or (3) a coexisting condition that requires increased medical attention and caregiver support (e.g., chromosomal syndrome) [41].

To better understand the efficacy of PAP therapy in pediatric patients with OSA, future research needs to examine the dose response of PAP and clinical outcomes, to help establish a benchmark for adherence. FACILITATORS AND BARRIERS TO PAP ADHERENCE Understanding facilitators and barriers to PAP usage can be critical to improving adherence rates in the pediatric OSA population. A summary of modifiable (can be changed through reasonable measures) and non-modifiable (cannot easily be changed) facilitators and barriers to PAP adherence are outlined in Table 3. Facilitators A stable family structure whereby the caregiver and patient work together toward using PAP has been associated with increased adherence as reported by Prashad et al where mean PAP usage was 381 ± 80 min/night, although the study was limited by a sample size of 7 adolescents [51]. Caregiver support is invited by adolescents where adolescents reported they appreciated friendly reminders to use PAP which was associated with improved adherence rates [40,51]. Further, an authoritative parenting style

Fig. 1. PAP Compliance Data of an Adolescent with OSA. This compliance report shows PAP usage and efficacy data over a 30 day period. Usage data provides detailed information on average, median and median PAP usage as well as usage days 4 h. Efficacy data metrics vary between manufacturers, but typically include Apnea Hypopnea Index (AHI) and leak rate, as well as mean pressure and 90th or 95th percentile pressure when in Auto CPAP mode. Figure has been adapted from compliance report.

A. Parmar et al. / Paediatric Respiratory Reviews 31 (2019) 43–51

47

Fig. 2. Summary of PAP Usage Data over 30 days.

impacts positively on PAP adherence with caregivers explaining the importance and benefits of therapy to their child while enforcing PAP use [51]. Higher PAP adherence rates have been observed in pediatric OSA patients with a co-existing developmental disability who depend solely on their caregiver to administer PAP compared with otherwise healthy children with OSA, (Odds Ratio = 2.55, 95%CI = 1.27–5.13; p = 0.007) [50]. Caregiver self-efficacy is also associated with increased PAP adherence, which may be because caregivers who are confident in the ability to administer PAP are more likely to help their child with therapy [39]. Interestingly, patient self-efficacy is not associated with PAP usage [39], further highlighting the important role caregivers play in PAP adherence in pediatric OSA. Children and adolescents with a family member (e.g., parent, sibling) on PAP therapy have also reported significantly greater usage (3.6 ± 0.6 vs. 2.3 ± 0.39 h/night of all nights; p = 0.04) [38]. This may be because family members can act as a ‘‘role-model” to their fellow PAP user and may be better equipped to troubleshoot concerns (e.g., issues with machine, mask etc.) [38]. Pediatric PAP users who are more knowledgeable on the negative effects of disuse (e.g., poor quality sleep and daytime fatigue are also more likely to adhere to therapy [51]. Hawkins et al reported females are twice as likely to adhere to PAP therapy over males (odds ratio = 2.41, 95% CI = 1.20–4.85; p = 0.01) in 140 patients [50]. Generally, treatment adherence in chronic illness is greater in girls compared to boys, which may be attributed to lifestyle and parenting style differences between the sexes [52]. Finally, the length of time since the initial PAP prescription is positively associated with adherence (r = 0.35; p = 0.01) [48], which may be because patients have had a greater opportunity to incorporate PAP into their nightly routine [51]. It important to develop this routine at PAP initiation, as early adaption to PAP is crucial to long term adherence [40]. Barriers Difeo et al reports that lower maternal education is a barrier to PAP usage as children with mothers who were high school educated used PAP for 2 h/night while children with mothers who were college educated used PAP for 4 h/night (N = 56) [36]. In pediatric populations, parental education level predicts child health outcomes as well as treatment adherence [53] This may be because parents with higher education levels have a better understanding of their child’s condition and the adverse consequences associated with poor adherence [36]. Difeo et al also reported African American children used PAP for fewer hours per night compared to other races (2.5 ± 2.4 vs 4.2 ± 2.8 hours per night, p = 0.02), which may be due to different cultural attitudes about PAP, as well as differences in family demographics [36].

Other barriers include discomfort with the design of the PAP interface or tubing [40,51]. For example, many adolescents complained about the interface shifting positions during sleep making their face ‘‘itchy, sweaty or sore”. Some adolescents found it difficult to stay asleep with the mask on, causing them to become frustrated with PAP and decrease adherence [40]. The PAP machine itself may also be an inconvenience to move around due its weight and size which is challenging for older children who constantly change their sleep environments (e.g., separate parent homes, sleeping over at a friend’s house) [40]. Finally, some patients may be discouraged from using PAP because they do not perceive its therapeutic benefits as adolescents have reported no difference in energy levels and daytime sleepiness after using PAP [40]. Finally adolescents with OSA are likely to have poorer adherence rates, especially with increasing age [7]. Adolescents are in a transition phase of life where they are moving from complete dependence from their caregiver to a more autonomous lifestyle [54]. Furthermore, adolescents may find it difficult to incorporate a complex treatment regimen like PAP, into an already challenging developmental period marked with major biological and psychosocial changes [51]. Adolescents with a rebellious personality type are less likely to adhere to therapy, however yelling/scolding to force PAP onto the patient may further deter usage [51]. Addressing barriers using an individualized approach with caregivers and adolescents together will allow targeted solutions to improve PAP.

STRATEGIES AND INTERVENTIONS TO IMPROVE CPAP ADHERENCE IN YOUTH There are limited interventional studies targeting PAP adherence in the pediatric OSA population. In one study (n = 46, mean age 14.9 ± 6.0 years), the introduction of a dedicated respiratory therapist for education and strategies around PAP adherence resulted in improved PAP adherence [55]. Specifically, patients were divided into 3 groups; 0% PAP use; PAP use for 1–50% of nights, and PAP use for greater than 50% of nights [55]. Adherence rates improved by 24% in participants with baseline use of 0% and by 22% in participants with baseline usage between 1 and 50%, but no improvement in those with greater than 50% use at baseline for reasons that are unclear [55]. It can be speculated that this group had fewer barriers and greater facilitators to PAP adherence initially. Another study (mean age = 11.4 ± 3.9 years) provided patients with education and systematic exposure to PAP equipment with a respiratory therapist and psychologist [56]. With this multi-disciplinary support, 5 of the 12 patients used PAP for >4 h per night on 75% of all nights (mean 88.5%, range 78.6–95.2%), however this study is limited with a small sample size and the fact that 5 participants were lost to follow-up [56].

48

Table 2 PAP Adherence Rates in Children and Adolescents OSA. Author & Year

N

Male (%)

Population Age (years) and Sex

BMI or BMI-Z Score

Obese (%)

AHI pre-PAP

AHI postPAP

Nightly PAP usage (hours)

Adherent (%)

Adherence Definition

Notes

Waters [42] 1995 Massa [43] 2002 O’Donnell [32] 2006 Marcus [44] 2006

73

NR

5.7 ± 0.5

NR

NR

27.3 ± 20.2

2.6 ± 2.7

NR

86

Subjective adherence data

66

59

5.9 ± 5.1

NR

6.1

NR

NR

NR

Uong [45] 2007 Castorenamaldanado [33] 2008 Nakra [46] 2008

27

4.7 (IQR 1.4–7.0),

NR

3.0 ± 5.0

5.3 ± 2.5

NR

NR

56.5

28.4 ± 31.8

3.8 ± 4.1

7.0 ± 2.1

70.4 73 54 48 31 44

PAP use for > 4 h/night and  5 nights/week >3 h/night >4 h/night >5 h/night >6 h/night NR (compliance reports from devices used)

50

66

10 ± 5.1

NR

15.2

21

81 (BiPAP) 62 (CPAP) 56

10 ± 4 (BiPAP) 11 ± 4 (CPAP)

2.1 ± 1.1

13.6

39.8 kg/m2 2

*

64 *

Subjective adherence data Follow-up ranged from 8 to 979 days BiPAP (N = 16) CPAP (N = 13)

Patients adherent 73% of the week for 18.1 months

48

77

6 (4–7)

21 ± 5.3 kg/m

NR

68 (48–97)

6 (4–8)

4.5 ± 2.6

25

52

13.1 ± 3.0

2.8 ± 0.3

NR

8.7 ± 9.6

NR

NR

Nixon [34] 2011

30

70

9.1 ± 5.3

NR

NR

22.6 ± 16.0 (consistent) 22.9 ± 22.6 (intermittent)

NR

7.2 ± 2.0 (consistent) 4.7 ± 2.7 (intermittent)

33

>=4 h on 70 % of nights

Beebe [47] 2011

13

67% (PA) 71% (PNA)

14.8 ± 1.8 (PA) 14.4 ± 1.5 (PNA)

2.64 ± 0.17 (PA) 2.64 ± 0.28 (PNA)

100

10.0 ± 6.8 (PA) 9.3 ± 5.7 (PNA)

NR

NR

53

PAP usage 21% of total sleep time

Marcus [21] 2012 Marcus [35] 2012

52

69

12.0 ± 4.0

2.0 ± 0.9

69

18.1 ± 14.7

2.0 ± 2.3

2.8 ± 2.4

NR

NA

56

77

12.0 ± 4.0

2.1 ± 0.8 CPAP group

22.0 ± 21.0

2.0 ± 3.0

3.4 ± 2.3(M1) 2.1 ± 2.5 (M3)

NR

NA

18.0 ± 15.0

2.0 ± 2.0

3.1 ± 2.7(M1) 3.1 ± 2.8(M3)

NR

NA

M1-22 ± 9 nights/month M3-19 ± 9 nights/ month

19 ± 16

NR

3 ± 3 (M1); 2.8 ± 2.7 (M3) 3.4 ± 2.8

NR

NA

M1-22 ± 8 nights/month M3-19 ± 9 nights/ month

40.8 ± 35

% Days used  4 h

56

68

12 ± 4

NR

69 CPAP group 70 Biflex group 71

51

51

13.3 ± 2.5

73.5

73.5┼

17.7 ± 21.7

NR

62

58

10 ± 5

31.0 ± 21.0 kg (weight)

NR

NR

NR

8:17 ± 2:30 h:min per night

72

>8h/night

14

71.4

13.4 ± 1.9

2.2 ± 1

NR

27.1 ± 39.1

0.6 (0–21.1)

NR

NR

NR

65

Difeo [36] 2012 Simon [48] 2012 Ramirez [37] 2013

Kureshi [49] 2014

2.1 ± 1.0 Biflex group

11 of the 25 OSA patients completed the CPAP treatment and 14 were nonadherent Consistent use of CPAP is defined by use > 1 hour/ night for > 86% of nights (<1 skipped per day or week) compared to intermittent use Participants PAP usage range: 0–88% PNA = Patients who are Non-adherent PA = Patients who are adherent 60 ± 25 nights used over three months M1-24 ± 6 nights/month M3-18 ± 10 nights/month

CPAP/BPAP used 26.5 ± 5 nights/month OSA (N = 51) Neuromuscular (N = 6) Lung disease (N = 5) 24 ± 6 of 30 nights (subjective measure as participants contacted every two weeks over 3 months) nasal expiratory PAP

A. Parmar et al. / Paediatric Respiratory Reviews 31 (2019) 43–51

NR

66.6

11.3 (IQR 5.4– 25.9) 27 ± 32

Continued to use nCPAP 6 months after initiation Use every night (mean use over 2.5 ± 1.8 years) NR

49

Note: Studies comprised a clinically heterogeneous group of children with many medical comorbidities. AHI = Apnea Hypopnea Index; BPAP = Bilevel positive airway pressure; CPAP = Continuous positive airway pressure; IQR = Interquartile Range; M1 = Month 1; M3 = Month 3; NA = Not Applicable; nCPAP = Nasal continuous positive airway pressure; NR = Not Reported; PAP = Positive Airway Pressure; PA = Patients who are adherent; PNA = Patients who are non-adherent; W1 = Week 1. * Median value. ┼ Overweight or Obese.

1.1 61.9 21

16 (IQR11-17)

30 kg/m2

71

14.1

3.1

28.6

>4h/night for > 50% of all nights

M1- 74.2% (35.4, 93.5) of days used; NA NR NR 13.8 (7.1–29.7) 67.4 141

Xanthopoulos [39] 2017 Alebraheem [40] 2018

11.9 (IQR 7.9–15.5)

NR

54.7

NR 21

Puri [38] 2016

60

Prashad [51] 2016

71.4

15.2 (IQR 12–18)

2.48

85.7

25.4 (IQR4-78.3)

6.4 ± 1.3 (high use) 0.5 ± 0.4 (low use) 2.9 (IQR 0.6–5.8)

NR

NA

33% of patients had a family member using PAP (this group also had greater adherence) High use (n = 7) Low use (n = 7) Zero use (n = 7) NR 3.5 ± 2.7 (W1) 2.9 ± 2.4 (M1) 2.8 ± 2.4 (M3) NR NR 13.2 ± 3.7

1.8 ± 1.4

65

9.1 ± 11.7 NR 9.8 ± 5.9 61.4

0.5 ± 2.6

6.9 ± 5.5

55 (CPAP) 44 (BPAP) 56 Machaalani [41] 2016

65.5

0.1 ± 2.0

NR

24.9 ± 22.8

21.2 ± 21.5

9.3 ± 3.6

91

NA

4 h on 70 % of nights 75 6.8 ± 2.8

NA = Non-adherent group 4 h on 70 % of nights

4.7 ± 4.3 5.4 ± 8.3 (NA) 5.6 ± 6.7 140 Hawkins [50] 2016

54.3

12.0 ± 5.7 12.7 ± 4.7 (NA)

NR

NR

20.3 ± 26.8 16.5 ± 21.2 (NA)

NR

49

Notes AHI postPAP N Author & Year

Table 2 (continued)

Male (%)

Population Age (years) and Sex

BMI or BMI-Z Score

Obese (%)

AHI pre-PAP

Nightly PAP usage (hours)

Adherent (%)

Adherence Definition

A. Parmar et al. / Paediatric Respiratory Reviews 31 (2019) 43–51 Table 3 A summary of facilitators and barriers to PAP adherence. Facilitator Modifiable

 Caregiver support  Caregiver self-efficacy  Authoritative parenting style  Stable family structure  Knowledge of PAP benefits  Early adaptation to PAP  PAP apart of bedtime routine

Non-modifiable

 Female sex  Developmental delay  Length of time PAP since initial PAP prescription  Family member on PAP acting as a ‘‘role-model”

Barrier  Poor communication between caregivers and child (e.g., yelling)  Discomfort of PAP machine interface or tubing  Weight of PAP machine hindering portability  Lack of symptom relief/ therapeutic benefits  Embarrassed about using PAP  Low maternal education  African American race  Older age (adolescents)  Rebellious personality type

Behavioral therapy may improve PAP adherence, there are very few studies with small sample sizes that assess its long-term efficacy making it difficult to generalize results. Behavioral therapy (e.g., positive reinforcing tactics) resulted in mean PAP usage from less than one hour per night, to greater than 5 h per night [57] in 11 children aged 2–15 year [57] as observed in other very small case series [58]. In summary, intervention studies to improve PAP adherence in pediatric OSA patients are scarce and include a limited number of patients. Of particular concern is the lack of intervention studies targeting PAP use among adolescents with OSA who transition to adult care and will require PAP throughout their lifetime. Poor PAP adherence in adults has detrimental effects on nearly all key indicators of health, including cardiovascular (hypertension) [59], cerebrovascular (e.g. stroke) [60], and mental health [61]. Therefore, improving PAP adherence prior to transition is crucial for long-term health outcomes of patients with OSA. MODEL OF CARE TO OPTIMIZE PAP DELIVERY DURING PEDIATRIC TO ADULT TRANSITION Transitioning from pediatric to adult health care teams is an important life event for youth with medical conditions. Additionally, newly transitioned youth are simultaneously undergoing other life changes (e.g., starting university, moving away from home) and managing their chronic condition may become a lower priority. As a result, newly transitioned youth are at an increased risk for poor adherence, loss to follow-up and overall poor health outcomes [62]. Starting the discussion around transition in early adolescence can help improve readiness of patients and their respective caregivers [63]. It is especially important for patients to have sufficient knowledge of their condition and the importance of adhering to treatment [64]. For the pediatric OSA population on PAP, this includes a solid understanding of how to use and administer therapy independently as well as the importance of adherence. Challenges related to PAP use and adherence should be addressed prior to transition, and pediatric sleep clinical teams should work with patients and their families to promote gradual selfmanagement of PAP. For patients with OSA on PAP therapy, transitioning to adult care must be collaborative effort involving patients, their families and both pediatric and adult health care teams. The goals of transition should include: (1) enhancing knowledge of OSA and PAP to

50

A. Parmar et al. / Paediatric Respiratory Reviews 31 (2019) 43–51

both the patients and their caregiver with educational resources (e.g., PAP maintenance and usage reports) and useful tools (e.g., medical summaries, health passport), (2) a joint clinic visit that includes both pediatric and adult teams to improve continuity of care and help orient the patient and their caregiver to a new health care system, (3) educate adult health care providers of the unique needs of young adults (e.g., promoting caregiver support with PAP therapy) and (4) communicate important medical information to adult sleep specialists and coordinate care with other adult medical specialists if the pediatric patient with OSA has comorbidities (e.g., congenital heart disease). Successful transition programs for adolescents with OSA are urgently needed to help improve long-term health and societal outcomes for patients with OSA. SUMMARY AND FUTURE DIRECTIONS FOR RESEARCH PAP therapy is increasingly being used in children and adolescents with OSA. With advancing technology, PAP devices are becoming increasingly sophisticated allowing better monitoring of PAP functionality and usage by patients. Although PAP is effective in treating OSA, the limited data available show adherence is suboptimal especially in adolescents. Future research on designing and implementing effective interventions to improve PAP adherence is needed. Improving transition from the pediatric to adult health care system is also an important clinical priority and should be done as a collaborative effort with patients, their families and a multidisciplinary health care team. Finally, there are no data on effective interventions to improve the transition process, an important research priority for improving care of the pediatric OSA population as they transition to adulthood.

Directions for future research

Research efforts should focus on developing and assessing the efficacy of interventions designed to improve PAP adherence rates in the pediatric OSA population. Strategies for effective transition interventions from pediatric to adult health care are urgently needed for youth with OSA and their families. References [1] American Thoracic Society. Cardiorespiratory sleep studies in children. Establishment of normative data and polysomonographic predictors of morbidity. Am J Respir Crit Care Med 1999;160:1381–7. [2] Bixler EO, Vgontzas AN, Lin HM, et al. Sleep disordered breathing in children in a general population sample: prevalence and risk factors. Sleep 2009;32 (6):731–6. [3] Mezzanotte WS, Tangel DJ, White DP. Influence of sleep onset on upper-airway muscle activity in apnea patients versus normal controls. Am J Respir Crit Care Med 1996;153(6 Pt. 1):1880–7. [4] Marcus CL, Moore RH, Rosen CL, et al. A randomized trial of adenotonsillectomy for childhood sleep apnea. N Engl J Med 2013. [5] Al-Saleh S, Riekstins A, Forrest CR, Philips JH, Gibbons J, Narang I. Sleep-related disordered breathing in children with syndromic craniosynostosis. J Craniomaxillofac Surg 2011;39(3):153–7. [6] Carberry JC, Amatoury J, Eckert DJ. Personalized management approach for OSA. Chest 2018;153(3):744–55. [7] Tapia IE, Marcus CL. Fitting positive airway pressure adherence into teenage life: Don’t Push It! Ann Am Thorac Soc 2018;15(1):22–3. [8] Verhulst SL, Van Gaal L, De Backer W, Desager K. The prevalence, anatomical correlates and treatment of sleep-disordered breathing in obese children and adolescents. Sleep Med Rev 2008;12(5):339–46. [9] MacLean JE, DeHaan K, Chowdhury T, et al. The scope of sleep problems in Canadian children and adolescents with obesity. Sleep Med 2018;47:44–50. [10] Schwab R, Pasirstein M, Pierson R, et al. Identification of upper airway anatomic risk factors for obstructive sleep apnea with volumetric magnetic resonance imaging. Am J Respir Crit Care Med 2003;168(5):522–30. [11] Li A, Chan D, Wong E, Yin J, Nelson E, Fok T. The effects of obesity on pulmonary function. Arch Dis Child 2003;88(4):361–3. [12] Narang I, McCrindle BW, Manlhiot C, et al. Intermittent nocturnal hypoxia and metabolic risk in obese adolescents with obstructive sleep apnea. Sleep Breath 2018;22(4):1037–44.

[13] Patinkin ZW, Feinn R, Santos M. Metabolic consequences of obstructive sleep apnea in adolescents with obesity: a systematic literature review and metaanalysis. Child Obes 2017;13(2):102–10. [14] Yilmaz E, Sedky K, Bennett DS. The relationship between depressive symptoms and obstructive sleep apnea in pediatric populations: a meta-analysis. J Clin Sleep Med 2013;9(11):1213–20. [15] Beebe DW. Neurobehavioral morbidity associated with disordered breathing during sleep in children: a comprehensive review. Sleep 2006;29(9):1115–34. [16] Tarasiuk A, Greenberg-Dotan S, Simon-Tuval T, et al. Elevated morbidity and health care use in children with obstructive sleep apnea syndrome. Am J Respir Crit Care Med 2007;175(1):55–61. [17] Marcus CL, Brooks LJ, Draper KA, et al. Diagnosis and management of childhood obstructive sleep apnea syndrome. Pediatrics 2012;130(3): e714–55. [18] Mitchell R, Kelly J. Outcome of adenotonsillectomy for obstructive sleep apnea in obese and normal-weight children. Otolaryngol Head Neck Surg 2007;137 (1):43–8. [19] Smith DF, Benke JR, Yaster S, Boss EF, Ishman SL. A pilot staging system to predict persistent obstructive sleep apnea in children following adenotonsillectomy. Laryngoscope 2013;123(7):1817–22. [20] Bhattacharjee R, Kheirandish-Gozal L, Spruyt K, et al. Adenotonsillectomy outcomes in treatment of obstructive sleep apnea in children: a multicenter retrospective study. Am J Respir Crit Care Med 2010;182(5):676–83. [21] Marcus CL, Radcliffe J, Konstantinopoulou S, et al. Effects of positive airway pressure therapy on neurobehavioral outcomes in children with obstructive sleep apnea. Am J Respir Crit Care Med 2012;185(9):998–1003. [22] Drager LF, Lee CH. Treatment of obstructive sleep apnoea as primary or secondary prevention of cardiovascular disease: where do we stand now? Curr Opin Pulm Med 2018;24(6):537–42. [23] Katz SL, MacLean JE, Hoey L, et al. Insulin resistance and hypertension in obese youth with sleep-disordered breathing treated with positive airway pressure: a prospective multicenter study. J Clin Sleep Med 2017;13(9): 1039–47. [24] Amin R, Sayal P, Syed F, Chaves A, Moraes TJ, MacLusky I. Pediatric long-term home mechanical ventilation: twenty years of follow-up from one Canadian center. Pediatr Pulmonol 2014;49(8):816–24. [25] Castro-Codesal ML, Dehaan K, Bedi PK, et al. Longitudinal changes in clinical characteristics and outcomes for children using long-term non-invasive ventilation. PLoS One 2018;13(1):e0192111. [26] Kushida CA, Halbower AC, Kryger MH, et al. Evaluation of a new pediatric positive airway pressure mask. J Clin sleep Med JCSM 2014;10(9): 979–84. [27] Roberts SD, Kapadia H, Greenlee G, Chen ML. Midfacial and dental changes associated with nasal positive airway pressure in children with obstructive sleep apnea and craniofacial conditions. J Clin Sleep Med JCSM 2016;12 (4):469–75. [28] Sawyer AM, Gooneratne NS, Marcus CL, Ofer D, Richards KC, Weaver TE. A systematic review of CPAP adherence across age groups: clinical and empiric insights for developing CPAP adherence interventions. Sleep Med Rev 2011;15 (6):343–56. [29] Weaver TE, Maislin G, Dinges DF, et al. Relationship between hours of CPAP use and achieving normal levels of sleepiness and daily functioning. Sleep 2007;30 (6):711–9. [30] Bakker JP, Weaver TE, Parthasarathy S, Aloia MS. Adherence to CPAP: What should we be aiming for, and how can we get there? Chest 2019. [31] Rotenberg BW, Murariu D, Pang KP. Trends in CPAP adherence over twenty years of data collection: a flattened curve. J Otolaryngol Head Neck Surgery Le Journal d’oto-rhino-laryngologie et de chirurgie cervico-faciale. 2016;45(1). 43 43. [32] O’Donnell AR, Bjornson CL, Bohn SG, Kirk VG. Compliance rates in children using noninvasive continuous positive airway pressure. Sleep 2006;29 (5):651–8. [33] Castorena-Maldonado A, Torre-Bouscoulet L, Meza-Vargas S, Vazquez-Garcia JC, Lopez-Escarcega E, Perez-Padilla R. Preoperative continuous positive airway pressure compliance in children with obstructive sleep apnea syndrome: assessed by a simplified approach. Int J Pediatr Otorhinolaryngol 2008;72 (12):1795–800. [34] Nixon GM, Mihai R, Verginis N, Davey MJ. Patterns of continuous positive airway pressure adherence during the first 3 months of treatment in children. J Pediatr 2011;159(5):802–7. [35] Marcus CL, Beck SE, Traylor J, et al. Randomized, double-blind clinical trial of two different modes of positive airway pressure therapy on adherence and efficacy in children. J Clin Sleep Med 2012;8(1):37–42. [36] DiFeo N, Meltzer LJ, Beck SE, et al. Predictors of positive airway pressure therapy adherence in children: a prospective study. J Clin Sleep Med 2012;8 (3):279–86. [37] Ramirez A, Khirani S, Aloui S, et al. Continuous positive airway pressure and noninvasive ventilation adherence in children. Sleep Med 2013;14 (12):1290–4. [38] Puri P, Ross KR, Mehra R, et al. Pediatric positive airway pressure adherence in obstructive sleep apnea enhanced by family member positive airway pressure usage. J Clin Sleep Med 2016;12(7):959–63. [39] Xanthopoulos MS, Kim JY, Blechner M, et al. Self-efficacy and short-term adherence to continuous positive airway pressure treatment in children. Sleep 2017;40(7).

A. Parmar et al. / Paediatric Respiratory Reviews 31 (2019) 43–51 [40] Alebraheem Z, Toulany A, Baker A, Christian J, Narang I. Facilitators and barriers to positive airway pressure adherence for adolescents. A qualitative study. Ann Am Thorac Soc 2018;15(1):83–8. [41] Machaalani R, Evans CA, Waters KA. Objective adherence to positive airway pressure therapy in an Australian paediatric cohort. Sleep Breath 2016;20 (4):1327–36. [42] Waters KA, Everett FM, Bruderer JW, Sullivan CE. Obstructive sleep apnea: the use of nasal CPAP in 80 children. Am J Respir Crit Care Med 1995;152 (2):780–5. [43] Massa F, Gonsalez S, Laverty A, Wallis C, Lane R. The use of nasal continuous positive airway pressure to treat obstructive sleep apnoea. Arch Dis Child 2002;87(5):438–43. [44] Marcus CL, Rosen G, Ward SL, et al. Adherence to and effectiveness of positive airway pressure therapy in children with obstructive sleep apnea. Pediatrics 2006;117(3):e442–51. [45] Uong EC, Epperson M, Bathon SA, Jeffe DB. Adherence to nasal positive airway pressure therapy among school-aged children and adolescents with obstructive sleep apnea syndrome. Pediatrics 2007;120(5):e1203–11. [46] Nakra N, Bhargava S, Dzuira J, Caprio S, Bazzy-Asaad A. Sleep-disordered breathing in children with metabolic syndrome: the role of leptin and sympathetic nervous system activity and the effect of continuous positive airway pressure. Pediatrics 2008;122(3):e634–42. [47] Beebe DW, Byars KC. Adolescents with obstructive sleep apnea adhere poorly to positive airway pressure (PAP), but PAP users show improved attention and school performance. PLoS One 2011;6(3):e16924. [48] Simon SL, Duncan CL, Janicke DM, Wagner MH. Barriers to treatment of paediatric obstructive sleep apnoea: Development of the adherence barriers to continuous positive airway pressure (CPAP) questionnaire. Sleep Med 2012;13 (2):172–7. [49] Kureshi SA, Gallagher PR, McDonough JM, et al. Pilot study of nasal expiratory positive airway pressure devices for the treatment of childhood obstructive sleep apnea syndrome. J Clin Sleep Med 2014;10(6):663–9. [50] Hawkins SM, Jensen EL, Simon SL, Friedman NR. Correlates of pediatric CPAP adherence. J Clin Sleep Med 2016;12(6):879–84. [51] Prashad PS, Marcus CL, Maggs J, et al. Investigating reasons for CPAP adherence in adolescents: a qualitative approach. J Clin Sleep Med JCSM 2013;9 (12):1303–13.

51

[52] DiMatteo MR. Variations in patients’ adherence to medical recommendations: a quantitative review of 50 years of research. Med Care 2004;42(3):200–9. [53] DeWalt DA, Hink A. Health literacy and child health outcomes: a systematic review of the literature. Pediatrics 2009;124(Suppl. 3):S265–74. [54] Taddeo D, Egedy M, Frappier J-Y. Adherence to treatment in adolescents. Paediatrics Child Health. 2008;13(1):19–24. [55] Jambhekar SK, Com G, Tang X, et al. Role of a respiratory therapist in improving adherence to positive airway pressure treatment in a pediatric sleep apnea clinic. Respir Care 2013;58(12):2038–44. [56] Harford KL, Jambhekar S, Com G, et al. Behaviorally based adherence program for pediatric patients treated with positive airway pressure. Clin Child Psychol Psychiatry 2013;18(1):151–63. [57] Koontz KL, Slifer KJ, Cataldo MD, Marcus CL. Improving pediatric compliance with positive airway pressure therapy: the impact of behavioral intervention. Sleep 2003;26(8):1010–5. [58] Slifer KJ, Kruglak D, Benore E, et al. Behavioral training for increasing preschool children’s adherence with positive airway pressure: a preliminary study. Behav Sleep Med 2007;5(2):147–75. [59] Kendzerska T, Gershon AS, Hawker G, Leung RS, Tomlinson G. Obstructive sleep apnea and risk of cardiovascular events and all-cause mortality: a decade-long historical cohort study. PLoS Med 2014;11(2):e1001599. [60] Yaggi HK, Concato J, Kernan WN, Lichtman JH, Brass LM, Mohsenin V. Obstructive sleep apnea as a risk factor for stroke and death. N Engl J Med 2005;353(19):2034–41. [61] Garbarino S, Bardwell WA, Guglielmi O, Chiorri C, Bonanni E, Magnavita N. Association of anxiety and depression in obstructive sleep apnea patients: a systematic review and meta-analysis. Behav Sleep Med 2018:1–23. [62] Canadian Association of Pardiatric Health Centres (CAPHC) NTCoP. A Guideline for Transition From Paediatric to Adult Health Care for Youth with Special Health Care Needs: A National Approach. https://childhealthbc.ca/sites/ default/files/caphc_transition_to_adult_health_care_guideline_may_2017.pdf. Published 2016. Accessed. [63] White PH, Cooley WC. Supporting the health care transition from adolescence to adulthood in the medical home. Pediatrics 2018;142(5). [64] Vajro P, Ferrante L, Lenta S, Mandato C, Persico M. Management of adults with paediatric-onset chronic liver disease: strategic issues for transition care. Dig Liver Dis 2014;46(4):295–301.