Methods
This was a cross-sectional, prospective study approved by the Human
Research Ethics Committee at the Children’s Hospital at Westmead
(LNR/12/SCHN/280). Patients diagnosed with neuromuscular disorders
managed through the Neurogenetics clinic at the Children’s Hospital at
Westmead were invited to participate in the study. Controls were
siblings or friends of neuromuscular patients or children of staff
members who had no previous significant respiratory health issues. The
inclusion criteria were a proven underlying neuromuscular disease [via
genetics, muscle biopsy or nerve conduction studies], age 8 to 18
years, cognitive capacity to perform seated and supine spirometry and
willingness to have an overnight polysomnogram [PSG]. Written
informed consent was provided by the parent or primary caregiver and
children gave their verbal consent to perform the test. The recruitment
of patients and healthy controls ran for 24 months,
Data collection was performed during two visits. During the first visit,
demographic data was recorded and pulmonary function testing was
performed. At the second visit overnight polysomnography parameters were
recorded. Demographic information was gathered on the following: (1)
diagnosis (2) age at diagnosis, (3) height, (4) weight, (5) BMI, (6)
gender, (7) use of wheelchair or walking aids and (8) other medical
conditions (e.g. asthma). Testing was offered during their routine
clinic visits, scheduled at six monthly intervals. Forced vital capacity
(FVC) and Forced Expiratory Volume in one second (FEV1)
were measured with a Lilly type pneumograph (Viasys Healthcare,
California) according to ATS/ERS
standards.(24) Children were tested in a
conventional upright seated position followed by a supine position while
wearing a nose clip. As per ATS/ERS guidelines, the best effort,
determined as the measurement with the highest sum of FVC and
FEV1, was recorded for the study. (23) Values were
expressed as a percentage of predicted normal values (based on healthy
children of the same age, gender, and height). Reference values were
derived from published data.(24) As there
are no published reference standards for supine FVC, percent predicted
supine FVC was calculated using predicted values for upright FVC.
Children who were unable to produce acceptable and repeatable spirometry
in sitting positions according to standardized ATS/ERS criteria were
excluded. Children with acceptable and repeatable sitting lung function
were asked to perform spirometry in the supine position during the same
clinic visit.
Overnight polysomnography was only performed in the children with NMD,
and all were undertaken at the David Read Sleep Unit, in The Children’s
Hospital at Westmead, NSW, Australia, within 6 months of performing
pulmonary function tests. Children established on non-invasive
ventilation [NIV] previously had their most recent PSG parameters of
the diagnostic component of sleep study accessed for this study.
Polysomnography was performed in accordance with the 1997 American
Thoracic Society (ATS) guidelines using the Sandman Elite® Version 9.2
system (Embla Systems, Broomfield, CO, USA). Data was collected
according to standardized recommendations, commenced between 19:30 and
21:00, and ended at 06:00 the following morning. Data analyses were
performed in accordance with the 2007 American Academy of Sleep Medicine
guidelines.(25) The modified Epworth
Sleepiness Scale (mESS) questionnaire was completed by the child or the
parent at the time of the polysomnography.
Respiratory events were scored if they were at least two respiratory
cycles long, and significant oxygen desaturations were defined as ≥ 3%
desaturation from baseline. Children were classified as having sleep
disordered breathing [SDB] if polysomnography results showed an
apnoea-hypopnoea-index [AHI] >1.0
events/h.(26) The severity of SDB was
further classified: mild SDB was defined as an AHI of 1.0 to 4.99
events/h, moderate SDB defined as 5 events/h to 9.99 events/h and severe
SDB defined as an AHI > 10 events/h. Nocturnal
hypoventilation was defined according to AASM as > 25 % of
sleep time with a TcCO2 >50 mmHg or a
PCO2 rise of >10mmHg from baseline
(25, 27).
(25, 28)
Pearson correlations and linear regression models were used to examine
associations between the measures of respiratory function and
polysomnography. Sensitivity and specificity results were calculated.
Logistic regression was used to examine the ability of change in % FVC
to predict a binary outcome of an AHI ≥ 5 events/hr. All analyses were
conducted in SAS version 9.3 (SAS Institute Inc., Cary, NC, USA). There
was no adjustment made for multiple statistical comparisons. A p-value
of <0.05 was considered statistically significant.