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.