Diagnosis of Patients With Low or Intermediate Suspicion of SAHS or With Comorbidity: Standard Laboratory Polysomnography Compared With Three Nights of Home Respiratory Polygraphy.
Condition: Obstructive Sleep Apnea Syndrome
MeSH terms: Sleep Apnea Syndromes; Sleep Apnea, Obstructive
Study type: Interventional

Summary: 
      Study Objectives: Obstructive sleep apnea (OSA) diagnosis using simplified methods such as
      home respiratory polygraphy (HRP) is only recommended in patients with a high pre-test
      probability. The aim is to determine the diagnostic efficacy, therapeutic decision-making and
      costs of OSA diagnosis using PSG or three consecutive studies of HRP in patients with
      mild-moderate suspicion of sleep apnea or with co-morbidity that can mask OSA symptoms.

      Design and Setting: Randomized, blinded, crossover study of three nights of HRP (3N-HRP) vs.
      PSG. The diagnostic efficacy was evaluated with ROC curves. Therapeutic decisions to assess
      concordance between the two different approaches were analyzed by sleep physicians and
      respiratory physicians (staff and residents) using agreement level and kappa coefficient. The
      costs of each diagnostic strategy were considered.
    

Detailed description: 
      Study subjects The study population consisted of subjects who were referred to the sleep unit
      of the Clínic Hospital, Barcelona, Spain, or the San Pedro de Alcantara Hospital, Cáceres,
      Spain, with a mild-moderate clinical suspicion of OSA or with notorious co-morbidity that
      induced frequent symptoms which mimicked those of OSA or could reduce sleep time.

      The inclusion criteria were: a) Patients with snoring and/or some observed apneas during
      sleep. b) Epworth scale less than 15. c) Subjects with notorious co-morbidity. d) Age between
      18 and 75 years.

      The exclusion criteria were as follows: high suspicion of sleep apnea (heavy snoring,
      breathing pauses and somnolence that makes social life or working difficult, without any
      other causes of hypersomnia); diagnosis of OSA; severe heart disease or resistant systemic
      hypertension; suspicion of non-apneic sleep disorders, such as narcolepsy, REM behavior
      disorders, and restless leg syndrome; psychophysical disability that would impede the
      application of the home polygraphy device or major co-morbidity (unstable heart disease,
      unstable pulmonary disease or disabling stroke); and lack of informed consent for the
      protocol approved by the ethics committees of the two centres.

      Protocol We compared 3N-HRP with laboratory-standard PSG in randomized patients who met the
      inclusion and exclusion criteria. The subjects were studied on a random basis for one night
      in a sleep lab (standard PSG) and for three consecutive nights with HRP. Once the first test
      had started, the second test was scheduled for within the following two days. PSG and HRP
      were scored separately and the technicians and physicians were blinded to any identifying
      information about the patients, as well as to any previous results.

      Measurements Clinical data: Gender, age, weight, height, body mass index (BMI), waist-hip
      ratio, neck circumference, systolic and diastolic blood pressure, and alcohol intake measured
      as ≤ 60 gr/day or > 60 gr/day, and tobacco consumption.

      Co-morbidity: Notable cardiovascular, metabolic or lung diseases, as well as diagnosis of
      insomnia, anxiety, depression, fibromyalgia, chronic fatigue syndrome, or psychiatric
      treatment.

      Symptoms related to OSA: Episodes of nocturnal choking, nocturia, morning headache, or
      morning tiredness. These data were collected in four degrees of intensity (never, sometimes,
      frequently, and always). Sleepiness was measured by the Epworth Sleepiness Scale and the
      American Sleep Disorders Association Sleepiness Scale (ASDA).

      Other questionnaires: a) FOSQ (Functional Outcomes of Sleep Questionnaire), which assesses
      the impact of excessive sleepiness on multiple activities of everyday. b) Euroqol-5D (EQ-5D),
      which is a standardized instrument for use as a measure of health outcome.

      Sleep studies. Standard laboratory PSG (Somté PSG, Compumedics Limited 2006, Abbotsford,
      Victoria, Australia) was performed according to the technical specifications of the American
      Academy of Sleep Medicine (AASM). The recorded variables were electroencephalogram (EEG),
      with derivations F4-M1, C4-M1, and O2-M1; electro-oculogram (EOG); chin electromyogram (EMG);
      leg electromyogram; electrocardiogram (ECG). Respiratory variables measured by linearized
      nasal pressure prongs and oronasal thermal flow waveform; respiratory effort signals measured
      by inductive bands that recorded rib-cage and abdominal movements; oxygen saturation; body
      position and snoring. A type 3 portable sleep apnea testing was used to perform HRP
      (Sleep&Go, Bitmed, Sibel S.A. Barcelona, Spain). Recorded variables were: flow measured by
      linearized nasal pressure prongs, thermal flow, body position, rib-cage and abdominal
      movements measured by inductive bands, and oxygen saturation. After a detailed explanation of
      the use of the HRP device (set-up and withdrawal) in the hospital setting, it was taken home
      and returned by the patient after three home studies.

      A valid PSG or HRP had at least 180 recorded minutes. Moreover, a valid HRP had to have at
      least 3 hours of flow or bands and oximetry measurements for scoring. The periods that were
      considered as "awake" because of erratic breathing were not considered for scoring. Mean
      values were obtained for the three nights of HRP. If one study was considered not to be
      valid, this was removed and the mean values were obtained from the other two nights with HRP.
      If two studies in the same patient were considered not to be valid, the patient was excluded.

      The PSG and HRP were scored manually, separately, and blinded by independent technicians.
      Sleep staging was performed using the standardized AASM criteria. The respiratory variables
      obtained from HRP and PSG were scored according to the AASM criteria: apnea defined as a drop
      in the peak signal excursion of ≈90% from the pre-event baseline with a duration ≥ 10
      seconds; and hypopnea defined as a discernible reduction in the amplitude of the airflow
      signal (≈30% of pre-event baseline) of at least 10 seconds of duration, associated with an
      arousal and/or ≥ 3% oxygen desaturation from the pre-event baseline. For HRP, hypopnea was
      defined as a discernible reduction in the amplitude of the airflow signal (≈30% of pre-event
      baseline) of at least 10 seconds of duration, associated with ≥ 3% oxygen desaturation.

      Therapeutic decision-making In addition to the real treatment decision of the physicians from
      the two sleep units, other 15 reviewers (five sleep medicine specialists; five respiratory
      physicians; and five respiratory resident physicians who had been trained for at least 3
      months in a sleep lab) from other 5 sleep laboratories in Spain, via a website showing
      clinical data from the patients and data from the sleep studies, take the therapeutic
      decisions. The reviewers chose one of two options: 1) CPAP treatment; 2) no CPAP
      treatment/other therapeutic measures. Each patient was presented twice (with PSG or HRP
      information), blinded and non-consecutively. The criteria for recommending CPAP were an AHI
      between 5 and 30 with significant symptoms or consequences or an AHI ≥30, taking less into
      account symptoms or consequences, according to the Spanish Sleep Network guidelines.

      Statistics It was estimated that, after accepting an alpha risk of 0.05 and beta risk of 0.2
      in a two-sided test, 55 subjects were needed for a minimum difference in AHI of 7.0 units to
      be recognized as statistically significant. The standard deviation was assumed to be 18. A
      dropout rate of 5% was anticipated.

      Outcomes to be studied and statistical analysis The means of the data obtained from the
      3N-HRP were compared with PSG data. Student's t-test and Bland-Altman plots were used to
      determine the agreement of the AHI measurements obtained by PSG and HRP. ANOVA was used to
      assess the variability between each of the nights of HRP. The efficacy of the diagnostic test
      was evaluated using sensitivity and specificity; positive and negative likelihood ratios [LR
      (+) and LR (-)]; and the percentage of patients with positive and negative diagnosis. The
      post-test probability of obtaining a true positive when the test was positive or negative was
      calculated, based on the pre-test probability (prevalence of the disease) and the positive
      and negative LRs. Receiver operating characteristic (ROC) curves were plotted for the mean of
      the 3N-HRP with the different polysomnographic AHI cut-off points (≥5, ≥10, ≥15, ≥ 30) for
      OSA diagnosis to determine the best ROC curve based on area under the curve (AUC)
      measurements.

      Therapeutic decision making The reviewers were grouped as sleep medicine specialists,
      respiratory medicine physicians and resident physicians. A median of the therapeutic
      decisions of each group was obtained. Agreement level (100 minus the sum of false positives
      and negatives) and Cohen's kappa coefficient was used to determine the agreement between
      therapeutic decisions. All the analyses were developed with the "Statistical Package for
      Social Sciences" (SPSS, 21.0 for Windows; SPSS Inc., Chicago, IL).

      Cost analysis We considered the costs of the each diagnostic strategy in an analysis of two
      equally effective alternatives.

      Test, patient and total costs for PSG and HRP The estimated test costs of PSG and HRP were
      obtained from the financial department from the two hospitals involved. These costs included
      the following: personnel involved, equipment depreciation, and fungible material. Patient
      costs were estimated according to the average costs for each patient of traveling from home
      to hospital and back by taxi. We considered a round trip to the hospital in the case of PSG
      and two round trips to pick up and return the HRP device. To estimate the costs per patient,
      the test and patient costs were divided by the number of patients with a valid recording. To
      obtain the total costs of PSG and HRP we added up the test and patient costs.

      Test, patient and total costs for equal diagnostic efficacy for PSG and HRP For PSG, the test
      cost for equal diagnostic efficacy was the sum of the test cost and the cost of repeated PSGs
      due to invalid recordings. For HRP, the test cost for equal diagnostic efficacy was the sum
      of the test cost and the following: the costs of PSG for patients with invalid HRP
      recordings; the cost of PSG in patients with indeterminate diagnostic results ("gray zone")
      and false positive and false negative results. To calculate the patient costs for equal
      diagnostic efficacy, we also considered the transport costs due to repetitions of tests. To
      calculate the costs per patient, these costs were divided by the number of patients who
      completed the trial. Total PSG and HRP costs for equal diagnostic efficacy were obtained by
      adding up the test and patient costs.
    

Intervention name(s): Home Respiratory Polygraphy; Standard Polysomnography
Intervention type(s): Device; Device
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Investigator)
Primary purpose: Diagnostic