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* From Centre Médical de Forcilles (Drs. Herer, Roig, and Poujol), Férolles-Attilly, France; and Service de Pneumologie (Drs. Roche and Huchon) and Département dInformatique Médicale et de Biostatistiques (Dr. Carton), Université de Paris René Descartes, Hôpital Ambroise-Paré, Boulogne, France.
Correspondence to: Gérard J. Huchon, MD, FCCP, Service de Pneumologie et Réanimation, Hôpital de lHôtel-Dieu 1 Place du Parvis de Notre Dame, F-75181 Paris Cedex 4, France; e-mail: gerard.huchon{at}htd.ap-hop-paris.fr
| Abstract |
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Methods: We studied a population of 102
consecutive patients referred by an obesity clinic for suspected OSA,
in whom body mass index was
25 kg/m2. The following
tests were performed: clinical score (CS), pulmonary function tests
(PFTs), measurement of arterial blood gas tensions, nocturnal
oximetry, and full-night PSG.
Results: Six of 34 women
and 34 of 68 men had OSA, defined by an apnea-hypopnea index
15. CS
and the cumulative time spent below 80% arterial oxygen saturation
(SaO2) were higher, and
PaO2, minimal SaO2, and
mean nocturnal SaO2
(mSaO2) were lower in OSA patients than in
non-OSA patients. Logistic regression showed that sex, CS, and the
ratio of FEV1 over forced expiratory volume in 0.5 s
(an index of upper airway obstruction on flow-volume curves) and
mSaO2, expressed as categorical variables, were
independent predictors of OSA. None of these individual variables had a
satisfactory diagnostic value for the diagnosis of OSA. A logistic
regression model including sex and all continuous variables would have
allowed us to predict the presence or absence of OSA confidently in
72.5% of the population, in whom the positive predictive value of the
model was 94% and the negative predictive value was 90%.
Conclusion: In obese patients referred to a respiratory sleep laboratory and evaluated by CS, PFTs, arterial blood gases, and oximetry, no individual sign or symptom may accurately predict the presence or absence of OSA. Provided that it is validated in prospective studies, a logistic regression model using these variables may be useful for the prediction of OSA.
Key Words: clinical score obesity obstructive sleep apnea oximetry polysomnography upper airway obstruction
| Introduction |
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Despite recent debates on which measurements best describe OSA, the "gold standard" for the diagnosis of this disease remains polysomnography (PSG), which is expensive and time-consuming. Therefore, investigations have been proposed for appropriate case finding before PSG is performed in patients referred for sleep evaluation, in order to limit the number of PSG tests done.5 6 7 8 9 10 However, predictive factors and their diagnostic values are likely to differ according to the characteristics of the population studied (eg, sex, obesity, underlying respiratory diseases), making it inappropriate to extrapolate results from a given population to patients referred to another laboratory, and making it necessary to determine the best predictive factors for various populations.9 Besides, most studies on predictors of OSA have not included the results of pulmonary function tests (PFTs) and blood gas measures in the analysis.5 6 7 8 9 10
Because obesity is a strong risk factor for OSA,2 practitioners who care for obese patients must frequently suspect the presence of OSA. Therefore, we studied the predictive values of clinical evaluation, PFTs, arterial blood gas tensions, and nocturnal oximetry for OSA case finding in a population of consecutive overweight patients. Because female patients represent approximately one third of patients referred to our laboratoryquite a high proportion compared with that reported in other studieswe also assessed the effect of sex on these predictive values.
| Materials and Methods |
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25 kg/m2.
In each patient, a clinical score (CS) was established and PFTs,
nocturnal oximetry, and full-night PSG were performed.
Clinical Score
We used a CS derived from Williams et al,10
including four features: habitual snoring, interrupted nocturnal
breathing as reported by the spouse or roommates, excessive daytime
sleepiness, and arterial hypertension. Each feature was assigned a
score of 0 or 1, with a highest possible value of 4 for the whole
score. BMI was not included in the score because it was
25
kg/m2 in all patients.
Pulmonary Function Testing
PFTs included spirometry and flow-volume curve analysis (Medical
Graphics Corp; St. Paul, MN). The predicted values of the European
Community for Coal and Steel were used for PFTs.11
Flow-volume curves were examined for the presence of
"saw-toothing,"12
and the following flow ratios used
for the diagnosis of upper airway obstruction (UAO)13
14
15
were calculated: the ratio of the forced expiratory flow after 50% of
the FVC over the forced inspiratory flow after 50% of the FVC
(FEF50/FIF50), the ratio of
peak expiratory flow over FEF50
(PEF/FEF50), and the ratio of
FEV1 over forced expiratory volume in 0.5 s
(FEV1/FEV0.5). Arterial
blood samples were obtained by radial artery puncture while the patient
was seated.
Oximetry
Pulse oximetry was performed overnight 1 to 7 days prior to
PSG. The recording was done in the sleep laboratory with portable
systems, ie, either a Biox 3740 (Ohmeda; Louisville, CO), a Pulsox-8
(Minolta, AVL Medical Instruments; Cergy-Pontoise, France), or an
OLV-1100 (Nihon-Kohden; Tokyo, Japan) oximeter. Stored data were
digitized for computer analysis, and the following indices were
calculated: minimal nocturnal arterial oxygen saturation
(minSaO2), mean nocturnal
SaO2 (mSaO2), and
cumulative time spent with an SaO2 below 90%
(CT90) and below 80% (CT80). Oximetry was not
performed during the same night as PSG.
PSG
All patients underwent a full-night PSG including two channels
of EEG, one channel of electro-oculogram, and one channel of submental
electromyogram. Thoracoabdominal movements were recorded with
inductance plethysmography. Airflow at the nose and mouth was assessed
by a thermistor. All signals were recorded and stored on semiautomated
scoring systems (Minisomno; SEFAM; Nancy, France; or Medatec; Brussels,
Belgium). Apnea was defined as cessation of oronasal airflow for > 10
s. Obstructive apneas were scored when airflow was absent but
respiratory efforts were present. Hypopnea was defined as a reduction
of oronasal airflow to
50% of the value prevailing during a
preceding period of normal breathing of
10 s. OSA was defined as a
combined obstructive apnea-hypopnea index (AHI) of
15
events/h.16
17
Statistical Analysis
We used Students t tests to study differences in
CS, pulmonary function variables, arterial blood gases, and results of
nocturnal pulse oximetry between patients with OSA (AHI
15/h) and
patients without OSA (AHI < 15/h). We assessed the correlations
between these variables and AHI using the nonparametric Spearman rank
test because AHI was not normally distributed according to the
Shapiro-Wilks test.
Then, we used receiver operating characteristics (ROC) curves to
determine the most accurate diagnostic thresholds for variables that
correlated to AHI or differed in OSA and non-OSA patients. The obtained
thresholds were used to transform the continuous variables into
categorical variables, and Pearsons
2 test
was performed to study differences in distribution of these categorical
variables between OSA and non-OSA patients. Multivariate logistic
regression analysis was used to determine which categorical variables
were independently predictive of OSA and to study the interaction
between predictive variables and sex. Logistic regression analysis was
also used to develop a model for prediction of OSA. The probability of
having OSA (P) was calculated using the following equation:
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Finally, individual data were analyzed to determine if some ranges or combinations of ranges of variables were highly predictive of either the presence or the absence of OSA.
Results are expressed as mean ± SD unless indicated. We considered a p value < 0.05 to be significant. Logistic regression analysis was repeated with an AHI threshold of 10 for definition of OSA. Statistical analysis was performed with BMDP (BMDP Statistical Software; Los Angeles, CA), SPSS (SPSS Inc; Chicago, IL) and SAS (SAS Institute; Cary, NC) statistical software. ROC curve analysis was performed with ROC Analyzer software (RM Centor and J Keightley; Richmond, VA).
| Results |
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where y' is used to calculate P' as described above. P' correlated to AHI less strongly than P (r = 0.29; p < 0.01); the only useful feature that could be derived from the plot of P' against AHI was that a value of P' < 0.25 (n = 13, 12.7% of patients) had a negative predictive value of 80% for exclusion of OSA (Fig 3 , right). Results of multivariate analysis were not altered by using a different AHI threshold to define OSA, ie, 10 or 15 events/h (Table 4) .
Finally, individual data analysis found that all patients who had a CS
of 4, FEV1/FEV0.5 ratio
1.3, and mSaO2
85%
(ie, 3% of the population) had OSA confirmed by PSG,
whereas all patients who had a CS of < 2,
FEV1/FEV0.5 ratio < 1.3,
and mSaO2 > 85%
(ie, 5% of the population) had the diagnosis of OSA
eliminated by PSG. We were unable to define any other ranges or
combinations of ranges of variables with intermediate as opposed to low
predictive value.
| Discussion |
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To study the clinical features of patients with suspected OSA, we
used a CS derived from Williams et al,10
who showed that
BMI, hypertension, snoring, and gasping or choking observed by a
partner were significant predictors of sleep apnea severity. BMI had to
be excluded in the score we used because all our patients were
overweight (BMI
25 kg/m2). Other authors have
developed similar scores based on neck circumference instead of
BMI,7
22
but the predictive value of this index has been
questioned.9
The relationships between OSA, abnormalities of resting diurnal gas exchanges, and pulmonary function are controversial. We observed a lower diurnal PaO2 in patients with OSA than in patients without OSA. Because only a small proportion of OSA patients had an associated bronchial obstruction (6/40, 15%), this resting hypoxemia may be in part explained by high BMI. Indeed, several studies conducted in predominantly obese populations found values of PaO2 similar to those of our patients.23 24 25 Among them, Gold et al23 also found a higher PaCO2 in sleep apnea patients than in control subjects, which was not the case in our study; this discrepancy is likely related to a higher proportion of overlap syndromes in their population, because their patients with OSA had lower FEV1 and FVC than patients without OSA, which we did not find. Some studies have even suggested that lower lung volumes and increased airway resistance contribute to the severity of OSA.26 However, AHI did not correlate to indices of bronchial obstruction (ie, FEV1 and FEV1/FVC) in our patients. Other studies also suggested that the development of hypercapnia in OSA patients requires the presence of an associated bronchial obstruction.24 27 However, this was not found in a study of 111 patients in which the only predictive factors of hypercapnia were PaO2 and female sex,25 although the sex-related difference in PaCO2 did not reach significance in a subsequent analysis of this population.28 In our study, there was no trend toward a higher PaCO2 in women than in men, despite a higher BMI.
As in other studies of flow-volume curves and UAO indices, we found that the saw-tooth pattern12 and the FEF50/FIF50 ratio29 are not useful for OSA case finding. Conversely, we found that the FEV1/FEV0.5 ratio, which has been shown to detect UAO when > 1.5, was a predictor of OSA in the logistic regression analysis when > 1.3.15 However, there was a great overlap between patients with OSA and patients without OSA (Fig 2) .
Various oximetric indices have been studied for case finding of OSA, with sensitivities ranging from 40 to 100% and specificities ranging from 39 to 100%.6 In patients with OSA, we found that minSaO2 and mSaO2 were lower, and CT80 higher, than in patients without OSA. Indeed, AHI was negatively correlated with minSaO2 and mSaO2, and positively correlated with CT80. Finally, mSaO2 was a predictor of OSA according to logistic regression analysis. After determination of optimal thresholds by ROC curves, the oximetric criteria were the variables that had the best diagnostic values, as expressed by the area under the ROC curve30 (Table 3) ; however, this diagnostic value was not good enough to be useful as a screening technique (Fig 2) . This limitation was also pointed out by Gyulay and coworkers,31 who analyzed home nocturnal oximetry. In fact, a combination of independent clinical, functional, and oximetric features allowed prediction of the presence or absence of OSA with an accuracy of 100% in only a small number of patients (8%), and we could not find any other clinically useful combination of variables. Despite a trend toward a higher CT80 for men with OSA, logistic regression did not show any interaction between sex and oximetric data.
Logistic regression analysis provided a model that would have allowed to diagnose or exclude OSA confidently in 72.5% of our population. However, this model is rather complex because it includes 19 variables, which makes it unlikely to be used in clinical practice. A more simple equation, on the other hand, would not be accurate enough to be useful. In any case, such a model must be validated by prospective testing in other series of patients before being used in practice.9
Finally, the choice of PSG as a reference test for measurement of respiratory events, and of AHI for expression of results and discrimination between OSA and non-OSA subjects, may be controversial, because some studies found a poor correlation between AHI and some important clinical features of OSA such as daytime sleepiness.32 However, PSG remains the "gold standard" for the diagnosis of OSA despite extensive research on new diagnostic methods, and it seemed important to use the same reference test as in most studies in this field.9 16 17 For the same reason, an AHI threshold of 15 events/h was chosen for the diagnosis of OSA.33 We confirmed, however, that changing this cut-off value to 10 events/h did not modify our results.
We conclude that individual clinical, functional, and oximetric features do not adequately predict OSA in an overweight population (one third of which was female), and do not provide significant sex-related discrepancies. A predictive model developed by logistic regression analysis may be useful in 72.5% of patients, but this model is complex and its validity needs to be further tested in other series of patients.
| Acknowledgements |
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| Footnotes |
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Received for publication February 3, 1999. Accepted for publication July 6, 1999.
| References |
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