Introduction

Obstructive sleep apnea syndrome (OSAS) is a common disorder caused by repeated episodes of airflow cessation (apneas) leading to arterial hypoxemia and sleep disruption [1]. This syndrome may have a number of consequences that deeply affect the quality of life, such as excessive daytime sleepiness, neurocognitive deterioration, and endocrinologic and metabolic effects [2]. Metabolic syndrome (MS) that is, itself, emerging as a highly prevalent public health problem, may be linked with OSAS. In fact, the presence of OSAS may increase the risk of developing some aspects of metabolic syndrome [3], [4]. Moreover, clinical studies have shown a statistically significant correlation between the severity of OSAS and obesity, hypertension, diabetes mellitus, dyslipidaemia and metabolic syndrome [5]. However, little is known about the possible association between early-stage OSAS and MS components in active workers.

Only limited knowledge is also available concerning the relationship between the presence of OSAS and psychological problems, although this syndrome is known to have an impact on neurocognitive functioning. Employees with OSAS run a major risk of long-term work disability caused by injuries and mental disorders [6]. Self-reported symptoms of OSAS are an independent risk factor for subsequent long-term sick leave and permanent work disability [7]. Both OSAS and hypertension related to this syndrome are significant predictors of impairment in workers [8]. However, all the above studies have focused on advanced cases of OSAS. Again, nothing is known about the mental health of active workers with previously undiagnosed OSAS.

The aim of occupational medicine is to continuously improve the health of workers. For this reason, many health promotion campaigns are conducted in major companies. The main objective of these programs is to identify a risk factor that can be removed or minimized, thereby improving occupational health. OSAS may constitute a risk factor that requires an occupational prevention program. The first objective of this study was therefore to evaluate the importance of OSAS as a risk factor. In order to do this we aim to assess the prevalence of OSAS among previously undiagnosed “healthy” subjects working in various fields and study the association between OSAS and MS components and mental health.

Before undertaking a campaign to promote health, it is necessary to check the availability of resources in the country and productive area where you intend to introduce measures of prevention. In Italy, industrial production is characterized mainly by the presence of small businesses with fewer than 50 workers. Health promotion in these companies is more difficult than in large firms, owing to the lack of financial resources and organizational structures needed to support it.

The second objective of our study was to ascertain whether a health promotion program, conducted by a clinician performing health surveillance without the use of additional resources can achieve measurable results in a sample of small companies in the Latium region of Italy.

Methods

Results

The clinical and demographic characteristics of the subjects, both as a group and classified by gender, are reported in Table 1. The descriptive statistics indicate a group of experienced workers (13.8±9.1 years) with a low number (37.3%) of smokers and a normal mean BMI range (24.5±4.3 Kg/cm²). 4.3% (n = 7) of subjects had an ESS score >10, indicating daytime sleepiness.

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Table 1. Medical and demographic data for participants.

https://doi.org/10.1371/journal.pone.0097188.t001

In the gender comparison, males reported a significantly higher consumption of alcohol than females (p<0.011). A greater frequency of enlarged neck circumference, increased neck-chin angle, and Mallampati grade 3–4 (p<0.024) was found in males than in females. The score of the SDS questionnaire on sleep disorders was significantly higher in males than in females (p<0.025), whereas no significant difference between genders was observed in the scores of the ESS questionnaire on sleepiness and the GHQ on mental health.

We identified 25 subjects (12.3%) with a clinical suspicion of OSAS. None of the workers reached the level of 17 points on the ESS scale, considered to be the cut-off point for greater diagnostic specificity. Only 3 workers with suspected OSAS were affected by mild sleepiness (ESS score >10). Two of the latter had parameters indicating a complete metabolic syndrome (obesity, plus two other metabolic disorders).

In data regarding MS only, 50 subjects (24.5%) presented one or more risk factors (obesity, dyslipidemia, hypertension, or diabetes). The prevalence of workers with suspect OSAS having at least one MS components was 52.0%. Logistic regression analysis showed that clinical suspicion of OSAS was significantly associated with the presence of metabolic disorders (OR = 3.83; 95%CI 1.45–10.13) in a model that included other personal factors (sex, age, smoking habit, alcohol consumption, and sedentary life). Age, male gender and lack of physical activity were significantly associated with the presence of metabolic syndrome components (Table 2).

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Table 2. Association between suspected OSAS and personal factors (age, sex, smoking habit, alcohol use, lack of physical exercise) and the presence of at least one components of metabolic syndrome (obesity, hypertension, dyslipidemia, diabetes).

https://doi.org/10.1371/journal.pone.0097188.t002

Psychological problems, as measured by the GHQ12 mean score, were significantly higher in OSAS than in non-OSAS subjects (25.7+7.2 vs. 21.8+4.0, test t p<0.000). Workers with OSAS had a significantly increased risk of having a GHQ12 score in the highest quartile, (OR = 4.67; 95%CI = 1.72–12.64) in a multivariate logistic regression model that included age, gender, smoking habit, alcohol use, and physical activity (Table 3).

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Table 3. Associations between suspected OSAS and personal factors (age, sex, smoking habit, alcohol use, lack of physical exercise) and GHQ12 score in the highest quartile.

https://doi.org/10.1371/journal.pone.0097188.t003

During the follow-up survey carried out in 2013, all workers who had been sent to their own doctors with a diagnosis of suspected OSAS, and an invitation to perform additional tests under the NHS, were questioned on the outcome. A worker with severe systolic-diastolic hypertension resistant to therapy had been diagnosed with OSAS. Effective treatment of OSAS with continuous positive airway pressure for 3 months had significantly reduced blood pressure. Two workers with abdominal obesity had received confirmation of the OSAS diagnosis and were following positive airway pressure therapy associated with nutritional therapy. One worker had the OSAS diagnosis confirmed and had been treated with mandibular advance device therapy. In the case of another worker who had undergone further medical investigations, the diagnosis of OSAS had been ruled out. The majority of workers (20/25 = 80%) had not heeded the invitation of the occupational physician and had not carried out any further investigation. The reasons most frequently given for failing to adhere to the invitation were lack of time, lack of health service availability, and especially the conviction that they were in a satisfactory state of health.

Discussion

The present study confirms that obstructive sleep apnea is a rather frequent and underdiagnosed condition, and that daytime sleepiness is not uncommon. This is very worrisome. Reduction in vigilance and attention could be fatal in some job categories such as drivers and operators of dangerous machines. Moreover, the risk of cardiovascular disease and the psychological problems associated with OSAS could lead to serious health consequences.

Although this is a small-scale study, our assumptions are also valid for selected populations. As we know, the occupational physician can only examine healthy workers. In fact, medical examination in the workplace is not possible during illness, even when it is of short duration. This can cause an undervaluation of the workers’ state of illness. Moreover, workers are selected from the general population. In fact, the so-called “healthy worker effect” refers precisely to the fact that the occupational population have a better level of health than the general population. Although we tested a selected population, we found a 12.3% prevalence of suspected OSAS, and 4.3% of workers reported feeling very drowsy during work.

In this sample, 24.5% suffered from obesity, or high blood pressure, diabetes or dyslipidemia. OSAS was significantly associated with these metabolic disorders. The cross-sectional nature of these observations prevents us from making causal considerations, however a recent review [19] shows that obesity predisposes to OSAS, and the increasing prevalence of OSAS is influenced by the worldwide ongoing epidemic of obesity [20]. It has been observed, indeed, that obesity and OSAS tend to cluster in the same workplace [21]. Many markers of cardiovascular risk, such as sympathetic activation, systemic inflammation, and endothelial dysfunction, are significantly increased in obese patients with OSAS compared to those without OSAS [22]–[25]. This fact suggests that OSAS is not simply an epiphenomenon of obesity. Moreover, findings from animal models and patients with OSAS show that intermittent hypoxia exacerbates the metabolic dysfunction of obesity, augmenting insulin resistance and nonalcoholic fatty liver disease [26], [27]. In patients with the metabolic syndrome, OSAS is independently associated with increased glucose and triglyceride levels as well as markers of inflammation, arterial stiffness, and atherosclerosis [28], [29]. Several cohort studies have consistently shown that OSAS is associated with increased cardiovascular mortality, independent of obesity [30]–[32]. Taken together, these results support the concept that OSA exacerbates the cardiometabolic risk attributed to obesity and metabolic syndrome. However, it has been demonstrated that recognition and treatment of OSAS may decrease the cardiovascular risk in patients with metabolic syndrome [33]–[36].

An interesting result of our study was the association observed between suspected OSAS and psychological problems. To our knowledge, this aspect has never been studied in previous research on patients with suspected OSAS although this syndrome is known to be linked to a number of complications such as psychiatric conditions that significantly impair the quality of life. For example, OSAS may be associated with depression in adolescents and with Down Syndrome in young adults [37]. These macroscopic effects are the result of deep physiological alterations. In fact, at cellular level, OSAS can cause intermittent hypoxia, hormonal imbalance, and/or systemic inflammation which may influence cognitive functions [38]. However, in patients with OSAS, mental fatigue and cognitive impairment are directly correlated to the severity of nocturnal disordered breathing [39]. Clearly, the severity of the pathology is very important because a cognitive consequence is expected only in severe and advanced cases, not in recently diagnosed OSAS patients with minimal co-morbidities [40], or in suspected cases identified during screening.

Mood disorders in patients with OSAS have also been studied, especially in relation to the way in which these problems may affect adherence to treatment; however the nature of the relationship between OSAS and depression and anxiety is still unclear [41]. In fact, recent research on depression and anxiety in obstructive sleep apnea syndrome led to inconsistent findings: prevalence figures fluctuated considerably for both depression (7–63%) and anxiety (11–70%) [42]. Moreover, the reported associations were often contrasting. In some cross-sectional studies, OSAS patients had higher scores for depression and anxiety than the control group [43], while in other studies, OSAS was not associated with severe symptoms of depression and anxiety [44]. These differences are probably due to the methods used to measure psychological disorders.

In the present study, we used a particularly sensitive tool to measure mental health. The GHQ is possibly the most common assessment of mental well-being [45]. In fact, it is used to detect minor psychiatric (non-psychotic) disorders in the general population and within community or non-psychiatric clinical settings. It focuses on two main areas: inability to carry out normal functions and the appearance of new and distressing psychological phenomena. The GHQ assesses the respondent’s current state and determines whether it differs from his or her usual state. Therefore, it is sensitive to short-term psychiatric disorders, but not to long-standing attributes of the respondent. This instrument, which was designed to detect psychiatric morbidity, has also performed very well in trans-cultural comparisons of community-based populations [46]. We can therefore assume that the GHQ measures an early, and possibly transient worsening of psychological conditions in workers with recent onset of sleep apnea. We conclude, in accordance with the literature, that the relationships between early-stage OSA and psychological disturbances are weak but significant.

In our study, prevalence values for metabolic syndrome were lower than those estimated in the general Italian population and other industrialized countries. The third National Health and Nutrition Examination Survey (NHANES III) recorded a 21.8% prevalence of metabolic syndrome in the total population [47]. In NHANES III the prevalence of abdominal obesity was approximately 50% in females and 30% in males. This was also higher than the value found in our study, as were the US population levels of impaired HDL-cholesterol, hyperglycemia and hypertension. The few data available for Italy confirm that metabolic syndrome and its components occur more frequently than was observed in our sample. The Italian Longitudinal Study on Aging (ILSA) reported a metabolic syndrome prevalence of 25.9% [48]. A study conducted in the Marche Region of Italy found a metabolic syndrome prevalence of 11.5% in the 36 to 42 age group and of 22.5% in subjects between the age of 43 and 60 years [49]. This demonstrated that in our sample group at least, the health level of employees was higher than that of the general population – a fact that must be taken into account in the planning of action for health. It also indicated that the subjects taking part in our study were not prompted in because they were suffering from one of the pathologies under investigation. This was important since we know that being affected by any morbid condition induces individuals to be more precise when recalling all the possible causal factors for that illness. This phenomenon, known as “recall bias”, can give rise to fictitious associations. Compared with what may occur in case-control studies, the limited number of sick subjects in our survey reduced the impact of such an effect.

Unfortunately, in our study, the majority of workers with suspected OSAS failed to respond to advice suggesting they undergo other tests to confirm the diagnosis. In the few cases in which subjects followed the advice of the occupational physician, a significant clinical improvement was observed.

This experience demonstrated that health promotion during compulsory health surveillance is effective in only a limited number of workers. The main reason for ignoring the physician’s advice seemed to be unawareness on the part of the workers of the importance of the detrimental effects of OSAS. A multilevel effort that includes specific information about the health risks associated with OSAS and incentives for workers who participate in the programs proposed, might effectively help to safeguard workers’ health. Since small enterprises lack financial resources and training structures, these services must be provided by public or consortium facilities.

The main limitation of this study concerned sample selection, as all the companies were located in the same region and were under the health surveillance of the same doctor (NM). These conditions obviously prevented us from extending our findings to other situations. One of the strengths of the study was the high level of participation at baseline. Another strength was the inclusion of general workers in the study population. Previous studies on the prevalence and risk factors of occupational OSAS had mainly targeted at-risk workers, so that results were not applicable to a more general population of workers. A further strength was the broad set of clinical issues examined; these included an objective evaluation of the risk of OSAS, an assessment of sleepiness, blood tests and clinical examination to diagnose metabolic syndrome and screening for psychological disorders. All these tests were included during the routine medical surveillance of workers without a significant burden of time for the performance of medical examinations.

The data collected show that OSAS is an important risk factor that is widely prevalent in the general population of workers, and that this syndrome is strongly correlated with metabolic syndrome and mental disorders. It is therefore an ideal candidate for health intervention.

Health promotion programs conducted in small enterprises and based exclusively on services provided by the NHS, without a spending commitment for training and incentives on the part of employers, have a beneficial but limited impact on the health of workers. Only a few workers accepted the invitation of the occupational physician to undergo more specialized tests to confirm or refute the diagnosis of OSAS. However, excellent results were obtained for those who followed this advice. We are confident that a prevention program comprising educational, health and organizational activities could actually prevent OSAS and its physical and psychological consequences in the general population of workers.