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ORIGINAL ARTICLE
Year : 2022  |  Volume : 66  |  Issue : 5  |  Page : 12-16  

Prevalence of overlap syndrome in patients with obstructive sleep apnea in a quaternary care center of Kerala


1 Senior Resident, Department of Respiratory Medicine, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeethem, Kochi, Kerala, India
2 Clinical Professor and HOD, Department of Respiratory Medicine, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeethem, Kochi, Kerala, India
3 Associate Professor, Department of Respiratory Medicine, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeethem, Kochi, Kerala, India
4 Professor, Department of Respiratory Medicine, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeethem, Kochi, Kerala, India
5 Junior Resident, Department of Respiratory Medicine, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeethem, Kochi, Kerala, India

Date of Submission10-Aug-2022
Date of Decision15-Aug-2022
Date of Acceptance17-Aug-2022
Date of Web Publication11-Nov-2022

Correspondence Address:
Asmita Anilkumar Mehta
Department of Respiratory Medicine, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeethem Ponekkara, Kochi - 682 041, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijph.ijph_1085_22

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   Abstract 


Background: The coexistence of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) is termed “Overlap syndrome (OS).” Objectives: The present study aimed at estimating the prevalence of OS among patients diagnosed with OSA. Methods: It was a prospective observational study conducted on patients presenting to respiratory medicine outpatient department (sleep clinic) with symptoms of sleep-disordered breathing and was found to have OSA by overnight polysomnography. These patients were then subjected to spirometry to diagnose COPD. Results: The prevalence of OS in the study population was found to be 41.3%. Excessive daytime sleepiness was found to be higher in overlap group patients (P = 0.033), the difference was statistically significant. The mean age (59.9 ± 9.6 years) was found to be high in the OS group compared to those without the same. The mean forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and FEV1/FVC (pre- and postbronchodilator) spirometry parameters were found to be lower in patients with OS. Conclusion: The study showed that the prevalence of OS in the present study was 41.3%. Excessive daytime sleepiness and age >60 years were risk factors for OS in a patient with OSA. OS patients had lower pulmonary function values.

Keywords: Chronic obstructive pulmonary disease, daytime sleepiness, obstructive sleep apnea, overlap syndrome


How to cite this article:
Nair S, Paul T, Mehta AA, Haridas N, Kunoor A, Sudhakar N. Prevalence of overlap syndrome in patients with obstructive sleep apnea in a quaternary care center of Kerala. Indian J Public Health 2022;66, Suppl S1:12-6

How to cite this URL:
Nair S, Paul T, Mehta AA, Haridas N, Kunoor A, Sudhakar N. Prevalence of overlap syndrome in patients with obstructive sleep apnea in a quaternary care center of Kerala. Indian J Public Health [serial online] 2022 [cited 2022 Dec 1];66, Suppl S1:12-6. Available from: https://www.ijph.in/text.asp?2022/66/5/12/360650




   Introduction Top


The term “Overlap syndrome (OS)” was coined by David Flenley in 1980 for the coexistence of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) regardless of the severity of one or the other.[1] He considered OS to have significant clinical and therapeutic implications, different from the presentation and management of each underlying disorder. The prevalence reported is highly variable and depends on the severity of COPD, definitions used for diagnosis, and the diagnostic techniques.[2] It has been suggested that patients with OS are at a higher risk of developing respiratory insufficiency, pulmonary hypertension, daytime hypercapnia, and more profound nocturnal hypoxemia.[3] Untreated OSA can cause nocturnal hypoxemia, pulmonary hypertension, heart failure, cardiac arrhythmia, and insulin resistance.[4] Patients with OSA have high levels of tumor necrosis factor-alpha and interleukin 6 which causes inflammation.[1],[2],[3],[4],[5] This chronic inflammatory stimulus may result in worsening of respiratory status in patients with underlying COPD, which is also characterized by chronic inflammation throughout the airways, parenchyma, and pulmonary vasculature.

The primary aim of the study was to estimate the prevalence of OS among patients diagnosed with OSA by polysomnography. The secondary aim was to study the clinical profile and factors associated with OS.


   Materials and Methods Top


The study was commenced after receiving authorization certificate from both scientific and ethical committees of Amrita Institute of Medical Sciences and Research Centre.

Study design

It was a prospective observational study conducted at quaternary care hospital in the department of respiratory medicine during November 2015–July 2017.

All patients >18 years who presented with symptoms of sleep-disordered breathing (loud snoring, excessive daytime sleepiness, apneic spells or nocturnal awakening, early morning headache or fatigue) were included in the study. A clinical pro forma was used to collect a detailed history, baseline demographics such as age and sex, Epworth's Sleepiness Score, and anthropometric parameters such as height, weight, body mass index (BMI), and neck circumference. All participants with high Epworth's Sleepiness Score of >10 were subjected to standard overnight polysomnography[6] Informed consent was taken before participation in the study.[7] Arousals were scored according to the American Sleep Disorders Association criteria.[8] Sleep study parameters collected from polysomnography were Apnea–Hypopnea Index (AHI), Respiratory Disturbance Index, total sleep time, Stage 1, Stage 2, Stage 3, and rapid eye movement (REM) stage. OSA was defined as an AHI >5/h with daytime symptoms or AHI >15 without daytime symptoms which is diagnosed from full-channel polysomnography. All patients who were diagnosed with OSA (AHI ≥5) were included in the study and they underwent spirometry. A detailed history including duration of shortness of breath, smoking status, cough, and thorough clinical examination was done for all patients. The following data were collected: forced vital capacity (FVC), forced expiratory volume in 1s (FEV1), total lung capacity, FEV1/FVC ratio, and postbronchodilator response of FEV1. COPD was defined as a postbronchodilator FEV1/FVC ratio < 70%. The severity of COPD was determined based on the percent of predicted FEV1.[4] Patients were divided into two groups based on the presence and absence of OS. Arterial blood gas analysis was done whenever indicated.

Statistical analysis

Data analysis was done using IBM SPSS Statistics version 20 for windows (SPSS Inc, Chicago, Illinois, USA). All the continuous parameters were presented as mean ± standard deviation. All categorical variables were presented as frequency or percentage. The prevalence of OS was measured using percentage. For finding the association between two categorical variables, Chi-square test was used. The mean parameters of spirometry, arterial blood gas analysis, BMI, and stages of sleep between patients with and without OS were compared using an independent sample t-test. The mean spirometric parameters before and after giving bronchodilator were compared using paired sample t-test. The percentage increases of spirometric parameters from the baseline between patients with OS and without OS were compared using Mann–Whitney U-test. Pearson's correlation coefficient was used for finding the correlation between age and spirometric parameters in patients with and without OS. P < 0.05 was considered statistically significant.


   Results Top


There were 80 patients included in the present study. The baseline characteristics of the study population are shown in [Table 1]. The prevalence of OS in our study population (OSA) was found to be 41.3%. The study group was divided into two groups based on the presence or absence of OS.
Table 1: Associations between overlap syndrome and clinical factors

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The association between OS and other various clinical factors is furnished in [Table 2]. There were 90.9% of the study participants with OS (n = 47) and 68.1% of the study participants without OS (n = 33) with excessive daytime sleepiness. The presence of excessive daytime sleepiness was 4.96 times higher in patients with OS compared to those without (P = 0.033). No other clinical factors were showing a statistically significant association with OS.

The mean age was found to be significantly high in study participants with the OS group (59.9 ± 9.6 years) than in patients without the OS group (54.3 ± 9.6 years). Other factors such as BMI and AHI were not found to have an association with the OS group.
Table 2: Comparison of sleep parameters S1, S2, S3, rapid eye movement, and total sleep time between the study participants without overlap syndrome and with overlap syndrome

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There were 37.9% of males compared to 50% of females who had OS, respectively. However, the association between sex and OS was found to be insignificant (P = 0.469).

The association between the grades of OSA and the severity of COPD was also found to be insignificant [Table 1].

OS was found to be present in 39% of smokers and 43.5% of nonsmokers. The association between smoking and OS was found to be insignificant (P = 0.821).

The mean FEV1 (pre- and postbronchodilator) was found to be significantly lower in patient with the OS group (mean FEV1 prebronchodilator 55.12 ± 17.43 and mean FEV1 postbronchodilator 60.45 ± 18.13) than in patients without OS (mean FEV1 prebronchodilator 77.67 ± 16.47 and FEV1 postbronchodilator 81.72 ± 16.25). The mean FVC (pre- and postbronchodilator) and mean FEV1/FVC (pre- and postbronchodilator) were found to be lower in patients with OS and significantly higher in patients without OS group (P < 0.001) [Table 1].

Out of all the patients for whom ABG was done, 14.8% of the patients with OS and 4.3% of the patients without OS showed acidosis (PH <7.35). Low PH was clinically high in the OS group than in patients without the OS group but that was also statistically insignificant (P = 0.799). Similarly, was no statistically significant association found between PCO2 and PaO2 and OS as shown in [Table 1].

With sleep parameters, the mean S2 among OS group was 160 ± 101 min and without the OS group was 300 ± 71. The duration difference in average N2 stage among patients with and without OS was found to be significant (P = 0.005). The mean total sleep time among OS group was 384.8 ± 79.9 and without the OS group was 480.5 ± 62.03. The average total sleep time stage among patients with and without OS was found to be significantly high (P =– 0.017) [Table 1].


   Discussion Top


In our study, we found that the mean age was significantly high in study participants in the OS group (59.9 ± 9.6 years) than in patients with only OSA (54.3 ± 9.6 years). As the study cohort included patients from health-care facilities and not the community, the results should be taken with caution. The explanation can be due to the lack of awareness about sleep apnea and COPD among the younger population. The mean BMI (31.58 ± 5.51 in the OS group and 30.28 ± 4.7 in patients without OS) in our study was found to be slightly higher in the OS group when compared to those without OS [Table 1]. It was previously proven that being overweight but not obese was protective for OSA patients from COPD, and that BMI was a significant predictor of COPD but only in those with moderate-to-severe OSA. However, the difference was not statistically significant (P = 0.278). This can be due to the average BMI among the Indian population is toward the lower range.

OS was present in 37.9% of males compared to 50% of females in the present study. Based on a cohort study, active cigarette smoking showed a significant association with OS compared to OSA versus COPD alone.[9],[10],[11] In the present study, there was no association between smoking and OS (P = 0.821).

In the present study, the mean AHI was lower in the OS group. This finding was similar to the study done Rizzi et al.,[10] which also showed lower mean AHI in the OS group (P = 0.05) in the contrast OSA group. However, we could not find any association between mean AHI and OS.

In the previously mentioned study, Greenberg Dotan et al.[12] found that among women, the difference in COPD prevalence between OSA and control was greater than among men. In the present study with gender as parameter, among males and females, 37.9% and 50% had OS, respectively, but the association between sex and OS was found to be insignificant (P = 0.469). This finding might state that there is a possible gender-based difference in the extent to which the pro-inflammatory state engendered or obstructive lung disease affects upper airway physiology in women more than among men.

In the present study, the mean FEV1 was significantly lower in the OS group compared to those with OSA. The mean FVC (pre- and postbronchodilator) and mean FEV1/FVC (pre- and postbronchodilator) were also found to be lower in patients with OS than in patients without OS group (P < 0.001). This was similar to the study by López-Acevedo et al.[9]

In our study, low PaO2 (<60), high PaCo2 (>45), and low PH (<7.35) were found in the OS group when compared to OSA alone but the difference was statistically insignificant. In a study by Rizzi et al.[10] also, PaCO2 was significantly higher in OS than in OSA alone group (P = 0.001).

We found that the association between mean N2, non-REM (NREM), and total sleep time was reduced among OS group when compared to OSA alone. The association between the stages of sleep has been earlier studied by Rizzi et al.,[10] who found the mean sleep efficiency, and the duration of Stage N1, NREM, and REM stages were reduced in the OS group than in OSA alone (P = 0.05).

Consistent with the literature, it was observed in the present study that the severity of OSA and COPD were not directly associated with each other. The frequency of OS as well as the factors associated with OS are shown in [Table 2][13],[14],[15],[16],[17],[18],[19]. The lack of awareness of OSA symptoms in patients with severe chronic disease also contributes to this variance.

The strength of our study is that the evidence of OSA and COPD was based on PSG and spirometry results. The limitation is size and selection of the cohort which was done from a quaternary health care facility may not be representative of the general population.


   Conclusion Top


We conclude that there was no association between COPD and AHI. The risk of OS or indirectly of COPD, among those with OSA increased with smoking and aging but decreased with being overweight.

The age and increased daytime sleepiness among OSA patients were associated with moderate-to-severe obstructive patterns in spirometry and indirectly OS. There was no high PCO2 in ABG in OS patients as expected. Participants who have COPD and typical risk factors for OSA such as obesity, chronic snoring, enlarged neck, daytime sleepiness, and hypertension should be considered for further testing for OS.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

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Rizzi M, Palma P, Andreoli A, Greco M, Bamberga M, Antivalle M, et al. Prevalence and clinical feature of the “overlap syndrome”, obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD), in OSA population. Sleep Breath 1997;2:68-72.  Back to cited text no. 10
    
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López-Acevedo MN, Torres-Palacios A, Elena Ocasio-Tascón M, Campos-Santiago Z, Rodríguez-Cintrón W. Overlap syndrome: An indication for sleep studies? A pilot study. Sleep Breath 2009;13:409-13.  Back to cited text no. 11
    
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Calderon E, Carmona C, Arenas M, Fuentes MA, Sanchez A, Capote F. E studio comparativo de pacientes con enfermedad pulmonar obstructivacr_onica con y sin sındrome de apneas obstructivas durante el sueno. Arch Bronconeumol 1999;35:539-43.  Back to cited text no. 13
    
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Sanders MH, Newman AB, Haggerty CL, Redline S, Lebowitz M, Samet J, et al. Sleep and sleep-disordered breathing in adults with predominantly mild obstructive airway disease. Am J Respir Crit Care Med 2003;167:7-14.  Back to cited text no. 16
    
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