Insomnia in Older Adults with Chronic Obstructive Pulmonary Disease (COPD) in Hong Kong: A Case-Control Study

Abstract

This study aimed to determine the frequency and sociodemographic/clinical correlates of insomnia in Chinese patients aged ≥60 years suffering from chronic obstructive pulmonary disease (COPD). In this case-control study of 142 outpatients with COPD and 218 sex- and age-matched control subjects, COPD patients were recruited from a prospective study sample hospitalized in Hong Kong for acute COPD exacerbation (≥2 major COPD symptoms or >1 major+minor COPD symptoms for ≥2 consecutive days). Controls were recruited from social centres in Hong Kong. Activity of daily living was assessed with the Instrumental Activities of Daily Living Scale, life events were evaluated using the Life Event Scale, depressive symptoms were ascertained with the Geriatric Depression Scale, and quality of life was measured using the Medical Outcomes Study Short Form-12. Early, middle and late insomnia were measured using items 4, 5 and 6 of the Hamilton Rating Scale for Depression. The frequency of ≥1 type of insomnia was 47.2% in patients and 25.7% in controls; frequencies of early, middle and late insomnia in patients were 24.6%, 31.0%, and 26.1%, respectively, compared to 14.7%, 14.7% and 11.9% in controls. Group differences were non-significant after controlling for relevant covariates. However, in multiple logistic regression analysis, more physical illnesses (p = 0.02, OR = 1.3, 95% CI = 1.1–1.7) and more severe depressive symptoms (p = 0.009, OR = 1.1, 95% CI = 1.03–1.3) were independently associated with any type of insomnia in COPD patients, accounting for 21.3% of the variance. A significant proportion of older adult Chinese COPD patients suffer from insomnia that warrants more attention in clinical practice.

Keywords :

• China
• chronic obstructive pulmonary disease
• depression
• elderly
• insomnia

Introduction

Chronic obstructive pulmonary disease (COPD) is a common and progressive disease (1). The clinical presentation of COPD is characterized by intermittent exacerbations of chronic dyspnoea, sputum production and cough. The disabling symptom profile and progressive course of COPD have a serious impact on various aspects of the patients’ life. Since cure is still not possible for most patients, the main treatment goals are improvement of functional status and quality of life (QOL) in addition to the reduction of acute exacerbations.

More than half of COPD patients complain of insomnia, which has far-reaching clinical and prognostic implications because insomnia may lead to poorer overall health, impaired quality of life, and greater use of general medical services (2, 3). Several Western studies examined the association between insomnia and COPD. A number of clinical variables, such as tobacco use, anxiety, depression, oxygen desaturation and poor oxygenation have been associated with insomnia (2, 4–6). Preliminary evidence suggests that cross-cultural or ethnic differences exist in the prevalence and contributing factors of insomnia (7, 8). Therefore, Western findings may not be fully applicable to patients with different ethnic and cultural backgrounds. To the best of our knowledge, no prior study has addressed insomnia in Chinese patients with COPD.

The aim of this study was to examine the frequency and type of insomnia in Chinese patients with COPD aged 60 years and above and to explore its demographic and clinical correlates.

Methods

Study setting and participants

This study was part of an ongoing project entitled ìAcute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD)î (9) that follows patients originally admitted to the Prince of Wales Hospital (PWH) in Hong Kong with acute exacerbation of COPD between 1 May 2004 and 30 April 2005. AECOPD patients had pre-existing COPD and at least two of its major symptoms (increased dyspnea, increased sputum purulence and sputum amount), or one major and one minor symptom (nasal discharge/­congestion, wheezing sore throat, cough) for at least 2 consecutive days. Patients were offered participation in the study if they were of Chinese ethnicity, were able to communicate, could tolerate a 1-hour interview and understood the purpose and procedures of the study. Patients were recruited consecutively from the PWH Respiratory Outpatient Clinic. Control subjects without history of COPD matched to age and sex were recruited from social centres in the Shatin and Tai Po districts of Hong Kong.

Approval for the study was obtained from the Joint Chinese University of Hong Kong –New Territories East Cluster (CUHK-NTEC) Clinical Research Ethics committee. All subjects provided written consent prior to entering the study.

Data collection

Each patient and control subject received a face-to-face interview conducted by two trained psychiatrists. Subjects’ socio-demographic data were collected using a form specifically designed for this study.

The GOLD (The Global Initiative for Chronic Obstructive Lung Disease) guideline was used to classify the severity of airflow limitation based on spirometry (10): (1) Stage 1 mild COPD: FEV1 ≥ 80% of predicted value; (2) Stage 2 moderate COPD: FEV1 ≥ 50% and <80% of predicted value; (3) Stage 3 severe COPD: FEV1 ≥ 30% and <50% of predicted value; (4) Stage 4 very severe COPD: FEV1 < 30% of predicted value.

Following procedures employed in earlier studies, sleep problems during the previous two weeks were surveyed targeting three basic types (11, 12): early, middle and late insomnia using items 4, 5 and 6 of the Hamilton Rating Scale for Depression (HAMD). There are three possible scores for each item. For item-4 (insomnia early), 0 = No difficulty falling asleep; 1 = Complains of occasional difficulty falling asleep - more than 1/2 hour; 2 = Complains of nightly difficulty falling asleep. For item-5 (insomnia middle), 0 = No difficulty; 1 = Patient complains of being restless and disturbed during the night; 2 = Waking during the night - any getting out of bed (except for purposes of voiding). For item-6 (insomnia late), 0 = No difficulty; 1 = Waking in early hours of the morning but goes back to sleep; 2 = Unable to fall asleep again if he gets out of bed. If subjects were rated as ì1î or ì2î on at least one of the three items, they were classified as ìhaving insomnia.î

The number of hospital admissions in the past year was recorded from the medical notes. Activities of daily living (ADL) were measured with the locally-adapted instrumental Activities of Daily Living Scale (IADL) (13). The IADL covers the use of telephone and public transportation, shopping, cooking, laundry, medication and financial management. In the local version of the IADL, each of these activities was rated on a four-point scale ranging from 0 to 3. A higher total score indicates worse functional disability.

Depressive symptoms were evaluated using the locally validated Chinese version of the 15-item Geriatric Depression Scale (GDS) with higher scores reflecting more severe depressive symptoms (14, 15). Life events were measured using a modified version of the Life Event Scale (LES) (16). This modified scale has been used extensively in the Chinese population (17). The subjects were asked whether they had experienced significant life events in the preceding 3 years.

Subjects’ QOL was measured with the validated ­Chinese version of Medical Outcomes Study Short Form-12 (SF-12) and the St. George's Respiratory Questionnaire (SGRQ) (18). The SF-12 is a generic instrument of QOL containing 12 items. The SF-12 has two domains: the physical component score (PCS) and the mental component score (MCS), with higher scores indicating better QOL. The locally validated Cantonese version of the Mini-Mental State Examination (MMSE) (19, 20) was administered to screen for cognitive impairment.

The inter-rater reliability of the above instruments between two trained psychiatrists obtained in 60 older psychiatric patients was satisfactory (Intra-class correlation coefficients >0.9).

Statistical analyses

The data were analyzed with SPSS 20.0 for Windows (SPSS Inc., Chicago, IL, USA). The comparisons between patients and controls and between insomnia and non-insomnia patients regarding basic socio-demographic and clinical characteristics were performed with independent sample t-test, Mann–Whitney U-test, and chi-square test, as appropriate. The comparison between patients and controls with respect to frequency of insomnia was conducted by multiple logistic regression analysis with the ìEnterî method; insomnia was the dependent variable, group membership (patients vs. controls) was the independent variable, and other variables that significantly differed between the two groups in univariate analyses were entered as covariates. In COPD patients, the independent demographic and clinical correlates of insomnia were also examined by multiple logistic regression analysis with the ìEnterî method with any type of insomnia as the dependent variable and the variables that significantly differed between the insomnia and non-insomnia patient groups in univariate analyses entered as covariates. Two-tailed tests were used in all analyses, with the significance level set at 0.05.

Results

A total of 154 COPD patients and 225 controls were approached and invited to participate in this study; 142 patients and 218 controls met the study criteria, agreed to particpate and completed the assessments.

Table 1 shows the basic demographic variables and sleep problems in both groups, and the patients’ clinical characteristics. The frequencies of early, middle and late and any type of insomnia were 24.6%, 31.0%, 26.1% and 47.2% respectively, while the corresponding values for the controls were 14.7%, 14.7%, 11.9% and 25.7%. Compared to the controls, COPD patients had less religious beliefs, better financial perception, more physical illnesses, worse functional ability and physical QOL, more severe depressive symptoms, and more insomnia. After controlling for variables that significantly differed between the two groups in multiple logistic regression analyses, the significant difference between the two groups with respect to insomnia early (p = 0.96, OR 1.0, 95% CI 0.5–1.9), insomnia middle (p = 0.40, OR 1.3, 95% CI 0.7−2.5), insomnia late (p = 0.55, OR 1.2, 95% CI 0.6–2.5) and any type of insomnia (p = 0.32, OR 1.3, 95% CI 0.8–2.3) disappeared.

Table 1.  Basic demographic and clinical characteristics of the study sample

	Controls (n = 218)		COPD patients (n = 142)		Statistics
	N	%	N	%	X2	df	p
Male	164	75.2	118	83.1	3.1	1	0.08
Married/cohabitating	155	71.1	106	74.6	0.5	1	0.46
Living with others	177	81.2	123	86.6	1.8	1	0.18
Education					5.2	2	0.08
Illiterate or primary school	147	67.4	106	74.6
Junior and senior high school	58	26.6	34	23.9
College and above	13	6.0	2	1.4
Religious belief	136	62.4	62	43.7	12.8	1	<0.001
Financial perception					13.2	2	0.001
Poor	75	34.4	24	16.9
Moderate	54	24.8	44	31.0
Good	89	40.8	74	52.1
COPD severity
Mild (FEV1 >80% predicted normal)	—	—	9	6.3
Moderate (FEV1 50–80% predicted normal)	—	—	22	15.5
Severe(FEV1 30–50% predicted normal)	—	—	65	45.8
Very severe (FEV1 <30% predicted normal)	—	—	46	32.4
Insomnia early	32	14.7	35	24.6	5.6	1	0.02
Insomnia middle	32	14.7	44	31.0	13.7	1	<0.001
Insomnia late	26	11.9	37	26.1	11.9	1	0.001
Any type of insomnia	56	25.7	67	47.2	17.7	1	<0.001
	Mean	SD	Mean	SD	T / Z	df	p
Age (year)	75.0	6.9	73.9	6.2	1.5	358	0.13
MMSE total	26.5	3.5	26.0	4.2	1.3	358	0.20
No. of physical illnesses	1.9	1.3	3.0	1.7	−5.5	—a	<0.001
IADL total	3.2	5.4	5.8	5.7	−6.0	—a	<0.001
Life events in the past year	0.7	1.1	0.4	0.7	−1.7	—a	0.09
GDS	2.8	3.1	4.7	4.1	−4.8	—a	<0.001
PCS	50.4	16.0	38.7	19.9	6.2	358	<0.001
MCS	57.6	16.7	56.4	23.9	0.5	358	0.59

a = Mann–Whitney U-test; MMSE = Mini-Mental State Examination; IADL = Instrumental Activities of Daily Living Scale; GDS = Geriatric Depression Scale; PCS = physical component score of Medical Outcomes Study; MCS = mental component score of Medical Outcomes Study.

Table 2 presents the socio-demographic and clinical characteristics of COPD patients with and without any type of insomnia. Patients with sleep problems had more physical illnesses, worse functional ability and more severe depressive symptoms.

Table 2.   Basic demographic and clinical characteristics of COPD patients

	Non-insomnia (n = 75)		Insomnia (n = 67)		Statistics
	N	%	N	%	X2	df	P
Male	64	85.3	54	80.6	0.6	1	0.45
Married/cohabitating	57	76.0	49	73.1	0.2	1	0.70
Living with others	67	89.3	56	83.6	1.0	1	0.32
Education					2.3	2	0.32
Illiterate or primary school	57	76.0	49	73.1
Junior and senior high school	18	24.0	16	23.9
College and above	­ —	—	2	3.0
Religious belief	34	45.3	28	41.8	0.2	1	0.67
Financial perception					1.1	2	0.56
Poor	15	20.0	9	13.4
Moderate	23	30.7	21	31.3
Good	37	49.3	37	55.2
COPD severity					3.5	3	0.33
Mild (FEV1 >80% predicted normal)	5	6.7	4	6.0
Moderate (FEV1 50-80% predicted normal)	14	18.7	8	11.9
Severe(FEV1 30-50% predicted normal)	29	38.7	36	53.7
Very severe (FEV1 <30% predicted normal)	27	36.0	19	28.4
	Mean	SD	Mean	SD	T / Z	df	p
Age (year)	74.1	6.0	73.7	6.3	0.3	140	0.74
MMSE total	26.4	4.2	25.4	4.3	1.4	140	0.16
No. of physical illnesses	2.6	1.7	3.4	1.6	−3.4	—a	0.001
IADL total	4.9	4.9	6.9	6.4	−2.1	140	0.03
Life events in the past year	3.6	3.6	5.8	4.2	−0.1	—a	0.93
GDS	0.4	0.6	0.4	0.8	−3.3	—a	0.001
PCS	38.3	19.6	39.0	20.4	−0.2	140	0.84
MCS	57.6	24.3	55.2	23.6	0.6	140	0.55

a = Mann–Whitney U-test; MMSE = Mini-Mental State Examination; IADL = Instrumental Activities of Daily Living Scale; GDS = Geriatric Depression Scale; PCS = physical component score of Medical Outcomes Study; MCS = mental component score of Medical Outcomes Study.

In multiple logistic regression analysis, more physical illnesses (p = 0.02, OR 1.3, 95% CI 1.1–1.7) and more severe depressive symptoms (p = 0.009, OR 1.1, 95% CI 1.03–1.3) were independently associated with any type of insomnia in COPD patients. These two significant correlates accounted for 21.3% of the variance.

Discussion

To the best of our knowledge, this was the first controlled study that examined insomnia in Chinese patients with COPD. The finding that 47.2% of COPD patients reported any type of insomnia is consistent with the higher end of the results of other surveys in Western samples (21.4%–60.6%) (2, 21). The diversity of findings in prior studies is likely due to the inconsistent definitions of insomnia.

For example, different used insomnia symptoms, insomnia symptoms accompanied by daytime consequences, dissatisfaction with sleep quality, or quantity and insomnia diagnosis. In addition, variations in the prior study results are also likely due to different time frames (e.g., current, past month, past year or lifetime), as well as different samples (e.g., different severities of COPD, with or without additional comorbidities) and sampling methods (22). Therefore, comparisons of results across these different studies should be made with caution.

Insomnia in COPD can be related to diminished physical activity, less time spent outdoors, nocturnal dyspnea, reduced exposure to bright light, and sleeping during the day as a means of dealing with disease-related fatigue at the expense of nighttime sleep (23). Cough and excessive mucus production can also delay sleep onset, and laborious breathing associated with chronic airflow limitation in the horizontal position may further contribute to insomnia (24).

Consistent with findings in the literature (2, 21) all types of insomnia were more common in patients than in controls in this study. However, the differences disappeared after controlling for variables that significantly differed between the two groups, suggesting that probably the frequent insomnia in COPD is secondary to some mediating and moderating factors, such as physical comorbidity, impaired daily functioning and poor QOL. In previous studies (2), insomnia was only compared directly between patients and controls, and confounders were not controlled for. Our results suggest that future studies need to account for relevant covariates.

Similar to previous findings (2, 25, 26), depressive symptoms were independently associated with insomnia. However, because of its cross-sectional design, this study cannot establish the causality and directionality between depressive symptoms and insomnia. Moreover, some unmeasured factors, such as family and work stress and substance use, may be associated with both depressive symptoms and insomnia (27). We also found that insomnia was closely associated with physical comorbidity, confirming findings of earlier studies (28–30).

Similar to earlier findings (4), severity of airflow limitation was not associated with insomnia in this study. Poor QOL was also linked to COPD and insomnia in prior studies (31, 32). This study could not confirm this finding, which might be due to its small sample size.

There are several methodological limitations to this study. First, the sample size was still relatively small and due to the cross-sectional design, causality between insomnia and other variables could not be explored. Second, patients and controls were interviewed in the medical clinic and social centres, respectively. Therefore the raters were not blinded to the subjects’ health status. Third, the most physically frail patients who could not tolerate the interview were not included. These patients might have a higher rate of insomnia. Further, insomnia was only evaluated using three items of the HAMD, rather than specific measures on insomnia. Moreover, there is lack of agreement on the best definition and measures of insomnia in the literature. For example, different approaches have been used in the literature, such as insomnia with or without a specific timeframe (33), insomnia symptoms with daytime consequences (34), or dissatisfaction with sleep quality or quantity (35).

In conclusion, given the harmful consequences of insomnia coupled with its high frequency found in this survey, attempts should be made to address insomnia in COPD patients. Because of the significant correlations with insomnia, more attention should be paid to Chinese COPD patients’ physical comorbidity and depressive symptoms. Longitudinal studies are warranted to investigate the socio-demographic and clinical predictors of insomnia related to COPD and to assess the efficacy of antidepressant and other treatments for both the severity of insomnia and COPD.

Declaration of Interest Statement

Dr. Correll has been a consultant and/or advisor to or has received honoraria from: Actelion, Alexza; American Academy of Child and Adolescent Psychiatry, Bristol-Myers Squibb, Cephalon, Eli Lilly, Genentech, Gerson Lehrman Group, IntraCellular Therapies, Lundbeck, Medavante, Medscape, Merck, National Institute of Mental Health, Janssen/J&J, Otsuka, Pfizer, ProPhase, Roche, Sunovion, Takeda, Teva, and Vanda. He has received grant support from BMS, Feinstein Institute for Medical Research, Janssen/J&J, National Institute of Mental Health (NIMH), National Alliance for Research in Schizophrenia and Depression (NARSAD), and Otsuka. He has been a Data Safety Monitoring Board member for Cephalon, Eli Lilly, Janssen, Lundbeck, Pfizer, Takeda, and Teva. The remaining authors had no conflicts of interest in conducting this study or preparing the manuscript. The authors are responsible for the content and writing of the paper.