Palliative and Supportive Care (2015), 13, 575– 581.

# Cambridge University Press, 2014 1478-9515/14

doi:10.1017/S1478951513001119

Assessment of sleep disturbance in lung cancer

patients: Relationship between sleep disturbance
and pain, fatigue, quality of life, and
psychological distress

MARE NISHIURA,1 ATSUHISA TAMURA, M.D., PH.D.,

2
HIDEAKI NAGAI, 2
M.D., PH.D., AND
EISUKE MATSUSHIMA, M.D., PH.D.1
1
Section of Liaison, Psychiatry and Palliative Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical
and Dental University, Bunkyo-ku, Tokyo, Japan
2
Center for Pulmonary Diseases, National Hospital Organization, Tokyo National Hospital, Kiyose-shi, Tokyo, Japan
(RECEIVED October 31, 2013; ACCEPTED November 20, 2013)

ABSTRACT
Objective: We investigated the prevalence of sleep disturbance and psychological distress in lung
cancer patients. We also examined the association between sleep disturbance and psychological
distress, pain, fatigue, and quality of life in the same population.
Method: Fifty lung cancer patients were evaluated. Sleep disturbance was assessed using the
Athens Sleep Insomnia Scale (AIS) and psychological distress using the Hospital Anxiety and
Depression Scale (HADS). Quality of life (QOL), pain, and fatigue were assessed employing the
European Organization of Research and Treatment Quality of Life Questionnaire –Cancer 30
(EORTC QLQ – C30).
Results: We observed that 56% of lung cancer patients had sleep disturbance (AIS score 6)
and 60% had psychological distress (total HADS score 11). Patients with sleep disturbance had
a HADS score of 14.6 + 5.8, a fatigue score of 45.3 + 22.0, and a pain score of 27.2 + 26.2. In
contrast, patients without sleep disturbance had a lower HADS score of 9.9 + 8.1 ( p , 0.05) and
a higher fatigue score of 28.5 + 18.0 ( p , 0.01) and a pain score of 8.7 + 15.8 ( p , 0.01). In
addition, we found a lower QOL in patients with sleep disturbance (46.3 + 20.2) than in those
without (65.2 + 20.7) ( p , 0.05). We also observed a significant correlation between the AIS,
HADS, fatigue, QOL, and pain scores.
Significance of Results: Lung cancer patients suffered from combined symptoms related to
sleep. Sleeping pills improved sleep induction but were not sufficient to provide sleep quality
and prevent daytime dysfunction. Daytime dysfunction was specifically associated with
psychological distress. Additionally, the type of sleep disturbance was related to other patient
factors, including whether or not they received chemotherapy.
KEYWORDS: Sleep disturbance, Lung cancer, Quality of life, Psychological distress, Fatigue

INTRODUCTION difficulty sleeping (Owen et al., 1999; Savard &

Sleep disorders are common in cancer patients. Some
30 to 52% of newly diagnosed cancer patients have
Address correspondence and reprint requests to: Mare Nish-
iura, Section of Liaison, Psychiatry and Palliative Medicine,
Graduate School of Medical and Dental Sciences, Tokyo Medical
and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan.
E-mail: marelppm@tmd.ac.jp.
575
Morin, 2001; Davidson et al., 2002; Fiorentino & An-
coli-Israel, 2007), which is a significantly higher
prevalence rate than in healthy adults or noncancer
patients (Owen et al., 1999; Davidson et al., 2002;
Vena et al., 2006; Le Guen et al., 2007). In clinical
practice, however, sleep is not assessed by healthcare
professionals (Savard & Morin, 2001). In a study of
982 patients with various cancers—including breast,
576
gastrointestinal, genitourinary, gynecological, lung,
and nonmelanoma skin cancers—the prevalence of
several manifestations of sleep disturbance was high-
est or second highest in lung cancer patients, with an
average prevalence in all cancer patients of 30.5 ver-
sus 36.8% in those with lung cancer (Davidson et al.,
2002). In Japan, despite the high prevalence and sta-
tus of lung cancer as the most common type of cancer
diagnosed (Ministry of Health, Labour, and Welfare,
2011), few studies have examined sleep disturbance
in lung cancer patients.
Sleep disturbance impairs quality of life (QOL)
(Fortner et al., 2002) and results in a range of psycho-
logical and somatic conditions, such as increased fa-
tigability and irritability, cognitive impairment,
mood change, poor coordination, psychomotor retar-
dation, and decreased pain tolerance (Chuman,
1983).
A new diagnosis of cancer has been associated
with the onset of sleep disturbance (Davidson et al.,
2002). Patients experience stress related to the ongo-
ing series of medical events they are subjected to,
such as diagnosis, hospital admission, surgery, and
treatment, which in turn may induce psychological
distress. The relationship between psychological
symptoms and sleep therefore warrants evaluation.
Several studies have reported that the combined
occurrence of sleep disturbance, pain, fatigue,
anxiety, and psychological distress can occur toge-
ther in a phenomenon termed “symptom clusters”
(Donovan et al., 2007; Theobald, 2007; Dirksen,
2009; Cheng, 2011). Clinician consideration of not
only sleep disturbance but also psychological distress
and other symptoms should improve the overall qual-
ity of life of patients; however, few studies have inves-
tigated the prevalence of sleep disturbance and its
association with psychological distress, fatigue,
pain, and QOL in lung cancer patients in Japan.
In the present study, we evaluated the prevalence
of sleep disturbance in lung cancer patients in Japan
and compared patients with and without sleep dis-
turbance in regard to psychological distress, QOL,
pain, and fatigue. In addition, we also examined
the association between sleep disturbance and
psychological distress, QOL, pain, and fatigue.
METHOD
Participants
Subjects were recruited at the Center for Pulmonary
Diseases at the National Hospital Organization at
Tokyo National Hospital. They were interviewed for
assessment of the following enrollment criteria: (1)
diagnosis of lung cancer (including recurrence of can-
cer), (2) 20 years of age or older, (3) no history of de-
Nishiura et al.
pression (as assessed by medical chart review), (4)
no serious cognitive difficulties, and (5) ability to
complete the questionnaire. Subjects consisted of
consecutive admissions to the hospital or were inpa-
tients who met the enrollment criteria. The study
was approved by the ethics committee of the National
Hospital Organization at Tokyo National Hospital.
All patients provided written informed consent.
Measures
Sleep Disturbance
Sleep disturbance was measured using the Athens
Insomnia Scale (AIS) (Soldatos et al., 2000), a self-ad-
ministered instrument that consists of eight items
and has shown good internal reliability and validity
(Soldatos et al., 2003). The Japanese version of the
AIS has also been validated (Okajima et al., 2011).
The first five items assess difficulty with sleep induc-
tion, waking during the night, early morning wak-
ing, total sleep time, and sleep quality. The last
three items pertain to the next-day consequences of
insomnia, such as problems with sense of well-being,
functioning capacity, and sleepiness during the day.
Each item of the AIS is rated on a 0-to-3 scale, with
0 corresponding to “no problem at all” and 3 to a
“very serious problem.” Patients were requested to
give a positive rating if they had experienced the
item at least three times a week during the last
month. The total score on these eight items ranged
from 0 to 24, with a score 6 considered to represent
sleep disturbance.
Psychological Distress
Psychological distress was measured using the Hos-
pital Anxiety and Depression Scale (HADS) (Zig-
mond et al., 1983). The HADS consists of 14 items
and has two subscales: anxiety (7 items) and de-
pression (7 items). Each item of the HADS is rated
from 0 to 3, and the total score ranges from 0 to 42,
with a higher score indicating severe depression
and anxiety. A total score equal to or greater than
11 was set as the cutoff for psychological distress (Ku-
gaya et al., 1998). HADS has also been validated in a
cancer population (Herrmann, 1997).
Quality of Life, Pain, and Fatigue
Quality of life, pain, and fatigue were measured by
the European Organization of Research and Treat-
ment Quality of Life Questionnaire –Cancer 30
(EORTC QLQ –C30), version 3 (Aaronson et al.,
2008). The QLQ –C30 consists of 30 items that assess
5 functional domains (physical, role, emotional, cog-
nitive, and social functioning), 8 cancer-related
symptoms (including pain and fatigue), financial
Sleep disturbance in lung cancer patients 577

difficulty, and global health status. Scores for each Table 1. Characteristics of the study population
item range from 1 (not at all) to 4 (very much) and
are then transformed to a range of from 0 to 100. N 50
Higher scores for global health status show a better Age (years)
Mean 71.8 + 3.5
quality of life, while lower scores for the eight symp- Sex
tom items and financial difficulty show a better sta- Male 35
tus. The Japanese version of the QLQ – C30 was Female 15
used for our study. Quality of life, pain, and fatigue Receiving chemotherapy
were used as outcome variables. Yes (inpatient) 21
Yes (outpatient) 10
No 19
Living situation
Statistical Analysis Living alone 8
Living with family 41
Patients were divided into two groups (poor sleepers: Living in elderly care facility 1
AIS 6, good sleepers: AIS ,6), and the means and Sleeping pill (including minor
standard deviations of the HADS score, QOL, fati- tranquilizer)
gue, and pain of the two groups were calculated. Yes 16
The cutoff score on HADS was set at 11 based on No 34
the Japanese version of HADS, and patients with a
total HADS score of 11 or greater in this version
were identified as having potential adjustment dis- Questionnaire responses indicated sleep dis-
order and major depression (Kugaya et al., 1998). turbance in 32% of patients (n ¼ 16), who were ac-
In order to examine the relationship between cordingly prescribed sleeping medications (e.g.,
chemotherapy and sleep disturbance, patients were triazolam, brotizolam, zolpidem, and etizolam). The
divided into a chemotherapy group and a nonchemo- duration of effect for these sleeping pills generally
therapy group, and sleep disturbance was analyzed. ranges from 2 to 6 hours.
The mean and standard deviation for each item of the AIS values (average value + SD) for all partici-
AIS score and total AIS score were then calculated. pants were 0.88 + 0.75 for sleep induction, 0.52 +
Differences in scores between the two groups were 0.65 (waking during the night), 0.84 + 0.71 (early
compared using the Mann – Whitney U test. Signifi- morning waking), 0.66 + 0.59 (total sleep time),
cance was set at p , 0.05 for all analyses. Corre- 0.74 + 0.69 (sleep quality), 0.54 + 0.68 (well-being
lations among AIS score, HADS score, QOL, during the day), 0.92 + 0.67 (functioning capacity
fatigue, and pain were calculated employing Spear- during the day), and 1.10 + 0.42 (sleeping during
man’s rank correlation coefficient. All statistical pro- the day).
cedures were performed using PASW statistics
software, version 18. Comparison of AIS Scores for Outcome
Variables
Table 2 compares outcome variables between the AIS
RESULTS 6 and AIS ,6 groups. For each parameter, patients
with sleep disturbance (AIS 6) had the following
Patient Characteristics scores: total HADS, 14.6 + 5.8; fatigue, 45.3 + 22.0;
A total of 50 lung cancer patients participated in our QOL, 46.3 + 20.2; and pain, 27.2 + 26.2. In contrast,
study. The characteristics of the study population are patients without sleep disturbance (AIS ,6) had the
presented in Table 1. It has been reported that the
average age of Japanese lung cancer patients is 68 Table 2. Comparison of AIS scores (AIS ≥6 and AIS
years old (n ¼ 15,185) (Kawaguchi et al., 2010). In ,6) for outcome variables
our study, the mean age was 71.8 + 3.5 years, which
is almost representative for Japanese lung cancer AIS ≥6 AIS ,6
statistics. More than half of the patients received che- (Patient with Sleep (Patient Without p
motherapy. In all patients, the prevalence of sleep Variable Disturbance) Sleep Disturbance) Value
disturbance (AIS 6) was 56% (n ¼ 28), and major HADS 14.6 + 5.8 9.9 + 8.1 0.01
psychological distress (HADS 11) was 60% (n ¼ Fatigue 45.3 + 22.0 28.5 + 18.0 0.003
30). A high rate of sleep disturbance was observed, QOL 46.3 + 20.2 65.2 + 20.7 0.01
which is consistent with previous findings (Kaye Pain 27.2 + 26.2 8.7 + 15.8 0.002
et al., 1983; Malone et al., 1994; Engstrom et al.,
1999; Davidson et al., 2002). Data represent mean + SD.
578 Nishiura et al.

Table 3. AIS items of patients with or without chemotherapy

Patients with Chemotherapy Patients without Chemotherapy p

Variable (n ¼ 31) (n ¼ 19) Value

Total AIS score 7.2 + 3.2 4.5 + 2.5 0.017

Sleep induction 1.06 + 0.73 0.61 + 0.69 0.021
Waking during the night 0.61 + 0.72 0.39 + 0.50 0.277
Early morning waking 1.04 + 0.71 0.53 + 0.61 0.012
Total sleep time 0.75 + 0.64 0.56 + 0.51 0.548
Sleep quality 0.93 + 0.75 0.50 + 0.51 0.046
Well-being during the day 0.75 + 0.74 0.28 + 0.45 0.029
Functioning capacity during 1.04 + 0.60 0.72 + 0.73 0.115
the day
Sleeping during the day 1.18 + 0.37 1.00 + 0.47 0.203

Table 4. Correlation of AIS score and predictive factors

AIS Score (Sleep Disturbance) HADS QOL Fatigue

HADS 0.466**
QOL – 0.444** – 0.553**
Fatigue 0.415** 0.562** – 0.531**
Pain 0.405** 0.525** – 0.452** 0.518**

**p , 0.01.

following scores: total HADS, 9.9 + 8.1 ( p , 0.05); fa- 0.466 at absolute value. Significant correlations
tigue, 28.5 + 18.0 ( p , 0.01); QOL, 65.2 + 20.7 ( p , were also seen among predictive factors, with corre-
0.05); and pain, 8.7 + 15.8 ( p , 0.01). Patients with lation coefficients ranging from 0.452 to 0.562 at ab-
sleep disturbance had significantly higher scores for solute value.
HADS, fatigue, and pain, and a significantly lower
score for QOL than those without sleep disturbance, Correlation Between HADS Score and
showing that both the physical and psychological Individual Factors in the AIS
states of patients with sleep disturbance were worse
than that of those without. Correlations between HADS score and the eight
items of the AIS are presented in Table 5. Six items
of the AIS were significantly associated with HADS
Association of Chemotherapy and Sleep
score, with a correlation coefficient ranging from
Disturbance
0.286 to 0.454. In contrast, no correlation was ob-
To demonstrate the association of chemotherapy and served for waking during the night and early morn-
sleep disturbance, both the total score and the score ing. Furthermore, the correlations observed in
on each item of the AIS were compared for patients
with and without chemotherapy (Table 3). There
Table 5. Correlation of HADS score and AIS items
was a significant difference between patients with
and without chemotherapy regarding total score Correlation
and AIS scores on sleep induction, early morning AIS Item Coefficient
waking, sleep quality, and well-being during the day.
Sleep induction 0.286*
Awakenings during the night 0.114
Correlation Among Predictive Factors Early morning awakening 0.116
Total sleep time 0.394**
The correlations among AIS score and predictive fac- Sleep quality 0.436**
tors were calculated to determine which predictive Well-being during the day 0.427**
factors were associated with sleep disturbance, Functioning capacity during the day 0.454**
(Table 4). The AIS score significantly correlated Sleepiness during the day 0.308*
with all other predictive factors, with Spearman’s
rank correlation coefficients ranging from 0.405 to *p,0.05; **p , 0.01.
Sleep disturbance in lung cancer patients
Table 5 show an association of psychological status
with not only quality of sleep but also daytime func-
tioning.
Association of Sleep Medication and Sleep
Disturbance
To demonstrate the association of sleeping pills and
sleep disturbance, each item of the AIS was com-
pared for patients taking and not taking sleeping
pills (Table 6). In the first five items related to sleep,
the AIS scores for sleep induction and waking during
the night did not significantly differ between those
patients taking and those not taking sleeping pills.
In contrast, AIS scores were statistically significant
for early morning waking, total sleep time, and sleep
quality. This result demonstrates that only the AIS
scores for sleep induction and waking during the
night in patients with sleeping pills were not statisti-
cally different from those without, meaning that
sleeping pills improved sleep induction but not to a
sufficient level.
DISCUSSION
In this study, we observed that more than half of lung
cancer patients (28 of 50) had sleep disturbance. Fur-
ther, patients with sleep disturbance exhibited worse
psychological and physiological symptoms compared
to those without.
The average age of patients in our study was
71.8 + 3.5 years. This may explain the higher preva-
lence of sleep disturbance compared to previous
studies, given the higher prevalence in elderly
people, which can be up to 25% in those in their 60s
and 33% in those in their 70s (Foley et al., 1999).
Nocturnal polyuria is common in the elderly
(Fultz et al., 1996) due to the urinary symptoms as-
sociated with vesical dysfunction in patients with
prostatic involvement. In this study, however, the
AIS scores on each item indicated that the main
cause of sleep disturbance was not nocturnal
Table 6. AIS items of patients with or without sleeping pills
AIS Item Patients with Sleeping Pills
Sleep induction 1.06 + 0.77
Awakenings during the night 0.69 + 0.79
Early morning awakening 1.13 + 0.81
Total sleep time 0.94 + 0.57
Sleep quality 1.00 + 0.63
Well-being during the day 0.75 + 0.68
Functioning capacity during the day 0.81 + 0.54
Sleepiness during the day 1.00 + 0.37
Data represent mean + SD.
579
polyuria, given the lower score for waking during
the night, but rather sleepiness during the day due
to both tumor- and chemotherapy-related effects (Da-
vidson et al., 2002). Table 3 shows that the AIS scores
for the chemotherapy group were significantly differ-
ent from those without in the items of total score,
sleep induction, early morning sleep quality, and
well-being during the day. This prevalence of exces-
sive daytime sleepiness and daytime dysfunction in
our patients with lung cancer is consistent with pre-
vious reports (Ginsburg et al., 1995; Cronin et al.,
2001; Davidson et al., 2002) and indicates that che-
motherapy contributes to sleep disturbance. How-
ever, the severity of side effects is considered to be
dependent on the drug. For example, patients treated
with Gefitinib have a better QOL than those taking
paclitaxel (Oizumi et al., 2012). In our study, the
rate of patients being treated with molecularly targe-
ted drugs was 20% (n ¼ 6), and the rate was in-
creased. The relationship between type of drug and
sleep disturbance was therefore not due to small
study size.
Pain medications have side-effect profiles that po-
tentially disrupt sleep (Cronin et al., 2001). Opioids
or nonsteroidal antiinflammatory drugs (NSAIDs),
commonly used for pain relief in cancer patients,
can decrease the quality of sleep. In particular,
opioids significantly decrease slow-wave sleep and
rapid eye movement sleep, which is associated with
fatigue or decreased sleep quality (Cronin et al.,
2001; Caldwell et al., 2002). Aspirin and ibuprofen in-
crease waking during the night and decrease sleep ef-
ficacy (Trenkwalder et al., 2008), while NSAIDs
suppress the production of melatonin during the
night (Murphy et al., 1994). In our study, opioids
were not prescribed and NSAIDs were prescribed
for only 18% of patients.
Sleep disturbance has been shown to correlate
with psychological distress, fatigue, and pain. In
the present study, sleep disturbance was also signifi-
cantly associated with psychological distress, fatigue,
and pain, and with similar correlation coefficients.
Patients Without Sleeping Pills p Value
0.82 + 0.71 0.290
0.52 + 0.61 0.477
0.64 + 0.63 0.036
0.52 + 0.56 0.023
0.61 + 0.69 0.048
0.42 + 0.64 0.068
0.88 + 0.74 0.793
1.12 + 0.46 0.386
580
Results indicated that patients with sleep disturb-
ance had a lower QOL. Regarding the relationship
between pain and sleep disturbance, sleep loss has
been found to lead to decreased pain threshold
(Roehrs et al., 2006), and increased pain has been re-
lated to sleep disturbance (Fortner et al., 2002; Mer-
cadante et al., 2004). In addition, pain may interfere
with the mechanisms of induction and maintenance
of sleep.
Previous studies have reported that psychological
distress is associated with sleep disturbance (Mysta-
kidou et al., 2005; Fava et al., 2006; Chen et al.,
2008). We therefore focused on the relationship be-
tween psychological distress and each AIS item.
Psychological distress was significantly associated
with all items, except for “awakenings during the
night” and “early morning awakening,” and particu-
larly affected daytime impairment. Concerning
daytime impairment, many patients with sleep dis-
turbance experience a strong sense of fatigue and
pain. This in turn leads to increased psychological
distress and decreased QOL, and thereby exacer-
bates the original sleep disturbance.
The rate of sleep disturbance in our study was
greater than 50%, and sleeping pills were prescribed
to 30% of patients, which is similar to that reported
by previous investigators (21.5%) (Davidson et al.,
2002). All sleeping pills prescribed were short-acting
compounds, which improved items such as “sleep
induction” and “awakenings during the night” but
did not improve maintenance of sleep. Therefore,
longer-acting compounds are needed to improve
both induction and maintenance of sleep, depending
on the requirements of the individual patient.
In addition, the combination of sleeping pills and
antidepressants has been reported to cause a more
rapid improvement in the symptoms of depression
and a greater magnitude of antidepressant benefit
than antidepressants alone (Price et al., 2009). The
effective treatment of anxiety and depression was
also reported to lead to an improvement in symptoms
related to both sleep and pain (Chung & Tso, 2010).
Due to confirmation of the association of sleep dis-
turbance and psychological distress, the combination
of sleeping pills and antidepressants is a possible
treatment for improvement of symptoms.
Our study has several limitations that should be
noted. First, our purpose was to collect data on the
prevalence of sleep disturbance in a wide range of
lung cancer patients. We therefore included patients
who were diagnosed at different times, at different
stages of lung cancer, receiving or not receiving che-
motherapy, and inpatients and outpatients. Some
patients had a recurrence of cancer, and it was diffi-
cult to define their stage. This limits the generaliz-
ability of our findings and the ability to show
Nishiura et al.
causality. Second, we did not evaluate the association
between severity of illness or performance status and
sleep disturbance. Third, many study variables were
assessed with one or a very limited number of items
that do not take into account the multidimensional
aspects of these symptoms. Finally, the study design
was longitudinal in nature and therefore does not
provide information about the course of sleep dis-
turbance over time or in relation to temporal events.
We found that more than half of the patients (28 of
50) had sleep disturbance, which was higher than
previously reported (Malone, 1994; Herrmann,
1997; Davidson et al., 2002; Aaronson et al., 2008).
We also identified a correlation with the presence of
an association between AIS, HADS, fatigue, QOL,
and pain scores. It is therefore important that clini-
cians be aware that lung cancer patients can suffer
from sleep disorder symptoms, especially patients
undergoing chemotherapy, and to consider the treat-
ment and selection of medication depending on the
symptoms of individual patients.
ACKNOWLEDGMENTS
This study was supported by the National Hospital Organ-
ization, Tokyo National Hospital, in Japan.
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