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Original Research COPD
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Pain and Its Clinical Associations in Individuals With COPD A Systematic Review Annemarie L. Lee, PhD; Samantha L. Harrison, PhD; Roger S. Goldstein, MBChB, FCCP; and Dina Brooks, PhD
Pain is emerging as a clinical complication in COPD, but the clinical impact of this comorbidity and the measurement properties of instruments used to assess pain require evaluation.
BACKGROUND:
METHODS: Electronic searches of five databases were performed up to September 2014 for the two phases of this review. To be included in phase 1, studies reported the clinical associations of pain and prevalence in individuals with COPD. To be included in phase 2, studies reported measurement properties of an instrument assessing pain in COPD. Two independent reviewers rated the quality of quantitative and qualitative evidence (phase 1) and the measurement properties using the four-point Consensus‐Based Standards for the Selection of Health Status Measurement Instruments (COSMIN) checklist (phase 2).
Of the 358 studies identified in the literature, nine met the inclusion criteria for phase 1 and five for phase 2. The mean (SD) quality score (of 16) for the quantitative studies was 13.1 (1.7). The pooled prevalence of pain in moderate to very severe COPD was 66% (95% CI, 44%-85%). Higher pain intensity was associated with increased dyspnea, fatigue, poorer quality of life, and a greater quantity of specific comorbidities. Of the two identified instruments (Brief Pain Inventory and McGill Pain Questionnaire), the measurement properties analyzed were construct validity, internal consistency, and criterion-predictive validity, with variable findings based on “fair” or “poor” quality studies. RESULTS:
In people with COPD, pain has negative clinical associations with symptoms and quality-of-life measures. Further research exploring the measurement properties of instruments assessing pain is required. CHEST 2015; 147(5):1246-1258
CONCLUSIONS:
Manuscript received October 29, 2014; revision accepted January 18, 2015; originally published Online First February 5, 2015. ABBREVIATIONS: BPI 5 Brief Pain Inventory; COSMIN 5 ConsensusBased Standards for the Selection of Health Status Measurement Instruments; HRQOL 5 health-related quality of life; MPQ 5 McGill Pain Questionnaire AFFILIATIONS: From the Department of Respiratory Medicine (Drs Lee, Harrison, Goldstein, and Brooks), West Park Healthcare Centre; and Department of Physical Therapy (Drs Lee, Harrison, Goldstein, and Brooks) and Department of Medicine (Dr Goldstein), University of Toronto, Toronto, ON, Canada.
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FUNDING/SUPPORT:
The authors have reported to CHEST that no funding was received for this study. CORRESPONDENCE TO: Dina Brooks, PhD, Department of Physical Therapy, University of Toronto, 160-500 University Ave, Toronto, ON, M5G 1V7, Canada; e-mail: [email protected] © 2015 AMERICAN COLLEGE OF CHEST PHYSICIANS. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details. DOI: 10.1378/chest.14-2690
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Common symptoms in individuals with COPD are dyspnea, fatigue, and anxiety, all of which are associated with impaired health-related quality of life (HRQOL) and reduced exercise tolerance.1,2 More recently, there is increased awareness that pain is a commonly reported symptom in COPD. Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or is described in terms of such damage.3 In COPD, pain appears to affect between 45% and 94% of individuals,1,4-9 including 21% to 77% with end-stage lung disease.10-14 Pain has been reported in the spinal and chest wall regions,4,8,15 with higher pain levels linked to greater breathlessness,5,16 but its interaction with other symptoms of COPD are less clear. COPD is often accompanied by comorbidities,17,18 and individuals experiencing pain may have a higher proportion of musculoskeletal disorders.7,8,16,19 The current recommendations for assessing and evaluating the impact of pain are to incorporate the sensory and affective dimension of
Materials and Methods This review was completed in two phases based on the two aims and is reported according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines.23 Phase 1 aimed to identify the association of pain characteristics, including prevalence in COPD with clinical features to give a contextual framework for any associations evident. Phase 2 identified instruments used to assess pain in COPD and their measurement properties. Phase 1: Pain Characteristics and Clinical Associations A systematic search was undertaken by one author (A. L. L.) of five databases, from inception to September 2014 (Fig 1), with reference lists of retrieved articles inspected to identify additional papers and authors contacted when necessary. The search strategy for MEDLINE is outlined in e-Appendix 1 and was adapted for other databases. Inclusion Criteria: Following duplicate removal, studies were screened by two independent reviewers (A. L. L. and S. L. H.). This included review of citations’ titles and abstracts from retrieved studies, followed by a full-text review of potentially eligible studies according to the inclusion criteria (Table 1). Any disagreement regarding eligibility was resolved by a consensus meeting, with consultation with a third reviewer (D. B.) when necessary. Data Extraction and Quality Assessment: Data extraction was performed by one investigator (A. L. L.) (checked by a second investigator) using a standardized template. For quantitative studies, quality appraisal was conducted using the Critical Review Form–Quantitative Studies.24 This tool evaluates method rigor and bias, with a total score of 16. For qualitative studies, the Critical Appraisal Skills Program (CASP)25 was used, evaluating scientific rigor, credibility, and relevance.26 Appraisal was completed independently by two reviewers, with any disagreement resolved by consensus. Phase 2: Instrument Measurement Properties A similar search strategy of the same databases applied in phase 1 was undertaken by one author (A. L. L.). Search terms were customized for
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pain and its impact.20,21 With the emerging interest in understanding the extent and implications of pain in this population,22 there is a need to explore this issue further by determining the specific characteristics of pain experiences and its clinical associations in COPD. The measurement and clinical associations of pain are complex. It is, therefore, important to determine whether the available assessment tools capture all of its dimensions. A better understanding of their measurement properties will assist clinicians in selecting the instruments best suited to assess pain in COPD. Therefore, the primary aim of this systematic review was to determine the association between pain prevalence and specific pain characteristics with clinical features of COPD. The secondary aim was to explore the measurement properties of instruments assessing pain in COPD. This trial was registered with PROSPERO (CRD42014010618).
each database, with a validated sensitive search fi lter for finding studies on measurement properties of instruments applied.25 The search strategy for MEDLINE is described in e-Appendix 2. Inclusion Criteria: Following removal of duplicates, studies were screened by two independent reviewers (A. L. L. and S. L. H.). This included screening of titles and abstracts from all retrieved studies followed by full-text review of potentially eligible studies, based on the inclusion criteria (Table 2) with any disagreements resolved by consensus. Data Extraction and Quality Assessment: Data were extracted using a standardized template. Two independent reviewers (A. L. L. and S. L. H.) evaluated the study quality using the Consensus-Based Standards for the Selection of Health Status Measurement Instruments (COSMIN) checklist.27 This is a validated tool composed of 10 sections, each scoring the quality of one measurement property. Within each section, items are individually scored based on a four-point scale (excellent, good, fair, or poor) with an overall quality score for each property obtained using the lowest score recorded among the items, as recommended.28 Analysis Analysis of prevalence was based on the response to a question of “do you have pain?” in any instrument used. For studies which reported outcomes for the same series of patients, 4-6,16,29 the prevalence was included only once in the meta-analysis. The pooled prevalence of pain was analyzed using MetaXL 1.3, a tool for meta-analysis in Microsoft Excel (EpiGear International Pty Ltd). The data were first transformed using the variance stabilizing double arcsine transformation. 30 The quality effects model was then applied to determine the prevalence rate and 95% CI. This model was selected over the fixed or random effects models to explicitly address heterogeneity in pooled proportions caused by differences in study quality and distribution, 31,32 allowing greater weighting to high-quality studies. MetaXL ensures that the pooled proportions add up to one. Heterogeneity assumption was assessed by the Q-test and I2 test. Clinical implications of pain were reported narratively.
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Figure 1 – Study flow from identification to inclusion of final studies for phase 1. CINAHL 5 Cumulative Index to Nursing and Allied Health Literature; EMBASE 5 Excerpta Medica Database.
Results Phase 1: Pain Characteristics and Clinical Associations
A total of 437 articles were identified; following references checks of included articles, an additional nine papers were identified. After removing 13 duplicates, 358 were reviewed for title and abstract, and 34 fulltext articles were reviewed, with nine meeting the inclusion criteria (Fig 1). Study characteristics are outlined 1248 Original Research
on Table 3, with two authors contacted for further information.6,7 Quality Assessment: The mean (SD) quality score of quantitative studies22 was 13.1 (1.7) of 16 (Table 4). Common methodologic flaws were sampling biases, inadequate blinding, and inadequate sample size justification. The qualitative study15 evaluation is outlined in e-Table 1. Although study aims were clear, with appropriate methodology applied, participants were awaiting
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TABLE 1
] Inclusion Criteria for Phase 1
Criterion
Specifics
Participants
Participants diagnosed with COPD, in a stable clinical state or experiencing an acute exacerbation
Study design
Cohort, case-control, cross-sectional and qualitative study designs
Pain prevalence
Reports of pain prevalence (point prevalence or pain in the past wk[s]/mo[s]/y[s]) based on valid or nonvalid questionnaires specific to pain, patient interviews, or medical record review. Instruments outlining prevalence were consistent with the current recommendations of the International Association for the Study of Pain for assessing pain.21
Pain characteristics and associations
Pain severity, frequency, duration, location, and implemented treatment strategies. Associations of pain with symptoms (breathing, fatigue), psychologic symptoms (anxiety, depression), physical activity, exercise tolerance or muscle strength, HRQOL, disease severity, comorbidities.
Only studies published in English were included. HRQOL 5 health-related quality of life.
lung transplantation, suggesting recruitment bias. Interviews were semistructured, with analysis undertaken until saturation, although it is unclear how themes were derived. Study Characteristics: Six studies were conducted in Norway,4-6,15,16,29 two studies in Canada,7,8 and one study in the United States.19 Three studies included both COPD and healthy control subjects,4,7,19 of which two studies matched populations for age and sex.8,19 All patients were in a stable clinical state, with moderate to very severe lung disease.2 One study incorporated qualitative analysis of pain experiences.15 The definition of pain varied considerably between studies. Five studies based prevalence on experience of pain within the past 24 h or past week according to the Brief Pain Inventory (BPI).5-8,15 One study established the presence of pain according to the question, “Are you generally bothered by pain”16 while two studies used a nonvalidated (yes/no) query.4,29 Prevalence was reported in nine studies (Table 5). Of these, six studies reported on a different series of patients with COPD.4,6-8,15,19 Prevalence (pain within the last 24 h or previous 7 days) was examined in six studies.4-8,29 Overall, the pooled prevalence was 66% (95% CI, 44%-85%) (Fig 2). The heterogeneity of I2 of 93% and Q 5 73 suggests strong variability between TABLE 2
studies.8 Compared with healthy control subjects, prevalence was greater in COPD.4,7,19 Common pain regions were lower back/lumbar (29%-48%),4,6,8,19 chest (16%-38%),4,6,8,15 upper back/ thorax (16%-24%),4,6,8 neck/cervical (13%-46%),4,6,8,15,19 lower limb (14%-98%),4,6,8 and upper limb (41%-64%).4,6,8,15 Two studies reported more pain locations in COPD compared with control subjects,7,19 while the 2011 report by Bentsen et al4 found no difference between groups. Five studies reported pain severity at its worst, ranging from 2.7 to 7.3 on the numerical rating scale of the BPI5,8,15,29 and from 1.0 to 1.3 cm on the McGill Pain Questionnaire (MPQ) Visual Analog Scale.7,8 Of the two studies comparing pain severity between groups, one found a higher severity in COPD,7 and one found no difference.4 The average duration that pain had been experienced by participants with COPD was 18 years in one study.4 Two studies found that pain interference in COPD was up to 5.4 times greater on the BPI interference scale compared with control subjects,7,8 although the 2011 report by Bentsen et al4 found no difference between groups. Greater pain intensity was related to higher levels of breathlessness.5,16 One study described more fatigue in
] Inclusion Criteria for Phase 2
Criterion
Specifics
Participants
Participants diagnosed with COPD, in a stable clinical state or experiencing an acute exacerbation in all stages of disease severity
Instrument/questionnaire
Developed to measure the presence of pain
Measurement properties
Information reported for one or more measurement properties including reliability, internal consistency, measurement error, criterion concurrent validity, criterion/predictive validity, construct validity/hypothesis testing, responsiveness
Only studies published in English were included.
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Cross-sectional
Cross-sectional
Cross-sectional
Cross-sectional
Cohort
Borge et al6/2011
Bentsen et al4/2011
Bentsen et al16/2012
HajGhanbari et al7/2012
Roberts et al19/2013
Cross-sectional
Cross-sectional
Borge et al5/2010
Bentsen et al29/2013
Cross-sectional and qualitative
Lohne et al15/2010
Study Design
] Details of Study Characteristics
Study/Year
TABLE 3
COPD: 100
COPD: 7,952 Control: 15,904
COPD: 47 Control: 47
COPD: 100
COPD: 100 Control: 333
COPD: 154
COPD: 154
COPD: 16
No. of Participants
Age (Mean [SD]), y; Sex
66 (8); 49% female
COPD: 69; 58% female Control: 68; 58% female
COPD: 70 (7); 43% female Control: 68 (9); 43% female
COPD with pain: 65 (9.2) COPD without pain: 67.9 (7.3); 49% female
COPD: 65 (9) Control: 58 (11) Sex NR
64 (10); 49% female
65 (10); 48% female
58; 75% female
Disease Severity
Measurement Tools
FEV1: 46 (15)% pred
(Continued)
9-item questionnaire: Pain–yes/no, NRS for pain at worst and least and now with scale 0-10 Future expectations: positive or negative
CMS-defined chronic conditions ICD-9-CM diagnosis code (procedure-based pain, prescription for pain medication) Pain diagnoses (neurologic, inflammatory, mechanical/compressive, muscular and injury-related pain)
BPI (short form) MPQ TSK CHAMPS SF-36
COPD: FEV1: 45 (19)% pred
NR
Pain question (Are you generally bothered by pain?) SGRQ Comorbidities
9-item questionnaire: Pain–yes/no, NRS for pain at worst and least and now with scale 0-10 Cause of pain Body diagram from BPI
COPD: FEV1: 48 (16)% pred
COPD with pain: FEV1: 48 (16)% pred COPD without pain: FEV1: 45 (14)% pred
BPI (short form) RQOLQ QOLS
BPI (short form) HADS LFS GSDS RQOLQ
BPI (short form) Qualitative assessment
FEV1: 1.6 (0.7) L
FEV1: 59 (23)% pred
FEV1: 21 (6)% pred
BPI 5 Brief Pain Inventory; CHAMPS 5 Community Health Activities Model Program for Seniors Questionnaire; CMS 5 Centers for Medicare and Medicaid Services; GSDS 5 General Sleep Disturbance Scale; HADS 5 Hospital Anxiety and Depression Scale; ICD-9 CM 5 International Classification of Diseases, Ninth Revision, Clinical Modification; LFS 5 Lee Fatigue Scale; MPQ 5 McGill Pain Questionnaire; NR 5 not reported; NRS 5 numerical rating scale; % pred 5 percent predicted; QOLS 5 Quality-of-Life Scale; RQOLQ 5 Respiratory Quality-of-Life Questionnaire; SF-36 5 Short Form 36; SGRQ 5 St. George’s Respiratory Questionnaire; TSK 5 Tampa Scale for Kinesiophobia
MPQ BPI (long form) Charlson Index (with common musculoskeletal conditions) FEV1: 43% pred 72; 52% female COPD: 54 Cross-sectional HajGhanbari et al /2014
Measurement Tools Disease Severity Age (Mean [SD]), y; Sex No. of Participants Study Design
8
Study/Year
] (continued) TABLE 3
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those with higher pain levels,5 although a 2013 report by Bentsen et al29 found no relationship. Higher pain intensity in COPD was associated with poorer HRQOL,5,8 poorer sleep quality,5,8,29 less physical activity, and an increased pain-related fear of movement.7,15 Pain negatively impacted on anxiety and depression,5 with reports that both pain and breathlessness contributed to severe anxiety.15 A higher proportion of individuals with COPD and pain had at least one comorbidity,4,16 with higher pain severity and interference associated with more comorbidites.7,8 Common comorbidities were musculoskeletal conditions,4,16,19 endocrine disorders,4,8 depression, and cancer.4,19 No difference in lung function was evident in those with COPD with or without pain.5,16 Approaches to pain management included pain medication,8,15,19 physical modalities, and acupuncture,8,16 with medication and acupuncture used more frequently in COPD than in the general population.16,19 Phase 2: Instrument Measurement Properties
A total of 248 studies were retrieved from the databases. Following duplicate removal, 218 studies were reviewed in full text and abstract form, with five meeting the inclusion criteria. With the exception of one study,33 all were included in phase 1.5-8 The measurement properties for the two identified instruments are summarized in e-Table 2 and included construct validity/hypothesis testing,5-8,33 internal consistency,6 and criterion-predictive validity.7 Overall, the studies scored “fair” or “poor” for the measurement properties evaluated. The poorest scoring areas were design requirements (lack of a prior hypotheses and sample size). Measurement Properties: High internal consistency for BPI pain intensity and interference was found (e-Table 2).6 For criterion-predictive validity of the BPI, a strong relationship between the MPQ pain severity score and the BPI pain intensity (r 5 0.82) and BPI interference (r 5 0.66) was evident.7 The construct validity explored the relationships between pain intensity or interference and other COPD outcome measures, with a weak to moderate relationship with disease severity5,7 and symptoms5 for the BPI and a moderate relationship with exercise capacity for both the BPI and MPQ.7,33 A weak-to-moderate relationship was evident between pain severity measured on the BPI and MPQ and comorbidities5,7,8,33 as well as HRQOL6,7,33 (e-Table 2).
Discussion Patients with moderate to severe COPD have a high prevalence of pain (66%) compared with healthy control 1251
TABLE 4
] Quality Assessment of Observational Studies Quality Appraisal Score
Study/Year
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
Lohne et al15/2010
9
9
9
3
3
9
9
9
9
3
3
3
3
9
9
9
10
Total
Borge et al5/2010
9
9
9
3
3
9
3
9
9
9
9
9
9
9
9
9
13
Borge et al6/2011
9
9
9
3
3
9
9
9
9
9
3
9
9
9
9
3
12
Bentsen et al /2011
9
9
9
3
3
9
9
9
9
9
9
9
9
9
9
9
14
Bentsen et al16/2012
9
9
9
3
3
9
9
3
3
9
9
9
9
9
9
9
12
HajGhanbari et al7/2012
9
9
9
3
9
9
9
9
9
9
9
9
9
9
9
9
15
4
Bentsen et al29/2013
9
9
9
9
3
9
9
9
9
9
9
9
9
9
9
9
15
Roberts et al19/2013
9
9
9
9
9
9
9
3
3
9
9
9
9
9
9
9
15
HajGhanbari et al8/2014
9
9
9
3
3
9
9
9
9
9
3
9
9
9
9
3
12 Mean (SD) 13.1 (1.8)
Key to scoring (Law et al24 all items 9 for yes, 3 for no, except biases [3 for yes, 9 for no]). 1 5 Was the study purpose stated clearly? 2 5 Was relevant background literature reviewed? 3 5 Was the design appropriate for the study question? 4 5 Were there any biases present (minimum response rate of 80% for sample bias, blinding of investigators when physical measure were taken)? 5 5 Was sample size justified? 6 5 Was the sample described in detail? (had to include the number of participants by sex, age, and a description of where the cohort was sampled from). 7 5 Was informed consent obtained? (if not described, assume no). 8 5 Were the outcome measures valid? (if all not described, assume no). 9 5 Were the outcome measures reliable? (if all not described, assume no). 10 5 Results were reported in terms of statistical significance? 11 5 Drop outs were reported? 12 5 Clinical importance was reported? 13 5 Were the statistical analysis methods appropriate? 14 5 Conclusions were appropriate given the study methods? 15 5 Are there implications for clinical practice given the results of the study (based on the experience of the reviewers)? 16 5 Were limitations of the study acknowledged and described by the authors?
subjects. Pain experiences have a positive association with dyspnea and a negative association with HRQOL. Possible contributing factors are comorbid conditions. There was insufficient information to establish the measurement properties of the instruments used in COPD, with the evidence rated as fair. Heterogeneity in the prevalence of pain was evident. This may be attributed to the differing methods of population sampling; the use of convenience sampling and self-selection may have introduced some bias. The differing sample sizes between studies are also a likely factor. The variation appears to be unaffected by the time frame of pain reporting.4,5,7,8,15,19 In addition, it is unlikely to be influenced by slightly different pain definitions used in both validated or nonvalidated questionnaires to establish the presence of pain, with prevalence reported using nonvalidated questionnaires4,16,29 within the 95% CI of the pooled prevalence (44%-85%). While this suggests that asking patients if they experience pain may be sufficient to determine prevalence, clinically, this approach should be considered with caution when using nonvalidated questionnaires, in which measurement properties have not been established. A systematic review reported pain prevalence as a subdomain of HRQOL to be 67%20; this, together with our findings, suggests that pain is a common problem in COPD. 1252 Original Research
In comparison with the previous review,22 we determined the basis of pain prevalence from unidimensional and multidimensional pain scales, as per the current recommendations for assessing pain.20,21 van Dam van Isselt et al22 also used HRQOL tools, which inquired about the presence of pain. The primary purpose of these instruments is to measure health status or quality of life rather than to assess pain. In addition, the internal consistency of selected HRQOL tools could influence the strength of the link between pain prevalence and impact, which may increase the risk of overestimating any clinical associations. Finally, our objective was to establish the clinical association of pain within the context of pain prevalence in COPD, a different goal to the previous review.22 The role of disease severity in pain prevalence rates is unclear. One review found a strong positive correlation between lung function and pain prevalence (rho 5 0.79), suggesting that pain is more common in those with moderate rather than severe COPD.20 However, our findings of similar prevalence rates between disease severity classifications,4,5,7,8,15 together with the lack of relationship between pain intensity and lung function,4,29 suggest that other factors may influence pain experience.
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NR
Shoulders: 33% Lx region: 29% LL: 58% Tx region: 21% Chest: 18% Head: 12% UL: 31% Cx region: 17% Buttocks: 13%
72% (n 5 111)
72% (n 5 111)
COPD: 45% (n 5 45) Control: 34% (n 5 113)
Borge et al5/2010
Borge et al6/2011
Bentsen et al4/2011 COPD: Cx region: 44% Chest: 36% Tx region: 24% Lx region: 47% UL: 42% LL: 69% Buttocks: 18% Control: Cx region: 46% Chest: 47% Tx region: 23% Lx region: 51% UL: 60% LL: 84% Buttocks: 31%
Shoulder/neck/UL: 50% Chest: 38% Entire body: 13%
94% (n 5 13)
Pain Regions
Lohne et al15/2010
Prevalence
] Outcomes of Prevalence Studies
Study/Year
TABLE 5
a
NR
18 (17)
NR
NR
NR
NR
NR
NR
NR
Pain Frequency
Pain Duration, y
3.7 (1.9)b
2.7 (2.3)a
5.3 (2.9)
Pain Severity
(Continued)
Higher prevalence of pain in COPD vs control (P 5 .02) No difference in pain locations between groups No difference in current pain, worst, least, or level of interference between groups Higher proportion of those with COPD and pain had MI, US, DM, Ca, OP, asthma (all P , .05) compared with general population with pain
No difference in lung disease, number of comorbidities between those with or without pain Pain intensity (r 5 0.32) and pain interference (r 5 0.60) are related to disease-specific QOL Model including age, sex, lung function, pain intensity (b 5 0.20, P , .05) explained 30% of variance and inclusion of pain interference (b 5 0.52, P , .001) explained 40% of variance in disease-specific QOL Pain intensity (r 5 20.25) and pain interference (r 5 20.33) negatively associated with global QOL Model of age, education, and pain intensity and interference (b 5 20.21, P , .01) explained 13% of the variance in global QOL
Higher pain intensity related to breathlessness (r 5 0.26), fatigue (r 5 0.48), anxiety (r 5 0.44), depression (r 5 0.32), sleeping difficulty (r 5 0.51) Breathlessness related to pain intensity (b 5 0.24, P , .01, R2 5 10%)
Qualitative analysis
Outcomes Related to Clinical Impact
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] (continued)
45% (n 5 45) NR
COPD: pain located in neck and trunk, LL, and UL
96% (n 5 45)
HajGhanbari et al7/2012
Bentsen et al29/2013
NR
Pain Regions
45% (n 5 45)
Prevalence
Bentsen et al16/2012
Study/Year
TABLE 5
7.3 (1.6)a
2.8 (3.5)a 1.0 (0.4)b
NR
Pain Severity
NR
...
NR
Pain Duration, y
NR
...
NR
Pain Frequency Outcomes Related to Clinical Impact
(Continued)
Those with negative outlook for future had a higher pain intensity (OR 2.49, P 5 .049) Pain was not associated with anxiety, depression, or fatigue Higher pain intensity associated with sleeplessness (OR 3.19, P 5 .022) Pain was not associated with lung function, occurrence of exacerbation, or comorbidity (P . .05)
Higher severity of pain in COPD on BPI (2.8 cm vs 1.2 cm) and MPQ (1.0 cm vs 0.4 cm), both P , .001 Higher proportion of those COPD with moderate to very severe pain (P , .002), and pain located in neck/trunk and LL (P , .005) and UL (P , .04) vs control Greater level of moderate to very high pain interference in COPD (P , .002) Greater level of pain-related fear of movement or re-injury in COPD (P , .0001) Total energy expenditure moderately related to higher pain interference (r 5 20.29) Strong correlation between pain severity and physical component of SF-36 (r 5 20.45 to 20.70) Number of comorbidities significant independent correlate of pain severity in COPD (MPQ R2 5 0.33, BPI R2 5 0.33)
Those with pain were more likely to have a comorbidity (89% vs 65%, P 5 .016), a greater number of comorbidities (P , .0001) and a higher level of breathlessness (P 5 .003) There was no difference in lung function or disease severity between those with or without pain (P . .05) A higher percentage with pain reported chronic pain (22% vs 0%, P , .001) and musculoskeletal conditions (24% vs 4%, P 5 .003) compared with those without pain No difference in the prevalence of other comorbid conditions in those with or without pain (P . .05) Greater breathlessness was associated with pain (OR 5 1.03, P 5 .003) Number of comorbidities, breathlessness, and lung function explained 23% of variability in pain
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] (continued)
Cx region: 36% Tx region: 16% Lx region: 48% UL: 41% LL: 98% Buttocks: 14%
81% (n 5 44)
HajGhanbari et al8/2014 NR
NR
NR
3.6 (1.3)a 1.3 (0.9)b
Pain Duration, y
Pain Severity
NR
NR
Pain Frequency
Higher number of comorbidities correlated to high pain intensity (MPQ r 5 0.40, BPI r 5 0.36) and pain interference (r 5 0.50) Higher pain intensity in those with musculoskeletal comorbidity (4.0 cm vs 2.6 cm, P , .05) and endocrine disorder (4.3 cm vs 3.0 cm, P , .05) No difference in pain intensity with cardiovascular comorbidity. No relationship between comorbid condition and frequency of pain in location 73% of COPD experienced moderate to very high pain interference with daily activities, highest with normal work, walking, general activity, sleep, and relationships with others
Higher proportion of chronic pain in those with COPD (P , .001) Higher proportion with neuropathic pain (27% vs 21%), inflammatory pain (70% vs 65%), back pain (36% vs 27%), neck pain (13% vs 10%), muscle pain (22% vs 19%) (all P , .001) Chronic pain based on recurrent pain diagnoses in COPD (49%) vs control 41%, P , .001 Those with COPD and chronic pain had more chest pain, painful respiration compared with those without pain (P , .01), but no difference in dyspnea symptoms or cough Those with COPD and pain had a higher proportion of OA/RA (38% vs 15%, P 5 .004), depression (17% vs 6%, P 5 .01), psychoses (15% vs 5%, P 5 .02), and cancer (P , .05)
Outcomes Related to Clinical Impact
Ca 5 cancer; Cx 5 cervical; DM 5 diabetes mellitus; LL 5 lower limb; Lx 5 lumbar; MI 5 myocardial infarction; NR 5 not reported; OA 5 osteoarthritis; OP 5 osteoporosis; QOL 5 quality of life; RA 5 rheumatoid arthritis; Tx 5 thoracic; UL 5 upper limb; USA 5 unstable angina. See Table 3 legend for expansion of other abbreviations. aNRS 5 Numerical Rating Scale–Brief Pain Inventory. bVAS 5 Visual Analog Scale–McGill Pain Questionnaire.
COPD: Back pain: 36% Neck pain: 13% Control: Back pain: 27% Neck pain 10%
Pain Regions
COPD: 60% (n 5 4,755) Control: 52% (n 5 3,180)
Prevalence
Roberts et al19/2013
Study/Year
TABLE 5
The negative influence of pain experiences upon anxiety and its interference with daily activities, sleep, and HRQOL indicate that pain warrants clinical attention. The simultaneous occurrence of symptoms in patients with very severe COPD,15 particularly breathlessness and anxiety,45,46 may account for the pain-related fear of movement.7 This, together with reduced exercise capacity in those with COPD and pain,33 suggests it may be important to consider the effect of pain on pulmonary rehabilitation. Figure 2 – Meta-analysis of point prevalence of pain in COPD.
Comorbidities may be one of those factors, with a higher frequency of concurrent conditions in those with COPD experiencing pain compared with healthy control subjects4,19 or individuals with COPD without pain.16 The specific contribution of comorbidities appears variable. Current findings suggest that a greater pain intensity was associated with specific comorbidities, although this did not influence pain locations.8 However, another study found comorbidity quantity to be insignificant.6 With healthy control subjects aged-matched,4,7 it is unlikely that age-related comorbidities are relevant. Only one study reported the type of pain (neuropathic, inflammatory) experienced by patients.19 While this provides some insight into possible etiologies, further evaluation including the history of symptom experience is necessary to identify possible causes of pain in COPD. The increase in breathlessness associated with higher pain intensity5,15,16 may be related to the altered respiratory mechanics observed in COPD.34 A similar relationship has been described between muscle overload, altered respiration, and pain in individuals without COPD diagnosed with low back pain.35 The relationship between pain and breathlessness is complex, with shared characteristics and common neural pathways which subserve discomfort in both symptoms.36 Further exploration of the interaction between these symptoms is required to identify the contribution of respiratory mechanics to pain. Pain intensity was classed as mild to moderate, based on values established in other conditions including cancer and osteoarthritis.37-39 While greater than those without COPD,7 it is comparable to individuals with cystic fibrosis and asthma.40-44 The lack of consistent reporting of the least, average, and worst pain6-8,29 limits the ability to determine the dimensions of pain intensity in COPD. In addition, greater knowledge of the frequency and duration are needed to fully understand the pain experience. 1256 Original Research
A variety of treatment options have been suggested to tackle pain in COPD,16,19 however, their effectiveness was not evaluated in this review due to the minimal reporting.16,19 Further research is required to evaluate the effectiveness of interventions to manage pain in COPD. This is the first review exploring the measurement properties of instruments assessing pain in COPD. The assessment burden of the two questionnaires is low, making either a feasible choice. The BPI and the MPQ provide insight into the relationships between pain and key clinical factors in COPD. Although all relevant measurement properties of each instrument specific to pain have not been established, the construct validity of the BPI is the most comprehensive, suggesting this tool may be the optimal choice in clinical practice until further research is completed. The decision to exclude papers which only reported pain prevalence and clinical associations may have influenced the overall prevalence in COPD subgroups, particularly those with end-stage disease.11,47 In addition, the classifications of pain intensity have largely been based on other chronic conditions; these should be further validated in COPD. Although the COSMIN scoring system is designed to evaluate studies on measurement properties, no study included in this review had this as its primary aim, which may influence the low COSMIN scores observed. In conclusion, this review illustrates that pain is a common problem in people with moderate to very severe COPD. The associations between pain and HRQOL, fatigue, and breathlessness suggest that pain has important clinical repercussions. While comorbidities may influence the pain experience, the possible etiologies of pain require clarification. Greater exploration of patient experiences of pain through qualitative studies is warranted. There is limited information regarding the properties of current pain outcome measures. Further work to establish other measurement properties of the BPI and MPQ, including internal consistency, reliability, and responsiveness, is of clinical value.
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Acknowledgments Author contributions: A. L. L. is the guarantor for this study. A. L. L. contributed to the development of the research design and concept, data analysis, and manuscript preparation and review; S. L. H. contributed to the development of the research design, data analysis, and review of the manuscript; and R. S. G. and D. B. contributed to the development of the research design and concept, data analysis, and review of the manuscript. Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Additional information: The e-Appendixes and e-Tables can be found in the Supplemental Materials section of the online article.
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References 1. Blinderman CD, Homel P, Billings JA, Tennstedt S, Portenoy RK. Symptom distress and quality of life in patients with advanced chronic obstructive pulmonary disease. J Pain Symptom Manage. 2009;38(1):115-123. 2. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Revised 2011. GOLD website. http://www.goldcopd. org/guidelines-global-strategy-fordiagnosis-management.html. Accessed August 4, 2014. 3. Task Force on Taxonomy of the International Association for the Study of Pain. Part III: Pain terms, a current list with definitions and notes on usage. In: Merskey H, Bogduk N, eds. Classification of Chronic Pain: Descriptions of Chronic Pain Syndromes and Definitions of Pain Terms. 2 ed. Seattle, WA: IASP Press; 1994:209-214. 4. Bentsen SB, Rustøen T, Miaskowski C. Prevalence and characteristics of pain in patients with chronic obstructive pulmonary disease compared to the Norwegian general population. J Pain. 2011;12(5):539-545. 5. Borge CR, Wahl AK, Moum T. Association of breathlessness with multiple symptoms in chronic obstructive pulmonary disease. J Adv Nurs. 2010; 66(12):2688-2700. 6. Borge CR, Wahl AK, Moum T. Pain and quality of life with chronic obstructive pulmonary disease. Heart Lung. 2011;40(3):e90-e101. 7. HajGhanbari B, Holsti L, Road JD, Reid WD. Pain in people with chronic obstructive pulmonary disease (COPD). Respir Med. 2012;106(7):998-1005. 8. HajGhanbari B, Yamabayashi C, Garland SJ, Road JD, Reid WD. The relationship between pain and comorbid health conditions in people with chronic obstructive pulmonary disease. Cardiopulm Phys Ther J. 2014;25(1):29-35. 9. Synnot A, Williams M. Low back pain in individuals with chronic airflow limita-
journal.publications.chestnet.org
14.
15.
16.
17.
18.
19.
20.
21.
tion and their partners—a preliminary prevalence study. Physiother Res Int. 2002;7(4):215-227. Skilbeck J, Mott L, Page H, Smith D, Hjelmeland-Ahmedzai S, Clark D. Palliative care in chronic obstructive airways disease: a needs assessment. Palliat Med. 1998;12(4):245-254. Elkington H, White P, Addington-Hall J, Higgs R, Edmonds P. The healthcare needs of chronic obstructive pulmonary disease patients in the last year of life. Palliat Med. 2005;19(6):485-491. Claessens MT, Lynn J, Zhong Z, et al. Dying with lung cancer or chronic obstructive pulmonary disease: insights from SUPPORT. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments. J Am Geriatr Soc. 2000;48(suppl 5):S146-S153. White P, White S, Edmonds P, et al. Palliative care or end-of-life care in advanced chronic obstructive pulmonary disease: a prospective community survey. Br J Gen Pract. 2011;61(587):e362-e370. Janssen DJ, Spruit MA, Uszko-Lencer NH, Schols JM, Wouters EF. Symptoms, comorbidities, and health care in advanced chronic obstructive pulmonary disease or chronic heart failure. J Palliat Med. 2011;14(6):735-743. Lohne V, Heer HC, Andersen M, Miaskowski C, Kongerud J, Rustøen T. Qualitative study of pain of patients with chronic obstructive pulmonary disease. Heart Lung. 2010;39(3):226-234. Bentsen SB, Rustøen T, Miaskowski C. Differences in subjective and objective respiratory parameters in patients with chronic obstructive pulmonary disease with and without pain. Int J Chron Obstruct Pulmon Dis. 2012;7:137-143. Crisafulli E, Costi S, Luppi F, et al. Role of comorbidities in a cohort of patients with COPD undergoing pulmonary rehabilitation. Thorax. 2008;63(6):487-492. Jørgensen NR, Schwarz P, Holme I, Henriksen BM, Petersen LJ, Backer V. The prevalence of osteoporosis in patients with chronic obstructive pulmonary disease: a cross sectional study. Respir Med. 2007;101(1):177-185. Roberts MH, Mapel DW, Hartry A, Von Worley A, Thomson H. Chronic pain and pain medication use in chronic obstructive pulmonary disease. A cross-sectional study. Ann Am Thorac Soc. 2013;10(4):290-298. Royal College of Physicians/British Pain Society/British Geriatic Society. The assessment of pain in older people: national guidelines. In: Turner-Stokes H, Higgins B, eds. Concise Guidance to Good Practice. A Series of Evidence-Based Guidelines for Clinical Management. No. 8. London, England: Royal College of Physicians of London; 2007. Powell RA, Downing J, Ddungu H, Mwangi-Powell FN. Pain history and pain assessment. In: Koph A, Patel NB, eds. Guide to Pain Management in LowResource Settings. Seattle, WA: International Association for the Study of Pain; 2010.
22. van Dam van Isselt EF, GroenewegenSipkema KH, Spruit-van Eijk M, et al. Pain in patients with COPD: a systematic review and meta-analysis. BMJ Open. 2014;4(9):e005898. 23. Moher D, Liberati A, Tetzlaff J, Altman DG; The PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7): e1000097. 24. Law M, Stewart D, Pollock N, Letts L, Bosch J, Westmorland M. Guidelines for critical review form: quantitative studies. 1998. McMaster University School of Rehabilitation Science website. http:// www.canchild.ca/en/canchildresources/ resources/quantguide.pdf. Accessed September 2014. 25. Critical Appraisal Skills Programme (CASP). Making sense of evidence. 10 questions to help you make sense of qualitative research. 2006. CASP UK website. http://www.casp-uk.net/. Accessed August 21, 2014. 26. Kitto SC, Chesters J, Grbich C. Quality in qualitative research. Med J Aust. 2008;188(4):243-246. 27. Terwee CB, Jansma EP, Riphagen II, de Vet HC. Development of a methodological PubMed search filter for finding studies on measurement properties of measurement instruments. Qual Life Res. 2009;18(8):1115-1123. 28. Terwee CB, Mokkink LB, Knol DL, Ostelo RW, Bouter LM, de Vet HC. Rating the methodological quality in systematic reviews of studies on measurement properties: a scoring system for the COSMIN checklist. Qual Life Res. 2012;21(4):651-657. 29. Bentsen SB, Gundersen D, Assmus J, Bringsvor H, Berland A. Multiple symptoms in patients with chronic obstructive pulmonary disease in Norway. Nurs Health Sci. 2013;15(3):292-299. 30. Barendregt JJ, Doi SA, Lee YY, Norman RE, Vos T. Meta-analysis of prevalence. J Epidemiol Community Health. 2013; 67(11):974-978. 31. Perera R, Heneghan C. Interpreting meta-analysis in systematic reviews. Evid Based Med. 2008;13(3):67-69. 32. Doi SA, Thalib L. A quality-effects model for meta-analysis. Epidemiology. 2008;19(1):94-100. 33. HajGhanbari B, Garland SJ, Road JD, Reid WD. Pain and physical performance in people with COPD. Respir Med. 2013;107(11):1692-1699. 34. Gosselink R. Breathing techniques in patients with chronic obstructive pulmonary disease (COPD). Chron Respir Dis. 2004;1(3):163-172. 35. Hodges PW, Heijnen I, Gandevia SC. Postural activity of the diaphragm is reduced in humans when respiratory demand increases. J Physiol. 2001;537(pt 3): 999-1008. 36. Lansing RW, Gracely RH, Banzett RB. The multiple dimensions of dyspnea: review and hypotheses. Respir Physiol Neurobiol. 2009;167(1):53-60.
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37. Serlin RC, Mendoza TR, Nakamura Y, Edwards KR, Cleeland CS. When is cancer pain mild, moderate or severe? Grading pain severity by its interference with function. Pain. 1995;61(2): 277-284.
41.
38. Li KK, Harris K, Hadi S, Chow E. What should be the optimal cut points for mild, moderate, and severe pain? J Palliat Med. 2007;10(6):1338-1346.
42.
39. Kapstad H, Hanestad BR, Langeland N, Rustøen T, Stavem K. Cutpoints for mild, moderate and severe pain in patients with osteoarthritis of the hip or knee ready for joint replacement surgery. BMC Musculoskelet Disord. 2008;9:55.
43.
40. Stenekes SJ, Hughes A, Grégoire MC, Frager G, Robinson WM, McGrath PJ. Frequency and self-management of pain, dyspnea, and cough in cystic
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44.
fibrosis. J Pain Symptom Manage. 2009;38(6):837-848. Sermet-Gaudelus I, De Villartay P, de Dreuzy P, et al. Pain in children and adults with cystic fibrosis: a comparative study. J Pain Symptom Manage. 2009; 38(2):281-290. Flume PA, Ciolino J, Gray S, Lester MK. Patient-reported pain and impaired sleep quality in adult patients with cystic fibrosis. J Cyst Fibros. 2009;8(5): 321-325. Kelemen L, Lee AL, Button BM, Presnell S, Wilson JW, Holland AE. Pain impacts on quality of life and interferes with treatment in adults with cystic fibrosis. Physiother Res Int. 2012;17(3):132-141. Lunardi AC, Marques da Silva CC, Rodrigues Mendes FA, Marques AP, Stelmach R, Fernandes Carvalho CR.
Musculoskeletal dysfunction and pain in adults with asthma. J Asthma. 2011;48(1):105-110. 45. Keil DC, Stenzel NM, Kühl K, et al. The impact of chronic obstructive pulmonary disease-related fears on diseasespecific disability. Chron Respir Dis. 2014;11(1):31-40. 46. Smoller J, Pollack M, Otto M, Rosenbaum J, Kradin R. Pain anxiety, dyspnea and respiratory disease. Theoretical and clinical considerations. Am J Respir Crit Care Med. 1996;154(1): 6-17. 47. Solano JP, Gomes B, Higginson IJ. A comparison of symptom prevalence in far advanced cancer, AIDS, heart disease, chronic obstructive pulmonary disease and renal disease. J Pain Symptom Manage. 2006;31(1):58-69.
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Original Research COPD
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Pain and Its Clinical Associations in Individuals With COPD A Systematic Review Annemarie L. Lee, PhD; Samantha L. Harrison, PhD; Roger S. Goldstein, MBChB, FCCP; and Dina Brooks, PhD
Pain is emerging as a clinical complication in COPD, but the clinical impact of this comorbidity and the measurement properties of instruments used to assess pain require evaluation.
BACKGROUND:
METHODS: Electronic searches of five databases were performed up to September 2014 for the two phases of this review. To be included in phase 1, studies reported the clinical associations of pain and prevalence in individuals with COPD. To be included in phase 2, studies reported measurement properties of an instrument assessing pain in COPD. Two independent reviewers rated the quality of quantitative and qualitative evidence (phase 1) and the measurement properties using the four-point Consensus‐Based Standards for the Selection of Health Status Measurement Instruments (COSMIN) checklist (phase 2).
Of the 358 studies identified in the literature, nine met the inclusion criteria for phase 1 and five for phase 2. The mean (SD) quality score (of 16) for the quantitative studies was 13.1 (1.7). The pooled prevalence of pain in moderate to very severe COPD was 66% (95% CI, 44%-85%). Higher pain intensity was associated with increased dyspnea, fatigue, poorer quality of life, and a greater quantity of specific comorbidities. Of the two identified instruments (Brief Pain Inventory and McGill Pain Questionnaire), the measurement properties analyzed were construct validity, internal consistency, and criterion-predictive validity, with variable findings based on “fair” or “poor” quality studies. RESULTS:
In people with COPD, pain has negative clinical associations with symptoms and quality-of-life measures. Further research exploring the measurement properties of instruments assessing pain is required. CHEST 2015; 147(5):1246-1258
CONCLUSIONS:
Manuscript received October 29, 2014; revision accepted January 18, 2015; originally published Online First February 5, 2015. ABBREVIATIONS: BPI 5 Brief Pain Inventory; COSMIN 5 ConsensusBased Standards for the Selection of Health Status Measurement Instruments; HRQOL 5 health-related quality of life; MPQ 5 McGill Pain Questionnaire AFFILIATIONS: From the Department of Respiratory Medicine (Drs Lee, Harrison, Goldstein, and Brooks), West Park Healthcare Centre; and Department of Physical Therapy (Drs Lee, Harrison, Goldstein, and Brooks) and Department of Medicine (Dr Goldstein), University of Toronto, Toronto, ON, Canada.
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FUNDING/SUPPORT:
The authors have reported to CHEST that no funding was received for this study. CORRESPONDENCE TO: Dina Brooks, PhD, Department of Physical Therapy, University of Toronto, 160-500 University Ave, Toronto, ON, M5G 1V7, Canada; e-mail: [email protected] © 2015 AMERICAN COLLEGE OF CHEST PHYSICIANS. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details. DOI: 10.1378/chest.14-2690
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Common symptoms in individuals with COPD are dyspnea, fatigue, and anxiety, all of which are associated with impaired health-related quality of life (HRQOL) and reduced exercise tolerance.1,2 More recently, there is increased awareness that pain is a commonly reported symptom in COPD. Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or is described in terms of such damage.3 In COPD, pain appears to affect between 45% and 94% of individuals,1,4-9 including 21% to 77% with end-stage lung disease.10-14 Pain has been reported in the spinal and chest wall regions,4,8,15 with higher pain levels linked to greater breathlessness,5,16 but its interaction with other symptoms of COPD are less clear. COPD is often accompanied by comorbidities,17,18 and individuals experiencing pain may have a higher proportion of musculoskeletal disorders.7,8,16,19 The current recommendations for assessing and evaluating the impact of pain are to incorporate the sensory and affective dimension of
Materials and Methods This review was completed in two phases based on the two aims and is reported according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines.23 Phase 1 aimed to identify the association of pain characteristics, including prevalence in COPD with clinical features to give a contextual framework for any associations evident. Phase 2 identified instruments used to assess pain in COPD and their measurement properties. Phase 1: Pain Characteristics and Clinical Associations A systematic search was undertaken by one author (A. L. L.) of five databases, from inception to September 2014 (Fig 1), with reference lists of retrieved articles inspected to identify additional papers and authors contacted when necessary. The search strategy for MEDLINE is outlined in e-Appendix 1 and was adapted for other databases. Inclusion Criteria: Following duplicate removal, studies were screened by two independent reviewers (A. L. L. and S. L. H.). This included review of citations’ titles and abstracts from retrieved studies, followed by a full-text review of potentially eligible studies according to the inclusion criteria (Table 1). Any disagreement regarding eligibility was resolved by a consensus meeting, with consultation with a third reviewer (D. B.) when necessary. Data Extraction and Quality Assessment: Data extraction was performed by one investigator (A. L. L.) (checked by a second investigator) using a standardized template. For quantitative studies, quality appraisal was conducted using the Critical Review Form–Quantitative Studies.24 This tool evaluates method rigor and bias, with a total score of 16. For qualitative studies, the Critical Appraisal Skills Program (CASP)25 was used, evaluating scientific rigor, credibility, and relevance.26 Appraisal was completed independently by two reviewers, with any disagreement resolved by consensus. Phase 2: Instrument Measurement Properties A similar search strategy of the same databases applied in phase 1 was undertaken by one author (A. L. L.). Search terms were customized for
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pain and its impact.20,21 With the emerging interest in understanding the extent and implications of pain in this population,22 there is a need to explore this issue further by determining the specific characteristics of pain experiences and its clinical associations in COPD. The measurement and clinical associations of pain are complex. It is, therefore, important to determine whether the available assessment tools capture all of its dimensions. A better understanding of their measurement properties will assist clinicians in selecting the instruments best suited to assess pain in COPD. Therefore, the primary aim of this systematic review was to determine the association between pain prevalence and specific pain characteristics with clinical features of COPD. The secondary aim was to explore the measurement properties of instruments assessing pain in COPD. This trial was registered with PROSPERO (CRD42014010618).
each database, with a validated sensitive search fi lter for finding studies on measurement properties of instruments applied.25 The search strategy for MEDLINE is described in e-Appendix 2. Inclusion Criteria: Following removal of duplicates, studies were screened by two independent reviewers (A. L. L. and S. L. H.). This included screening of titles and abstracts from all retrieved studies followed by full-text review of potentially eligible studies, based on the inclusion criteria (Table 2) with any disagreements resolved by consensus. Data Extraction and Quality Assessment: Data were extracted using a standardized template. Two independent reviewers (A. L. L. and S. L. H.) evaluated the study quality using the Consensus-Based Standards for the Selection of Health Status Measurement Instruments (COSMIN) checklist.27 This is a validated tool composed of 10 sections, each scoring the quality of one measurement property. Within each section, items are individually scored based on a four-point scale (excellent, good, fair, or poor) with an overall quality score for each property obtained using the lowest score recorded among the items, as recommended.28 Analysis Analysis of prevalence was based on the response to a question of “do you have pain?” in any instrument used. For studies which reported outcomes for the same series of patients, 4-6,16,29 the prevalence was included only once in the meta-analysis. The pooled prevalence of pain was analyzed using MetaXL 1.3, a tool for meta-analysis in Microsoft Excel (EpiGear International Pty Ltd). The data were first transformed using the variance stabilizing double arcsine transformation. 30 The quality effects model was then applied to determine the prevalence rate and 95% CI. This model was selected over the fixed or random effects models to explicitly address heterogeneity in pooled proportions caused by differences in study quality and distribution, 31,32 allowing greater weighting to high-quality studies. MetaXL ensures that the pooled proportions add up to one. Heterogeneity assumption was assessed by the Q-test and I2 test. Clinical implications of pain were reported narratively.
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Figure 1 – Study flow from identification to inclusion of final studies for phase 1. CINAHL 5 Cumulative Index to Nursing and Allied Health Literature; EMBASE 5 Excerpta Medica Database.
Results Phase 1: Pain Characteristics and Clinical Associations
A total of 437 articles were identified; following references checks of included articles, an additional nine papers were identified. After removing 13 duplicates, 358 were reviewed for title and abstract, and 34 fulltext articles were reviewed, with nine meeting the inclusion criteria (Fig 1). Study characteristics are outlined 1248 Original Research
on Table 3, with two authors contacted for further information.6,7 Quality Assessment: The mean (SD) quality score of quantitative studies22 was 13.1 (1.7) of 16 (Table 4). Common methodologic flaws were sampling biases, inadequate blinding, and inadequate sample size justification. The qualitative study15 evaluation is outlined in e-Table 1. Although study aims were clear, with appropriate methodology applied, participants were awaiting
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TABLE 1
] Inclusion Criteria for Phase 1
Criterion
Specifics
Participants
Participants diagnosed with COPD, in a stable clinical state or experiencing an acute exacerbation
Study design
Cohort, case-control, cross-sectional and qualitative study designs
Pain prevalence
Reports of pain prevalence (point prevalence or pain in the past wk[s]/mo[s]/y[s]) based on valid or nonvalid questionnaires specific to pain, patient interviews, or medical record review. Instruments outlining prevalence were consistent with the current recommendations of the International Association for the Study of Pain for assessing pain.21
Pain characteristics and associations
Pain severity, frequency, duration, location, and implemented treatment strategies. Associations of pain with symptoms (breathing, fatigue), psychologic symptoms (anxiety, depression), physical activity, exercise tolerance or muscle strength, HRQOL, disease severity, comorbidities.
Only studies published in English were included. HRQOL 5 health-related quality of life.
lung transplantation, suggesting recruitment bias. Interviews were semistructured, with analysis undertaken until saturation, although it is unclear how themes were derived. Study Characteristics: Six studies were conducted in Norway,4-6,15,16,29 two studies in Canada,7,8 and one study in the United States.19 Three studies included both COPD and healthy control subjects,4,7,19 of which two studies matched populations for age and sex.8,19 All patients were in a stable clinical state, with moderate to very severe lung disease.2 One study incorporated qualitative analysis of pain experiences.15 The definition of pain varied considerably between studies. Five studies based prevalence on experience of pain within the past 24 h or past week according to the Brief Pain Inventory (BPI).5-8,15 One study established the presence of pain according to the question, “Are you generally bothered by pain”16 while two studies used a nonvalidated (yes/no) query.4,29 Prevalence was reported in nine studies (Table 5). Of these, six studies reported on a different series of patients with COPD.4,6-8,15,19 Prevalence (pain within the last 24 h or previous 7 days) was examined in six studies.4-8,29 Overall, the pooled prevalence was 66% (95% CI, 44%-85%) (Fig 2). The heterogeneity of I2 of 93% and Q 5 73 suggests strong variability between TABLE 2
studies.8 Compared with healthy control subjects, prevalence was greater in COPD.4,7,19 Common pain regions were lower back/lumbar (29%-48%),4,6,8,19 chest (16%-38%),4,6,8,15 upper back/ thorax (16%-24%),4,6,8 neck/cervical (13%-46%),4,6,8,15,19 lower limb (14%-98%),4,6,8 and upper limb (41%-64%).4,6,8,15 Two studies reported more pain locations in COPD compared with control subjects,7,19 while the 2011 report by Bentsen et al4 found no difference between groups. Five studies reported pain severity at its worst, ranging from 2.7 to 7.3 on the numerical rating scale of the BPI5,8,15,29 and from 1.0 to 1.3 cm on the McGill Pain Questionnaire (MPQ) Visual Analog Scale.7,8 Of the two studies comparing pain severity between groups, one found a higher severity in COPD,7 and one found no difference.4 The average duration that pain had been experienced by participants with COPD was 18 years in one study.4 Two studies found that pain interference in COPD was up to 5.4 times greater on the BPI interference scale compared with control subjects,7,8 although the 2011 report by Bentsen et al4 found no difference between groups. Greater pain intensity was related to higher levels of breathlessness.5,16 One study described more fatigue in
] Inclusion Criteria for Phase 2
Criterion
Specifics
Participants
Participants diagnosed with COPD, in a stable clinical state or experiencing an acute exacerbation in all stages of disease severity
Instrument/questionnaire
Developed to measure the presence of pain
Measurement properties
Information reported for one or more measurement properties including reliability, internal consistency, measurement error, criterion concurrent validity, criterion/predictive validity, construct validity/hypothesis testing, responsiveness
Only studies published in English were included.
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Cross-sectional
Cross-sectional
Cross-sectional
Cross-sectional
Cohort
Borge et al6/2011
Bentsen et al4/2011
Bentsen et al16/2012
HajGhanbari et al7/2012
Roberts et al19/2013
Cross-sectional
Cross-sectional
Borge et al5/2010
Bentsen et al29/2013
Cross-sectional and qualitative
Lohne et al15/2010
Study Design
] Details of Study Characteristics
Study/Year
TABLE 3
COPD: 100
COPD: 7,952 Control: 15,904
COPD: 47 Control: 47
COPD: 100
COPD: 100 Control: 333
COPD: 154
COPD: 154
COPD: 16
No. of Participants
Age (Mean [SD]), y; Sex
66 (8); 49% female
COPD: 69; 58% female Control: 68; 58% female
COPD: 70 (7); 43% female Control: 68 (9); 43% female
COPD with pain: 65 (9.2) COPD without pain: 67.9 (7.3); 49% female
COPD: 65 (9) Control: 58 (11) Sex NR
64 (10); 49% female
65 (10); 48% female
58; 75% female
Disease Severity
Measurement Tools
FEV1: 46 (15)% pred
(Continued)
9-item questionnaire: Pain–yes/no, NRS for pain at worst and least and now with scale 0-10 Future expectations: positive or negative
CMS-defined chronic conditions ICD-9-CM diagnosis code (procedure-based pain, prescription for pain medication) Pain diagnoses (neurologic, inflammatory, mechanical/compressive, muscular and injury-related pain)
BPI (short form) MPQ TSK CHAMPS SF-36
COPD: FEV1: 45 (19)% pred
NR
Pain question (Are you generally bothered by pain?) SGRQ Comorbidities
9-item questionnaire: Pain–yes/no, NRS for pain at worst and least and now with scale 0-10 Cause of pain Body diagram from BPI
COPD: FEV1: 48 (16)% pred
COPD with pain: FEV1: 48 (16)% pred COPD without pain: FEV1: 45 (14)% pred
BPI (short form) RQOLQ QOLS
BPI (short form) HADS LFS GSDS RQOLQ
BPI (short form) Qualitative assessment
FEV1: 1.6 (0.7) L
FEV1: 59 (23)% pred
FEV1: 21 (6)% pred
BPI 5 Brief Pain Inventory; CHAMPS 5 Community Health Activities Model Program for Seniors Questionnaire; CMS 5 Centers for Medicare and Medicaid Services; GSDS 5 General Sleep Disturbance Scale; HADS 5 Hospital Anxiety and Depression Scale; ICD-9 CM 5 International Classification of Diseases, Ninth Revision, Clinical Modification; LFS 5 Lee Fatigue Scale; MPQ 5 McGill Pain Questionnaire; NR 5 not reported; NRS 5 numerical rating scale; % pred 5 percent predicted; QOLS 5 Quality-of-Life Scale; RQOLQ 5 Respiratory Quality-of-Life Questionnaire; SF-36 5 Short Form 36; SGRQ 5 St. George’s Respiratory Questionnaire; TSK 5 Tampa Scale for Kinesiophobia
MPQ BPI (long form) Charlson Index (with common musculoskeletal conditions) FEV1: 43% pred 72; 52% female COPD: 54 Cross-sectional HajGhanbari et al /2014
Measurement Tools Disease Severity Age (Mean [SD]), y; Sex No. of Participants Study Design
8
Study/Year
] (continued) TABLE 3
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those with higher pain levels,5 although a 2013 report by Bentsen et al29 found no relationship. Higher pain intensity in COPD was associated with poorer HRQOL,5,8 poorer sleep quality,5,8,29 less physical activity, and an increased pain-related fear of movement.7,15 Pain negatively impacted on anxiety and depression,5 with reports that both pain and breathlessness contributed to severe anxiety.15 A higher proportion of individuals with COPD and pain had at least one comorbidity,4,16 with higher pain severity and interference associated with more comorbidites.7,8 Common comorbidities were musculoskeletal conditions,4,16,19 endocrine disorders,4,8 depression, and cancer.4,19 No difference in lung function was evident in those with COPD with or without pain.5,16 Approaches to pain management included pain medication,8,15,19 physical modalities, and acupuncture,8,16 with medication and acupuncture used more frequently in COPD than in the general population.16,19 Phase 2: Instrument Measurement Properties
A total of 248 studies were retrieved from the databases. Following duplicate removal, 218 studies were reviewed in full text and abstract form, with five meeting the inclusion criteria. With the exception of one study,33 all were included in phase 1.5-8 The measurement properties for the two identified instruments are summarized in e-Table 2 and included construct validity/hypothesis testing,5-8,33 internal consistency,6 and criterion-predictive validity.7 Overall, the studies scored “fair” or “poor” for the measurement properties evaluated. The poorest scoring areas were design requirements (lack of a prior hypotheses and sample size). Measurement Properties: High internal consistency for BPI pain intensity and interference was found (e-Table 2).6 For criterion-predictive validity of the BPI, a strong relationship between the MPQ pain severity score and the BPI pain intensity (r 5 0.82) and BPI interference (r 5 0.66) was evident.7 The construct validity explored the relationships between pain intensity or interference and other COPD outcome measures, with a weak to moderate relationship with disease severity5,7 and symptoms5 for the BPI and a moderate relationship with exercise capacity for both the BPI and MPQ.7,33 A weak-to-moderate relationship was evident between pain severity measured on the BPI and MPQ and comorbidities5,7,8,33 as well as HRQOL6,7,33 (e-Table 2).
Discussion Patients with moderate to severe COPD have a high prevalence of pain (66%) compared with healthy control 1251
TABLE 4
] Quality Assessment of Observational Studies Quality Appraisal Score
Study/Year
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
Lohne et al15/2010
9
9
9
3
3
9
9
9
9
3
3
3
3
9
9
9
10
Total
Borge et al5/2010
9
9
9
3
3
9
3
9
9
9
9
9
9
9
9
9
13
Borge et al6/2011
9
9
9
3
3
9
9
9
9
9
3
9
9
9
9
3
12
Bentsen et al /2011
9
9
9
3
3
9
9
9
9
9
9
9
9
9
9
9
14
Bentsen et al16/2012
9
9
9
3
3
9
9
3
3
9
9
9
9
9
9
9
12
HajGhanbari et al7/2012
9
9
9
3
9
9
9
9
9
9
9
9
9
9
9
9
15
4
Bentsen et al29/2013
9
9
9
9
3
9
9
9
9
9
9
9
9
9
9
9
15
Roberts et al19/2013
9
9
9
9
9
9
9
3
3
9
9
9
9
9
9
9
15
HajGhanbari et al8/2014
9
9
9
3
3
9
9
9
9
9
3
9
9
9
9
3
12 Mean (SD) 13.1 (1.8)
Key to scoring (Law et al24 all items 9 for yes, 3 for no, except biases [3 for yes, 9 for no]). 1 5 Was the study purpose stated clearly? 2 5 Was relevant background literature reviewed? 3 5 Was the design appropriate for the study question? 4 5 Were there any biases present (minimum response rate of 80% for sample bias, blinding of investigators when physical measure were taken)? 5 5 Was sample size justified? 6 5 Was the sample described in detail? (had to include the number of participants by sex, age, and a description of where the cohort was sampled from). 7 5 Was informed consent obtained? (if not described, assume no). 8 5 Were the outcome measures valid? (if all not described, assume no). 9 5 Were the outcome measures reliable? (if all not described, assume no). 10 5 Results were reported in terms of statistical significance? 11 5 Drop outs were reported? 12 5 Clinical importance was reported? 13 5 Were the statistical analysis methods appropriate? 14 5 Conclusions were appropriate given the study methods? 15 5 Are there implications for clinical practice given the results of the study (based on the experience of the reviewers)? 16 5 Were limitations of the study acknowledged and described by the authors?
subjects. Pain experiences have a positive association with dyspnea and a negative association with HRQOL. Possible contributing factors are comorbid conditions. There was insufficient information to establish the measurement properties of the instruments used in COPD, with the evidence rated as fair. Heterogeneity in the prevalence of pain was evident. This may be attributed to the differing methods of population sampling; the use of convenience sampling and self-selection may have introduced some bias. The differing sample sizes between studies are also a likely factor. The variation appears to be unaffected by the time frame of pain reporting.4,5,7,8,15,19 In addition, it is unlikely to be influenced by slightly different pain definitions used in both validated or nonvalidated questionnaires to establish the presence of pain, with prevalence reported using nonvalidated questionnaires4,16,29 within the 95% CI of the pooled prevalence (44%-85%). While this suggests that asking patients if they experience pain may be sufficient to determine prevalence, clinically, this approach should be considered with caution when using nonvalidated questionnaires, in which measurement properties have not been established. A systematic review reported pain prevalence as a subdomain of HRQOL to be 67%20; this, together with our findings, suggests that pain is a common problem in COPD. 1252 Original Research
In comparison with the previous review,22 we determined the basis of pain prevalence from unidimensional and multidimensional pain scales, as per the current recommendations for assessing pain.20,21 van Dam van Isselt et al22 also used HRQOL tools, which inquired about the presence of pain. The primary purpose of these instruments is to measure health status or quality of life rather than to assess pain. In addition, the internal consistency of selected HRQOL tools could influence the strength of the link between pain prevalence and impact, which may increase the risk of overestimating any clinical associations. Finally, our objective was to establish the clinical association of pain within the context of pain prevalence in COPD, a different goal to the previous review.22 The role of disease severity in pain prevalence rates is unclear. One review found a strong positive correlation between lung function and pain prevalence (rho 5 0.79), suggesting that pain is more common in those with moderate rather than severe COPD.20 However, our findings of similar prevalence rates between disease severity classifications,4,5,7,8,15 together with the lack of relationship between pain intensity and lung function,4,29 suggest that other factors may influence pain experience.
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1253
NR
Shoulders: 33% Lx region: 29% LL: 58% Tx region: 21% Chest: 18% Head: 12% UL: 31% Cx region: 17% Buttocks: 13%
72% (n 5 111)
72% (n 5 111)
COPD: 45% (n 5 45) Control: 34% (n 5 113)
Borge et al5/2010
Borge et al6/2011
Bentsen et al4/2011 COPD: Cx region: 44% Chest: 36% Tx region: 24% Lx region: 47% UL: 42% LL: 69% Buttocks: 18% Control: Cx region: 46% Chest: 47% Tx region: 23% Lx region: 51% UL: 60% LL: 84% Buttocks: 31%
Shoulder/neck/UL: 50% Chest: 38% Entire body: 13%
94% (n 5 13)
Pain Regions
Lohne et al15/2010
Prevalence
] Outcomes of Prevalence Studies
Study/Year
TABLE 5
a
NR
18 (17)
NR
NR
NR
NR
NR
NR
NR
Pain Frequency
Pain Duration, y
3.7 (1.9)b
2.7 (2.3)a
5.3 (2.9)
Pain Severity
(Continued)
Higher prevalence of pain in COPD vs control (P 5 .02) No difference in pain locations between groups No difference in current pain, worst, least, or level of interference between groups Higher proportion of those with COPD and pain had MI, US, DM, Ca, OP, asthma (all P , .05) compared with general population with pain
No difference in lung disease, number of comorbidities between those with or without pain Pain intensity (r 5 0.32) and pain interference (r 5 0.60) are related to disease-specific QOL Model including age, sex, lung function, pain intensity (b 5 0.20, P , .05) explained 30% of variance and inclusion of pain interference (b 5 0.52, P , .001) explained 40% of variance in disease-specific QOL Pain intensity (r 5 20.25) and pain interference (r 5 20.33) negatively associated with global QOL Model of age, education, and pain intensity and interference (b 5 20.21, P , .01) explained 13% of the variance in global QOL
Higher pain intensity related to breathlessness (r 5 0.26), fatigue (r 5 0.48), anxiety (r 5 0.44), depression (r 5 0.32), sleeping difficulty (r 5 0.51) Breathlessness related to pain intensity (b 5 0.24, P , .01, R2 5 10%)
Qualitative analysis
Outcomes Related to Clinical Impact
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] (continued)
45% (n 5 45) NR
COPD: pain located in neck and trunk, LL, and UL
96% (n 5 45)
HajGhanbari et al7/2012
Bentsen et al29/2013
NR
Pain Regions
45% (n 5 45)
Prevalence
Bentsen et al16/2012
Study/Year
TABLE 5
7.3 (1.6)a
2.8 (3.5)a 1.0 (0.4)b
NR
Pain Severity
NR
...
NR
Pain Duration, y
NR
...
NR
Pain Frequency Outcomes Related to Clinical Impact
(Continued)
Those with negative outlook for future had a higher pain intensity (OR 2.49, P 5 .049) Pain was not associated with anxiety, depression, or fatigue Higher pain intensity associated with sleeplessness (OR 3.19, P 5 .022) Pain was not associated with lung function, occurrence of exacerbation, or comorbidity (P . .05)
Higher severity of pain in COPD on BPI (2.8 cm vs 1.2 cm) and MPQ (1.0 cm vs 0.4 cm), both P , .001 Higher proportion of those COPD with moderate to very severe pain (P , .002), and pain located in neck/trunk and LL (P , .005) and UL (P , .04) vs control Greater level of moderate to very high pain interference in COPD (P , .002) Greater level of pain-related fear of movement or re-injury in COPD (P , .0001) Total energy expenditure moderately related to higher pain interference (r 5 20.29) Strong correlation between pain severity and physical component of SF-36 (r 5 20.45 to 20.70) Number of comorbidities significant independent correlate of pain severity in COPD (MPQ R2 5 0.33, BPI R2 5 0.33)
Those with pain were more likely to have a comorbidity (89% vs 65%, P 5 .016), a greater number of comorbidities (P , .0001) and a higher level of breathlessness (P 5 .003) There was no difference in lung function or disease severity between those with or without pain (P . .05) A higher percentage with pain reported chronic pain (22% vs 0%, P , .001) and musculoskeletal conditions (24% vs 4%, P 5 .003) compared with those without pain No difference in the prevalence of other comorbid conditions in those with or without pain (P . .05) Greater breathlessness was associated with pain (OR 5 1.03, P 5 .003) Number of comorbidities, breathlessness, and lung function explained 23% of variability in pain
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] (continued)
Cx region: 36% Tx region: 16% Lx region: 48% UL: 41% LL: 98% Buttocks: 14%
81% (n 5 44)
HajGhanbari et al8/2014 NR
NR
NR
3.6 (1.3)a 1.3 (0.9)b
Pain Duration, y
Pain Severity
NR
NR
Pain Frequency
Higher number of comorbidities correlated to high pain intensity (MPQ r 5 0.40, BPI r 5 0.36) and pain interference (r 5 0.50) Higher pain intensity in those with musculoskeletal comorbidity (4.0 cm vs 2.6 cm, P , .05) and endocrine disorder (4.3 cm vs 3.0 cm, P , .05) No difference in pain intensity with cardiovascular comorbidity. No relationship between comorbid condition and frequency of pain in location 73% of COPD experienced moderate to very high pain interference with daily activities, highest with normal work, walking, general activity, sleep, and relationships with others
Higher proportion of chronic pain in those with COPD (P , .001) Higher proportion with neuropathic pain (27% vs 21%), inflammatory pain (70% vs 65%), back pain (36% vs 27%), neck pain (13% vs 10%), muscle pain (22% vs 19%) (all P , .001) Chronic pain based on recurrent pain diagnoses in COPD (49%) vs control 41%, P , .001 Those with COPD and chronic pain had more chest pain, painful respiration compared with those without pain (P , .01), but no difference in dyspnea symptoms or cough Those with COPD and pain had a higher proportion of OA/RA (38% vs 15%, P 5 .004), depression (17% vs 6%, P 5 .01), psychoses (15% vs 5%, P 5 .02), and cancer (P , .05)
Outcomes Related to Clinical Impact
Ca 5 cancer; Cx 5 cervical; DM 5 diabetes mellitus; LL 5 lower limb; Lx 5 lumbar; MI 5 myocardial infarction; NR 5 not reported; OA 5 osteoarthritis; OP 5 osteoporosis; QOL 5 quality of life; RA 5 rheumatoid arthritis; Tx 5 thoracic; UL 5 upper limb; USA 5 unstable angina. See Table 3 legend for expansion of other abbreviations. aNRS 5 Numerical Rating Scale–Brief Pain Inventory. bVAS 5 Visual Analog Scale–McGill Pain Questionnaire.
COPD: Back pain: 36% Neck pain: 13% Control: Back pain: 27% Neck pain 10%
Pain Regions
COPD: 60% (n 5 4,755) Control: 52% (n 5 3,180)
Prevalence
Roberts et al19/2013
Study/Year
TABLE 5
The negative influence of pain experiences upon anxiety and its interference with daily activities, sleep, and HRQOL indicate that pain warrants clinical attention. The simultaneous occurrence of symptoms in patients with very severe COPD,15 particularly breathlessness and anxiety,45,46 may account for the pain-related fear of movement.7 This, together with reduced exercise capacity in those with COPD and pain,33 suggests it may be important to consider the effect of pain on pulmonary rehabilitation. Figure 2 – Meta-analysis of point prevalence of pain in COPD.
Comorbidities may be one of those factors, with a higher frequency of concurrent conditions in those with COPD experiencing pain compared with healthy control subjects4,19 or individuals with COPD without pain.16 The specific contribution of comorbidities appears variable. Current findings suggest that a greater pain intensity was associated with specific comorbidities, although this did not influence pain locations.8 However, another study found comorbidity quantity to be insignificant.6 With healthy control subjects aged-matched,4,7 it is unlikely that age-related comorbidities are relevant. Only one study reported the type of pain (neuropathic, inflammatory) experienced by patients.19 While this provides some insight into possible etiologies, further evaluation including the history of symptom experience is necessary to identify possible causes of pain in COPD. The increase in breathlessness associated with higher pain intensity5,15,16 may be related to the altered respiratory mechanics observed in COPD.34 A similar relationship has been described between muscle overload, altered respiration, and pain in individuals without COPD diagnosed with low back pain.35 The relationship between pain and breathlessness is complex, with shared characteristics and common neural pathways which subserve discomfort in both symptoms.36 Further exploration of the interaction between these symptoms is required to identify the contribution of respiratory mechanics to pain. Pain intensity was classed as mild to moderate, based on values established in other conditions including cancer and osteoarthritis.37-39 While greater than those without COPD,7 it is comparable to individuals with cystic fibrosis and asthma.40-44 The lack of consistent reporting of the least, average, and worst pain6-8,29 limits the ability to determine the dimensions of pain intensity in COPD. In addition, greater knowledge of the frequency and duration are needed to fully understand the pain experience. 1256 Original Research
A variety of treatment options have been suggested to tackle pain in COPD,16,19 however, their effectiveness was not evaluated in this review due to the minimal reporting.16,19 Further research is required to evaluate the effectiveness of interventions to manage pain in COPD. This is the first review exploring the measurement properties of instruments assessing pain in COPD. The assessment burden of the two questionnaires is low, making either a feasible choice. The BPI and the MPQ provide insight into the relationships between pain and key clinical factors in COPD. Although all relevant measurement properties of each instrument specific to pain have not been established, the construct validity of the BPI is the most comprehensive, suggesting this tool may be the optimal choice in clinical practice until further research is completed. The decision to exclude papers which only reported pain prevalence and clinical associations may have influenced the overall prevalence in COPD subgroups, particularly those with end-stage disease.11,47 In addition, the classifications of pain intensity have largely been based on other chronic conditions; these should be further validated in COPD. Although the COSMIN scoring system is designed to evaluate studies on measurement properties, no study included in this review had this as its primary aim, which may influence the low COSMIN scores observed. In conclusion, this review illustrates that pain is a common problem in people with moderate to very severe COPD. The associations between pain and HRQOL, fatigue, and breathlessness suggest that pain has important clinical repercussions. While comorbidities may influence the pain experience, the possible etiologies of pain require clarification. Greater exploration of patient experiences of pain through qualitative studies is warranted. There is limited information regarding the properties of current pain outcome measures. Further work to establish other measurement properties of the BPI and MPQ, including internal consistency, reliability, and responsiveness, is of clinical value.
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Acknowledgments Author contributions: A. L. L. is the guarantor for this study. A. L. L. contributed to the development of the research design and concept, data analysis, and manuscript preparation and review; S. L. H. contributed to the development of the research design, data analysis, and review of the manuscript; and R. S. G. and D. B. contributed to the development of the research design and concept, data analysis, and review of the manuscript. Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Additional information: The e-Appendixes and e-Tables can be found in the Supplemental Materials section of the online article.
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11.
12.
13.
References 1. Blinderman CD, Homel P, Billings JA, Tennstedt S, Portenoy RK. Symptom distress and quality of life in patients with advanced chronic obstructive pulmonary disease. J Pain Symptom Manage. 2009;38(1):115-123. 2. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Revised 2011. GOLD website. http://www.goldcopd. org/guidelines-global-strategy-fordiagnosis-management.html. Accessed August 4, 2014. 3. Task Force on Taxonomy of the International Association for the Study of Pain. Part III: Pain terms, a current list with definitions and notes on usage. In: Merskey H, Bogduk N, eds. Classification of Chronic Pain: Descriptions of Chronic Pain Syndromes and Definitions of Pain Terms. 2 ed. Seattle, WA: IASP Press; 1994:209-214. 4. Bentsen SB, Rustøen T, Miaskowski C. Prevalence and characteristics of pain in patients with chronic obstructive pulmonary disease compared to the Norwegian general population. J Pain. 2011;12(5):539-545. 5. Borge CR, Wahl AK, Moum T. Association of breathlessness with multiple symptoms in chronic obstructive pulmonary disease. J Adv Nurs. 2010; 66(12):2688-2700. 6. Borge CR, Wahl AK, Moum T. Pain and quality of life with chronic obstructive pulmonary disease. Heart Lung. 2011;40(3):e90-e101. 7. HajGhanbari B, Holsti L, Road JD, Reid WD. Pain in people with chronic obstructive pulmonary disease (COPD). Respir Med. 2012;106(7):998-1005. 8. HajGhanbari B, Yamabayashi C, Garland SJ, Road JD, Reid WD. The relationship between pain and comorbid health conditions in people with chronic obstructive pulmonary disease. Cardiopulm Phys Ther J. 2014;25(1):29-35. 9. Synnot A, Williams M. Low back pain in individuals with chronic airflow limita-
journal.publications.chestnet.org
14.
15.
16.
17.
18.
19.
20.
21.
tion and their partners—a preliminary prevalence study. Physiother Res Int. 2002;7(4):215-227. Skilbeck J, Mott L, Page H, Smith D, Hjelmeland-Ahmedzai S, Clark D. Palliative care in chronic obstructive airways disease: a needs assessment. Palliat Med. 1998;12(4):245-254. Elkington H, White P, Addington-Hall J, Higgs R, Edmonds P. The healthcare needs of chronic obstructive pulmonary disease patients in the last year of life. Palliat Med. 2005;19(6):485-491. Claessens MT, Lynn J, Zhong Z, et al. Dying with lung cancer or chronic obstructive pulmonary disease: insights from SUPPORT. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments. J Am Geriatr Soc. 2000;48(suppl 5):S146-S153. White P, White S, Edmonds P, et al. Palliative care or end-of-life care in advanced chronic obstructive pulmonary disease: a prospective community survey. Br J Gen Pract. 2011;61(587):e362-e370. Janssen DJ, Spruit MA, Uszko-Lencer NH, Schols JM, Wouters EF. Symptoms, comorbidities, and health care in advanced chronic obstructive pulmonary disease or chronic heart failure. J Palliat Med. 2011;14(6):735-743. Lohne V, Heer HC, Andersen M, Miaskowski C, Kongerud J, Rustøen T. Qualitative study of pain of patients with chronic obstructive pulmonary disease. Heart Lung. 2010;39(3):226-234. Bentsen SB, Rustøen T, Miaskowski C. Differences in subjective and objective respiratory parameters in patients with chronic obstructive pulmonary disease with and without pain. Int J Chron Obstruct Pulmon Dis. 2012;7:137-143. Crisafulli E, Costi S, Luppi F, et al. Role of comorbidities in a cohort of patients with COPD undergoing pulmonary rehabilitation. Thorax. 2008;63(6):487-492. Jørgensen NR, Schwarz P, Holme I, Henriksen BM, Petersen LJ, Backer V. The prevalence of osteoporosis in patients with chronic obstructive pulmonary disease: a cross sectional study. Respir Med. 2007;101(1):177-185. Roberts MH, Mapel DW, Hartry A, Von Worley A, Thomson H. Chronic pain and pain medication use in chronic obstructive pulmonary disease. A cross-sectional study. Ann Am Thorac Soc. 2013;10(4):290-298. Royal College of Physicians/British Pain Society/British Geriatic Society. The assessment of pain in older people: national guidelines. In: Turner-Stokes H, Higgins B, eds. Concise Guidance to Good Practice. A Series of Evidence-Based Guidelines for Clinical Management. No. 8. London, England: Royal College of Physicians of London; 2007. Powell RA, Downing J, Ddungu H, Mwangi-Powell FN. Pain history and pain assessment. In: Koph A, Patel NB, eds. Guide to Pain Management in LowResource Settings. Seattle, WA: International Association for the Study of Pain; 2010.
22. van Dam van Isselt EF, GroenewegenSipkema KH, Spruit-van Eijk M, et al. Pain in patients with COPD: a systematic review and meta-analysis. BMJ Open. 2014;4(9):e005898. 23. Moher D, Liberati A, Tetzlaff J, Altman DG; The PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7): e1000097. 24. Law M, Stewart D, Pollock N, Letts L, Bosch J, Westmorland M. Guidelines for critical review form: quantitative studies. 1998. McMaster University School of Rehabilitation Science website. http:// www.canchild.ca/en/canchildresources/ resources/quantguide.pdf. Accessed September 2014. 25. Critical Appraisal Skills Programme (CASP). Making sense of evidence. 10 questions to help you make sense of qualitative research. 2006. CASP UK website. http://www.casp-uk.net/. Accessed August 21, 2014. 26. Kitto SC, Chesters J, Grbich C. Quality in qualitative research. Med J Aust. 2008;188(4):243-246. 27. Terwee CB, Jansma EP, Riphagen II, de Vet HC. Development of a methodological PubMed search filter for finding studies on measurement properties of measurement instruments. Qual Life Res. 2009;18(8):1115-1123. 28. Terwee CB, Mokkink LB, Knol DL, Ostelo RW, Bouter LM, de Vet HC. Rating the methodological quality in systematic reviews of studies on measurement properties: a scoring system for the COSMIN checklist. Qual Life Res. 2012;21(4):651-657. 29. Bentsen SB, Gundersen D, Assmus J, Bringsvor H, Berland A. Multiple symptoms in patients with chronic obstructive pulmonary disease in Norway. Nurs Health Sci. 2013;15(3):292-299. 30. Barendregt JJ, Doi SA, Lee YY, Norman RE, Vos T. Meta-analysis of prevalence. J Epidemiol Community Health. 2013; 67(11):974-978. 31. Perera R, Heneghan C. Interpreting meta-analysis in systematic reviews. Evid Based Med. 2008;13(3):67-69. 32. Doi SA, Thalib L. A quality-effects model for meta-analysis. Epidemiology. 2008;19(1):94-100. 33. HajGhanbari B, Garland SJ, Road JD, Reid WD. Pain and physical performance in people with COPD. Respir Med. 2013;107(11):1692-1699. 34. Gosselink R. Breathing techniques in patients with chronic obstructive pulmonary disease (COPD). Chron Respir Dis. 2004;1(3):163-172. 35. Hodges PW, Heijnen I, Gandevia SC. Postural activity of the diaphragm is reduced in humans when respiratory demand increases. J Physiol. 2001;537(pt 3): 999-1008. 36. Lansing RW, Gracely RH, Banzett RB. The multiple dimensions of dyspnea: review and hypotheses. Respir Physiol Neurobiol. 2009;167(1):53-60.
1257
37. Serlin RC, Mendoza TR, Nakamura Y, Edwards KR, Cleeland CS. When is cancer pain mild, moderate or severe? Grading pain severity by its interference with function. Pain. 1995;61(2): 277-284.
41.
38. Li KK, Harris K, Hadi S, Chow E. What should be the optimal cut points for mild, moderate, and severe pain? J Palliat Med. 2007;10(6):1338-1346.
42.
39. Kapstad H, Hanestad BR, Langeland N, Rustøen T, Stavem K. Cutpoints for mild, moderate and severe pain in patients with osteoarthritis of the hip or knee ready for joint replacement surgery. BMC Musculoskelet Disord. 2008;9:55.
43.
40. Stenekes SJ, Hughes A, Grégoire MC, Frager G, Robinson WM, McGrath PJ. Frequency and self-management of pain, dyspnea, and cough in cystic
1258 Original Research
44.
fibrosis. J Pain Symptom Manage. 2009;38(6):837-848. Sermet-Gaudelus I, De Villartay P, de Dreuzy P, et al. Pain in children and adults with cystic fibrosis: a comparative study. J Pain Symptom Manage. 2009; 38(2):281-290. Flume PA, Ciolino J, Gray S, Lester MK. Patient-reported pain and impaired sleep quality in adult patients with cystic fibrosis. J Cyst Fibros. 2009;8(5): 321-325. Kelemen L, Lee AL, Button BM, Presnell S, Wilson JW, Holland AE. Pain impacts on quality of life and interferes with treatment in adults with cystic fibrosis. Physiother Res Int. 2012;17(3):132-141. Lunardi AC, Marques da Silva CC, Rodrigues Mendes FA, Marques AP, Stelmach R, Fernandes Carvalho CR.
Musculoskeletal dysfunction and pain in adults with asthma. J Asthma. 2011;48(1):105-110. 45. Keil DC, Stenzel NM, Kühl K, et al. The impact of chronic obstructive pulmonary disease-related fears on diseasespecific disability. Chron Respir Dis. 2014;11(1):31-40. 46. Smoller J, Pollack M, Otto M, Rosenbaum J, Kradin R. Pain anxiety, dyspnea and respiratory disease. Theoretical and clinical considerations. Am J Respir Crit Care Med. 1996;154(1): 6-17. 47. Solano JP, Gomes B, Higginson IJ. A comparison of symptom prevalence in far advanced cancer, AIDS, heart disease, chronic obstructive pulmonary disease and renal disease. J Pain Symptom Manage. 2006;31(1):58-69.
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