Chronic Pain and Pain Medication Use in Chronic ... - ATS Journals

ORIGINAL RESEARCH Chronic Pain and Pain Medication Use in Chronic Obstructive Pulmonary Disease A Cross-Sectional Study Melissa H. Roberts1, Douglas W. Mapel1, Ann Hartry2, Ann Von Worley1, and Heather Thomson2 1 LCF Research, Health Services Research Division, Albuquerque, New Mexico; and 2Endo Pharmaceuticals, Health Economics & Outcomes Research, Malvern, Pennsylvania

Abstract Rationale: Pain is a common problem for patients with chronic obstructive pulmonary disease (COPD). However, pain is minimally discussed in COPD management guidelines. Objectives: The objective of this study was to describe chronic pain prevalence among patients with COPD compared with similar patients with other chronic diseases in a managed care population in the southwestern United States (age > 40 yr). Methods: Using data for the period January 1, 2006 through December 31, 2010, patients with COPD were matched to two control subjects without COPD but with another chronic illness based on age, sex, insurance, and healthcare encounter type. Odds ratios (OR) for evidence of chronic pain were estimated using conditional logistic regression. Pulmonary function data for 200 randomly selected patients with COPD were abstracted.

Measurements and Main Results: Retrospectively analyzed recurrent pain-related utilization (diagnoses and treatment) was considered evidence of chronic pain. The study sample comprised 7,952 patients with COPD (mean age, 69 yr; 42% male) and 15,904 patients with other chronic diseases (non-COPD). Patients with COPD compared with non-COPD patients had a higher percentage of chronic pain (59.8 vs. 51.7%; P , 0.001), chronic use of painrelated medications (41.2 vs. 31.5%; P , 0.001), and chronic use of short-acting (24.2 vs. 15.1%; P , 0.001) and long-acting opioids (4.4 vs. 1.9%; P , 0.001) compared with non-COPD patients. In conditional logistic regression models, adjusting for age, sex, Hispanic ethnicity, and comorbidities, patients with COPD had higher odds of chronic pain (OR, 1.56; 95% confidence interval [CI], 1.43–1.71), chronic use of pain-related medications (OR, 1.60; 95% CI, 1.46–1.74), and chronic use of short-acting or long-acting opioids (OR, 1.74; 95% CI, 1.57–1.92). Conclusions: Chronic pain and opioid use are prevalent among adults with COPD. This finding was not explained by the burden of comorbidity.

(Received in original form March 7, 2013; accepted in final form May 28, 2013 ) This work was supported by Endo Pharmaceuticals, Malvern, Pennsylvania. Author Contributions: M.H.R. acquired the data; had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis; contributed to the study concept and design; provided data interpretation; and drafted, revised critically for important intellectual content, and provided final approval of the manuscript version to be published. D.W.M. contributed to the study concept and design, data analysis, and interpretation and drafted, revised critically for important intellectual content, and provided final approval of the manuscript version to be published. A.H. contributed to data interpretation and revised critically for important intellectual content and provided final approval of the manuscript version to be published. A.V.W. performed the chart reviews, contributed to the data analysis and interpretation, revised critically for important intellectual content, and provided final approval of the manuscript version to be published. H.T. contributed to data interpretation, revised critically for important intellectual content, and provided final approval of the manuscript version to be published. Correspondence and requests for reprints should be addressed to Melissa H. Roberts, Ph.D.(c), M.S., 2309 Renard Place SE, Suite 103, Albuquerque, NM 87106. E-mail: [email protected] Prior abstract publication/presentation: A related abstract was presented at the ATS 2013 International Conference in Philadelphia, PA, May 17–22, 2013. This article has an online supplement, which is accessible from this issue’s table of contents at www.atsjournals.org Ann Am Thorac Soc Vol 10, No 4, pp 290–298, Aug 2013 Copyright © 2013 by the American Thoracic Society DOI: 10.1513/AnnalsATS.201303-040OC Internet address: www.atsjournals.org

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States, recently surpassing 290

stroke (1), and is among the top five causes of medical disability (2). COPD prevalence is projected to increase over the next

decade, especially among women. Although it is clear that COPD causes tremendous morbidity and mortality, we understand

AnnalsATS Volume 10 Number 4 | August 2013

ORIGINAL RESEARCH relatively little about improving the quality of life for these patients. Patients with COPD suffer from very high rates of depression and anxiety (3), factors known to influence quality of life. As well, pain has been consistently noted to be an important determinant of overall health status and quality of life in COPD population studies (4–6). A few studies also suggest that there is a high prevalence of physical pain among patients with COPD. In a recent cross-sectional survey examining patients in Norway, 45% of patients with COPD reported chronic pain symptoms versus 34% of adults without COPD but with similar demographics (7). This higher prevalence of pain is supported by an earlier study finding higher narcotic use among patients with COPD than among age- and gender-matched control subjects (8). In a larger and more recent nationwide survey of COPD use and treatment, higher use of pain medication compared with short-acting b-agonists and corticosteroids was noted among patients with COPD (9). Although pain may be common among patients with COPD, there is almost no discussion of pain in COPD management guidelines. The Global Initiative for Chronic Obstructive Lung Disease (GOLD), an international guideline for disease management, does not mention chronic pain and discusses opioids only in the context of the relief of dyspnea (3). The combined statement on COPD of four major international medical societies also

does not mention pain as a comorbidity or problem in management (10). Reasons patients with COPD might have an increased risk for chronic pain remain unclear, although one possibility is a higher risk for other chronic illnesses associated with physical pain, such as osteoarthritis (OA) (8). The objective of this study was to describe the prevalence of chronic pain in a population-based cohort of individuals with COPD as compared with age- and gender-matched patients with other chronic diseases. This study was designed to examine the following hypotheses: (1) Patients with COPD have a higher prevalence of chronic pain than patients of the same age and sex who have chronic illnesses other than COPD; (2) patients with COPD patients use more pain-related medications in general, and opioid pain medications in particular, than matched control subjects; and (3) the presence of chronic comorbid illnesses among patients with COPD does not fully explain the higher prevalence of chronic pain and pain medication use in COPD. Some of the results of these studies have been previously reported in the form of an abstract and oral presentation (11).

Methods The study time period was January 1, 2006 through December 31, 2010. The study

sample was selected from members of a regional managed care plan in the southwestern United States that covers approximately 220,000 persons annually and offers Medicare and Medicaid managed care plans in addition to commercial plans. Included individuals had an International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis code of COPD (chronic bronchitis [491.xx], emphysema [492.xx], or chronic airway obstruction [496]) or at least one of the following Centers for Medicare and Medicaid (CMS)-defined chronic conditions: osteo- or rheumatoid arthritis (OA/RA), ischemic heart disease, heart failure, chronic kidney disease, diabetes, cancer (colorectal, endometrial, female breast, lung, or prostate), atrial fibrillation, stroke/transient ischemic attack, or Alzheimer’s and related disorders/senile dementia (12). Individuals were included if they had a qualifying diagnosis associated with an inpatient stay or two separate outpatient encounters (to include emergency department visits). There were no exclusion criteria. The study and waiver of informed consent was approved by the institutional review board Ethical and Independent Review Services (#11284–01) (13). Individuals in the COPD and comparison groups were matched based on a healthcare event to minimize confounding due to time and/or types of healthcare utilization (e.g., to avoid matching someone

Table 1. Chronic pain definitions Type of Evidence for Chronic Pain

Definition

Diagnoses

a. Diagnoses: neuropathic, inflammatory, mechanical/compressive, muscle, injury b. Two or more diagnoses with a minimum of 42 d and maximum of 60 d between dates Nonpharmacy treatments (procedures) a. These include interventional, moderate sedation, physiotherapy, stimulation procedures (see Table E2 for more detail*) b. Two or more treatments with a minimum of 42 days and maximum of 60 days between dates A. Specific pain medications Outpatient pharmacy claims a. These include antirheumatic drug therapy, artificial joint fluid, mild analgesics, muscle relaxants/antispasmodics, short- and long-acting opioids, and topical pain relief. b. Two or more prescriptions with a minimum of 28 d and maximum of 60 d between prescription claim dates. Prescriptions can be from different categories. B. Other pain-related medications a. These include anticonvulsants, antidepressants, antipsychotics/sleep agents, anxiolytics/ sedatives/hypnotics b. Two or more prescriptions with a minimum of 28 d and maximum of 60 d between prescription claim dates c. Evidence of a pain-related diagnosis in the period 30 d before or after first prescription claim. Pain-related diagnoses are: neuropathic, inflammatory, mechanical/compressive, muscle, injury *Behavioral medicine and experimental treatments were not included because these were rarely used.

Roberts, Mapel, Hartry, et al.: Chronic Pain in COPD and Other Chronic Diseases

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ORIGINAL RESEARCH with an inpatient experience with someone who has never been hospitalized). Matched individuals were age 40 years or older at the matching event and were required to have at least 15 months continuous health plan enrollment, 3 months of which were before the matching event. Two individuals with non-COPD chronic disease were matched to each individual with COPD. In addition to type of event (discharge from an inpatient stay [IP], outpatient [OP], and emergency department [ED]) and timing of event (66 mo), individuals were matched based on known confounding factors for experience of pain: age (62 yr), sex, and insurance coverage on matching event date (see Figure E1 in the online supplement). Within the COPD group, individuals with evidence of a spirometry test were randomly selected for chart abstraction to

obtain 200 individuals with confirmed airflow limitation according to GOLD criteria (3). Evidence of pain was indicated by an ICD-9-CM diagnosis code (IP, OP, ED), by a claim for a procedure-based pain therapy, or by an outpatient prescription claim for pain medication. Most studies of pain have focused on specific types of pain (e.g., low back pain, migraine), and a comprehensive list of pain-related ICD9-CM diagnosis codes was not available. Consequently, we constructed a set of painrelated diagnosis codes based on observed health plan claims data for enrollees aged > 40 years who had been prescribed shortacting or long-acting opioids during the study period and from peer-reviewed guidelines and studies (details are provided in the online supplement) (14–35). We

identified five major categories for pain diagnoses (neurological, inflammatory, mechanical/compressive, muscular, and injury-related pain), and within mechanical/compressive we further categorized pain according to location (neck, back, and other). Pain-related procedures were categorized into six categories: behavioral (biofeedback), experimental (low-level laser therapy), interventional (e.g., injections, infusions), pain medication (moderate sedation), physiotherapy (e.g., acupuncture, physical therapy), and stimulation (e.g., electrical stimulation, ultrasonic stimulation). Outpatient prescription pain medications were grouped into specific pain medications and pain-related medications (Table 1). We designated as pain-related those anticonvulsant and antidepressant

Table 2. Chronic obstructive pulmonary disease and matched chronic disease sample demographics and prevalence of chronic disease COPD Non-COPD

Individuals, n Age categories, % 40–54 yr 55–64 yr 65–74 yr 751 yr Mean age, yr Male, % Hispanic, % CMS morbidities, % Alzheimer’s, related disorders Atrial fibrillation Cancers (colorectal, endometrial, female breast, lung, and/or prostate) COPD CKD Diabetes Heart failure IHD AMI (within IHD) OA/RA Stroke/TIA Only one of above morbidities Number of morbidities (mean) Elixhauser morbidities, % Depression Psychoses

Non-COPD* Alzh/ Dem

Cancers

CKD

Diabetes

IHD

OA/ RA

Stroke/ TIA

7,952

15,904

1,289

1,841

4,584

6,594

3,472

6,439

1,616

12.9 18.4 32.7 35.9 69.3 42.0 28.0

14.2‡ 18.5 35.4† 31.9† 68.4† 42.0 41.3†

1.6† 3.3† 16.0† 79.2† 80.2† 31.0† 35.8†

8.0† 16.5 41.8† 33.7 70.0x 48.0† 34.1†

7.9† 12.2† 35.8‡ 44.1† 72.0† 42.3 38.5†

16.0† 21.2† 37.1† 25.7† 66.8† 44.8‡ 51.4†

8.5† 15.6‡ 35.7‡ 40.2† 71.0† 57.6† 38.3†

13.7 19.1 35.1‡ 32.0† 68.4† 32.8† 40.7†

8.7† 12.1† 30.8 48.3† 72.7† 39.2x 37.7†

8.9 15.4 11.8

8.1x 8.3† 11.6

100.0† 14.6 7.8†

5.5† 6.7† 100.0†

9.3 11.3† 9.8‡

5.8† 6.2† 7.3†

8.3 15.5 8.4†

5.8† 6.3† 6.9†

19.0† 16.8 8.7‡

100.0 30.5 28.8 27.5 31.8 6.0 31.0 12.5 21.6 3.0

28.8‡ 41.5† 10.7† 21.8† 3.4† 40.5† 10.2† 52.7† 1.8†

33.1 29.5 20.7† 22.4† 5.5 29.2 23.8† 20.6 2.9‡

24.3† 26.2x 7.9† 15.8† 2.2† 24.3† 7.7† 38.3† 2.2†

100.0† 48.2† 19.1† 26.4† 5.1x 31.3 12.5 18.1† 2.7†

33.5‡ 100.0† 11.5† 21.4† 3.4† 24.9† 8.2† 36.2† 2.2†

34.8† 22.3† 40.6† 25.5† 27.6 8.5† 100.0† 15.0† 15.4† 2.2† 27.8‡ 100.0† 14.1x 7.2† 18.4‡ 46.3† 2.9‡ 2.0†

35.5† 33.3‡ 21.0† 30.2 5.6 28.6 100.0† 19.3x 3.0

17.7 11.1

12.2† 7.2†

21.4‡ 15.5†

11.2† 4.8†

11.6† 7.4†

11.7† 7.6†

11.1† 6.3†

13.8† 7.6†

17.0 10.3

Definition of abbreviations: Alzh/Dem = Alzheimer’s disease/senile dementia; CKD = chronic kidney disease; COPD = chronic obstructive pulmonary disease; IHD = ischemic heart disease; OA/RA = osteo and/or rheumatoid arthritis; TIA = transient ischemic attack. *Characteristics for individuals with atrial fibrillation and heart failure not shown; characteristics are similar to those with IHD. † P , 0.001 for comparison to COPD. ‡ P , 0.01 for comparison to COPD. x P , 0.05 for comparison to COPD.

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ORIGINAL RESEARCH medications associated with a pain-related diagnosis because they are often prescribed to provide relief from chronic pain because of their neurochemical effects on pain processing (36). Use of these medications was only categorized as painrelated when use was associated with a pain-related diagnosis. Before our analysis of chronic pain in the matched sample, we first reviewed the prevalence of any indication of pain in the larger unmatched enrolled population among individuals age 40 years and older meeting enrollment criteria and individuals also meeting criteria for one of the study chronic conditions. We then constructed the matched sample in which, along with type of insurance and utilization, we matched patients by sex and age because being female

or older are characteristics previously found to be associated with increased rates of pain (14). Individuals were selected and matched using a cross-sectional design, and chronic pain was identified through a longitudinal examination of events. A second event during the 12-month period after the matching event that met definition requirements (Table 1) was considered to be the initial date of chronic pain. Chronic pain events within each of the three areas (diagnoses, procedures, and pharmacy) were tracked for continuity. Subsequent events occurring within the defined window of time for chronic pain (Table 1) were considered continuations of the same event. If more than 60 days transpired between events, then a chronic pain event was

considered to have ended, and any subsequent pain signaled a new pain event. Pearson x2 tests for frequencies and Student’s t test for means were used for univariate comparisons. In addition to P values, 95% confidence intervals (CIs) for absolute percentage differences were calculated. Logistic regressions were conducted to estimate odds ratios (OR) for evidence after matching of chronic pain, chronic use of pain medications, and chronic use of short- or long-acting opioids. Because matched observations were not independent observations, logistic regressions used a generalized linear model with a generalized estimating equation to adjust for dependency introduced by the matching. The repeated subject variable was the matched “pair” of one COPD and two

Table 3. Chronic obstructive pulmonary disease and matched chronic disease sample: prevalences of postindex pain-related diagnoses and treatments

Individuals, n Any evidence of Chronic Pain (from diagnoses, procedures or outpatient prescriptions), % Pain-related diagnoses, % Neuropathic Inflammatory Mechanical/compressive back Mechanical/compressive neck Mechanical/compressive other Muscle Injury At least one pain-related diagnosis, % Evidence of chronic pain based on diagnoses, % Pain-related procedures, %: Interventional Moderate sedation Physiotherapy Stimulation At least one pain-related procedure, % Evidence of chronic pain based on procedures, % Outpatient pain and pain-related medications, % Pain-related medications Anticonvulsants Antidepressants Antipsychotics and sleep agents Anxiolytics, sedatives and hypnotics Pain medications Antirheumatic drug therapy Mild analgesics Muscle relaxants/antispasmodics Short-acting opioid medications Long-acting opioid medications At least one outpatient pain or pain-related medication, % Evidence of chronic pain based on outpatient prescriptions, % Chronic use of short-acting opioids, % Chronic use of long-acting opioids, %

COPD

Non-COPD

Percentage Difference

95% CI

P Value

7,952 59.8

15,904 51.7

8.1

6.7–9.4

,0.001

26.5 70.1 35.9 13.0 49.1 15.3 22.3 85.3 48.4

20.9 64.7 26.7 9.9 32.1 12.8 19.2 78.0 41.3

5.6 5.4 9.2 3.1 17.0 2.5 3.1 7.3 7.1

4.4–6.7 4.1–6.6 7.9–10.5 2.3–4.0 15.7–18.3 1.6–3.5 2.0–4.2 6.3–8.3 5.7–8.4

,0.001 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001

16.2 2.8 14.7 10.6 30.1 11.8

13.9 1.4 14.2 9.7 26.5 11.3

2.3 1.4 0.5 0.9 3.6 0.5

1.3–3.3 0.9–1.8 20.5–1.4 0.1–1.7 2.4–4.8 20.3–1.4

,0.001 ,0.001 0.35 0.03 ,0.001 0.23

16.4 34.1 6.9 15.1

10.9 23.4 4.5 9.2

5.5 10.7 2.5 5.9

4.6–6.5 9.5–12.0 1.8–3.1 5.0–6.8

,0.001 ,0.001 ,0.001 ,0.001

2.9 24.6 15.2 49.2 6.6 70.9

2.7 24.4 11.7 37.6 2.9 60.7

0.2 0.2 3.4 11.6 3.7 10.2

20.3–0.6 21.0–1.3 2.5–4.4) 10.2–12.9 3.1–4.4 8.9–11.5

0.45 0.77 ,0.001 ,0.001 ,0.001 ,0.001

41.2

31.5

9.6

8.3–10.9

,0.001

24.2 4.4

15.1 1.9

9.1 2.5

8.0–10.2 2.0–3.0

,0.001 ,0.001

Definition of abbreviation: CI = confidence interval; COPD = chronic obstructive pulmonary disease.


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ORIGINAL RESEARCH non-COPD individuals. In addition to the CMS morbidities, we used the Elixhauser morbidities to further characterize health status of individuals. We used the comorbidity tool from the Healthcare Cost and Utilization Project to identify Elixhauser morbidities for each individual (37, 38). Covariates included in regression analyses were age, sex, Hispanic ethnicity, baseline CMS and selected Elixhauser morbidities, and number of comorbidities. As a supplemental analysis, we calculated adjusted relative prevalence ratios using a log-Poisson generalized linear model with a generalized estimating equation to have a more complete picture of the associations between factors and chronic pain (39). There were no missing variable values in the data collected. A prior study observed pain prevalence percentages that translated into an OR of approximately 1.60 for experience of chronic pain among individuals with COPD

compared with non-COPD, adjusted for age and sex (7). Assuming there were two control subjects matched to each case and a correlation of 0.20 between cases and controls, approximately 215 patients with COPD were needed to detect a significant OR of 1.60 using an a significance level of 0.05 and a power of 80%. We included osteo and/or rheumatoid arthritis, conditions known to be associated with high levels of chronic pain, as conditions the comparison group could have. We therefore conducted a sensitivity analysis excluding individuals with only OA/RA and patients with or without COPD who had the same matching ID as the excluded patients with OA/RA. Sensitivity analyses were conducted for the logistic regression analyses reviewing postindex chronic use of pain medications overall and chronic use of short- or long-acting opioids in particular. Analyses were performed using SAS (version 9.2) statistical software. All analyses

were two-tailed with a P value of , 0.05 to determine statistical significance.

Results The COPD cohort was slightly older than the non-COPD chronic disease control cohort; mean ages were 69.3 compared with 68.4 years (Table 2). Although patients with COPD and non-COPD individuals were equally matched by sex (42.0% male), the male/female ratio among the various chronic diseases varied. There was also a lower proportion of Hispanic persons in the COPD cohort and a substantially increased proportion of Hispanics among persons with diabetes, consistent with prior epidemiologic surveys in the region. On average, patients with COPD had more chronic conditions than patients without COPD (3.0 vs. 1.8; P , 0.001). Although only 21.6% of patients with COPD had only COPD, 52.7% of non-

Table 4. Odds ratios for characteristics associated with chronic pain Characteristic

Unadjusted: COPD Adjusted* COPD Male vs, female Hispanic vs Non-Hispanic Age 55–64 vs. 40–54 yr Age 65–74 vs. 40–54 yr Age > 75 vs. 40–54 yr CMS morbidities (other than COPD): Atrial fibrillation Alzheimer’s, related disorders, senile dementia Cancers (colorectal, endometrial, female breast, lung, and/or prostate) Chronic kidney disease Diabetes Heart failure Ischemic heart disease Osteo/rheumatoid arthritis Stroke/transient ischemic attack Having multiple morbidities: impact of each additional CMS morbidity (up to 3) Other morbidities: Depression Psychoses

Chronic Pain, OR (95% CI)

Chronic Use of Pain or Pain-Related Outpatient Medications, OR (95% CI)

1.39 (1.31–1.47)

1.52 (1.56–1.78)

1.81 (1.70–1.94)

1.56 0.66 0.99 0.77 0.49 0.41

1.60 0.70 1.05 0.65 0.34 0.25

1.74 0.81 1.05 0.57 0.26 0.21

(1.43–1.71) (0.62–0.69) (0.93–1.05) (0.70–0.85) (0.45–0.54) (0.37–0.45)

(1.46–1.74) (0.66–0.75) (0.99–1.12) (0.59–0.72) (0.31–0.37) (0.23–0.28)

Chronic Use of Short or LongActing Opioids, OR (95% CI)

(1.57–1.92) (0.75–0.87) (0.97–1.13) (0.51–0.63) (0.23–0.29) (0.19–0.24)

1.10 (0.99–1.23) 1.09 (0.97–1.23)

0.95 (0.85–1.07) 1.20 (1.06–1.35)

0.97 (0.85–1.10) 1.00 (0.86–1.15)

1.34 (1.21–1.49)

1.03 (0.93–1.15)

1.02 (0.90–1.16)

1.28 1.17 1.20 1.20 4.15 1.35 0.99

1.22 1.11 1.23 1.11 3.06 1.14 1.06

1.16 1.01 1.32 1.03 2.60 1.07 1.16

(1.17–1.41) (1.07–1.28) (1.08–1.33) (1.09–1.33) (3.80–4.52) (1.21–1.51) (0.91–1.07)

2.22 (2.03–2.43) 1.95 (1.74–2.19)

(1.11–1.33) (1.02–1.21) (1.11–1.36) (1.01–1.23) (2.81–3.32) (1.03–1.27) (0.98–1.14)

2.61 (2.40–2.84) 2.15 (1.94–2.39)

(1.05–1.29) (0.92–1.12) (1.18–1.49) (0.93–1.16) (2.37–2.85) (0.95–1.22) (1.06–1.26)

1.95 (1.78–2.13) 1.66 (1.48–1.85)

Definition of abbreviations: CI = confidence interval; CMS = Centers for Medicare and Medicaid; COPD = chronic obstructive pulmonary disease; OR = odds ratio. *Odds ratios from conditional logistic regression models. Unadjusted is the effect of COPD alone; adjusted summarizes models in which all listed factors were included.

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ORIGINAL RESEARCH COPD patients had just one chronic illness. The high percentage without another morbidity among the non-COPD patients was driven by the high percentage of OA/ RA (n = 2,982) and patients with diabetes (n = 2,387) who only had the one morbidity. The COPD cohort had significantly higher prevalences of cardiovascular comorbidities but had a substantially lower rate of diabetes (Table 2). The OA/RA prevalence in COPD (31.0%) was not outside the range of OA/ RA prevalence among the other chronic diseases in the non-COPD patients (24.3– 31.3%). Overall, 59.8% of those with COPD and 51.7% of those with other chronic conditions had evidence of chronic pain during the follow-up period (Table 3). These percentages were similar to those calculated for the chronic disease population of 40,447 individuals before matching (61.8 vs. 53.9% for 2010; data not shown). The percentage of patients with any inflammatory pain was slightly higher among those with COPD (70.1 vs. 64.7%; P , 0.001). The largest differences were observed for any mechanical/compressive back pain (9.2%; 95% CI, 7.9–10.5%) and mechanical/compressive pain other than neck and back (17.0%; 95% CI, 15.7– 18.3%). Overall, 48.4% of patients with COPD, compared with 41.3% of patients without COPD, had evidence of chronic pain based on recurrent pain diagnoses (P , 0.001). Significant percentage differences for outpatient pain and pain-related medications were observed, most notably for any use of antidepressants (10.7%; 95% CI, 9.5–12.0), anxiolytics/sedatives/ hypnotics (5.9%; 95% CI, 5.0–6.8), anticonvulsants (5.5%; 95% CI, 4.6–6.5%), short-acting opioid medications (11.6%; 95% CI, 10.2–12.9), and long-acting opioid medications (3.7%; 95% CI, 3.1–4.4). Overall, 41.2% of patients with COPD, compared with 31.5% of patients without COPD, had evidence of chronic use of pain or pain-related medications (P , 0.001). A significantly higher percentage of patients with COPD compared with non-COPD patients had evidence of chronic use of short-acting opioid medications (24.2 vs. 15.1%; P , 0.001) or long-acting opioid medications (4.4 vs. 1.9%; P , 0.001). In conditional multivariable logistic regression models that considered the

matched aspect of the study sample in addition to adjustment for patient sex, age, and Hispanic ethnicity, the CMS morbidities that were most strongly associated with evidence of chronic pain and chronic use of pain or pain-related medications (specifically, chronic use of short- or long-acting opioids) as measured by OR were COPD and OA/RA (Table 4). The strongest association was estimated for OA/RA; all ORs for OA/RA were greater than 2.5. Additionally, having multiple CMS morbidities was significantly associated with the chronic use of opioids (OR, 1.16; 95% CI, 1.06–1.26). Estimated adjusted ORs for COPD were 1.56 (95% CI, 1.43–1.71) for chronic pain based on recurrent diagnoses, procedures, or outpatient prescription use; 1.60 (95% CI, 1.46–1.74) for chronic use of pain or painrelated medications; and 1.74 (95% CI, 1.57–1.92) for chronic use of short- or longacting opioid medications. Using relative

prevalence ratios (PR) instead of ORs, patients with COPD are estimated to have a prevalence of chronic pain 15% greater than individuals without COPD (PR, 1.15; 95% CI, 1.09–1.20), a 27% higher prevalence of chronic use of pain or painrelated outpatient medications (PR, 1.27; 95% CI, 1.19–1.34), and 47% higher prevalence of chronic use of short or longacting opioids (PR, 1.47; 95% CI, 1.36– 1.60). In sensitivity testing of this model, we found that the OR estimates were not affected if all persons who only had OA/RA and no other disease (and their matched counterparts) were excluded from the analysis. Examination of use of medications within the pain and pain-related medication categories showed that there was no particular medication within a category that was driving the differential use by patients with COPD and non-COPD patients. The higher use observed for categories with

Figure 1. Comparison of abstracted chronic obstructive pulmonary disease (COPD) sample characteristics in the follow-up period between patients with and without chronic pain. Percentage of patients by GOLD staging for airflow obstruction and having any use of indicated COPD medications or any occurrence of indicated dyspnea symptoms, chest pain, or cough in the 12 months after study matching date. GOLD = Global Initiative for Obstructive Lung Disease; ICS = inhaled corticosteroid; LABA = long-acting b-agonist; SABA = short-acting b-agonist. *P , 0.001; †P , 0.01; ‡P , 0.05.


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ORIGINAL RESEARCH significant differences summarized in Table 3 was observed across the component medications within the categories. Abstracted medical records of 200 patients with COPD with airflow obstruction confirmed by spirometry showed no difference in evidence of chronic pain by GOLD COPD stage. Chronic pain was more evident among individuals using short-acting b-agonists (60.4 vs. 43.3%; P = 0.02) (Figure 1). Among patients with COPD with chronic pain, there was a significantly higher percentage with OA/ RA (37.5 vs. 15.4%; P = 0.004) and with depression (16.7 vs. 5.8%; P = 0.01) or psychoses (14.6 vs. 4.8%; P = 0.02) (Figure 2). Almost all patients with COPD with pain had inflammatory pain (83.3 vs. 41.3%; P , 0.001), and the second most frequent type of pain among patients with COPD was mechanical/compressive back pain (57.3 vs. 24.0%; P , 0.001).

Discussion We found that chronic pain is highly prevalent in COPD, and, in adjusted regression models, COPD is second only to OA/RA in its association with measures of chronic pain. Compared with patients with chronic disease other than COPD, patients with COPD had a 47% higher prevalence of chronic use of pain or pain-related outpatient prescription medications, a 27% higher prevalence of chronic use of short-acting or longacting opioid medications, and a 15% higher prevalence of chronic pain. Having an additional morbidity was associated with higher odds of chronic use of opioids, and, although patients with COPD tend to have more comorbidities including OA/RA, these comorbidities do not fully explain their increased use of opioids.

Figure 2. Comparison of abstracted chronic obstructive pulmonary disease sample pain-related characteristics in the follow-up period between patients with and without chronic pain. Percentage of patients with comorbidities and any occurrence of indicated pain-related diagnoses, procedures, and medications in the 12 months after study matching date. *P , 0.001; ‡P , 0.05.

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Recognizing that patients with COPD have a high prevalence of chronic pain may create an opportunity to improve their treatment. COPD treatment studies have traditionally focused on airflow obstruction and mechanisms of inflammation. More recent investigations have assessed comorbidities including depression, with growing emphasis on nonpharmacologic therapies such as pulmonary rehabilitation that reduce symptoms and improve quality of life. Our study design cannot prove any causal associations, but there are several intriguing observations. Depression and anxiety were increased in our COPD cohort, and depression was an independent factor associated with chronic opioid use. This lends support to the “vicious COPD circle” concept proposed by Lohne and colleagues, wherein severe and incomprehensible pain leads to sleep disturbance, anxiety, depression, and helplessness, which then lead to worsening dyspnea and associated upper body pain (40). It is not known whether targeting pain control could improve overall health status in COPD or if improved COPD management could reduce pain. However, in a clustercontrolled study examining the benefits of implementing COPD guidelines in primary care clinics, significant improvement in the SF-36 pain score was demonstrated even though pain management was not part of the guidelines (41). There are very few studies that have focused on pain in COPD, but our study is consistent with published data. In a crosssectional study including 100 patients with COPD in Norway with and without chronic pain plus 993 individuals > 42 years of age without COPD, Bentsen and colleagues found that 45% of patients with COPD reported being bothered by pain compared with 34% without, adjusted for age and sex. Comparatively these percentages represent an OR of approximately 1.60, which is similar to the ORs that we estimated in our analyses. The Norwegian patients with COPD were more likely to localize pain symptoms to the chest, shoulders, neck, and thorax, but no differences between patients with COPD and non-COPD patients in pain intensity scores or number of pain locations were noted (7). Similar to our finding of a significant association between number of comorbidities and chronic pain, Norwegian patients with COPD with pain had a significantly higher number of


ORIGINAL RESEARCH comorbidities (P , 0.001), with a higher percentage having skeletal/muscle diseases (24 vs. 4%; P = 0.003) and osteoarthritis (22 vs. 7%; P = 0.05) (42). In addition, higher percentages of patients with pain reported easily getting exhausted, cough and/or breathing that disturbed sleep, and cough that hurt or led to tiredness (42). In a clinical survey of 47 patients with COPD and 47 age- and gender-matched healthy persons, patients with COPD had substantially more pain as assessed by a battery of pain questionnaires, and patients with COPD were more than three times more likely to have neck and body pain (43). Although very few COPD studies have specifically assessed pain as their primary goal, some quality of life studies have included the SF-36 or EuroQOL 5-D as global health status instruments, which contain a pain score as a domain. Although most studies report a composite score instead of individual subscales, the few that report a pain score have been generally consistent with findings in our study. For example, a study comparing quality of life in men and women with COPD matched for age and percent of predicted FEV1 found that women had significantly worse SF-36

pain scores and worse scores in all SF-36 domains except general health and social functioning (44). We did not find a correlation between percent of predicted FEV1 and pain utilization. Similarly, in an analysis of data from the ISOLDE study, bodily pain did not correlate with declining lung function, even though other SF-36 subscales were negatively affected (45). An analysis of the EuroQOL 5-D by COPD severity also did not find an association between pain score and FEV1 (46). In an EQ-5D survey of 1,475 patients with COPD from Sweden, only 13.6% reported no problems with pain, as compared with 49.4% with no depression problems and 48.6% having no mobility problems (47). There are study limitations that should be considered. Our analysis basis was painrelated healthcare use as an estimate of overall pain, and although this system has been applied to other chronic illnesses, there is uncertainty about how closely healthcare use reflects pain symptoms. COPD was established by claims data, and there may be misclassification of patients. However, the healthcare use among the 200 patients confirmed to have COPD by spirometry standards in our chart abstraction was remarkably similar to that of the overall

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