Association Between Transient Opioid Use and Short-Term Respiratory Exacerbation Among Adults With Chronic Obstructive Pulmonary Disease: A Case-Crossover Study

Abstract

The association of historical opioid use with health care use and death among patients with chronic obstructive pulmonary disease (COPD) has been tested. Using Mississippi Medicaid data, we examined the association of transient or short-term opioid use and acute respiratory exacerbations among adults with COPD. We used a case-crossover design and 2013–2017 Mississippi Medicaid administrative claims data. A total of 1,972 qualifying exacerbation events occurred in 1,354 beneficiaries. The frequency and dose of opioid exposure in the 7 days before the exacerbation were examined and compared with the opioid exposure in 10 control windows, each 7 days long, before the exacerbation. Adjusted odds ratios were estimated using conditional logistic regression models to estimate the risk of opioid use on exacerbations after accounting for use of bronchodilators, corticosteroids, benzodiazepines, and β-blockers. Overall, opioid exposure in the 7 days before an exacerbation was significantly associated with acute respiratory exacerbation (odds ratio = 1.81; 95% confidence interval: 1.60, 2.05). Each 25-mg increase in morphine equivalent daily dose was associated with an 11.2% increase in the odds of an acute respiratory exacerbation (odds ratio = 1.11; 95% confidence interval: 1.04, 1.20). Transient use of opioids was significantly associated with acute respiratory exacerbation of COPD.

Evaluating the use of methods to mitigate bias from non‐transient medications in the case‐crossover design: A systematic review

“…Of the 114 included articles, the case‐crossover design was the most common (100, 88%), 18–117 followed by the case‐time‐control (19, 17%), 38,63,67,71,86,118–131 and case‐case‐time‐control (4, 3%) 33,47,48,86 . (Table 1) The most common outcomes measured in these studies were hospitalization (43, 38%), cardiovascular events (22, 19%) and fall‐related injury/fracture (15, 13%).…”

“…Researchers sometime use multiple control windows in case‐crossover studies to increase study power and use washout periods to eliminate carryover effects of drugs or to account for non‐adherence to medications, especially when non‐transient medications are evalauted 10 . Of 48 articles that used multiple control windows, half of the articles reported no washout period between each control period 19,24,25,27,28,37,39,41,44,46,53,55,59,66,72,73,77,79,81,84,90,103,104,106,113,114 . It is unclear whether these multiple control windows were analyzed as a single large control window or time‐dependent control windows.…”

Gabapentin and Opioids Utilization in Patients With Diabetic Neuropathy Enrolled in Medicare (2012–2016): A Cohort Study

“…All opioid products except buprenorphine and naloxone and their combinations were included, as these drugs are usually used for treatment of opioid dependence. 22…”

“…All opioid products except buprenorphine and naloxone and their combinations were included, as these drugs are usually used for treatment of opioid dependence. 22 Within the User cohort, patients were categorized into 3 groups based on their drug utilization during the 12-month observation period. Those who initiated gabapentin first (without concomitant opioids) were classified as the Gabapentin Initiator group.…”