Temporal trends in dual bronchodilator prescribing before and after GOLD 2023 publication

Introduction

Chronic obstructive pulmonary disease (COPD) exacerbations are a major cause of hospitalization and readmission and contribute substantially to morbidity and healthcare utilization (1-3). In the United States, COPD exacerbations account for approximately 700,000 hospitalizations annually and are associated with 30-day readmission rates approaching 20% (2).

Long-acting bronchodilator (LABD) therapy is a central component of COPD management. Long-acting muscarinic antagonists (LAMA) and long-acting beta agonists (LABA) reduce symptoms and exacerbation risk in COPD, while dual LABD therapy consisting of combined LABA/LAMA treatment has been shown to reduce exacerbations and hospitalizations compared with monotherapy in patients at increased exacerbation risk (4-6). Accumulating evidence supporting dual LABD therapy was incorporated into the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2023 recommendations, which recommend dual LABD therapy for patients hospitalized with COPD exacerbation. However, little is known about how discharge prescribing patterns changed following the publication of these recommendations. The objective of this study was to evaluate trends in dual LABD prescribing before and after publication of the GOLD 2023 recommendations among patients hospitalized with COPD exacerbation. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1325/rc).

Methods

We conducted a retrospective cohort study of patients with a clinical diagnosis of COPD admitted to Henry Ford Hospital, a large tertiary-care academic medical center in Detroit, Michigan, between December 2017 and July 2024. Patients were included if they were 18 years or older and had a clinician-documented diagnosis of a COPD exacerbation during their hospital admission. COPD exacerbations were identified using International Classification of Diseases (ICD)-10 diagnostic codes specific to acute exacerbations of COPD (e.g., J44.1 and J44.0). Diagnoses and medication data were obtained from the electronic medical record, including admission documentation, discharge medication reconciliation, and pharmacy prescribing records. To reduce potential selection bias and repeated sampling of the same individuals, only index hospitalizations were included. Repeat hospitalizations from the same patient were not analyzed. Patients were excluded if pneumonia was considered the primary respiratory diagnosis during hospitalization. All eligible patients meeting the inclusion criteria during the study period were included.

The GOLD report was published on April 1, 2023. Patients admitted before May 1, 2023 were categorized as pre-guideline, while those admitted on or after May 1, 2023 were categorized as post-guideline.

Guideline-concordant discharge prescribing was defined as the prescription of a dual LABD regimen (LABA/LAMA) at the time of discharge. This included formulation delivered through a single inhaler, including triple therapy regimens containing an inhaled corticosteroid (ICS), or separate prescriptions using multiple inhalers. Each of these configurations met the criteria for guideline-concordant discharge prescribing.

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Institutional Review Board of Henry Ford Health (No. 16265), and the requirement for informed consent was waived due to the retrospective nature of the study and the use of de-identified data to protect patient privacy.

Statistical analysis

All analyses were performed using Stata software, Version 16.1 (StataCorp, College Station, TX, USA). Continuous variables were compared using independent Student’s t-tests and expressed as means ± standard deviations. Categorical variables were expressed as percentages and analyzed using chi-square tests. Logistic regression was employed to identify predictors of discharge on dual LABD regimen. Candidate variables included age, admission service, prior inhaler use, and guideline period. Variables meeting prespecified criteria in univariate analysis were entered into multivariable models. Variables associated with discharge prescribing in univariate analyses, along with clinically relevant baseline differences between cohorts, including age and Charlson comorbidity score, were included in multivariable logistic regression models.

Missing data for variables included in multivariable analyses were minimal and were handled using complete-case analysis, with observations containing missing values excluded from analyses requiring those variables. Statistical significance was set at P<0.05. Temporal trends in dual LABD prescribing were evaluated graphically by quarter over the study period. We conducted a Breslow-Day test for homogeneity to assess whether the absolute risk differences in guideline-concordant prescribing varied significantly across pre-admission inhaler groups before and after guideline implementation. An additional regression analysis including pre- versus post-guideline period and pulmonary service admission as independent variables was performed to assess whether prescribing differences persisted after adjustment for temporal period and admission service.

An interrupted time series analysis was performed using quarterly rates of dual LABD prescribing to evaluate temporal trends before and after publication of the GOLD 2023 report. Segmented linear regression models included terms for time, post-guideline period, and change in slope following guideline publication. Newey-West standard errors with a lag of 1 quarter were used to account for autocorrelation.

Results

A total of 17,116 admissions with COPD documented in the medical record were screened. Among these, 2,537 hospitalizations met criteria for COPD exacerbation, with 2,139 occurring before publication of the GOLD 2023 report (pre-guideline period) and 398 occurring afterward (post-guideline period). The remaining admissions were excluded because they did not meet COPD exacerbation criteria, represented repeat hospitalizations, or had pneumonia identified as the primary respiratory diagnosis.

Baseline characteristics are shown in Table 1. Compared with the pre-guideline cohort, patients in the post-guideline cohort were younger and less likely to have prior pulmonary function testing. Pre-admission dual LABD use was also more common in the post-guideline period. Compared with the pre-guideline cohort, patients in the post-guideline period were less frequently admitted to subspecialty medicine services and more frequently admitted to intensive care services. Missing data for variables included in multivariable analyses were minimal, and complete-case analysis retained all 2,537 admissions included in the primary analysis.

Overall, more patients were discharged on dual LABD therapy in the post-guideline period [224 (56.3%)] compared with the pre-guideline period [813 (38.0%), P<0.001]. Pre-admission dual LABD use was modestly more common in the post-guideline cohort [141 (35.4%)] compared with the pre-guideline cohort [613 (28.7%), P=0.01]. In adjusted patient-level analysis, post-guideline admission and pulmonary service admission remained independently associated with discharge on dual LABD therapy. Among patients discharged on regimens containing both LABA and LAMA components, most received triple therapy containing LABA/LAMA/ICS rather than LABA/LAMA-only therapy [963/1,037 (92.9%) vs. 74/1,037 (7.1%)].

Temporal trends in dual LABD prescribing are shown in Figure 1. Interrupted time series analysis demonstrated a significant increase in dual LABD prescribing over time prior to publication of the GOLD 2023 report (0.91 percentage-point increase per quarter, P<0.001). Although prescribing rates remained numerically higher following guideline publication, there was no statistically significant immediate level change (P=0.07) or change in prescribing slope after publication (P=0.10).

Figure 1 Temporal trends in discharge prescribing of dual LABD therapy before and after publication of the GOLD 2023 report. Quarterly proportions of patients hospitalized with COPD exacerbation who were discharged on dual LABD therapy between December 2017 and July 2024. The dashed vertical line indicates publication of the GOLD 2023 report. COPD, chronic obstructive pulmonary disease; GOLD, Global Initiative for Chronic Obstructive Lung Disease; LABD, long-acting bronchodilator.

Dual LABD prescribing increased across most service types in the post-guideline period (Table 2). Statistically significant increases were observed in pulmonary, infectious disease, general medicine, medical intensive care unit (MICU), and subspecialty medicine services.

Discharge prescribing of dual LABD therapy differed according to pre-admission inhaler regimen. While there was increased guideline-concordant prescribing across all inhaler categories in the post-guideline period (Figure 2), the greatest differences between the pre- and post-guideline periods were observed in those admitted with no or a single LABD. In patients with no pre-admission LABD, the proportion discharged on dual LABD increased from 14.7% (127 of 1,020 patients) in the pre-guidelines group to 32.9% (51 of 155 patients) in the post-guidelines group (absolute risk difference: 18.2 percentage points, P<0.001). In patients admitted on a single LABD, the proportion discharged on a dual LABD increased from 24.7% (163 of 763 patients) to 39.2% (40 of 102 patients) (absolute risk difference: 14.5 percentage points, P=0.002). For patients already on dual LABD therapy before admission, the proportion discharged on a dual LABD increased from 85.3% (523 of 754 patients) to 94.3% (122 of 129 patients) (absolute risk difference: 9.0 percentage points, P=0.004). Statistical comparisons between these groups revealed that the increase in discharge on dual LABD therapy differed significantly by pre-admission inhaler type, with a greater effect observed in those previously not on LABD compared to those already on dual LABD therapy (P<0.05 for comparisons between no LABD vs. dual LABD and single LABD vs. dual LABD).

Figure 2 Discharge prescribing of dual LABD therapy according to pre-admission inhaler regimen before and after publication of the GOLD 2023 report. GOLD, Global Initiative for Chronic Obstructive Lung Disease; LABD, long-acting bronchodilator.

After adjustment for age and Charlson comorbidity score, significant predictors of discharge on dual LABD therapy included the post-guideline period (OR 2.43, 95% CI: 1.85–3.20, P<0.001), admission to the pulmonary service (OR 1.57, 95% CI: 1.21–2.03, P=0.001), use of a single LABD prior to admission (OR 1.84, 95% CI: 1.45–2.32, P<0.001), and use of dual LABD prior to admission (OR 35.84, 95% CI: 27.12–47.37, P<0.001) compared with no pre-admission LABD therapy (Table 3). Admission to non-pulmonary subspecialty services, age, and most Charlson comorbidity categories were not independently associated with discharge on dual LABD therapy.

Discussion

Clinical guidelines are intended to promote evidence-based care and reduce unnecessary variability in clinical practice (7). In this retrospective cohort study, discharge prescribing of dual LABD therapy increased over the study period and remained higher during the post-guideline period following publication of the GOLD 2023 report. Interrupted time series analysis demonstrated that prescribing rates were already increasing prior to publication of the GOLD 2023 report, suggesting that evolving clinical practice patterns and accumulating evidence supporting dual LABD therapy likely preceded formal incorporation into GOLD recommendations. Admission to the pulmonary service was also independently associated with discharge on dual LABD therapy.

The increase in dual LABD prescribing observed during the post-guideline period may reflect continued incorporation of updated COPD management recommendations into clinical practice. Higher rates of dual LABD prescribing among patients admitted to the pulmonary service may reflect greater familiarity with evolving COPD literature and guideline-directed management among pulmonary specialists.

Pre-admission inhaler regimen was also associated with discharge prescribing patterns. Differences between the pre- and post-guideline periods were most pronounced among patients admitted without pre-admission dual LABD therapy or with single-agent LABD therapy, while patients already receiving dual LABD therapy prior to admission demonstrated smaller differences between periods. This pattern may reflect a ceiling effect among patients already receiving dual LABD therapy before hospitalization.

Pulmonary involvement in the care of patients hospitalized with COPD has previously been associated with improved clinical outcomes. For example, Hossri and colleagues demonstrated that patients who received a pulmonary consultation during hospitalization had lower readmission rates compared to those who did not (8). In our study, admission to the pulmonary service was independently associated with discharge on dual LABD therapy. This finding may reflect differences in specialty-specific prescribing practices and familiarity with COPD management. Similar associations between specialty involvement and adherence to evidence-based management have been observed in other areas of medicine, including heart failure management under cardiology specialists and reductions in unnecessary antibiotic use through infectious disease-led antimicrobial stewardship programs (9,10). Interestingly, receipt of a pulmonary consultation without admission to the pulmonary service was not independently associated with discharge on dual LABD therapy. This finding may reflect differences in implementation of consultant recommendations by primary admitting teams, variability in timing of pulmonary consultation relative to discharge planning, or differences in continuity of medication management when pulmonary specialists are directly responsible for inpatient care.

A limitation of this study is the use of a historical comparison group, as prescribing patterns may have been influenced by secular trends independent of publication of the GOLD 2023 report. Interrupted time series analysis demonstrated that dual LABD prescribing rates were already increasing significantly prior to guideline publication, suggesting that evolving provider preferences, institutional practice patterns, and accumulating evidence supporting dual LABD therapy likely contributed to prescribing changes over time. Although prescribing rates remained significantly and numerically higher during the post-guideline period, there was no statistically significant immediate level or slope change following guideline publication. Accordingly, the observational design of this study limits the ability to determine the independent causal effect of guideline publication on prescribing practices.

As a retrospective study relying in part on ICD-10 diagnostic codes to identify COPD exacerbations, this analysis is subject to potential misclassification bias. Although clinician-documented diagnoses were used in conjunction with coding data, some patients may have been incorrectly classified or excluded. Additionally, exclusion of patients in whom pneumonia was considered the primary respiratory diagnosis may limit generalizability to patients with overlapping infectious and obstructive presentations.

Despite these limitations, prior studies have demonstrated reasonable accuracy of ICD-10 coding for identifying COPD exacerbations in hospitalized patients (11-13). Additionally, any misclassification present would likely have affected both pre- and post-guideline periods similarly, making differential bias between groups less likely.

Additionally, the post-guideline observation period was relatively short compared with the pre-guideline period and may not fully capture longer-term prescribing trends or the sustainability of prescribing changes over time. This study focused on prescribing practices and did not evaluate patient-level clinical outcomes such as readmissions or mortality. Accordingly, the observed increases in dual LABD prescribing should be interpreted as changes in process-of-care measures rather than demonstrated improvements in patient outcomes, and the clinical impact of these prescribing trends remains uncertain.

Provider-level awareness of evolving COPD recommendations and variability in prescribing behavior were also not assessed. In addition, exacerbation severity and post-discharge adherence to prescribed dual LABD therapy were not evaluated. Most patients meeting the study definition of guideline-concordant therapy received triple therapy containing LABA/LAMA/ICS rather than LABA/LAMA-only therapy, which may limit interpretation of prescribing patterns specifically related to ICS use following publication of the GOLD 2023 report. As this was a single-center study conducted at a large tertiary-care academic center, findings may not be fully generalizable to other practice settings or healthcare systems.

Conclusions

Discharge prescribing of dual LABD therapy for patients hospitalized with COPD exacerbation increased over the study period and remained higher following publication of the GOLD 2023 recommendations. Temporal trend analysis suggested that prescribing patterns were already evolving prior to formal publication of the GOLD recommendations, likely reflecting increasing incorporation of emerging evidence into clinical practice. Admission to the pulmonary service and pre-admission inhaler regimen were independently associated with discharge on dual LABD therapy. Differences between pre- and post-guideline periods were most pronounced among patients not previously receiving dual LABD therapy. Future studies should evaluate longer-term prescribing trends and determine whether observed changes in discharge prescribing are associated with improved clinical outcomes such as reduced readmissions, exacerbations, or mortality.

Acknowledgments

Portions of this work were previously presented as a poster at the CHEST Annual Meeting 2023.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1325/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1325/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1325/prf

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1325/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Institutional Review Board of Henry Ford Health (No. 16265), and the requirement for informed consent was waived due to the retrospective nature of the study and the use of de-identified data to protect patient privacy.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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