Is there an indication for using concomitant Inhaled and systemic corticosteroids routinely?

Comment by InpharmD Researcher

Current guidelines (GOLD 2025 and GINA 2025) recommend systemic corticosteroids for acute exacerbations but do not address their routine concomitant use with inhaled corticosteroids (ICS). Evidence from randomized controlled trials and systematic reviews in acute asthma demonstrates insufficient or inconsistent clinical benefit with the addition of ICS to systemic corticosteroids, although one meta-analysis reported reduced hospital admissions with high-dose ICS plus systemic corticosteroids despite inconsistent secondary outcomes. Similarly, retrospective data in chronic obstructive pulmonary disease (COPD) exacerbations showed no significant clinical differences between combination therapy and systemic corticosteroid monotherapy, while in advanced lung cancer patients receiving immunotherapy, ICS use did not compromise outcomes but systemic corticosteroids were associated with worse survival. Overall, current evidence does not support the routine concomitant use of inhaled and systemic corticosteroids.

Background

Both the 2025 GOLD and GINA guidelines for COPD and asthma, respectively, do not address concomitant use of inhaled corticosteroids (ICS) and systemic corticosteroids. While in the GOLD guidelines, exacerbations of COPD may require treatment using systemic corticosteroids that could overlap with current ICS, this is an acute phase of treatment and not meant for routine exposure. GOLD does not recommend systemic corticosteroids for more than 5 days, which includes hospital exposure. The same principle applies within the GINA guidelines which recommends systemic corticosteroids primarily for moderate or severe exacerbations, especially if patients fail to respond to ICS-containing medications. However, GINA does provide slightly more context, suggesting systemic corticosteroids can be continued for 5-7 days in adults, or 3-5 days in children post-exacerbation. During this time, maintenance ICS-containing medication dose may be increased in the next 2-4 weeks, meaning that concomitant exposure is possible in this timeframe. [1], [2]

Systemic corticosteroids remain the cornerstone of treatment for acute asthma exacerbations, and the routine addition of ICS has not been shown to provide consistent additional benefit when systemic corticosteroids are already administered. Evidence from randomized controlled trials summarized in two Cochrane systematic reviews demonstrates that the concomitant use of ICS with systemic corticosteroids did not result in statistically significant reductions in relapse rates, hospital admissions, symptom scores, quality of life, or adverse events compared with systemic corticosteroids alone in patients treated for acute asthma and discharged from the emergency department (ED). Similarly, when ICS were administered early in the ED setting alongside systemic corticosteroids, subgroup analyses showed conflicting evidence regarding reductions in hospital admissions, and there was insufficient evidence of clinically important improvements in pulmonary function or clinical outcomes attributable to concomitant therapy. Although ICS therapy reduced hospital admissions when compared with placebo in patients not receiving systemic corticosteroids, and modest improvements in pulmonary function were observed in some analyses, these benefits were not consistently demonstrated when ICS were used in addition to systemic corticosteroids. Both systematic reviews concluded that there is insufficient evidence to support the routine concomitant use of inhaled and systemic corticosteroids in acute asthma management, and further research is needed to clarify their role when used together. [3], [4]

A 2020 meta-analysis evaluated the efficacy of ICS in the treatment of acute asthma exacerbations in ED settings, including their use in addition to systemic corticosteroids (SCS). The analysis included 25 randomized controlled trials involving 2,733 participants and compared ICS plus SCS versus SCS alone as the primary comparison. The addition of ICS to SCS was associated with a statistically significant reduction in hospital admission rates compared with SCS alone, with a fixed-effects odds ratio (OR) of 0.73 (95% confidence interval [CI] 0.57 to 0.94), based on seven studies involving 1,433 participants. Lung function outcomes were inconsistently reported and did not consistently demonstrate statistically significant differences; however, moderate evidence indicated improvements in clinical scores and vital signs with the addition of ICS to SCS. Adverse events were infrequently reported and were primarily limited to mild symptoms such as nausea and vomiting. The authors concluded that there is moderate evidence supporting the efficacy of high-dose ICS administered in addition to SCS in reducing hospital admission rates in patients presenting with moderate-to-severe acute asthma exacerbations in the ED, although heterogeneity among studies and limitations in reported outcomes were noted, and further research is needed to define the optimal role of ICS in both ED and outpatient settings. [5]

References: [1] 2025 GOLD Report. Global initiative for chronic obstructive lung disease. Accessed February 25, 2026. https://goldcopd.org/2025-gold-report/
[2] Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2025 update. Accessed February 25, 2026. https://ginasthma.org
[3] Edmonds ML, Milan SJ, Camargo CA Jr, Pollack CV, Rowe BH. Early use of inhaled corticosteroids in the emergency department treatment of acute asthma. Cochrane Database Syst Rev. 2012;12(12):CD002308. Published 2012 Dec 12. doi:10.1002/14651858.CD002308.pub2
[4] Edmonds ML, Milan SJ, Brenner BE, Camargo CA Jr, Rowe BH. Inhaled steroids for acute asthma following emergency department discharge. Cochrane Database Syst Rev. 2012;12(12):CD002316. Published 2012 Dec 12. doi:10.1002/14651858.CD002316.pub2
[5] Kearns N, Maijers I, Harper J, Beasley R, Weatherall M. Inhaled Corticosteroids in Acute Asthma: A Systemic Review and Meta-Analysis. J Allergy Clin Immunol Pract. 2020;8(2):605-617.e6. doi:10.1016/j.jaip.2019.08.051
Literature Review

A search of the published medical literature revealed 2 studies investigating the researchable question:

Is there an indication for using concomitant Inhaled and systemic corticosteroids routinely?

Level of evidence

C - Multiple studies with limitations or conflicting results  Read more→



Please see Tables 1-2 for your response.


Impact of concurrent systemic and inhaled corticosteroid use on clinical outcomes in advanced lung cancer patients receiving immune checkpoint inhibitors
Design

Retrospective cohort study

N= 368

Objective To examine the association between concurrent systemic corticosteroids (SCS) and inhaled corticosteroids (ICS) on clinical outcomes in advanced lung cancer patients treated with immune checkpoint inhibitors (ICIs)
Study Groups

SCS users (n= 122)

ICS users (n= 51)

No steroid treatment (n= 195)

Inclusion Criteria Adults (age ≥18 years) with advanced lung cancer who initiated ICIs between September 1 2016 and September 30 2023 at West China Hospital of Sichuan University
Exclusion Criteria Received less than two cycles of PD-(L)1 immunotherapy, or received other concomitant chemotherapy or targeted therapy. Enrolled in clinical trials potentially receiving placebos
Methods

Time-dependent Cox regression models were applied to account for immortal-time bias. Exposure included concurrent SCS, ICS versus no steroid treatment. Clinical outcomes including overall survival (OS), progression-free survival (PFS), and tumor response were assessed.

Duration September 1 2016 to September 30 2023
Outcome Measures

Primary: Overall survival (OS), Progression-free survival (PFS)

Secondary: Tumor response, Disease control rate (DCR), Objective response rate (ORR)

Baseline Characteristics   Overall (n= 368) No Steroids (n= 195) Concurrent SCS (n= 122) Concurrent ICS (n= 51) p-Value
Age, years 66.0 (58.0, 71.1) 65.0 (57.0, 70.0) 64.3 (57.0, 71.0) 70.2 (64.7, 75.0) < 0.001
Sex - Male 320 (87.0%) 164 (84.1%) 107 (87.7%) 49 (96.1%) 0.074
BMI, kg/m2 22.7 (20.5, 25.0) 22.6 (20.5, 25.0) 22.7 (20.3, 24.5) 23.0 (22.0, 25.0) 0.174
Smoking status - Ever 239 (64.9%) 122 (62.6%) 81 (66.4%) 36 (70.6%) 0.519
ECOG PS - 0–1 330 (89.7%) 183 (93.8%) 105 (86.1%) 42 (82.4%) 0.016
Histology - Adenocarcinoma 178 (48.4%) 93 (47.7%) 66 (54.1%) 19 (37.3%) 0.007
PD-L1 TPS - Positive (≥ 1%) 316 (85.9%) 163 (83.6%) 104 (85.2%) 49 (96.1%) 0.072
Brain metastasis - Yes 62 (16.8%) 36 (18.5%) 24 (19.7%) 2 (3.9%) 0.028
COPD - Yes 83 (22.6%) 18 (9.2%) 20 (16.4%) 45 (88.2%) < 0.001
Results   SCS (n= 122) ICS (n= 51) No Steroids (n= 195) p-Value
Progression-free survival (PFS), months 11.0 25.0 17.0 0.002
Overall survival (OS), months 21.0 42.0 35.0 0.002
Objective response rate (ORR) 9.0% 21.6% 19.0% 0.032
Disease control rate (DCR) 85.2% 96.1% 93.3% 0.020
Adverse Events Not specifically reported in the study
Study Author Conclusions

Concurrent systemic corticosteroid use may adversely affect the clinical outcomes of advanced lung cancer patients receiving immunotherapy, whereas inhaled corticosteroid use did not appear to compromise ICI efficacy. These findings highlight the critical need for cautious consideration when combining ICIs with systemic corticosteroids and emphasize the importance of treating both cancer and lung comorbidity simultaneously.

Critique

The study provides valuable insights into the impact of corticosteroid use on ICI efficacy in advanced lung cancer patients, with a robust methodology using time-dependent Cox regression to account for immortal-time bias. However, as a retrospective single-center study, it may be subject to selection bias and unmeasured confounding. The exclusion of patients receiving fewer than two cycles of PD-(L)1 inhibitors or those on combination therapies limits the generalizability of the findings. Additionally, the lack of detailed data on corticosteroid dosing and duration, as well as the inclusion of both NSCLC and SCLC patients, may introduce variability in the results.

 

References:
[1] [1] Liu Y, Zhang J, Yang L, et al. Impact of concurrent systemic and inhaled corticosteroid use on clinical outcomes in advanced lung cancer patients receiving immune checkpoint inhibitors. Respir Res. 2026;27(1):59. Published 2026 Jan 19. doi:10.1186/s12931-025-03482-5
Systemic Steroid and Nebulized Budesonide Combination Therapy Versus Systemic Steroid Monotherapy in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease in a Community Hospital: A Retrospective Cohort Study
Design

Single-center retrospective cohort study

N= 128

Objective To evaluate clinical outcomes and costs of inhaled corticosteroid (ICS) and systemic corticosteroid combination therapy versus systemic corticosteroid monotherapy for treatment of acute exacerbations of chronic obstructive pulmonary disease (AECOPD)
Study Groups

Combination therapy (n= 50)

Monotherapy (n= 78)

Inclusion Criteria Hospitalized patients aged 41 to 85 years old who received ≥40 mg/day of systemic prednisone equivalents between April 3, 2017 to July 31, 2017 and April 3, 2018 to July 31, 2018 with a primary discharge diagnosis of AECOPD
Exclusion Criteria Documented history of lobectomy, lung cancer, primary pulmonary hypertension, sarcoidosis, lung transplant, interstitial lung disease, lupus, idiopathic pulmonary fibrosis and/or intubated in the field prior to admit
Methods Patients were divided into two cohorts: those who received >2 doses of ICS (combination therapy) and those who received ≤2 doses of ICS (monotherapy) while on systemic corticosteroid therapy. Data collection included patient demographics, COPD medications, BAP-65 criteria, and COPD related pharmacotherapy during hospitalization. Outcomes measured included progression of respiratory support, increase in daily dose of systemic corticosteroids, hospital length of stay (LOS), COPD 30-day readmissions, in-hospital mortality, and nebulized budesonide costs.
Duration April 3, 2017 to July 31, 2017 and April 3, 2018 to July 31, 2018
Outcome Measures

Primary: Progression of respiratory support or ≥20% increase in daily dose of systemic corticosteroids

Secondary: Hospital length of stay (LOS), COPD 30-day readmissions, in-hospital mortality, nebulized budesonide costs

Baseline Characteristics   Combination therapy (n= 50) Monotherapy (n= 78) p-Value
Mean age—years (IQR) 64.74 (9.3) 64.56 (9.2) 0.91
Male sex (%) 22 (44) 34 (44) 0.96
Tobaccoism (%) 41 (82) 67 (86) 0.55
Mean weight—kg (IQR) 87.05 (32.1) 88.81 (34.5) 0.77
BMI <20 (%) 5 (10) 10 (13) 0.78
BMI 20-29 (%) 27 (54) 33 (42) 0.21
BMI ≥30 (%) 18 (36) 35 (45) 0.36
Home SABA (%) 38 (76) 46 (59) 0.04
Home ICS (%) 31 (62) 35 (45) 0.05
Results   Combination therapy (n= 50) Monotherapy (n= 78) p-Value
Increase in systemic corticosteroids ≥20% per day (%) 2 (4) 4 (5) 0.76
Progression to NIV or MV (%) 6 (12) 6 (8) 0.53
Increased level of care (%) 1 (2) 3 (4) 0.65
In-hospital mortality (%) 2 (4) 1 (1) 0.36
30-d COPD readmission (%) 8 (16) 7 (9) 0.22
Mean hospital LOS—days (IQR) 4.8 (2.4) 3.9 (2.2) 0.04
Adverse Events No specific adverse events reported
Study Author Conclusions Outcomes showed no clinical difference between combination therapy and monotherapy. This study suggests monotherapy may be more cost-effective while providing similar outcomes for the treatment of hospitalized patients with AECOPD.
Critique The study provides valuable insights into the cost-effectiveness of monotherapy versus combination therapy in AECOPD treatment. However, the retrospective design and single-center setting may limit the generalizability of the findings. Additionally, the study was not powered to detect small differences in clinical outcomes, which could impact the interpretation of non-significant results.

 

References:
[1] [1] Nguyen D, Larson T, Leinbach H, Guthrie E. Systemic Steroid and Nebulized Budesonide Combination Therapy Versus Systemic Steroid Monotherapy in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease in a Community Hospital: A Retrospective Cohort Study. Hosp Pharm. 2021;56(6):786-791. doi:10.1177/0018578720965417