Characteristics of the main included studies.
| First author (reference) | Participants (n) | Primary efficacy outcome | Main findings |
|---|---|---|---|
| Lipson et al. [7] | 10,355 | The frequency of moderate to severe treatment-related worsening events per year. | The combination of fluticasone furoate, umeclidinium, and vilanterol demonstrated superior effectiveness in reducing the frequency of serious COPD flare-ups compared to either fluticasone furoate and vilanterol alone, or umeclidinium and vilanterol together. Furthermore, this triple therapy regimen led to fewer hospital admissions for COPD-related reasons compared to the umeclidinium-vilanterol combination. |
| Yang et al. [8] | 49,982 | The associations between ICS treatment and the risk of pneumonia in COPD patients. | ICS therapy elevates the likelihood of pneumonia development among COPD sufferers. This heightened risk is particularly noticeable with ICS formulations that include fluticasone, whereas budesonide-based ICS appear to have a lesser impact. |
| Calverley et al. [9] | 6,112 | Mortality rates across all causes were evaluated, along with the incidence of flare-ups, overall health conditions, and lung function measurements, when comparing the combined treatment to a placebo. | Although the combination therapy group showed a decrease in deaths across all causes, this decline was not statistically significant enough when contrasted with the placebo group, failing to reach the established threshold. During the 3 years of the study, treatment with the combination regimen resulted in significantly fewer exacerbations and improved health status and lung function, as compared with placebo. |
| Beech et al. [10] | 75 | This research explores the distribution of COPD subtypes, determined by analyzing sputum samples for both inflammatory cell types and the presence of specific bacteria using qPCR technology. A key area of interest is understanding the frequency of the COPD subtype characterized by high levels of H. influenzae bacteria and neutrophils, as well as investigating if the eosinophilic subtype exists separately from H. influenzae colonization. | The rate of H. influenzae colonization was roughly 25%, compared to low colonization for other bacterial species. H. influenzae colonization is associated with sputum neutrophilia, while eosinophilic inflammation and H. influenzae colonization rarely coexist. |
| Lea et al. [11] | 20 | The objective is to determine the responses of COPD macrophages to H. influenzae, M. catarrhalis, and S. pneumoniae, with a focus on the release of chemotactic mediators and the expression of proteins that regulate apoptosis. | Differential cytokine secretion by macrophages in response to common bacterial species associated with COPD may elucidate the pronounced neutrophilic airway inflammation linked to H. influenzae, while not accounting for that associated with S. pneumoniae. Additionally, the regulation of macrophage apoptosis may serve as a significant mechanism contributing to the ongoing colonization of H. influenzae in individuals with COPD. |
| Yang et al. [12] | 23,139 | To assess the advantages and disadvantages of ICS administered alone compared to a placebo in individuals with stable COPD, focusing on both objective and subjective outcomes. | The use of inhaled ICS as a standalone treatment for COPD is likely to lead to a decrease in the rates of clinically significant exacerbations. It may also contribute to a reduction in the decline of FEV1, although the clinical significance of this effect remains uncertain. Additionally, ICS is likely to produce a modest enhancement in health-related quality of life, though this improvement does not reach the threshold for a minimally clinically important difference. |
| Janson et al. [13] | 9,893 | Yearly pneumonia event rates, admission to hospital related to pneumonia, and mortality. | There is an intraclass difference between inhaled corticosteroid/long-acting β2-agonist regarding the risk of pneumonia and pneumonia-related mortality in the treatment of patients with COPD. |
| Morjaria et al. [14] | 5,992 | The objective is to assess the incidence and frequency of pneumonia episodes and exacerbations of COPD among patients who are enrolled in the study, categorized by their use of no ICS, fluticasone propionate (FP), and other ICS formulations. | The use of ICS was linked to a rise in the rates of respiratory adverse events; however, it remains unclear whether this was a result of more severe illness at the time of entry. Subgroup analysis indicated that the increased morbidity in the ICS group was primarily associated with participants receiving FP at randomization. |
| Rabe et al. [15] | 8,509 | The estimated average number of moderate or severe COPD exacerbations experienced by each patient per year, based on on-treatment data from the modified intention-to-treat analysis. | Patients receiving triple therapy with twice-daily budesonide (at 160 μg or 320 μg), glycopyrrolate, and formoterol experienced a reduced rate of moderate or severe COPD exacerbations compared to those on glycopyrrolate-formoterol or budesonide-formoterol. |
| Pu et al. [16] | 1,375 | This study aims to conduct a meta-analysis and an indirect treatment comparison to evaluate the effectiveness and safety of various systemic corticosteroid (SCS) dosages in individuals experiencing COPD exacerbations. | For patients experiencing COPD exacerbations, a low-dose SCS regimen (starting at or below 40 mg prednisone equivalents per day) proved both adequate and safer compared to higher doses (starting above 40 mg PE/day). Furthermore, the lower dose was no less effective in improving lung function (FEV1) and preventing treatment failure. |
| Papi et al. [17] | 1,532 | A comparison was conducted between a single inhaler delivering beclometasone dipropionate, formoterol fumarate, and glycopyrronium (BDP/FF/G) and another single inhaler containing indacaterol and glycopyrronium (IND/GLY), assessing the frequency of moderate-to-severe COPD exacerbations over 52 weeks. | When compared to IND/GLY, extrafine BDP/FF/G offered a significant reduction in the rate of moderate-to-severe exacerbations for patients with symptomatic COPD, severe or very severe airflow limitation, and a history of exacerbations despite maintenance therapy, without an associated increase in pneumonia risk. |
| Patel et al. [6] | 5,102 | To review the latest scientific evidence of adverse systemic effects associated with ICS use in asthma (excluding adrenal insufficiency, which was recently reviewed elsewhere). | There are limited studies that suggest ICS use increases the risk of respiratory infections, cataracts, and loss of BMD in people with asthma; there were several biases and limitations associated with the studies. This review emphasizes the urgent need for further, carefully designed longitudinal cohort studies to better understand the risk of systemic adverse effects. These studies must be detailed enough to determine the specific ICS drugs, patient characteristics, and dosages that contribute most significantly to each adverse outcome. |
| Ekbom et al. [18] | 7,340 | The study aims to identify factors that increase the likelihood of pneumonia-related hospital admissions within the general population, with a particular focus on asthma and the role of inhaled ICS use in individuals with this condition. | There is a notable disparity in pneumonia risk across different ICS drugs, and FP stands out as a contributor to increased risk. |
ICS: inhaled corticosteroids; COPD: chronic obstructive pulmonary disease; PE: pulmonary embolism; BMD: bone mineral density; PE/day: prednisone equivalent/day; H. influenzae: Haemophilus influenzae.