Advances in inhaled corticosteroids for the treatment of chronic obstructive pulmonary disease: what is their value today?

Cazzola, Mario; Ora, Josuel; Calzetta, Luigino; Rogliani, Paola; Matera, Maria Gabriella

doi:10.1080/14656566.2022.2076592

Cited by 5 publications

(8 citation statements)

References 102 publications

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“… 6 ICSs are indicated in COPD patients when there is an overlap with asthma or frequent exacerbations associated with high blood eosinophil counts (BEC). 7 Furthermore, CSs may play a cardioprotective role, reduce the risk of lung cancer, and possibly improve survival. 7 However, ICSs have little to no impact on the underlying inflammation in most COPD patients, 8 particularly in those who continue to smoke.…”

Section: The Unmet Need For New Anti-inflammatory Therapies For Copdmentioning

confidence: 99%

Novel Anti-Inflammatory Approaches to COPD

Cazzola¹,

Hanania²,

Page³

et al. 2023

COPD

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Airway inflammation, driven by different types of inflammatory cells and mediators, plays a fundamental role in COPD and its progression. Neutrophils, eosinophils, macrophages, and CD4 + and CD8 + T lymphocytes are key players in this process, although the extent of their participation varies according to the patient's endotype. Anti-inflammatory medications may modify the natural history and progression of COPD. However, since airway inflammation in COPD is relatively resistant to corticosteroid therapy, innovative pharmacological anti-inflammatory approaches are required. The heterogeneity of inflammatory cells and mediators in annethe different COPD endo-phenotypes requires the development of specific pharmacologic agents. Indeed, over the past two decades, several mechanisms that influence the influx and/or activity of inflammatory cells in the airways and lung parenchyma have been identified. Several of these molecules have been tested in vitro models and in vivo in laboratory animals, but only a few have been studied in humans. Although early studies have not been encouraging, useful information emerged suggesting that some of these agents may need to be further tested in specific subgroups of patients, hopefully leading to a more personalized approach to treating COPD.

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Section: The Unmet Need For New Anti-inflammatory Therapies For Copdmentioning

confidence: 99%

Novel Anti-Inflammatory Approaches to COPD

Cazzola¹,

Hanania²,

Page³

et al. 2023

COPD

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“…Although these drugs are known to effectively suppress airway inflammation in subjects with asthma, their effect on the inflammation in COPD remains unclear [ 27 ]. The value of ICS in the treatment of COPD and understanding of which patients may benefit from ICS therapy is becoming clearer, but a consensus is still lacking [ 28 ]. The current GOLD report recommends the use of ICS in patients with severe impairment and at high risk of exacerbation [ 29 ].…”

Section: Inflammation and Oxidative Stressmentioning

confidence: 99%

“…It has been suggested that the heterogeneity of patients with COPD necessitates different treatment strategies for different subgroups of patients [ 31 ]. In the past, ICS have been considered more effective in frequent exacerbators or those with an overlap between COPD and asthma [ 28 ]. In the recent 2023 GOLD report [ 29 ], emphasis is given to the use of ICS combined with a long-acting beta-agonist (LABA) and a long-acting muscarinic-antagonist (LAMA) in individuals with a blood eosinophil count ≥ 300 cells/µL (Fig.…”

Section: Inflammation and Oxidative Stressmentioning

confidence: 99%

Use of thiols and implications for the use of inhaled corticosteroids in the presence of oxidative stress in COPD

Cazzola¹,

Page²,

Wedzicha³

et al. 2023

Respir Res

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Background Oxidative stress and persistent airway inflammation are thought to be important contributors to the development of chronic obstructive pulmonary disease (COPD). This review summarizes the evidence for targeting oxidative stress and inflammation in patients with COPD with mucolytic/antioxidant thiols and inhaled corticosteroids (ICS), either alone or in combination. Main body Oxidative stress is increased in COPD, particularly during acute exacerbations. It can be triggered by oxidant air pollutants and cigarette smoke and/or by endogenous reactive oxygen species (ROS) released from mitochondria and activated inflammatory, immune and epithelial cells in the airways, together with a reduction in endogenous antioxidants such as glutathione (GSH). Oxidative stress also drives chronic inflammation and disease progression in the airways by activating intracellular signalling pathways and the release of further inflammatory mediators. ICS are anti-inflammatory agents currently recommended for use with long-acting bronchodilators to prevent exacerbations in patients with moderate-to-severe COPD, especially those with eosinophilic airway inflammation. However, corticosteroids can also increase oxidative stress, which may in turn reduce corticosteroid sensitivity in patients by several mechanisms. Thiol-based agents such as erdosteine, N-acetyl L-cysteine (NAC) and S-carboxymethylcysteine (S-CMC) are mucolytic agents that also act as antioxidants. These agents may reduce oxidative stress directly through the free sulfhydryl groups, serving as a source of reducing equivalents and indirectly though intracellular GSH replenishment. Few studies have compared the effects of corticosteroids and thiol agents on oxidative stress, but there is some evidence for greater antioxidant effects when they are administered together. The current Global Initiative for Chronic Obstructive Lung Disease (GOLD) report supports treatment with antioxidants (erdosteine, NAC, S-CMC) in addition to standard-of-care therapy as they have been demonstrated to reduce COPD exacerbations. However, such studies have demonstrated that NAC and S-CMC reduced the exacerbation risk only in patients not treated with ICS, whereas erdosteine reduced COPD exacerbations irrespective of concomitant ICS use suggesting that erdosteine has additional pharmacological actions to ICS. Conclusions Further clinical trials of antioxidant agents with and without ICS are needed to better understand the place of thiol-based drugs in the treatment of patients with COPD.

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“…Consequently, ICSs are discouraged or should be limited to the lowest possible dose while optimizing bronchodilation. Nonetheless, ICSs are indicated in COPD patients when there is an overlap with asthma or frequent exacerbations with high blood eosinophil count values [ 118 ]. However, the blood eosinophil count above which using an ICS can be beneficial has not yet been established [ 118 ].…”

Section: What Do the Guidelines Say About Using Inhaled Corticosteroi...mentioning

confidence: 99%

“…Nonetheless, ICSs are indicated in COPD patients when there is an overlap with asthma or frequent exacerbations with high blood eosinophil count values [ 118 ]. However, the blood eosinophil count above which using an ICS can be beneficial has not yet been established [ 118 ]. Furthermore, the impact of eosinophilia on the effect of ICSs in COPD with bronchiectasis when a chronic bronchial infection is present is still unknown [ 119 ].…”

Section: What Do the Guidelines Say About Using Inhaled Corticosteroi...mentioning

confidence: 99%

Inhaled Corticosteroids in Adults with Non-cystic Fibrosis Bronchiectasis: From Bench to Bedside. A Narrative Review

Martínez‐García

Oscullo

García-Ortega

et al. 2022

Drugs

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Due to their potent anti-inflammatory capacity (particularly in predominantly eosinophilic inflammation) and immunosuppressive properties, inhaled corticosteroids (ICSs) are widely used in asthmatic patients and also in individuals with chronic obstructive pulmonary disease (COPD) who suffer multiple exacerbations or have peripheral eosinophilia. However, there is little evidence for their use in non-cystic fibrosis bronchiectasis (hereafter, bronchiectasis). According to data extracted from large databases of bronchiectasis in adults, ICSs are used in more than 50% of patients without any scientific evidence to justify their efficacy and contrary to the recommendations of international guidelines on bronchiectasis that generally advise against their use. Indeed, bronchiectasis is a disease with predominantly neutrophilic inflammation and a high likelihood of chronic bacterial bronchial infection. Furthermore, it is known that due to their immunosuppressive properties, ICSs can induce an increase in bacterial infections. This manuscript aims to review the basic properties of ICSs, how they impact bronchiectasis in adults, the current position of international guidelines on this treatment, and the current indications and future challenges related to ICS use in bronchiectasis.

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Advances in inhaled corticosteroids for the treatment of chronic obstructive pulmonary disease: what is their value today?

Cited by 5 publications

References 102 publications

Novel Anti-Inflammatory Approaches to COPD

Novel Anti-Inflammatory Approaches to COPD

Use of thiols and implications for the use of inhaled corticosteroids in the presence of oxidative stress in COPD

Inhaled Corticosteroids in Adults with Non-cystic Fibrosis Bronchiectasis: From Bench to Bedside. A Narrative Review

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