Use of inhaled corticosteroids and risk of acquiring<i>Pseudomonas aeruginosa</i>in patients with chronic obstructive pulmonary disease

Eklöf, Josefin; Ingebrigtsen, Truls Sylvan; Sørensen, Rikke; Saeed, Mohammad; Alispahic, Imane Achir; Sivapalan, Pradeesh; Boel, Jonas Bredtoft; Bangsborg, Jette; Østergaard, Christian Richter; Dessau, Ram Benny; Jensen, Ulrich Stab; Hansen, Ejvind Frausing; Lapperre, Thérèse S.; Meteran, Howraman; Wilcke, Torgny; Seersholm, Niels; Jensen, Jens‐Ulrik Stæhr

doi:10.1136/thoraxjnl-2021-217160

Cited by 30 publications

(19 citation statements)

References 34 publications

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“…Therefore, the long-term treatment of COPD patients with ICS might have blunted the normal response that is orchestrated by alveolar macrophages after PA infection, both in terms of TLR2 expression and effective cytokine production, impairing the management of the infectious process. This observation supports the finding in the clinical studies of Eklöf et al [ 15 ] and Shafiek et al [ 5 ], who found that high doses of ICS could be a risk factor for PA in severe COPD patients.…”

Section: Discussionsupporting

confidence: 91%

Effects of Inhaled Corticosteroids on the Innate Immunological Response to Pseudomonas aeruginosa Infection in Patients with COPD

Cerón-Pisa

Shafiek

Martín-Medina

et al. 2022

IJMS

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Inhaled corticosteroids (ICS) use is associated with an increased risk of Pseudomonas aeruginosa (PA) infection in patients with COPD. We aimed to evaluate the effects of ICS on alveolar macrophages in response to PA in COPD patients with and without baseline ICS treatment (COPD and COPD + ICS, respectively) as well as smoker and nonsmoker controls. To do so, cells were infected with PA and cotreated with budesonide (BUD) or fluticasone propionate (FLU). The analysis of NF-κB and c-jun activity revealed a significant increase in both factors in response to PA cotreated with BUD/FLU in smokers but not in COPD or COPD + ICS patients when compared with PA infection alone. The expression of Toll-like receptor 2 (TLR2) and the transcription factor c-jun were induced upon PA infection in nonsmokers only. Moreover, in the smoker and COPD groups, there was a significant increase in TLR2 and a decrease in c-jun expression when treated with BUD/FLU after PA infection, which were not observed in COPD + ICS patients. Therefore, the chronic use of ICS seemingly makes the macrophages tolerant to BUD/FLU stimulation compared with those from patients not treated with ICS, promoting an impaired recognition of PA and activity of alveolar macrophages in terms of altered expression of TLR2 and cytokine production, which could explain the increased risk of PA infection in COPD patients under ICS treatment.

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Section: Discussionsupporting

confidence: 91%

Effects of Inhaled Corticosteroids on the Innate Immunological Response to Pseudomonas aeruginosa Infection in Patients with COPD

Cerón-Pisa

Shafiek

Martín-Medina

et al. 2022

IJMS

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“…Interestingly, in line with our data, a recent study by Eklöf et al found that ICS was a risk factor for acquiring PsA infection as a dose-dependent risk compared with those not using ICS in severe COPD Danish cohort. 38…”

Section: Open Accessmentioning

confidence: 99%

Inhaled corticosteroid dose is associated withPseudomonas aeruginosainfection in severe COPD

et al. 2021

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IntroductionPatients with chronic obstructive pulmonary disease (COPD) with frequent exacerbations (ExCOPD) are commonly treated with inhaled corticosteroids (ICS) and are at risk of infections caused by potential pathogenic bacteria (PPB) including Pseudomonas aeruginosa (PsA).ObjectivesTo investigate the association between the use of ICS and PsA infection among ExCOPD.MethodsCase–control study with longitudinal follow-up that recruited ExCOPD after a hospitalisation due to exacerbation between 2012 and 2020. Patients with isolation of PsA (COPD-PsA) in sputum either during admission or follow-up were compared with those with other or no PPB. Clinical, functional characteristics, DDD, use of ICS and survival were evaluated. Cox regression analysis was performed to evaluate the risk factors associated to PsA infection and mortality.Results358 patients (78% male, mean age 73±9 years) were enrolled and followed up for a median of 4 years (IQR=3–8). 173 patients (48.3%) had at least a positive culture for PsA. COPD-PsA had more frequent exacerbations, more severe airflow limitation and higher mortality (69.4% vs 46.5%, p<0.001). There were no differences in the use of ICS between groups but the dose of ICS was significantly higher among COPD-PsA (median of 500 µg fluticasone propionate equivalents (IQR=250–1000) vs 400 µg (IQR=200–1000), p=0.007). Blood eosinophil count (BEC) was not different between ICS users and non-users. In multivariate analysis, the dose of ICS was an independent risk factor for PsA infection and mortality but not ICS use.ConclusionsICS dose, but not its use, could be a risk factor for PsA infection in patients with severe COPD regardless of BEC.

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“…In addition to the increase in local adverse effects observed in the aforementioned clinical studies, the use of ICSs was generally associated with an increased likelihood of acquiring an infection with P. aeruginosa or non-tuberculous mycobacteria and developing pneumonia, at least in certain subgroups of COPD patients, especially those with lower eosinophil counts [ 102 – 104 ].…”

Section: Literature Review On the Use Of Icss In Bronchiectasis In Ra...mentioning

confidence: 99%

“…In most of these overlapping patients, a bronchial infection with PPMs, including P. aeruginosa , is also present and is sometimes chronic. Studies show that ICSs in COPD patients increase the risk of pneumonia, atypical mycobacteriosis, and bronchial infection with P. aeruginosa [ 102 – 104 ]. ICS users had suppressed IFN expression with increased exacerbation severity through greater viral loads and mucus hypersecretion.…”

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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Use of inhaled corticosteroids and risk of acquiringPseudomonas aeruginosain patients with chronic obstructive pulmonary disease

Cited by 30 publications

References 34 publications

Effects of Inhaled Corticosteroids on the Innate Immunological Response to Pseudomonas aeruginosa Infection in Patients with COPD

Effects of Inhaled Corticosteroids on the Innate Immunological Response to Pseudomonas aeruginosa Infection in Patients with COPD

Inhaled corticosteroid dose is associated withPseudomonas aeruginosainfection in severe COPD

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

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