Scientific rationale for the possible inhaled corticosteroid intraclass difference in the risk of pneumonia in COPD

Janson, Christer; Stratelis, Georgios; Miller‐Larsson, Anna; Harrison, Tim; Larsson, Kjell

doi:10.2147/copd.s143656

Cited by 60 publications

(57 citation statements)

References 60 publications

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“…Differences in outcome between ICSs and placebo may be due to uneven distribution of baseline characteristics because patients with more severe disease received more intensive treatment; however, patient subgroups based on the ICS they received were well matched, such that baseline characteristics cannot explain differences between fluticasone and other ICSs 74. Fluticasone differs structurally from beclomethasone and budesonide because it has a fluorine moiety, which leads to distribution in the lipid membranes and slower clearance from lungs and other tissue, which may impact lung immunity and inflammatory responses 74,76. This study also suggested that the use of LAMA therapy may ameliorate some of the respiratory adverse effects of ICSs, supporting their use in combination 74.…”

Section: Effect Of Icss On Pneumonia Risk In Patients With Copdmentioning

confidence: 99%

Inhaled corticosteroids for chronic obstructive pulmonary disease: what is their role in therapy?

Tashkin¹,

Strange²

2018

COPD

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Inhaled corticosteroids (ICSs) are a mainstay of COPD treatment for patients with a history of exacerbations. Initial studies evaluating their use as monotherapy failed to show an effect on rate of pulmonary function decline in COPD, despite improvements in symptoms and reductions in exacerbations. Subsequently, ICS use in combination with long-acting β2-agonists (LABAs) was shown to provide improved reductions in exacerbations, lung function, and health status. ICS-LABA combination therapy is currently recommended for patients with a history of exacerbations despite treatment with long-acting bronchodilators alone. The presence of eosinophilic bronchial inflammation, detected by high blood eosinophil levels or a history of asthma or asthma–COPD overlap, may define a population of patients in whom ICSs may be of particular benefit. Prospective clinical studies to determine an appropriate threshold of eosinophil levels for predicting the beneficial effects of ICSs are needed. Further study is also required in COPD patients who continue to smoke to assess the impact of cell- and tissue-specific changes on ICS responsiveness. The safety profile of ICSs in COPD patients is confounded by comorbidities, age, and prior use of systemic corticosteroids. The risk of pneumonia in patients with COPD is increased, particularly with more advanced age and worse disease severity. ICS-containing therapy also has been shown to increase pneumonia risk; however, differences in study design and the definition of pneumonia events have led to substantial variability in risk estimates, and some data indicate that pneumonia risk may differ by the specific ICS used. In summary, treatment with ICSs has a role in dual and triple therapy for COPD to reduce exacerbations and improve symptoms. Careful assessment of COPD phenotypes related to risk factors, triggers, and comorbidities may assist in individualizing treatment while maximizing the benefit-to-risk ratio of ICS-containing COPD treatment.

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Section: Effect Of Icss On Pneumonia Risk In Patients With Copdmentioning

confidence: 99%

Inhaled corticosteroids for chronic obstructive pulmonary disease: what is their role in therapy?

Tashkin¹,

Strange²

2018

COPD

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“…In some of these studies, there was uncertainty over the diagnosis of pneumonia because there was no radiologic confirmation, [27][28][29] but some others confirmed that ICS especially fluticasone was related with higher radiologically proven pneumonia risk in COPD patients. 30 In our study, the diagnosis of pneumonia depends on radiographic confirmation based on current pneumonia guidelines. 2 The study was not designed to test the relationship of ICS use and pneumonia risk but to test whether the ICS use had an impact on the clinical, radiologic and laboratory characteristics of CAP.…”

Section: Discussionmentioning

confidence: 97%

“…In the previous studies, the relationship between ICS use in patients with COPD and pneumonia was overwhelmingly researched. In some of these studies, there was uncertainty over the diagnosis of pneumonia because there was no radiologic confirmation, but some others confirmed that ICS especially fluticasone was related with higher radiologically proven pneumonia risk in COPD patients …”

Section: Discussionmentioning

confidence: 99%

The effect of inhaled corticosteroids in the outcomes of community‐acquired pneumonia: ICCAP study (TURKCAP Database)

Baha

Köktürk

Bahçecioğlu

et al. 2020

Clinical Respiratory J

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Objective We aimed to investigate the effect of inhaled corticosteroids (ICS) in the outcomes of community‐acquired pneumonia (CAP), as well as to determine if ICS usage is exist among the risk factors for mortality in those patients. Materials and Methods In this retrospective cross‐sectional multicentre study, 1069 hospitalised CAP patients were investigated using CAP Database of Turkish Thoracic Society (TURKCAP Database). The patients were divided into two groups, depending on their ICS use. The data were analysed by appropriate statistical methods. Results 172 (75.8%) of the 227 patients who were on ICS had COPD and 37 (16.3%) had asthma. There were fewer patients with fever among ICS‐users compared to non‐ICS users (P = 0.013), and less muscle pain (P = 0.015) and fewer GIS symptoms (P = 0.022). No statistically significant difference was found between ICS use/ type of ICS and the duration of hospitalisation (P = 0.286). The multivariate regression analysis showed that patients using ICS had lower body temperature and, less crackles/bronchial sound. In the multivariate logistic regression model lung cancer (OR: 6.75), glucose (OR: 1.01) and CURB‐65 (OR: 1.72) were significantly associated with mortality in the CAP patients. ICS usage were not found to be associated with mortality. Conclusion The use of ICS by the patients with CAP admitted to the hospital is not independently related with any radiological pattern, hospitalisation duration and mortality. ICS usage may diminish fever response and may suppress the findings of crackles and/or bronchial sounds. This needs further confirmation.

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“…Chronic bronchitis is a key pathological feature of chronic obstructive pulmonary disease (70). Clinical management of chronic bronchitis may include LABA/GCS interventions including formoterol/budesonide combination (71)(72)(73). LABA/GCS are transcriptionally active in airway epithelial cells resulting in broad anti-inflammatory activities (49).…”

Section: Discussionmentioning

confidence: 99%

“…LABA/GCS are transcriptionally active in airway epithelial cells resulting in broad anti-inflammatory activities (49). Despite their widespread use, recent analyses of LABA/GCS efficacy and mechanisms have demonstrated that these compounds may suppress antiviral immunity, which could increase susceptibility to subsequent bacterial infections (12,(71)(72)(73)(74). Importantly, the efficacy of LABA/GCS therapies may be compromised by tobacco smoke exposure (8,13), which could be contributing to the reduced efficacy in certain patient populations.…”

Section: Discussionmentioning

confidence: 99%

A comparative analysis of cannabis and tobacco smoke exposure on human airway epithelial cell gene expression, immune phenotype, and response to formoterol and budesonide treatment

Aguiar

Huff

Tse

et al. 2019

Preprint

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Word Count -271Global recreational cannabis use is a potentially important public health issue that would benefit from experimental evidence to inform policy, regulations, and individual user practices. Comparative analyses between cannabis and tobacco smoke, the latter long reported to have negative impacts on respiratory health, may help provide context and provide clinically relevant evidence.To address this unmet need we performed a comparative study between cannabis and tobacco smoke exposure in the Calu-3 human airway epithelial cells using concentration-response and pharmacological intervention study designs with outcome measurements of cell viability, epithelial cell barrier function, cytokine profile, and transcriptomics.Our results demonstrate that cannabis smoke exposure reduces epithelial cell barrier function without impacting cell viability, accompanied by a cytokine profile associated with inflammation (elevated IL-6 and IL-8), barrier repair (elevated TGF-α and PDGF-AA) and suppressed antiviral immunity (decreased IP-10 and RANTES). Transcriptomic analyses revealed a cannabis smoke induced signature associated with suppressed antiviral genes and induction of oncogenic and oxidative stress pathways. Similar trends were observed for tobacco smoke exposure. A formoterol/budesonide intervention was unable to prevent cannabis smoke-induced reductions in antiviral pathways or normalize induction of oncogenic and oxidative stress responses.Our results show striking similarities between cannabis and tobacco smoke exposure on impairing barrier function, suppressing antiviral pathways, potentiating of pro-inflammatory mediators, and inducing oncogenic and oxidative stress gene expression signatures. Furthermore, we demonstrate that an intervention with formoterol and budesonide is unable to completely normalized cannabisinduced responses. Collectively our data suggest that cannabis smoke exposure is not innocuous and may possess many of the deleterious properties of tobacco smoke, warranting additional studies to support public policy, government regulations, and individual user practices.

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Scientific rationale for the possible inhaled corticosteroid intraclass difference in the risk of pneumonia in COPD

Cited by 60 publications

References 60 publications

Inhaled corticosteroids for chronic obstructive pulmonary disease: what is their role in therapy?

Inhaled corticosteroids for chronic obstructive pulmonary disease: what is their role in therapy?

The effect of inhaled corticosteroids in the outcomes of community‐acquired pneumonia: ICCAP study (TURKCAP Database)

A comparative analysis of cannabis and tobacco smoke exposure on human airway epithelial cell gene expression, immune phenotype, and response to formoterol and budesonide treatment

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