Risk of Pneumonia with Inhaled Corticosteroid versus Long-Acting Bronchodilator Regimens in Chronic Obstructive Pulmonary Disease: A New-User Cohort Study

DiSantostefano, Rachael L.; Sampson, Tim; Le, Hoa Van; Hinds, David; Davis, Kourtney J.; Bakerly, Nawar Diar

doi:10.1371/journal.pone.0097149

Cited by 47 publications

(45 citation statements)

References 43 publications

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“…Several other recent case-control studies confirm previous reports of an increased, dose-related pneumonia risk with ICS use in patients with COPD [Thornton Snider et al 2012;Yawn et al 2013;DiSantostefano et al 2014]. One study also reported a 90% relative increase in the risk of recurrent pneumonia among high-risk individuals who survived a first episode of pneumonia [Eurich et al 2013].…”

supporting

confidence: 76%

Inhaled corticosteroids and the increased risk of pneumonia: what’s new? A 2015 updated review

Iannella

Luna

Waterer

2016

Ther Adv Respir Dis

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There is a considerable amount of evidence that supports the possibility of an increased risk of pneumonia associated with prolonged use of inhaled corticosteroids (ICS) in patients with chronic obstructive pulmonary disease (COPD). However, as yet, no statistically significant increase in pneumonia-related 30-day mortality in patients on ICS has been demonstrated. The lack of objective pneumonia definitions and radiological confirmations have been a major source of bias, because of the similarities in clinical presentation between pneumonia and acute exacerbations of COPD. One of the newer fluticasone furoate studies overcomes these limitations and also provides an assessment of a range of doses, suggesting that the therapeutic window is quite narrow and that conventional dosing has probably been too high, although the absolute risk may be different compared to other drugs. Newer studies were not able to rule out budesonide as responsible for pneumonia, as previous evidence suggested, and there is still need for evidence from head-to-head comparisons in order to better assess possible intra-class differences. Although the exact mechanisms by which ICS increase the risk of pneumonia are not fully understood, the immunosuppressive effects of ICS on the respiratory epithelium and the disruption of the lung microbiome are most likely to be implicated. Given that COPD represents such a complex and heterogeneous disease, attempts are being made to identify clinical phenotypes with clear therapeutic implications, in order to optimize the pharmacological treatment of COPD and avoid the indiscriminate use of ICS. If deemed necessary, gradual withdrawal of ICS appears to be well tolerated. Vaccination against pneumococcus and influenza should be emphasized in patients with COPD receiving ICS. Physicians should keep in mind that signs and symptoms of pneumonia in COPD patients may be initially indistinguishable from those of an exacerbation, and that patients with COPD appear to be at increased risk of developing pneumonia as a complication of ICS therapy.

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supporting

confidence: 76%

Inhaled corticosteroids and the increased risk of pneumonia: what’s new? A 2015 updated review

Iannella

Luna

Waterer

2016

Ther Adv Respir Dis

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“…Nevertheless, long-term use of ICS in patients with COPD is still controversial. The most important adverse effects are increased risks of pneumonia, diabetes and fractures [54][55][56]. In the WISDOM study, withdrawal of ICS was not associated with an increased risk of exacerbations [57].…”

Section: Inhaled Corticosteroidsmentioning

confidence: 99%

Exacerbations of COPD

2018

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Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. While COPD is a mainly chronic disease, a substantial number of patients suffer from exacerbations. Severe exacerbations are related to a significantly worse survival outcome. This review summarises the current knowledge on the different aspects of COPD exacerbations. The impact of risk factors and triggers such as smoking, severe airflow limitation, bronchiectasis, bacterial and viral infections and comorbidities is discussed. More severe exacerbations should be treated with β-agonists and anticholinergics as well as systemic corticosteroids. Antibiotic therapy should only be given to patients with presumed bacterial infection. Noninvasive ventilation is indicated in patients with respiratory failure. Smoking cessation is key to prevent further COPD exacerbations. Other aspects include choice of pharmacotherapy, including bronchodilators, inhaled corticosteroids, phosphodiesterase-4 inhibitors, longterm antibiotics and mucolytics. Better education and self-management as well as increased physical activity are important. Influenza and pneumococcal vaccination is recommended. Treatment of hypoxaemia and hypercapnia reduce the rate of COPD exacerbations, while most interventional bronchoscopic therapies increase exacerbation risk within the first months after the procedure.

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“…The risk of pneumonia is increased in patients with COPD and further increased in those with a history of exacerbations and more severe disease 69,70. ICS-containing therapy for COPD has generally been associated with an increased risk of nonfatal pneumonia 70.…”

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

confidence: 99%

“…ICS-containing therapy for COPD has generally been associated with an increased risk of nonfatal pneumonia 70. A 2009 meta-analysis of 18 studies of ICS therapy in COPD estimated an approximately 60% increased risk of pneumonia without a significant increase in pneumonia-related death or overall mortality 71.…”

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

confidence: 99%

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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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Risk of Pneumonia with Inhaled Corticosteroid versus Long-Acting Bronchodilator Regimens in Chronic Obstructive Pulmonary Disease: A New-User Cohort Study

Cited by 47 publications

References 43 publications

Inhaled corticosteroids and the increased risk of pneumonia: what’s new? A 2015 updated review

Inhaled corticosteroids and the increased risk of pneumonia: what’s new? A 2015 updated review

Exacerbations of COPD

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

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