Phosphodiesterase 4 inhibitors for chronic obstructive pulmonary disease

Chong, Jimmy; Leung, Bonnie; Poole, Phillippa

doi:10.1002/14651858.cd002309.pub5

Cited by 113 publications

(74 citation statements)

References 66 publications

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“…Finally, targeted inhibition of other anti-inflammatory pathways to prevent AECOPD, the mechanism of action of the oral PDE-4 inhibitor roflumilast, has not been associated with increased pneumonia rates in clinical trials to date [Chong et al 2013;Yan et al 2014]. Also, in the large REACT trial, in which roflumilast was administered to patients with severe COPD already under treatment with LABA/ICS combination, there were no differences in the rate of pneumonia between the LABA/ICS + roflumilast group versus the LABA/ICS-only group [Martinez et al 2015].…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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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“…Phosphodiesterase 4 highly expressed in inflammatory cells including neutrophils, macrophages, T cells and endothelial cells [38]. Insights from the respiratory system have shown that inhibition of phosphodiesterase 4 in immune cells and the subsequent elevation of cAMP results in an anti-inflammatory effect [38][39][40].…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…Insights from the respiratory system have shown that inhibition of phosphodiesterase 4 in immune cells and the subsequent elevation of cAMP results in an anti-inflammatory effect [38][39][40]. Specific inhibitors of this isoenzyme are being developed for use in the treatment of a wide range of disease states with an inflammatory component, including dermatological, neurological and respiratory conditions [38,[41][42][43][44][45][46]. With respect to the reduction in TNF-α by pentoxifylline observed in this study, Shaw [11] has comprehensively reviewed the potential mechanisms which include: Suppression of TNF-α gene transcription by pentoxifylline [47], attenuation of the response of TNF-α to endotoxin [48], and attenuation of Interleukin-2, a cytokine which stimulates TNF-α production [6], Primarily used to treat peripheral arterial disease patients due to the improved circulation obtained through its ability to alter erythrocyte deformability, pentoxifylline also enhances capillary microcirculation [2,11].…”

Section: Discussionmentioning

confidence: 99%

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Effects of pentoxifylline on inflammatory markers and blood pressure

Brie

Sahebkar

Penson

et al. 2016

Journal of Hypertension

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“…In a Cochrane review of 29 randomised controlled trials (15 trials with roflumilast and 14 trials with cilomilast), treatment with roflumilast compared with placebo was associated with a reduced likelihood of COPD exacerbation (odds ratio (OR) 0.77, 95% CI 0.71-0.83) [63]. The most common adverse effects are gastrointestinal in nature.…”

Section: Phosphodiesterase-4 Inhibitormentioning

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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Phosphodiesterase 4 inhibitors for chronic obstructive pulmonary disease

Abstract: Trusted evidence. Informed decisions. Better health.

Cited by 113 publications

References 66 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

Effects of pentoxifylline on inflammatory markers and blood pressure

Exacerbations of COPD

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