The Use of Statins and Lung Function in Current and Former Smokers

Keddissi, Jean I.; Younis, Walid G.; Chbeir, Elie A.; Daher, Nadim; Dernaika, Tarek A.; Kinasewitz, Gary T.

doi:10.1378/chest.07-0298

Cited by 104 publications

(95 citation statements)

References 30 publications

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“…Observational and epidemiological studies have suggested that some treatments, such as statins and angiotensin converting enzyme (ACE) inhibitors, used for comorbid diseases, may apparently benefit COPD, with a reduction in exacerbations and mortality [178][179][180]. This may reflect beneficial effects of these drugs on the comorbidities, associated with COPD, such as cardiovascular disease, but there may also be a therapeutic effect on the inflammatory disease process of COPD.…”

Section: Pulmonary Rehabilitationmentioning

confidence: 99%

“…Th17 cells may play a role in orchestrating neutrophilic inflammation in COPD through the effect of IL-17 on epithelial cells to release CXCL1 and CXCL8 [189]. All of these studies on the pleiotropic effects of statins suggest that they may have a beneficial effect in COPD and this may contribute to the reduction in exacerbations in COPD patients treated with statins in observational studies [178][179][180]190]. Through their pleiotropic effects, statins may have beneficial effects not only on cardiovascular disease but also other comorbidities associated with COPD, including diabetes, osteoporosis and lung cancer [191].…”

Section: Statinsmentioning

confidence: 99%

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Systemic manifestations and comorbidities of COPD

Barnes¹,

Celli²

2009

Eur Respir J

1,478

1,113

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Increasing evidence indicates that chronic obstructive pulmonary disease (COPD) is a complex disease involving more than airflow obstruction. Airflow obstruction has profound effects on cardiac function and gas exchange with systemic consequences. In addition, as COPD results from inflammation and/or alterations in repair mechanisms, the ''spill-over'' of inflammatory mediators into the circulation may result in important systemic manifestations of the disease, such as skeletal muscle wasting and cachexia. Systemic inflammation may also initiate or worsen comorbid diseases, such as ischaemic heart disease, heart failure, osteoporosis, normocytic anaemia, lung cancer, depression and diabetes. Comorbid diseases potentiate the morbidity of COPD, leading to increased hospitalisations, mortality and healthcare costs. Comorbidities complicate the management of COPD and need to be evaluated carefully. Current therapies for comorbid diseases, such as statins and peroxisome proliferator-activated receptor-agonists, may provide unexpected benefits for COPD patients. Treatment of COPD inflammation may concomitantly treat systemic inflammation and associated comorbidities. However, new broad-spectrum anti-inflammatory treatments, such as phosphodiesterase 4 inhibitors, have significant side-effects so it may be necessary to develop inhaled drugs in the future. Another approach is the reversal of corticosteroid resistance, for example with effective antioxidants. More research is needed on COPD comorbidities and their treatment.

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Section: Pulmonary Rehabilitationmentioning

confidence: 99%

Section: Statinsmentioning

confidence: 99%

Systemic manifestations and comorbidities of COPD

Barnes¹,

Celli²

2009

Eur Respir J

1,478

1,113

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show abstract

“…Statins have been proposed as potential novel treatments for respiratory diseases, including bronchial asthma (1,2). Reductions in chronic obstructive pulmonary disease morbidity and mortality, and improvements in lung function, have been attributed to statin use (1,(3)(4)(5). Statins are also associated with lower asthma exacerbation rates and reduced endotracheal intubation rates for respiratory failure (6).…”

mentioning

confidence: 99%

Simvastatin Inhibits Airway Hyperreactivity

Zeki

Franzi

Kenyon

2009

Am J Respir Crit Care Med

109

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Rationale: Statin use has been linked to improved lung health in asthma and chronic obstructive pulmonary disease. We hypothesize that statins inhibit allergic airway inflammation and reduce airway hyperreactivity via a mevalonate-dependent mechanism. Objectives: To determine whether simvastatin attenuates airway inflammation and improves lung physiology by mevalonate pathway inhibition. Methods: BALB/c mice were sensitized to ovalbumin over 4 weeks and exposed to 1% ovalbumin aerosol over 2 weeks. Simvastatin (40 mg/kg) or simvastatin plus mevalonate (20 mg/kg) was injected intraperitoneally before each ovalbumin exposure. Measurements and Main Results: Simvastatin reduced total lung lavage leukocytes, eosinophils, and macrophages (P , 0.05) in the ovalbumin-exposed mice. Cotreatment with mevalonate, in addition to simvastatin, reversed the antiinflammatory effects seen with simvastatin alone (P , 0.05). Lung lavage IL-4, IL-13, and tumor necrosis factor-a levels were all reduced by treatment with simvastatin (P , 0.05). Simvastatin treatment before methacholine bronchial challenge increased lung compliance and reduced airway hyperreactivity (P 5 0.0001). Conclusions: Simvastatin attenuates allergic airway inflammation, inhibits key helper T cell type 1 and 2 chemokines, and improves lung physiology in a mouse model of asthma. The mevalonate pathway appears to modulate allergic airway inflammation, while the beneficial effects of simvastatin on lung compliance and airway hyperreactivity may be independent of the mevalonate pathway. Simvastatin and similar agents that modulate the mevalonate pathway may prove to be treatments for inflammatory airway diseases, such as asthma.

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“…Exacerbation severity also decreases, with a significant fall in the number of intubations and in mortality associated with or following exacerbation [72][73][74]. Likewise, statins impact the decline in FEV1 [75,76]. Finally, COPD patients receiving statins show improved exercise tolerance, with improvement in performance correlating with a reduction in C-reactive protein, suggesting an effect on peripheral inflammation [77].…”

Section: Copd and Inflammation: New Data For New Treatmentsmentioning

confidence: 99%

Beyond corticosteroids: future prospects in the management of inflammation in COPD

Roche¹,

Marthan²,

Berger³

et al. 2011

Eur Respir Rev

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Inflammation plays a central role in the pathophysiology of chronic obstructive pulmonary disease (COPD). Exposure to cigarette smoke induces the recruitment of inflammatory cells in the airways and stimulates innate and adaptive immune mechanisms. Airway inflammation is involved in increased bronchial wall thickness, increased bronchial smooth muscle tone, mucus hypersecretion and loss of parenchymal elastic structures. Oxidative stress impairs tissue integrity, accelerates lung ageing and reduces the efficacy of corticosteroids by decreasing levels of histone deacetylase-2. Protease-antiprotease imbalance impairs tissues and is involved in inflammatory processes. Inflammation is also present in the pulmonary artery wall and at the systemic level in COPD patients, and may be involved in COPD-associated comorbidities.Proximal airways inflammation contributes to symptoms of chronic bronchitis while distal and parenchymal inflammation relates to airflow obstruction, emphysema and hyperinflation. Basal levels of airways and systemic inflammation are increased in frequent exacerbators.Inhaled corticosteroids are much less effective in COPD than in asthma, which relates to the intrinsically poor reversibility of COPD-related airflow obstruction and to molecular mechanisms of resistance relating to oxidative stress. Ongoing research aims at developing new drugs targeting more intimately COPD-specific mechanisms of inflammation, hypersecretion and tissue destruction and repair. Among new anti-inflammatory agents, phosphodiesterase-4 inhibitors have been the first to emerge.

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The Use of Statins and Lung Function in Current and Former Smokers

Cited by 104 publications

References 30 publications

Systemic manifestations and comorbidities of COPD

Systemic manifestations and comorbidities of COPD

Simvastatin Inhibits Airway Hyperreactivity

Beyond corticosteroids: future prospects in the management of inflammation in COPD

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