Risk of cardiovascular comorbidity in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis.
Chen Wenjia,Thomas Jamie,Sadatsafavi Mohsen,FitzGerald J Mark
The Lancet. Respiratory medicine
BACKGROUND:Chronic obstructive pulmonary disease (COPD) is a systemic inflammatory disorder associated with increased comorbid prevalence of cardiovascular diseases. We aimed to quantify the magnitudes of association between overall and specific types of cardiovascular disease, major cardiovascular risk factors, and COPD. METHODS:We searched Cochrane, Medline, and Embase databases for studies published between Jan 1, 1980, and April 30, 2015, on the prevalence of cardiovascular disease and its risk factors in patients with COPD versus matched controls or random samples from the general public. We assessed associations with random-effects meta-analyses. We studied heterogeneity and biases with random-effects meta-regressions, jackknife sensitivity analyses, assessment of funnel plots, and Egger tests. FINDINGS:We identified 18,176 unique references and included 29 datasets in the meta-analyses. Compared with the non-COPD population, patients with COPD were more likely to be diagnosed with cardiovascular disease (odds ratio [OR] 2·46; 95% CI 2·02-3·00; p<0·0001), including a two to five times higher risk of ischaemic heart disease, cardiac dysrhythmia, heart failure, diseases of the pulmonary circulation, and diseases of the arteries. Additionally, patients with COPD reported hypertension more often (OR 1·33, 95% CI 1·13-1·56; p=0·0007), diabetes (1·36, 1·21-1·53; p<0·0001], and ever smoking (4·25, 3·23-5·60; p<0·0001). The associations between COPD and these cardiovascular disease types and cardiovascular disease risk factors were consistent and valid across studies. Enrolment period, age, quality of data, and COPD diagnosis partly explained the heterogeneity. INTERPRETATION:The coexistence of COPD, cardiovascular disease, and major risk factors for cardiovascular disease highlights the crucial need for the development of strategies to screen for and reduce cardiovascular risks associated with COPD. FUNDING:Canadian Institutes of Health Research.
10.1016/S2213-2600(15)00241-6
Pathogenesis of HIV-Related Lung Disease: Immunity, Infection, and Inflammation.
Cribbs Sushma K,Crothers Kristina,Morris Alison
Physiological reviews
Despite anti-retroviral therapy (ART), human immunodeficiency virus-1 (HIV)-related pulmonary disease continues to be a major cause of morbidity and mortality for people living with HIV (PLWH). The spectrum of lung diseases has changed from acute opportunistic infections resulting in death to chronic lung diseases for those with access to ART. Chronic immune activation and suppression can result in impairment of innate immunity and progressive loss of T cell and B cell functionality with aberrant cytokine and chemokine responses systemically as well as in the lung. HIV can be detected in the lungs of PLWH and has profound effects on cellular immune functions. In addition, HIV-related lung injury and disease can occur secondary to a number of mechanisms including altered pulmonary and systemic inflammatory pathways, viral persistence in the lung, oxidative stress with additive effects of smoke exposure, microbial translocation, and alterations in the lung and gut microbiome. Although ART has had profound effects on systemic viral suppression in HIV, the impact of ART on lung immunology still needs to be fully elucidated. Understanding of the mechanisms by which HIV-related lung diseases continue to occur is critical to the development of new preventive and therapeutic strategies to improve lung health in PLWH.
10.1152/physrev.00039.2018
Pharmacology and Therapeutics of Bronchodilators Revisited.
Matera M G,Page C P,Calzetta L,Rogliani P,Cazzola M
Pharmacological reviews
Bronchodilators remain the cornerstone of the treatment of airway disorders such as asthma and chronic obstructive pulmonary disease (COPD). There is therefore considerable interest in understanding how to optimize the use of our existing classes of bronchodilator and in identifying novel classes of bronchodilator drugs. However, new classes of bronchodilator have proved challenging to develop because many of these have no better efficacy than existing classes of bronchodilator and often have unacceptable safety profiles. Recent research has shown that optimization of bronchodilation occurs when both arms of the autonomic nervous system are affected through antagonism of muscarinic receptors to reduce the influence of parasympathetic innervation of the lung and through stimulation of -adrenoceptors ( -ARs) on airway smooth muscle with -AR-selective agonists to mimic the sympathetic influence on the lung. This is currently achieved by use of fixed-dose combinations of inhaled long-acting -adrenoceptor agonists (LABAs) and long-acting muscarinic acetylcholine receptor antagonists (LAMAs). Due to the distinct mechanisms of action of LAMAs and LABAs, the additive/synergistic effects of using these drug classes together has been extensively investigated. More recently, so-called "triple inhalers" containing fixed-dose combinations of both classes of bronchodilator (dual bronchodilation) and an inhaled corticosteroid in the same inhaler have been developed. Furthermore, a number of so-called "bifunctional drugs" having two different primary pharmacological actions in the same molecule are under development. This review discusses recent advancements in knowledge on bronchodilators and bifunctional drugs for the treatment of asthma and COPD. SIGNIFICANCE STATEMENT: Since our last review in 2012, there has been considerable research to identify novel classes of bronchodilator drugs, to further understand how to optimize the use of the existing classes of bronchodilator, and to better understand the role of bifunctional drugs in the treatment of asthma and chronic obstructive pulmonary disease.
10.1124/pr.119.018150
Chronic obstructive pulmonary disease.
Barnes Peter J,Burney Peter G J,Silverman Edwin K,Celli Bartolome R,Vestbo Jørgen,Wedzicha Jadwiga A,Wouters Emiel F M
Nature reviews. Disease primers
Chronic obstructive pulmonary disease (COPD) is a common disease with high global morbidity and mortality. COPD is characterized by poorly reversible airway obstruction, which is confirmed by spirometry, and includes obstruction of the small airways (chronic obstructive bronchiolitis) and emphysema, which lead to air trapping and shortness of breath in response to physical exertion. The most common risk factor for the development of COPD is cigarette smoking, but other environmental factors, such as exposure to indoor air pollutants - especially in developing countries - might influence COPD risk. Not all smokers develop COPD and the reasons for disease susceptibility in these individuals have not been fully elucidated. Although the mechanisms underlying COPD remain poorly understood, the disease is associated with chronic inflammation that is usually corticosteroid resistant. In addition, COPD involves accelerated ageing of the lungs and an abnormal repair mechanism that might be driven by oxidative stress. Acute exacerbations, which are mainly triggered by viral or bacterial infections, are important as they are linked to a poor prognosis. The mainstay of the management of stable disease is the use of inhaled long-acting bronchodilators, whereas corticosteroids are beneficial primarily in patients who have coexisting features of asthma, such as eosinophilic inflammation and more reversibility of airway obstruction. Apart from smoking cessation, no treatments reduce disease progression. More research is needed to better understand disease mechanisms and to develop new treatments that reduce disease activity and progression.
10.1038/nrdp.2015.76
Advances in Chronic Obstructive Pulmonary Disease.
Annual review of medicine
Chronic obstructive pulmonary disease (COPD) is a common respiratory disorder with significant morbidity and mortality. Despite its prevalence, COPD is underdiagnosed, and many patients do not receive a diagnosis until the disease is clinically advanced. Recent basic science and clinical research have focused on the early physiologic and pathobiologic changes in COPD with the hopes of improving diagnosis, providing targets for disease-modifying therapy, and identifying patients most likely to benefit from early intervention. Available treatments for COPD have grown substantially in the past 20 years with the introduction of new oral and inhaled medications as well as novel surgical and bronchoscopic procedures. This article summarizes some of the recent advances in our understanding of disease pathogenesis and treatment paradigms.
10.1146/annurev-med-080919-112707