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Challenges and Opportunities in COPD

Challenges and Opportunities in COPD

Velin Stratev, and Odd-Magne Fjeldstad


Chronic obstructive pulmonary disease (COPD) is chronic disease that affects mostly the lungs but there is growing evidence that it is also a systemic condition associated with a number of accompanying diseases known as comorbidities. Chronic inflammation and oxidative stress are the highlight pathogenic processes that interrelate COPD and comorbidities with additional disease specific risk factors and mechanisms. Through complex interactions COPD increases the risk for certain comorbidities and they in turn have negative impact on health status and contribute to mortality in COPD patients. Treatment of comorbidities in terms of coexistence with COPD may require more specific personalized therapeutic approach. Here we review the pathogenic mechanisms which define COPD as a systemic disease; the most common comorbidities of COPD: cardiovascular disease, diabetes and metabolic syndrome, cachexia, osteoporosis, depression/anxiety and obstructive sleep apnea; the pathways which connect these diseases with COPD and the latest treatment approaches.

Abdelilah Benslimane, Khaoula El Kinany, Inge Huybrechts, Zineb Hatime, Meimouna Mint Sidi Deoula, Mohamed Chakib Benjelloun, Mohamed El Biaz, Chakib Nejjari, and Karima El Rhazi


Objective: The protective effect of the Mediterranean diet (MD) is known for several diseases, but the evidence in low- and middle-income countries is still missing. This article assesses the impact of MD and its components on Chronic Obstructive Pulmonary Disease (COPD) among Moroccan adults.

Methods: In a population-based cross-sectional study, a total of 744 adults with acceptable spirometry according to the GOLD guidelines were randomly selected from a sample frame of Moroccan adults who lived in the areas of the Saïs district-Fez city. Dietary data were collected through a validated food frequency questionnaire. The Mediterranean Diet Score (MDS) was used to assess adherence to the Mediterranean food model. A value of 0 or 1 has been assigned to each of the eight indicated food components according to their beneficial or deleterious effect on health.

Results: Although no significant associations were found between COPD and the overall MD. score, associations were found between some of the MD components and COPD when stratifying for overall MDS adherence level (low, middle, or high adherence). For the high adherence group, the high consumption of cereals, fruits, and nuts was inversely associated with COPD risk with OR = 0.64; 95% CI = 0.26-0.89, and OR = 0.67; 95% CI = 0.44-0.96, respectively. The high consumption of meat and dairy products was positively associated with the risk of COPD, with an OR of 1.37 (95% CI = 1.22-2.87) and an OR of 1.83 (95% CI = 1.21-2.76), respectively.

Conclusion: The results of this study confirmed previous results showing significant associations of COPD risk with some components of MDS. Extensive studies are needed to explore MDS components better and suggest more effective interventions to maintain healthy eating habits and reduce COPD risk.

Rino Frizzelli


Chronic obstructive pulmonary disease (COPD) is a slowly progressive disease characterized by inflammation that involves the airways, lung parenchyma, and pulmonary vasculature commonly associated with lung function decline and alveolar impairment of gas exchange. All these alterations can lead to hypoxemia. In COPD hypoxemia presenting refractory to the very high concentration of inspired O2 with a drop of       SpO2 (peripheral saturation) > 5% during the upright position and an improvement in recumbency (platypnea/orthodoxy syndrome) can be suspected for right-to-left shunt, e.g. intrapulmonary shunt or most frequently a patent foramen ovale.

Among COPD patients, several studies showed a higher prevalence of patent foramen ovale than in the general population (70% versus 35%). Chest imaging and echocardiogram with bubble contrast should be the first clinical assessment to differentiate subjects with intracardiac shunt (such as in Patent foramen ovale) from those with extracardiac (or intrapulmonary) one.

Definitive treatment of right-to-left shunt involves percutaneous closure but the literature provides conflicting data about indications and results, particularly regarding the selection of COPD patients to be subjected to such intervention. Several key factors should be taken into account from a clinical and ethical point of view: first periprocedural complications, then echocardiographic assessment of right ventricular systolic and diastolic performance should be performed to rule out severe pulmonary hypertension and to avoid further post-procedure clinical deterioration; in addition, quality of life should be assessed.

In our experience, among 12 patients with patent foramen ovale 5 were affected by COPD GOLD III with refractory hypoxaemia. After evaluation of right ventricular performance, only 2 patients were eligible for patent foramen ovale closure with the Amplatzer device; long-term follow-up showed discontinuation of oxygen therapy and improvement in quality of life. Therefore, COPD patients with hypoxemia refractory to high O2 supplementation must be thoroughly assessed taking into account a careful history and a targeted physical examination. The presence of patent foramen ovale should raise suspicion of a right-to-left shunt. If a patent foramen ovale is identified, evaluation of pulmonary function, right ventricular systolic reserve, and severity of pulmonary hypertension is mandatory for closure.

The development of a multidisciplinary team to conduct a multicenter study is necessary to understand if and when the right-to-left shunt in COPD can benefit from this novel therapy.

Amir Pelleg, Ph.D, Peter J. Barnes, FRS, and Edward S Schulman, M.D


Adenosine 5’-triphosphate (ATP) is found in every cell of the body, where it plays a critical role in cellular metabolism and energetics. ATP is released from cells under physiologic and pathophysiologic conditions; extracellular ATP acts as an autocrine and paracrine agent. Its effects on targeted cells are mediated by subtypes of purinergic receptors (P2R). In the lungs, relatively large amounts of ATP are released under inflammatory conditions. Extracellular ATP triggers a central vagal reflex by activating the purinergic receptor P2XR, localized on pulmonary vagal sensory nerve terminals. This results in coughing, bronchoconstriction, and the release of pro-inflammatory neuropeptides via the axon reflex. COPD patients manifest higher sensitivity to aerosolized ATP than healthy subjects, and the levels of ATP in COPD patients’ lungs are three times higher than those found in healthy subjects. This review succinctly details (i) the sources and mechanisms of ATP’s release into the extracellular space, (ii) the ways extracellular ATP is eliminated, (iii) the deleterious effects of ATP in the lungs in general and in COPD in particular, and (iv) the rationale for the blockade of these actions of ATP in the lungs as a novel therapeutic approach in the management of COPD patients.

Mehak Swami, DO, and Karin Provost, DO, PhD


Breathlessness is a distressing symptom, uniformly faced at some point in the disease process in all patients with Chronic Obstructive Pulmonary Disease (COPD). Despite maximal medical therapy and pulmonary rehabilitation, patients with COPD continue to experience refractory dyspnea, pain, poor appetite, limitations of physical activity, emotional distress, depression, and an overall poor health-related quality of life. Our current GOLD ABE pharmacologic treatment algorithm provides maximal disease-specific therapy directed at optimization of physiologic airflow obstruction and exacerbation frequency, however, leaving a gap in how best to approach the complex and multifactorial symptom of refractory breathlessness that occurs despite these pharmacologic interventions and pulmonary rehabilitation. The comprehensive and multidisciplinary approach of specialty palliative care may well fill this gap in our treatment algorithms. In this review, we will review the growing body of literature on the definitions and role of primary and specialty palliative care in the treatment of patients with COPD, review the components of a structured palliative care intervention in advanced lung disease, review the current pharmacologic and non-pharmacologic treatments for breathlessness, identify the barriers to palliative care intervention, and consider the future direction of palliative care engagement in patients with COPD.