Evidence-based recommendations on the clinical use of cardiopulmonary exercise testing (CPET) in lung and heart disease are presented, with reference to the assessment of exercise intolerance, prognostic assessment and the evaluation of therapeutic interventions (e.g.drugs, supplemental oxygen, exercise training). A commonly used grading system for recommendations in evidence-based guidelines was applied, with the grade of recommendation ranging from A, the highest, to D, the lowest.For symptom-limited incremental exercise, CPET indices, such as peak O₂uptake (V′O₂),V′O₂at lactate threshold, the slope of the ventilation–CO₂output relationship and the presence of arterial O₂desaturation, have all been shown to have power in prognostic evaluation. In addition, for assessment of interventions, the tolerable duration of symptom-limited high-intensity constant-load exercise often provides greater sensitivity to discriminate change than the classical incremental test. Field-testing paradigms (e.g.timed and shuttle walking tests) also prove valuable.In turn, these considerations allow the resolution of practical questions that often confront the clinician, such as: 1) “When should an evaluation of exercise intolerance be sought?”; 2) “Which particular form of test should be asked for?”; and 3) “What cluster of variables should be selected when evaluating prognosis for a particular disease or the effect of a particular intervention?”

The World Health Organization has recently defined the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection a pandemic. The infection, that may cause a potentially very severe respiratory disease, now called coronavirus disease 2019 (COVID-19), has airborne transmissionviadroplets. The rate of transmission is quite high, higher than common influenza. Healthcare workers are at high risk of contracting the infection particularly when applying respiratory devices such as oxygen cannulas or noninvasive ventilation. The aim of this article is to provide evidence-based recommendations for the correct use of “respiratory devices” in the COVID-19 emergency and protect healthcare workers from contracting the SARS-CoV-2 infection.

Circulating CD34+ cells are haemopoietic progenitors that may play a role in tissue repair. No data are available on circulating progenitors in chronic obstructive pulmonary disease (COPD).Circulating CD34+ cells were studied in 18 patients with moderate-to-severe COPD (age: mean±sd68±8 yrs; forced expiratory volume in one second: 48±12% predicted) and 12 controls, at rest and after endurance exercise. Plasma concentrations of haematopoietic growth factors (FMS-like tyrosine kinase 3 (Flt3) ligand, kit ligand), markers of hypoxia (vascular endothelial growth factor (VEGF)) and stimulators of angiogenesis (VEGF, hepatocyte growth factor (HGF)) and markers of systemic inflammation (tumour necrosis factor (TNF)-α, interleukin (IL)-6, IL-8) were measured.Compared with the controls, the COPD patients showed a three-fold reduction in CD34+ cell counts (3.3±2.5versus10.3±4.2 cells·µL⁻¹), and a 50% decrease in AC133+ cells. In the COPD patients, progenitor-derived haemopoietic and endothelial cell colonies were reduced by 30–50%. However, four COPD patients showed progenitor counts in the normal range associated with lower TNF-α levels. In the entire sample, CD34+ cell counts correlated with exercise capacity and severity of airflow obstruction. After endurance exercise, progenitor counts were unchanged, while plasma Flt3 ligand and VEGF only increased in the COPD patients. Plasma HGF levels were higher in the COPD patients compared with the controls and correlated inversely with the number of progenitor-derived colonies.In conclusion, circulating CD34+ cells and endothelial progenitors were decreased in chronic obstructive pulmonary disease patients and could be correlated with disease severity.

We tested the hypothesis that heliox breathing, by reducing lung dynamic hyperinflation (DH) and dyspnea (Dys) sensation, may significantly improve exercise endurance capacity in patients with chronic obstructive pulmonary disease [ n = 12, forced expiratory volume in 1 s = 1.15 (SD 0.32) liters]. Each subject underwent two cycle ergometer high-intensity constant work rate exercises to exhaustion, one on room air and one on heliox (79% He-21% O₂). Minute ventilation (V̇e), carbon dioxide output, heart rate, inspiratory capacity (IC), Dys, and arterial partial pressure of CO₂ were measured. Exercise endurance time increased significantly with heliox [9.0 (SD 4.5) vs. 4.2 (SD 2.0) min; P < 0.001]. This was associated with a significant reduction in lung DH at isotime (Iso), as reflected by the increase in IC [1.97 (SD 0.40) vs. 1.77 (SD 0.41) liters; P < 0.001] and a decrease in Dys [6 (SD 1) vs. 8 (SD 1) score; P < 0.001]. Heliox induced a state of relative hyperventilation, as reflected by the increase in V̇e [38.3 (SD 7.7) vs. 35.5 (SD 8.8) l/min; P < 0.01] and V̇e/carbon dioxide output [36.3 (SD 6.0) vs. 33.9 (SD 5.6); P < 0.01] at peak exercise and by the reduction in arterial partial pressure of CO₂ at Iso [44 (SD 6) vs. 48 (SD 6) Torr; P < 0.05] and at peak exercise [46 (SD 6) vs. 48 (SD 6) Torr; P < 0.05]. The reduction in Dys at Iso correlated significantly ( R = −0.75; P < 0.01) with the increase in IC induced by heliox. The increment induced by heliox in exercise endurance time correlated significantly with resting increment in resting forced expiratory in 1 s ( R = 0.88; P < 0.01), increase in IC at Iso ( R = 0.70; P < 0.02), and reduction in Dys at Iso ( R = −0.71; P < 0.01). In chronic obstructive pulmonary disease, heliox breathing improves high-intensity exercise endurance capacity by increasing maximal ventilatory capacity and by reducing lung DH and Dys.

Chronic obstructive pulmonary disease (COPD) has traditionally been considered a disease of the lungs secondary to cigarette smoking and characterized by airflow obstruction due to abnormalities of both airway (bronchitis) and lung parenchyma (emphysema). It is now well known that COPD is associated with significant systemic abnormalities, such as renal and hormonal abnormalities, malnutrition, muscle wasting, osteoporosis, and anemia. However, it is still unclear whether they represent consequences of the pulmonary disorder, or whether COPD should be considered as a systemic disease. These systemic abnormalities have been attributed to an increased level of systemic inflammation. Chronic inflammation, however, may not be the only cause of the systemic effects of COPD. Recent data from humans and animal models support the view that emphysema may be a vascular disease. Other studies have highlighted the role of repair failure, bone marrow abnormality, genetic and epigenetic factors, immunological disorders and infections as potential causes of COPD systemic manifestations. Based on this new evidence, it is reasonable to consider COPD, and emphysema in particular, as ‘a disease with a significant systemic component’ if not a ‘systemic disease’ per se. The aim of this review is to give an overview of the most relevant and innovative hypothesis about the extrapulmonary manifestations of COPD.