Inflammation, oxidative stress and apoptosis, which are involved in chronic obstructive pulmonary disease (COPD) pathogenesis, may activate the p38 subgroup of mitogenactivated protein kinases (MAPKs). Therefore, the aim of the present study was to evaluate the expression of the phosphorylated, active form of p38 MAPK (phospho-p38) in the lungs of COPD patients.Surgical specimens were obtained from 18 smokers with COPD at different stages of disease severity, plus nine smoking and eight nonsmoking subjects with normal lung function. Phosphop38+ cells were quantified by immunohistochemistry in both alveolar spaces and alveolar walls. Moreover, a Western blot analysis of phospho-p38 and total p38a isoform expressed by alveolar macrophages was performed.Phospho-p38+ alveolar macrophages and phospho-p38+ cells in alveolar walls were increased in patients with severe and mild/moderate COPD, compared with smoking and nonsmoking controls. Moreover, they were inversely correlated to values of forced expiratory volume in one second (FEV1) and FEV1/forced vital capacity. Western blot analysis showed that phosphorylated p38, but not the total p38a isoform, was specifically increased in alveolar macrophages from COPD patients.Activation of the p38 mitogen-activated protein kinase pathway appears to be involved in the pathogenesis of chronic obstructive pulmonary disease. The present findings suggest that this protein may be a suitable pharmacological target for therapeutic intervention.

Oxygen therapy is first-line treatment for hypoxaemic acute respiratory failure (ARF). High-flow nasal oxygen therapy (HFNO) represents an alternative to conventional oxygen therapy. HFNO provides humidified, titrated oxygen therapy matching or even exceeding the patients' inspiratory demand. The application of HFNO is becoming widespread in Intensive Care Units (ICUs), favoured by increasing evidence based on numerous studies supporting its efficacy. The mechanisms of action and physiological effects of HFNO are not yet fully understood. Pharyngeal dead space washout, decrease in airway resistance, generation of a positive end-expiratory pressure, and enhanced delivery of oxygen are all alleged to be potential mechanisms. The emerging evidence suggests that HFNO is effective in improving oxygenation in most patients with hypoxaemic ARF of different aetiologies. Notwithstanding the potential benefit of HFNO in the management of hypoxaemia, further large cohort studies are necessary to clarify the indications, contraindications and factors associated with HFNO failure. HFNO may also be valuable in reducing the need for tracheal intubation in the management of post-extubation ARF. In addition, HFNO has been proposed to limit oxygen desaturation by prolonging apnoeic oxygenation during intubation both in ICUs and operating theatres.

BackgroundHigh-flow nasal cannula (HFNC) has become a frequently used non-invasive form of respiratory support in acute settings, however evidence supporting its use has only recently emerged. These guidelines provide evidence-based recommendations for the use of HFNC alongside other noninvasive forms of respiratory support in adults with acute respiratory failure (ARF).Materials and methodologyThe European Respiratory Society Task Force panel included expert clinicians and methodologists in pulmonology and intensive care medicine. The Task Force used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) methods to summarise evidence and develop clinical recommendations for the use of HFNC alongside conventional oxygen therapy (COT) and non-invasive ventilation (NIV) for the management of adults in acute settings with ARF.ResultsThe Task Force developed 8 conditional recommendations, suggesting using: 1) HFNC over COT in hypoxemic ARF, 2) HFNC over NIV in hypoxemic ARF, 3)HFNC over COT during breaks from NIV, 4) either HFNC or COT in post-operative patients at low risk of pulmonary complications, 5) either HFNC or NIV in post-operative patients at high risk of pulmonary complications, 6) HFNC over COT in non-surgical patients at low risk of extubation failure, 7) NIV over HFNC for patients at high risk of extubation failure unless there are relative or absolute contraindications to NIV, 8) trialling NIV prior to use of HFNC in patients with chronic obstructive pulmonary disease (COPD) and hypercapnic ARF.ConclusionsHFNC is a valuable intervention in adults with ARF. These conditional recommendations can assist clinicians in choosing the most appropriate form of non-invasive respiratory support to provide to patients in different acute settings.

Airway smooth muscle (ASM) plays a key role in bronchomotor tone, as well as in structural remodeling of the bronchial wall. Therefore, ASM contraction and proliferation significantly participate in the development and progression of asthma. Many contractile agonists also behave as mitogenic stimuli, thus contributing to frame a hyperresponsive and hyperplastic ASM phenotype. In this review, the molecular mechanisms and signaling pathways involved in excitation-contraction coupling and ASM cell growth will be outlined. Indeed, the recent advances in understanding the basic aspects of ASM biology are disclosing important cellular targets, currently explored for the implementation of new, more effective anti-asthma therapies.