This document has been developed by an international committee and has been endorsed by both the ATS and the ERS. It places pulmonary rehabilitation within the concept of integrated care. The World Health Organization has defined integrated care as "a concept bringing together inputs, delivery, management and organization of services related to diagnosis, treatment, care, rehabilitation and health promotion" (1). Integration of services improves access, quality, user satisfaction, and efficiency of medical care. As such, pulmonary rehabilitation provides an opportunity to coordinate care and focus on the entire clinical course of an individual's disease.Building on previous statements (2, 3), this document presents recent scientific advances in our understanding of the multisystemic effects of chronic respiratory disease and how pulmonary rehabilitation addresses the resultant functional limitations. It was created as a comprehensive statement, using both a firm evidence-based approach and the clinical expertise of the writing committee. As such, it is complementary to two current documents on pulmonary rehabilitation: the American College of Chest Physicians and American Association of Cardiovascular and Pulmonary Rehabilitation (AACVPR) evidence-based guidelines (4), which formally grade the level of scientific evidence, and the AACVPR Guidelines for Pulmonary Rehabilitation Programs (5), which give practical recommendations.

To assess physiologic effects of continuous positive airway pressure (CPAP) and positive end-expiratory pressure (PEEP) during noninvasive pressure support ventilation (PSV) in patients with acute exacerbation of chronic obstructive pulmonary disease (COPD), we measured in seven patients the breathing pattern, lung mechanics, diaphragmatic effort (PTPdi), and arterial blood gases under four conditions: (1) spontaneous breathing (SB); (2) CPAP; (3) PSV of 10 cm H2O; and (4) PSV plus PEEP (PEEP + PSV). CPAP and PEEP were set between 80 and 90% of dynamic intrinsic PEEP (PEEPidyn) measured during SB and PSV, respectively. PEEPidyn was obtained (1) from the decrease in pleural pressure (delta Ppl) preceding inspiration, and (2) subtracting the fall in gastric pressure (delta Pga) caused by relaxation of the abdominal muscles from the delta Ppl decrease. Abdominal muscle activity made PEEPidyn overestimated in almost all instances (p < 0.0001). PSV increased minute ventilation, improved gas exchange, and decreased PTPdi. PEEP added to PSV, likewise CPAP compared with SB, further significantly decreased the diaphragmatic effort (PTPdi went from 322 +/- 111 to 203 +/- 63 cm H2O.s) by counterbalancing PEEPidyn, which went from 5.4 +/- 4.0 to 3.1 +/- 2.3 cm H2O. These data support the use of low levels of PEEP (80 to 90% of PEEPidyn) to treat acute exacerbation of COPD by means of mask PSV.

Due to the exponential growth of the number of subjects affected by coronavirus disease 2019 (COVID-19), the entire Italian health care system had to respond promptly and in a very short time with the need of semi-intensive and intensive care units. Moreover, trained dedicated COVID-19 teams consisting of physicians were coming from different specialties (intensivists or pneumologists and infectiologists), while respiratory therapists and nurses have been recruited to work on and on without rest. However, due to still limited and evolving knowledge of COVID-19, there are few recommendations concerning the need in respiratory rehabilitation and physiotherapy interventions. The presentation of this paper is the result of a consensus promoted by the Italian societies of respiratory health care professionals who Vitacca et al.

To investigate the mechanisms underlying ventilator-dependence in patients with chronic obstructive pulmonary disease (COPD), and to assess the effects of the combination of positive end-expiratory pressure (PEEP) and pressure-support ventilation (PSV) on inspiratory muscle effort, we investigated respiratory mechanics in eight ventilator-dependent COPD patients. The patients' breathing pattern, lung mechanics, diaphragmatic effort (PTPdi), diaphragmatic tension-time index (TTdi), and arterial blood gases were measured during both spontaneous breathing (SB) and ventilatory assistance consisting of PSV alone (15, 20, and 25 cm H2O) and PSV combined with a PEEP of 5 cm H2O (reducing PSV to 10, 15, and 20 cm H2O, respectively, to maintain equivalent inspiratory pressure). The different levels of ventilatory support were delivered in a randomized sequence. Maximal inspiratory (MIP), esophageal (PpImax) and transdiaphragmatic (Pdi(max)) pressures and respiratory drive (P(0.1)) were measured at the beginning of the procedure during SB. We found a high P(0.1) (6.1 +/- 1.7 cm H2O), which seemed to rule out an impairment of respiratory-center output. Apparently, inspiratory muscle strength was compatible with successful weaning (38.5 +/- 8.8, 50.9 +/- 9.7, and 51.8 +/- 9.5 cm H2O for MIP, PPImax and Pdi(max), respectively). However, abnormal respiratory mechanics (particularly an intrinsic positive end-expiratory pressure (PEEPi) of 8.3 +/- 1.9 cm H2O and pulmonary resistance 24.7 +/- 9.5 cm H2O/L/s imposed an excessive load on the inspiratory muscles, as indicated by a high PTPdi (499 +/- 122 cm H2O x s). Increasing levels of PSV progressively and significantly unloaded the patients' inspiratory muscles, although at pressures above 20 cm H2O uncoupling occurred between patient and ventilator respiratory frequency. Application of PEEP during PSV improved ventilatory assistance by further reducing the inspiratory effort (by 17% on average) and by ameliorating patient-ventilator interaction. We conclude that the excessive mechanical load, and in particular the high PEEPi, is the major determinant of ventilator-dependence in COPD patients. Application of PEEP improves the efficiency of PSV in unloading these patients' inspiratory muscles, and can sometimes improve patient-ventilator interaction.

Patients with Chronic Obstructive Pulmonary Disease (COPD) and tracheostomy are at high risk for exacerbations and hospitalizations. Macrolide treatment has shown to reduce exacerbations in moderate-to-severe COPD. To evaluate the safety and the efficacy of long-term azithromycin use in outpatients with severe COPD and tracheostomy. A multicenter, randomized, uncontrolled, pilot trial evaluating the safety and the efficacy of azithromycin 500 mg three day-a-week for 6 months (AZI) vs. standard of care (SC) in severe COPD outpatients with tracheostomy. Patients were monitored for six months of treatment plus six months of follow up. The primary outcome was the reduction in the number of exacerbations and hospitalizations. A total of 22 patients was randomized (11 to SC and 11 to AZI). Patients in AZI had a significant lower cumulative number of exacerbations after the first 3 months of treatment when compared to patients in SC (p = 0.001), as well as hospitalizations (p = 0.02). Kaplan-Meier survival curves for time to first exacerbation showed a significant reduction in AZI of the rates of first exacerbation when compared to SC (log rank test = 12.14, p < 0.001), as well as to first hospitalization (log-rank = 4.09, p = 0.04). Azithromycin significantly improved the quality of life in comparison to SC. No serious adverse events in the AZI group were reported. Long-term azithromycin treatment seems to be safe and effective in severe COPD outpatients with tracheostomy in reducing exacerbations, hospitalizations, as well as in improving quality of life.

There is a need of consensus about the pulmonary rehabilitation (PR) in patients with COVID-19 after discharge from acute care. To facilitate the knowledge of the evidence and its translation into practice, we developed suggestions based on experts’ opinion. A steering committee identified areas and questions sent to experts. Other international experts participated to a RAND Delphi method in reaching consensus and proposing further suggestions. Strong agreement in suggestions was defined when the mean agreement was >7 (1 = no agreement and 9 = maximal agreement). Panelists response rate was >95%. Twenty-three questions from 4 areas: Personnel protection equipment, phenotypes, assessments, interventions, were identified and experts answered with 121 suggestions, 119 of which received high level of concordance. The evidence-based suggestions provide the clinicians with current evidence and clinical experts opinion. This framework can be used to facilitate clinical decision making within the context of the individual patient. Further studies will evaluate the clinical usefulness of these suggestions.

Background: Whether blood eosinophil counts and exhaled nitric oxide (FeNO) are associated with important outcomes in mild asthma is unclear. Methods: This question was explored in a pre-specified analysis of a 52week, open-label, randomized, parallel-group trial in patients with mild asthma receiving only reliever inhalers, comparing salbutamol 200µg asneeded, maintenance budesonide 200µg twice-daily with salbutamol as needed, and budesonide/formoterol 200/6µg as-needed. Outcomes were compared between patients with blood eosinophils of <0.15, 0.15-<0.3 and ≥0.3x109/L; FeNO of <20, 20-50 and >50ppb; and a composite score based on both. Results: The proportion of patients randomised to as-needed salbutamol having a severe exacerbation increased progressively with increasing blood eosinophil sub-group (4.1%, 6.5% and 19.5%; p=0.014). There were no significant interactions between either biomarker and the effect of as-needed budesonide/formoterol compared with as-needed salbutamol for either exacerbations or severe exacerbations. However, there were significant interactions between blood eosinophil sub-groups and the effect of maintenance budesonide compared with as needed salbutamol for exacerbations (p<0.001) and severe exacerbations (p<0.001). Maintenance budesonide was more effective than as-needed salbutamol in patients with eosinophils ≥0.3x109/L for exacerbations (odds ratio 0.13; 95% CI 0.05-0.33) and severe exacerbations (0.11; 0.03-0.45). This was not the case for eosinophils <0.15x109/L (odds ratio for exacerbations 1.15; 0.51-1.28 and severe exacerbations 5.72; 0.97-33.6). There was no consistent interaction between treatment response and FeNO or the composite score. Conclusions: In patients with mild asthma the effects of as-needed budesonide/formoterol on exacerbations are independent of biomarker profile, whereas the benefits of maintenance inhaled budesonide are greater in patients with high blood eosinophil counts.

This study, featuring the largest cohort so far reported in the literature, shows that PR is equally effective in the more severe COPD patients, i.e. those with CRF, and supports the prescription of PR also in these patients.