Monitoring COPD patients: systemic and bronchial eosinophilic inflammation in a 2-year follow-up.

BACKGROUND: High blood eosinophils seem to predict exacerbations and response to inhaled corticosteroids (ICS) treatment in patients with chronic obstructive pulmonary disease (COPD). The aim of our study was to prospectively evaluate for 2 years, blood and sputum eosinophils in COPD patients treated with bronchodilators only at recruitment. METHODS: COPD patients in stable condition treated with bronchodilators only underwent monitoring of lung function, blood and sputum eosinophils, exacerbations and comorbidities every 6 months for 2 years. ICS was added during follow-up when symptoms worsened. RESULTS: 63 COPD patients were enrolled: 53 were followed for 1 year, 41 for 2 years, 10 dropped-out. After 2 years, ICS was added in 12/41 patients (29%) without any statistically significant difference at time points considered. Blood and sputum eosinophils did not change during follow-up. Only FEV1/FVC at T0 was predictive of ICS addition during the 2 year-follow-up (OR:0.91; 95% CI: 0.83-0.99, p = 0.03). ICS addition did not impact on delta (T24-T0) FEV1, blood and sputum eosinophils and exacerbations. After 2 years, patients who received ICS had higher blood eosinophils than those in bronchodilator therapy (p = 0.042). Patients with history of ischemic heart disease increased blood eosinophils after 2 years [p = 0.03 for both percentage and counts]. CONCLUSIONS: Blood and sputum eosinophils remained stable during the 2 year follow-up and were not associated with worsened symptoms or exacerbations. Almost 30% of mild/moderate COPD patients in bronchodilator therapy at enrollment, received ICS for worsened symptoms in a 2 year-follow-up and only FEV1/FVC at T0 seems to predict this addition. History of ischemic heart disease seems to be associated with a progressive increase of blood eosinophils.

Unlocking the Long-Term Effectiveness of Benralizumab in Severe Eosinophilic Asthma: A Three-Year Real-Life Study.

Background: Benralizumab has been shown to restore good control of severe eosinophilic asthma (SEA). Robust data on benralizumab effectiveness over periods longer than 2 years are scarce. Methods: This retrospective multicentric study was conducted on 108 Italian SEA patients treated with benralizumab for up to 36 months. Partial and complete clinical remission (CR) were assessed. Data were analyzed with descriptive statistics or using linear, logistic, and negative binomial mixed-effect regression models. Results: At 36 months, benralizumab reduced the exacerbation rate by 89% and increased the forced expiratory volume in 1 second (FEV1) (+440 mL at 36 months, p < 0.0001). Benralizumab improved asthma control as well as sinonasal symptoms in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP). Up to 93.33% of patients either reduced or discontinued OCS; benralizumab also decreased ICS use and other asthma medications. Overall, 84.31% of patients achieved partial or complete CR. Conclusions: Benralizumab improved asthma and sinonasal outcomes up to 36 months. These findings support the potential of benralizumab to induce CR, emphasizing its role as a disease-modifying anti-asthmatic drug for the management of SEA. Further research is warranted to expand these findings by minimizing data loss and assessing benralizumab's long-term safety.

Predicting Response to In-Hospital Pulmonary Rehabilitation in Individuals Recovering From Exacerbations of Chronic Obstructive Pulmonary Disease / Predicción de la respuesta a la rehabilitación pulmonar hospitalaria en personas que se recuperan de exacerbaciones de la enfermedad pulmonar obstructiva crónica

Background: Predicting the response to pulmonary rehabilitation (PR) could be valuable in defining admission priorities. We aimed to investigate whether the response of individuals recovering from a COPD exacerbation (ECOPD) could be forecasted using machine learning approaches. Method: This multicenter, retrospective study recorded data on anthropometrics, demographics, physiological characteristics, post-PR changes in six-minute walking distance test (6MWT), Medical Research Council scale for dyspnea (MRC), Barthel Index dyspnea (BId), COPD assessment test (CAT) and proportion of participants reaching the minimal clinically important difference (MCID). The ability of multivariate approaches (linear regression, quantile regression, regression trees, and conditional inference trees) in predicting changes in each outcome measure has been assessed. Results: Individuals with lower baseline 6MWT, as well as those with less severe airway obstruction or admitted from acute care hospitals, exhibited greater improvements in 6MWT, whereas older as well as more dyspnoeic individuals had a lower forecasted improvement. Individuals with more severe CAT and dyspnea, and lower 6MWT had a greater potential improvement in CAT. More dyspnoeic individuals were also more likely to show improvement in BId and MRC. The Mean Absolute Error estimates of change prediction were 44.70m, 3.22 points, 5.35 points, and 0.32 points for 6MWT, CAT, BId, and MRC respectively. Sensitivity and specificity in discriminating individuals reaching the MCID of outcomes ranged from 61.78% to 98.99% and from 14.00% to 71.20%, respectively. Conclusion: While the assessed models were not entirely satisfactory, predictive equations derived from clinical practice data might help in forecasting the response to PR in individuals recovering from an ECOPD. Future larger studies will be essential to confirm the methodology, variables, and utility.(AU)

Dupilumab Efficacy on Asthma Functional, Inflammatory, and Patient-Reported Outcomes across Different Disease Phenotypes and Severity: A Real-Life Perspective.

Dupilumab is currently approved for the treatment of Type 2 severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). Few studies have specifically reported on dupilumab efficacy on asthma outcomes as a primary objective in a real-life setting, in patients with and without CRSwNP. Our study aimed to explore the efficacy of dupilumab on functional, inflammatory, and patient-reported outcomes in asthma patients across different disease phenotypes and severity, including mild-to-moderate asthma coexisting with CRSwNP. Data from 3, 6, and 12 months follow-up were analyzed. Asthma (FEV1%, Tiffeneau%, ACT, FeNO, oral steroid use, exacerbation rate, and blood eosinophilia) and polyposis (SNOT22, VAS, NPS) outcomes showed a rapid (3 months) and sustained (6 and 12 months) significant change from baseline, despite most of the patients achieving oral steroid withdrawal. According to the sensitivity analysis, the improvement was not conditioned by either the presence of polyposis or severity of asthma at baseline. Of note, even in the case of milder asthma forms, a significant further improvement was recorded during dupilumab treatment course. Our report provides short-, medium-, and long-term follow-up data on asthma outcomes across different diseases phenotypes and severity, contributing to the real-world evidence related to dupilumab efficacy on upper and lower airways T2 inflammation.

Predicting Response to In-Hospital Pulmonary Rehabilitation in Individuals Recovering From Exacerbations of Chronic Obstructive Pulmonary Disease.

BACKGROUND: Predicting the response to pulmonary rehabilitation (PR) could be valuable in defining admission priorities. We aimed to investigate whether the response of individuals recovering from a COPD exacerbation (ECOPD) could be forecasted using machine learning approaches. METHOD: This multicenter, retrospective study recorded data on anthropometrics, demographics, physiological characteristics, post-PR changes in six-minute walking distance test (6MWT), Medical Research Council scale for dyspnea (MRC), Barthel Index dyspnea (BId), COPD assessment test (CAT) and proportion of participants reaching the minimal clinically important difference (MCID). The ability of multivariate approaches (linear regression, quantile regression, regression trees, and conditional inference trees) in predicting changes in each outcome measure has been assessed. RESULTS: Individuals with lower baseline 6MWT, as well as those with less severe airway obstruction or admitted from acute care hospitals, exhibited greater improvements in 6MWT, whereas older as well as more dyspnoeic individuals had a lower forecasted improvement. Individuals with more severe CAT and dyspnea, and lower 6MWT had a greater potential improvement in CAT. More dyspnoeic individuals were also more likely to show improvement in BId and MRC. The Mean Absolute Error estimates of change prediction were 44.70m, 3.22 points, 5.35 points, and 0.32 points for 6MWT, CAT, BId, and MRC respectively. Sensitivity and specificity in discriminating individuals reaching the MCID of outcomes ranged from 61.78% to 98.99% and from 14.00% to 71.20%, respectively. CONCLUSION: While the assessed models were not entirely satisfactory, predictive equations derived from clinical practice data might help in forecasting the response to PR in individuals recovering from an ECOPD. Future larger studies will be essential to confirm the methodology, variables, and utility.

Pulmonary rehabilitation and risk of fall in elderly with chronic obstructive pulmonary disease.

BACKGROUND: Few data are available on the effects of pulmonary rehabilitation (PR) on risk of fall in over 80 individuals with chronic obstructive pulmonary disease (COPD). We investigated the effectiveness of PR on the risk of fall in older as compared to younger than 80 individuals. METHODS: Parallel-group retrospective exploratory study of individuals undergone in-hospital PR. The risk of fall was defined as a gait speed ≤0.8 m/s (primary outcome). Outcome measures (exercise capacity, physical performance, symptoms, and health status) were also assessed. RESULTS: As compared to younger, individuals over 80 suffered from more severe symptoms, a reduction in physical performance and in exercise capacity and greater risk of fall (P=0.0001). The proportion of participants at risk of fall increased with age, and after PR decreased significantly without any significant difference between age groups. However, 53.4% of older individuals were still at risk of fall, as compared to 17.5% of those under 80 (P=0.0001). After PR, both populations had improved outcomes measures, without any significant between group differences. CONCLUSIONS: In individuals with COPD pulmonary rehabilitation reduced the risk of fall, while improving outcome measures independent of age, however, more than 50% of those over 80 were still at risk of fall. The pulmonary rehabilitation programs for individuals over 80 should include strategies effective in reducing the risk of fall.

Brittle Asthma: Still on Board?

(1) Background: "Brittle Asthma" was considered an asthma clinical phenotype and deemed to be life-threatening in the early 2000s; then, this definition disappeared. The purpose of this review is to examine what has historically been referred to as this term and see whether it may be applied to modern clinical practice, thus acquiring fresh relevance and meaning. (2) Methods: A non-systematic search of the literature was conducted using both MeSH and free-text phrases. No limitations on the research design or type of publication were applied. (3) Results: Reliable data regarding "Brittle Asthma" are lacking due to the paucity of current data and the few studies available. After a few years of reworking, it was divided into two sub-classes: one characterized by a wide PEF variability despite high-dose therapy and the other by sudden acute attacks in otherwise apparently normal airway functions or well-controlled asthma. Their characteristics were hardly defined because of their low prevalence. Data regarding risk factors, atopy, mechanisms, and treatments were analyzed. (4) Conclusions: Over time, different terminology has been introduced to define asthma severity and control. It would be worth investigating whether the term "Brittle Asthma" previously used may be helpful to find new hints to stratify patients and improve disease management.

European Respiratory Society short guidelines for the use of as-needed ICS/formoterol in mild asthma

Recent clinical trials of as-needed fixed-dose combination of inhaled corticosteroid (ICS)/formoterol have provided new evidence that may warrant a reconsideration of current practice. A Task Force was set up by the European Respiratory Society to provide evidence-based recommendations on the use of as-needed ICS/formoterol as treatment for mild asthma. The Task Force defined two questions that were assessed using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. The Task Force utilised the outcomes to develop recommendations for a pragmatic guideline for everyday clinical practice. The Task Force suggests that adults with mild asthma use as-needed ICS/formoterol instead of regular ICS maintenance treatment plus as-needed short-acting ß2-antagonist (SABA) and that adolescents with mild asthma use either as-needed ICS/formoterol or ICS maintenance treatment plus as-needed SABA (conditional recommendation; low certainty of evidence). The recommendation for adults places a relatively higher value on the reduction of systemic corticosteroid use and the outcomes related to exacerbations, and a relatively lower value on the small differences in asthma control. Either treatment option is suggested for adolescent patients as the balance is very close and data more limited. The Task Force recommends that adult and adolescent patients with mild asthma use as-needed ICS/formoterol instead of as-needed SABA (strong recommendation; low certainty of evidence). This recommendation is based on the benefit of as-needed ICS/formoterol in mild asthma on several outcomes and the risks related to as-needed SABA in the absence of anti-inflammatory treatment. The implementation of this recommendation is hampered in countries (including European Union countries) where as-needed ICS/formoterol is not approved for mild asthma.

European Respiratory Society short guidelines for the use of as-needed ICS/formoterol in mild asthma.

Recent clinical trials of as-needed fixed-dose combination of inhaled corticosteroid (ICS)/formoterol have provided new evidence that may warrant a reconsideration of current practice. A Task Force was set up by the European Respiratory Society to provide evidence-based recommendations on the use of as-needed ICS/formoterol as treatment for mild asthma. The Task Force defined two questions that were assessed using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. The Task Force utilised the outcomes to develop recommendations for a pragmatic guideline for everyday clinical practice. The Task Force suggests that adults with mild asthma use as-needed ICS/formoterol instead of regular ICS maintenance treatment plus as-needed short-acting ß2-antagonist (SABA) and that adolescents with mild asthma use either as-needed ICS/formoterol or ICS maintenance treatment plus as-needed SABA (conditional recommendation; low certainty of evidence). The recommendation for adults places a relatively higher value on the reduction of systemic corticosteroid use and the outcomes related to exacerbations, and a relatively lower value on the small differences in asthma control. Either treatment option is suggested for adolescent patients as the balance is very close and data more limited. The Task Force recommends that adult and adolescent patients with mild asthma use as-needed ICS/formoterol instead of as-needed SABA (strong recommendation; low certainty of evidence). This recommendation is based on the benefit of as-needed ICS/formoterol in mild asthma on several outcomes and the risks related to as-needed SABA in the absence of anti-inflammatory treatment. The implementation of this recommendation is hampered in countries (including European Union countries) where as-needed ICS/formoterol is not approved for mild asthma.

Asthma control conundrum in clinical practice - Data from a two-stage Delphi survey and literature review.

Definitions and measures of asthma control used in clinical trials and practice often vary, as highlighted in the manuscript, "Is asthma control more than just an absence of symptoms? An expert consensus statement". Furthermore, the authors discussed differences between patients and healthcare professionals (HCPs) in terms of understanding and managing asthma. Given these disparities, there is a need for consensus regarding what constitutes well-controlled asthma and, especially, how best it can be measured and recorded. In the current work, we describe our data and provide more detail on the methodology from a two-stage Delphi survey and a structured literature review, which were designed to reach a consensus definition of asthma control and alleviate misalignments between patients and HCPs. Survey data were collected using a two-stage Delphi technique; a method used to collate expert opinions over a series of sequential questionnaires to reach a consensus. The collated Delphi survey data were compared with results from a comprehensive, structured literature review of 216 publications, to assess if there was a correlation between existing guidance and measures of asthma control used in clinical trials and standard clinical practice. In order to collate and interpret findings from the Delphi survey, responses from 82 panelists (73 HCPs and 9 authors) were qualitatively analyzed, quantitatively categorized, and presented as percentages or counts in Excel databases, which are detailed in the current work. Searches conducted using PubMed and Cochrane identified 664 manuscripts, and Embase was used to identify 89 congress abstracts. After applying a stringent screening method using predefined key words, the structured literature review consisted of 185 peer-reviewed manuscripts and 31 congress abstracts, and assessed existing guidance and measures of asthma control used in clinical trials. In this publication, we provide further insight into the predefined keywords, search strings, and strategy applied to identify manuscripts and congress abstracts for inclusion/exclusion, and detail methods for data extraction. Together, the data from the Delphi survey and structured literature review aimed to provide greater insights into challenges and approaches in achieving asthma control in clinical practice, with the potential for results to be used to guide a universally accepted definition and measure of asthma control that can be used and understood by patients, HCPs, and researchers. Qualitative and quantitative methodology and analysis from the Delphi survey and literature review search strategy can potentially be used to identify disparities and explore expert opinion and relevant literature in other therapeutic areas to guide a consensus where disparities exist.

Symptom versus exacerbation control: an evolution in GINA guidelines?

The article traces the concept of asthma control within GINA guidelines over the past 25 years. In the first 15 years after 1995, the main objective of asthma management was to obtain the control of all clinical and functional characteristics of asthma. A landmark study (GOAL) showed for the first time that a good control of asthma is a reasonable outcome that can be achieved in a large proportion of asthmatics with a regular appropriate treatment. In the following years, more emphasis was placed on the role of exacerbations as critical manifestations of poor asthma control, whose frequency is associated with excessive FEV1 decline and increased risk of death. Accordingly, the 2014 GINA report makes a clear distinction between the control of the day-by-day symptoms and the reduction in the risk of severe exacerbations, stating that both conditions should be obtained. The 2019 update included a significant change in the management of mild asthma, prioritizing the prevention of exacerbations to that of mild symptoms. This view was repeated in the 2021 update, where the prevention of exacerbations, together with an acceptable symptom control with a minimal use of rescue medication, appeared to be the real main goal of asthma management. While a discrepancy between current symptoms and exacerbations may be present in mild asthma, a significant relationship between these two features is observed in moderate-severe asthma: a persistent poor symptom control is a major risk factor for exacerbations, whereas achieving symptom control through regular treatment is associated with a reduction in exacerbation rate. Thus, the opinion that frequent symptoms are not important in the absence of acute exacerbations should be discouraged, whereas education of patients to a good symptom perception and to improve adherence to regular treatment should be implemented. Furthermore, the persistence of risk factors, such as increased airway inflammation, even in a patient with minor daily symptoms, should be considered for optimizing treatment.

Complications of SARS-CoV-2 Infection During Cardiac Rehabilitation: A Case Series.

INTRODUCTION: Vaccination strongly reduces the risk of hospitalization and death due to coronavirus disease 2019 (COVID-19). However, the severity of the acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and the degree of protection exerted over time by vaccination remains to be fully elucidated among hospitalized comorbid and vulnerable patients with SARS-CoV-2 infection. METHODS: We report a case series of nine hospitalized vulnerable patients who developed a SARS-CoV-2 infection during a cardiac rehabilitation inpatient program. RESULTS: Age ranged from 50 to 81 years. All but one patient had received at least three doses of anti-COVID-19 vaccine more than 4 months before the cardiac event. Indications for cardiac rehabilitation included acute coronary syndromes, congestive heart failure, heart valve surgery, and coronary artery bypass graft. After the confirmed diagnosis of SARS-CoV-2 infection, all patients developed symptoms. Eight patients developed at least one SARS-CoV-2-related complication, including a significant increase in high-sensitivity troponin I levels, new-onset hypoxemia, persistent atrial fibrillation, non-sustained ventricular tachycardia and recurrent sinus arrest, pericardial effusion, and a persistent increase in blood pressure. CONCLUSION: Almost all patients developed complications which, however, did not evolve towards more severe expressions of the disease. These data suggest that even in this new phase of the pandemic, vaccination may exert a potential role to reduce the risk of progression towards more severe disease of SARS-CoV-2 infection in vulnerable patients with cardiovascular comorbidities.

Thyroid hormones modifications among COVID-19 patients undergoing pulmonary rehabilitation.

Introduction: Patients with severe COVID-19 often experience long-lasting disabilities that can improve after pulmonary rehabilitation. Moreover patients with severe COVID-19 display thyroid function alterations due to a non-thyroidal illness syndrome (NTIS). The aim of our study was to evaluate thyroid function parameters among patients hospitalized for COVID-19 who were eligible or not to respiratory rehabilitation and their modifications during follow-up. Materials and methods: Post-COVID-19 patients referred to a Respiratory Rehabilitation Unit were evaluated. Outpatients, not candidate for rehabilitation, were enrolled as Control group. Patients who had completed a 4-week-rehabilitation program were enrolled as Rehabilitation Group. All patients were evaluated at T0 (4 weeks after the discharge home in Control Group and after completion of rehabilitation in Rehabilitation Group) and at T1 (3 months after T0). Results: The final study group included 39 patients (20 in the Rehabilitation group and 19 in the Control group). Patients in the Rehabilitation Group had more frequently received invasive or non-invasive ventilation, had a longer length-of-stay in referring hospitals, had a higher number of comorbidities and displayed a worse performance at 6-minute-walking-test (6MWT) and Short-Physical-Performance-Battery-test (SPPB). FT3 values were lower at T0 in the Rehabilitation Group, while TSH and FT4 values were similar in the two groups. While no significant modifications in thyroid-function-parameters were observed in the Control Group, a significant increase in FT3 value was observed in the Rehabilitation Group at T1. Participants of both groups had improved the results of 6MWT at T1, while SPPB values improved only in the Rehabilitation Group. Conclusions: COVID-19 patients after pulmonary rehabilitation experience an increase in FT3 values during follow-up, paralleled with an amelioration of functional capabilities.

Effect of Pulmonary Rehabilitation on COPD Assessment Test Items in Individuals Classified as GOLD Group E.

BACKGROUND: A new Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification has been proposed, based also on COPD Assessment Test (CAT). OBJECTIVES: The aim of this large, multicenter, retrospective study was to determine the impact of pulmonary rehabilitation (PR) on CAT items in individuals with COPD, GOLD group E, recovering from an exacerbation (ECOPD). As secondary aims, we evaluated whether gender, associated chronic respiratory failure (CRF), and age might influence results. METHODS: Data of 2,213 individuals with available paired pre- and post-PR CAT were analyzed. Other common outcome measures were also assessed. RESULTS: After PR, total CAT improved from 20.8 ± 7.8 to 12.4 ± 6.9 (p = 0.000), and 1,911 individuals (86.4%) reached the minimal clinically important difference (MCID). All CAT items improved significantly without any significant difference among them. However, item "confidence with disease" improved significantly more in males than in females (p = 0.009). Total CAT and six out of eight items improved significantly more in individuals with CRF than in those without (all p < 0.001). Total CAT and three items improved significantly more in younger than in older individuals (p = 0.023). Only presence of CRF was significantly associated with the probability of improving total CAT more than the MCID. CONCLUSION: In individuals with COPD, GOLD group E, recovering from ECOPD, PR improves all CAT items; however, gender, associated CRF and age may influence the effect size, suggesting the need to evaluate all items in addition to total CAT score.

Bacterial load and related innate immune response in the bronchi of rapid decliners with chronic obstructive pulmonary disease.

BACKGROUND: Characterization of COPD patients with rapid lung functional decline is of interest for prognostic and therapeutic reasons. We recently reported an impaired humoral immune response in rapid decliners. OBJECTIVE: To determine the microbiota associated to markers of innate immune host response in COPD patients with rapid lung functional decline. METHODS: In COPD patients monitored for at least 3 years (mean ± SD: 5.8 ± 3 years) for lung functional decline, the microbiota and related markers of immune response was measured in bronchial biopsies of patients with different lung functional decline (rate of FEV1% lung functional decline: no decline FEV1%, ≤20 ml/year n = 21, slow decline FEV1%, >20 ≤ 70 ml/year, n = 14 and rapid decline FEV1%, >70 ml/year, n = 15) using qPCR for microbiota and immunohistochemistry for cell-receptors and inflammatory markers. MAIN RESULTS: Pseudomonas aeruginosa and Streptococcus pneumoniae were increased in rapid decliners vs slow decliners, S. pneumoniae was also increased compared to non decliners. In all patients, S. pneumoniae (copies/ml) positively correlated with pack-years consumption, lung function decline, TLR4, NOD1, NOD2 scored in bronchial epithelium and NOD1/mm2 in lamina propria. CONCLUSION: These data show an imbalance of microbiota components in rapid decliners which is associated to the expression of the related cell-receptors in all COPD patients. These findings may help in the prognostic stratification and treatment of patients.

mRNA Metabolism and Hypertension.

Hypertension is the most frequent cardiovascular risk factor all over the world. It remains a leading contributor to the risk of cardiovascular events and death. In the year 2015, about 1.5 billion of adult people worldwide had hypertension (as defined by office systolic blood pressure ≥ 140 mmHg or office diastolic blood pressure ≥ 90 mmHg). Moreover, the number of hypertensive patients with age ranging from 30 to 79 years doubled in the last 30 years (from 317 million men and 331 million women in the year 1990 to 652 million men and 626 million women in 2019) despite stable age-standardized prevalence worldwide. Despite such impressive growth, the proportion of controlled hypertension is very low. A better understanding of the pathogenesis of hypertension may contribute to the development of innovative therapeutic strategies. In this context, alterations of the messenger RNA metabolism have been recently evaluated as contributors to the pathogenesis of hypertension, and pharmacological modulation of RNA metabolism is under investigation as potential and novel therapeutic armamentarium in hypertension.

Airflow grades, outcome measures and response to pulmonary rehabilitation in individuals after an exacerbation of severe chronic obstructive pulmonary disease.

BACKGROUND: Individuals with COPD may be staged according to symptoms and exacerbation history (GOLD groups: A-D) and on airflow obstruction (GOLD grades: 1-4). Guidelines recommend pulmonary rehabilitation (PR) for these individuals, including those recovering from an exacerbation (ECOPD) OBJECTIVE: To evaluate whether in individuals with clinically severe COPD, recovering from an ECOPD, the effect size of an in-hospital PR program would be affected by airflow severity grades and assessed outcome measures. METHODS: Retrospective, multicentre study. Participants were compared according to different GOLD airflow grades. In addition to the MRC dyspnoea scale, six-minute walking distance test and COPD assessment test (CAT), Barthel dyspnoea index (Bid), and Short Physical Performance Battery (SPPB) were assessed, evaluating the proportion of individuals reaching the minimum clinically important difference (MCID) (responders). RESULTS: Data of 479 individuals, completing the program were evaluated. Most of the participants were allocated in GOLD grades 4, (57.6%) and 3 (22.1%). All outcome measures significantly improved after PR (p < 0.05), without any significant difference in the proportion of responders in any measure. CONCLUSIONS: in individuals with severe COPD, recovering from ECOPD the success rate of PR does not depend on airflow severity, or outcome measure assessed. In addition to the most used outcome measures, also Bid and SPPB are sensitive to PR.

The spike effect of acute respiratory syndrome coronavirus 2 and coronavirus disease 2019 vaccines on blood pressure.

Among the various comorbidities potentially worsening the clinical outcome in patients hospitalized for the acute respiratory syndrome coronavirus-2 (SARS-CoV-2), hypertension is one of the most prevalent. However, the basic mechanisms underlying the development of severe forms of coronavirus disease 2019 (COVID-19) among hypertensive patients remain undefined and the direct association of hypertension with outcome in COVID-19 is still a field of debate. Experimental and clinical data suggest that SARS-CoV-2 infection promotes a rise in blood pressure (BP) during the acute phase of infection. Acute increase in BP and high in-hospital BP variability may be tied with acute organ damage and a worse outcome in patients hospitalized for COVID-19. In this context, the failure of the counter-regulatory renin-angiotensin-system (RAS) axis is a potentially relevant mechanism involved in the raise in BP. It is well recognized that the efficient binding of the Spike (S) protein to angiotensin converting enzyme 2 (ACE2) receptors mediates the virus entry into cells. Internalization of ACE2, downregulation and malfunction predominantly due to viral occupation, dysregulates the protective RAS axis with increased generation and activity of angiotensin (Ang) II and reduced formation of Ang1,7. Thus, the imbalance between Ang II and Ang1-7 can directly contribute to excessively rise BP in the acute phase of SARS-CoV-2 infection. A similar mechanism has been postulated to explain the raise in BP following COVID-19 vaccination ("Spike Effect" similar to that observed during the infection of SARS-CoV-2). S proteins produced upon vaccination have the native-like mimicry of SARS-CoV-2 S protein's receptor binding functionality and prefusion structure and free-floating S proteins released by the destroyed cells previously targeted by vaccines may interact with ACE2 of other cells, thereby promoting ACE2 internalization and degradation, and loss of ACE2 activities.