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.

Genetics of Hypertension: From Monogenic Analysis to GETomics.

Arterial hypertension is the most frequent cardiovascular risk factor all over the world, and it is one of the leading drivers of the risk of cardiovascular events and death. It is a complex trait influenced by heritable and environmental factors. To date, the World Health Organization estimates that 1.28 billion adults aged 30-79 years worldwide have arterial hypertension (defined by European guidelines as office systolic blood pressure ≥ 140 mmHg or office diastolic blood pressure ≥ 90 mmHg), and 7.1 million die from this disease. The molecular genetic basis of primary arterial hypertension is the subject of intense research and has recently yielded remarkable progress. In this review, we will discuss the genetics of arterial hypertension. Recent studies have identified over 900 independent loci associated with blood pressure regulation across the genome. Comprehending these mechanisms not only could shed light on the pathogenesis of the disease but also hold the potential for assessing the risk of developing arterial hypertension in the future. In addition, these findings may pave the way for novel drug development and personalized therapeutic strategies.

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.

Evaluation of physical activity before and after respiratory rehabilitation in normal weight individuals with asthma: a feasibility study.

Background: Individuals with asthma spend less time engaging in physical activity compared to the general population. Increasing physical activity has become a patient-centered goal for the treatment of treatable traits of individuals with asthma. There are data showing the possible effects of a pulmonary rehabilitation program on physical activity in obese individuals with asthma but not in normal-weight asthmatics. The objective of this feasibility study is to estimate the number of daily steps and time spent on activity in normal-weight individuals with asthma, measured before and after a pulmonary rehabilitation program. Methods: Normal-weight individuals with moderate to severe asthma were evaluated. The individuals measured their daily steps with an accelerometer for 5 days before and after a pulmonary rehabilitation program. The study was registered on ClinicalTrials.gov: NCT05486689. Results: In total, 17 participants were enrolled; one dropout and data on the time in activity of two individuals are missing due to a software error during the download. Data from 16 patients were analyzed. The median number of steps/day at baseline was 5,578 (25th, 75th percentiles = 4,874, 9,685) while the median activity time was 214 min (25th, 75th percentiles = 165, 239). After the rehabilitation program, the number of daily steps increased by a median value of 472 (p-value = 0.561) and the time in activity reduced by 17 min (p-value = 0.357). We also found a significant difference in quality of life, muscle strength, and exercise capacity. Conclusions: The results of this study make it possible to calculate the sample size of future studies whose main outcome is daily steps in normal-weight individuals with asthma. The difficulties encountered in downloading time in activity data do not allow the same for this outcome. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT05486689.

Global burden of new-onset hypertension associated with severe acute respiratory syndrome coronavirus 2 infection.

Several reports documented a specific effect of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on blood pressure (BP), during and after the acute phase of infection. Clinical studies demonstrated that coronavirus disease 2019 (COVID-19) is associated with an increased risk of a persistent increase in BP requiring a new or intensified anti-hypertensive treatment during hospitalization. The picture is further complicated by the evidence from large databases showing an increased risk of new-onset hypertension in COVID-19 survivors on the long term. To further elucidate the epidemiological burden of this phenomenon, we performed a pooled analysis of 4 studies reporting crude incidence rates of new-onset hypertension among COVID-19 patients and contemporary controls. Overall, COVID-19 was associated with a 65% increased risk of new-onset hypertension when compared with controls (p<0.0001); furthermore, incidence of new-onset hypertension was 9% and 5% among COVID-19 patients and controls, respectively. In both the acute phase and recovery from infection, the interaction between spike proteins of SARS-CoV-2 and angiotensin converting enzyme 2 (ACE2) receptors remain the most plausible mechanism explaining the raise in BP (ranking new onset hypertension as one of the most prevalent cardiovascular sequelae of COVID-19). In this area of research, it is worth to mention that new variants of SARS-CoV-2 exhibit specific mutations in the spike protein that promotes entry into viral cells via ACE2. Thus, the enhanced spike affinity for ACE2 of new variants has the potential to increase the risk of new-onset hypertension when compared with the original Wuhan strain.

Sex-related differences in non-ischemic myocardial injury in the emergency department: A real-world perspective.

BACKGROUND: Myocardial injury is associated with adverse outcomes. No data are reported about sex differences in incidence and factors associated with myocardial injury in an emergency department (ED) setting from a real-world perspective. We aimed to assess whether sex plays a major role in the diagnosis of myocardial injury in the ED. METHODS: In this subanalysis of a retrospective study, patients presenting at the ED with at least one high-sensitivity cardiac troponin T (hs-cTnT) value and without acute coronary syndromes diagnosis were compared. RESULTS: 31,383 patients were admitted to the ED, 4660 had one hs-cTnT value, and 3937 were enrolled: 1943 females (49.4%) and 1994 males (50.6%). The diagnosis of myocardial injury was higher among men (36.8% vs. 32.9%, p < 0.01). Male sex was independently associated with myocardial injury. An older age, an elevated NT-proB-type Natriuretic Peptide and a lower estimated glomerular filtrate rate were independently associated with myocardial injury in both sexes. CONCLUSIONS: In the ED, from a real-world perspective, myocardial injury occurred more frequently in males, and it was associated with older age and the presence of cardiac, lung, and kidney disease but not higher hs-cTnT values.

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.

Interpretation of Ambulatory Blood Pressure Monitoring for Risk Stratification in Hypertensive Patients: The 'Ambulatory Does Prediction Valid (ADPV)' Approach.

Several outcome-based prospective investigations have provided solid data which support the prognostic value of 24 h ambulatory blood pressure over and beyond cardiovascular traditional risk factors. Average 24 h, daytime, and nighttime blood pressures are the principal components of the ambulatory blood pressure profile that have improved cardiovascular risk stratification beyond traditional risk factors. Furthermore, several additional ambulatory blood pressure measures have been investigated. The correct interpretation in clinical practice of ambulatory blood pressure monitoring needs a standardization of methods. Several algorithms for its clinical use have been proposed. Implementation of the results of ambulatory blood pressure monitoring in the management of individual subjects with the aim of improving risk stratification is challenging. We suggest that clinicians should focus attention on ambulatory blood pressure components which have been proven to act as the main independent predictors of outcome (average 24 h, daytime, and nighttime blood pressure, pulse pressure, dipping status, BP variability).

Rethinking the Role of the Renin-Angiotensin System in the Pandemic Era of SARS-CoV-2.

After assessing the levels of spread and severity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, academic literature focused on the pathophysiology of coronavirus disease 2019 (COVID-19) [...].

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.

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.

Analysis of Patients with Asthma and Mixed Granulocytic Inflammatory Pattern in Sputum.

BACKGROUND: Patients with asthma usually present airway inflammation classified as eosinophilic, neutrophilic, mixed granulocytic, and paucigranulocytic pattern according to sputum inflammatory cells. OBJECTIVE: The aim of the study was to analyze clinical and biological characteristics of patients with asthma and mixed granulocytic pattern in comparison with the other groups. METHODS: Induced sputum was used to assess airway inflammation; lung function was evaluated as well as blood leukocytes and disease control. History of comorbidities was collected. RESULTS: We retrospectively analyzed 231 subjects with asthma; patients with mixed granulocytic pattern were more frequently male compared with paucigranulocytic subjects, older than eosinophilic and paucigranulocytic patients with increased number and vitality of sputum cells compared to eosinophilic and paucigranulocytic patients and higher cumulative illness rating score, related to increased age. Smoking history, age of disease onset, and ICS treatment were not associated with higher mixed granulocytic pattern occurrence. Subjects with neutrophilic inflammation (mixed granulocytic and neutrophilic patterns considered altogether) were more frequently obese. In subjects under 67 years of age (median of the enrolled subjects), arterial hypertension was the only comorbidity more frequent in mixed granulocytic than in the other groups. 137/231 subjects were re-valuated during follow-up. Lung function of patients with mixed granulocytic, neutrophilic, and paucigranulocytic patterns improved less than that of eosinophilic patients. CONCLUSION: Aging and presence of comorbidities, in particular obesity and hypertension, are characteristics of patients with asthma and mixed granulocytic pattern. They could respond less well to treatment than eosinophilic patients.