Co-infection of SARS-CoV-2 with Chlamydia or Mycoplasma pneumoniae: a case series and review of the literature.

INTRODUCTION: The novel coronavirus SARS-CoV-2 has spread all over the world causing a global pandemic and representing a great medical challenge. Nowadays, there is limited knowledge on the rate of co-infections with other respiratory pathogens, with viral co-infection being the most representative agents. Co-infection with Mycoplasma pneumoniae has been described both in adults and pediatrics whereas only two cases of Chlamydia pneumoniae have been reported in a large US study so far. METHODS: In the present report, we describe a series of seven patients where co-infection with C. pneumoniae (n = 5) or M. pneumoniae (n = 2) and SARS-CoV-2 was detected in a large teaching hospital in Rome. RESULTS AND CONCLUSION: An extensive review of the updated literature regarding the co-infection between SARS-CoV-2 and these atypical pathogens is also performed.

"Metabolic and cardiovascular response to exercise in patients with type 1 diabetes".

PURPOSE: Physical activity is an effective therapeutic tool for cardiovascular risk prevention. However, exercise aerobic capacity of patients with type 1 diabetes (T1DM) has not been thoroughly investigated. Aim of the present study is to evaluate exercise aerobic capacity in patients with T1DM compared to a normal control population. METHODS: This observational study included 17 T1DM patients and 17 matched healthy volunteers. Cardiopulmonary exercise test (CPET) was conducted on an electronically-braked cycle ergometer. Blood samples were collected for evaluation of glycemia and lactate levels. RESULTS: Mean oxygen uptake at peak exercise (V'O2,peak) was significantly lower in T1DM subjects (V'O2,peak T1DM 2200 ± 132ml/min vs V'O2,peak Healthy subjects of 2659 ± 120 ml/min p = 0.035). Cardiovascular response analysis did not show statistically significant differences. Respiratory exchange ratio (RER) was significantly higher in healthy subjects at peak exercise and at the first minute of recovery (p = 0.022, p = 0.024). Peak exercise lactate levels were significantly higher in healthy subjects. There was no statistical correlation between CPET results and diabetes-related parameters. CONCLUSIONS: Patients affected by T1DM have a worse exercise tolerance than normal subjects. The two groups differed by RER which can be greatly influenced by the substrate type utilized to produce energy. Because of the impaired carbohydrate utilization, T1DM subjects may use a larger amount of lipid substrates, such hypothesis could be strengthened by the lower lactate levels found in T1DM group at peak exercise. The lack of correlation between exercise tolerance and disease-related variables suggests that the alterations found could be independent from the glycemic levels.

Intrarenal hemodynamic and oxidative stress in patients with obstructive sleep apnea syndrome.

BACKGROUND: Oxygen desaturation and reoxygenation, related to intermittent hypoxia cycles due to upper airway obstruction, are major pathophysiologic features of obstructive sleep apnea syndrome (OSAS) and are thought to be responsible for an increased risk of cardiovascular diseases. Continuous positive airway pressure (CPAP) is therefore considered the gold standard in the management of OSAS. Further data demonstrated a high prevalence of OSAS in patients with altered renal function despite the underlying pathophysiological mechanisms that have not been clarified. This study aims to provide evidence on the reported high prevalence of endothelial dysfunction and alterations of the intrarenal hemodynamic in patients affected by OSAS. Furthermore, we evaluated the effect of a CPAP therapy on these endpoints. METHODS: Twenty patients were enrolled in a prospective study and underwent ultrasound examination to assess endothelial dysfunction, by collecting brachial flow-mediated dilation (FMD) and intrarenal artery stiffness, pre- and post a 30-day treatment with CPAP. RESULTS: Endothelial dysfunction and intrarenal artery stiffness significantly improved in all patients after a month of CPAP. In particular, we observed a significant reduction in the renal resistance index (RI) (p < 0.001) and systolic/diastolic ratio (S/D) ratio (p < 0.001) and a significant increase of FMD (p < 0.001). The apnea-hypopnea index (AHI) showed a negative correlation with Δ FMD (p < 0.05, r = -0.46). Conversely, a positive correlation exists between Δ RI and the oxygen desaturation index (ODI) (specificare la sigla) (p < 0.05, r = 0.46). CONCLUSIONS: Our study firstly showed a significant effect of CPAP on renal perfusion and endothelial function in OSAS patients without concomitant cardiovascular comorbidities.

Exercise tolerance in systemic sclerosis patients without pulmonary impairment: correlation with clinical variables.

OBJECTIVES: In systemic sclerosis (SSc) patients pulmonary vasculopathy (PV) is present in the early stage of disease and impairs dilation of affected pulmonary blood vessels, impeding pulmonary blood flow during exercise. Abnormal gas exchange findings were early investigated by cardiopulmonary exercise test (CPET). METHODS: A total of 34 female and 6 male [median age 49 (20-63) years] SSc patients with normal chest imaging and pulmonary function tests were enrolled. Twenty healthy controls age and sex matched [16 female and 4 male; median age 51 (35-73) years] were also recruited. All subjects underwent a full clinical examination, including a nailfold video capillaros copy (NVC). An incremental symptom-limited CPET was performed with estimation of minute ventilation (VE), workload (WR), peak oxygen uptake (pVO22), and ventilatory efficiency (VE/VCO2 slope). RESULTS: A reduced exercise tolerance (pVO2<80% of predicted) was documented in 18 out of 40 subjects (45%). Six out of 18 patients with a reduced exercise tolerance showed indirect signs of ventilation perfusion mismatch (VE/ VCO2 slope >34). Patients with digital ulcers (DUs) history showed VE/VCO2slope values significantly higher [31.4 (18-39.6)] than in patients without DUs history [26.9 (22-29.4)] (p<0.0001). VE/VCO2slope values also significantly differed between the three capillaroscopic groups: early [26.3 (18-29.4)], active [28 (26.8-39.6)], and late [32.9 (22.4-39)] (p<0.0001). A positive correlation was found between the VE/ VCO2slope and both Disease Activity Index (p<0.0001, r=0.59) and Disease Severity Scale (p<0.0001, r=0.73). CONCLUSIONS: In SSc patients without evidence of pulmonary and cardiac involvement, CPET might be useful in disclosing an early PV.

When GETomics meets aging and exercise in COPD.

The term GETomics has been recently proposed to illustrate that human health and disease are actually the final outcome of many dynamic, interacting and cumulative gene (G) - environment (E) interactions that occur through the lifetime (T) of the individual. According to this new paradigm, the final outcome of any GxE interactions depends on both the age of the individual at which such GxE interaction occurs as well as on the previous, cumulative history of previous GxE interactions through the induction of epigenetic changes and immune memory (both lasting overtime). Following this conceptual approach, our understanding of the pathogenesis of chronic obstructive pulmonary disease (COPD) has changed dramatically. Traditionally believed to be a self-inflicted disease induced by tobacco smoking occurring in older men and characterized by an accelerated decline of lung function with age, now we understand that there are many other risk factors associated with COPD, that it occurs also in females and young individuals, that there are different lung function trajectories through life, and that COPD is not always characterized by accelerated lung function decline. In this paper we discuss how a GETomics approach to COPD may open new perspectives to better understand its relationship with exercise limitation and the ageing process.

COVID-19 and kidney: role of SARS-CoV-2 infection in the induction of renal damage.

OBJECTIVE: SARS-CoV-2 causes acute respiratory disease, interstitial and alveolar pneumonia, and involves numerous organs and systems such as the kidney, heart, digestive tract, blood, and nervous system. We aimed to evaluate the incidence of renal manifestations in patients diagnosed with COVID-19 infection. PATIENTS AND METHODS: We performed a monocentric, cross-sectional, observational study, conducted on 114 patients with SARS-CoV-2. Clinical and laboratory parameters [renal function, serum electrolytes, inflammatory state, blood gas analysis, Interleukin 6 (IL-6) and urinalysis] were evaluated. The same values were checked out after two months (T1), however after negativization. RESULTS: We enrolled 114 patients (59 males) with a mean age of 63.8 ± 13.9 years. We found hematuria in 48 patients (55.8%), proteinuria in 33 patients (38.4%), leukocyturia in 61 patients (70.9%), acute kidney injury (AKI) in 28 patients (24.6%), AKI in chronic kidney disease (CKD) in 24 patients (21.1%). Moreover, we found a significant increase of inflammatory indexes as C Reactive Protein (CRP), lactic dehydrogenase (LDH), alpha 1 and alpha 2 globulins with a subsequent reduction at T1 (p = 0.016, p < 0.001, p = 0.005, p = 0.007; respectively). Hemoglobin and erythrocyte values significantly decreased (p < 0.001, p = 0.003, respectively), and we found lymphopenia (p < 0.001). Also, we found elevated levels of the D-Dimer (p < 0.001) and a significant increase in the International Normalized Ratio (INR) (p = 0.038). We also showed a significant improvement after negativization in oxygen partial pressure (p = 0.001) and oxygen saturation (p < 0.001) and a significant increase in pH (p = 0.018) and bicarbonate concentration (p = 0.042). Moreover, we found a significant increase in IL-6 (p = 0.004). Also, we reported mild hyponatremia and hypokalemia with subsequent significant recovery (p < 0.001, p < 0.001, respectively) and mild hypochloremia with a recovery to the limits of statistical significance (p = 0.053). At the entrance, we found an increase in serum glucose with a significant reduction during recovery (p < 0.001). CONCLUSIONS: The prevalence of AKI and/or CKD and/or abnormal urinalysis in patients diagnosed with COVID-19 on admission seems to be high and appears as a negative prognostic factor. Urinalysis appears to be very useful in unveiling the potential kidney impairment of COVID-19 patients; therefore, urinalysis could be used to reflect and predict the disease severity. We also recommend a careful evaluation of metabolic alterations, inflammatory states, and electrolytic disorders in COVID-19 patients.

Circulating endothelial progenitor cells and chronic pulmonary diseases.

Circulating endothelial progenitor cells (EPCs) are bone marrow-derived cells that contribute to vascular healing and remodelling under physiological and pathological conditions. Although controversies exist regarding the definition and origin of EPCs, it has been widely demonstrated that they are involved in several diseases and that they have therapeutic implications. Chronic obstructive pulmonary disease (COPD) is characterised by airflow limitation that is not fully reversible, associated with abnormalities of airways (bronchitis) and parenchyma (emphysema), reduced exercise tolerance and systemic inflammation. Growing evidence has also suggested that endothelial dysfunction may play a role in COPD. Although it is not clear whether endothelial dysfunction represents a cause or a consequence of COPD, several studies have highlighted the importance of EPCs in this disease, suggesting that the bone marrow could be a novel target of COPD. The present review summarises the role of EPCs in pulmonary diseases, with particular emphasis on COPD. The aim is to improve understanding as to the possible role of EPCs in COPD pathophysiology. This may help in the identification of novel diagnostic and therapeutic tools in COPD.

Effects of non-invasive ventilation on renal and endothelial function in patients with respiratory failure.

OBJECTIVE: Non-invasive positive pressure ventilation (NIV) is now an indispensable safeguard in the management of many pathologies. However, sometimes the positive end-expiratory pressure (PEEP) showed harmful effects on renal function, although effects on renal hemodynamic are unclear. We aimed at evaluating the effects of NIV on renal and endothelial function, in patients with chronic or acute respiratory failure. PATIENTS AND METHODS: We performed a longitudinal, prospective, interventional study. We enrolled 17 hospitalized and non-hospitalized patients (11 males) with indication to NIV and stable hemodynamic parameters. Patients were treated with NIV and followed up at T0, at T1 (at the end of the NIV cycle) and at T2 (fifteen days after). RESULTS: 17 patients (11 males) with a mean age of 71.94 ± 14.89 years were enrolled. A significant increase in flow mediated dilation (FMD) was found (p = 0.004). We showed a significant improvement, after NIV, in the values of pH (p = 0.0002), pCO2 (p = 0.0001), pO2 (p = 0.04), lactates (p = 0.04), sO2 (p = 0.02) and in the P/F Ratio (p = 0.004). We also showed a significant reduction of serum glucose (p = 0.01) and a significant increase of serum chlorine (p = 0.047), while we did not report a significant increase of creatinine (p = 0.297) or a significant change in diuresis. CONCLUSIONS: In our study NIV has no significant effects on renal function in patients with respiratory failure. Probably these patients required low PEEP values, which were less harmful to lung parenchyma and not effective on systemic hemodynamic. Furthermore, NIV has improved endothelial function in the short term, likely by reducing oxidative stress, as improvements of the gas-analysis parameters showed. Therefore, NIV could help to reduce cardiovascular risk of patients improving endothelial function.

Cardiopulmonary exercise testing in the functional and prognostic evaluation of patients with pulmonary diseases.

Exercise testing is increasingly utilized to evaluate the level of exercise intolerance in patients with lung and heart diseases. Cardiopulmonary exercise testing (CPET) is considered the gold standard to study a patient's level of exercise limitation and its causes. The 2 CPET protocols most frequently used in the clinical setting are the maximal incremental and the constant work rate tests. The aim of this review is to focus on the main respiratory diseases for which exercise tolerance is indicated; for example, chronic obstructive pulmonary disease, interstitial lung disease, primary pulmonary hypertension and cystic fibrosis. This review also focuses on the variables/indices that are utilized in the functional and prognostic evaluation. The recognition of abnormal response patterns of ventilatory, cardiac and metabolic limitation to exercise may help in the diagnostic evaluation. In addition, CPET indexes can provide important functional and prognostic information regarding patients with pulmonary disease. Exercise indices, such as peak oxygen uptake (V'O(2 peak)), ventilatory equivalents for carbon dioxide production (V'(E)-/V'CO(2)) and arterial oxygen saturation (S(p)O(2)), have in fact proven to be better predictors of prognosis than lung function measurements obtained at rest. Moreover, useful information on the effects of therapeutic interventions may be obtained by CPET by studying the changes in endurance capacity during high-intensity constant work rate protocols.

Resistant hypertension and obstructive sleep apnea syndrome in therapy with continuous positive airway pressure: evaluation of blood pressure, cardiovascular risk markers and exercise tolerance.

OBJECTIVE: Resistant hypertension (RH) may be associated with Obstructive Sleep Apnea (OSA), determining a remarkable increase in cardiovascular risk. The aim of the study was to assess the effect of six months with continuous positive airway pressure (CPAP) treatment on blood pressure (BP) values, cardiovascular risk markers, and exercise tolerance in patients with RH and OSA. PATIENTS AND METHODS: Twenty-four patients with RH and OSA were recruited and 24-hour ambulatory BP, intima-media thickness (IMT), flow mediated dilation (FMD), renal resistive index (RRI), and endurance cardiopulmonary exercise testing (CPET) were obtained at enrollment and after 6-month treatment. RESULTS: Significant reduction in clinic systolic and diastolic BP, IMT, and RRI (p = 0.003, p = 0.009, p = 0.020, p = 0.04, respectively) and increase in the left ventricular ejection fraction (p = 0.035) were observed after a 6-month therapy with CPAP. Moreover, improvement in all polysomnographic parameters (number of apneas/hypopneas per hour (p < 0.001), number of episodes of night-time hemoglobin desaturation (ODI) (p = 0.010)), an improvement in Epworth Sleepiness Scale (p < 0.001), as well as in endurance time during constant workload CPET (p = 0.017) were observed too. CONCLUSIONS: CPAP treatment for six months reduces BP and improves cardiovascular risk and exercise tolerance in patients with RH and OSA. An extended cardiovascular assessment, including exercise testing, might be helpful in this population, given the possible reversibility of some endothelial dysfunction and atherosclerotic markers with CPAP treatment, as reported in our study.

Outcomes for COPD pharmacological trials: from lung function to biomarkers.

The American Thoracic Society/European Respiratory Society jointly created a Task Force on "Outcomes for COPD pharmacological trials: from lung function to biomarkers" to inform the chronic obstructive pulmonary disease research community about the possible use and limitations of current outcomes and markers when evaluating the impact of a pharmacological therapy. Based on their review of the published literature, the following document has been prepared with individual sections that address specific outcomes and markers, and a final section that summarises their recommendations.

Treatment of exercise-induced asthma, respiratory and allergic disorders in sports and the relationship to doping: Part II of the report from the Joint Task Force of European Respiratory Society (ERS) and European Academy of Allergy and Clinical Immunology (EAACI) in cooperation with GA(2)LEN.

AIM: The aims of part II is to review the current recommended treatment of exercise-induced asthma (EIA), respiratory and allergic disorders in sports, to review the evidence on possible improvement of performance in sports by asthma drugs and to make recommendations for their treatment. METHODS: The literature cited with respect to the treatment of exercise induced asthma in athletes (and in asthma patients) is mainly based upon the systematic review given by Larsson et al. (Larsson K, Carlsen KH, Bonini S. Anti-asthmatic drugs: treatment of athletes and exercise-induced bronchoconstriction. In: Carlsen KH, Delgado L, Del Giacco S, editors. Diagnosis, prevention and treatment of exercise-related asthma, respiratory and allergic disorders in sports. Sheffield, UK: European Respiratory Journals Ltd, 2005:73-88) during the work of the Task Force. To assess the evidence of the literature regarding use of beta(2)-agonists related to athletic performance, the Task Force searched Medline for relevant papers up to November 2006 using the present search words: asthma, bronchial responsiveness, exercise-induced bronchoconstriction, athletes, sports, performance and beta(2)-agonists. Evidence level and grades of recommendation were assessed according to Sign criteria. RESULTS: Treatment recommendations for EIA and bronchial hyper-responsiveness in athletes are set forth with special reference to controller and reliever medications. Evidence for lack of improvement of exercise performance by inhaled beta(2)-agonists in healthy athletes serves as a basis for permitting their use. There is a lack of evidence of treatment effects of asthma drugs on EIA and bronchial hyper-responsiveness in athletes whereas extensive documentation exists in treatment of EIA in patients with asthma. The documentation on lack of improvement on performance by common asthma drugs as inhaled beta(2)-agonists with relationship to sports in healthy individuals is of high evidence, level (1+). CONCLUSIONS: Exercise induced asthma should be treated in athletes along same principles as in ordinary asthma patients with relevance to controller and reliever treatment after careful diagnosis. There is very high level of evidence for the lack of improvement in athletic performance by inhaled beta2-agonists.

Exercise-induced asthma, respiratory and allergic disorders in elite athletes: epidemiology, mechanisms and diagnosis: part I of the report from the Joint Task Force of the European Respiratory Society (ERS) and the European Academy of Allergy and Clinical Immunology (EAACI) in cooperation with GA2LEN.

AIMS: To analyze the changes in the prevalence of asthma, bronchial hyperresponsiveness (BHR) and allergies in elite athletes over the past years, to review the specific pathogenetic features of these conditions and to make recommendations for their diagnosis. METHODS: The Task Force reviewed present literature by searching Medline up to November 2006 for relevant papers by the search words: asthma, bronchial responsiveness, EIB, athletes and sports. Sign criteria were used to assess level of evidence and grades of recommendation. RESULTS: The problems of sports-related asthma and allergy are outlined. Epidemiological evidence for an increased prevalence of asthma and BHR among competitive athletes, especially in endurance sports, is provided. The mechanisms for development of asthma and bronchial hyperresponsiveness in athletes are outlined. Criteria are given for the diagnosis of asthma and exercise induced asthma in the athlete. CONCLUSIONS: The prevalence of asthma and bronchial hyperresponsiveness is markedly increased in athletes, especially within endurance sports. Environmental factors often contribute. Recommendations for the diagnosis of asthma in athletes are outlined.

Dilated cardiomyopathy due to thrombotic microangiopathy as the only manifestation of antiphospholipid syndrome: a case report.

Dilated cardiomyopathy due to thrombotic microangiopathy has been rarely reported as a clinical manifestation of antiphospholipid syndrome (APS). We describe the case of a 39-year-old woman affected by systemic lupus erythematosus (SLE) and positive antiphospholipid antibodies (aPL) who presented with orthopnea and peripheral oedema. Diagnosis of dilated cardiomyopathy due to myocardial thrombotic microangiopathy was made and treatment with anticoagulants prevented the worsening of the clinical condition. Interestingly, at variance with other cases, our patient showed no extracardiac signs of APS. The review of the current literature has confirmed that dilated cardiomyopathy due to thrombotic microangiopathy is a rare manifestation of APS.

Survival After Lung Transplant for Cystic Fibrosis in Italy: A Single Center Experience With 20 Years of Follow-up.

OBJECTIVES: Lung transplantation is currently the only treatment for end-stage respiratory failure in patients with cystic fibrosis (CF). In this study we retrospectively analyzed our experience since the start of the transplantation program in 1996 with focus on survival analysis. METHODS: All patients with CF who underwent lung transplant at our center were included (1996-2016). Survival analysis after lung transplant was performed using the Kaplan-Meier estimate, comparing by sex and by 4 eras (1996-2000, 2001-2005, 2006-2010, and 2011-2016). RESULTS: In a 20-year period, 243 patients with CF were listed for lung transplant; 123 patients (61 male, 62 female) underwent transplant, and 85 died while waiting for donor organs. The mean (SD) and median age at transplant was 27.7 (8.7) years and 26.9 years (range, 9.1 - 52.1 years), respectively. Mean (SD) forced expiratory volume in the first second was 27.6 (9.7)% predicted; 115 patients (92.0%) were pancreatic insufficient, and 43 patients (34.0%) had CF-related diabetes. Removing patients with CF who died within the first 3 postoperative months, the mean (SD) and median survival after transplant were 8.2 (5.7) years and 7.5 years (range, 3 months-20 years), respectively. Overall post-lung transplant 1-year survival was 93.6%, 5-year survival was 71.4%, 10-year survival was 53.6%, 15-year survival was 36.7%, and 20-year survival was 31.6%. We found no difference in survival between sex (P = .22) and among the 4 eras (P = .56). CONCLUSIONS: Survival after lung transplant in our single center is similar to international data.

Clinical use of Heliox in asthma and COPD.

Heliox is a low density gas mixture of helium and oxygen commonly used in deep diving (> 6 ATM). This mixture has been also used for clinical purposes, particularly in the critical care setting. Due to of its physical proprieties, Heliox breathing reduces air flow resistances within the bronchial tree; in patients with obstructive lung diseases Heliox may also reduce the work of breathing and improve pulmonary gas exchange efficiency. Beneficial effects have been documented in severe asthma attacks and in patients with chronic obstructive pulmonary disease. A reduction in WOB during mechanical ventilation and an increase in exercise endurance capacity have also been described in COPD. Heliox has been also used in the treatment of upper airways obstruction, bronchiolitis and bronchopulmonary dysplasia. Despite the encouraging results, Heliox use in routine practice remains controversial because of technical implications and high costs.