Paolo Marinelli

INDACO project: a pilot study on incidence of comorbidities in COPD patients referred to pneumology units

BackgroundChronic Obstructive Pulmonary Disease (COPD) is often associated with comorbidities, especially cardiovascular, that have a heavy burden in terms of hospitalization and mortality. Since no conclusive data exist on the prevalence and type of comorbidities in COPD patients in Italy, we planned the INDACO observational pilot study to evaluate the impact of comorbidities in patients referred to the outpatient wards of four major hospitals in Rome.MethodsFor each patient we recorded anthropometric and anamnestic data, smoking habits, respiratory function, GOLD (Global initiative for chronic Obstructive Lung Disease) severity stage, Body Mass Index (BMI), number of acute COPD exacerbations in previous years, presence and type of comorbidities, and the Charlson Comorbidity Index (CCI).ResultsHere we report and discuss the results of the first 169 patients (124 males, mean age 74±8 years). The prevalence of patients with comorbidities was 94.1% (25.2% of cases presented only one comorbidity, 28.3% two, 46.5% three or more). There was a high prevalence of arterial hypertension (52.1%), metabolic syndrome (20.7%), cancers (13.6%) and diabetes (11.2%) in the whole study group, and of anxiety-depression syndrome in females (13%). Exacerbation frequency was positively correlated with dyspnea score and negatively with BMI. Use of combination of bronchodilators and inhaled corticosteroids was more frequent in younger patients with more severe airways obstruction and lower CCI.ConclusionsThese preliminary results show a high prevalence of comorbidities in COPD patients attending four great hospitals in Rome, but they need to be confirmed by further investigations in a larger patients cohort.

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

PurposePhysical 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.MethodsThis 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.ResultsMean oxygen uptake at peak exercise (VʹO2,peak) was significantly lower in T1DM subjects (V′O2,peak T1DM 2200 ± 132ml/min vs VʹO2,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.ConclusionsPatients 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.

Effect of camptocormia on lung volumes in Parkinson's disease

Camptocormia is defined as an abnormal flexion of the thoracolumbar spine of 45°, or more, that typically increases during walking or standing and completely disappears in the supine position. Camptocormia may occur in patients with Parkinsons disease; when it does, it is usually associated with greater disease severity. Respiratory complications, which may be secondary to abnormal chest function, are one of the most frequent causes of death in patients with Parkinsons disease. No data on lung volumes are available for Parkinsons disease patients with camptocormia. The aim of this study was to evaluate the effect of camptocormia on lung function. Eleven patients with Parkinsons disease and camptocormia and ten age-matched healthy subjects underwent lung spirometry (in the standing position, inclining the trunk forward at approx. 45° and supine) measurement of arterial oxygen-hemoglobin saturation and heart rate. We found that Parkinsons disease with camptocormia is not associated with major clinical changes in lung volumes.

A Simplified Approach for the Estimation of the Ventilatory Compensation Point

UNLABELLED Incremental cardiopulmonary exercise test with gas exchange measurement is the gold standard for the identification of the ventilatory compensation point (VCP). It has previously been demonstrated that the change in the slope of increment of minute ventilation over HR (ΔV˙E/ΔHR) can be used alternatively to the ventilatory equivalent for CO₂ (V˙E/V˙CO₂) method for detection of VCP in healthy subjects undergoing cycle ergometer (C) incremental exercise. The same evaluation during treadmill (T) incremental exercise and comparison between C and T have not yet been performed. PURPOSE We analyzed, during both C and T incremental exercises, the V˙E/HR and the respiratory rate (RR)/HR relationships, expressed either as slope or as an absolute value. We hypothesized that changes in the slope of increment of the two relationships could represent a reliable method for VCP detection, regardless of exercise mode and protocol. METHODS Fourteen healthy male subjects (age = 31 ± 7 yr (mean ± SD)) underwent two T incremental exercises--fast (FT) and slow (ST) protocols (8 km·h⁻¹, 2% (F(T)) and 1% (S(T)) grade per minute)--and one C incremental exercise (30 W·min⁻¹). O₂ uptake (V˙O₂), V˙CO₂, V˙E, HR, and RR were measured breath by breath. RESULTS A good between-method agreement in the detection of VCP by the ΔV˙(E)/ΔV˙CO₂, ΔV˙(E)/ΔHR, and the ΔRR/ΔHR slope changes was found in both T protocols and C. No differences (C vs T and F(T) vs S(T)) were found in the slope of the ΔV˙(E)/ΔHR and ΔRR/ΔHR relationships after the VCP and in the V˙(E)/HR and RR/HR absolute values at VCP. CONCLUSIONS In healthy young males, the ΔV˙E/ΔHR and ΔRR/ΔHR relationships during T and C incremental exercises can be reliably used to detect the VCP as an alternative to the ventilatory equivalent method.

Impaired flow-mediated dilation in hospitalized patients with community-acquired pneumonia

BACKGROUND Community-acquired pneumonia (CAP) is complicated by cardiovascular events as myocardial infarction and stroke but the underlying mechanism is still unclear. We hypothesized that endothelial dysfunction may be implicated and that endotoxemia may have a role. METHODS Fifty patients with CAP and 50 controls were enrolled. At admission and at discharge, flow-mediated dilation (FMD), serum levels of endotoxins and oxidative stress, as assessed by serum levels of nitrite/nitrate (NOx) and isoprostanes, were studied. RESULTS At admission, a significant difference between patients with CAP and controls was observed for FMD (2.1±0.3 vs 4.0±0.3%, p<0.001), serum endotoxins (157.8±7.6 vs 33.1±4.8pg/ml), serum isoprostanes (341±14 vs 286±10 pM, p=0.009) and NOx (24.3±1.1 vs 29.7±2.2μM). Simple linear correlation analysis showed that serum endotoxins significantly correlated with Pneumonia Severity Index score (Rs=0.386, p=0.006). Compared to baseline, at discharge CAP patients showed a significant increase of FMD and NOx (from 2.1±0.3 to 4.6±0.4%, p<0.001 and from 24.3±1.1 to 31.1±1.5μM, p<0.001, respectively) and a significant decrease of serum endotoxins and isoprostanes (from 157.8±7.6 to 55.5±2.3pg/ml, p<0.001, and from 341±14 to 312±14 pM, p<0.001, respectively). Conversely, no changes for FMD, NOx, serum endotoxins and isoprostanes were observed in controls between baseline and discharge. Changes of FMD significantly correlated with changes of serum endotoxins (Rs=-0.315; p=0.001). CONCLUSIONS The study provides the first evidence that CAP is characterized by impaired FMD with a mechanism potentially involving endotoxin production and oxidative stress.

Early Markers of Cardiovascular Risk in Autosomal Dominant Polycystic Kidney Disease

Background/Aims: Cardiovascular disease is the most frequent cause of morbidity and mortality in autosomal dominant polycystic kidney disease (ADPKD) patients, often before the onset of renal failure, and the pathogenetic mechanism is not yet well elucidated. The aim of the study was to identify early and noninvasive markers of cardiovascular risk in young ADPKD patients, in the early stages of disease. Methods: A total of 26 patients with ADPKD and 24 control group, matched for age and sex, were enrolled, and we have assessed inflammatory indexes, mineral metabolism, metabolic state and markers of atherosclerosis and endothelial dysfunction (carotid intima media thickness (IMT), ankle brachial index (ABI), flow mediated dilation (FMD), renal resistive index (RRI), left ventricular mass index (LVMI)) and cardiopulmonary exercise testing (CPET), maximal O2 uptake (V’O2max), and O2 uptake at lactic acid threshold (V’O2@LT). Results: The ADPKD patients compared to control group, showed a significant higher mean value of LVMI, RRI, homocysteine (Hcy), Homeostasis Model Assessment-insulin resistance (HOMA-IR), serum uric acid (SUA), Cardiac-troponinT (cTnT) and intact parathyroid hormone (iPTH) (p<0.001, p<0.001, p<0.001, p<0.001, p<0.001, p=0.007, p=0.019; respectively), and a lower value of FMD and 25-hydroxyvitaminD (25-OH-VitD) (p<0.001, p<0.001) with reduced parameters of exercise tolerance, as V’O2max, V’O2max/Kg and V’O2max (% predicted) (p<0.001, p<0.001, p=0.018; respectively), and metabolic response indexes (V’O2@LT, V’O2 @LT%, V’O2@LT/Kg,) (p<0.001, p=0.14, p<0.001; respectively). Moreover, inflammatory indexes were significantly higher in ADPKD patients, and we found a positive correlation between HOMA-IR and C-reactive protein (CRP) (r=0.507, p=0.008), and a negative correlation between HOMA-IR and 25-OH-VitD (r=-0.585, p=0.002). Conclusion: In our study, ADPKD patients, in the early stages of disease, showed a greater insulin resistance, endothelial dysfunction, inflammation and mineral metabolism disorders, respect to control group. Moreover, these patients presented reduced tolerance to stress, and decreased anaerobic threshold to CPET. Our results indicate a major and early cardiovascular risk in ADPKD patients. Therefore early and noninvasive markers of cardiovascular risk and CPET should be carried out, in ADPKD patients, in the early stages of disease, despite the cost implication.

A 22-year-old woman with unexplained exertional dyspnoea

A 22-year-old woman was referred to our respiratory outpatient clinic to undergo a cardiopulmonary exercise test (CPET), following presentation with a 2-year history of progressive unexplained exertional dyspnoea (ED). Specifically, she described dyspnoea precipitated by walking or running, which gradually improved with rest. She denied chest pain, cough, asthenia or muscular weakness. Until the age of 20, she practised regular non-competitive physical activity. The patient had at term natural childbirth and normal psychophysical development. Menstrual period, started at the age of 14 years, was regular; no pregnancy, nor miscarriage. She was a lifelong non-smoker with no history of illicit substance use or occupational exposure (university student). Her past history included multinodular euthyroid goitre for which she was prescribed regular levothyroxine (75 μg/100 μg on alternate days). She also reported intermittent gastrointestinal discomfort, which had been ascribed to lactose intolerance for which, however, she was not prescribed a lactose-free diet. Her family history revealed an uncle deceased during childhood for ‘cardiac arrhythmia’. Cardiorespiratory and neurological examination was unremarkable. She was normotensive (blood pressure (BP) 100/60 mm Hg, heart rate (HR) 98 bpm in sinus rhythm), not tachypnoeic (respiratory rate 16 breaths/min) and had preserved oxygen saturation (SatO2 98%). Her body mass index was 19.3. Pulmonary function tests showed normal flow indices (FVC 3.52 L—88% of pred; FEV1 3.35 L—96% of pred; Tiffeneau index FEV1/FVC 0.95) and preserved lung volumes and gas transfer (total lung capacity 3.94 L—90% of pred; diffusing capacity of the lungs for carbon monoxide, 96% of pred). A high-resolution chest tomography showed no sign of lung disease. Cardiological (including rest, stress and Holter ECG, as well as cardiac ultrasounds) and neurological (including electromyography) exams showed no abnormalities. Routine blood tests (cell count, glucose and electrolyte levels, iron and ferritin profile, lipid screening, kidney and liver function), erythrocyte sedimentation rate, C reactive protein and muscular enzyme …