Abstract Background COVID-19 infection can lead to a constellation of long-lasting post-infectious sequelae, including myocardial dysfunction, whose outcome is strongly affected by a fine-tuned balance between pro- and anti-inflammatory systemic immune responses. Plasma cytokines are key mediators of this immunological balance. In this preliminary study we evaluated the cross-sectional association between the circulating levels of the main pro- and anti-inflammatory cytokines and cardiac magnetic resonance (CMR) abnormalities. Methods 71 subjects (59% female, mean age 52±14) with previous diagnosis of COVID-19 infection were enrolled at our institution for MULTICOVID protocol, comprehensive of CMR and biomarkers assessment performed >3 months and <1 year following the first negative swab test. CMR protocols consisted of conventional sequences (cine, T2-weighted imaging, and late gadolinium enhancement [LGE]) and quantitative mapping sequences (T1, T2, and extracellular volume [ECV] mapping). Plasma levels of cytokines TNF-α, IL-1β, IL-1α, IFN-α2, IL-6, IL-8, IL-13, IL-10, IL-17A, IL-18, IP-10, MIG and MCP-1 were quantified by Multiplex Immunoassays on the Luminex technology platform. Soluble cardiologic and biochemical biomarkers were measured by routine laboratory analysis. Results After a median of 9 (IQR 6–11) months following negative swab, CMR was normal in 48 subjects, while in 23 (32%) it revealed tissue characterization abnormalities (myocardial late enhancement and/or edema). By multivariate regression analysis (adjusted for age, sex, vaccination, severity degrees of the initial COVID disease, presence of comorbidities, smoke, time interval between COVID diagnosis and CMR assessment) the cytokine ratio TNF-α/(IL-10+IL-13) was independently associated (OR=2.89, 95% CI 1.19–7.04, p=0.02) with CMR abnormalities. Interestingly, the cumulative pro-/anti-inflammatory cytokine ratio (IL-1β+TNF-α+IFN-α2+IL-6+IL-17A+IL-8)/(IL-10+IL-13) showed a positive (OR=1.70, 95% CI: 1.04–2.75) and significant (p=0.03) association with CMR imaging aspects. Also, the ratio IFN-α2/(IL-10+IL-13), although without achieving a complete statistical significance (p=0.09), was associated positively with CMR findings. Conclusions The preliminary results of this cross-sectional study suggest that the systemic inflammatory environment, long-lasting unbalanced towards a prevalent cytokine-driven pro-inflammatory condition following COVID infection, could affect the development of CMR-detectable myocardial edema and fibrosis in long-term post-COVID subjects. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Tuscany Region

Background: Chronic Obstructive Pulmonary Disease (COPD) requires continuous patient management caused by frequent exacerbations with consequent hospitalizations and a worsening of the patient's quality of life.Pulmonary rehabilitation improves exercise tolerance, but many patients do not have access to these programs. Aim:We assumed that 3 months of controlled respiratory training (CRT), providing benefits on well-being in healthy subjects, can represent a valid strategy to improve health status and better disease management in COPD patients. Design: Quality improvement in health careSetting: Outpatients attending the rehabilitation treatment room of a single centre.Population: 34 patients with COPD (according GOLD 2019 classification) were enrolled. Methods:Patients were divided into TREAT group (n = 18, 16 males, age 73.83 ± 6.71 years) and control group (CTR: 13 males, age 74.06 ± 6.38 years).Before and after CRT a battery of psychological questionnaires were assessed.T Results: REAT group in Post-CRT, as compared to CTR, showed a reduction in depressive symptoms (BDI, p<0.05;POMS depression, p<0.05), anger (p<0.01),stress perception (PSS, p<0.05), and anxiety levels (BAI, p=0.05).Also, CRT improved general health (p<0.01) and vitality (p<0.05). Conclusions:This preliminary study demonstrated that CRT is effective to improve quality of life and well-being perception in patients with COPD.Larger studies will need to confirm the long-term clinical and psychological benefits of this holistic approach, addictive to the traditional clinical practice, not only for symptomatic COPD, but also more generally to all patients with chronic diseases. Clinical rehabilitation impact:In clinical settings, for COPD patients, who experience the chronic nature of illness, we propose an additive holistic approach to the traditional clinical practice to improve health-related quality of life, and thus, a better disease management.

In PH the measure of pulmonary function tests (PFT) and arterial blood gases (ABG) are used to identify underlying lung disease. We wondered if there could be a relationship among indices of PFT, ABG (paO2, paCO2), gas exchange (A-a DO2, a-ADCO2, VDphy/VT) and haemodynamic variables in a population of PH patients. Methods: Sixteen patients with suspicion of PH underwent PFT, diffusing lung capacity (DLCO), ABG, gas exchange, right heart cath; physiological dead space to tidal volume was measured. Mean values and their SD were calculated. The relationships between the observed variables were evaluated by their mutual information. The global network was reconstructed using the ARACNE algorithm (Margolin A, et al.: ARACNE. BMC Bioinformatics, 2006; 20:1-7). Modules in the network were identified applying a multidimensional scaling procedure to the adjaceny matrix and, succesively, clustering the variables with a model-based bayesian approach (Fraley C, et al. JASA, 2002; 97:611-631). We conducted the analyses with R statistical software. Results: Pulmonary gas exchange was on average impaired with increased A-a DO2; a-A DCO2 as well as physiological dead space were abnormal thus indicating impairment of ventilation perfusion distribution ratio. The three most influential variables in the networks were: PCW (betweeness=20), RAP (betweeness=18) and VDphy/VT (betweeness=14). Three modules were identified: a (RAP, FEV1, VDphy/VT, CI, TLC); b (PCW, PVR, mPAP); g (aADO2, aADCO2, DsbHb, PaCO2). The three modules were well separated. VDphy and PVR were significantly correlated (p: 0,042; R: 0.53). Conclusions: It turns out from our results a narrow relationships between VDphy and RAP, CI and PVR.

Reportedly, patients with scleroderma-related pulmonary hypertension (SSc-PAH) respond poorly to new vasoactive drugs (NVD). Forty-nine SSc-PAH patients underwent right heart catheterization (RHC) and, according to NVD availability, divided as follows: Group 1 (n = 23, from 1999 to 2004, poor availability), and Group 2 (n = 26, from 2005 to 2010, good availability). Before diagnostic RHC, NVD had been given to 30 % of the patients in Group 1, and 58 % of those in Group 2 (p = 0.049). At diagnosis, patients in Group 1 had greater heart dilatation (p < 0.01), higher mean pulmonary artery pressure (p < 0.05), lower pulmonary artery capacitance (p < 0.05), and lower carbon monoxide lung diffusing capacity (DLco, p < 0.05) than those in Group 2. At a median follow-up time of 15.5 months, DLco further decreased in Group 1 (p < 0.05), whereas cardiac index increased in Group 2 (p < 0.05). At 36 months of follow-up, 72.4 % of the patients in Group 2 were still alive as opposed to 30.4 % in Group 1 (p = 0.02). In multivariate analysis, DLco and mixed venous oxygen saturation (SvO2) were independent predictors of survival. A value of DLco <7.2 mL/mmHg/min was associated with a hazard ratio (HR) of 5.3 (p < 0.001); for SvO2 <63.8 %, the HR was 3.7 (p < 0.01).NVD have beneficial effects in patients with SSc-PAH. Both DLco and SvO2 are predictors of survival and may assist in planning treatment.

The objective of the study is to assess the effects of emphysema on peak oxygen uptake (\( \dot{V}{\text{O}}_{{ 2 {\text{peak}}}} \)) during a cardiopulmonary exercise test in patients with chronic obstructive pulmonary disease (COPD). We measured \( \dot{V}{\text{O}}_{{ 2 {\text{peak}}}} \) and oxygen pulse in 80 patients with stable COPD exercising maximally. Oxygen saturation was measured by pulse oximetry (SpO2), and the ventilatory response assessed by the ratio of tidal volume (V T) at peak to slow vital capacity (SVC) at baseline, and by the percent increase of peak V T over baseline. Computed tomography imaging (CT scan) served as the reference diagnostic standard for emphysema. Based on the panel-grading (PG) method, emphysema was rated absent or mild (PG ≤ 30, n = 54), or moderate to severe (PG > 30, n = 26). Multiple quantile regression was applied to estimate the effects of PG > 30 on \( \dot{V}{\text{O}}_{{ 2 {\text{peak}}}} \). At peak exercise, the patients with PG > 30 had significantly lower \( \dot{V}{\text{O}}_{ 2} \), oxygen pulse and SpO2, and featured a blunted ventilatory response with respect to those with PG ≤ 30 (p < 0.001). With multiple quantile regression, the effects of PG > 30 on \( \dot{V}{\text{O}}_{{ 2 {\text{Peak}}}} \) were only partially explained by the degree of lung hyperinflation, a substantial component being imputable to impairment of lung diffusing capacity. In conclusion, chronic obstructive pulmonary disease patients with moderate to severe emphysema feature significantly lower exercise tolerance than those with no or mild emphysema. Our findings underscore the need of tailoring therapeutic interventions for COPD to the predominant clinical phenotype to improve exercise capacity.

Patients with inoperable chronic thromboembolic pulmonary hypertension (Inop-CTEPH) treated with conventional therapy have a poor survival. We compare the 3-year survival between those treated with conventional therapy and those treated with conventional therapy and a combination of novel drugs. We also evaluate the clinical course. A total of 34 Inop-CTEPH consecutive patients were evaluated from 1991 to 2009 including right heart catheterization (RHC) and perfusion lung scan (PLS): 7 underwent surgical treatment while 27 were confirmed inoperable. Of these 27 patients, 12 evaluated from 1991 to 2003 (Group 1) were treated with conventional therapy and 15 evaluated from 2004 to 2009 (Group 2) were treated with conventional and novel therapies. At baseline, no group difference emerged at RHC. Based on clinical course, novel drugs and oxygen supplementation were given to patients of Group 2. Seven of these who had worse clinical course repeated RHC and four of them also PLS during therapy. Those without repeat RHC had baseline pulmonary artery mean pressure and brain natriuretic peptide (NT-proBNP) lower and mixed venous saturation (SvO2) and exercise test higher (p = 0.022, 0.015, 0.044 and 0.003, respectively). During therapy, those with repeat RHC had total pulmonary vascular resistance reduced (p = 0.012), base excess increased (p = 0.002) and significant redistribution of pulmonary blood flow at PLS. At the 3-year follow-up, survival was 86% in Group 2 and 31% in Group 1 (p = 0.031). In Inop-CTEPH patients, the clinical course may help to select drugs and the level of oxygen supply that can improve hemodynamics, gas exchange and long-term survival.

BACKGROUND:Patients with hepatic cirrhosis frequently show idiopathic hyperventilation at rest, despite no concomitant cardiopulmonary disease. The aim of the study was to determine whether altered chemosensitivity either to hypoxia or hypercapnia could underlie inappropriate hyperventilation in cirrhotic patients.METHODS:We consecutively recruited 30 biopsy proven cirrhotic patients equally distributed in the three Child's classes A, B and C (age 54 ± 8 years, mean ± SD). All patients underwent evaluation of chemosensitivity to hypoxia and to hypercapnia and blood sampling for brain natriuretic peptide, norepinephrine and progesterone, besides full clinical characterization. We also recruited 10 age- and gender-matched healthy controls (age 55 ± 7 years).RESULTS:Overall, 18 patients (60%) showed an increased chemosensitivity to carbon dioxide (CO(2)), while 8 patients (27%) showed enhanced chemosensitivity to hypoxia. Child's class C patients had lower arterial partial pressure of CO(2) (PaCO(2)), higher rest ventilation, increased chemosensitivity to hypercapnia, plasma level of norepinephrine and serum progesterone levels when compared to class A patients and controls (all p < 0.05). Rest ventilation was positively related to pH (R = 0.41, p = 0.023), chemosensitivity to hypercapnia (R = 0.54, p = 0.002), and progesterone (R = 0.53, p = 0.016) and negatively to PaCO(2) (R = 0.61, p < 0.001), but not to hemoglobin level and chemosensitivity to hypoxia. Chemosensitivity to hypercapnia was positively related to PaCO(2) (R = 0.74, p < 0.001), serum progesterone (R = 0.50, p = 0.016), and to plasma norepinephrine (R = 0.57, p = 0.004).CONCLUSIONS:Enhanced chemosensitivity to hypercapnia was found in more decompensated cirrhotic patients and was associated with sympathetic overactivity and elevated serum progesterone, likely representing a key mechanism underlying the "unexplained" hyperventilation observed in such patients.

PURPOSE: It's still uncertain the role of some functional indices, other than FEV1, as tools which reflect the quality of life and define the exercise tolerance in Chronic Obstructive Pulmonary Disease (COPD). The present study is designed to assess during exercise the role of these functional parameters which are related to the behaviour of small airways when expiratory flow-limitation is present.

PURPOSE:To appraise the role of chest radiography (CXR) in the clinical assessment of pulmonary complications occurring as a result of liver disease of any cause, a standardised reading of CXR was compared both with the results of lung function studies and with the severity of liver disease in 60 consecutive patients with cirrhosis candidates to liver transplant.MATERIALS AND METHODS:CXR were scored for signs of cardiomegaly, enlargement of central and or peripheral vessels, hyperkinetic circulatory and/or intravascular volume states, abnormally increased interstitial lung markings, and pleural effusion by three independent observers.RESULTS:The CXR score of this complete vascular-interstitial deficiency showed a high interobserver reproducibility and was significantly increased in those patients with a more decompensated liver cirrhosis. Moreover, a larger number of CXR signs of vascular and interstitial deficiency was present in those patients who had a more severe cirrhosis (Child-Pugh class 3). Functional indices of pulmonary gas exchange and diffusing capacity were worse in patients with end-stage liver cirrhosis, and for some indices the correlation was statistically significant. The comparison between lung function and CXR score showed that on average lung function impairment was significantly less severe in patients with lower CXR scores.CONCLUSIONS:In conclusion, the information derived from a standardised reading of CXR is valuable in the clinical assessment of the pulmonary damage induced by liver cirrhosis as it allows discrimination of classes of severity of liver disease and of lung function impairment. When integrated with physiologic measurements and, if necessary, with high resolution tomographic studies, chest radiography helps to discriminate patients with advanced liver cirrhosis and progressing towards a hepatopulmonary syndrome, who need a proper therapeutic management.

The purpose of this study was to evaluate plasma levels of vasoactive factors which may play a role in the altered vascular tone of pulmonary circulation during hepatic failure. In the 85 patients with hepatic dysfunction studied we obtained: ET-1:0.66+/-0.30, 1.35+/-0.30, 1.73+/-0.41 fmol/ml; Big-ET-1:1.42+/-0.14, 1.91+/-0.22, 2.26+/-0.20 fmol/ml; NO: 58.3+/-2.91, 68.0+/-4.44, 72.12+/-8.73 mumol/l; AM:14.7+/-1.78, 18.9+/-1.70, 23.14+/-3.08 pmol/l; ANP:17.8+/-3.96, 20.7+/-4.66, 23.7+/-5.25 pg/ml; BNP:27.4+/-6.23, 49.0+/-17.7, 63.5+/-16.1 pg/ml; DNP:230.8+/-18.6, 287.3+/-19.6, 270.7+/-27.8 pg/ml for Child-Pugh class A n=20, class B n=36, class C n=29, respectively. The vasoactive peptide increase, associated with the progression of hepatic dysfunction, suggests that they may, by the way, contribute to circulatory and gas exchange modifications.

PURPOSE: Abnormal oxygenation is a common finding in patients suffering from cirrhosis, ranging from asymptomatic increase in the alveolar to arterial oxygen gradient, (A-a)O2, to a severe respiratory failure. Diffusion limitation, VA/Q disequilibrium and intrapulmonary shunt, as determinants of hypoxemia, however don't appear to have same relevance.

The complexity of assessing the impact of palliative care is much greater than in other fields of medicine, due to the shortcomings of traditional outcome indicators. We conducted a prospective study to describe the patient's quality of life at the outset and during palliative care at home and to define some potential indicators of palliative care outcomes with the aim of assessing the quality of home care as provided by a palliative care unit. Seventy-three patients who received care at home were assessed. The median survival in palliative home care was 29 days. To evaluate the degree of symptom distress, we used an Italian version of the Symptom Distress Scale. Assessing the quality-of-life pattern over time, we observed that palliative care was effective in mitigating pain and, at least in part, in stimulating appetite, curbing nausea, and controlling psychological aspects. The subscales referring to social and functional aspects steadily worsened. The difficulties encountered (the high percentage of missing data, the considerable number of patients treated for less than 10 days, etc.) should be a warning against using only one assessment instrument. It is worthwhile defining the various potential outcomes of palliative care even though all results will not always be measurable in every patient. Only a global assessment, a “multiple outcomes approach,” based on different indicators, would allow for evaluation of the outcome of the care process.