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Antonia Pierobon,1 Elisa Sini Bottelli,1 Laura Ranzini,1 Claudio Bruschi,2 Roberto Maestri,3 Giorgio Bertolotti,4 Marinella Sommaruga,5 Valeria Torlaschi,1 Simona Callegari,1 Anna Giardini1 1Psychology Unit, 2Department of Pulmonary Rehabilitation, 3Department of Biomedical Engineering, Istituti Clinici Scientifici Maugeri, IRCCS, Montescano, 4Psychology Unit, Istituti Clinici Scientifici Maugeri, IRCCS, Tratate, 5Clinical Psychology and Social Support Unit, Istituti Clinici Scientifici Maugeri, IRCCS, Camaldoli, Italy Abstract: In addition to clinical comorbidities, psychological and neuropsychological problems are frequent in COPD and may affect pulmonary rehabilitation delivery and outcome. The aims of the study were to describe a COPD population in a rehabilitative setting as regards the patients depressive symptoms, anxiety, mild cognitive impairment (MCI) and self-reported adherence and to analyze their relationships; to compare the COPD sample MCI scores with normative data; and to investigate which factors might predict adherence to prescribed physical exercise. This was a multicenter observational cross-sectional study. Of the 117 eligible stable COPD inpatients, 84 were enrolled according to Global initiative for chronic Obstructive Lung Disease (GOLD) criteria (mainly in Stage III–IV). The assessment included Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), anxiety, depression and self-reported pharmacological and nonpharmacological adherence. From the MMSE, 3.6% of patients were found to be impaired, whereas from the MoCA 9.5% had a likely MCI. Patients referred had mild-severe depression (46.7%), anxiety (40.5%), good pharmacological adherence (80.3%) and difficulties in following prescribed diet (24.1%) and exercise (51.8%); they struggled with disease acceptance (30.9%) and disease limitations acceptance (28.6%). Most of them received good family (89%) or social (53%) support. Nonpharmacological adherence, depression, anxiety and MCI showed significant relations with 6-minute walking test, body mass index (BMI) and GOLD. Depression was related to autonomous long-term oxygen therapy modifications, disease perception, family support and MCI. In the multivariate logistic regression analysis, higher BMI, higher depression and lower anxiety predicted lower adherence to exercise prescriptions (P=0.0004, odds ratio =0.796, 95% CI =0.701, 0.903; P=0.009, odds ratio =0.356, 95% CI =0.165, 0.770; and P=0.05, odds ratio =2.361, 95% CI =0.995, 5.627 respectively). In COPD patients, focusing on pharmacological and nonpharmacological adherence enhance the possibility of tailored pulmonary rehabilitation programs. Keywords: depression, anxiety, mild cognitive impairment, adherence, COPD, pulmonary rehabilitation

Simonetta Baldi,1 Gian Domenico Pinna,2 Claudio Bruschi,1 Fabrizio Caldara,3 Roberto Maestri,2 Elena Dacosto,1 Antonella Rezzani,1 Ermanno Popovich,1 Ezio Bellinzona,1 Paola Crotti,1 Silvia Montemartini,1 Claudio Fracchia1 1Department of Pneumology, 2Department of Biomedical Engineering, Scientific Institute of Montescano, Salvatore Maugeri Foundation, Istituto Di Ricovero e Cura a Carattere Scientifico, Montescano (Pavia), 3Center of Thermal Studies Pietro d’Abano, AbanoTerme, Padua, Italy Background: Inspiratory resistive breathing (IRB) challenges affect respiratory muscle endurance in healthy individuals, which is considered to be an interleukin 6 (IL-6)–dependent mechanism. Whether nonpharmacological thermal therapies promote the endurance of loaded inspiratory muscles in chronic obstructive pulmonary disease (COPD) is unclear. The objectives of this study were to compare the effects of two thermal interventions on endurance time (ET) and plasma IL-6 concentration following an IRB challenge.Methods: This study was a randomized, parallel-group, unblinded clinical trial in a single-center setting. Forty-two patients (aged 42–76 years) suffering from mild to severe COPD participated in this study. Both groups completed 12 sessions of the mud bath therapy (MBT) (n=22) or leisure thermal activity (LTA) (n=19) in a thermal spa center in Italy. Pre- and postintervention spirometry, maximum inspiratory pressure, and plasma mediators were obtained and ET and endurance oxygen expenditure (VO2Endur) were measured following IRB challenge at 40% of maximum inspiratory pressure.Results: There was no difference in ΔIL-6 between the intervention groups. But, IRB challenge increased cytokine IL-6 plasma levels systematically. The effect size was small. A statistically significant treatment by IRB challenge effect existed in ET, which significantly increased in the MBT group (P=0.003). In analysis of covariance treatment by IRB challenge analysis with LnVO2Endur as the dependent variable, ΔIL-6 after intervention predicted LnVO2Endur in the MBT group, but not in the LTA group. Adverse events occurred in two individuals in the MBT group, but they were mainly transient. One patient in the LTA group dropped out.Conclusion: MBT model improves ET upon a moderate IRB challenge, indicating the occurrence of a training effect. The LnVO2Endur/ΔIL-6 suggests a physiologic adaptive mechanism in respiratory muscles of COPD patients allocated to treatment. Both thermal interventions are safe. Keywords: hydrotherapy, cytokine IL-6, inspiratory resistive breathing, balneotherapy, pulmonary rehabilitation

Simonetta Baldi,1 Paul E Jose,2 Claudio Bruschi,1 Gian Domenico Pinna,3 Roberto Maestri,3 Antonella Rezzani,1 Ezio Bellinzona,1 Claudio Fracchia,1 Elena Dacosto,1 Paola Crotti,1 Silvia Montemartini1 1Department of Pneumology, Scientific Institute of Montescano, Salvatore Maugeri Foundation IRCCS, Montescano, Pavia, Italy; 2School of Psychology, Victoria University, Wellington, New Zealand; 3Department of Biomedical Engineering, Scientific Institute of Montescano, Salvatore Maugeri Foundation IRCCS, Montescano, Pavia, ItalyObjectives: To explore the mediating role of protein interleukin-6 (IL-6) on the relationship between forced expiratory volume in 1 second (FEV1) and 6-minute walk distance (6MWD) and, further, to determine whether status variables (such as age, sex, and body mass index [BMI]) operate as moderators of this mediation relationship.Design: Moderated mediation model.Setting: An inpatient pulmonary rehabilitation center in Italy.Participants: All 153 patients involved in the screening of a randomized controlled clinical trial (ClinicalTrials.gov identifier: NCT01253941) were included in this study. All patients were Global initiative for chronic Obstructive Lung Disease (GOLD) stages I–IV and were aged 70.1±9.1 years.Measurements: At run-in phase of the protocol, clinical and functional screening included BMI, fasting plasma levels of protein (IL-6), spirometry, and standardized 6-minute walking test, measured at the start of the respiratory rehabilitation program.Methods: The size of the indirect effect of the initial variable (FEV1) upon the outcome variable (6MWD) through the intervening variable (IL-6) was computed and tested for statistical significance. Moderated mediation analyses were subsequently conducted with age, sex, and BMI.Results: FEV1 averaged 53.4%±21.2%, and 6MWD 66.4%±41.3% of predicted. Median protein IL-6 was 6.68 pg/mL (interquartile range: 5.96). A bootstrapped mediation test supported the predicted indirect pathway (P=0.003). The indirect effect through IL-6 log units accounted for 17% of the total effect between FEV1 and 6MWD. Age functioned as a significant moderator of the mediational pattern. For individuals aged 70 years it was not significant (0.04, 95% CI: –0.010 to 0.142, P=0.10).Conclusion: This moderated mediation result based on concurrent data suggests, but does not prove, a causal role of systemic inflammatory syndrome on progression from functional impairment to “frailty” status and substantial disability in aging chronic obstructive pulmonary disease. Keywords: COPD, chronic airflow obstruction, aging, mediation analysis

Paced breathing (PB) around 0.25 Hz has been advocated as a means to avoid confounding and to standardize measurements in short-term investigations of autonomic cardiovascular regulation. Controversy remains, however, as to whether it causes any alteration in autonomic control. We addressed this issue in 40 supine, middle-aged, healthy volunteers by assessing the changes induced by PB (0.25 Hz for 8 min) on 1) ventilatory parameters, 2) the indexes of autonomic control of cardiovascular function, and 3) the spectral indexes of cardiovascular variability. Subjects were grouped into group 1 (n = 31), if spontaneous breathing was regular and within the high-frequency (HF) band (0.15-0.45 Hz), or group 2 (n = 9), if it was irregular or slow ( heart rate variability; controlled breathing; baroreflex sensitivity; spectral analysis

Pinna, G. D., R. Maestri, A. Mortara, and M. T. La Rovere. Cardiorespiratory interactions during periodic breathing in awake chronic heart failure patients. Am. J. Physiol. Heart Circ. Physiol. 278: H932-H941, 2000.--We applied spectral techniques to the analysis of cardiorespiratory signals ]instantaneous lung volume (ILV), instantaneous tidal volume (ITV), arterial [O.sub.2] saturation ([MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII]) at the ear, heart rate (HR), systolic (SAP), and diastolic (DAP) arterial pressure] during nonapneic periodic breathing (PB) in 29 awake chronic heart failure (CHF) patients and estimated the timing relationships between respiratory and slow cardiovascular ([is less than] 0.04 Hz) oscillations. Our aim was 1) to elucidate major mechanisms involved in cardiorespiratory interactions during PB and 2) to test the hypothesis of a central vasomotor origin of PB. All cardiovascular signals were characterized by a dominant ([is greater than or equal to] 84% of total power) oscillation at the frequency of PB (mean [+ or -] SE: 0.022 [+ or -] 0.0008 Hz), highly coherent ([is greater than or equal to] 0.89), and delayed with respect to ITV (ITV-HR, 2.4 [+ or -] 0.72 s; ITV-SAP, 6.7 [+ or -] 0.65 s; ITV-DAP, 3.2 [+ or -] 0.61 s; P [is less than] 0.01). [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] was highly coherent with (coherence function = 0.96 [+ or -] 0.009) and almost opposite in phase to ITV. These findings demonstrate the existence of a generalized cardiorespiratory rhythm led by the ventilatory oscillation and suggest that 1) the cyclic increase in inspiratory drive and cardiopulmonary reflexes and 2) mechanical effects of PB-induced changes in intrathoracic pressure are the more likely sources of the HR and blood pressure oscillations, respectively. The timing relationship between ITV and blood pressure signals excludes the possibility that PB represents the effect of a central vasomotor rhythm. chemoreceptors; cardiopulmonary receptors; cardiovascular variability; spectral analysis