Airflow grades, outcome measures and response to pulmonary rehabilitation in individuals after an exacerbation of severe chronic obstructive pulmonary disease.

BACKGROUND: Individuals with COPD may be staged according to symptoms and exacerbation history (GOLD groups: A-D) and on airflow obstruction (GOLD grades: 1-4). Guidelines recommend pulmonary rehabilitation (PR) for these individuals, including those recovering from an exacerbation (ECOPD) OBJECTIVE: To evaluate whether in individuals with clinically severe COPD, recovering from an ECOPD, the effect size of an in-hospital PR program would be affected by airflow severity grades and assessed outcome measures. METHODS: Retrospective, multicentre study. Participants were compared according to different GOLD airflow grades. In addition to the MRC dyspnoea scale, six-minute walking distance test and COPD assessment test (CAT), Barthel dyspnoea index (Bid), and Short Physical Performance Battery (SPPB) were assessed, evaluating the proportion of individuals reaching the minimum clinically important difference (MCID) (responders). RESULTS: Data of 479 individuals, completing the program were evaluated. Most of the participants were allocated in GOLD grades 4, (57.6%) and 3 (22.1%). All outcome measures significantly improved after PR (p < 0.05), without any significant difference in the proportion of responders in any measure. CONCLUSIONS: in individuals with severe COPD, recovering from ECOPD the success rate of PR does not depend on airflow severity, or outcome measure assessed. In addition to the most used outcome measures, also Bid and SPPB are sensitive to PR.

Postural changes in lung volumes in patients with heart failure and Cheyne-Stokes respiration: Relationship with sleep apnea severity.

BACKGROUND AND AIM: It has been proposed that the increased severity of sleep apnea frequently observed in heart failure (HF) patients with Cheyne-Stokes respiration (CSR) when sleeping in the supine compared to the lateral position, may be caused by the concomitant reduction in functional residual capacity (FRC). We assessed positional changes in FRC in patients with CSR and investigated the relationship between these changes in the laboratory and corresponding changes in CSR severity during sleep. METHODS: After a diagnostic polysomnography, 18 HF patients with dominant CSR and an apnea-hypopnea index (AHI)≥15 events/h underwent a standard pulmonary function test in the sitting position. Measurements were repeated in the supine, left lateral and right lateral. The latter two measurements were averaged to obtain a single lateral measurement. RESULTS: The FRC in the seated position was 3.0 ± 0.5 L (85 ± 13% of predicted), decreased to 2.3 ± 0.3 L (-21 ± 8%, p < 0.0001) in the supine position, and increased to 2.8 ± 0.4 L (+21 ± 12%, p < 0.0001) from the supine to the lateral position (-5±8% vs seated, p = 0.013). During sleep, the AHI and the apnea index (AI) decreased from 47 ± 15 events/h to 26 ± 12 events/h (-46 ± 20%, p < 0.0001) and from 29 ± 21 events/h to 12 ± 10 events/h (-61 ± 40%, p < 0.001) from the supine to the lateral position. Changes in the AI were significantly correlated with corresponding changes in FRC (ρ = -0.55, p = 0.032). CONCLUSION: In patients with HF and CSR, lying in the supine position causes a significant reduction in FRC in the context of a chronically reduced FRC. The negative correlation between postural changes in FRC and AI supports the hypothesis that the reduction in lung gas stores in the supine position may promote/exacerbate respiratory control instability.

Renin Angiotensin System Blockers and Risk of Mortality in Hypertensive Patients Hospitalized for COVID-19: An Italian Registry.

BACKGROUND: It is uncertain whether exposure to renin-angiotensin system (RAS) modifiers affects the severity of the new coronavirus disease 2019 (COVID-19) because most of the available studies are retrospective. METHODS: We tested the prognostic value of exposure to RAS modifiers (either angiotensin-converting enzyme inhibitors [ACE-Is] or angiotensin receptor blockers [ARBs]) in a prospective study of hypertensive patients with COVID-19. We analyzed data from 566 patients (mean age 75 years, 54% males, 162 ACE-Is users, and 147 ARBs users) hospitalized in five Italian hospitals. The study used systematic prospective data collection according to a pre-specified protocol. All-cause mortality during hospitalization was the primary outcome. RESULTS: Sixty-six patients died during hospitalization. Exposure to RAS modifiers was associated with a significant reduction in the risk of in-hospital mortality when compared to other BP-lowering strategies (odds ratio [OR]: 0.54, 95% confidence interval [CI]: 0.32 to 0.90, p = 0.019). Exposure to ACE-Is was not significantly associated with a reduced risk of in-hospital mortality when compared with patients not treated with RAS modifiers (OR: 0.66, 95% CI: 0.36 to 1.20, p = 0.172). Conversely, ARBs users showed a 59% lower risk of death (OR: 0.41, 95% CI: 0.20 to 0.84, p = 0.016) even after allowance for several prognostic markers, including age, oxygen saturation, occurrence of severe hypotension during hospitalization, and lymphocyte count (adjusted OR: 0.37, 95% CI: 0.17 to 0.80, p = 0.012). The discontinuation of RAS modifiers during hospitalization did not exert a significant effect (p = 0.515). CONCLUSIONS: This prospective study indicates that exposure to ARBs reduces mortality in hospitalized patients with COVID-19.

The respiratory rehabilitation Maugeri network service reconfiguration after 1 year of COVID-19.

As part of the Italian Health Service the respiratory ICS Maugeri network were reconfigured and several in-hospital programs were suspended to be substituted by workforce and facilities reorganization for acute and post-acute COVID-19 care need. The present review shows the time course variation of respiratory ICS network in terms of admissions diagnosis and outcomes. A comparative review of the admissions and outcome measures data (anthropometric, admission diagnosis, provenience, comorbidities, disability, symptoms, effort tolerance, disease impact, length of stay and discharge destinations) over 1 year period (March 2020-March 2021) was undertaken and compared to retrospective data from a corresponding 1 year (March 2019-March 2020) period to determine the impact of the network relocation on the delivery of pulmonary specialist rehabilitation to patients with complex needs during the pandemic episode. One of the changes implemented at the respiratory Maugeri network was the relocation of the Pulmonary Rehabilitation units from its 351 beds base to a repurposed 247 beds and a reduction in total number of admitted patients (n=3912 in pre-COVID time; n=2089 in post COVID time). All respiratory diagnosis, except COVID sequelae, decreased (chronic respiratory failure-CRF, COPD, obstructive sleep apnoea syndrome-OSAS, interstitial lung disease-ILD, tracheostomized patients and other mixed diseases decreased of 734, 705, 157, 87, 79 and 326 units respectively). During the pandemic time, 265 post COVID sequelae with CRF were admitted for rehabilitation (12.62%), % of patients coming from acute hospital increased, LOS and NIV use remained stable while CPAP indication decreased. Disease impact, dyspnea and effort tolerance as their improvements after rehabilitation, were similar in the two periods.  Only baseline disability, expressed by Barthel index, seems higher in the 2° observation time as its improvement. Hospital deaths and transfers to acute hospitals were higher during pandemic crisis while home destination decreased. This review demonstrated impact of coronavirus pandemic situation, specifically the relocation of the respiratory inpatient rehabilitation wards in a huge Italian network.

Joint effect of heart failure and coronary artery disease on the risk of death during hospitalization for COVID-19.

AIMS: heart failure (HF) and coronary artery disease (CAD) are independent predictors of death in patients with COVID-19. The adverse prognostic impact of the combination of HF and CAD in these patients is unclear. METHODS AND RESULTS: we analysed data from 954 consecutive patients hospitalized for SARS-CoV-2 in five Italian Hospitals from February 23 to May 22, 2020. The study was a systematic prospective data collection according to a pre-specified protocol. All-cause mortality during hospitalization was the outcome measure. Mean duration of hospitalization was 33 days. Mortality was 11% in the total population and 7.4% in the group without evidence of HF or CAD (reference group). Mortality was 11.6% in the group with CAD and without HF (odds ratio [OR]: 1.6, p = 0.120), 15.5% in the group with HF and without CAD (OR: 2.3, p = 0.032), and 35.6% in the group with CAD and HF (OR: 6.9, p<0.0001). The risk of mortality in patients with CAD and HF combined was consistently higher than the sum of risks related to either disorder, resulting in a significant synergistic effect (p<0.0001) of the two conditions. Age-adjusted attributable proportion due to interaction was 64%. Adjusting for the simultaneous effects of age, hypotension, and lymphocyte count did not significantly lower attributable proportion which persisted statistically significant (p = 0.0360). CONCLUSION: The combination of HF and CAD exerts a marked detrimental impact on the risk of mortality in hospitalized patients with COVID-19, which is independent on other adverse prognostic markers.

Interaction Between Arousals and Ventilation During Cheyne-Stokes Respiration in Heart Failure Patients: Insights From Breath-by-Breath Analysis.

Study Objectives: Arousals from sleep during the hyperpneic phases of Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) in patients with heart failure are thought to cause ventilatory overshoot and a consequent longer apnea, thereby sustaining and exacerbating ventilatory instability. However, data supporting this model are lacking. We investigated the relationship between arousals, hyperpnea and post-hyperpnea apnea length during CSR-CSA. Methods: Breath-by-breath changes in ventilation associated with the occurrence of arousal were evaluated in 18 heart failure patients with CSR-CSA, apnea-hypopnea index ≥15/h and central apnea index ≥5/h. The change in apnea length associated with the presence of arousal during the previous hyperpnea was also evaluated. Potential confounding variables (chemical drive, sleep stage) were controlled for. Results: Arousals were associated with a large increase in ventilation at the beginning of the hyperpnea (+76 ± 35%, p < 0.0001), that rapidly declined during its crescendo phase. Around peak hyperpnea, the change in ventilation was -8 ± 26% (p = 0.14). The presence of arousal during the hyperpnea was associated with a median increase in the length of the subsequent apnea of +4.6% (Q1, Q2: -0.7%, 20.5%; range: -8.5%, 36.2%) (p = 0.021). The incidence of arousals occurring at the beginning of hyperpnea and mean ventilation in the region around its peak were independent predictors of the change in apnea length (p = 0.004 and p = 0.015, respectively; R2 = 0.78). Conclusions: Arousals from sleep during CSR-CSA in heart failure patients are associated with a rapidly decreasing ventilatory overshoot at the beginning of the hyperpnea, followed by a tendency toward a slight ventilatory undershoot around its peak. On average, arousals are also associated with a modest increase in post-hyperpnea apnea length; however, large increases in apnea length (>20%) occur in about a quarter of the patients.

Arterial oxygen saturation during Cheyne-Stokes respiration in heart failure patients: does measurement site matter?

OBJECTIVE: Despite the fact that the ear is the site to monitor arterial oxygen saturation by pulse oximetry (SpO2) closest to carotid chemoreceptors, sleep studies almost invariably use finger probes. This study aimed to assess the timing and morphological differences between SpO2 signals at the ear and finger during Cheyne-Stokes respiration (CSR) in heart failure (HF) patients. METHODS: We studied 21 HF patients with CSR during a 40-min in-laboratory resting recording. SpO2 was recorded by: (1) two identical bedside pulse-oximeters with an ear (SpO2_Ear) and a finger probe (SpO2_Finger), and (2) a standard polysomnograph with a finger probe (SpO2_PSG). We estimated the delays between signals and, for each signal, computed the mean and minimum SpO2, the magnitude of cyclic desaturations and the overall time spent with SpO2<90% (T90%). RESULTS: The SpO2_Finger signal was significantly delayed [bias: 12.7 s (95% limits of agreement: 2.2, 23.0 s)] and slightly but not significantly downward-shifted with respect to SpO2_Ear. SpO2_PSG was almost synchronous with SpO2_Finger; however, a further significant downward shift was observed relative to the latter. In particular, minimum SpO2_PSG was significantly lower [-2.1% (- 4.8, 0.6%)], and desaturations and T90% were significantly higher than SpO2_Finger [1.2% (-1.3, 3.7%), and 13.9% (-12.3, 40.0%), respectively]. CONCLUSION: During CSR in HF patients, the marked delay between SpO2_Ear and SpO2_Finger makes the interpretation of the timing relationship between peripheral chemoreceptor stimulation and ventilatory events rather difficult. The observed discrepancies between SpO2_PSG and SpO2_Finger, which may be due to differences in the processing of raw SpO2 signals, call for a standardization of processing algorithms.

Physiological and clinical characteristics of patients with COPD admitted to an inpatient pulmonary rehabilitation program: A real-life study.

BACKGROUND AND OBJECTIVE: Patient selection criteria and experimental interventions of randomized controlled trials may not reflect how things work in practice. The aim of this study was to describe the characteristics of chronic obstructive pulmonary disease (COPD) patients undergoing an inpatient pulmonary rehabilitation program (PRP) and the correlates of success. METHODS: Retrospective database review of 975 consecutive patients transferred from acute care hospitals after an acute exacerbation (group A: 14.6%) or admitted from home (group B: 75.4%), from 2010 to 2017. Patients were also divided according to the associated registered main diagnosis: COPD (group 1: 30.6%); COPD and respiratory failure (group 2: 51.7%); COPD and obstructive sleep apnea (group 3: 17.6%). Baseline correlates of post-PRP changes in six minute walking test (6MWT) were also evaluated. RESULTS: Global Initiative for Chronic Obstructive Lung Disease stages 3 and 4 were the most commonly represented in group 2 (p=0.0001). Comorbidity Index of all patients was 3.9±1.8. The overall in-hospital mortality rate was 1.3% (5.6% vs 0.6%, in groups A and B, respectively; p=0.0001). Hypertension, cardiac diseases and obesity were observed in 65.2, 52.2 and 29.6% of patients, respectively. Post-PRP 6MWT increased in all groups. Age, male gender, airway obstruction and baseline 6MWT were correlated with a post-PRP 30 meter increase in 6MWT. CONCLUSION: Confirming data of literature, this real-life study shows the characteristics of COPD patients undergoing an inpatient PRP with significant improvement in exercise capacity, independent of whether in stable state or after a recent exacerbation or of the associated main diagnosis.

Exercise Training After Pulmonary Endarterectomy for Patients with Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: After undergoing a procedure of pulmonary endarterectomy (PEA), patients with chronic thromboembolic pulmonary hypertension (CTEPH) may still experience reduced exercise capacity. Data on effects of exercise training in these patients are scant. OBJECTIVES: To evaluate the effectiveness of exercise training after PEA for CTEPH and if the presence of "residual pulmonary hypertension" may affect the outcome. METHODS: Retrospective data analysis of CTEPH patients undergoing inpatient exercise training after PEA. According to predefined criteria, patients were divided into those with (group 1) and without (group 2) a "good" post-surgery hemodynamic response. Assessments of the 6-min walking distance test (6-min walking distance test [6 MWT]: primary outcome) were performed before and after surgery (before training), after training and at 3-month follow-up. Hemodynamic and lung function data were also analyzed. RESULTS: Data of 84 and 26 patients of groups 1 and 2, respectively, were analyzed. After surgery patients showed a reduction in 6 MWT, which significantly reversed after training and further improved at 3 months (p = 0.0001), without any significant difference between groups. The percentage of patients reaching the minimal clinically important difference in 6 MWT was similar between groups. The sig-nificant (p = 0.0001) post-surgery improvement in hemodynamics was maintained at 3 months without any significant difference between groups. New York Heart Association functional class improved in parallel to the hemodynamic improvement. CONCLUSIONS: Exercise training in patients with CTEPH after PEA, an inpatient exercise training program, improves exercise capacity for up to 3 months, independently of the post-surgery hemodynamic response.

Screening for neuropsychological impairment in COPD patients undergoing rehabilitation.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a complex multi-component disorder characterized by progressive irreversible respiratory symptoms and extrapulmonary comorbidities, including anxiety-depression and mild cognitive impairment (MCI). However, the prevalence of these impairments is still uncertain, due to non-optimal screening methods. This observational cross-sectional multicentre study aimed to evaluate the prevalence of anxiety-depressive symptoms and MCI in COPD patients, identify the most appropriate cognitive tests to screen MCI, and investigate specific cognitive deficits in these patients and possible predictive factors. MATERIALS AND METHODS: Sixty-five stable COPD inpatients (n = 65, aged 69.9±7.6 years, mainly stage III-IV GOLD) underwent the following assessments: Hospital Anxiety and Depression Scale (HADS), Geriatric Depression Scale (GDS) or Beck Depression Inventory-II (BDI-II), Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and a complete neuropsychological battery (ENB-2) including different cognitive domains (attention, memory, executive functions, and perceptive and praxis abilities). RESULTS: Moderate-severe anxiety was present in 18.5% of patients and depressive symptoms in 30.7%. The prevalence of MCI varied according to the test: 6.2% (MMSE), 18.5% (MoCA) and 50.8% (ENB-2). In ENB-2, patients performed significantly worse compared to Italian normative data on digit span (5.11±0.9 vs. 5.52±1.0, p = 0.0004), trail making test-B (TMT-B) (176.31±99.5 vs. 135.93±58.0, p = 0.004), overlapping pictures (26.03±8.9 vs. 28.75±8.2, p = 0.018) and copy drawing (1.370.6 vs. 1.61±0.5, p = 0.002). At logistic regression analysis, only COPD severity (p = 0.012, odds ratio, OR, 4.4 [95% CI: 1.4-14.0]) and anxiety symptoms (p = 0.026, OR 4.6 [1.2-17.7]) were significant and independent predictors of the deficit in copy drawing, which assesses visuospatial and praxis skills. CONCLUSION: Given the prevalence of neuropsychological impairments in COPD patients, the routine adoption in rehabilitation of screening tools for mood and cognitive function, including digit span, TMT-B and copy drawing, may be useful to detect psychosocial comorbidities and personalize the rehabilitative program.

Chronic thromboembolic pulmonary hypertension: Reversal of pulmonary hypertension but not sleep disordered breathing following pulmonary endarterectomy.

BACKGROUND: It has been hypothesized that pre-capillary pulmonary hypertension (PH) may trigger sleep disordered breathing (SDB). In patients with chronic thromboembolic PH (CTEPH), pulmonary endarterectomy (PEA) is potentially effective to improve PH. We assessed the pre- and post-operative prevalence of SDB in CTEPH patients submitted to PEA and the relationship between SDB and clinical, pulmonary and hemodynamic factors. METHODS: Unattended cardiorespiratory recording was performed the night before and one month after elective PEA in 50 patients. RESULTS: Before the intervention SDB prevalence (obstructive or central AHI ≥ 5/h) was 64%: 18 patients (66% female) had No-SDB, 22 (68% female) had dominant obstructive (dOSA), and 10 (20% female) had dominant central sleep apnea (dCSA). There were no differences in risk factors and the need for supplemental oxygen. Mean right atrial (mRAP) and pulmonary artery pressures (mPAP) showed a more compromised profile from No-SDB to dOSA and dCSA (mRAP: 5.5 ±â€¯3.9 vs 7.0 ±â€¯4.5 vs 9.7 ±â€¯4.3 mm Hg (p = 0.054), mPAP: 39 ±â€¯12 vs 48 ±â€¯11 vs 51 ±â€¯16 mm Hg (p = 0.0.47)). By contrast, cardiac index did not differ. At post-intervention, the prevalence of SDB was 68%: 16 patients had No-SDB, while 30 had dOSA and 4 dCSA, with no relationship with the relief from PH. Interestingly, 5 patients with previous CSA moved to the OSA group and 2 normalized. CONCLUSIONS: Prevalence of SDB is high in patients with CTEPH even after resolution of PH. Our data support the hypothesis that pre-capillary PH may trigger CSA but not OSA, and suggest that OSA may play a role in the development of CTEPH.

COPD patients' self-reported adherence, psychosocial factors and mild cognitive impairment in pulmonary rehabilitation.

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.

Medicinal clays improve the endurance of loaded inspiratory muscles in COPD: a randomized clinical trial of nonpharmacological treatment.

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.

Differential impact of body position on the severity of disordered breathing in heart failure patients with obstructive vs. central sleep apnoea.

AIMS: Obstructive (OSA) and central sleep apnoea (CSA) are a common comorbidity in patients with heart failure. The purpose of this study was to assess and compare the impact of body position on the severity of sleep apnoea in these two groups of patients. METHODS AND RESULTS: Standard polysomnography was performed in consecutive, clinically stable, optimally treated patients with moderate-to-severe heart failure and systolic dysfunction. Patients with an apnoea-hypopnoea index (AHI) ≥15/h (n = 120) were included in the study. The severity of sleep-disordered breathing was quantified by the AHI, the mean value of oxygen desaturations (O2 desat) and the apnoea ratio. Data from the right and left positions were combined into a single lateral position. Positional sleep apnoea was defined as a >50% reduction in the AHI between the supine and the lateral position. Twenty-nine and 91 subjects had dominant OSA and CSA, respectively. The AHI markedly decreased from the supine to the lateral position in both groups [OSA: (median [q1,q3]) 50.3 [36.9, 67.6]/h vs. 10.4 [7.0, 18.5]/h, P < 0.0001; CSA: 47.4 [37.6, 56.0]/h vs. 19.3 [11.9, 33.3]/h]. The reduction was greater in OSA patients (p = 0.027). Similarly, O2 desat and the apnoea ratio decreased in the lateral position (P < 0.0001). Positional sleep apnoea was observed in 76% of OSA and 53% of CSA patients (P = 0.028). CONCLUSION: This study demonstrates that the lateral sleeping position has a major beneficial effect on the severity of sleep-disordered breathing in heart failure patients, and that this improvement is greater in subjects with OSA than in those with CSA.

The mediating role of cytokine IL-6 on the relationship of FEV1 upon 6-minute walk distance in chronic obstructive pulmonary disease.

OBJECTIVES: 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, the standardized indirect effect was significant (0.122, 95% confidence interval [CI]: 0.044-0.254, P=0.004), and for individuals >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.

Assessment of the peripheral ventilatory response to CO2 in heart failure patients: reliability of the single-breath test.

The assessment of chemoreflex sensitivity in heart failure patients is gaining increasing interest since recent studies demonstrated that augmented chemosensitivity is an independent predictor of mortality and represents an important pathogenic factor in the development of Cheyne-Stokes respiration. The single-breath CO2 test is a well-established method to quantify peripheral hypercapnic chemoreflex sensitivity. As the original criteria for the computation of the chemoreflex sensitivity in healthy subjects need to be modified in heart failure patients to take into account impaired cardiac function, the effects of such modifications on measurement reliability deserve investigation. Hence, we devised this study to assess the reliability of the single-breath CO2 test in heart failure patients. In 27 clinically stable, mild-to-moderate heart failure patients (age (mean±SD): 64±10 years, left ventricular ejection fraction: 34±7%, NYHA class: 2.7±0.4), the test was administered on two consecutive days in the same conditions. Reliability was assessed by the standard error of measurement (SEM) and by the intraclass correlation coefficient (ICC). The mean value of the chemoreflex sensitivity on the two days was: 0.25 ± 0.12 and 0.24 ± 0.12 l min(-1) mmHg(-1) (p = 0.45), respectively. The SEM was 0.05 l min(-1) mmHg(-1), indicating large intra-subject variability. Consequently, in order to be 95% confident that a real change has occurred between two measurements taken on the same individual (test-retest), the observed difference must be higher than ±0.15 l min(-1) mmHg(-1), which is about 60% of the mean value across our population. The ICC was 0.71, indicating thatintra-subject variability, although high, is a limited (29%) portion of inter-subject variability. Intra-subject variability should be carefully taken into account when using the single-breath CO2 test in assessing changes in individual patients. The observed ICC indicates that this test may provide useful information for diagnostic/classification purposes.

A computerized integrated system for the assessment of central and peripheral chemoreflex sensitivity.

The assessment of chemoreflex sensitivity (CRS) is of major importance in studies investigating the adaptation of ventilation to the needs of human body. Increased sensitivity of chemoreceptors to both hypoxia and hypercapnia has recently been shown to be a powerful and independent prognosticator in heart failure (HF) patients, thus highlighting the importance of the assessment of CRS also in the clinical setting. In spite of this, the measurement of CRS is currently limited to the research setting. One possible reason might be the lack of suitable commercial equipments. On the basis of these considerations, we designed a system to carry out a comprehensive assessment of CRS, including both central and peripheral chemoreceptors. The system is based on the integration of different commercial devices and is entirely managed by a custom software written in Matlab language. The main features of our system are: (1) the implementation of standard methods (the Read's rebreathing test, the CO2 single breath test and the transient hypoxia test) suitable for both pathological and healthy subjects, (2) data quality assurance and reduction of subjective judgment in the analysis through advanced analysis procedures and statistical outliers rejection, and (3) full interactive control of every step of the recording and analysis procedures. The system is currently used in our Institution in the assessment of CRS in HF patients, chronic obstructive pulmonary disease patients and healthy subjects. It has proven to be very effective and easy to use even by clinical personnel without a specific background in respiratory function assessment.

Fat-free mass change after nutritional rehabilitation in weight losing COPD: role of insulin, C-reactive protein and tissue hypoxia.

BACKGROUND: Fat-free mass (FFM) depletion marks the imbalance between tissue protein synthesis and breakdown in chronic obstructive pulmonary disease (COPD). To date, the role of essential amino acid supplementation (EAAs) in FFM repletion has not been fully acknowledged. A pilot study was undertaken in patients attending pulmonary rehabilitation. METHODS: 28 COPD patients with dynamic weight loss > 5% over the last 6 months were randomized to receive EAAs embedded in a 12-week rehabilitation program (EAAs group n = 14), or to the same program without supplementation (C group n = 14). Primary outcome measures were changes in body weight and FFM, using dual X-ray absorptiometry (DEXA). RESULTS: At the 12th week, a body weight increment occurred in 92% and 15% of patients in the EAAs and C group, respectively, with an average increase of 3.8 +/- 2.6 kg (P = 0.0002) and -0.1 +/- 1.1 kg (P = 0.81), respectively. A FFM increment occurred in 69% and 15% of EAAs and C patients, respectively, with an average increase of 1.5 +/- 2.6 kg (P = 0.05) and -0.1 +/- 2.3 kg (P = 0.94), respectively. In the EAAs group, FFM change was significantly related to fasting insulin (r(2) 0.68, P < 0.0005), C-reactive protein (C-RP) (r(2) = 0.46, P < 0.01), and oxygen extraction tension (PaO(2x)) (r(2) = 0.46, P < 0.01) at end of treatment. These three variables were highly correlated in both groups (r > 0.7, P < 0.005 in all tests). CONCLUSIONS: Changes in FFM promoted by EAAs are related to cellular energy and tissue oxygen availability in depleted COPD. Insulin, C-RP, and PaO(2x) must be regarded as clinical markers of an amino acid-stimulated signaling to FFM accretion.

Effect of bronchodilatation on single breath pulmonary uptake of carbon monoxide in chronic obstructive pulmonary disease.

We studied 21 COPD patients in stable clinical conditions to evaluate whether changes in lung function induced by cumulative doses of salbutamol alter diffusing capacity for carbon monoxide (DL(CO)), and whether this relates to the extent of emphysema as assessed by high resolution computed tomography (HRCT) quantitative analysis. Spirometry and DL(CO) were measured before and after cumulative doses of inhaled salbutamol (from 200 microg to 1000 microg). Salbutamol caused significant increments of forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and flows at 30% of control FVC taken from both partial and maximal forced expiratory maneuvers. Functional residual capacity and residual volume were reduced, while total lung capacity did not change significantly. DL(CO) increased progressively with the incremental doses of salbutamol, but this became significant only at the highest dose (1000 microg) and was independent of the extent of emphysema, as assessed by radiological parameters. No significant changes were observed in CO transfer factor (DLCO/VA) and alveolar volume (VA). The results suggest that changes in lung function induced by cumulative doses of inhaled salbutamol are associated with a slight but significant increase in DL(CO) irrespective of the presence and extent of emphysema.

Environmental tobacco smoke may induce early lung damage in healthy male adolescents.

STUDY OBJECTIVE: Childhood exposure to environmental tobacco smoke (ETS) adversely affects dynamic spirometric indexes as a result of combined early life (including in utero) and current exposure to parental smoking. The aim of our study was to investigate the effect of ETS on lung function and to identify the most sensitive functional parameter for evaluating lung damage. DESIGN: Cross-sectional survey. SETTING: Health survey on secondary school children. SUBJECTS: Eighty adolescents boys (mean age +/- SD, 16 +/- 1 years) classified in three groups: 21 smokers, 30 nonsmokers, and 29 passive smokers. MEASUREMENTS: Standardized questionnaire on the smoking habits of the subjects and their parents; assay of urinary cotinine level and measurement of the cotinine/creatine ratio (CCR); and lung function tests, including measurements of lung volumes, spirometric dynamic parameters, and the single-breath diffusing capacity of the lung for carbon monoxide (DLCO). RESULTS: Passive smokers presented a higher residual volume than nonsmokers, and a lower maximal expiratory flow at 25% of FVC (MEF(25)) and DLCO. Passive smokers whose mothers had smoked during pregnancy had significantly lower MEF(25) percentage, DLCO, carbon monoxide transfer coefficient, and diffusion capacity of the alveolar-capillary membrane (DM) values than did passive smokers whose mothers had given up smoking during pregnancy. Nevertheless, the MEF(25) and DM values of subjects with mothers who had given up smoking during pregnancy were lower than those observed in nonsmokers (p < 0.05), suggesting a negative effect of passive smoking independent of the mother's smoking habit during pregnancy. A statistically significant, negative correlation was found between CCR and DLCO in smokers (r = - 0.63, p < 0.01) and in passive smokers (r = - 0.91, p < 0.001), but not in nonsmokers (r = 0.26, p = not significant), suggesting a dose-effect relationship. CONCLUSIONS: Current exposure to ETS in healthy male adolescents is associated with lung function impairment independently of the effects of maternal smoking during pregnancy. More information may be obtained from determining static lung volumes and DLCO.