Use of inhaled devices during a hospital exacerbation of COPD: a summary of an interdisciplinary audit held at ICS Maugeri Pavia, Italy (March-June 2019).

To date treatment protocols in Respiratory and or Internal departments across Italy for treatment of chronic obstructive pulmonary disease (COPD) patients at hospital admission with relapse due to exacerbation do not find adequate support in current guidelines. Here we describe the results of a recent clinical audit, including a systematic review of practices reported in literature and an open discussion comparing these to current real-life procedures. The process was dived into two 8-hour-audits 3 months apart in order to allow work on the field in between meeting and involved 13 participants (3 nurses, 1 physiotherapist, 2 internists and 7 pulmonologists). This document reports the opinions of the experts and their consensus, leading to a bundle of multidisciplinary statements on the use of inhaled drugs for hospitalized COPD patients. Recommendations and topics addressed include: i) monitoring and diagnosis during the first 24 h after admission; ii) treatment algorithm and options (i.e., short and long acting bronchodilators); iii) bronchodilator dosages when switching device or using spacer; iv) flow measurement systems for shifting to LABA+LAMA within 48 h; v) when nebulizers are recommended; vi) use of SMI to deliver LABA+LAMA when patient needs SABA <3 times/day independently from flow limitation; vii) use of DPI and pre-dosed MDI to deliver LABA+LAMA or TRIPLE when patient needs SABA <3 times/day, with inspiratory flow > 30 litres/min; viii) contraindication to use DPI; ix) continuation of LABA-LAMA when patient is already on therapy; x) possible LABA-LAMA dosage increase; xi) use of SABA and/or SAMA in addition to LABA+LABA; xii) use of SABA+SAMA restricted to real need; xiii) reconciliation of drugs in presence of comorbidities; xiv) check of knowledge and skills on inhalation therapy; xv) discharge bundle; xvi) use of MDI and SMI in tracheostomized patients in spontaneous and ventilated breathing.

Minimal Clinically Important Difference in Barthel Index Dyspnea in Patients with COPD.

Background: The Barthel Index dyspnea (BId) is responsive to physiological changes and pulmonary rehabilitation in patients with chronic obstructive pulmonary disease (COPD). However, the minimum clinically important difference (MCID) has not been established yet. Aim: To identify the MCID of BId in patients with COPD stratified according to the presence of chronic respiratory failure (CRF) or not. Materials and Methods: Using the Medical Research Council (MRC) score as an anchor, receiver operating characteristic curves and quantile regression were retrospectively evaluated before and after pulmonary rehabilitation in 2327 patients with COPD (1151 of them with CRF). Results: The median post-rehabilitation changes in BId for all patients were -10 (interquartile range = -17 to -3, p<0.001), correlating significantly with changes in MRC (r = 0.57, 95% CI = 0.53 to 0.59, p<0.001). Comparing different methods of assessment, the MCID ranged from -6.5 to -9 points for patients without and -7.5 to -12 points for patients with CRF. Conclusion: The most conservative estimate of the MCID is -9 points in patients with COPD, without and -12 in those with CRF. This estimate may be useful in the clinical interpretation of data, particularly in response to intervention studies.

Implementation of a real-world based ICF set for the rehabilitation of respiratory diseases: a pilot study.

BACKGROUND: International Classification Functioning (ICF) Core Sets represent a holistic approach to functioning within rehabilitation field. Information-reporting efficacy of a rehabilitation-based Respiratory ICF set applied on a large scale throughout the ICS Maugeri network was tested. METHODS: A prospective multi-center study (May-November 2018) was conducted for all respiratory inpatients consecutively admitted for rehabilitation. Doctors, physiotherapists, psychologists, nurses used an electronic Respiratory ICF set (33 items among the ICF body functions, activity and participations components) at admission and at discharge to assess the disability changes. The ICF report qualifiers, from 0 (no impairment) to 4 (maximum impairment), guided clinical, diagnostic and rehabilitation prescriptions. RESULTS: 1886 patients (69.6±10.8 years; M=1045) were admitted (589 chronic obstructive pulmonary disease, 494 chronic respiratory failure [CRF], 21 prolonged mechanical ventilation [PMV], 496 with other respiratory diseases), of whom 15 died, and 117 were transferred to acute care. The mean length of stay was 23.1±11.8 days (range 1-122). The mean time to fill in the ICF set was 23.16±0.70 min. The rate of filled charts improved from 16% in May to 100% in November. The baseline distribution of the more severe qualifiers (>2) progressively increased from the whole sample to the PMV subgroup. After rehabilitation, in the whole sample and in the CRF and PMV subgroups, the severity qualifiers significantly decreased (P<0.0001), showing a positive effect of the intervention on patients' disability. CONCLUSIONS: Routine use of a Respiratory ICF set for chronic respiratory diseases helps to prepare a personalized rehabilitation program discriminating disability level in different respiratory diseases and assessing disability outcomes pre-post rehabilitation.

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.

The role of tele-medicine in patients with respiratory diseases.

INTRODUCTION: Tele-medicine is a clinical application connecting a patient with specialized care consultants by means of electronic platforms, potentially able to improve patients' self-management and allow for the care of patients with limited access to health services. This article summarizes the use of tele-medicine as a tool in managing patients suffering from some pathological respiratory conditions. Areas covered: We searched papers published between 1990 and 2017 dealing with tele-medicine and respiratory diseases, chronic obstructive pulmonary disease, asthma, interstitial lung disease, chronic respiratory failure, neuromuscular diseases, critical illness, home mechanical ventilation, and also legal and economic issues. Controlled trials report different results on feasibility, cost-effectiveness, and safety of tele-medicine. Expert commentary: Progress in tele-medicine widens the horizons in respiratory medicine: this tool may potentially reduce health care costs by moving some medical interventions from centralized locations in to patient's home, also allowing for the delivery of care in countries with limited access to it. Legal, safety, and privacy problems, as well as reimbursement issues, must still be defined and solved. At present time, we still need much more evidence to consider this modality as a real option in the management of these patients.

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.

Peripheral muscle strength training in bed-bound patients with COPD receiving mechanical ventilation: effect of electrical stimulation.

STUDY OBJECTIVE: To compare the effects of active limb mobilization (ALM) with or without electrical stimulation (ES) on muscle strength, respiratory rate (RR), heart rate, oxygen saturation, and time needed to transfer from bed to chair in two groups of patients with COPD. DESIGN: Randomized, controlled study. SETTING: Respiratory high-dependency care unit. PATIENTS: Twenty-four bed-bound patients with chronic hypercapnic respiratory failure due to COPD who were receiving mechanical ventilation, with marked peripheral muscle hypotonia and atrophy. METHODS: Patients were randomly assigned either to ALM alone or to ALM plus ES (ALM/ES). ES was applied using square-wave alternate, symmetric, and compensated impulses for 30 min bid. The duration of treatment was 28 days for all patients. RESULTS: Muscle strength improved significantly in the overall group of patients (from 1.75 +/- 0.73 to 3.44 +/- 0.65, p < 0.05). Comparing the change (end minus beginning) of the analyzed variables, ALM/ES significantly improved muscle strength (2.16 +/- 1.02 vs 1.25 +/- 0.75, p = 0.02) and RR (- 1.91 +/- 1.72 vs 0.41 +/- 1.88, p = 0.004), and decreased the number of days needed to transfer from bed to chair (10.75 +/- 2.41 days vs 14.33 +/- 2.53 days, p = 0.001). CONCLUSION: In bed-bound patients with COPD receiving mechanical ventilation, with marked peripheral muscle hypotonia and atrophy, application of ES in addition to classical ALM significantly improved muscle strength and decreased the number of days needed to transfer from bed to chair.

Changes in the practice of non-invasive ventilation in treating COPD patients over 8 years.

OBJECTIVE: We reviewed data of 208 episodes of acute respiratory failure due to chronic obstructive pulmonary disease treated by non-invasive ventilation (NIV) in our Respiratory Intensive Care Unit (RICU) from its opening in 1992 to 1999. MATERIAL AND METHODS: We assessed whether the rate of NIV success, the severity of the disease, and the associated costs changed in this period during which the staff and the equipment did not change. RESULTS: The failure rate was constant over the years (17.2% on average). The severity of the episodes of ARF, defined by pH and APACHE II at admission, worsened during the years. The statistical change point test allowed us to identify 1997 as the year of a significant change in the severity of admission pH and therefore to identify two different periods: 1992-1996 (mean pH = 7.25+/-0.07) and 1997-1999 (7.20+/-0.08; P<0.001). In this latter period the risk of failure for a patient with a pH <7.25 was threefold lower than in 1992-1996. In 1997-1999 an increasing number of episodes of ARF with a pH >7.28 were treated in the Medical Ward (20% vs 60%). This allowed a significant reduction of daily cost per patient treated with NIV (558+/-8 Euros vs 470+/-14 Euros, respectively; P<0.01). CONCLUSIONS: We conclude that, over time, experience with NIV may progressively allow more severely ill patients to be treated without changing the rate of success. The daily cost of NIV per patient can be reduced by treating less severely ill patients outside the RICU.

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.

Osteopathic manipulative treatment effectiveness in severe chronic obstructive pulmonary disease: a pilot study.

OBJECTIVES: Few and contrastingly data are available about use of osteopathic manipulative treatment (OMT) in patients with chronic obstructive pulmonary disease (COPD). DESIGN: Comparing the effects of the combination of pulmonary rehabilitation and OMT compared with pulmonary rehabilitation (PR) in patients with severely impaired COPD. SETTING: Rehabilitative pulmonary department. INTERVENTIONS: Patients underwent exercise training, OMT, educational support and nutritional and psychological counselling. MAIN OUTCOMES MEASURES: Exercise capacity through 6 min walk test (6MWT--primary outcome) and pulmonary function test (secondary outcomes) were evaluated at the beginning and at the end of the training. Patients were randomly assigned to receive PR+soft manipulation (G1) or OMT+PR (G2) for 5 days/week for 4 weeks. RESULTS: 20 stable COPD patients (5 female--mean age, 63.8±5.1 years; FEV1 26.9±6.3% of predicted) referred for in-patient pulmonary rehabilitation were evaluated. Respect to the baseline, 6 MWT statistically improved in both group. In particular, G2 group gained 72.5±7.5 m (p=0.01) and G1 group 23.7±9.7 m. Between group comparison showed a difference of 48.8 m (95% CI: 17 to 80.6 m, p=0.04). Moreover, in G2 group we showed a decrease in residual volume (RV--from 4.4±1.5 l to 3.9±1.5 l, p=0.05). Between group comparison showed an important difference (-0.44 l; 95% CI: -0.26 to -0.62 l, p=0.001). Furthermore, only in G2 group we showed an increase in FEV1. CONCLUSIONS: This study suggests that OMT+PR may improve exercise capacity and reduce RV in severely impaired COPD patients with respect to PR alone.

Patients' characterization, hospital course and clinical outcomes in five Italian respiratory intensive care units.

BACKGROUND: Respiratory intensive care units (RICU) dedicated to weaning could be suitable facilities for clinical management of "post-ICU" patients. METHODS: We retrospectively analyzed the time course of patients' characteristics, clinical outcomes and medical staff utilization in five Italian RICUs by comparing three periods of 5 consecutive years (from 1991 to 2005). RESULTS: A total of 3,106 patients (age 76 +/- 4 years; 72% males) were analyzed. The number of co-morbidities per patient (from 1.8 to 3.0, p = 0.05) and the previous intensive care unit (ICU) stay (from 25 to 32 days, p = 0.002) increased over time. The doctor-to-patient ratio significantly decreased over time (from 1:3 to 1:5, p < 0.01), whereas the physiotherapist-to-patient ratio mildly increased (from 1:6 to 1:4.5, p < 0.05). The overall weaning success rate decreased (from 87 to 66%, p < 0.001), and the discharge destination changed (p < 0.001) over time; fewer patients were discharged to home (from 22 to 10%), and more patients to nursing home (from 3 to 6%), acute hospitals (from 6 to 10%) and rehabilitative units (from 70 to 75%). The mortality rate increased over time (from 9 to 15%). Significant correlations between the doctor-to-patient ratio and the rates of weaning success (r = 0.679, p = 0.005), home discharge (r = 0.722, p = 0.002) and the RICU length of stay (LOS) (r = -0.683, p = 0.005) were observed. CONCLUSIONS: The clinical outcomes of our units worsened over 15 years, likely as consequence of admitting more severely ill patients. The potential further negative influence of reduced medical staff availability on weaning success, home discharge and LOS warrants future prospective investigations.

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.