Monitoring COPD patients: systemic and bronchial eosinophilic inflammation in a 2-year follow-up.

BACKGROUND: High blood eosinophils seem to predict exacerbations and response to inhaled corticosteroids (ICS) treatment in patients with chronic obstructive pulmonary disease (COPD). The aim of our study was to prospectively evaluate for 2 years, blood and sputum eosinophils in COPD patients treated with bronchodilators only at recruitment. METHODS: COPD patients in stable condition treated with bronchodilators only underwent monitoring of lung function, blood and sputum eosinophils, exacerbations and comorbidities every 6 months for 2 years. ICS was added during follow-up when symptoms worsened. RESULTS: 63 COPD patients were enrolled: 53 were followed for 1 year, 41 for 2 years, 10 dropped-out. After 2 years, ICS was added in 12/41 patients (29%) without any statistically significant difference at time points considered. Blood and sputum eosinophils did not change during follow-up. Only FEV1/FVC at T0 was predictive of ICS addition during the 2 year-follow-up (OR:0.91; 95% CI: 0.83-0.99, p = 0.03). ICS addition did not impact on delta (T24-T0) FEV1, blood and sputum eosinophils and exacerbations. After 2 years, patients who received ICS had higher blood eosinophils than those in bronchodilator therapy (p = 0.042). Patients with history of ischemic heart disease increased blood eosinophils after 2 years [p = 0.03 for both percentage and counts]. CONCLUSIONS: Blood and sputum eosinophils remained stable during the 2 year follow-up and were not associated with worsened symptoms or exacerbations. Almost 30% of mild/moderate COPD patients in bronchodilator therapy at enrollment, received ICS for worsened symptoms in a 2 year-follow-up and only FEV1/FVC at T0 seems to predict this addition. History of ischemic heart disease seems to be associated with a progressive increase of blood eosinophils.

Home-based exercise program for people with residual disability following hospitalization for COVID-19: Randomized control trial.

BACKGROUND: The best exercise program for individuals with effort intolerance or hypoxia at rest and/or during exercise post-COVID-19 treatment who have already had in-hospital rehabilitation remains unknown. OBJECTIVE: We evaluated the efficacy of a home-based rehabilitation exercise program intervention that included teleconsultations with a specialist nurse. METHODS: This was a multicenter randomized controlled trial for individuals who had been diagnosed with, and treated for, COVID-19. Despite inpatient rehabilitation they still had effort intolerance; this was defined as being a) only able to walk <70 % of the predicted distance during the six-minute walking test (6MWT) and/or b) oxygen desaturation all day long/during effort. The primary outcome was effort tolerance, as evaluated by the 6MWT. Secondary outcomes were dyspnea, fatigue, spirometry, respiratory muscle evaluations, and oxygenation. The Intervention group performed 4 weeks of a self-directed exercise program with bi-weekly physiotherapist video calls; the Control group participated in physical activity howsoever they wished. Exercises were divided into 4 intensity levels according to disability and oxygen desaturation. The program progressively increased from low (walking, free-body exercise, sit-to-stand, and balance exercises) to high (speed walking with a pedometer, cycle ergometer, and strengthening exercises). RESULTS: We included 79 participants: 40 in the Intervention and 39 in the Control group. Mean (SD) age was 67.1 (10.3) years; 72 % (n = 57) were male. No intergroup differences in effort tolerance were found [Intervention 77.6 (75.4)m vs Control 49.5 (73.3)m (p = 0.109)]. Participants with 6MWT distance results < lower limit of normality values showed best improvements in mean (SD) effort tolerance: Intervention, 120.1 (75.8)m vs Control, 59.1 (75.6)m (p = 0.035). After 2 months, mean (SD) 6MWT distances in the 2 groups were similar: Intervention, 475.9 (82.4)m vs Control, 469.2 (118.9)m (p = 0.807). CONCLUSIONS: In individuals with residual disability post-COVID-19 and after inpatient rehabilitation, a home-based exercise program with teleconsultation significantly improves effort tolerance but only for people who had severe effort intolerance at baseline. DATABASE REGISTRATION: ClinicalTrials.gov number, NCT04821934.

Pulmonary rehabilitation and risk of fall in elderly with chronic obstructive pulmonary disease.

BACKGROUND: Few data are available on the effects of pulmonary rehabilitation (PR) on risk of fall in over 80 individuals with chronic obstructive pulmonary disease (COPD). We investigated the effectiveness of PR on the risk of fall in older as compared to younger than 80 individuals. METHODS: Parallel-group retrospective exploratory study of individuals undergone in-hospital PR. The risk of fall was defined as a gait speed ≤0.8 m/s (primary outcome). Outcome measures (exercise capacity, physical performance, symptoms, and health status) were also assessed. RESULTS: As compared to younger, individuals over 80 suffered from more severe symptoms, a reduction in physical performance and in exercise capacity and greater risk of fall (P=0.0001). The proportion of participants at risk of fall increased with age, and after PR decreased significantly without any significant difference between age groups. However, 53.4% of older individuals were still at risk of fall, as compared to 17.5% of those under 80 (P=0.0001). After PR, both populations had improved outcomes measures, without any significant between group differences. CONCLUSIONS: In individuals with COPD pulmonary rehabilitation reduced the risk of fall, while improving outcome measures independent of age, however, more than 50% of those over 80 were still at risk of fall. The pulmonary rehabilitation programs for individuals over 80 should include strategies effective in reducing the risk of fall.

Thyroid hormones modifications among COVID-19 patients undergoing pulmonary rehabilitation.

Introduction: Patients with severe COVID-19 often experience long-lasting disabilities that can improve after pulmonary rehabilitation. Moreover patients with severe COVID-19 display thyroid function alterations due to a non-thyroidal illness syndrome (NTIS). The aim of our study was to evaluate thyroid function parameters among patients hospitalized for COVID-19 who were eligible or not to respiratory rehabilitation and their modifications during follow-up. Materials and methods: Post-COVID-19 patients referred to a Respiratory Rehabilitation Unit were evaluated. Outpatients, not candidate for rehabilitation, were enrolled as Control group. Patients who had completed a 4-week-rehabilitation program were enrolled as Rehabilitation Group. All patients were evaluated at T0 (4 weeks after the discharge home in Control Group and after completion of rehabilitation in Rehabilitation Group) and at T1 (3 months after T0). Results: The final study group included 39 patients (20 in the Rehabilitation group and 19 in the Control group). Patients in the Rehabilitation Group had more frequently received invasive or non-invasive ventilation, had a longer length-of-stay in referring hospitals, had a higher number of comorbidities and displayed a worse performance at 6-minute-walking-test (6MWT) and Short-Physical-Performance-Battery-test (SPPB). FT3 values were lower at T0 in the Rehabilitation Group, while TSH and FT4 values were similar in the two groups. While no significant modifications in thyroid-function-parameters were observed in the Control Group, a significant increase in FT3 value was observed in the Rehabilitation Group at T1. Participants of both groups had improved the results of 6MWT at T1, while SPPB values improved only in the Rehabilitation Group. Conclusions: COVID-19 patients after pulmonary rehabilitation experience an increase in FT3 values during follow-up, paralleled with an amelioration of functional capabilities.

An overview of Cochrane systematic reviews for pulmonary rehabilitation interventions in people with chronic obstructive pulmonary disease: a mapping synthesis.

INTRODUCTION: There is a global unmet need for rehabilitation to meet which the World Health Organization, in collaboration with Cochrane Rehabilitation, is developing the Package of Interventions for Rehabilitation with the aim of identifying rehabilitation interventions relevant to a range of key health conditions, including chronic obstructive pulmonary disease (COPD). The purpose of this paper is to describe the best available evidence on pulmonary rehabilitation interventions for people with COPD. EVIDENCE ACQUISITION: An Overview of Cochrane Systematic Reviews (CSRs). Through the search strategy, COPD-related systematic reviews published from January 2009 to November 2021 were identified. Data were extracted on each reported outcome related to an intervention and judgements about the quality of evidence were made, using the GRADE approach. EVIDENCE SYNTHESIS: Seventeen reviews were analyzed, for a total of 314 primary studies that included 22,206 participants. CSRs provided information on the effectiveness of rehabilitation on functioning, activity, quality of life, anxiety, depression, mortality, and health care resource utilization. CONCLUSIONS: Our findings report that comprehensive pulmonary rehabilitation programs and water exercises improve the exercise capacity and quality of life (QoL) in people with COPD. Different exercise modalities, intensities, and settings for different muscle groups, breathing exercises, and counseling can improve exercise capacity, QoL, dyspnea, hospitalizations, and physical activity. It is uncertain whether breathing exercise, low-intensity exercise, neuromuscular electrical stimulation, and psychological intervention have an effect on exercise capacity, dyspnea, QoL, and physical activity. The protocol was registered on OSF (registration DOI: 10.17605/OSF.IO/8A26Q).

Dyspnea: a map of Cochrane evidence relevant to rehabilitation for people with post COVID-19 condition.

INTRODUCTION: Rehabilitation focuses on impairments, activity limitations and participation restrictions being informed by the underlying health condition. In the current absence of direct "evidence on" rehabilitation interventions for people with post COVID-19 condition (PCC), we can search and synthesize the indirect "evidence relevant to" coming from interventions effective on the symptoms of PCC in other health conditions. The World Health Organization (WHO) required this information to inform expert teams and provide specific recommendations in their Guidelines. With this overview of reviews with mapping we aimed to synthesize in a map the Cochrane evidence relevant to rehabilitation for dyspnea due to PCC. EVIDENCE ACQUISITION: We searched the last five years' Cochrane Systematic Review (CSRs) using the terms "dyspnea" and its synonyms in the Cochrane Library. We extracted and summarized all the available evidence using a map. We grouped the included CSRs for health conditions and interventions, indicating the effect and the quality of evidence. EVIDENCE SYNTHESIS: We found 371 CSRs published between 2016 and 2021 and included 15 in this overview. We found eight studies on chronic obstructive pulmonary disease, two on cancer, and one for bronchiectasis, chronic respiratory disease, cystic fibrosis, idiopathic pulmonary fibrosis and interstitial lung disease. Effective interventions included pulmonary rehabilitation, also in combination with exercise training, non-invasive ventilation, upper limb training and multicomponent integrated interventions, with very low- to moderate-quality evidence. CONCLUSIONS: These results are the first step of indirect evidence to generate helpful hypotheses for clinical practice and future research on dyspnea in adults with PCC. They served as the basis for one recommendation on treatments for dyspnea as a PCC symptom published in the current WHO Guidelines for clinical practice.

Analysis of Patients with Asthma and Mixed Granulocytic Inflammatory Pattern in Sputum.

BACKGROUND: Patients with asthma usually present airway inflammation classified as eosinophilic, neutrophilic, mixed granulocytic, and paucigranulocytic pattern according to sputum inflammatory cells. OBJECTIVE: The aim of the study was to analyze clinical and biological characteristics of patients with asthma and mixed granulocytic pattern in comparison with the other groups. METHODS: Induced sputum was used to assess airway inflammation; lung function was evaluated as well as blood leukocytes and disease control. History of comorbidities was collected. RESULTS: We retrospectively analyzed 231 subjects with asthma; patients with mixed granulocytic pattern were more frequently male compared with paucigranulocytic subjects, older than eosinophilic and paucigranulocytic patients with increased number and vitality of sputum cells compared to eosinophilic and paucigranulocytic patients and higher cumulative illness rating score, related to increased age. Smoking history, age of disease onset, and ICS treatment were not associated with higher mixed granulocytic pattern occurrence. Subjects with neutrophilic inflammation (mixed granulocytic and neutrophilic patterns considered altogether) were more frequently obese. In subjects under 67 years of age (median of the enrolled subjects), arterial hypertension was the only comorbidity more frequent in mixed granulocytic than in the other groups. 137/231 subjects were re-valuated during follow-up. Lung function of patients with mixed granulocytic, neutrophilic, and paucigranulocytic patterns improved less than that of eosinophilic patients. CONCLUSION: Aging and presence of comorbidities, in particular obesity and hypertension, are characteristics of patients with asthma and mixed granulocytic pattern. They could respond less well to treatment than eosinophilic patients.

Effect of pulmonary rehabilitation on heart rate recovery in adult individuals with asthma or chronic obstructive pulmonary disease.

Introduction: Heart rate recovery (HRR) after exercise is a marker of disease severity and prognosis in cardiovascular and respiratory disorders. More than 30% of adult individuals with asthma may show a slow HRR. Pulmonary rehabilitation improves exercise capacity in individuals with asthma or chronic obstructive pulmonary disease (COPD). Aim: The study aimed to evaluate the effect of pulmonary rehabilitation on HRR in individuals with asthma as compared to those with COPD. Methods: Retrospective analysis of HRR one minute after the six-minute walking test (6MWT) was performed before and after an exercise training program. The COPD Assessment Test (CAT), Barthel Index-Dyspnea (BI-D), Medical Research Council (MRC) score for dyspnea, and the Five-Times-Sit-to-Stand test (5STS) were also assessed as secondary outcome measures. Results: Slow HRR prevalence was significantly lower in individuals with asthma than with COPD (29.1 vs. 46.7%, respectively: p = 0.003). Post-program HRR did not change in more than 70% of individuals in either population and improved in 16% of both populations, whereas it actually worsened in 12 and 10% of individuals with asthma and COPD, respectively. The outcome measures significantly improved in both populations, irrespective of baseline HRR. Conclusion: In individuals with asthma or COPD, exercise training does not significantly improve HRR.

The Role of Blood Gas Analysis in the Post-Acute Phase of COVID-19 Pneumonia

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Heart rate recovery in adult individuals with asthma.

Slow heart rate recovery (HRR) after exercise is a predictor of overall mortality in individuals with and without cardiovascular or respiratory disorders. No data on adults with asthma are available. The purpose of the study is to evaluate the prevalence of slow HRR in these individuals as compared with those with chronic obstructive pulmonary disease (COPD). We performed a retrospective analysis of baseline characteristics and physiological response to the six-minute walking distance test of stable individuals with asthma or COPD. Slow HRR was defined as HRpeak - HR at 1 minute after end exercise <12 bpm. Individuals with asthma walked significantly longer (median (IQR): 455 (385-512) vs 427 (345-485) meters; p=0.005) with a lower prevalence of slow HRR (30.3% vs 49.0%, respectively: p<0.001) than those with COPD. Individuals with asthma and slow HRR were older and walked less than those with normal HRR, without any difference in airway obstruction or in disease severity. Multivariate analysis showed that only the difference HRpeak - baseline HR (∆HR), was a predictor of slow HRR in both groups. More than 30% of adult individuals with asthma may show slow HRR. Only exercise ∆HR but no baseline characteristic seems to predict the occurrence of slow HRR.

Respiratory rehabilitation for patients with COVID-19 infection and chronic respiratory failure: a real-life retrospective study by a Lombard network.

The Lombardy region has been one of the areas most affected by the COVID-19 pandemic since the first months of 2020, providing real-life experiences in the acute phase. It is unclear how the respiratory rehabilitation network responded to this emergency. The aims of this retrospective study were: i) to analyze clinical, functional, and disability data at admission; ii) describe assessment tools and rehabilitative programs; iii) evaluate improvement after rehabilitation. The study was conducted on data collected from ten pulmonary rehabilitation centers in Lombardy, between the period of March 1st 2020 to March 1st 2021, in patients with respiratory failure recovering from COVID-19 both at admission and discharge. The study included demographics, comorbidities, nutritional status, risk of falls, disability status (Barthel index; Short Physical Performance Battery (SPPB); 6 minutes walking test (6MWT), symptoms (dyspnoea with Barthel Dyspnoea and MRC Dyspnoea Scale), length of stay, discharge destination, need for mechanical ventilation, respiratory function, assessment/outcomes indices, and prescribed rehabilitative programs. 413 patients were analyzed. Length of stay in acute and rehabilitative units was less than 30 days. Fifty % of patients used non-invasive ventilation during their stay. Functional status was mildly compromised for forced volumes and oxygenation, while severely compromised for diffusion capacity. Independency was low while physical performance status very low.  At discharge, 318 (77%) patients were sent home, 83 (20.1%) were transferred to an acute unit and 12 (2.9%) passed away. Barthel Index and 6MWT were the most used, while MRC score was the least used outcome parameter. The 5 main rehabilitative activities were walking (90.8 %), transfer from bed to armchair (77.5%), limb mobilization in bed (76%), balance (71.2%), and cycle-ergometer or treadmill (43.1%). A huge difference was found in admission, discharge, and delta change among different rehabilitative centers. When available, all outcomes showed a significant improvement. With the limitation of a retrospective study with a clear amount of missing data, COVID-19 subjects admitted to rehabilitative centers presented a reduced physical performance, symptoms of dyspnoea, and severe disability. The 6MWT and Barthel index were the most used measurement.

Time course of exercise capacity in patients recovering from COVID-19-associated pneumonia.

OBJECTIVE: High prevalences of muscle weakness and impaired physical performance in hospitalized patients recovering from COVID-19-associated pneumonia have been reported. Our objective was to determine whether the level of exercise capacity after discharge would affect long-term functional outcomes in these patients. METHODS: From three to five weeks after discharge from acute care hospitals (T0), patients underwent a six-minute walk test (6MWT) and were divided into two groups according to the distance walked in percentage of predicted values: <75% group and ≥75% group. At T0 and three months later (T1), patients completed the Short Physical Performance Battery and the Euro Quality of Life Visual Analogue Scale, and pulmonary function and respiratory muscle function were assessed. In addition, a repeat 6MWT was also performed at T1. RESULTS: At T0, 6MWD values and Short Physical Performance Battery scores were lower in the <75% group than in the ≥75% group. No differences were found in the Euro Quality of Life Visual Analogue Scale scores, pulmonary function variables, respiratory muscle function variables, length of hospital stay, or previous treatment. At T1, both groups improved their exercise capacity, but only the subjects in the <75% group showed significant improvements in dyspnea and lower extremity function. Exercise capacity and functional status values returned to predicted values in all of the patients in both groups. CONCLUSIONS: Four weeks after discharge, COVID-19 survivors with exercise limitation showed no significant differences in physiological or clinical characteristics or in perceived health status when compared with patients without exercise limitation. Three months later, those patients recovered their exercise capacity.

The severity of acute exacerbations of COPD and the effectiveness of pulmonary rehabilitation.

BACKGROUND AND AIM: Pulmonary rehabilitation is effective also in patients recovering from acute exacerbations of COPD (AECOPD). We aimed to evaluate whether levels of dyspnoea affect the outcome of pulmonary rehabilitation in patients recovering from AECOPD requiring different levels of care. MATERIALS AND METHODS: Retrospective data analysis of 1057 patients recovering from AECOPD requiring either hospital (Hospital group: 291) or home management (Home group: 766), undergone post AECOPD in-patient pulmonary rehabilitation. The 6-min walking distance (6MWD) test was the primary outcome, stratified by the Barthel index Dyspnoea (Bid). Data of modified Medical Research Council scale, Short Physical Performance Battery, COPD Assessment Test were also analysed, when available. RESULTS: In overall population 6MWD improved significantly from 278 (129) to 335 (139) meters (p < 0.001). As compared to Home, 6MWD improved more in Hospital group [by 81.9 (79.6) vs 48.9 (94.4) meters respectively, p < 0.001] also when stratified by Bid levels (all: p < 0.01). In Hospital group, 6MWD improved significantly more in patients with Bid level 3 than levels 4 and 5 (p < 0.05). Hospital group showed a greater proportion of patients reaching the Minimal Clinically Important Difference for 6MWD (75.9 vs 56.7% in Hospital and Home group respectively p < 0.001). All other available outcome measures significantly (p < 0.01) improved independent of the Bid levels. There was no significant correlation between baseline severity of airflow obstruction and effect of the program. CONCLUSIONS: In-patient pulmonary rehabilitation results in clinically meaningful improvement in patients recovering from AECOPD, independent of severity of dyspnoea. However, the levels of dyspnoea severity and the care required by AECOPD influenced the magnitude of success.

The Maugeri daily activity profile: a tool to assess physical activity in patients with chronic obstructive pulmonary disease.

Patients with chronic obstructive pulmonary disease (COPD) report reduced physical activity (PA). There are only few tools available to assess PA and sedentary behavior in these patients, and none of them aims to differentiate between sedentary and active patterns. The aim of the study was to evaluate an easy tool to profile daily activity time in a cohort of patients with COPD, compared to healthy subjects; the study was set at the Istituti Clinici Scientifici Maugeri (ICS), IRCCS of Tradate and Lumezzane, Italy, and at the Ente Ospedaliero Cantonale Novaggio, Switzerland (Italian Speaking). The populations were inpatients with COPD, healthy subjects. The items of the Maugeri Daily Activity (MaDA) profile were chosen based on literature, interviews with patients and health professionals. Time spent during sleep (ST), when awake (AT), active (ACT) or in sedentary behavior (SET) were recorded. Lung function tests, arterial blood gases, the modified Medical Research Council (mMRC), the six-minute walking distance test (6MWD), the COPD Assessment Test (CAT), and the body-mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index were also assessed in patients. Sixty patients with COPD and 60 healthy controls filled in the questionnaire. As compared to controls, patients showed longer AT and SET. Active time of patients was significantly correlated with mMRC, CAT, Bode Index and 6MWD, but not with demographics, anthropometrics or stages of disease. Using this tool, we found that patients with COPD spent longer time awake and in sedentary behavior. The MaDA may be useful to evaluate PA in patients with COPD.

Pulmonary Rehabilitation in Patients Recovering from COVID-19.

BACKGROUND: In hospitalized patients recovering from the SARS-coronavirus-2 disease 19 (COVID-19), high prevalence of muscle weakness and physical performance impairment has been observed. OBJECTIVES: The aim of this study was to evaluate the effectiveness of pulmonary rehabilitation in these subjects in a real-life setting. METHODS: Retrospective data analysis of patients recovering from COVID-19, including those requiring assisted ventilation or oxygen therapy, consecutively admitted to an in-patient pulmonary rehabilitation program between April 1 and August 15, 2020. Short Physical Performance Battery (SPPB: primary outcome), Barthel Index (BI), and six-min walking distance were assessed as outcome measures. RESULTS: Data of 140 patients were analyzed. After rehabilitation, patients showed improvements in SPPB {from: (median [IQR]) 0.5 (0-7) to 7 (4-10), p < 0.001} and BI (from 55 [30-90] to 95 [65-100], p < 0.001), as well as in other assessed outcome measures. The proportion of patients unable at admission to stand, rise from a chair and walk was significantly reduced (p < 0.00). CONCLUSIONS: Pulmonary rehabilitation is possible and effective in patients recovering from COVID-19. Our findings may be useful to guide clinicians taking care of patients surviving COVID-19 infection.