Ernesto Crisafulli

Role of comorbidities in a cohort of patients with COPD undergoing pulmonary rehabilitation

Background: Chronic obstructive pulmonary disease (COPD) is often associated with other chronic diseases. These patients are often admitted to hospital based rehabilitation programmes. Objectives: To determine the prevalence of chronic comorbidities in patients with COPD undergoing pulmonary rehabilitation and to assess their influence on outcome. Design: Observational retrospective cohort study. Setting: A single rehabilitation centre. Patients: 2962 inpatients and outpatients with COPD (73% male, aged 71 (SD 8) years, forced expiratory volume in 1 s (FEV1) 49.3 (SD 14.8)% of predicted), graded 0, 1 or ⩾2 according to the comorbidity categories and included in a pulmonary rehabilitation programme. Measurements: The authors analysed the number of self-reported comorbidities and recorded the Charlson Index. They then calculated the percentage of patients with a predefined positive response to pulmonary rehabilitation (minimum clinically important difference (MCID)), as measured by improvement in exercise tolerance (6 min walking distance test (6MWD)), dyspnoea (Medical Research Council scale) and/or health related quality of life (St George’s Respiratory Questionnaire (SGRQ)). Results: 51% of the patients reported at least one chronic comorbidity added to COPD. Metabolic (systemic hypertension, diabetes and/or dyslipidaemia) and heart diseases (chronic heart failure and/or coronary heart disease) were the most frequently reported comorbid combinations (61% and 24%, respectively) among the overall diseases associated with COPD. The prevalence of patients with MCID was different across the comorbidity categories and outcomes. In a multiple categorical logistic regression model, the Charlson Index (OR 0.72 (96% CI 0.54 to 0.98) and 0.51 (96% CI 0.38 to 0.68) vs 6MWD and SGRQ, respectively), metabolic diseases (OR 0.57 (96% CI 0.49 to 0.67) vs 6MWD) and heart diseases (OR 0.67 (96% CI 0.55 to 0.83) vs SGRQ) reduced the probability to improve outcomes of rehabilitation. Conclusions: Most patients with COPD undergoing pulmonary rehabilitation have one or more comorbidities. Despite the fact that the presence of comorbidities does not preclude access to rehabilitation, the improvement in exercise tolerance and quality of life after rehabilitation may be reduced depending on the comorbidity.

Efficacy of standard rehabilitation in COPD outpatients with comorbidities.

A prospective study was performed to confirm the prevalence pattern of the most frequent co-morbidities and to evaluate whether characteristics of patients, specific comorbidities and increasing number of comorbidities are independently associated with poorer outcomes in a population with complex chronic obstructive pulmonary disease (COPD) submitted for pulmonary rehabilitation (PR). 316 outpatients (mean±sd age 68±7 yrs) were studied. The outcomes recorded were comorbidities and proportion of patients with a pre-defined minimally significant change in exercise tolerance (6-min walk distance (6MWD) +54 m), breathlessness (Medical Research Council (MRC) score -1 point) and quality of life (St George’s Respiratory Questionnaire -4 points). 62% of patients reported comorbidities; systemic hypertension (35%), dyslipidaemia (13%), diabetes (12%) and coronary disease (11%) were the most frequent. Of these patients, >45% improved over the minimum clinically important difference in all the outcomes. In a logistic regression model, baseline 6MWD (OR 0.99, 95% CI 0.98–0.99; p = 0.001), MRC score (OR 12.88, 95% CI 6.89–24.00; p = 0.001) and arterial carbon dioxide tension (OR 1.08, 95% CI 1.00–1.15; p = 0.034) correlated with the proportion of patients who improved 6MWD and MRC, respectively. Presence of osteoporosis reduced the success rate in 6MWD (OR 0.28, 95% CI 0.11–0.70; p = 0.006). A substantial prevalence of comorbidities in COPD outpatients referred for PR was confirmed. Only the individuals disability and the presence of osteoporosis were independently associated with poorer rehabilitation outcomes.

Pneumonic and Nonpneumonic Exacerbations of COPD: Inflammatory Response and Clinical Characteristics

BACKGROUND Community-acquired pneumonia (CAP) is a frequent event in patients with COPD, although it is not currently considered an acute exacerbation of COPD (AECOPD). To our knowledge, no studies have compared the inflammatory response of patients with COPD who develop CAP or AECOPD. The aim of our study was to compare clinical and evolutive manifestations and biologic signaling of AECOPD and CAP + COPD. METHODS Prospective data were collected from 249 consecutively hospitalized patients with COPD. Comparative analyses were performed in patients with AECOPD (n = 133) and patients with CAP + COPD (n = 116). Measures of clinical characteristics, blood biomarkers, and evolution were recorded on admission, after 3 and 30 days, and in a follow-up period of 30 days, 90 days, and 1 year. RESULTS Patients with CAP + COPD had higher FEV1 compared with patients with COPD without pneumonia. In-hospital and long-term outcomes (1 year) were similar for both populations. However, patients with AECOPD had more readmissions, and patients with CAP had more prior episodes of pneumonia. At day 1 and day 3, patients with CAP + COPD had significantly (P < .001) higher serum levels of C-reactive protein (CRP), procalcitonin, tumor necrosis factor-α, and IL-6. Repetition of the analyses after stratifying patients based on severity of disease, current inhaled pharmacotherapy, and noninfectious AECOPD cause confirmed higher levels of the same biomarkers in patients with CAP + COPD. Chills, pleuritic pain, sputum purulence, and CRP levels at day 1 were independent clinical predictors of CAP + COPD. CONCLUSIONS Our study confirms that two different clinical and inflammatory profiles exist in hospitalized patients with COPD in response to CAP (stronger response) and AECOPD, although with similar short-term and long-term outcomes.

Original ResearchCOPDPneumonic and Nonpneumonic Exacerbations of COPD: Inflammatory Response and Clinical Characteristics

BACKGROUND Community-acquired pneumonia (CAP) is a frequent event in patients with COPD, although it is not currently considered an acute exacerbation of COPD (AECOPD). To our knowledge, no studies have compared the inflammatory response of patients with COPD who develop CAP or AECOPD. The aim of our study was to compare clinical and evolutive manifestations and biologic signaling of AECOPD and CAP + COPD. METHODS Prospective data were collected from 249 consecutively hospitalized patients with COPD. Comparative analyses were performed in patients with AECOPD (n = 133) and patients with CAP + COPD (n = 116). Measures of clinical characteristics, blood biomarkers, and evolution were recorded on admission, after 3 and 30 days, and in a follow-up period of 30 days, 90 days, and 1 year. RESULTS Patients with CAP + COPD had higher FEV1 compared with patients with COPD without pneumonia. In-hospital and long-term outcomes (1 year) were similar for both populations. However, patients with AECOPD had more readmissions, and patients with CAP had more prior episodes of pneumonia. At day 1 and day 3, patients with CAP + COPD had significantly (P < .001) higher serum levels of C-reactive protein (CRP), procalcitonin, tumor necrosis factor-α, and IL-6. Repetition of the analyses after stratifying patients based on severity of disease, current inhaled pharmacotherapy, and noninfectious AECOPD cause confirmed higher levels of the same biomarkers in patients with CAP + COPD. Chills, pleuritic pain, sputum purulence, and CRP levels at day 1 were independent clinical predictors of CAP + COPD. CONCLUSIONS Our study confirms that two different clinical and inflammatory profiles exist in hospitalized patients with COPD in response to CAP (stronger response) and AECOPD, although with similar short-term and long-term outcomes.

Effects of early inpatient rehabilitation after acute exacerbation of COPD

We have undertaken an observational retrospective cohort study to assess feasibility and clinical effectiveness of early rehabilitation in patients recovering from acute exacerbation of COPD (AECOPD). A cohort of 1826 inpatients (73% male, age 70+/-8 yrs, FEV(1) 50+/-16% pred.) admitted to a pulmonary rehabilitation (PR) program and completing at least 15 sessions were divided into categories according to their dyspnoea grade (Medical Research Council--MRC scores 2-5) as assessed before AECOPD. The pre-post changes in 6-minute walking distance (6MWD) test, perceived end-effort dyspnoea (Borg scale), and self-reported quality of life (St. Georges respiratory Questionnaire: SGRQ) were measured throughout. Absolute change in 6MWD (52 [95%CI 45-59], 65 [95%CI 60-70], 63 [95%CI 59-66], and 70 [95%CI 67-74] meters in MRC 2-5 respectively) and the percentage of patients achieving the minimal clinically important difference (MCID) of +54 m (40, 55, 57, and 61%, respectively, p=0.001) differed across MRC grades. Proportion of patients able to reach > or = 350 m at the 6MWD after PR was higher in MRC 4 and 5 (18 and 22%) as compared to MRC 2 and 3 (6 and 15%). Early PR in a cohort of AECOPD patients is feasible and it is associated to clinically meaningful improvement in exercise tolerance independent on the severity of dyspnoea. The proportion of patients reaching the limit of > or = 350 m after this intervention is higher in the most severe patients.

Functional recovery following physical training in tracheotomized and chronically ventilated patients

BACKGROUND: Rehabilitation is a non-pharmacologic therapy that can restore health and reverse the patients disability, but the efficacy of rehabilitation in critically ill patients is not well documented. METHODS: In a prospective cohort study, we assessed whether the degree of change in functional status after comprehensive rehabilitation influenced clinical outcomes in 77 tracheotomized patients (mean ± SD age 75 ± 7 y) admitted for difficult weaning to our regional weaning center. The care plan, including peripheral muscle training, was delivered daily. We recorded admission demographic, anthropometric, and functional characteristics. We measured the change in basic activities of daily living score (ΔBADL), survival, and weaning success rate as clinical outcomes. We performed the Pearson correlation analysis and linear regression, with ΔBADL as the dependent variable, to test the predictive power of the baseline measurements. RESULTS: Sixty-seven patients (87%) survived, and 55 of them (74%) succeeded in weaning during their stay in the weaning center. The mean ± SD ΔBADL improvement was 2.5 ± 2.0 points (median 2 points). Baseline performance of the latissimus dorsi predicted ΔBADL (β = 0.388, 95% CI 0.111–1,664, P = .03). The probability of remaining ventilator-free (P = .043) and survival (P = .001) differed across the 4 ΔBADL categories (0 = no change, 1–2 = least improvement, and > 2 = improvement above median change). CONCLUSIONS: Mortality rate and weaning success differ according to ΔBADL following active rehabilitation/training in tracheotomized, ventilated, difficult-to-wean patients. The performance of the latissimus dorsi was the only significant predictor of change.

Effects of beclomethasone/formoterol fixed combination on lung hyperinflation and dyspnea in COPD patients

Background Chronic obstructive pulmonary disease (COPD) is a common disease characterized by airflow obstruction and lung hyperinflation leading to dyspnea and exercise capacity limitation. Objectives The present study was designed to evaluate whether an extra-fine combination of beclomethasone and formoterol (BDP/F) was effective in reducing air trapping in COPD patients with hyperinflation. Fluticasone salmeterol (FP/S) combination treatment was the active control. Methods COPD patients with forced expiratory volume in one second <65% and plethysmographic functional residual capacity ≥120% of predicted were randomized to a doubleblind, double-dummy, 12-week, parallel group, treatment with either BDP/F 400/24 μg/day or FP/S 500/100 μg/day. Lung volumes were measured with full body plethysmography, and dyspnea was measured with transition dyspnea index. Results Eighteen patients were evaluable for intention to treat. A significant reduction in air trapping and clinically meaningful improvement in transition dyspnea index total score was detected in the BDP/F group but not in the FP/S group. Functional residual capacity, residual volume (RV) and total lung capacity significantly improved from baseline in the BDP/F group only. With regard to group comparison, a significantly greater reduction in RV was observed with BDP/F versus FP/S. Conclusion BDP/F extra-fine combination is effective in reducing air trapping and dyspnea in COPD patients with lung hyperinflation.

Repeated Pulmonary Rehabilitation in Severe and Disabled COPD Patients

Background: The optimal frequency of delivering a pulmonary rehabilitation program (PR) is not yet a well established issue. It is still unclear whether repeated PR at established intervals will result in effective maintenance or further improvement in the patient’s health status. Objectives: To investigate whether more frequently repeated PR in patients with COPD (1) leads to similar short and long-term physiological gains, and (2) decreases the burden due to hospitalization. Methods: Thirty-five disabled COPD patients (FEV1 below 50% predicted, MRC score 3) in a stable state were studied in a randomized controlled trial. After completing an initial inpatient PR program, they were randomly assigned to either group 1 (performing a second and a third PR after 6 and 12 months) or group 2 (performing only a second PR after 12 months). Results: Lung functions, exercise capacity (by means of a timed walk test – 6MWT), peak-effort dyspnea (D) and leg fatigue (F), and health-related quality of life by means of SGRQ were assessed prior to (T1, T3, T5) and after (T2, T4, T6) each PR program: the same measures were taken on an outpatient basis at T3 in group 2. The number of hospital admissions (HA) and days spent in the hospital (DH) were also recorded over the year. The two groups did not differ in any parameter at baseline. 6MWD, D, F and SGRQ improved to the same level (p = 0.05) after each PR in both groups. However, the baseline level of D, F and SGRQ symptoms and impact scores progressively improved over time in group 1 but not in group 2. After 12 months, a larger amount of patients in Group 1, as compared to Group 2, reported H10 DH/year (p < 0.0001). Conclusions: In severe and disabled COPD, a more frequently repeated inpatient PR may lead to some additional physiological and clinical benefits over 1 year.

COPD and the metabolic syndrome: an intriguing association

Chronic Obstructive Pulmonary Disease (COPD) has been recently recognized as a condition involving more than the lungs. The presence of common factors in COPD and in other chronic extra-pulmonary diseases, as well as the co-existence of these conditions in the same adult individual, supports the hypothesis of a shared pathogenetic pathway. We will here review the interplay between coexisting COPD and the metabolic syndrome (MS), based on the most updated knowledge. We will discuss this clinical condition from the definition, to the pathophysiology and to the clinical implications. Basically, MS is more likely to be present in a COPD patients, and increased levels of circulatory pro-inflammatory proteins from both the lung and adipose tissue coincide in these patients. The relative impact of the coexisting COPD and MS may depend on several factors: the presence of physical inactivity and of systemic inflammation related to a smoking habit, sedentary lifestyle, airway inflammation and obstruction, adipose tissue and inflammatory marker activation. More studies will be required to elucidate the association between COPD and MS and to formulate individualized management approaches for this specific disease phenotype.

Exercise Capacity as a Pulmonary Rehabilitation Outcome

Disabled patients with chronic respiratory disease and peripheral skeletal muscle disorders have limitations in their exercise capacity, which may be improved after specific training in a pulmonary rehabilitation (PR) program. Individual assessment of exercise capacity by clinically available exercise tests represents an important patient-centered outcome that should be embedded in the rehabilitation process. These measurements include laboratory (treadmill and/or cycle ergometer) and field (walking) tests. The cardiopulmonary exercise test, both performed with incremental (incremental-load test) or predetermined (constant-load or endurance test) loading, is an excellent means to describe the profile of an individual’s maximal exercise capacity and to record its change after PR. Among the variety of field-based tests, 6-min walking and shuttle walking are 2 simple tests widely used during PR. These tests are inexpensive and provide information on an individual’s functional abilities: the 6-min walking test has been shown to provide level of disability and functional status, whereas the shuttle walking test has been shown to be more suitable to detect change of physical performance following PR. Overall, several available physiologically targeted tests are useful to measure the patient’s tolerance to exercise, and many are even sensitive to change once intervention has taken place. In particular, endurance modality tests seem to provide better measurement of changes after PR than incremental exercise tests.