Raffaele Antonelli Incalzi

Predicting mortality of patients hospitalized for acutely exacerbated chronic obstructive pulmonary disease

PURPOSE To identify factors affecting the short-term prognosis of patients with acutely exacerbated chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS The 590 patients having COPD as primary disease who were hospitalized in the pneumology unit of a university hospital from 1981 to 1990 were studied. A standardized protocol for the treatment of acutely exacerbated COPD was adopted for all the patients. The patient records were retrospectively analyzed by two observers, and 23 clinical and laboratory variables defining the patient status on admission were collected. Age and arterial gas data were also taken into account, and the outcome mortality was recorded. Interobserver reproducibility was tested by computing the kappa coefficient and Spearmans rho for dichotomous and continuous variables, respectively. The relationship of clinical and laboratory factors to the outcome was assessed first by univariate analysis and then by a logistic regression analysis assessing the independent predictive role of variables previously shown to be univariately correlated with mortality. RESULTS The mortality rate was 14.4%. The logistic regression analysis identified four independent predictors of death: age (odds ratio [OR] 1.07; 95% confidence interval [CI] 1.04 to 1.11), alveolar-arterial oxygen gradient greater than 41 mm Hg (OR 2.33; 95% CI 1.39 to 3.90), ventricular arrhythmias (OR 1.91; 95% CI 1.10 to 3.31), and atrial fibrillation (OR 2.27; 95% CI 1.14 to 4.51). CONCLUSIONS Patients with acutely exacerbated COPD having a high risk of death can be identified at the time of admission. Variables reflecting heart dysfunction are important determinants of this risk. Among pulmonary function data, only alveolar-arterial oxygen gradient contributes to the predictive model.

Body mass index and mortality among older people living in the community.

OBJECTIVES: To determine if body mass index (BMI = weight/height2), predictive of mortality in seriously ill hospitalized and institutionalized patients, is also predictive of mortality in a longitudinal epidemiologic study.

Cognitive impairment: A key feature of congestive heart failure in the elderly

Abstract.Congestive heart failure (CHF) has been proposed as a possible cause of cognitive dysfunction but only a few studies have directly assessed cognitive performance in CHF. The aim of the present study was to compare the cognitive patterns of patients with CHF and patients having cardiovascular diseases uncomplicated by CHF (no-CHF group). In a multicenter observational casecontrol study, we studied 149 hospitalized elderly CHF patients in the New York Heart Association (NYHA) class II (CHFm, m: moderate), 159 CHF patients in NYHA class III–IV (CHFs, s: severe), and 207 no-CHF patients. Patients underwent a multidimensional assessment and neuropsychological tests for the following cognitive domains: attention, visual-spatial intelligence, verbal attainment, verbal and visuo-spatial memory. Neuropsychological performances of groups were compared by multivariate analysis. Correlates of an abnormal performance on at least three neuropsychological tests were assessed by logistic regression analysis. CHFs performed worse than no-CHF patients on 4 of the 7 neuropsychological measures, the largest difference being in tests of attention and verbal learning (p < 0.001). Prevalence of abnormal performance on at least 3 tests was 57.9 % in CHFs, 43% in CHFm and 34.3 % in no-CHF groups (chi square = 17.3, p < 0.0001). The following qualified as independent correlates of the outcome at logistic regression analysis: CHFs group membership (Odds Ratio—OR = 2.56, 95% Confidence Interval—CI = 1.49–4.40), depression (OR = 2.37, 95% CI = 1.54–3.66), hypertension (OR = 1.88, 95% CI = 1.18–2.99). Our results demonstrate that cognitive impairment is common among CHF patients and seems to be causally related to CHF severity, depression and hypertension. The cognitive dysfunction also characterizes a relevant fraction of patients with cardiovascular diseases uncomplicated by CHF.

Plasminogen activator inhibitor-1 (PAI-1): a key factor linking fibrinolysis and age-related subclinical and clinical conditions.

INTRODUCTION The close relationship existing between aging and thrombosis has growingly been studied in this last decade. The age-related development of a prothrombotic imbalance in the fibrinolysis homeostasis has been hypothesized as the basis of this increased cardiovascular and cerebrovascular risk. Fibrinolysis is the result of the interactions among multiple plasminogen activators and inhibitors constituting the enzymatic cascade, and ultimately leading to the degradation of fibrin. The plasminogen activator system plays a key role in a wide range of physiological and pathological processes. METHODS Narrative review. RESULTS Plasminogen activator inhibitor-1 (PAI-1) is a member of the superfamily of serine-protease inhibitors (or serpins), and the principal inhibitor of both the tissue-type and the urokinase-type plasminogen activator, the two plasminogen activators able to activate plasminogen. Current evidence describing the central role played by PAI-1 in a number of age-related subclinical (i.e., inflammation, atherosclerosis, insulin resistance) and clinical (i.e., obesity, comorbidities, Werner syndrome) conditions is presented. CONCLUSIONS Despite some controversial and unclear issues, PAI-1 represents an extremely promising marker that may become a biological parameter to be progressively considered in the prognostic evaluation, in the disease monitoring, and as treatment target of age-related conditions in the future.

Electrocardiographic Signs of Chronic Cor Pulmonale: A Negative Prognostic Finding in Chronic Obstructive Pulmonary Disease

BACKGROUND Chronic cor pulmonale (CCP) is a strong predictor of death in chronic obstructive pulmonary disease (COPD). The aims of this study were to assess the prognostic role of individual ECG signs of CCP and of the interaction between these signs and abnormal arterial blood gases. METHODS AND RESULTS Two hundred sixty-three patients (217 men) with COPD, mean age 67+/-9 years, were grouped according to whether they had no ECG signs (group 1, n=100) or >/=1 ECG signs (group 2, n=163) of CCP and were followed up for 13 years after an exacerbation of respiratory failure. The median survival was significantly shorter in group 2 than in group 1 (2.58 versus 3. 45 years, respectively; Mantel-Cox test, 9.58; P=0.002). The Cox regression analysis identified S1S2S3 pattern, right atrial overload (RAO), and alveolar-arterial oxygen gradient (PAO2-PaO2) >48 mm Hg during oxygen therapy as the strongest predictors of death, with hazard rate (HR)=1.81 (95% CI, 1.22 to 2.69), HR=1.58 (95% CI, 1.15 to 2.18), and HR=1.96 (95% CI, 1.19 to 3.25), respectively. The median survivals of patients having both S1S2S3 pattern and RAO (n=14) and of patients having either S1S2S3 pattern or RAO (n=77) were 1.33 and 2.70 years, respectively (P=0.022). Group 2 patients had a 3-year survival of 18% or 53%, depending on whether their PAO2-PaO2 during oxygen therapy was or was not >48 mm Hg. CONCLUSIONS Some ECG signs of CCP and PAO2-PaO2 >48 mm Hg during oxygen therapy qualified as a simple and inexpensive tool for targeting subsets of COPD patients with severe or very severe short-term prognosis.

Chronic Renal Failure: A Neglected Comorbidity of COPD

BACKGROUND To the best of our knowledge, the association between COPD and chronic renal failure (CRF) has never been assessed. Lean mass is frequently reduced in COPD, and the glomerular filtration rate (GFR) might be depressed in spite of normal serum creatinine (concealed CRF). We investigated the prevalence and correlates of both concealed and overt CRF in elderly patients with COPD. METHODS We evaluated 356 consecutive elderly outpatients with COPD enrolled in the Extrapulmonary Consequences of COPD in the Elderly Study and 290 age-matched outpatients free from COPD. The GFR was estimated using the Modification of Diet in Renal Disease Study Group equation. Patients were categorized as having normal renal function (GFR > or = 60 mL/min/1.73 m(2)), concealed CRF (normal serum creatinine and reduced GFR), or overt CRF (increased serum creatinine and reduced GFR). Independent correlates of CRF were investigated by logistic regression analysis. RESULTS The prevalence of concealed and overt CRF in patients with COPD was 20.8% and 22.2%, respectively. Corresponding figures in controls were 10.0% and 13.4%, respectively. COPD and age were significantly associated with both concealed CRF (COPD: odds ratio [OR] = 2.19, 95% CI = 1.17-4.12; age: OR = 1.06, 95% CI = 1.04-1.09) and overt CRF (COPD: OR = 1.94, 95% CI = 1.01-4.66; age: OR = 1.06, 95% CI = 1.04-1.10). Diabetes (OR = 1.96, 95% CI = 1.02-3.76), hypoalbuminemia (OR = 2.83, 95% CI = 1.70-4.73), and muscle-skeletal diseases (OR = 1.78, 95% CI = 1.01-3.16) were significant correlates of concealed CRF. BMI (OR = 1.05, 95% CI = 1.01-1.10) and diabetes (OR = 2.25, 95% CI = 1.26-4.03) were significantly associated with overt CRF. CONCLUSIONS CRF is highly prevalent in patients with COPD, even with normal serum creatinine, and might contribute to explaining selected conditions such as anemia that are frequent complications of COPD.

Cognitive Impairment in chronic obstructive pulmonary disease: a neuropsychological and spect study

Abstract. Some analogy exists between cognitive impairment in hypoxemic patients with chronic obstructive pulmonary disease (COPD) and Alzheimers disease (AD). We purposed to verify whether the analogy extends to the cerebral perfusion pattern. Ten normal subjects, 15 COPD patients with and 18 without hypoxemia, and 15 patients with mild AD matched for age and educational level underwent brain perfusion single photon emission computed tomography (SPECT) and neuropsychological assessment. Normal subjects and non hypoxemic COPD patients had comparable perfusion patterns. The average perfusion decreased from non hypoxemic to hypoxemic COPD and, then, to AD patients. Hypoperfusion of associative areas was the hallmark of AD, whereas the average perfusion of anterior cortical and subcortical regions did not distinguish AD and hypoxemic COPD patients. Both COPD groups scored higher than AD patients (p ≤ 0.01) in 13 cognitive tests but below the normal in selected tests of verbal attainment, attention and deductive thinking. Perfusion of anterior cortical and subcortical regions of the dominant hemisphere was directly correlated with the number of correctly performed neuropsychologic tests. In conclusion, anterior cerebral hypoperfusion and selected neuropsychological dysfunctions characterized hypoxemic COPD patients and could herald frontal-type cognitive decline with the worsening of the hypoxemia.

Does cognitive dysfunction conform to a distinctive pattern in obstructive sleep apnea syndrome

Obstructive sleep apnea (OSA) is a recognized cause of cognitive dysfunction. By using a cross‐sectional comparative study, we aimed to verify whether neuropsychological performance of untreated OSA patients conforms to a distinctive pattern. Forty‐nine newly diagnosed, untreated OSA patients, 27 with multi‐infarctual dementia (MID), 31 with mild to moderate dementia of Alzheimer type (DAT) and 63 with severe chronic obstructive pulmonary disease (COPD), all free from major comorbid dementing conditions were chosen for the study. The groups were matched for age and education. We found a bimodal distribution of cognitive performance in OSA group, which was therefore divided into two clusters having better (OSAb, n = 35) and worse (OSAw, n = 14) performance on a battery of 10 cognitive indexes. Cognitive performances of OSAb, OSAw, MID, DAT and COPD were compared by discriminant analysis. OSAb performed better than OSAw in all but one test. Deductive thinking and verbal attainment were more severely impaired in OSAw than in COPD patients. Constructive ability, deductive thinking and both verbal attainment and immediate memory were comparably impaired in OSAw and DAT. The mean neuropsychological scores of OSAw and MID were comparable, but 71% of OSAw patients had a distinctive cognitive profile, i.e. a group specific pattern of cognitive dysfunction, according to discriminant analysis. One of four newly diagnosed OSA patients had a severe and distinctive neuropsychological dysfunction mainly involving inductive and deductive thinking, and constructive ability. Some analogy with cognitive pattern of MID suggests that a mainly subcortical damage underlies this dysfunction.

Original ResearchCOPDChronic Renal Failure: A Neglected Comorbidity of COPD

BACKGROUND To the best of our knowledge, the association between COPD and chronic renal failure (CRF) has never been assessed. Lean mass is frequently reduced in COPD, and the glomerular filtration rate (GFR) might be depressed in spite of normal serum creatinine (concealed CRF). We investigated the prevalence and correlates of both concealed and overt CRF in elderly patients with COPD. METHODS We evaluated 356 consecutive elderly outpatients with COPD enrolled in the Extrapulmonary Consequences of COPD in the Elderly Study and 290 age-matched outpatients free from COPD. The GFR was estimated using the Modification of Diet in Renal Disease Study Group equation. Patients were categorized as having normal renal function (GFR > or = 60 mL/min/1.73 m(2)), concealed CRF (normal serum creatinine and reduced GFR), or overt CRF (increased serum creatinine and reduced GFR). Independent correlates of CRF were investigated by logistic regression analysis. RESULTS The prevalence of concealed and overt CRF in patients with COPD was 20.8% and 22.2%, respectively. Corresponding figures in controls were 10.0% and 13.4%, respectively. COPD and age were significantly associated with both concealed CRF (COPD: odds ratio [OR] = 2.19, 95% CI = 1.17-4.12; age: OR = 1.06, 95% CI = 1.04-1.09) and overt CRF (COPD: OR = 1.94, 95% CI = 1.01-4.66; age: OR = 1.06, 95% CI = 1.04-1.10). Diabetes (OR = 1.96, 95% CI = 1.02-3.76), hypoalbuminemia (OR = 2.83, 95% CI = 1.70-4.73), and muscle-skeletal diseases (OR = 1.78, 95% CI = 1.01-3.16) were significant correlates of concealed CRF. BMI (OR = 1.05, 95% CI = 1.01-1.10) and diabetes (OR = 2.25, 95% CI = 1.26-4.03) were significantly associated with overt CRF. CONCLUSIONS CRF is highly prevalent in patients with COPD, even with normal serum creatinine, and might contribute to explaining selected conditions such as anemia that are frequent complications of COPD.

Regimen complexity and medication nonadherence in elderly patients

Objective: To assess whether the number of daily administrations of individual drugs, as a measure of regimen complexity, contributes to the profile of an elderly patient who adheres poorly to the prescribed therapy. Population: Six hundred ninety patients over 64 years who were consecutively admitted to 11 acute medical care and three long term/rehabilitation wards in Italy. Main outcome measure: Self-reported adherence to drugs taken at home before admission was measured by a single question assessment for each listed drug supplemented with a latter question about the circumstances of the missed administration. For cognitively impaired patients the question was put to patients’ relatives or caregivers. Methods: A structured multidimensional assessment was performed to identify nonadherence and its potential correlates. Correlates of nonadherence were identified by multivariable logistic regression. Results: We recorded 44 cases (6.4%) of nonadherence to at least one drug. Being assisted by foreign caregivers (OR 2.17; 95% CI 1.02–4.63) and the use of at least one multiple daily dosing drug (OR 2.99; 95% CI 1.24–7.17) were significant independent correlates of medication nonadherence, while age, selected indexes of frailty and the cumulative number of prescribed drugs were not. Conclusion: Regimen complexity and type of assistance are independent correlates of medication nonadherence.