Chronic obstructive pulmonary disease is underdiagnosed and undertreated in São Paulo (Brazil): results of the PLATINO study

Chronic obstructive pulmonary disease (COPD) is a common disease in adults over 40 years of age and has a great social and economic impact. It remains little recognized and undertreated even in developed countries. However, there are no data about its diagnosis and treatment in Brazil. The objectives of the present study were to evaluate the proportion of COPD patients who had never been diagnosed and to determine if the COPD patients who had been identified were receiving appropriate treatment. The Latin American Project for the Investigation of Obstructive Lung Disease (PLATINO) was a randomized epidemiological study of adults over 40 years living in five metropolitan areas, including São Paulo. The studied sample was randomly selected from the population after a division of the metropolitan area of São Paulo in clusters according to social characteristics. All subjects answered a standardized questionnaire on respiratory symptoms, history of smoking, previous diagnosis of lung disease, and treatments. All subjects performed spirometry. The criterion for the diagnosis of COPD was defined by a post-bronchodilator FEV1/FVC ratio lower than 0.7. A total of 918 subjects were evaluated and 144 (15.8%) met the diagnostic criterion for COPD. However, 126 individuals (87.5%) had never been diagnosed. This undiagnosed group of COPD patients had a lower proportion of subjects with respiratory symptoms than the previously diagnosed patients (88.9 vs 54.8%) and showed better lung function with greater FEV1 (86.8 ± 20.8 vs 68.5 ± 23.6% predicted) and FVC (106.6 ± 22.4 vs 92.0 ± 24.1% predicted). Among the COPD patients, only 57.3% were advised to stop smoking and 30.6% received the influenza vaccine. In addition, 82.3% did not receive any pharmacological treatment. In conclusion, COPD is underdiagnosed and a large number of COPD patients are not treated appropriately.

MFG-E8, a clearance glycoprotein of apoptotic cells, as a new marker of disease severity in chronic obstructive pulmonary disease

Milk fat globule epidermal growth factor 8 (MFG-E8) is an opsonin involved in the phagocytosis of apoptotic cells. In patients with chronic obstructive pulmonary disease (COPD), apoptotic cell clearance is defective. However, whether aberrant MFG-E8 expression is involved in this defect is unknown. In this study, we examined the expression of MFG-E8 in COPD patients. MFG-E8, interleukin (IL)-1β and transforming growth factor (TGF)-β levels were measured in the plasma of 96 COPD patients (93 males, 3 females; age range: 62.12±10.39) and 87 age-matched healthy controls (85 males, 2 females; age range: 64.81±10.11 years) using an enzyme-linked immunosorbent assay. Compared with controls, COPD patients had a significantly lower plasma MFG-E8 levels (P<0.01) and significantly higher plasma TGF-β levels (P=0.002), whereas there was no difference in plasma IL-1β levels between the two groups. Moreover, plasma MFG-E8 levels decreased progressively between Global Initiative for Chronic Obstructive Lung Disease (GOLD) I and GOLD IV stage COPD. Multiple regression analysis showed that the forced expiratory volume in 1 s (FEV1 % predicted) and smoking habit were powerful predictors of MFG-E8 in COPD (P<0.01 and P=0.026, respectively). MFG-E8 was positively associated with the FEV1 % predicted and negatively associated with smoking habit. The area under the receiver operating characteristic curve was 0.874 (95% confidence interval: 0.798-0.95; P<0.01). Our findings demonstrated the utility of MFG-E8 as a marker of disease severity in COPD and that cigarette smoke impaired MFG-E8 expression in these patients.

Prevalence of Chronic Kidney Disease in newly diagnosed patients with Human immunodeficiency virus in Ilorin, Nigeria

AbstractIntroduction:Human immunodeficiency virus (HIV) the causative agent of Acquired immunodeficiency syndrome (AIDS) is an important cause of renal diseases in sub-Saharan Africa. There is paucity of studies on the burden of chronic kidney disease (CKD) among patients with HIV/AIDS in the North-Central zone of Nigeria.Methods:This is a cross-sectional study of 227 newly-diagnosed, antiretroviral naïve patients with HIV/AIDS seen at the HIV clinic of the Medical Out-patient Department (MOPD) of University of Ilorin Teaching Hospital (UITH). They were matched with 108 control group. Laboratory investigations were performed for the participants. CKD was defined as estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 and/or albumin creatinine ratio (ACR) > 30 mg/g.Results:There were 100 (44%) males among the patients and 47 (43.5%) among the control group. The mean ages of the patients and controls were 40.3 ± 10.3 years and 41.8 ± 9.5 years respectively. CKD was observed in 108 (47.6%) among the patients and 18 (16.7%) of the controls (p = 0.01). The median CD4 T-cell count was significantly lower in patients with CKD. Ninety-three (41.0%) of the patients had dipstick proteinuria of > 2 +. The median albumin creatinine ratio (ACR) was significantly higher among the HIV-positive patients (272.3 mg/g) compared with the HIV-negative controls (27.22 mg/g) p = 0.01. The CD4 T-cell count correlates positively with eGFR (r = 0.463, p = 0.001) and negatively with ACR (r = -0.806, p = 0.001).Conclusions:CKD is very common among patients with HIV/AIDS in Ilorin. Screening and early intervention for CKD should be part of the protocols in the management of these patients.

Economic burden of expected epidemiological changes in diseases related to tobacco, Mexico

OBJECTIVE: To determine health care costs and economic burden of epidemiological changes in diseases related to tobacco consumption. METHODS: A time-series analysis in Mexico (1994-2005) was carried out on seven health interventions: chronic obstructive pulmonary diseases, lung cancer with and without surgical intervention, asthma in smokers and non-smokers, full treatment course with nicotine gum, and full treatment course with nicotine patch. According with Box-Jenkins methodology, probabilistic models were developed to forecast the expected changes in the epidemiologic profile and the expected changes in health care services required for selected interventions. Health care costs were estimated following the instrumentation methods and validated with consensus technique. RESULTS: A comparison of the economic impact in 2006 vs. 2008 showed 20-90% increase in expected cases depending on the disease (p<0.05), and 25-93% increase in financial requirements (p<0.01). The study data suggest that changes in the demand for health services for patients with respiratory diseases related to tobacco consumption will continue showing an increasing trend. CONCLUSIONS: In economic terms, the growing number of cases expected during the study period indicates a process of internal competition and adds an element of intrinsic competition in the management of preventive and curative interventions. The study results support the assumption that if preventive programs remain unchanged, the increasing demands for curative health care may cause great financial and management challenges to the health care system of middle-income countries like Mexico.

Effect of melatonin administration on subjective sleep quality in chronic obstructive pulmonary disease

Disturbed sleep is common in chronic obstructive pulmonary disease (COPD). Conventional hypnotics worsen nocturnal hypoxemia and, in severe cases, can lead to respiratory failure. Exogenous melatonin has somnogenic properties in normal subjects and can improve sleep in several clinical conditions. This randomized, double-blind, placebo-controlled study was carried out to determine the effects of melatonin on sleep in COPD. Thirty consecutive patients with moderate to very severe COPD were initially recruited for the study. None of the participants had a history of disease exacerbation 4 weeks prior to the study, obstructive sleep apnea, mental disorders, current use of oral steroids, methylxanthines or hypnotic-sedative medication, nocturnal oxygen therapy, and shift work. Patients received 3 mg melatonin (N = 12) or placebo (N = 13), orally in a single dose, 1 h before bedtime for 21 consecutive days. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI) and daytime sleepiness was measured by the Epworth Sleepiness Scale. Pulmonary function and functional exercise level were assessed by spirometry and the 6-min walk test, respectively. Twenty-five patients completed the study protocol and were included in the final analysis. Melatonin treatment significantly improved global PSQI scores (P = 0.012), particularly sleep latency (P = 0.008) and sleep duration (P = 0.046). No differences in daytime sleepiness, lung function and functional exercise level were observed. We conclude that melatonin can improve sleep in COPD. Further long-term studies involving larger number of patients are needed before melatonin can be safely recommended for the management of sleep disturbances in these patients.

Dynamics of chest wall volume regulation during constant work rate exercise in patients with chronic obstructive pulmonary disease

This study evaluated the dynamic behavior of total and compartmental chest wall volumes [(V CW) = rib cage (V RC) + abdomen (V AB)] as measured breath-by-breath by optoelectronic plethysmography during constant-load exercise in patients with stable chronic obstructive pulmonary disease. Thirty males (GOLD stages II-III) underwent a cardiopulmonary exercise test to the limit of tolerance (Tlim) at 75% of peak work rate on an electronically braked cycle ergometer. Exercise-induced dynamic hyperinflation was considered to be present when end-expiratory (EE) V CW increased in relation to resting values. There was a noticeable heterogeneity in the patterns of V CW regulation as EEV CW increased non-linearly in 17/30 "hyperinflators" and decreased in 13/30 "non-hyperinflators" (P < 0.05). EEV AB decreased slightly in 8 of the "hyperinflators", thereby reducing and slowing the rate of increase in end-inspiratory (EI) V CW (P < 0.05). In contrast, decreases in EEV CW in the "non-hyperinflators" were due to the combination of stable EEV RC with marked reductions in EEV AB. These patients showed lower EIV CW and end-exercise dyspnea scores but longer Tlim than their counterparts (P < 0.05). Dyspnea increased and Tlim decreased non-linearly with a faster rate of increase in EIV CW regardless of the presence or absence of dynamic hyperinflation (P < 0.001). However, no significant between-group differences were observed in metabolic, pulmonary gas exchange and cardiovascular responses to exercise. Chest wall volumes are continuously regulated during exercise in order to postpone (or even avoid) their migration to higher operating volumes in patients with COPD, a dynamic process that is strongly dependent on the behavior of the abdominal compartment.

Long-term efficacy of a rural community-based integrated intervention for prevention and management of chronic obstructive pulmonary disease: a cluster randomized controlled trial in China's rural areas

This study aimed to assess the efficacy of a rural community-based integrated intervention for early prevention and management of chronic obstructive pulmonary disease (COPD) in China. This 18-year cluster-randomized controlled trial encompassing 15 villages included 1008 patients (454 men and 40 women in the intervention group [mean age, 54 ± 10 years]; 482 men and 32 women in the control group [mean age, 53 ± 10 years]) with confirmed COPD or at risk for COPD. Villages were randomly assigned to the intervention or the control group, and study participants residing within the villages received treatment accordingly. Intervention group patients took part in a program that included systematic health education, smoking cessation counseling, and education on management of COPD. Control group patients received usual care. The groups were compared after 18 years regarding the incidence of COPD, decline in lung function, and mortality of COPD. COPD incidence was lower in the intervention group than in the control group (10% vs 16%, <0.05). A decline in lung function was also significantly delayed in the intervention group compared to the control group of COPD and high-risk patients. The intervention group showed significant improvement in smoking cessation compared with the control group, and smokers in the intervention group had lower smoking indices than in the control group (350 vs 450, <0.05). The intervention group also had a significantly lower cumulative COPD-related death rate than the control group (37% vs 47%, <0.05). A rural community-based integrated intervention is effective in reducing the incidence of COPD among those at risk, delaying a decline in lung function in COPD patients and those at risk, and reducing mortality of COPD.

The epidemiology of acute viral gastroenteritis in hospitalized children in Cordoba city, Argentina: an insight of disease burden

Information concerning the disease burden of viral gastroenteritis has important implications for the use and monitoring the impact of public health policies. The present study, carried out in Córdoba city, Argentina, documents the epidemiology of severe viral diarrhea as well as the burden of viral gastrointestinal disease in the hospital children admission. A total of 133 stools were collected from hospitalized children (Town Childhood Hospital) suffering from acute diarrhea and studied for the presence of Group A rotavirus, astrovirus and adenovirus 40/41 by enzyme-immuno assay, between November 1997 and October 1998. Enteric viruses accounted for 42.1% of the total diarrheal cases analyzed. Group A rotaviruses, astroviruses, adenoviruses 40/41 and mixed infections were found in 35.3, 4.5, 1.5, and 0.8% studied specimens respectively. We estimated that 1 in 27 children in the 0-35 month-old cohort/range would be annually hospitalized for a viral gastroenteritis illness. The major impact on viral diarrhea lies on rotaviral infection, accouting for 84.0% of the viral diarrheal cases analyzed and for approximately one third of severe diarrheas requiring hospital admission in Córdoba City, Argentina.

MORBIDITY AND MORTALITY DUE TO AIDS: A STUDY OF BURDEN OF DISEASE AT A MUNICIPAL LEVEL

Introduction: The purpose of measuring the burden of disease involves aggregating morbidity and mortality components into a single indicator, the disability-adjusted life year (DALY), to measure how much and how people live and suffer the impact of a disease. Objective: To estimate the global burden of disease due to AIDS in a municipality of southern Brazil. Methods: An ecological study was conducted in 2009 to examine the incidence and AIDS-related deaths among the population residing in the city of Tubarao, Santa Catarina State, Brazil. Data from the Mortality Information System in the National Health System was used to calculate the years of life lost (YLL) due to premature mortality. The calculation was based on the difference between a standardized life expectancy and age at death, with a discount rate of 3% per year. Data from the Information System for Notifiable Diseases were used to calculate the years lived with disability (YLD). The DALY was estimated by the sum of YLL and YLD. Indicator rates were estimated per 100,000 inhabitants, distributed by age and gender. Results: A total of 131 records were examined, and a 572.5 DALYs were estimated, which generated a rate of 593.1 DALYs/100,000 inhabitants. The rate among men amounted to 780.7 DALYs/100,000, whereas among women the rate was 417.1 DALYs/100,000. The most affected age groups were 30-44 years for men and 60-69 years for women. Conclusion: The burden of disease due to AIDS in the city of Tubarao was relatively high when considering the global trend. The mortality component accounted for more than 90% of the burden of disease.

Effect of clarithromycin on the cell profile of bronchoalveolar lavage fluid in mice with neutrophil-predominant lung disease

OBJECTIVE: Macrolide antibiotics have anti-inflammatory properties in lung diseases. The aim of this study was to investigate the effect of clarithromycin in pulmonary cellular inflammatory response in mice. METHOD: Eight adult Swiss mice were studied. All animals received an intranasal challenge (80 µL) with dead Pseudomonas aeruginosa (1.0 x 10(12) CFU/mL). Bronchoalveolar lavage was performed 2 days later, with total cell count and differential cell analysis. The study group (n = 4) received clarithromycin treatment (50 mg/kg/day, intraperitoneal) for 5 days. Treatment was initiated 2 days before intranasal challenge. RESULTS: There was no significant difference in total cell count between the groups (mean: 2.0 x 10(6) and 1.3 x 10(6), respectively). In both groups, there was a predominance of neutrophils. However, the study group had a higher percentage of lymphocytes in the bronchoalveolar lavage than the control group (median of 19% vs 2.5%, P = .029). CONCLUSION: Clarithromycin alters the cytological pattern of bronchoalveolar lavage of Swiss mice with neutrophil pulmonary inflammation, significantly increasing the percentage of lymphocytes.

Are apolipoproteins A and B better than lipoproteins for assessing risk of obstructive coronary heart disease?

OBJECTIVE: To evaluate whether apolipoproteins A-I (Apo A-I) and B (Apo B) have, higher ensitivity (SN), specificity (SP) and positive predictive value (PPV) than lipoproteins (LP), total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL), and triglycerides (TGL) in assessing the risk of coronary heart disease (CHD). METHODS: This is a transversal case-control study of 241 patients, who were divided into two groups: 1) 145 patients with CHD, and 2) 96 patients without coronary disease. A model of logistic regression to evaluate the relation between the LPs and CHD was developed in which variables with a p-alpha <0.1 were included. RESULTS: Apo A-I levels were higher in the patients without CHD, (OR 2.08, CI 1.20-3.57). There were no statistical differences between the values of Apo A-I and the remaining lipid fractions (Apo A-I: 67%; Apo B: 100%; PPV: TC= 71%; TGC=71%; HDL=71%; LDL=71%). The costs of the tests in Reais were as follows: Apo A-I: R$ 56.60; Apo B-100: R$ 56.60; TC: R$ 9.94; HDL: R$ 21.30; LDL: R$ 28.40; TGL: R$ 14.20. CONCLUSION: Levels of Apo A-I and Apo B have no advantage over conventional lipoproteins in predicting the risk of CHD, despite the statistical association between Apo A-I and CHD; in addition, their costs are higher than those of the conventional lipoproteins.

New auxiliary indicators for the differential diagnosis of functional cardiorespiratory limitation in patients with chronic obstructive pulmonary disease and congestive heart failure

OBJECTIVE: To differentiate the nature of functional cardiorespiratory limitations during exercise in individuals with chronic obstructive pulmonary disease (COPD) or congestive heart failure (CHF) and to determine indicators that may help their classifications. METHODS: The study comprised 40 patients: 23 with COPD and 17 with CHF. All individuals underwent maximal cardiopulmonary exercise testing on a treadmill. RESULTS: The values of peak gas exchange ratio (R peak), peak carbon dioxide production (VCO2 peak), and peak oxygen ventilatory equivalent (V E O2 peak) were higher in the patients with CHF than in those with COPD, and, therefore, those were the variables that characterized the differences between the groups. For group classification, the differentiating functions with the R peak, VCO2 peak (L/min), and V E O2 peak variables were used as follows: group COPD: - 44.886 + 78.832 x R peak + 5.442 x VCO2 peak + 0.336 x V E O2 peak; group CHF: - 69.251 + 89.740 x R peak + 8.461 x VCO2 peak + 0.574 x V E O2 peak. The differentiating function, whose result is greater, correctly classifies the patient's group as 90%. CONCLUSION: The R peak, VCO2 peak, and V E O2 peak values may be used to identify the cause of the functional cardiorespiratory limitations in patients with COPD and CHF.

Classification of chronic obstructive pulmonary disease based on chest radiography

Objective Quantitative analysis of chest radiographs of patients with and without chronic obstructive pulmonary disease (COPD) determining if the data obtained from such radiographic images could classify such individuals according to the presence or absence of disease. Materials and Methods For such a purpose, three groups of chest radiographic images were utilized, namely: group 1, including 25 individuals with COPD; group 2, including 27 individuals without COPD; and group 3 (utilized for the reclassification /validation of the analysis), including 15 individuals with COPD. The COPD classification was based on spirometry. The variables normalized by retrosternal height were the following: pulmonary width (LARGP); levels of right (ALBDIR) and left (ALBESQ) diaphragmatic eventration; costophrenic angle (ANGCF); and right (DISDIR) and left (DISESQ) intercostal distances. Results As the radiographic images of patients with and without COPD were compared, statistically significant differences were observed between the two groups on the variables related to the diaphragm. In the COPD reclassification the following variables presented the highest indices of correct classification: ANGCF (80%), ALBDIR (73.3%), ALBESQ (86.7%). Conclusion The radiographic assessment of the chest demonstrated that the variables related to the diaphragm allow a better differentiation between individuals with and without COPD.

Concentration of CCL11, CXCL8 and TNF-alpha in sputum and plasma of patients undergoing asthma or chronic obstructive pulmonary disease exacerbation

Asthma and chronic obstructive pulmonary disease (COPD) are common respiratory illnesses characterized by chronic inflammation of the airways. The characterization of induced or spontaneously produced sputum is a useful technique to assess airway inflammation. In the present study, we compared the concentrations of CCL2, CCL11, CXCL8, and tumor necrosis factor-alpha (TNF-alpha) in plasma and induced sputum of patients with severe asthma or COPD and correlated the levels of these mediators with inflammatory cells in sputum. Asthmatic patients had elevated levels of eosinophils (40.1 ± 6.24%) in sputum whereas neutrophils (63.3 ± 4.66%) predominated in COPD patients. The levels of the chemokine CCL11 were markedly increased in sputum (708.7 ± 330.7 pg/ml) and plasma (716.6 ± 162.2 pg/ml) of asthmatic patients and correlated with the percentage of eosinophils in induced sputum. The concentrations of CXCL8 (817.0 ± 105.2 pg/ml) and TNF-alpha (308.8 ± 96.1 pg/ml) were higher in sputum of COPD patients and correlated with the percentage of neutrophils in induced sputum. There was also an increase in the concentrations of CXCL8 (43.2 ± 6.8 pg/ml) in sputum of asthmatic patients. These results validate that sputum is a suitable method to assess chemokines and cytokines associated with asthma and COPD. Moreover, the mechanisms involved in the synthesis of CCL11 and CXCL8/TNF-alpha would be helpful to better understand the inflammatory profile associated with asthma and COPD, respectively.

Relationship between disease severity and quality of life in patients with chronic obstructive pulmonary disease

Few studies have evaluated the relationship between Airways Questionnaire 20 (AQ20), a measure of the quality of life, scores and physiological outcomes or with systemic markers of disease in patients with chronic obstructive pulmonary disease (COPD). The aim of the present study was to investigate the relationship of forced expiratory volume in 1 s (FEV1), body mass index, fat-free mass index, 6-min walk test (6MWT) results, dyspnea sensation and peripheral oxygen saturation (SpO2) with the quality of life of COPD patients. Ninety-nine patients with COPD (mean age: 64.2 ± 9.2 years; mean FEV1: 60.4 ± 25.2% of predicted) were evaluated using spirometry, body composition measurement and the 6MWT. The baseline dyspnea index (BDI) and the Modified Medical Research Council (MMRC) scale were used to quantify dyspnea. Quality of life was assessed using the AQ20 and the St. George's Respiratory Questionnaire (SGRQ). The Charlson index was used to determine comorbidity. The body mass index/airflow obstruction/dyspnea/exercise capacity (BODE) index was also calculated. AQ20 and SGRQ scores correlated significantly with FEV1, SpO2, 6MWT, MMRC and BDI values as did with BODE index. In the multivariate analyses, MMRC or BDI were identified as predictors of AQ20 and SGRQ scores (P < 0.001 in all cases). Thus, the relationship between AQ20 and disease severity is similar to that described for SGRQ. Therefore, the AQ20, a simple and brief instrument, can be very useful to evaluate the general impact of disease when the time allotted for measurement of the quality of life is limited.