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.

Interrelationship between serum and sputum inflammatory mediators in chronic obstructive pulmonary disease

Little is known about airway inflammatory markers in chronic obstructive pulmonary disease (COPD). The objective of the present study was to identify and try to correlate pulmonary and peripheral blood inflammatory markers in COPD. In a cross-sectional study on patients with stable COPD, induced sputum and blood samples were collected for the determination of C-reactive protein, eosinophilic cationic protein, serum amyloid A protein, a-1 antitrypsin (a-1AT), and neutrophil elastase. Twenty-two patients were divided into two groups according to post-bronchodilator forced expiratory volume in the first second (%FEV1): group 1 (N = 12, FEV1 <40%) and group 2 (N = 10, FEV1 ³40%). An increase in serum elastase, eosinophilic cationic protein and a-1AT was observed in serum markers in both groups. Cytology revealed the same total number of cells in groups 1 and 2. There was a significantly higher number of neutrophils in group 1 compared to group 2 (P < 0.05). No difference in eosinophils or macrophages was observed between groups. Serum elastase was positively correlated with serum a-1AT (group 1, r = 0.81, P < 0.002 and group 2, r = 0.83, P < 0.17) and negatively correlated with FEV1 (r = -0.85, P < 0.03 and -0.14, P < 0.85, respectively). The results indicate the presence of chronic and persistent pulmonary inflammation in stable patients with COPD. Induced sputum permitted the demonstration of the existence of a subpopulation of cells in which neutrophils predominated. The serum concentration of all inflammatory markers did not correlate with the pulmonary functional impairment.

Ethnicity as a risk factor for obstructive sleep apnea: comparison of Japanese descendants and white males in São Paulo, Brazil

Some studies showed that Asians with obstructive sleep apnea (OSA) are thinner than Caucasians. Because obesity is a major risk factor for OSA, it was concluded that Asians are predisposed to OSA. However, body fat composition varies for a same body mass index (BMI) according to ethnicity. We firstly compared anthropometric characteristics, symptoms and associated disorders in all consecutive male Japanese descendants and white males with OSA referred for polysomnography. In a second analysis, all Japanese descendants were compared to a subgroup of white males, matched for apnea/hypopnea index and age. In the first analysis, age, symptoms, OSA severity and co-morbidities were similar among Japanese descendants (N = 54) and white patients (N = 466). However, Japanese descendants had a lower BMI than white patients: 27.1 (25.5-28.4) vs 29.4 (26.5-33.0) kg/m², respectively (P < 0.001). In the second analysis, Japanese descendants had a lower BMI than white patients (P < 0.001). Multiple linear regression considering the entire group revealed that age, BMI, neck circumference, Epworth sleepiness scale, ethnicity and %REM sleep were independent predictors for apnea/hypopnea index (P < 0.001). Ethnicity was no longer significantly associated with OSA severity when we adopted the World Health Organization criteria for obesity (≥25 and 30 kg/m² among Japanese descendants and white males, respectively). Japanese descendants with OSA have a lower BMI than white subjects of similar severity. However, ethnicity was not associated with OSA severity when an ethnical difference in obesity criteria was respected. Our data suggest that Japanese descendants are not predisposed to OSA.

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.

Relationship between the quality of life and the severity of obstructive sleep apnea syndrome

The effects of sleep disorders on the quality of life (QOL) have been documented in the literature. Excessive sleepiness and altered circadian rhythms may negatively affect ability to learn, employment, and interpersonal relations, and directly degrade QOL. The objective of the present study was to evaluate the impact of obstructive sleep apnea syndrome of varying severity on QOL. The study was conducted on 1892 patients aged 18 years or older referred by a physician to the Sleep Institute, São Paulo, with complaints related to apnea (snoring, excessive daytime sleepiness, hyperarousal, and fatigue). They were submitted to overnight polysomnography for the diagnosis of sleep disorders from August 2005 through April 2006. The patients completed the Epworth Sleepiness Scale and QOL SF-36 sleep questionnaires. They were classified as non-physically active and physically active and not-sleepy and sleepy and the results of polysomnography were analyzed on the basis of the apnea hypopnea index (AHI). The apneic subjects showed a reduction in QOL which was proportional to severity. There was a significant decrease in all domains (physical functioning, role physical problems, bodily pain, general health perceptions, vitality, social functioning, emotional problems, general mental health) for apneics with AHI >30, who generally were sleepy and did not participate in physical activities (P < 0.05). The present study provides evidence that the impact of sleep disorders on QOL in apneics is not limited to excessive daytime sleepiness and that physical activity can contribute to reducing the symptoms. Thus, exercise should be considered as an adjunct interventional strategy in the management of obstructive sleep apnea syndrome.

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.

Breathing pattern and thoracoabdominal motion during exercise in chronic obstructive pulmonary disease

Subjects with chronic obstructive pulmonary disease (COPD) present breathing pattern and thoracoabdominal motion abnormalities that may contribute to exercise limitation. Twenty-two men with stable COPD (FEV1 = 42.6 ± 13.5% predicted; age 68 ± 8 years; mean ± SD) on usual medication and with at least 5 years of diagnosis were evaluated at rest and during an incremental cycle exercise test (10 watts/2 min). Changes in respiratory frequency, tidal volume, rib cage and abdominal motion contribution to tidal volume and the phase angle that measures the asynchrony were analyzed by inductive respiratory plethysmography at rest and during three levels of exercise (30-50, 70-80, and 100% maximal work load). Repeated measures ANOVA followed by pre-planned contrasts and Bonferroni corrections were used for analyses. As expected, the greater the exercise intensity the higher the tidal volume and respiratory frequency. Abdominal motion contributed to the tidal volume increase (rest: 49.82 ± 11.19% vs exercise: 64.15 ± 9.7%, 63.41 ± 10%, and 65.56 ± 10.2%, respectively, P < 0.001) as well as the asynchrony [phase angle: 11.95 ± 7.24° at rest vs 22.2 ± 15° (P = 0.002), 22.6 ± 9° (P < 0.001), and 22.7 ± 8° (P < 0.001), respectively, at the three levels of exercise]. In conclusion, the increase in ventilation during exercise in COPD patients was associated with the major motion of the abdominal compartment and with an increase in the asynchrony independent of exercise intensity. It suggests that cycling exercise is an effective way of enhancing ventilation in COPD patients.

Systematic head and neck physical examination as a predictor of obstructive sleep apnea in class III obese patients

Our aim was to determine if anatomical abnormalities of the upper airway (UA) and facial skeleton of class III severely obese patients are related to the presence and severity of obstructive sleep apnea syndrome (OSAS). Forty-five patients (69% females, mean age 46.5 ± 10.8 years) with a body mass index (BMI) over 40 kg/m² underwent UA and facial skeletal examinations as well as polysomnography. Mean BMI was 49 ± 7 kg/m² and mean neck circumference was 43.4 ± 5.1 cm. Polysomnographic findings showed that 22% had a normal apnea-hypopnea index (AHI) and 78% had an AHI over 5. The presence of OSAS was associated with younger age (P = 0.02), larger neck circumference (P = 0.004), presence of a voluminous lateral wall (P = 0.0002), posteriorized soft palate (P = 0.0053), thick soft palate (P = 0.0014), long uvula (P = 0.04), thick uvula (P = 0.0052), and inferior turbinate hypertrophy (P = 0.04). A larger neck circumference (P = 0.02), presence of a voluminous lateral wall (P = 0.04), posteriorized soft palate (P = 0.03), and thick soft palate (P = 0.04) were all associated with OSAS severity. The prevalence of OSAS in this group was high. A larger neck circumference and soft tissue abnormalities of the UA were markers for both the presence and severity of OSAS. Conversely, no abnormalities in the facial skeleton were associated with OSAS in patients with morbid obesity.

Influence of renal denervation on blood pressure, sodium and water excretion in acute total obstructive apnea in rats

Obstructive apnea (OA) can exert significant effects on renal sympathetic nerve activity (RSNA) and hemodynamic parameters. The present study focuses on the modulatory actions of RSNA on OA-induced sodium and water retention. The experiments were performed in renal-denervated rats (D; N = 9), which were compared to sham (S; N = 9) rats. Mean arterial pressure (MAP) and heart rate (HR) were assessed via an intrafemoral catheter. A catheter was inserted into the bladder for urinary measurements. OA episodes were induced via occlusion of the catheter inserted into the trachea. After an equilibration period, OA was induced for 20 s every 2 min and the changes in urine, MAP, HR and RSNA were recorded. Renal denervation did not alter resting MAP (S: 113 ± 4 vs D: 115 ± 4 mmHg) or HR (S: 340 ± 12 vs D: 368 ± 11 bpm). An OA episode resulted in decreased HR and MAP in both groups, but D rats showed exacerbated hypotension and attenuated bradycardia (S: -12 ± 1 mmHg and -16 ± 2 bpm vs D: -16 ± 1 mmHg and 9 ± 2 bpm; P < 0.01). The basal urinary parameters did not change during or after OA in S rats. However, D rats showed significant increases both during and after OA. Renal sympathetic nerve activity in S rats increased (34 ± 9%) during apnea episodes. These results indicate that renal denervation induces elevations of sodium content and urine volume and alters bradycardia and hypotension patterns during total OA in unconscious rats.

Effect of three exercise programs on patients with chronic obstructive pulmonary disease

We compared the effect of three different exercise programs on patients with chronic obstructive pulmonary disease including strength training at 50_80% of one-repetition maximum (1-RM) (ST; N = 11), low-intensity general training (LGT; N = 13), or combined training groups (CT; N = 11). Body composition, muscle strength, treadmill endurance test (TEnd), 6-min walk test (6MWT), Saint George's Respiratory Questionnaire (SGRQ), and baseline dyspnea (BDI) were assessed prior to and after the training programs (12 weeks). The training modalities showed similar improvements (P > 0.05) in SGRQ-total (ST = 13 ± 14%; CT = 12 ± 14%; LGT = 11 ± 10%), BDI (ST = 1.8 ± 4; CT = 1.8 ± 3; LGT = 1 ± 2), 6MWT (ST = 43 ± 51 m; CT = 48 ± 50 m; LGT = 31 ± 75 m), and TEnd (ST = 11 ± 20 min; CT = 11 ± 11 min; LGT = 7 ± 5 min). In the ST and CT groups, an additional improvement in 1-RM values was shown (P < 0.05) compared to the LGT group (ST = 10 ± 6 to 57 ± 36 kg; CT = 6 ± 2 to 38 ± 16 kg; LGT = 1 ± 2 to 16 ± 12 kg). The addition of strength training to our current training program increased muscle strength; however, it produced no additional improvement in walking endurance, dyspnea or quality of life. A simple combined training program provides benefits without increasing the duration of the training sessions.

Three-year follow-up study of respiratory and systemic manifestations of chronic obstructive pulmonary disease

Few studies show patient outcomes over time in chronic obstructive pulmonary disease (COPD). In the present study, we monitored forced expiratory volume in the first second (FEV1) and other manifestations of the disease over 3 years in 133 COPD patients (69% males, age = 65 ± 9 years, FEV1 = 59 ± 25%) evaluated at baseline. During follow-up, 15 patients (11%) died and 23 (17%) dropped out. Measurements for 95 (72%) COPD patients alive after 3 years were analyzed. FEV1, body mass index (BMI), 6-min walking distance (6MWD), Medical Research Council scale (MRC), Saint George’s Respiratory Questionnaire (SGRQ), Charlson Comorbidity index, and BODE index were obtained at baseline and after 3 years. At baseline, 17 patients (18%) presented mild, 39% moderate, 19% severe, and 24% very severe COPD. Predicted FEV1 % and BMI did not change over the period (P > 0.05). FEV1 in liters [1.25 (0.96-1.72) vs 1.26 (0.88-1.60) L; P < 0.001], 6MWD (438 ± 86 vs 412 ± 100 m; P < 0.001), MRC [1 (1-2) vs 2 (1-3); P = 0.002], Charlson index [3 (3-4) vs4 (3-5); P = 0.009], BODE index (2.2 ± 1.8 vs 2.6 ± 2.3; P = 0.008), and total SGRQ (42 ± 19 vs 44 ± 19%; P = 0.041) worsened after 3 years compared to baseline measurements. These data show that COPD patients deteriorated during the 3-year follow-up despite the fact that they had only minor modifications in airway obstruction and body composition. They support the need for comprehensive patient assessment to better identify disease progression.

Anthropometric midarm measurements can detect systemic fat-free mass depletion in patients with chronic obstructive pulmonary disease

Our objective was to determine whether anthropometric measurements of the midarm (MA) could identify subjects with whole body fat-free mass (FFM) depletion. Fifty-five patients (31% females; age: 64.6 ± 9.3 years) with mild/very severe chronic obstructive pulmonary disease (COPD), 18 smokers without COPD (39% females; age: 49.0 ± 7.3 years) and 23 never smoked controls (57% females; age: 48.2 ± 9.6 years) were evaluated. Spirometry, muscle strength and MA circumference were measured. MA muscle area was estimated by anthropometry and MA cross-sectional area by computerized tomography (CT) scan. Bioelectrical impedance was used as the reference method for FFM. MA circumference and MA muscle area correlated with FFM and biceps and triceps strength. Receiver operating characteristic curve analysis showed that MA circumference and MA muscle area cut-off points presented sensitivity and specificity >82% to discriminate FFM-depleted subjects. CT scan measurements did not provide improved sensitivity or specificity. For all groups, there was no significant statistical difference between MA muscle area [35.2 (29.3-45.0) cm²] and MA cross-sectional area values [36.4 (28.5-43.3) cm²] and the linear correlation coefficient between tests was r = 0.77 (P < 0.001). However, Bland-Altman plots revealed wide 95% limits of agreement (-14.7 to 15.0 cm²) between anthropometric and CT scan measurements. Anthropometric MA measurements may provide useful information for identifying subjects with whole body FFM depletion. This is a low-cost technique and can be used in a wider patient population to identify those likely to benefit from a complete body composition evaluation.

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.

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.