Objective: Whether blood eosinophils (bEOS) in chronic obstructive pulmonary disease (COPD) are associated with disease progression is a topic of debate. We aimed to evaluate whether the differential white blood cell (WBC) count, symptoms and treatment may predict lung function decline and exacerbations in COPD patients. Methods: We retrospectively examined stable COPD patients with a minimum follow-up of 3 years at our outpatients' clinic. We collected information about lung volumes (FEV1, FVC), the total and differential WBC count, acute exacerbations of COPD (number in the 12 months before the beginning of the study=AE-COPD-B, and during the follow-up=AE-COPD-F), smoking status and treatment. FEV1 decline and AE-COPD-F were described by using a generalized linear model and a 2-level random intercept negative binomial regression, respectively. The models included eosinophil and neutrophil counts as potential predictors and were adjusted by sex, age, smoking status, AE-COPD-B, treatment with bronchodilators and inhaled corticosteroids (ICS). Results: Sixty-eight patients were considered, 36 bEOS- (<170 cells/µL, the median value) and 32 bEOS+ (=170 cells/µL). ?FEV1 was higher in bEOS+ than bEOS- (34.86 mL/yr vs 4.49 mL/yr, p=0.029). After adjusting for potential confounders, the eosinophil count was positively (ß=19.4; CI 95% 2.8, 36.1; p=0.022) and ICS negatively (ß=-57.7; CI 95% -91.5,-23.9; p=0.001) associated with lung function decline. bEOS were not found to be associated with the number of AE-COPD-F. Conclusion: In stable COPD patients, a higher level of blood eosinophils (albeit in the normal range) predicts a greater FEV1 decline, while ICS are associated with a slower progression of airflow obstruction.

Keywords: COPD; Blood eosinophils; FEV1 decline; Exacerbations; Biomarkers. Correspondence to:

Objective: To describe and analyze clinical symptoms and spirometric alterations of patients with chronic obstructive pulmonary disease (COPD) and history of exposure to wood and tobacco smoke. Methods: We retrospectively evaluated data related to 170 patients distributed into 3 groups: 34 exposed only to wood smoke, 59 patients exposed only to tobacco smoke and 77 patients exposed to both. Results: The groups did not differ significantly in terms of age (p = 0.225) or degree of exposure, considering each type of exposure in isolation or in combination (p = 0.164 and p = 0.220, respectively). Females predominated in the group exposed to wood smoke. There were no differences among the groups regarding respiratory symptoms (p > 0.05), and moderate dyspnea predominated in the three groups (p = 0.141). The group exposed to wood smoke presented higher percentages of forced expiratory volume in one second/forced vital capacity ratio and of forced expiratory volume in one second (p < 0.05). Positive results on bronchodilator testing occurred more frequently in the group exposed to tobacco smoke. The percentage of severe and extremely severe obstruction was significantly higher in the group exposed to tobacco smoke (44.1%) than in that exposed to wood smoke (11.8%; p = 0.006). Conclusions: Respiratory symptoms and pulmonary function alterations consistent with COPD were observed in the groups of patients exposed to wood smoke. However, those alterations were not as significant as the alterations observed in the groups exposed to tobacco smoke. This study emphasizes the importance of prospective studies in evaluating the risk of wood-smoke-related COPD in Brazil, as well as the need for preventive measures in this area.

Keywords: Pulmonary disease, chronic obstructive; Smoking; Air pollution, indoor; Smoke.

Objective: Lymphangioleiomyomatosis (LAM) is a rare, destructive disease of the lungs with a limited number of determinants of disease activity, which are a critical need for clinical trials. FGF23 has been implicated in several chronic pulmonary diseases. We aimed to determine the association between serum FGF23 levels and pulmonary function in a cohort of patients with LAM. Methods: This was a descriptive single-center study in which subjects with LAM and controls with unreported lung disease were recruited. Serum FGF23 levels were measured in all subjects. Clinical data, including pulmonary function testing, were retrospectively obtained from electronic medical records of LAM subjects. Associations between FGF23 levels and clinical features of LAM were explored via nonparametric hypothesis testing. Results: The sample comprised 37 subjects with LAM and 16 controls. FGF23 levels were higher in the LAM group than in the control group. In the LAM group, FGF23 levels above the optimal cutoff point distinguished 33% of the subjects who had nondiagnostic VEGF-D levels. Lower FGF23 levels were associated with impaired DLCO (p = 0.04), particularly for those with isolated diffusion impairment with no other spirometric abnormalities (p = 0.04). Conclusions: Our results suggest that FGF23 is associated with pulmonary diffusion abnormalities in LAM patients and elicit novel mechanisms of LAM pathogenesis. FGF23 alone or in combination with other molecules needs to be validated as a biomarker of LAM activity in future clinical research.

Keywords: Lymphangioleiomyomatosis; Fibroblast growth factor-23; Pulmonary diffusing capacity.

Introduction: Spirometry and analysis of blood gases data have been extensively used to assess ventilatory limitation and prognosis of COPD patients. However, functional physical tests, such as the six-minute walk test (6wt) have been used for the dynamic assessment of COPD patients. Objective: To determine correlations between respiratory function test data and the six-minute walk test in COPD patients. Patients and methods: 45 patients were submitted to clinical history survey and complete physical examination performed by the medical staff of the Pneumology Department of the Brasilia University Hospital, followed by spirometry, analysis of arterial blood gases, maximal respiratory pressures data, and the six-minute walk test. Results: Concerning the spirometric, analysis of blood gases and maximal respiratory pressures data, statistically significant positive correlations (p < 0.05) between FEV1, PaO2, SpO2, MEP and the six-minute walk test were obtained. Conclusions: For the studied group, the six minute walk test has significant correlation with FEV1, PaO2, SpO2 and MEP, and can be used as an alternative functional assessment of COPD patients.

Objectives: To determine whether, in stable patients with chronic obstructive pulmonary disease, administration of theophylline in combination with short-acting or long-acting inhaled β2-agonists is more efficacious than is a placebo or each of these drugs used in isolation. Methods: A systematic review and meta-analysis were carried out. All randomized and double-blind clinical trials found in the literature were selected. Results: A total of eight studies were included. In comparing the effect of theophylline combined with β2-agonists to that of a placebo, we found a statistically significant improvement in mean FEV1 (0.27 L; 95%CI: 0.11 to 0.43) and mean dyspnea (-0.78; 95%CI: -1.26 to -0.29). None of the meta-analyses performed detected any difference between the results obtained using theophylline combined with β2-agonists and those obtained using β2-agonists alone. When the administration of theophylline combined with β2-agonists was compared to that of theophylline alone, there was a statistically significant improvement in mean dyspnea (-0.19; 95%CI: -0.34 to 0.04). Conclusion: In patients with stable chronic obstructive pulmonary disease, theophylline combined with β2 agonists is more efficacious than is a placebo in terms of improving FEV1 and dyspnea. In addition, theophylline combined with β2 agonists is more efficacious than is theophylline in improving dyspnea. Furthermore, administration of theophylline combined with β2 agonists is no more efficacious, for any of the variables studied, than is the use of β2-agonists in isolation.

Keywords: Lung diseases, Obstructive; Bronchodilator agents; Xanthines; Pulmonary disease, Chronic obstructive.

Background: The six minutes walk test has been increasingly utilized to assess the effectiveness of different clinical and surgical treatment options in pulmonary diseases. However lack of standardization for their performance may influence measurements and jeopardize assessment of the functional capacity of patients with cardiopulmonary disease. Objective: To determine the possible effects of learning on the distance covered during the six minute walk test for bearers of chronic obstructive pulmonary disease. Method: A retrospective analysis of 35 medical records of COPD patients referred to the Pulmonary Rehabilitation Program of the University Hospital of Brasília was carried out. On alternate days these patients had performed two six minutes walk tests, spirometry and arterial blood gas analysis. Clinical and functional diagnosis was based upon the history of exposure to risk factors, mucus production, dyspnea and spirometric dysfunction after use of bronchodilators. The Student test was used for the comparison of results that were different. Results: The distances covered in the second six-minute walk test (515 ± 82 meters) were greater than those covered in the first six-minute walk test (480 ± 85 metros), with statistically significant differences (p<0.05). However measurements of the muscular effort and perception of dyspnea (Borg scale), peripheral blood oxygen saturation (SpO2), respiratory and heart rates did not disclose any statistically significant differences between the two tests (p<0.05). Conclusion: The present study suggests that in order to standardize the six minutes walk test, the procedure should be performed at least twice to better assess the functional capacity of patients, bearers of chronic obstructive pulmonary disease.

Keywords: Walking. Effectiveness. Lung diseases, obstrutive.

Chronic obstructive pulmonary disease is progressive and is characterized by abnormal inflammation of the lungs in response to inhalation of noxious particles or toxic gases, especially cigarette smoke. Although this infirmity primarily affects the lungs, diverse extrapulmonary manifestations have been described. The likely mechanisms involved in the local and systemic inflammation seen in this disease include an increase in the number of inflammatory cells (resulting in abnormal production of inflammatory cytokines) and an imbalance between the formation of reactive oxygen species and antioxidant capacity (leading to oxidative stress). Weakened physical condition secondary to airflow limitation can also lead to the development of altered muscle function. Chronic obstructive pulmonary disease presents diverse systemic effects including nutritional depletion and musculoskeletal dysfunction (causing a reduction in exercise tolerance), as well as other effects related to the comorbidities generally observed in these patients. These manifestations have been correlated with survival and overall health status in chronic obstructive pulmonary disease patients. In view of these facts, the aim of this review was to discuss findings in the literature related to the systemic manifestations of chronic obstructive pulmonary disease, emphasizing the role played by systemic inflammation and evaluating various therapeutic strategies.

Keywords: Pulmonary disease, chronic obstructive/complications; Nutritional status; Exercise tolerance;

Objective: Thymidine-dependent small-colony variants (TD-SCVs) of Staphylococcus aureus are being isolated with increasing frequency from patients with cystic fibrosis (CF). The aim of this study was to evaluate the relationship between TD-SCV isolation and pulmonary function in patients with CF, as well as to determine whether the emergence of TD-SCVs was associated with trimethoprim-sulfamethoxazole (TMP-SMX) use and with coinfection with other microorganisms. Methods: This was a retrospective case-control study including patients with CF who visited the Clinical Hospital Complex of the Federal University of Paraná, in Curitiba, Brazil, between 2013 and 2022. Demographic, clinical, and spirometric data, as well as information on TD-SCVs and other isolated microorganisms, were collected from the medical records of patients with CF and TD-SCVs (TD-SCV group; n = 32) and compared with those of a matched group of patients with CF without TD-SCVs (control group; n = 64). Results: Isolation of TD-SCVs was positively associated with TMP-SMX use (p = 0.009), hospitalization (p < 0.001), and impaired pulmonary function (p = 0.04). Conclusions: The use of TMP-SMX seems to contribute to the emergence of TD-SCVs, the isolation of which was directly associated with worse pulmonary function in our sample.

Keywords: Staphylococcus aureus/drug effects; Thymidine/metabolism; Trimethoprim, sulfamethoxazole drug combination/adverse effects; Lung/physiopathology; Cystic fibrosis/complications.

We report the case of a patient with chronic obstructive pulmonary disease and bronchiectasis, chronically using corticosteroids, who acquired pulmonary nocardiosis, which presented as multiple cavitated nodules. The principal symptoms were fever, dyspnea and productive cough with purulent sputum. Chest X-ray and computed tomography of the chest revealed nodules, some of which were cavitated, in both lungs. Sputum smear microscopy and culture revealed the presence of Nocardia spp. The patient was treated with imipenem and cilastatin, which produced an excellent clinical response.

Keywords: Pulmonary disease, chronic obstructive; Nocardia infections; Bronchiectasis.

Objective: To evaluate quality of sleep and pulmonary function in clinically stable adolescents with sickle cell anemia (SCA). Methods: A cross-sectional descriptive study involving 50 patients with SCA submitted to nocturnal polysomnography and spirometry at the Brasília University Hospital. Anthropometric, polysomnographic and pulmonary function data were analyzed. Patients were divided into two groups according to oxygen saturation by pulse oximetry (SpO2) during rapid eye movement (REM) sleep: SpO2 ≤ 93%; and SpO2 > 93%. Descriptive statistics, Student's t-test, chi-square test and Pearson's correlation coefficient were used. Results: Mean age was 13.9 ± 2.5 years. Total sleep time and REM sleep percentage were lower, whereas REM sleep latency, the number of awakenings, movement during sleep, changes in sleep stage, sleep-disordered breathing index and obstructive apnea index were higher. Two patients (4%) did not present REM. There were statistically significant differences between the groups in most of the polysomnographic variables. The SpO2 in REM sleep presented a strong positive correlation with waking SpO2 and with SpO2 in non-REM sleep, whereas it presented a strong negative correlation with the percentage of total sleep time during which SPO2 was < 90%. Mean spirometric values were within normal ranges. Residual volume and the residual volume/total lung capacity/functional residual capacity ratio were elevated. Conclusion: Sleep impairment in clinically stable patients with SCA is probably due to hemoglobin desaturation and not to individual alterations in pulmonary function.

Keywords: Sleep disorders; Polysomnography; Adolescent; Anemia, sickle cell; Spirometry.

Objective: To evaluate the presence and severity of symptoms of anxiety and depression in individuals with asthma or chronic obstructive pulmonary disease. Methods: In order to evaluate symptoms of anxiety and depression, specific instruments of quantification (the State-Trait Anxiety Inventory and the Beck Depression Inventory, respectively) were administered to patients at an outpatient clinic for the treatment of asthma and chronic obstructive pulmonary disease. The population comprised 189 randomly and prospectively selected patients that were divided into three study groups (each with a different therapeutic objective): 40 patients with controlled asthma, 100 patients with uncontrolled asthma, and 49 patients with chronic obstructive pulmonary disease. Included among the variables studied, as part of the methodology, were symptoms of anxiety and depression. The data obtained were compared taking into consideration demographic and functional aspects, as well as the severity of the symptoms of anxiety and depression. Results: Among the asthma patients, the prevalence of moderate or severe anxiety was significantly higher than that observed among those with chronic obstructive pulmonary disease (p <  0.001). The uncontrolled asthma group presented significantly higher rates of depressive symptoms than did the controlled asthma group (p < 0.05). Conclusion: The frequency of symptoms of anxiety and depression is greater among asthma patients than among patients with chronic obstructive pulmonary disease, which can make clinical control difficult.

Keywords: Anxiety; Depression; Asthma; Pulmonary disease; Chronic obstructive

Objective: The present study attempted to determine whether patients with chronic obstructive pulmonary disease (COPD) get the minimum daily amount of physical activity recommended in the guidelines established by the American College of Sports Medicine (ACSM), as well as to characterize the consequences of noncompliance with those guidelines. Methods: This study involved 23 patients (median age: 61 - range, 59-69 years; FEV1: 39% of predicted - range, 34-53%; BMI: 24 kg/m2 - range, 21-27 kg/m2). The following parameters were evaluated: daily physical activity (DynaPort activity monitor); pulmonary function; muscle force; exercise tolerance; quality of life; functional status; and various indices of disease severity (GOLD, BODE and MRC). Results: Based on compliance with the guidelines (minimum of 30 minutes of walking per day), 12 patients were considered "physically active", and 11 were considered "physically inactive". No significant differences were observed between the two groups in terms of age, gender, BMI, muscle force, ventilatory reserve, hyperinflation or quality of life. The inactive group presented more impaired pulmonary function and lower exercise tolerance, as well as lower MRC and BODE scores (p < 0.05). In their daily life, patients in the inactive group also walked for less time and more slowly than did those in the active group (p < 0.05). The MRC and BODE indices were superior to the GOLD index in predicting compliance with the guidelines, both presenting a specificity of 0.83, compared with 0.50 for the GOLD index. The BODE index score increased significantly with each day of inactivity. Conclusion: A large number of COPD patients do not walk more than 30 minutes per day and are therefore not getting the minimum daily amount of physical activity recommended by the ACSM. Inactivity correlates with a higher mortality rate. The MRC and BODE indices proved superior to the GOLD index in predicting whether patients are physically inactive in their daily lives.

Keywords: Pulmonary disease, chronic obstructive; Body mass index; Exercise tolerance; Exercise; Guidelines; Severity of illness index

Objective: To determine cell profiles, as well as to identify CD4+ and CD8+ lymphocyte subgroups, in induced sputum (IS) and peripheral venous blood (PVB) of patients with chronic obstructive pulmonary disease (COPD). Methods: Total cell counts and counts of individual cell types, including CD4+ and CD8+ T lymphocytes, were determined in the IS and PVB of 85 subjects (38 with COPD without exacerbation, 29 smokers without obstruction and 18 nonsmokers). Mann-Whitney and Spearman non-parametric tests were used in the statistical analysis, and values of p < 0.05 were considered statistically significant. Results: Comparing the IS of subjects with COPD to that of nonsmokers, neutrophil, eosinophil and CD8+ T lymphocyte counts were higher (respectively p = 0.005, p < 0.05 and p < 0.05), whereas the percentage of macrophages was lower (p = 0.003). There were weak linear correlations (r2 < 0.1) between each cell type in IS and forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio. Eosinophil and CD8+ T lymphocyte counts were also higher in PVB (p = 0.04 and p = 0.02). Conclusions: In patients with stable COPD, CD8+ T lymphocyte counts were higher in PVB, whereas total leukocyte counts were similar to those of the other two groups analyzed, suggesting systemic inflammatory involvement. The CD8+ T lymphocyte count in blood can be a useful marker of systemic inflammation and can help identify smokers who already present a COPD inflammatory pattern.

Keywords: Sputum; T-lymphocytes; Neutrophils; Macrophages; Eosinophils; Pulmonary disease, chronic obstructive.

Objective: To correlate the postbronchodilator (post-BD) inspiratory capacity (IC), % of predicted, with other markers of severity and prognostic factors in chronic obstructive pulmonary disease (COPD). Methods: Eighty stable patients with COPD performed forced vital capacity and slow vital capacity maneuvers, as well as the 6-min walk test, prior to and after receiving albuterol spray (400 μg). Patients were divided into four groups, based on post-BD forced expiratory volume in one second. Several variables were tested to establish correlations with the post-BD distance walked, using univariate and multivariate analysis. Post-BD IC was found to correlated with Global Initiative for Chronic Obstructive Lung Disease (GOLD) staging and with the Body mass index, airway Obstruction, Dyspnea, and Exercise capacity (BODE) index. Results: Multivariate regression analysis revealed that the distance walked, % predicted, correlated significantly with the IC post-BD, % predicted (p = 0.001), long-term oxygen use (p = 0.014), and number of medications used in the treatment (p = 0.044). IC ≤ 70% was observed in 56% patients in GOLD stages 3 or 4 vs. 20% in GOLD 1 or 2 (p < 0.001). IC ≤ 70% was observed in (60%) patients with BODE score 3 or 4 vs. (33%) BODE score 1 or 2 (p = 0.02). Conclusion: Post-BD IC% predicted is the best functional predictor of distance walked and is significantly associated with GOLD staging and BODE index. Therefore, We propose that the inspiratory capacity should be added to the routine evaluation of the COPD patients.

Keywords: Pulmonary disease, chronic obstructive; Walking; Respiratory function tests; Inspiratory capacity.

Objective: To compare the efficacy, safety, and tolerability of azithromycin and amoxicillin in the treatment of patients with infectious exacerbation of chronic obstructive pulmonary disease. Methods: This study was conducted at six medical centers across Brazil and included 109 patients from 33 to 82 years of age. Of those, 102 were randomized to receive either azithromycin (500 mg/day for three days, n = 49) or amoxicillin (500 mg every eight hours for ten days, n = 53). The patients were evaluated at the study outset, on day ten, and at one month. Based on the clinical evaluation of the signs and symptoms present on day ten and at one month, the outcomes were classified as cure, improvement, or treatment failure. The microbiological evaluation was made through the culture of sputum samples that were considered appropriate samples only after leukocyte counts and Gram staining. Secondary efficacy evaluations were made in order to analyze symptoms (cough, dyspnea, and expectoration) and pulmonary function. Results: There were no differences between the groups treated with azithromycin or amoxicillin in terms of the percentages of cases in which the outcomes were classified as cure or improvement: 85% vs. 78% (p = 0.368) on day ten; and 83% vs. 78% (p = 0.571) at one month. Similarly, there were no significant differences between the two groups in the secondary efficacy variables or the incidence of adverse effects. Conclusion: Azithromycin and amoxicillin present similar efficacy and tolerability in the treatment of acute exacerbation of chronic obstructive pulmonary disease.

Keywords: Amoxicillin/therapeutic use; Azithromycin/therapeutic use; Bronchitis, chronic/drug therapy;

Chronic obstructive pulmonary disease is an inflammatory disease. Together with oxidant stimuli, which directly affect lung structures, macrophages, neutrophils and CD8+ lymphocytes actively participate in the pathogenesis of the disease and promote biochemical reactions that result in progressive alteration of the upper airways and irreversible lung remodeling. The release of substances promoted by inflammatory cell recruitment and by oxidative stress lead to a temporary imbalance in the pulmonary defense mechanisms. Understanding the long-term maintenance of this imbalance is key to understanding the current physiopathology of the disease. The present study explores the cellular and molecular alterations seen in chronic obstructive pulmonary disease.

Keywords: Pulmonary disease, chronic obstructive/physiopathology; Lung/metabolism; Inflammation; Oxydants; Antioxidants; Oxidative stress

Objective: To quantify elastic fibers (EFs) and smooth muscle (SM) cells, as well as CD4+ and CD8+ T lymphocytes, in stable chronic obstructive pulmonary disease (COPD). Methods: Surgical specimens were obtained from 15 COPD patients, 18 smokers without airflow limitation, and 14 nonsmokers. Histological and immunohistochemical methods were employed in order to quantify EFs, SM cells, CD4+ T cells, and CD8+ T cells. Results: There was no significant difference in EF numbers among the three groups (p > 0.05). The number of EFs per unit area of lung tissue (mm2) and the percentage of EFs in the lung tissue were similar among the three groups. The numbers of SM cells were found to be higher in the COPD patients than in the smokers (p = 0.003) or in the nonsmokers (p = 0.009). There was a tendency toward an increase in CD8+ T-cell counts in the COPD patients. In specimens collected from the COPD patients, CD4+ T-cell counts were lower than in those collected from the smokers (p = 0.015) or from the nonsmokers (p = 0.003). There was a weak correlation between CD4+ T-cell count and the ratio of forced expiratory volume in one second to forced vital capacity (r2 = 0.003). Conclusions: The EF counts were similar among the three groups. Hypertrophy/hyperplasia of airway wall SM cells was found in the COPD patients and in the smokers, indicating that airway remodeling occurs in smokers. The CD4/CD8 ratio was lower in the COPD patients.

Keywords: Pulmonary disease, chronic obstructive; CD4 Lymphocyte Count; Elastic tissue; Muscle, smooth.

Long-acting b2-agonists can produce the same level of bronchodilation as anticholinergic drugs in patients with COPD, but due to their lipophilicity, the action persists for 12 h after inhalation. Comparative studies between salmeterol and formoterol demonstrate an equivalent potency of salmeterol 50 mcg and formoterol 24 or 12 mcg when administered respectively by a metered dose inhaler or a turbuhaler. One must consider the inhaler in order to establish the equivalent potency between these two agents. Patients with COPD and associated cardiac diseases can use the long-acting b2-agonists safely. In this particular high-risk group of patients, salmeterol, a partial agonist, is considered safer than formoterol. A reassessment of the bronchodilator therapy in COPD might be considered. Tiotropium bromide is a new anticholinergic drug, the action of which prolongs for more than 1-3 days. It is the most promising new bronchodilator for COPD patients.

Keywords: COPD, long-acting b2-agonists, bronchodilators