Objective: Pulmonary rehabilitation (PR) improves exercise capacity in most but not all COPD patients. The factors associated with treatment success and the role of chest wall mechanics remain unclear. We investigated the impact of PR on exercise performance in COPD with severe hyperinflation. Methods: We evaluated 22 COPD patients (age, 66 ± 7 years; FEV1 = 37.1 ± 11.8% of predicted) who underwent eight weeks of aerobic exercise and strength training. Before and after PR, each patient also performed a six-minute walk test and an incremental cycle ergometer test. During the latter, we measured chest wall volumes (total and compartmental, by optoelectronic plethysmography) and determined maximal workloads. Results: We observed significant differences between the pre- and post-PR means for six-minute walk distance (305 ± 78 vs. 330 ± 96 m, p < 0.001) and maximal workload (33 ± 21 vs. 39 ± 20 W; p = 0.02). At equivalent workload settings, PR led to lower oxygen consumption, carbon dioxide production (VCO2), and minute ventilation. The inspiratory (operating) rib cage volume decreased significantly after PR. There were 6 patients in whom PR did not increase the maximal workload. After PR, those patients showed no significant decrease in VCO2 during exercise, had higher end-expiratory chest wall volumes with a more rapid shallow breathing pattern, and continued to experience symptomatic leg fatigue. Conclusions: In severe COPD, PR appears to improve oxygen consumption and reduce VCO2, with a commensurate decrease in respiratory drive, changes reflected in the operating chest wall volumes. Patients with severe post-exercise hyperinflation and leg fatigue might be unable to improve their maximal performance despite completing a PR program.

Keywords: Pulmonary disease, chronic obstructive/rehabilitation; Exercise therapy; Respiratory therapy.

Background: Pulmonary rehabilitation is widely recommended for the treatment of chronic obstructive pulmonary disease. Objective: To evaluate the efficacy of pulmonary rehabilitation in improving exercise capacity, respiratory muscle strength and quality of life of chronic obstructive pulmonary disease patients. Method: This was an open, non-randomized clinical trial involving 27 clinically stable ex-smokers with chronic obstructive pulmonary disease who were enrolled in a pulmonary rehabilitation program. All were evaluated before and after pulmonary rehabilitation. Results: Mean age was 65 ± 5 years, mean body mass index was 25 ± 4 kg/m2, mean forced expiratory volume in one second was 55 ± 25% of predicted, mean ratio between forced expiratory volume in one second and forced vital capacity was 50 ± 12%, and mean arterial oxygen tension was 70 ± 7 mmHg. Comparison of pre- and post-pulmonary rehabilitation values revealed improvement in the distance walked in the 6-minute walk test (513 ± 99 m vs. 570 ± 104 m), maximum upper limb load (2 ± 1 kg vs. 3 ± 1 kg) and maximal inspiratory pressure (-89 ± 23 cmH2O vs. -102 ± 23 cmH2O), as well as in the activity domain, impact domain and total score on the Saint George's Respiratory Questionnaire. Conclusion: Pulmonary rehabilitation, when performed with care and with a focus on physical training, is efficacious in increasing not only the distance walked in the 6-minute walk test but maximum upper limb load, maximal inspiratory pressure and quality of life as well.

Keywords: Key words: Pulmonary rehabilitation. Chronic obstructive pulmonary disease. Quality of life. Respiratory muscles.

Objective: Making the differential diagnosis between asthma and chronic obstructive pulmonary disease (COPD) based on the response to inhaled bronchodilators by means of spirometry is controversial.The objective of this study was to identify the most useful spirometric variables in order to distinguish between asthma and COPD. Methods: Retrospective study conducted from April of 2004 to January of 2006, comparing the spirometric parameters of 103 nonsmoking patients with asthma to those of 108 patients with COPD who were smokers for more than 10 pack-years. All of the patients included in the study were older than 40 and presented stable disease at the time of the test. Results: Initial forced expiratory volume in one second (FEV1) was the same in the two groups (pre-bronchodilator FEV1 = 51%). However, patients with COPD were older (66 ± 9 years vs. 59 ± 11 years, p < 0.001) and more frequently male (73% vs. 27%, p < 0,001).After the use of the bronchodilator, the median absolute difference in FEV1 was 0.25 L (range, −0.09 to 1.13 L) in patients with asthma and 0.09 L (range, −0.1 to 0.73 L) in those with COPD (p < 0.001).The highest sensitivity (55%), specificity (91%) and likelihood ratio (6.1) for asthma diagnosis was obtained when the percentage increase in postbronchodilator FEV1 in relation to the predicted FEV1 (Δ%predFEV1) was equal to or greater than 10%.Isolated significant increases in forced vital capacity were more common in patients with COPD. Conclusions: In patients over the age of 40 and presenting obstructive lung disease, a Δ%predFEV1 ≥ 10% is the best spirometric parameter to distinguish asthma from COPD.

Keywords: Spirometry; Respiratory function tests; Lung diseases, obstructive.

Objective: To evaluate, using pulmonary function tests, the effectiveness of formoterol as a bronchodilator at 30 min after its administration in patients with poorly reversible COPD. Methods: A prospective study including 40 COPD patients not responding to the short-acting bronchodilator used in the spirometric test-variation of less than 200 mL and less than 7% of predicted in forced expiratory volume in one second (FEV1). All patients were classified as having stage II, III, or IV COPD (Brazilian Thoracic Society/Global Initiative for Chronic Obstructive Lung Disease) and presented FEV1 ≤ 70% of predicted value. The patients were randomized into two groups of 20, with similar clinical characteristics, receiving, via a dry powder inhaler, either formoterol or a placebo. The pulmonary function testing (plethysmography) was repeated at 30 min after formoterol or placebo administration. Results: In the formoterol group, the mean values obtained for FEV1, inspiratory capacity, and forced vital capacity were significantly greater than those obtained in the placebo group (p = 0.00065, p = 0.05, and p = 0.017, respectively), whereas that obtained for airway resistance was significantly lower (p = 0.010). Less pronounced differences were observed for residual volume, vital capacity and specific airway conductance, which were lower, higher and higher, respectively, in the formoterol group. Conclusions: In COPD patients not responding to the short-acting bronchodilator used in the spirometric test, formoterol promoted significant improvement in lung function at 30 min after of administration. Further studies are required to confirm whether formoterol can also be used as a medication for immediate relief of symptoms in COPD.

Keywords: Chronic obstructive pulmonary disease; Respiratory function tests; Bronchodilator agents.

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.

Background: Patients with chronic obstructive pulmonary disease usually present intolerance to physical exertion due to ventilatory limitation. L-carnitine has been used to enhance aerobic capacity in patients with chronic diseases, but no study seems to be available for this patient population. Objective: To evaluate the influence of L-carnitine supplementation (2 g/day) in chronic obstructive pulmonary disease patients undergoing physical training three times a week for six weeks. Method: Patients (mean age 69 ± 7 years, n = 30) with stable chronic obstructive pulmonary disease and < 65% of predicted forced expiratory volume in 1 second (FEV1) were separated into three groups of 10 patients each. Group 1 (G1, n = 10) received physical training and L-carnitine (2 g/day), group 2 (G2, n = 10) received physical training and placebo, and group 3 (G3, n = 10) received only L-carnitine (2 g/day). Spirometry and a 6-minute walking distance test were performed before and after intervention. Plasma levels of free carnitine were measured at the beginning and end of the study. Results: A significant increase in walking distance was found only in G1 and G2 (421 ± 100 to 508 ± 80.7 and 496 ± 78.7 to 526 ± 64.3 respectively). In addition, heart rates during physical training sessions were found to be significantly lower in G1 when compared to G2. There were no significant changes in spirometric variables, oxygen saturation or dyspnea in any group. Plasma levels of free L-carnitine were found to increase only in G3 (59.2 ± 13.8 to 102.3 ± 15.3 mmol/L). Conclusion: Oral L-carnitine supplementation combined with physical training may improve tolerance to physical exertion in chronic obstructive pulmonary disease patients.

Keywords: Chronic obstructive pulmonary disease. Carnitine/therapeutic use. Spirometry/methods. Exercise. Walking.

Objective: To characterize the presence, extent, and patterns of dynamic hyperinflation (DH) during treadmill exercise testing in patients with moderate to severe COPD. Methods: This was a cross-sectional study involving 30 non-hypoxemic patients (FEV1= 43 ± 14% of predicted) who were submitted to a cardiopulmonary exercise test on a treadmill at a constant speed (70-80% of maximum speed) to the tolerance limit (Tlim). Serial inspiratory capacity (IC) maneuvers were used in order to assess DH. Results: Of the 30 patients studied, 19 (63.3%) presented with DH (DH+ group), having greater pulmonary function impairment at rest than did those without DH (DH− group). None of the variables studied correlated with exercise tolerance in the DH− group, whereas Tlim, IC, and perception of dyspnea during exercise did so correlate in the DH+ group (p < 0.05). In the DH+ group, 7 and 12 patients, respectively, presented with a progressive and a stable pattern of DH (ΔICTlim,2min = −0.28 ± 0.11 L vs. 0.04 ± 0.10 L; p < 0.01). Patients with a progressive pattern of DH presented with higher perception of dyspnea/Tlim rate and lower exercise tolerance than did those with a stable pattern (354 ± 118 s and 465 ± 178 s, respectively; p < 0.05). Conclusions: The presence of DH is not a universal phenomenon during walking in COPD patients, even in those with moderate to severe airflow limitation. In the patients who presented DH, a progressive pattern of DH had a greater impact on exercise tolerance than did a stable pattern of DH.

Keywords: Pulmonary disease, chronic obstructive; Exercise; Exercise test; Inspiratory capacity.

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.

The objective of this study was to assess the efficacy of exercise training by means of a rehabilitative walking protocol. Twenty patients with COPD staged as III/IV according to the Global Initiative for Chronic Obstructive Lung Disease were included. Patients were evaluated at baseline and at the end of the exercise program regarding oxygen desaturation, sensation of dyspnea/fatigue, quality of life and six-minute walk distance. The comparison between the six-minute walk distance prior to and after training proved the efficacy of the protocol, which also resulted in a decrease in oxygen desaturation and in the sensation of dyspnea. This protocol can be easily put into practice.

Keywords: Activities of daily living; Pulmonary disease, chronic obstructive; Rehabilitation; Exercise therapy; Exercise test.

Background: Pulmonary Rehabilitation (PR) improves the quality of life of chronic obstructive pulmonary disease (COPD) patients. However, the influence of PR on the sleep pattern of these patients is unknown. Objective: To evaluate the influence of PR on the sleep patterns of patients with COPD. Method: A total of 27 patients (22 men/5 women) were submitted to polysomnographic, gasometric and anthropometric studies before and after six weeks of PR and were evaluated using the Epworth Sleepiness Scale. The results were analyzed using paired Student's t-test, ANOVA and Newman-Keuls multiple comparison test. Results: Mean age was 63.3 5.3 years, mean FEV1 was 54.8 25.4% of predicted, mean FEV1/FVC was 49.9 12.0% of predicted, mean resting PaO2 was 69.7 7.3 mmHg, and mean resting SaO2 was 93.7 2.1%. Polysomnography revealed sleep patterns to be fragmented, with frequent waking and reduced slow-wave sleep, as well as oxygen desaturation. The most significant drops in oxygen saturation occurred during rapid eye movement sleep. No significant differences were observed between pre- and post-PR values for the other variables studied (p > 0.05).Conclusion: In the group of patients studied, PR did not alter sleep patterns.

Keywords: Sleep. Pulmonary Disease. Chronic Obstructive. Lung Diseases, rehabilitation.

Objective: To assess the frequency of variation in forced expiratory volume in one second after bronchodilator use in a sample of patients with chronic obstructive pulmonary disease, correlating such variation with clinical and demographic variables and evaluating the frequency of response presented in forced vital capacity, slow vital capacity, inspiratory capacity, residual volume, airway resistance and specific airway conductance. Methods: A total of 64 patients with chronic obstructive pulmonary disease were submitted to whole body plethysmography, and reversibility of bronchoconstriction after the administration 400 µg of fenoterol was quantified. Results: A response in forced expiratory volume in one second was observed in 31% of the patients. Excluding patients presenting a response in forced expiratory volume in one second, 5% presented responses in 5 of the other 6 parameters, 10% presented responses in 4 parameters, 17.5% in 3 parameters, 27.5% in 2 parameters, and 25% in only 1 parameter. Conclusion: When included in the evaluation of bronchodilator response together with forced expiratory volume in one second, static lung volumes, airway resistance and airway conductance allowed a broader evaluation of those patients presenting a functional pharmacodynamic response. These results are in accordance with the observation that bronchodilator use provides clinical improvement and relief of dyspnea to many patients with chronic obstructive pulmonary disease, even to those in whom such treatment leads to no improvement in forced expiratory volume in one second.

Keywords: Pulmonary disease, chronic obstructive/drug therapy; Bronchodilator agents/therapeutic use; Airway resistance/drug effects; Respiratory function tests; Vital capacity; Forced expiratory volume

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: 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: Assess the relationship between adherence to long-term oxygen therapy (LTOT) with mortality in patients with chronic obstructive pulmonary disease (COPD) and chronic respiratory failure and their clinical features. Methods: Longitudinal retrospective analysis of 254 patients with COPD and chronic respiratory failure from 2008 to 2016. At baseline, we evaluated the diagnosis, spirometry values, arterial blood gas analysis, blood count, pulse oximetry, body composition and health questionnaires (dyspnea, quality of life, anxiety and depression). For referred adherence analysis to LTOT we included 199 patients, divided according to prescription of oxygen: 12h/day (G1), 15h/day (G2) and 24h/day (G3). The cause of death and dates were studied over the five-year period. Results: In five years we identified 124 deaths (62.3%). No significant difference was found in mortality between the adherence groups (p=0.75) nor did we find differences in the clinical parameters evaluated. LTOT prescription was not associated with mortality (p=0.07). In Cox regression analysis, there was no association between mortality and non-adherence to LTOT (HR: 0.75; IC95%: 0.21-2.70). The risk of mortality was increased in G3 compared with G1 (HR: 7.16; IC 95%: 1.44-35.38) and in those with a higher depression score (HR: 1.35; IC: 1.14-1.59). Conclusion: No association was found between LTOT adherence and mortality in patients with COPD and respiratory failure. There were no clinical differences between the adherence groups.

Keywords: Chronic obstructive pulmonary disease; Oxygen therapy; Cooperation and treatment adherence; Morbidity and mortality indicators.

Background: Chronic obstructive pulmonary disease is detrimental to lung mechanics and peripheral muscles. The physical programs developed for this condition are usually targeted to an improvement on aerobics capacity. Programs that approach specifically the changes in thoracic mobility and thoracic muscles are rare. Objective: To assess the effects of a physical exercise program designed to increase chest wall mobility on functional and psychosocial capacity in moderate to severe chronic obstructive pulmonary disease patients. Methods: Thirty patients with moderate to severe chronic obstructive pulmonary disease were studied. They were randomized to 2 groups: control group (CG) and treated group (TG). The CG was submitted to an educational program and the TG was submitted to an educational program plus a physical exercise program aiming to increase chest wall mobility. Variables included spirometry, thoracic mobility, quality of life, anxiety and depression levels and a six minute walk test (6MWT). Results: After 2 months of training, only the TG presented improvements on chest wall mobility (from 4.20 ± 0.58 cm to 5.27 ± 0.58 cm; p = 0.05) and 6MWT (from 469.73 ± 31.99 m to 500.60 ± 27.38 m; p = 0.01). It was also observed that the TG presented improvement on the St. George's Respiratory Questionnaire (SGRQ) score, Chronic Respiratory Questionnaire (CRQ), and Beck's depression scale after 2 months of treatment. Pulmonary function did not improve either in the CG or in the TG group. Conclusion: Our results suggest that exercises aimed to the increasing of chest wall mobility improve thoracic mobility, quality of life, submaximal exercise capacity, and reduce dyspnea and depression symptoms in chronic obstructive pulmonary disease patients.

Keywords: COPD. Thoracic mobility. Quality of life. Capacity of exercise. Dyspnea.

Pulmonary thromboembolism and exacerbation of chronic obstructive pulmonary disease are common conditions. Chronic obstructive pulmonary disease is a clinical risk factor for pulmonary thromboembolism. The presentation of acute pulmonary thromboembolism and acute exacerbation of chronic obstructive pulmonary disease often mimic each other so closely that they cannot be distinguished clinically. The structural abnormalities of the lungs in chronic obstructive pulmonary disease make also difficult to interpret the results of noninvasive tests like ventilation-perfusion lung scans. Therefore, diagnosing acute pulmonary thromboembolism in patients with underlying chronic obstructive pulmonary disease is a challenging task. In order to update knowledge of the subject and offer suggestions regarding conduct, we evaluated various studies addressing this theme, including case reports and case series. In addition, we reviewed diagnostic approaches to acute pulmonary thromboembolism, and we reflect upon that topic. The clinical probability of pulmonary thromboembolism concomitant to chronic obstructive pulmonary disease is typically intermediate, as is positivity on the ventilation-perfusion lung scan. Diagnostic algorithms should take that into consideration.

Keywords: Pulmonary disease, chronic obstructive/complications; Pulmonary embolism/diagnosis; Pulmonary embolism/epidemiology; Ventilation-perfusion ratio

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.

Introduction: The term quality of life has gained increasing importance in the scientific context. This study describes the adaptation of a disease-specific questionnaire developed by Paul Jones et al. in 1991, the St. George's Respiratory Questionnaire (SGRQ), to the Brazilian language and culture. This questionnaire evaluates the quality of life in patients with chronic obstructive pulmonary disease (COPD) and contains three domains (symptoms, activity, and impacts) divided in 76 items. The questionnaire is self-administrated, but it may be read to illiterate persons. Goal: To verify if the St. George's Respiratory Questionnaire is a valid tool to measure quality of life in patients with chronic obstructive pulmonary disease in Brazil. Methods: In order to validate the questionnaire in Brazil, it was initially translated into Portuguese and afterwards a back-translation into English, that was compared to the original version. A final Portuguese version was then written. This final version was, then, answered by 30 clinically stable COPD patients, according to the spirometry and oximetry values. Patients answered the questionnaire twice, within a 15 day interval. The length of time the patients took to answer the questionnaire and their doubts were noted. Wilcoxon test was used for the calculation of r probability between every single question between the two days; interclass correlation ratio was calculated to test the trustworthiness and reliability of the questionnaire. Results: Among the 30 participant patients, 10 were female and 20 were male. Mean age was 65.9 years. Most of the patients were found to be in stage 2 (56.7 %) of COPD, according to the American Thoracic Society classification. The interclass correlation ratio for the total score of the questionnaire was a = 0.79 and Wilcoxon p = 0.2110 (not statistically significant). The mean answering time for the two days of interview was, respectively, 11 minutes and 50 seconds and 10 minutes and 31 seconds. As concerns the doubts about the questions, the patients reported difficulties in answering Sections 4 and 5, each one of these questions written in a negative form. Conclusion: It can be concluded that the Brazilian version of the St. George's Respiratory Questionnaire is a valid and reliable tool to measure quality of life in patients with COPD in Brazil.

Keywords: obstructive lung diseases, questionnaire, quality of life, reproducibility of results, evolution studies