The aim of the present study was to compare pulmonary function among patients with different clinical forms and scores for risk of death and stroke. Patients were recruited from the Chagas Disease Ambulatory Service at the University of Rio Grande do Norte State (Mossoró, Brazil). The evaluation of pulmonary function was performed through spirometry techniques using a digital spirometer, and information about the clinical forms (cardiac, cardiodigestive, digestive and undetermined) and scores for risk of death (Rassi's risk-of-death score) and stroke was subsequently collected. Upon completion of the evaluation, comparisons of the values obtained between the groups for different clinical forms, risk stratification of stroke and Rassi's risk-of-death were made. The study cohort consisted of 72 patients. Individuals with a low risk of death had significantly higher values in the Tiffeneau index and individuals with a low risk of stroke presented with higher percentage values for forced vital capacity and forced expiratory volume in 1 sec. In addition, individuals with heart disease had worse percentage values for FVC and FEV1. In conclusion, the results showed that spirometry was an effective analytical technique and was associated with clinical forms, and death and stroke risk scores, in patients with Chagas disease, adding an important prognostic tool to those currently available.
Chagas disease is due to infection with the protozoan
Chronic chagasic cardiomyopathy is the most common clinical complication in patients with Chagas disease; it is characterized by severe myocarditis, infiltration of the lymphomononuclear cells, interstitial fibrosis and cardiomyocyte hypertrophy, which may lead to dilated cardiomyopathy, end-stage heart failure (HF) and death (
Congestive heart failure, a characteristic of chagasic patients, is also associated with significant impairment of cardiac function and decreased inspiratory muscle strength (
The interstitial congestion present in HF prevents alveolar distension, which contributes to the inefficiency of respiratory muscle function, a reduction in oxygen supply and pulmonary complacency. This set of changes results in a restrictive respiratory pattern that contributes to respiratory muscle overload and an uncontrolled breathing regulation mechanism (
Among the symptoms presented by affected patients, the sensation of exertion fatigue and dyspnea are notable, both of which restrict the activities of daily living (ADLs). The intensity of the dyspnea is disproportionate to the physical activity performed, which directly affects the quality of life and prognosis of the affected patient, thus having an important impact on the functional capacity of the individual (
In view of the aforementioned respiratory complications, the measurement of respiratory flows and volumes through spirometry becomes an important additional tool for a comprehensive evaluation of chagasic patients. The decrease in these parameters has an impact on the physical restriction, in addition to being associated with clinical outcomes of the chagasic patient, such as the risk of cardiovascular events in a short period and the risk of death (
As the characteristics of the disease can lead to dysfunction and restriction of lung volumes, spirometric values become essential to assess the dysfunction present in patients with Chagas disease. Functional complications are already known to be associated with spirometric values in patients with Chagas disease. In the present study, the associations between pulmonary functional capacity values are expanded, and to the best of our knowledge, this is the first study to evaluate and compare the pulmonary flows and volumes of patients with Chagas disease according to their clinical characteristics, verifying the differences between the different risk groups of death and stroke, as well as different clinical forms of the disease.
This study was a descriptive, cross-sectional study that included 72 individuals with Chagas disease, confirmed by a positive result in enzyme-linked immunoassays, indirect immunofluorescence assays and indirect hemagglutination assays. These individuals were treated clinically at the Chagas Disease Ambulatory Service of the Health Sciences College of the University of Rio Grande do Norte State (FACS-UERN; Mossoró, Brazil).
Patients with good cognition and understanding, those who were >18 years of age and those who agreed to participate in the survey were included in the study. Those patients who dropped out of the test protocol when already in progress, those who, due to physical limitation, were unable to complete one of the functional tests and those who had previously used bronchodilators were excluded.
The patients were initially informed about the objectives of the study and the methods to be applied, and were later questioned about their willingness to participate. After agreeing to participate, the patients were asked to sign an informed consent form. The research followed the criteria of the Declaration of Helsinki (1997) and respected the ethical principles of Resolution 466/2012 of the National Health Council in Brazil, which supports research involving human beings. The ethical aspects of the study were approved by the Research Ethics Committee of the University of Rio Grande do Norte State (approval nos. 1.510.620 and CAAE 53362316.8.0000.5294).
An initial evaluation was performed at the FACS-UERN Chagas Disease Ambulatory Service, where the medical history and sociodemographic data of the patients were collected and a life habits assessment was performed through an evaluation form prepared for the study. Echocardiography, chest X-ray, contrast-enhanced radiography of the colon and esophagus, and subsequent classification of the clinical forms of Chagas disease were performed. Risk stratification of stroke and Rassi's risk-of-death were also analyzed, according to the criteria described in the literature (
The pulmonary function evaluation was performed by spirometry, using a USB digital spirometer from the CareFusion® brand (Becton, Dickinson and Company), to characterize the degree of obstructive pulmonary disorder as an evaluation parameter.
The entire procedure was performed as described by Pereira
The values that were obtained from the patients were compared to predicted values adequate for the population evaluated, and the percentages were adjusted for sex, height, weight and age (
All data were tabulated and organized into worksheets using Microsoft Excel (version 16.0.9226.2156; Microsoft Corporation) and IBM SPSS Statistics (version 20; IBM Corp.) software. The normality of the data obtained was verified using the Kolmogorov-Smirnoff and Shapiro-Wilk tests.
The comparison of the test values obtained between the groups of patients stratified according to their clinical form and risk of death and stroke was performed using the t-test for independent samples when there was a normal distribution, and the Mann-Whitney when there was a non-normal distribution. P<0.05 was considered to indicate a statistically significant difference.
The percentages recorded are values obtained relative to predicted values for the population evaluated, adjusted for sex, height, weight and age (
Blood was initially collected from 82 patients who went to the FACS-UERN Chagas Disease Ambulatory Service to undergo laboratory and clinical examinations and periodic medical consultations. After applying the inclusion and exclusion criteria, 10 subjects were eliminated from the study and 72 patients (33 women and 39 men) remained; however, not all patients had a full set of clinical characteristics available, so when divided into the groups, there were 42 patients in the death risk group, 62 in the stroke risk group and 67 patients classified into different clinical forms. All patients were from the West Potiguar mesoregion of Rio Grande do Norte in Brazil, mainly from the city of Mossoró (25 patients). The majority (55.6%) of the patients lived in the urban area of these municipalities. The patient ages ranged from 26 to 69 years, with a mean [± standard deviation (SD)] of 48.3±10.9 years. The mean (± SD) weight was 70.1±13.7 kg, the mean (± SD) height was 1.60±0.09 m and the mean (± SD) BMI was 27.0±4.4.
It was observed that 4.2% of patients were reported with diabetes, 33.3% with hypertension, 5.6% with dyslipidemia and 34.3% with musculoskeletal disorders. It was also observed that 56.9% of the cohort used some form of medication, mainly antihypertensive drugs (30.6% of the total patients). With regard to lifestyle, only 18 (25%) patients performed regular physical activities and 21 (29.2%) were smokers or former smokers (data not shown).
The distribution of patients according to Rassi's risk-of-death score (
Regarding stroke risk scores (
In the clinical forms classification, 30 patients (41.7%) had an undetermined clinical form, while 18 (25.0%) had a cardiac form, 8 (11.1%) had a digestive form and 11 (15.3%) had a cardiodigestive form. In addition, 5 (6.9%) still needed to undergo complementary tests to determine their clinical form. For comparison purposes, the patients were divided into two groups, namely the cardiac group, with cardiac or cardiodigestive clinical forms, and the non-cardiac group, with undetermined and digestive clinical forms, as shown in
The comparison of the respiratory and functional parameters of the patients, taking into account the risk of death scores, showed that the group with low risk (scores 0 to 2) had significantly higher values for the Tiffeneau index (
When comparing the respiratory and functional parameters among the patients with the undetermined or digestive clinical form (non-cardiac group) and those with the cardiac or cardiodigestive forms (cardiac group), the percentage values of FVC and FEV1 were significantly higher in the non-cardiac group (
In the present study, the Tiffeneau index was significantly different between the groups with a high and a low risk of death in the chagasic patients. The index represents the association between FEV1 and FVC (FEV1/FVC), and has normal values between 0.70 and 0.80(
Physical activities and ADLs increase ventilatory demand, and airway obstruction in these efforts generates dynamic pulmonary hyperinflation. This imprisonment generates increasing difficulty for the aforementioned activities by the impairment of function and pulmonary mobility. Thus, a patient with poor pulmonary function tends to decrease the amount of activity undertaken, compromising their independence and functionality, and this set of factors is known to be associated with higher mortality (
In the present study, when the groups were divided according to the stroke risk score (
Georgiopoulou
A significant difference was also observed in the mean percentages of FVC and FEV1 among cardiac and non-cardiac patients. The same results cited previously in the studies by Georgiopoulou
A previous review has shown significant differences in functional capacity (maximum oxygen consumption values) among cardiac and non-cardiac chagasic patients (
In addition to the chronic oxidative stress caused by the pulmonary volume deficit previously mentioned (
The decrease in pulmonary volumes and capacities accompanied a higher risk of death and stroke related to the cardiac form of Chagas disease in the present study, which confirms previous discussions in the literature that associate the higher risk of clinical worsening with worse respiratory function (
Spirometry proved to be a good analytical tool in the present study and showed a good association with clinical forms and risk of death and stroke scores in patients with Chagas disease. Therefore, it is suggested that the spirometric parameters of Tiffeneau index, FVC value and FEV1 value may give indications that the patient is suffering from a clinical worsening of their condition.
To the best of our knowledge, this is the first study to find significant differences in the stratifications cited in chagasic patients, as some of these associations were only studied in other categories of patients.
Chagas disease is a pathology that can have a heterogeneous course. The condition is widely studied and the different clinical forms and prognostic instruments for the risk of stroke and death are already known. Thus, data that correlate with these disease progression variables are important to guide therapeutic approaches and predict injuries. The present study concluded that spirometry is a relatively simple yet important clinical tool that correlates with the risk of death and stroke, and the development of the most severe form of the disease. In view of the data, these patients should also be challenged to avoid a sedentary lifestyle and be physically active, as these are attitudes that directly influence lung function assessed by spirometry.
The authors offer their deepest thanks to the professionals at the Chagas Disease Ambulatory Service of the Health Sciences College of the University of Rio Grande do Norte State (Mossoró, Brazil) and Artmedica Clinic (Mossoró, Brazil) who provided technical support for the development of this study.
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
NMM and TAAMF were responsible for the conception and design of the study. NMM, VDA and LCCML collected the data, and NMM, MFA, CMA, CMB, EGCN, JVF and TAAMF performed the data analysis and interpretation. MFA and VDA contributed to the statistical analysis. NMM was primarily responsible for writing the manuscript, with contributions from LCCML, TAAMF, CMA, CMB, EGCN and JVF. CMA, CMB, EGCN and JVF also made a critical review and approved the final version for publication. NMM and TAAMF confirm the authenticity of all the raw data. All authors have read and approved the final manuscript.
The research followed the criteria of the Declaration of Helsinki (1997) and respected the ethical principles of Resolution 466/2012 of the National Health Council from Brazil. The ethical aspects were approved by the Research Ethics Committee of the University of Rio Grande do Norte State (grant nos. 1.510.620 and CAAE 53362316.8.0000.5294). Written informed consent was obtained from all participants.
Not applicable.
The authors declare that they have no competing interests.
Study design flowchart.
Comparison of the spirometric values in patients with a low and intermediate/high risk of death.
Rassi's risk of death score | |||
---|---|---|---|
Parameter | Low risk-group (n=24) | Intermediate/high-group (n=18) | P-value |
Spirometry | |||
FVC | 3.04±0.84 | 3.47±1.05 | 0.148 |
FVC percentage | 85.70±12.48 | 87.33±12.48 | 0.733 |
FEV1 | 2.63±0.69 | 2.84±0.89 | 0.390 |
FEV1 percentage | 90.75±11.55 | 87.83±18.65 | 0.536 |
Tiffeneau index | 88.79±7.44 | 82.27±7.41 | 0.008 |
Data are presented as the mean ± standard deviation.
aP-value calculated by Student's t-test.
bP<0.05.
Comparison of the spirometric values in patients with a low and intermediate/high risk of stroke.
Stroke risk score | |||
---|---|---|---|
Parameter | Low-risk group ((n=50) | Intermediate/high-risk group (n=12) | P-value |
Spirometry | |||
FVC | 3.38±0.95 | 3.19±0.82 | 0.533 |
FVC percentage | 91.64±13.43 | 81.16±17.56 | 0.026 |
FEV1 | 2.87±0.78 | 2.65±0.66 | 0.372 |
FEV1 percentage | 94.98±12.12 | 82.66±18.78 | 0.007 |
Tiffeneau index | 86.26±7.77 | 83.66±9.10 | 0.320 |
Data are presented as the mean ± standard deviation.
aP-value calculated by Student's t-test.
bP<0.05.
Comparison of the spirometric values in patients with the cardiac form and the non-cardiac form.
Clinical forms | |||
---|---|---|---|
Parameter | Cardiac group (n=29) | Non-cardiac group (n=38) | P-value |
Spirometry | |||
FVC | 3.25±0.87 | 3.47±0.98 | 0.594 |
FVC percentage | 82.89±13.83 | 94.16±14.79 | 0.005 |
FEV1 | 2.75±0.73 | 2.92±0.80 | 0.380 |
FEV1 percentage | 86.26±15.76 | 96.27±13.01 | 0.001 |
Tiffeneau index | 86.0(27) | 87.0(41) | 0.217 |
Values are presented as the median (IQR; Q3-Q1) or presented as the mean ± standard deviation.
aP-value calculated by Student's t-test.
bP<0.05.
cP-value calculated by the Mann-Whitney U test.