Mônica Corso Pereira

CFTR genotype and clinical outcomes of adult patients carried as cystic fibrosis disease

BACKGROUND There are nearly 2000 cystic fibrosis transmembrane regulator (CFTR) mutations that cause cystic fibrosis (CF). These mutations are classified into six classes; on the one hand, the first three classes cause severe disease involvement in early childhood, on the other hand, the Class IV, V and VI mutations cause minor severe disease in the same age. Nowadays, with therapeutic advances in CF management and competence of pediatricians, physicians of adults have to deal with two groups of CF patients: (i) adults diagnosed in childhood with severe mutations and (ii) adults who initiated symptoms in adulthood and with Class IV, V and VI mutations. The aim of this study was to analyze adults from a clinical center, treated as CF disease, screening the CFTR genotype and evaluating the clinical characteristics. METHODS Thirty patients followed as CF disease at the University Hospital were enrolled. After a complete molecular CFTR negative screening and sweat test levels between 40 and 59mEq/L, five patients were characterized as non-CF disease and were excluded. Molecular screening was performed by CFTR gene sequencing/MLPA or by specific mutation screening. Clinical data was obtained from medical records. The patients were divided into three groups: (1) patients with Class I, II and III mutations in two CFTR alleles; (2) genotype with at least one allele of Class IV, V or VI CFTR mutations and, (3) non-identified CFTR mutation+one patient with one allele with CFTR mutation screened (Class I). RESULTS There was an association of CFTR class mutation and sodium/chloride concentration in the sweat test (sodium: p=0.040; chloride: p=0.016), onset of digestive symptoms (p=0.012), lung function parameter (SpO2 - p=0.016), Bhalla score (p=0.021), age at diagnosis (p=0.008) and CF-related diabetes (p=0.029). There was an association between Pseudomonas aeruginosa chronic colonization (as clinical marker for the lung disease status) and lung impairment (FEV1% - p=0.027; Bhalla score - p=0.021), CF-related diabetes (p=0.040), chloride concentration in the sweat test (p=0.040) and chronic infection by microorganisms (Staphylococcus aureus - p=0.039; mucoid P. aeruginosa - p=0.001). There is no positive association with the status of other clinical markers and the CFTR genotype groups. For clinical association with pancreatic insufficiency (as clinical marker for digestive symptoms), no association was related. CONCLUSION The adults with CF diagnosed by sweat test have specific clinical and genotypic characteristics, being a population that should be studied to cause better future management. Some patients treated as CF disease by clinical symptoms, showed no disease, taking into account the sweat test and complete exon sequencing/MLPA screening.

Paresia diafragmática bilateral idiopática

We report the case of a patient with severe dyspnea upon reclining. Lung disease, neuromuscular disorders and heart disease were ruled out. However, during the course of the investigation, bilateral diaphragmatic paresis was discovered. A key sign leading to the diagnosis was evidence of paradoxical respiration in the dorsal decubitus position. When the patient was moved from the orthostatic position to the dorsal decubitus position, oxygenation and forced vital capacity worsened. The orthostatic fluoroscopy was normal. Maximal inspiratory pressure was severely reduced. The responses to transcutaneous electric stimulation of the diaphragm were normal. However, electric stimulation of the phrenic nerve produced no response, leading to the diagnosis of bilateral diaphragmatic paresis.

Cystic Fibrosis in Adults

The aim of this cross-sectional retrospective study was to describe clinical and functional characteristics and the microbiological profile of an adult population with cystic fibrosis. The study was performed at the Pulmonary Diseases Service of the Hospital of the Medical School of the State University of Campinas. The charts of 54 adults (27 males, 27 females) with cystic fibrosis were reviewed. Demographic, clinical, and microbiological data were collected. Clinical and functional characteristics of patients with chronic Pseudomonas infection were compared with those without it. The mean age of the patients was 41.8 years and the mean sweat chloride concentration was 106.4 mEq/L. Forty-nine percent had chronic respiratory symptoms only after 18 years of age, and 85% reported chronic production of purulent sputum. Six percent had diarrhea or fat in stools, and no patient suffered from diabetes mellitus. Pseudomonas was present in 48%, and 73% of them had the mucoid strain. Others agents found were Staphylococcus aureus (28%), Hemophylus sp. (34%), Aspergillus sp. (22%), Stenotrophomonas maltophilia (9%), Acinetobacter sp. (7%), and Burkholderia cepacia (2%). Nontuberculous mycobacteria were found in sputum from 9 patients (11%); 34 patients (67%) had obstructive ventilatory defect; and 47% had obstruction and restriction. Concerning the groups with and without Pseudomonas colonization, only the values of sweat chloride were significantly higher in chronic colonized patients. Less severe phenotypes of cystic fibrosis may be found among patients previously diagnosed as having bronchiectasis. Chronic colonization with Pseudomonas aeruginosa in this study was not associated with worse clinical status but colonized patients did show significantly higher levels of chloride in sweat.

Alveolar dead space and capnographic variables before and after thrombolysis in patients with acute pulmonary embolism.

Pulmonary embolism (PE) is a common condition. The central aim of this study was to describe the use of volumetric capnography (VCap) before and after fibrinolytic treatment of major PE. Lung scintigraphy was used as a base of comparison for the results of this treatment. We describe the cases of two conscious and spontaneously breathing patients (20- and by 24-year-old women) with major PE undergoing thrombolysis. Curves of CO2 were obtained VCap and associated with arterial blood gas analysis and D-dimer. The pattern of VCap was compared with the VCap of health volunteers. Parameters also calculated were: P(a-et)CO2 gradient, alveolar dead space fraction (AVDSf ), late dead space fraction (fDlate), and slope phase III (Slp III). The VCap results before and after thrombolysis for patients 1 and 2 were, respectively, P(a-et)CO2: 12.6 to 5.8 and 7.9 to 1.6 (mmHg); AVDSf: 0.46 to 0.18 and 0.25 to 0.05; fDlate: 0.46 to 0.21 and 0.24 to 0.04; Slp III: 1.75 to 5.10 and 1.21 to 5.61 (mmHg/L). Lung scintigraphy was used to compare VCap results from the two subjects with VCap results from healthy volunteers and pigs before and after treatment associated with arterial blood gas, D-dimer, and showed satisfactory agreement.

Volumetric capnography as a tool to detect early peripheric lung obstruction in cystic fibrosis patients

OBJECTIVE To compare spirometry and volumetric capnography (VCap) to determine if the capnographic values add more information about early lung disease in cystic fibrosis (CF) patients. METHODS This was a cross-sectional study involving CF patients: Group I (42 patients, 6-12 years of age); and Group II (22 patients, 13-20 years of age). The corresponding control groups were comprised of 30 and 50 healthy subjects, respectively. Forced vital capacity (FVC), forced expiratory volume in one second (FEV(1)), and the FEV(1)/FVC ratio was determined by spirometry. Using VCap, we measured peripheral oxygen saturation (SpO(2)), respiratory rate (RR), inspiratory time (IT), expiratory time (ET), and the phase III slope normalized by expiratory volume (phase III slope/Ve). RESULTS In comparison with control groups, all CF patients presented higher phase III slope/Ve values (p < 0.001) independent of the pulmonary disease stage. The phase III slope/Ve was significantly higher in the 24 patients who presented normal spirometry results (p = 0.018). The Group II patients showed lower FVC, FEV(1), FEV(1)/FVC (p < 0.05), and also lower SpO(2) values (p < 0.001) when compared with Group I patients. In comparison with Control Group II, the Group II patients presented higher RR (p < 0.001), and lower IT and ET values (p < 0.001). CONCLUSIONS Compared to the controls, all studied CF patients showed an increase in phase III slope/Ve values. VCap identified the heterogeneity of the ventilation distribution in the peripheral airways of CF patients who presented normal spirometry.

Distribution and morphometry of skeletal muscle fibers in patients with chronic obstructive pulmonary disease and chronic hypoxemia

This study was designed to assess the size and distribution of muscle fiber types in patients with severe chronic obstructive pulmonary disease and stable chronic hypoxemia. Brachial biceps biopsies were performed in 8 patients and 12 controls. Histochemistry was used to count and determine the cross‐sectional area of the various fiber‐types (1, 2a, and 2b). A significant reduction (P < 0.05) in the proportion of type 2a fibers and an increase in the proportion and cross‐sectional area of type 2b fibers were seen in hypoxemic patients. These findings suggest an adaptation of the muscle fibers to a low partial pressure of oxygen in arterial blood. Muscle Nerve 2004

Capnografia volumétrica como auxílio diagnóstico não-invasivo no tromboembolismo pulmonar agudo

Pulmonary thromboembolism is a common condition. Its diagnosis usually requires pulmonary scintigraphy, computed angiotomography, pulmonary arteriography and, in order to rule out other diagnoses, the measurement of D-dimer levels. Due to the fact that these diagnostic methods are not available in most Brazilian hospitals, the validation of other diagnostic techniques is of fundamental importance. We describe a case of a woman with chronic pulmonary hypertension who experienced a pulmonary thromboembolism event. Pulmonary scintigraphy, computed angiotomography and pulmonary arteriography were used in the diagnosis. The D-dimer test result was positive. Volumetric capnography was performed at admission and after treatment. The values obtained were compared with the imaging test results.

Capnografia volumétrica como meio de detectar obstrução pulmonar periférica precoce em pacientes com fibrose cística

OBJECTIVE: To compare spirometry and volumetric capnography (VCap) to determine if the capnographic values add more information about early lung disease in cystic fibrosis (CF) patients. METHODS: This was a cross-sectional study involving CF patients: Group I (42 patients, 6-12 years of age); and Group II (22 patients, 13-20 years of age). The corresponding control groups were comprised of 30 and 50 healthy subjects, respectively. Forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and the FEV1/FVC ratio was determined by spirometry. Using VCap, we measured peripheral oxygen saturation (SpO2), respiratory rate (RR), inspiratory time (IT), expiratory time (ET), and the phase III slope normalized by expiratory volume (phase III slope/Ve). RESULTS: In comparison with control groups, all CF patients presented higher phase III slope/Ve values (p < 0.001) independent of the pulmonary disease stage. The phase III slope/Ve was significantly higher in the 24 patients who presented normal spirometry results (p = 0.018). The Group II patients showed lower FVC, FEV1, FEV1/FVC (p < 0.05), and also lower SpO2 values (p < 0.001) when compared with Group I patients. In comparison with Control Group II, the Group II patients presented higher RR (p < 0.001), and lower IT and ET values (p < 0.001). CONCLUSIONS: Compared to the controls, all studied CF patients showed an increase in phase III slope/Ve values. VCap identified the heterogeneity of the ventilation distribution in the peripheral airways of CF patients who presented normal spirometry.

COPD phenotypes on computed tomography and its correlation with selected lung function variables in severe patients.

Background Computed tomography (CT) phenotypic characterization helps in understanding the clinical diversity of chronic obstructive pulmonary disease (COPD) patients, but its clinical relevance and its relationship with functional features are not clarified. Volumetric capnography (VC) uses the principle of gas washout and analyzes the pattern of CO2 elimination as a function of expired volume. The main variables analyzed were end-tidal concentration of carbon dioxide (ETCO2), Slope of phase 2 (Slp2), and Slope of phase 3 (Slp3) of capnogram, the curve which represents the total amount of CO2 eliminated by the lungs during each breath. Objective To investigate, in a group of patients with severe COPD, if the phenotypic analysis by CT could identify different subsets of patients, and if there was an association of CT findings and functional variables. Subjects and methods Sixty-five patients with COPD Gold III–IV were admitted for clinical evaluation, high-resolution CT, and functional evaluation (spirometry, 6-minute walk test [6MWT], and VC). The presence and profusion of tomography findings were evaluated, and later, the patients were identified as having emphysema (EMP) or airway disease (AWD) phenotype. EMP and AWD groups were compared; tomography findings scores were evaluated versus spirometric, 6MWT, and VC variables. Results Bronchiectasis was found in 33.8% and peribronchial thickening in 69.2% of the 65 patients. Structural findings of airways had no significant correlation with spirometric variables. Air trapping and EMP were strongly correlated with VC variables, but in opposite directions. There was some overlap between the EMP and AWD groups, but EMP patients had signicantly lower body mass index, worse obstruction, and shorter walked distance on 6MWT. Concerning VC, EMP patients had signicantly lower ETCO2, Slp2 and Slp3. Increases in Slp3 characterize heterogeneous involvement of the distal air spaces, as in AWD. Conclusion Visual assessment and phenotyping of CT in COPD patients is feasible and may help identify functional and clinically different subsets of patients. VC may provide useful information about the heterogeneous involvement of lung structures in COPD.

Latin America validation of FACED score in patients with bronchiectasis: an analysis of six cohorts

BackgroundThe FACED score is an easy-to-use multidimensional grading system that has demonstrated an excellent prognostic value for mortality in patients with bronchiectasis. A Spanish group developed the score but no multicenter international validation has yet been published.MethodsRetrospective and multicenter study conducted in six historical cohorts of patients from Latin America including 651 patients with bronchiectasis. Clinical, microbiological, functional, and radiological variables were collected, following the same criteria used in the original FACED score study. The vital status of all patients was determined in the fifth year of follow-up. The area under ROC curve (AUC-ROC) was used to calculate the predictive power of the FACED score for all-cause and respiratory deaths and both number and severity of exacerbations. The discriminatory power to divide patients into three groups of increasing severity was also analyzed.ResultsMean (SD) age of 48.2 (16), 32.9% of males. The mean FACED score was 2.35 (1.68). During the follow up, 95 patients (14.6%) died (66% from respiratory causes). The AUC ROC to predict all-cause and respiratory mortality were 0.81 (95% CI: 0.77 to 0.85) 0.84 (95% CI: 0.80 to 0.88) respectively, and 0.82 (95% CI: 078–0.87) for at least one hospitalization per year. The division into three score groups separated bronchiectasis into distinct mortality groups (mild: 3.7%; moderate: 20.7% and severe: 48.5% mortality; p < 0.001).ConclusionsThe FACED score was confirmed as an excellent predictor of all-cause and respiratory mortality and severe exacerbations, as well as having excellent discriminative capacity for different degrees of severity in various bronchiectasis populations.