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BACKGROUND: The combination of cystic fibrosis transmembrane conductance regulator (CFTR) modulators elexacaftor, tezacaftor and ivacaftor (ELX/TEZ/IVA) has been approved for treatment of cystic fibrosis (CF) patients (pwCF) homozygous and heterozygous for Phe508del. We aim to assess the long-term effects of ELX/TEZ/IVA therapy on clinical outcomes in severe pwCF. METHODS: Lung function, pulmonary exacerbation (PEx), sweat chloride concentration, body mass index (BMI) and the respiratory domain of the cystic fibrosis questionnaire-revised (CFQ-R RD) were prospectively evaluated in a cohort of pwCF who were candidates for inclusion in a compassionate program of ELX/TEZ/IVA therapy. All procedures were performed at baseline and then at 12 and 24 months after initiation of modulator therapy. The number of PExs in the year before the study enrollment was collected from our records. RESULTS: Thirty-six adult pwCF (median age 36.7 years; BMI 19.8 kg/m2; FEV1 36.5% predicted) were recruited from 2019. At 12 and 24 months after initiation, the absolute change in ppFEV1 (percent predicted forced expiratory volume in 1 s) from baseline was +12.5% (p < 0.0001) and +13% (p < 0.0001), respectively. A median of 4.0 exacerbations per patient was reported in the preceding year, while the median number of PExs was 0.0 and 1.0 after 12 and 24 months, respectively, of modulator therapy (both p < 0.0001). After 12 and 24 months of ELX/TEZ/IVA therapy, the CFQ-R RD score improved by 22.4 points (p < 0.0001) and 16.7 points (p < 0.0001), and sweat chloride levels decreased by 65.5 mmol/L (p < 0.0001) and 60 mmol/L (p < 0.0001), respectively. BMI significantly increased. CONCLUSIONS: Long-term ELX/TEZ/IVA combination therapy markedly impacts the clinical status of patients with severe CF, showing a sustained improvement in lung function and PEx rate.
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Fibrose Cística , Humanos , Adulto , Fibrose Cística/tratamento farmacológico , Fibrose Cística/genética , Cloretos , Pulmão , MutaçãoRESUMO
BACKGROUND: The aim of this study was to assess the long-term clinical impact of the application of e-health as part of a virtual model of care in patients with Cystic Fibrosis (CF). METHODS: Digital care group (DCG) were deemed suitable for using the NuvoAir Home platform to monitor their disease at home as part of a virtual model of care project. The usual care group (UCG) remained on usual care. NuvoAir Home platform consists of a smartphone application, Bluetooth spirometer and a clinician portal. Data on pulmonary function, Cystic Fibrosis Questionnaire-Revised (CFQR) and pulmonary exacerbations were collected at baseline and after twelve months. A survey for the digital care group was emailed to evaluate their experience using the technology. RESULTS: Between February 2020 and May 2020 a cohort of 43 CF patients were recruited for the DCG (26 females; mean age 31.6 ± 6.8; 16 homozygous for delta F508; FEV1 48.4 ± 16.3% predicted) and 36 CF patients for UCG (18 females; mean age 29.1 ± 9.4; 6 homozygous for delta F508; FEV1 77.0 ± 25.0% predicted). CFQ-R score improved significantly through 12 months in the DCG with a mean change of 13.8 points, p < 0.0001, and no changes for the UCG (p = 0.73). When we analyzed the subgroup of CF patients on digital and usual care who did not receive CFTR modulator therapy, we found a change in CFQ-R score which was significantly associated with the use of digital technology while adjusting for baseline differences (p = 0.020). There was no significant difference in the change in lung function and number of exacerbations. 90% of patients reported they understood their CF better using the NuvoAir Home platform. No changes in medical treatment were reported during that time. CONCLUSIONS: The application of digital technologies in the management of adults with CF showed an improvement in patients' quality of life. Using a virtual model of care was well accepted by CF patients and improved their understanding of their medical condition.
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Fibrose Cística , Adulto , Regulador de Condutância Transmembrana em Fibrose Cística , Feminino , Humanos , Masculino , Qualidade de Vida , Testes de Função Respiratória , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND: Over the last decades aggressive interventions have been successful to improve nutritional outcomes in people with cystic fibrosis (CF). As a result, with improvement of life expectancy and new CFTR modulators, overweight and obesity are progressively becoming a source of concern for adult population and in developed countries. METHODS: This was a multicenter, observational, cross-sectional study of 321 adults with CF at three large CF centers in Italy. Patients were divided into three groups according to BMI classes, overweight and obesity (OW) group including patients with BMI ≥25 kg/m2, normal weight (NW) group with BMI 18.6-24.9 kg/m2 and underweight (UW) group with BMI ≤18.5 kg/m2. RESULTS: We demonstrated that prevalence of OW in adults with CF in Italy is 22%. OW status is independently associated with male sex (OR 3.520, P = 0.001), pancreatic sufficiency (OR 2.873, P = 0.014) and older age at diagnosis (1.015, P = 0.042). BMI correlated with ppFEV1 (r = 0.337; P<0.0001) with median ppFEV1 significantly higher in patients with OW than comparisons. We also reported preliminary data on unfavorable cardiovascular risk factors in a subgroup of patients, where median blood levels [IQR] of cholesterol and systemic hypertension [%] were significantly higher in the OW group than in the NW and UW. CONCLUSIONS: People with CF and OW is a relevant patient group that might deserve better definition and proper clinical management.
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Fibrose Cística/complicações , Sobrepeso/complicações , Sobrepeso/epidemiologia , Adulto , Índice de Massa Corporal , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto JovemRESUMO
In the physiopathology of cystic fibrosis (CF), oxidative stress implications are recognized and widely accepted. The cystic fibrosis transmembrane conductance regulator (CFTR) defects disrupt the intracellular redox balance causing CF pathological hallmarks. Therefore, oxidative stress together with aberrant expression levels of detoxification genes and microRNAs (miRNAs/miRs) may be associated with clinical outcome. Using total RNA extracted from epithelial nasal cells, the present study analyzed the expression levels of oxidative stress genes and one miRNA using quantitative PCR in a representative number of patients with CF compared with in healthy individuals. The present pilot study revealed the existence of an association among CFTR, genes involved in the oxidative stress response and miR-125b. The observed downregulation of CFTR gene expression was accompanied by increased expression levels of Nuclear factor erythroid derived-2 like2 and its targets NAD(P)H:Quinone Oxidoreductase and glutathione S-transferase 1. Moreover, the expression levels of heme oxygenase-1 (HO-1) and miR-125b were positively correlated with a forced expiratory volume in 1 sec (FEV1) >60% in patients with CF with chronic Pseudomonas aeruginosa lung infection (r=0.74; P<0.001 and r=0.57; P<0.001, respectively). The present study revealed the activation of an inducible, but not fully functional, oxidative stress response to protect airway cells against reactive oxygen species-dependent injury in CF disease. Additionally, the correlations of HO-1 and miR-125b expression with an improved FEV1 value suggested that these factors may synergistically protect the airway cells from oxidative stress damage, inflammation and apoptosis. Furthermore, HO-1 and miR-125b may be used as prognostic markers explaining the wide CF phenotypic variability as an additional control level over the CFTR gene mutations.
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BACKGROUND: Regular physical activity (PA) is a valued part of cystic fibrosis (CF) care. Although the accelerometer, SenseWear Armband (SWA), accurately measures habitual PA in CF, it is mostly used for research purposes. For the first time, we analyzed different methods of measuring PA in daily life by the use of smartphones and other electronic devices such as smartwatch and Fitbit. METHODS: Twenty-four stable adults with CF (mean age 37.5 ± 11.5SD yrs.; FEV1 58 ± 19% predicted, BMI 22.9 ± 3.2) were studied. Daily PA was monitored for seven consecutive days. All patients wore the accelerometer SWA and at the same time they monitored PA with the electronic device they used routinely. They were allocated into one of four arms according to their device: Smartwatch, Fitbit, Android smartphones and iOS smartphones. PA related measurements included: duration of PA, energy expenditure, number of steps. RESULTS: There was a good agreement between SWA and Fitbit for number of steps (p = 0.605) and energy expenditure (p = 0.143). iOS smartphones were similar to SWA in monitoring the number of steps (p = 0.911). Significant differences were found between SWA and both Smartwatch and Android smartphones. CONCLUSIONS: Fitbit and iOS smartphones seem to be a valuable approach to monitor daily PA. They provide a good performance to measure step number compared to SWA.
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Fibrose Cística/fisiopatologia , Exercício Físico , Monitorização Ambulatorial/instrumentação , Telemedicina , Acelerometria , Atividades Cotidianas , Adulto , Fibrose Cística/psicologia , Metabolismo Energético , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Testes de Função Respiratória , Inquéritos e QuestionáriosRESUMO
INTRODUCTION: Malignant diseases are well-known complications after lung transplantation (LT). Among these, inflammatory myofibroblastic tumor (IMT) is a rare neoplasm with a not well-known and often aggressive biological behavior. MATERIAL AND METHODS: We hereby describe 2 cases of cystic fibrosis patients who underwent bilateral sequential LT (BSLT) complicated by IMT. RESULTS: A 26-year-old man presented a right endobronchial lesion 6 months after BSLT. Two consecutive fiber bronchoscopic biopsies showed granulation tissue. For the persistent lesion growth, the patient underwent a transthoracic biopsy showing histologic diagnosis of IMT. Therefore, he underwent to right pneumonectomy that was unfortunately complicated after 6 months with a late bronchopleural fistula and empyema with exitus 6 months later. A 31-year-old woman 1 year after BSLT presented with a left voluminous pleural-parenchymal lesion; the histologic examination after biopsy revealed an IMT. She underwent a removal of the lesion with a macroscopic R0 resection. Histologic, immunophenotypic, and cytogenetic examinations showed a strong overexpression of anaplastic lymphoma kinase requiring biological adjuvant therapies; however, the patient refused it. Four years later, she presented a recurrence treated with debulking procedure and adjuvant radiotherapy. At last follow-up, the patient was alive with stable disease and optimal graft function. CONCLUSIONS: Although IMT is a rare complication after lung transplant, to obtain a careful diagnosis, an early and aggressive treatment is mandatory.
Assuntos
Hospedeiro Imunocomprometido , Transplante de Pulmão/efeitos adversos , Granuloma de Células Plasmáticas Pulmonar/imunologia , Adulto , Fibrose Cística/cirurgia , Feminino , Humanos , MasculinoRESUMO
BACKGROUND: Burkholderia contaminans is one of the 20 closely related bacterial of the Burkholderia cepacia complex, a group of bacteria that are ubiquitous in the environment and capable of infecting people with cystic fibrosis (CF). This species is an emerging pathogen and it has been widely isolated from CF patients in Argentina, Spain, Portugal, Australia, Canada, USA with a low prevalence in Ireland, France, Russia, Switzerland, Czech Republic, and Italy. This is the first report of B. contaminans affecting two Italian CF patients attending the same CF Centre. We correlate B. contaminans colonisation with lung function decline and co-infection with other clinically relevant CF pathogens. CASE PRESENTATION: B. contaminans was identified by Multi Locus Sequence Typing in routine sputum analysis of two Caucasian CF women homozygous for Phe508del CFTR mutation. Sequence Type 102 was detected in both strains. It is known that B. contaminans ST102 was isolated both from CF and non-CF patients, with an intercontinental spread across the world. Random Amplified Polymorphic DNA analysis revealed the genetic relatedness between the two strains. We examined their susceptibility to antimicrobial agents, comparing the latter with that recorded for other B. contaminans isolated from different countries. We also described key virulence factors possibly linked with a clinical outcome. Specifically, we attempted to correlate colonization with the incidence of acute exacerbation of symptoms and lung function decline. CONCLUSIONS: This case presentation suggests that acquisition of B. contaminans ST102 is not directly associated with a lung function decline. We retain that the presence of other CF pathogens (i.e. MRSA and Trichosporon) along with B. contaminans ST102 might have contributed to the worsening of clinical conditions in our CF patients. The circumstances leading to the establishment of B. contaminans ST102 infections are still unknown. We highlight the importance to proper detect and typing bacteria implicated in CF infection by using molecular techniques.
Assuntos
Infecções por Burkholderia/complicações , Complexo Burkholderia cepacia/isolamento & purificação , Fibrose Cística/complicações , Adulto , Infecções por Burkholderia/microbiologia , Feminino , Humanos , Itália , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Tipagem de Sequências Multilocus , Escarro/microbiologia , Tomografia Computadorizada por Raios XRESUMO
Despite being a hallmark and an independent prognostic factor in several cardiopulmonary diseases, ventilatory efficiency-i.e., minute ventilation/carbon dioxide output relationship (VÌe/VÌco2)-has never been systematically explored in cystic fibrosis (CF). To provide a comprehensive frame of reference regarding measures of ventilatory efficiency in CF adults with normal to moderately impaired lung function and to confirm the hypothesis that VÌe/VÌco2 is a sensitive marker of early lung disease. CF patients were divided into three groups, according to their spirometry: normal (G1), mild impairment (G2), and moderate impairment (G3) in lung function. All participants underwent incremental cardiopulmonary exercise testing on a cycle ergometer. Lowest VÌe/VÌco2 ratio (nadir) and the slope and the intercept of the linear region of the VÌe/VÌco2 relationship were contrasted in a two-center retrospective analysis, involving 72 CF patients and 36 healthy controls (HC). Compared with HC, CF patients had significantly higher VÌe/VÌco2 nadir, slope, and intercept (P < 0.001, P < 0.001, and P = 0.049, respectively). Subgroup analysis revealed significant differences in nadir (P = 0.001) and slope (P = 0.012) values even between HC and G1. Dynamic hyperinflation related negatively with slope (P = 0.045) and positively with intercept (P = 0.001), while no impact on nadir was observed. Ventilatory inefficiency is a clear feature of adults with CF, even among patients with normal spirometry. VÌe/VÌco2 nadir seems to be the most reliable metric to describe ventilatory efficiency in CF adults. Further prospective studies are needed to clarify whether VÌe/VÌco2 could represent a useful marker in the evaluation of early lung disease in CF.NEW & NOTEWORTHY This is the first study to investigate ventilatory efficiency in a cohort of adult cystic fibrosis (CF) patients with nonsevere lung disease. The finding of impaired ventilatory efficiency in patients with normal lung function confirms the higher sensitivity of exercise testing in detecting early lung disease compared with spirometry. Dynamic hyperinflation plays a significant role in determining the behavior of VÌe/VÌco2 slope and intercept values with increasing lung function impairment. Apparently free from interference from mechanical constraints, VÌe/VÌco2 nadir seems the most reliable parameter to evaluate ventilatory efficiency in CF adults.
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Fibrose Cística/fisiopatologia , Exercício Físico/fisiologia , Pneumopatias/fisiopatologia , Pulmão/fisiopatologia , Ventilação Pulmonar/fisiologia , Adulto , Teste de Esforço/métodos , Feminino , Humanos , Masculino , Consumo de Oxigênio/fisiologia , Troca Gasosa Pulmonar/fisiologia , Fenômenos Fisiológicos Respiratórios , Estudos Retrospectivos , Espirometria/métodos , Adulto JovemRESUMO
The combination of the corrector lumacaftor with the potentiator ivacaftor has been approved for treatment of cystic fibrosis (CF) patients homozygous for the Phe508del CFTR mutation. There are no reports detailing the effect of lumacaftor-ivacaftor on physical activity (PA) and exercise tolerance. We performed incremental cardiopulmonary exercise testing (CPET) and we assessed PA pre- and post 2â¯years initiation of lumacaftor-ivacaftor in three CF adults. PA of mild intensity improved by +13% in patient 1, + 84% in patients 2 andâ¯+â¯89% in patient 3. Oxygen uptake increased both at anaerobic threshold and at peak exercise (patient 1â¯+â¯33%, patient 2â¯+â¯42% and patient 3â¯+â¯20%). Daily physical activities and exercise tolerance improved after two years of lumacaftor-ivacaftor therapy.
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Aminofenóis/administração & dosagem , Aminopiridinas/administração & dosagem , Benzodioxóis/administração & dosagem , Fibrose Cística , Tolerância ao Exercício/efeitos dos fármacos , Volume Expiratório Forçado/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos , Quinolonas/administração & dosagem , Atividades Cotidianas , Adulto , Agonistas dos Canais de Cloreto/administração & dosagem , Fibrose Cística/diagnóstico , Fibrose Cística/tratamento farmacológico , Fibrose Cística/fisiopatologia , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Combinação de Medicamentos , Monitoramento de Medicamentos/métodos , Exercício Físico , Tolerância ao Exercício/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Resultado do TratamentoRESUMO
BACKGROUND: The aim of this study was to investigate the relationship between dynamic hyperinflation and daily physical activity (DPA) in adults with cystic fibrosis (CF). METHODS: Thirty-four clinically stable CF were studied. All patients undertook incremental cardiopulmonary exercise testing (CPET). CPET-related measurements included: oxygen uptake (V'O2), carbon dioxide production (V'CO2), ventilatory profile, work rate (W), inspiratory capacity (IC), end-expiratory lung volume (EELV). PA was assessed using the accelerometer SenseWear Pro3 Armband. RESULTS: Exercise tolerance was reduced in most of patients and the mean V'O2,peak value was 75.2% of predicted (28.5 ± 4.8 ml/min/kg). Seventy % of patients responded to CPET with dynamic hyperinflation. Higher incidence of dynamic hyperinflation was found in CF males compared to CF females (p = 0.026). Patients who developed dynamic hyperinflation during CPET had higher vigorous PA (p = 0.01) and more total energy expenditure (p = 0.006) than patients who did not. EELVΔ was related to activities requiring vigorous intensity and total energy expenditure (R = 0.46, p = 0.001; R = 0.57, p < 0.001). CONCLUSIONS: In adults with CF and mild to moderate lung impairment, DPA might not be limited by dynamic hyperinflation.
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Fibrose Cística/fisiopatologia , Tolerância ao Exercício , Exercício Físico , Pulmão/fisiopatologia , Adulto , Teste de Esforço , Feminino , Volume Expiratório Forçado , Humanos , Capacidade Inspiratória , Itália , Modelos Lineares , Masculino , Análise Multivariada , Consumo de OxigênioRESUMO
RATIONALE: Cystic fibrosis transmembrane conductance regulator (CFTR) is expressed in human skeletal muscle cells. Variations of CFTR dysfunction among patients with cystic fibrosis may be an important determinant of maximal exercise capacity in cystic fibrosis. Previous studies on the relationship between CFTR genotype and maximal exercise capacity are scarce and contradictory. OBJECTIVES: This study was designed to explore factors influencing maximal exercise capacity, expressed as peak oxygen uptake (V.O2peak), with a specific focus on CFTR genotype in children and adults with cystic fibrosis. METHODS: In an international, multicenter, cross-sectional study, we collected data on CFTR genotype and cardiopulmonary exercise tests in patients with cystic fibrosis who were ages 8 years and older. CFTR mutations were classified into functional classes IV. RESULTS: The final analysis included 726 patients (45% females; age range, 861 yr; forced expiratory volume in 1 s, 16 to 123% predicted) from 17 cystic fibrosis centers in North America, Europe, Australia, and Asia, all of whom had both valid maximal cardiopulmonary exercise tests and complete CFTR genotype data. Overall, patients exhibited exercise intolerance (V.O2peak, 77.3 ± 19.1% predicted), but values were comparable among different CFTR classes. We did not detect an association between CFTR genotype functional classes IIII and either V.O2peak (percent predicted) (adjusted ß = −0.95; 95% CI, −4.18 to 2.29; P = 0.57) or maximum work rate (Wattmax) (adjusted ß = −1.38; 95% CI, −5.04 to 2.27; P = 0.46) compared with classes IVV. Those with at least one copy of a F508del-CFTR mutation and one copy of a class V mutation had a significantly lower V.O2peak (ß = −8.24%; 95% CI, −14.53 to −2.99; P = 0.003) and lower Wattmax (adjusted ß = −7.59%; 95% CI, −14.21 to −0.95; P = 0.025) than those with two copies of a class II mutation. On the basis of linear regression analysis adjusted for relevant confounders, lung function and body mass index were associated with V.O2peak. CONCLUSIONS: CFTR functional genotype class was not associated with maximal exercise capacity in patients with cystic fibrosis overall, but those with at least one copy of a F508del-CFTR mutation and a single class V mutation had lower maximal exercise capacity.
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Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística , Tolerância ao Exercício/genética , Adolescente , Adulto , Criança , Correlação de Dados , Estudos Transversais , Fibrose Cística/diagnóstico , Fibrose Cística/genética , Fibrose Cística/fisiopatologia , Teste de Esforço , Feminino , Volume Expiratório Forçado , Humanos , Cooperação Internacional , Masculino , Pessoa de Meia-Idade , Mutação , Consumo de OxigênioRESUMO
BACKGROUND: The aim of this study was to examine the relationship between pulmonary exacerbations and physical activity (PA) in adults with cystic fibrosis (CF). METHODS: We grouped adults with CF according to their exacerbation status in the year before study enrollment: (1) <1 exacerbation/year; (2) 1-2 exacerbations/year; and (3) >2 exacerbations/year. PA was assessed objectively by means of an accelerometer at the time of study enrollment. RESULTS: Patients with >2 exacerbations/year spent less time in PA; specifically, fewer activities of mild intensity [>3 metabolic equivalents (METs)], and lower active energy expenditure (P = 0.01 and P = 0.03, respectively). After correcting for relevant confounders, PA levels were not related to the exacerbation frequency in the preceding year. PA at moderate intensity (4.8-7.2 METs) or greater (> 7.2 METs) was independently associated with gender and FEV1 % predicted (P = 0.007 and P = 0.04, respectively). Compared with men, women had reduced vigorous activities (P = 0.01) and active energy expenditure (P = 0.01). CONCLUSIONS: Adult CF patients with more pulmonary exacerbations in the preceding year have more advanced disease and are less active than their peers. PA was independently associated with gender and airflow obstruction. Gender differences in PA are evident in CF adults.
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Fibrose Cística/fisiopatologia , Progressão da Doença , Metabolismo Energético , Atividade Motora , Acelerometria , Adulto , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Equivalente Metabólico , Pessoa de Meia-Idade , Capacidade de Difusão Pulmonar , Fatores Sexuais , Capacidade Pulmonar Total , Capacidade Vital , Adulto JovemRESUMO
BACKGROUND: The best clinical practice to investigate aerobic fitness includes measurements obtained during cardiopulmonary exercise testing (CPET), however it remains an underutilised clinical measure in cystic fibrosis (CF). To investigate this further, different methods of quantifying exercise capacity in CF are required. The possibility that measuring physical activity (PA) by a portable accelerometer could be used to assess the CF aerobic state and could be added among the CPET surrogates has not been investigated. The aim of this study was to examine the relationship between PA and exercise fitness both at submaximal and maximal levels in clinically stable adults with CF. METHODS: Thirty CF patients (FEV1 71 ± 19% predicted) and fifteen healthy controls undertook an incremental CPET on a cycle ergometer. CPET-related measurements included: oxygen uptake (V'O2), carbon dioxide production (V'CO2), ventilatory profile, heart rate (HR) and oxygen pulse (V'O2/HR) throughout exercise and at lactic threshold (LT) and peak. LT measures represent submaximal exercise related data. PA was assessed using the accelerometer SenseWear Pro3 Armband. RESULTS: Moderate (>4.8 metabolic equivalents (METS)) and moderate + vigorous (>7.2 METS) PA was related to V'O2 (p = 0.005 and p = 0.009, respectively) and work rate (p = 0.004 and p = 0.002, respectively) at LT. Moderate PA or greater was positively related to peak V'O2 (p = 0.005 and p = 0.003, respectively). Daily PA levels were similar in CF and healthy controls. Except for peak values, V'O2 profile and the V'O2 at LT were comparable between CF and healthy controls. CONCLUSIONS: In adult CF patients daily PA positively correlated with aerobic capacity. PA measurements are a valuable tool in the assessment of exercise performance in an adult CF population and could be used for interventional exercise trials to optimize exercise performance and health status. PA levels and parameters obtained at submaximal exercise are similar in CF and in healthy controls.
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Fibrose Cística/fisiopatologia , Tolerância ao Exercício/fisiologia , Atividade Motora/fisiologia , Consumo de Oxigênio/fisiologia , Aptidão Física , Acelerometria , Adulto , Dióxido de Carbono/metabolismo , Estudos de Casos e Controles , Teste de Esforço , Feminino , Frequência Cardíaca , Humanos , Masculino , Equivalente Metabólico , Ventilação Pulmonar/fisiologiaRESUMO
BACKGROUND: The aim of the present study was to determine whether different methods of recording physical activity (PA), i.e., accelerometers vs questionnaires, provided similar information in adults with cystic fibrosis (CF). METHODS: 20 CF (age 33 ± 8SD yrs, FEV1 68 ± 16% predicted) and 11 age-matched healthy controls completed the Habitual Activity Estimation Scale (HAES) questionnaire and wore a biaxial accelerometer (SenseWear Pro3 Armband). Exercise tolerance was measured in CF. RESULTS: Patients had similar values in PA compared with controls. None of PA categories estimated by HAES questionnaire correlated with PA categories measured by the accelerometer; in CF the HAES questionnaire overestimated the effective levels of PA measured by the accelerometer. There were no differences between weekdays and weekend days PA levels provided by the accelerometer. In CF the questionnaire detected different time reported during the "somewhat inactive" and "somewhat active" categories (z = 2.651; p = 0.008; z = -2.651; p = 0.008), weekdays vs weekend; patients reported more time spent in activity (somewhat active & very active) during the weekend (z = -2.203; p = 0.02). Peak oxygen uptake correlated with accelerometer activities of "moderate" (>4.8 metabolic equivalents (METS)) and "vigorous" (>7.2 METS) intensity (r = 0.503, p = 0.02; r = 0.545, p = 0.01). CONCLUSIONS: In adults with cystic fibrosis PA levels are better evaluated by the accelerometer and are similar to the controls. PA measured by the accelerometer is similar during the week and correlates with exercise tolerance.
Assuntos
Fibrose Cística/fisiopatologia , Exercício Físico , Acelerometria , Atividades Cotidianas , Adulto , Estudos de Casos e Controles , Fibrose Cística/psicologia , Tolerância ao Exercício/fisiologia , Feminino , Volume Expiratório Forçado/fisiologia , Hábitos , Humanos , Masculino , Monitorização Ambulatorial , Aptidão Física , Inquéritos e Questionários , Capacidade Vital/fisiologiaRESUMO
Chronic obstructive pulmonary disease (COPD) patients have reduced circulating hemopoietic progenitors. We hypothesized that severity of COPD parallels the decrease in progenitors and that the reduction in body mass index (BMI) could be associated with more severe bone marrow dysfunction. We studied 39 patients with moderate to very severe COPD (18 with low-BMI and 21 with normal-BMI) and 12 controls. Disease severity was associated to a greater reduction in circulating progenitors. Proangiogenetic and inflammatory markers correlated with disease severity parameters. Compared to normal-BMI patients, low-BMI patients showed: greater reduction in circulating progenitors; higher VEGF-A, VEGF-C, HGF, Ang-2, TNF-alpha, IL-6 and MCP-1 levels. Furthermore, among patients with similar pulmonary impairment, those who displayed low-BMI had a more markedly reduced number of CD34(+) cells and late endothelial progenitors. We show that the reduction in hematopoietic and endothelial progenitor cells correlates with COPD severity. Our findings also indicate that, in severe low-BMI COPD patients, bone marrow function seems to be further impaired and may lead to reduced reparative capacity.
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Índice de Massa Corporal , Transplante de Medula Óssea/métodos , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/cirurgia , Idoso , Análise de Variância , Antígenos CD/metabolismo , Contagem de Células Sanguíneas/métodos , Estudos de Casos e Controles , Ensaio de Unidades Formadoras de Colônias/métodos , Creatina Quinase/sangue , Citocinas/sangue , Células Endoteliais/fisiologia , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Lactato Desidrogenases/sangue , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Estatística como AssuntoRESUMO
Female genital schistosomiasis is not uncommon in endemic areas for schistosomiasis, but there are few reports in the Brazilian medical literature. Here, we describe the case of a 31-year-old woman with lower abdominal pain who was diagnosed as presenting a fallopian tube tumor caused by Manson's schistosomiasis. The diagnosis was delayed because her symptoms were considered nonspecific. Involvement of the parietal peritoneum of the ovarian fossa was observed during laparoscopy and confirmed by histological analysis. The left tube and the tumor were excised and schistosomiasis was treated with praziquantel. She presented a full recovery and options for future reproduction are under evaluation.
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Doenças das Tubas Uterinas/parasitologia , Schistosoma mansoni/isolamento & purificação , Esquistossomose mansoni/diagnóstico , Adulto , Animais , Anti-Helmínticos/uso terapêutico , Doenças das Tubas Uterinas/diagnóstico , Doenças das Tubas Uterinas/cirurgia , Feminino , Humanos , Laparoscopia , Praziquantel/uso terapêutico , Esquistossomose mansoni/tratamento farmacológicoRESUMO
Female genital schistosomiasis is not uncommon in endemic areas for schistosomiasis, but there are few reports in the Brazilian medical literature. Here, we describe the case of a 31-year-old woman with lower abdominal pain who was diagnosed as presenting a fallopian tube tumor caused by Manson's schistosomiasis. The diagnosis was delayed because her symptoms were considered nonspecific. Involvement of the parietal peritoneum of the ovarian fossa was observed during laparoscopy and confirmed by histological analysis. The left tube and the tumor were excised and schistosomiasis was treated with praziquantel. She presented a full recovery and options for future reproduction are under evaluation.
Esquistossomose genital feminina não é incomum em áreas endêmicas para esquistossomose, mas, há poucos relatos na literatura médica brasileira. Descrevemos aqui, o caso de uma paciente de 31 anos com dor abdominal no baixo ventre que recebeu o diagnóstico de tumor da trompa de falópio causada pela esquistossomose mansônica. O diagnóstico foi retardado porque os sintomas foram considerados inespecíficos. Havia envolvimento do peritônio parietal da fossa ovárica durante a laparoscopia, confirmado à histologia. A tuba esquerda e o tumor foram extirpados e a esquistossomose foi tratada com praziquantel. A paciente apresentou recuperação completa e opções para reprodução futura estão sob avaliação.
Assuntos
Adulto , Animais , Feminino , Humanos , Doenças das Tubas Uterinas/parasitologia , Schistosoma mansoni/isolamento & purificação , Esquistossomose mansoni/diagnóstico , Anti-Helmínticos/uso terapêutico , Doenças das Tubas Uterinas/diagnóstico , Doenças das Tubas Uterinas/cirurgia , Laparoscopia , Praziquantel/uso terapêutico , Esquistossomose mansoni/tratamento farmacológicoRESUMO
OBJETIVO: analisar a variabilidade interobservador no diagnóstico histopatológico de lesões mamárias consideradas pré-malignas antes e após o treinamento com o uso de critérios diagnósticos padronizados. MÉTODOS: foram utilizadas lâminas contendo cortes histológicos representativos de três tipos de lesões mamárias (hiperplasia ductal atípica, carcinoma ductal in situ e carcinoma ductal in situ com microinvasão) revistas por um especialista internacional em patologia mamária e cujos diagnósticos foram considerados como padrão de referência. As mesmas lâminas foram avaliadas em dois tempos por cinco patologistas da comunidade que receberam um protocolo específico para classificar as lesões. Na primeira avaliação, os casos foram analisados e classificados usando critérios específicos adotados em cada serviço. Num segundo tempo, os patologistas receberam um tutorial contendo critérios diagnósticos e imagens representativas e novamente classificaram as lesões empregando os critérios padronizados. Foi realizada análise interobservador usando concordância percentual e o índice de Kappa ponderado. RESULTADOS: houve grande variabilidade diagnóstica entre os patologistas na análise inicial sem o uso de critérios diagnósticos padronizados quanto ao diagnóstico, grau nuclear e grau histológico (os índices de Kappa ponderado quanto ao diagnóstico variaram de 0,15 a 0,40). Na segunda avaliação, utilizando-se critérios padronizados, houve significativa melhora na concordância diagnóstica entre os cinco patologistas quanto ao diagnóstico, grau nuclear e grau histológico (os índices de Kappa ponderado quanto ao diagnóstico variaram de 0,42 a 0,80). CONCLUSÕES: a concordância interobservador no diagnóstico e classificação das lesões pré-malignas da mama pode ser melhorada com o treinamento específico e o uso de critérios histopatológicos padronizados.
PURPOSE: to analyze interobserver variability in the histopathological diagnosis of premalignant breast lesions before and after training with diagnostic standardized criteria. METHODS: Slides containing histological sections representative of three kinds of breast lesions (atypical ductal hyperplasia, ductal carcinoma in situ and ductal carcinoma in situ with microinvasion), revised by an international specialist in breast pathology whose diagnoses were considered as golden standard, have been used. The same slides have been evaluated at two different times by five pathologists from the community according to a specific protocol for classifying the lesions. In the first evaluation, the cases were analyzed and classified according to the specific criteria adopted in each service. At the second time, the pathologists were given a tutorial containing diagnostic criteria and representative images, and the lesions were classified again, employing the standardized criteria. Interobserver analysis using percent agreement and weighted Kappa index has been performed. RESULTS: There has been a large diagnostic variation among the pathologists in the initial analysis without the use of standardized diagnostic criteria concerning the diagnostic, nuclear grade and histological grade (weighted Kappa indexes related to diagnosis varied from 0.15 to 0.40). In the second evaluation using standardized criteria, there has been a significant improvement in the diagnostic concordance among the five pathologists concerning the diagnosis, nuclear grade and histological grade (weighted Kappa indexes related to diagnosis have varied from 0.42 to 0.80). CONCLUSIONS: interobserver concordance related to diagnosis and classification of breast premalignant lesions may be improved with specific training and the use of standardized histopathological criteria.
Assuntos
Humanos , Feminino , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Intraductal não Infiltrante/diagnóstico , Doenças Mamárias/diagnóstico , Hiperplasia/diagnóstico , Invasividade NeoplásicaRESUMO
PURPOSE: to analyze interobserver variability in the histopathological diagnosis of premalignant breast lesions before and after training with diagnostic standardized criteria. METHODS: Slides containing histological sections representative of three kinds of breast lesions (atypical ductal hyperplasia, ductal carcinoma in situ and ductal carcinoma in situ with microinvasion), revised by an international specialist in breast pathology whose diagnoses were considered as golden standard, have been used. The same slides have been evaluated at two different times by five pathologists from the community according to a specific protocol for classifying the lesions. In the first evaluation, the cases were analyzed and classified according to the specific criteria adopted in each service. At the second time, the pathologists were given a tutorial containing diagnostic criteria and representative images, and the lesions were classified again, employing the standardized criteria. Interobserver analysis using percent agreement and weighted Kappa index has been performed. RESULTS: There has been a large diagnostic variation among the pathologists in the initial analysis without the use of standardized diagnostic criteria concerning the diagnostic, nuclear grade and histological grade (weighted Kappa indexes related to diagnosis varied from 0.15 to 0.40). In the second evaluation using standardized criteria, there has been a significant improvement in the diagnostic concordance among the five pathologists concerning the diagnosis, nuclear grade and histological grade (weighted Kappa indexes related to diagnosis have varied from 0.42 to 0.80). CONCLUSIONS: interobserver concordance related to diagnosis and classification of breast premalignant lesions may be improved with specific training and the use of standardized histopathological criteria.
Assuntos
Neoplasias da Mama/patologia , Lesões Pré-Cancerosas/patologia , Neoplasias da Mama/epidemiologia , Estudos Transversais , Feminino , Humanos , Variações Dependentes do Observador , Patologia/educação , Patologia/normas , Patologia/estatística & dados numéricos , Lesões Pré-Cancerosas/epidemiologiaRESUMO
O câncer colorretal (CCR) apresenta incidência e mortalidades elevadas. A colonoscopia é o melhor método para o diagnóstico precoce do CCR e das lesões precursoras. Ela, com magnificação de imagem (CM) vem sendo utilizada para melhora de resultados / Colorectal cancer (CRC) remains a major health problem due to its high incidence and mortality. Conventional colonoscopy (CC) represents the best mehod for early diagnosis of CRC and for diagnosis and treatment of precursor lesions. Magnifying colonoscopy (MC) has been used with the purpose of increasing the performance of CC...