Maria Ângela Gonçalves de Oliveira Ribeiro

Controvérsias na fibrose cística: do pediatra ao especialista

Objetivos: nos ultimos 70 anos, a fibrose cistica emergiu da obscuridade para o reconhecimento como a mais importante doenca hereditaria, potencialmente letal, incidente na raca branca. Embora seja uma doenca genetica, na qual o defeito basico acomete celulas de varios orgaos, nem todos os individuos expressam respostas clinicas na mesma intensidade. Varias manifestacoes clinicas, principalmente pulmonares e digestivas, podem ocorrer durante a vida dos pacientes fibrocisticos. O objetivo deste artigo e propiciar ao pediatra geral uma visao atualizada dos principais assuntos referentes a fibrose cistica. Fontes dos dados: revisao sistematica e atualizada em fonte de dados oficial (Medline). Sintese dos dados: foram revisados 79 artigos sobre fibrose cistica, de periodicos internacionais, colocando, de modo atual e critico, os principais eventos relacionados com a incidencia, a fisiopatogenia, as manifestacoes clinicas, o diagnostico e o tratamento da fibrose cistica. Conclusoes: apesar de nao existir cura para essa doenca, muitos conhecimentos novos sobre a etiologia e a fisiopatologia, adquiridos nas duas ultimas decadas, propiciaram uma nova abordagem para o tratamento da fibrose cistica. A compreensao dos mecanismos basicos da doenca pulmonar, bem como das manifestacoes digestivas na fibrose cistica, decorrente dos conhecimentos de pesquisas recentes, tem sido a chave para o aumento da sobrevida e a melhora da qualidade de vida dos pacientes.

Measurements of CFTR-Mediated Cl- Secretion in Human Rectal Biopsies Constitute a Robust Biomarker for Cystic Fibrosis Diagnosis and Prognosis

Background Cystic Fibrosis (CF) is caused by ∼1,900 mutations in the CF transmembrane conductance regulator (CFTR) gene encoding for a cAMP-regulated chloride (Cl−) channel expressed in several epithelia. Clinical features are dominated by respiratory symptoms, but there is variable organ involvement thus causing diagnostic dilemmas, especially for non-classic cases. Methodology/Principal Findings To further establish measurement of CFTR function as a sensitive and robust biomarker for diagnosis and prognosis of CF, we herein assessed cholinergic and cAMP-CFTR-mediated Cl− secretion in 524 freshly excised rectal biopsies from 118 individuals, including patients with confirmed CF clinical diagnosis (n = 51), individuals with clinical CF suspicion (n = 49) and age-matched non-CF controls (n = 18). Conclusive measurements were obtained for 96% of cases. Patients with “Classic CF”, presenting earlier onset of symptoms, pancreatic insufficiency, severe lung disease and low Shwachman-Kulczycki scores were found to lack CFTR-mediated Cl− secretion (<5%). Individuals with milder CF disease presented residual CFTR-mediated Cl− secretion (10–57%) and non-CF controls show CFTR-mediated Cl− secretion ≥30–35% and data evidenced good correlations with various clinical parameters. Finally, comparison of these values with those in “CF suspicion” individuals allowed to confirm CF in 16/49 individuals (33%) and exclude it in 28/49 (57%). Statistical discriminant analyses showed that colonic measurements of CFTR-mediated Cl− secretion are the best discriminator among Classic/Non-Classic CF and non-CF groups. Conclusions/Significance Determination of CFTR-mediated Cl− secretion in rectal biopsies is demonstrated here to be a sensitive, reproducible and robust predictive biomarker for the diagnosis and prognosis of CF. The method also has very high potential for (pre-)clinical trials of CFTR-modulator therapies.

Respiração bucal e anteriorização da cabeça: efeitos na biomecânica respiratória e na capacidade de exercício em crianças

OBJECTIVE To evaluate submaximal exercise tolerance and respiratory muscle strength in relation to forward head posture (FHP) and respiratory mode in children, comparing mouth-breathing (MB) children with nasal-breathing (NB) children. METHODS This was a controlled, analytical cross-sectional study involving children in the 8-12 year age bracket with a clinical otorhinolaryngology diagnosis of MB, recruited between October of 2010 and January of 2011 from the Mouth Breather Clinic at the State University of Campinas Hospital de Clínicas, located in the city of Campinas, Brazil. The exclusion criteria were obesity, asthma, chronic respiratory diseases, heart disease, and neurological or orthopedic disorders. All of the participants underwent postural assessment and the six-minute walk test (6MWT), together with determination of MIP and MEP. RESULTS Of the 92 children in the study, 30 presented with MB and 62 presented with NB. In the MB group, the differences between those with moderate or severe FHP and those with normal head posture, in terms of the mean MIP, MEP and six-minute walk distance (6MWD), were not significant (p = 0.079, p = 0.622, and p = 0.957, respectively). In the NB group, the mean values of MIP and MEP were higher in the children with moderate FHP than in those with normal head posture (p = 0.003 and p = 0.004, respectively). The mean MIP, MEP, and 6MWD were lower in the MB group than in the NB group. Values of MIP and MEP were highest in the children with moderate FHP. CONCLUSIONS Respiratory biomechanics and exercise capacity were negatively affected by MB. The presence of moderate FHP acted as a compensatory mechanism in order to improve respiratory muscle function.OBJECTIVE: To evaluate submaximal exercise tolerance and respiratory muscle strength in relation to forward head posture (FHP) and respiratory mode in children, comparing mouth-breathing (MB) children with nasal-breathing (NB) children. METHODS: This was a controlled, analytical cross-sectional study involving children in the 8-12 year age bracket with a clinical otorhinolaryngology diagnosis of MB, recruited between October of 2010 and January of 2011 from the Mouth Breather Clinic at the State University of Campinas Hospital de Clinicas, located in the city of Campinas, Brazil. The exclusion criteria were obesity, asthma, chronic respiratory diseases, heart disease, and neurological or orthopedic disorders. All of the participants underwent postural assessment and the six-minute walk test (6MWT), together with determination of MIP and MEP. RESULTS: Of the 92 children in the study, 30 presented with MB and 62 presented with NB. In the MB group, the differences between those with moderate or severe FHP and those with normal head posture, in terms of the mean MIP, MEP and six-minute walk distance (6MWD), were not significant (p = 0.079, p = 0.622, and p = 0.957, respectively). In the NB group, the mean values of MIP and MEP were higher in the children with moderate FHP than in those with normal head posture (p = 0.003 and p = 0.004, respectively). The mean MIP, MEP, and 6MWD were lower in the MB group than in the NB group. Values of MIP and MEP were highest in the children with moderate FHP. CONCLUSIONS: Respiratory biomechanics and exercise capacity were negatively affected by MB. The presence of moderate FHP acted as a compensatory mechanism in order to improve respiratory muscle function.

Effects of swimming on spirometric parameters and bronchial hyperresponsiveness in children and adolescents with moderate persistent atopic asthma

OBJECTIVE To investigate the medium-term benefits of a swimming program in schoolchildren and adolescents with moderate persistent atopic asthma (MPAA). METHODS A randomized, prospective study of children and adolescents (age 7-18 years) with MPAA was carried out at the Hospital de Clínicas of Universidade Estadual de Campinas (UNICAMP), Campinas, Brazil. After a 1-month run-in period, 61 patients (34 female) were randomized into two groups, a swimming group (n = 30) and a control group (n = 31), and followed for 3 months. Both patient groups received inhaled fluticasone (dry powder, 250 mcg twice a day) and salbutamol as needed. The swim training program consisted of two weekly classes over a 3-month period for a total of 24 sessions. Both groups underwent spirometric assessment and methacholine challenge test--provocative concentration of methacholine causing a 20% fall in FEV1 (PC₂₀)--before and after the study period. Maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) were measured only in the swimming group. RESULTS Significant increases in PC₂₀ (pre-training, 0.31±0.25; post-training, 0.63±0.78; p = 0.008), MIP (pre-training, 67.08±17.13 cm H₂O; post-training 79.46±18.66; p < 0.001), and MEP (pre-training, 71.69±20.01 cm H₂O; post-training, 78.92±21.45 cm H₂O; p < 0.001) were found in the swimming group. CONCLUSION Children and adolescents with MPAA subjected to a swim training program experienced a significant decrease in bronchial hyperresponsiveness, as determined by increased PC₂₀ values, when compared with asthmatic controls who did not undergo swim training. Participants in the swimming group also showed improvement in elastic recoil of the chest wall.

Ocorrência de desvios posturais em escolares do ensino público fundamental de Jaguariúna, São Paulo

OBJECTIVE: Evaluate the posture of students from a public school in Brazil and to identify the differences between normal deviation during growth and compensatory alterations. METHODS: Students from first to fourth grade of a public school in the city of Jaguariuna, Sao Paulo, Brazil, were evaluated. The students were positioned at sagital anterior and posterior coronal planes for postural assessment. Kendall points were used as the normal reference. RESULTS: 247 students were evaluated, 131 boys and 116 girls, and the main postural deviations found were: shoulder unbalance (50.2%), protracted shoulder (39.7%), abducted scapula (40.5%), knock-knee (29.6%), pelvic unbalance (21.5%), pelvic anteversion (19%), knee hyperextension (19%), medial rotation of hip (12.9%), protracted cervical (11.7%), head tilt (15.4%), thoracic hyperkyphosis (9.7%) and lumbar hyperlordosis (26.3%). CONCLUSIONS: A high incidence of postural alterations was detected in school children. Some of the postural alterations, such as abducted scapula, unbalance and protraction of the shoulders, knock-knee and lumbar hiperlordosis, normally occur and they are naturally corrected during growth. However, some postural problems, such as protraction and inclination of the cervical spine, were also prevalent and they require early intervention.

Capnografia volumétrica na identificação da não homogeneidade da ventilação em crianças e adolescentes com asma persistente controlada

OBJECTIVES To study changes in the variables of volumetric capnography in children and adolescents with asthma compared with a control group and to investigate their changes with the use of bronchodilators and bronchial provocation test with methacholine. METHODS One hundred and three patients with controlled persistent asthma and 40 healthy volunteers participated in the study. All of them underwent volumetric capnography and spirometry. All asthmatics repeated the tests after bronchodilator use. Among 103 asthma patients, 33 underwent methacholine challenge test, and measures were recorded on three occasions: before and after methacholine and after bronchodilator use. RESULTS Compared with the control group, asthmatics had an increase in the slope of phase III normalized by tidal volume and decreases in tidal volume, forced expiratory volume in one second, forced vital capacity, rate of obstruction and forced expiratory flow between 25 to 75% of forced vital capacity. After bronchodilator use, there was an increase in spirometric variables, volume of anatomic dead space, and decrease in the slope of phase II normalized by tidal volume, but the slope of phase III normalized by tidal volume did not change. After methacholine, there was an increase in this variable, which decreased after bronchodilator use. CONCLUSIONS The increase in the slope of phase III normalized by tidal volume in asthma patients suggests that these patients have ventilation inhomogeneity in the distal air spaces, which may reflect chronic structural disorders or reversible acute changes seen on the bronchial provocation test.

Exercise capacity, respiratory mechanics and posture in mouth breathers

UNLABELLED Chronic and persistent mouth or oral breathing (OB) has been associated with postural changes. Although posture changes in OB causes decreased respiratory muscle strength, reduced chest expansion and impaired pulmonary ventilation with consequences in the exercise capacity, few studies have verified all these assumptions. OBJECTIVE To evaluate exercise tolerance, respiratory muscle strength and body posture in oral breathing (OB) compared with nasal breathing (NB) children. MATERIAL AND METHOD A cross-sectional contemporary cohort study that included OB and NB children aged 8-11 years old. Children with obesity, asthma, chronic respiratory diseases, neurological and orthopedic disorders, and cardiac conditions were excluded. All participants underwent a postural assessment, maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), the six-minute walk test (6MWT), and otorhinolaryngologic evaluation. RESULTS There were 107 children (45 OB and 62 NB). There was an association between abnormal cervical posture and breathing pattern: 36 (80.0%) OB and 30 (48.4%) NB presented abnormal head posture (OR=4.27 [95% CI: 1.63-11,42], p<0.001). The mean MIP and MEP were lower in OB (p=0.003 and p=0.004). CONCLUSION OB children had cervical spine postural changes and decreased respiratory muscle strength compared with NB.

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.

Estoque domiciliar de medicamentos na comunidade ibiaense acompanhada pelo Programa Saúde da Família, em Ibiá-MG, Brasil

O objetivo do estudo foi examinar o estoque de medicamentos na comunidade Ibiaense acompanhada pelo Programa Saude da Familia (PSF). Buscou-se descrever as caracteristicas dos usuarios, as condicoes de armazenamento, as classes terapeuticas, as formas farmaceuticas e a procedencia dos medicamentos do estoque caseiro. Foram visitados 285 domicilios, no periodo de julho a setembro de 2004. Verificou-se que a media de medicamentos por domicilio foi de 8,4, e que 93,5% das familias entrevistadas apresentaram pelo menos um medicamento em estoque. Os medicamentos estocados em maior numero foram: analgesicos (11,15%), seguidos dos diureticos (6,42%), antibacterianos para uso sistemico (5,82%), anti-inflamatorios (5,08%) e antiacidos (4,10%). Embora seja consideravel o numero de medicamentos estocados nos domicilios, foi pequeno o numero de medicamentos sem prescricao medica procedentes do Sistema Publico de Saude, sendo este um reflexo favoravel dos servicos de Assistencia Farmaceutica do Municipio. Apesar disso, foi verificado um elevado percentual (41,6%) de medicamentos adquiridos em farmacias sem a devida prescricao medica (automedicacao). Foi encontrado um percentual de 18,5% de medicamentos vencidos. Verificou-se, tambem, que parte do estoque domiciliar resulta de prescricoes com quantidades superiores as necessarias para o tratamento (20%), do nao cumprimento do tratamento prescrito (17%) e da aquisicao por conta propria (9%). O estudo sugere a necessidade de orientacao dos usuarios em relacao a utilizacao e ao armazenamento dos medicamentos, a sistematizacao dos registros de dados e oferece subsidios para adocao de decisoes vinculadas ao processo de planejamento e execucao das acoes na Assistencia Farmaceutica.

Controversies in cystic fibrosis: from pediatrician to specialist

Objetivos: nos ultimos 70 anos, a fibrose cistica emergiu da obscuridade para o reconhecimento como a mais importante doenca hereditaria, potencialmente letal, incidente na raca branca. Embora seja uma doenca genetica, na qual o defeito basico acomete celulas de varios orgaos, nem todos os individuos expressam respostas clinicas na mesma intensidade. Varias manifestacoes clinicas, principalmente pulmonares e digestivas, podem ocorrer durante a vida dos pacientes fibrocisticos. O objetivo deste artigo e propiciar ao pediatra geral uma visao atualizada dos principais assuntos referentes a fibrose cistica. Fontes dos dados: revisao sistematica e atualizada em fonte de dados oficial (Medline). Sintese dos dados: foram revisados 79 artigos sobre fibrose cistica, de periodicos internacionais, colocando, de modo atual e critico, os principais eventos relacionados com a incidencia, a fisiopatogenia, as manifestacoes clinicas, o diagnostico e o tratamento da fibrose cistica. Conclusoes: apesar de nao existir cura para essa doenca, muitos conhecimentos novos sobre a etiologia e a fisiopatologia, adquiridos nas duas ultimas decadas, propiciaram uma nova abordagem para o tratamento da fibrose cistica. A compreensao dos mecanismos basicos da doenca pulmonar, bem como das manifestacoes digestivas na fibrose cistica, decorrente dos conhecimentos de pesquisas recentes, tem sido a chave para o aumento da sobrevida e a melhora da qualidade de vida dos pacientes.