Alfonso Eduardo Alvarez

Fibrose cística em um centro de referência no Brasil: características clínicas e laboratoriais de 104 pacientes e sua associação com o genótipo e a gravidade da doença

OBJECTIVE To identify the clinical, laboratory and radiographic characteristics of the cystic fibrosis patients under care at Universidade Estadual de Campinas (UNICAMP) in the last decade of the twentieth century, and to investigate the association of these characteristics with genotype and severity of the disease as measured by the Shwachman score. METHODS Descriptive, retrospective and cross-sectional study of the patients assisted at UNICAMP hospitals Cystic Fibrosis Clinic from July 1990 to July 2000. RESULTS One hundred and four patients were studied; 53.8% male; 93.3% Caucasian; 89.4% presented with respiratory symptoms; 59.6% presented with digestive symptoms; 5.8% had meconium ileus; 4.8% had diabetes. The mean age at onset of symptoms was 3 months, and the mean age at diagnosis was 2 years and 4 months. At diagnosis, 69.9 and 56.6% of the patients had weight and height below 10th percentile, respectively; in 10.6%, sweat chloride was < 60 mEq/l. Staphylococcus aureus was found in 80.2%, Pseudomonas aeruginosa in 76%, and Burkholderia cepacia in 5.2%. DeltaF508 homozygosis was observed in 18.75%, whereas 62.50% of the patients were DeltaF508 heterozygous. A moderate/severe Shwachman score was found in 15.7%. Eighteen patients died in that period (17.3%). The mean age at death was 7 years and 8 months; median survival after diagnosis was 18 years and 4 months. Patients who have at least one DeltaF508 mutation have more frequent alterations in fecal fat levels when compared to patients who do not have this mutation (p < 0.05). There were no differences in any parameter between DeltaF508 homozygous and heterozygous patients. CONCLUSIONS The clinical and laboratory characteristics of the 104 patients studied were similar to the characteristics described for patients in other countries. Exceptions are the higher age at diagnosis and lower survival. Our results support the recommendation for early diagnosis and the need for more treatment opportunities in the population of cystic fibrosis patients.OBJECTIVE: To identify the clinical, laboratory and radiographic characteristics of the cystic fibrosis patients under care at Universidade Estadual de Campinas (UNICAMP) in the last decade of the twentieth century, and to investigate the association of these characteristics with genotype and severity of the disease as measured by the Shwachman score. METHODS: Descriptive, retrospective and cross-sectional study of the patients assisted at UNICAMP hospitals Cystic Fibrosis Clinic from July 1990 to July 2000. RESULTS: One hundred and four patients were studied; 53.8% male; 93.3% Caucasian; 89.4% presented with respiratory symptoms; 59.6% presented with digestive symptoms; 5.8% had meconium ileus ; 4.8% had diabetes. The mean age at onset of symptoms was 3 months, and the mean age at diagnosis was 2 years and 4 months. At diagnosis, 69.9 and 56.6% of the patients had weight and height below 10th percentile, respectively; in 10.6%, sweat chloride was < 60 mEq/l. Staphylococcus aureus was found in 80.2%, Pseudomonas aeruginosa in 76.0%, and Burkholderia cepacia in 5.2%. DF508 homozygosis was observed in 18.75%, whereas 62.50% of the patients were DF508 heterozygous. A moderate/severe Shwachman score was found in 15.7%. Eighteen patients died in that period (17.3%). The mean age at death was 7 years and 8 months; median survival after diagnosis was 18 years and 4 months. Patients who have at least one DF508 mutation have more frequent alterations in fecal fat levels when compared to patients who do not have this mutation (p < 0.05). There were no differences in any parameter between DF508 homozygous and heterozygous patients. CONCLUSIONS: The clinical and laboratory characteristics of the 104 patients studied were similar to the characteristics described for patients in other countries. Exceptions are the higher age at diagnosis and lower survival. Our results support the recommendation for early diagnosis and the need for more treatment opportunities in the population of cystic fibrosis patients.

Recommendations for Long-term Home Oxygen Therapy in Children and Adolescents☆

OBJECTIVE To advise pediatricians, neonatologists, pulmonologists, pediatric pulmonologists, and other professionals in the area on the main indications and characteristics of long-term home oxygen therapy in children and adolescents. DATA SOURCE A literature search was carried out in the MEDLINE/PubMed database (1990 to 2011). Additionally, references from selected studies were included. As consistent scientific evidence does not exist for many aspects, some of the recommendations were based on clinical experience. DATA SYNTHESIS Long-term home oxygen therapy has been a growing practice in pediatric patients and is indicated in bronchopulmonary dysplasia, cystic fibrosis, bronchiolitis obliterans, interstitial lung diseases, and pulmonary hypertension, among others. The benefits are: decrease in hospitalizations, optimization of physical growth and neurological development, improvement of exercise tolerance and quality of sleep, and prevention of pulmonary hypertension/cor pulmonale. The levels of oxygen saturation indicative for oxygen therapy differ from those established for adults with chronic obstructive pulmonary disease, and vary according to age and disease. Pulse oximetry is used to evaluate oxygen saturation; arterial blood gas is unnecessary. There are three available sources of oxygen: gas cylinders, liquid oxygen, and oxygen concentrators. The flows used are usually smaller, as are the number of hours/day needed when compared to the use in adults. Some diseases show improvement and oxygen therapy discontinuation is possible. CONCLUSIONS Long-term home oxygen therapy is increasingly common in pediatrics and has many indications. There are relevant particularities when compared to its use in adults, regarding indications, directions for use, and monitoring.

Associação entre deficiência de alfa-1-antitripsina e a gravidade da fibrose cística

OBJETIVO: Verificar a distribuicao dos genotipos da alfa-1-antitripsina e correlacionar com a gravidade da doenca pulmonar em pacientes fibrocisticos. METODO: Estudo clinico-laboratorial de corte transversal, com 70 pacientes fibrocisticos do Hospital Universitario da UNICAMP. Os fibrocisticos tiveram diagnostico confirmado clinica e laboratorialmente. A gravidade da fibrose cistica foi avaliada pelo escore de Shwachman. Todos os pacientes foram analisados para os alelos S e Z de alfa-1-antitripsina usando a reacao em cadeia da polimerase. RESULTADOS: Nove pacientes (12,8%) foram heterozigotos para os alelos S ou Z ou heterozigoto composto (SZ). Nenhuma diferenca significativa foi encontrada na gravidade clinica da fibrose cistica entre os genotipos da alfa-1-antitripsina. Nenhuma diferenca com significância estatistica foi encontrada quando os pacientes foram separados pela presenca ou ausencia da mutacao DF508. CONCLUSAO: Neste estudo, o primeiro realizado no Brasil sobre a associacao entre deficiencia de alfa-1-antitripsina e fibrose cistica, nao encontramos uma associacao entre essa deficiencia e a gravidade da fibrose cistica.

Association between alpha 1 antitrypsin deficiency and cystic fibrosis severity

OBJECTIVE To ascertain the distribution of alpha 1 antitrypsin genotypes and correlate it with the severity of pulmonary disease in patients with cystic fibrosis. METHOD A clinical and laboratory cross sectional study of 70 patients at the Universidade Estadual de Campinas teaching hospital. Cystic fibrosis diagnoses was confirmed by both clinical and laboratory methods. The severity of cystic fibrosis was evaluated by Shwachman score. All the patients were tested for the presence of S and Z alleles for alpha 1 antitrypsin deficiency using polymerase chain reaction. RESULTS Nine (12.8%) patients were heterozygous for S or Z alleles or the heterozygote compound (SZ). No significant differences were found in clinical severity of Cystic fibrosis between genotypes of alpha 1 antitrypsin. No significant differences were found when the patients were divided according to the presence or absence of the DeltaF508 mutation. CONCLUSION In this study, the first undertaken in Brazil into the association of alpha 1 antitrypsin deficiency and cystic fibrosis, we did not find an association between the deficiency and cystic fibrosis severity.

Respiratory syncytial virus in Brazilian infants – Ten years, two cohorts

Abstract Background Each year, a considerable amount of children will experience at least one episode of acute viral bronchiolitis (AVB) during their first year of life. About 10% of them will be hospitalized, with significant physical and economic burdens. Objectives To compare two cohorts of infants with AVB, from same region, in a ten-year interval, regarding epidemiologic factors and viral etiology. Study design Cohorts: 142 (2004) and 172 (2014) infants at ages zero to 12 months; clinical diagnosis of AVB; medical care in hospital and genetic screening of nasopharyngeal secretion for respiratory viruses. Results The comparative analysis showed a difference in the percentage of respiratory syncytial virus (RSV) positive patients [2004 (33.1%); 2014 (70.3%)] (p<0.01). No differences were noted regarding gender, breastfeeding, tobacco exposure, crowding and maternal education. There was a difference as to the month of incidence (seasonality) of AVB (higher in April 2014). There was a higher age at attendance in the first cohort, and lower birth weight and gestational age ratios in the second cohort (p<0.05). There were no differences in hospitalization time, need of mechanical ventilation and number of deaths, however a difference regarding co-morbidities was noted (higher in 2004) (p<0.001). Conclusion None of the analyzed variables had an impact on severity features. Virology and immunology must be considered in this kind of situation, by studying genetic variants and the maturation of the immune system in AVB by RSV or other viruses.

Association between single nucleotide polymorphisms in TLR4, TLR2, TLR9, VDR, NOS2 and CCL5 genes with acute viral bronchiolitis

Abstract Background Acute viral bronchiolitis is the leading cause of hospitalization among infants during the first year of life. Most infants hospitalized for bronchiolitis do not present risk factors and are otherwise healthy. Our objective was to determine the genetic features associated with the risk and a severe course of bronchiolitis. Methods We prospectively evaluated 181 infants with severe bronchiolitis admitted at three hospitals over a 2-year period, who required oxygen therapy. The control group consisted of 536 healthy adults. Patients were evaluated for the presence of comorbidities (premature birth, chronic respiratory disease, and congenital heart disease), underwent nasopharyngeal aspirate testing for virus detection by multiplex-PCR, and SNPs identification in immune response genes. Patient outcomes were assessed. Results We observed association between SNP rs2107538*CCL5 and bronchiolitis caused by respiratory syncytial virus(RSV) and RSV-subtype-A, and between rs1060826*NOS2 and bronchiolitis caused by rhinovirus. SNPs rs4986790*TLR4, rs1898830*TLR2, and rs2228570*VDR were associated with progression to death. SNP rs7656411*TLR2 was associated with length of oxygen use; SNPs rs352162*TLR9, rs187084*TLR9, and rs2280788*CCL5 were associated with requirement for intensive care unit admission; while SNPs rs1927911*TLR4, rs352162*TLR9, and rs2107538*CCL5 were associated with the need for mechanical ventilation. Conclusions Our findings provide some evidence that SNPs in CCL5 and NOS2 are associated with presence of bronchiolitis and SNPs in TLR4, TLR2, TLR9, VDR and CCL5 are associated with severity of bronchiolitis.