Luísa Pereira

The clinical course of Burkholderia cepacia complex bacteria respiratory infection in cystic fibrosis patients

Bacteria of the Burkholderia cepacia complex (Bcc), a group of nine related species, are opportunistic pathogens in cystic fibrosis (CF) patients, associated with a poor prognosis and patient-to-patient transmissibility. The pulmonary deterioration in Bcc-colonised/ infected patients has a heterogeneous pattern leading, sometimes, to a fulminant development - the cepacia syndrome. To evaluate the relationship between colonisation/ infection by the different Bcc species and the clinical course, the authors carried out a retrospective study of 31 CF patients with Bcc bacteria isolations followed at Hospital de Santa Maria from January 1995 to March 2006. Patients were categorised into two groups: Group I, with intermittent isolations and Group II with chronic isolations. The prevalence of Bcc species was as follows: B. cepacia 57%, B. cenocepacia 43%, B. multivorans 7%, B. stabilis 13%. Three of the patients died of cepacia syndrome. The species B. cepacia and B. stabilis, usually less frequent in CF populations of Europe and America, were isolated in a considerable percentage of the patients examined. No correlation could be established between the species and the clinical outcome. Deteriorated but not stable patients from group II, whose lung function and pulmonary exacerbation caused hospitalisation could be retrospectively analysed, exhibited significant differences in the number of hospitalisations and pulmonary function (FEV1) in the year prior to and the years following Bcc isolation. Based on the available data, it is not currently possible to outline preventive measures through the molecular characterisation of Bcc isolates, reinforcing the notion that the recommended control measures must be followed.

Non-invasive ventilation in complex obstructive sleep apnea--a 15-year experience of a pediatric tertiary center.

INTRODUCTION Obstructive sleep apnea (OSA) affects approximately 1-3% of pediatric population and is associated with significant morbidity. As adenotonsillar hypertrophy (ATH) is its primary cause in children, elective adenotonsillectomy is the first treatment of choice. Noninvasive ventilation (NIV) has been increasingly considered as an option, mainly for children with complex diseases, ineligible or waiting for surgeries, or after surgery failure. OBJECTIVES To describe the experience in the management of children with complex OSA, and to evidence the feasibility and advantages of NIV. METHODS This was a retrospective cohort study of 68 children on NIV, in whom complex OSA was the main indication for ventilation, in a Pediatric Respiratory Unit at a University Hospital between January 1997 and March 2012. Demographic and clinical data were collected on the underlying diagnosis, therapeutic interventions prior to NIV, NIV related issues and outcome. RESULTS Forty (59%) children were male, median age at starting NIV was 6 years and 7 months, with interquartile range (IQR) of 15-171 months. Twenty-two (32%) were infants and 25 (37%) adolescents. The most common diagnosis was congenital malformations and genetic disorders in 34 (50%) patients. Nine patients had cerebral palsy, 8 were post treatment for central nervous system tumors and 6 had inborn errors of metabolism. Three children had ATH and three obesity. The majority of patients (76%) had exclusively obstructive OSA and started CPAP. Ten patients had minor complications. Twenty-two patients stopped NIV due to clinical improvement, 8 were non-compliant and 8 patients died. NIV median duration was 21.5 months (IQR: 7-72). CONCLUSIONS NIV is feasible and well tolerated by children with OSA associated with complex disorders, and has been shown to have few complications even in infants and toddlers.

Are there any differences in the community acquired pneumonias admitted to hospital over the past decade

The past few years have seen a decline in community acquired pneumonia (CAP) in children in the western world, although this has gone hand-in-hand with more serious cases needing hospital admission. Our study characterises cases of CAP admitted to hospital and compares this data with a 2001 study. We collected data on 63 admissions over a six-month period. The majority were aged 0-2 years old. Chest X-ray showed consolidation/atelectasy in 58 (92.1%) and pleural effusion (PE) in 17 (27.0%), of which 11 were empyema (17.4% of all admissions). The bacterial agent was isolated in five cases: Streptococcus pyogenes (two, pleural fluid), Streptococcus pneumoniae (two, blood culture) and Haemophilus influenzae (one, blood culture). Sixty-one children (96.8%) were prescribed antibiotherapy. The median length of hospital stay was five days. Patients with PE were older, had a longer course of fever, higher inflammatory parameters, longer hospital stay and longer course of iv antibiotics. Compared to the prior study we found greater severity of CAP, with higher prevalence of PE and empyema. Nevertheless there was a shorter course of fever during hospital stay and shorter hospital stay. We also noticed less antibiotic prescription prior to admission and greater prescription of ampicillin during hospital stay. In the literature, the higher severity of CAP has been partially attributed to the emergence of more aggressive serotypes of Stretococcus pneumoniae not included in the heptavalent vaccine. There is therefore a greater interest in new vaccines containing them. Complicated CAP should be referred to centres specialising in its diagnosis and management.

Infecção respiratória por bactérias do complexo Burkholderia cepacia: Evolução clínica em doentes com fibrose quística

Bacteria of the Burkholderia cepacia complex (Bcc), a group of nine related species, are opportunistic pathogens in cystic fibrosis (CF) patients, associated with a poor prognosis and patient-to-patient transmissibility. The pulmonary deterioration in Bcc-colonised/ infected patients has a heterogeneous pattern leading, sometimes, to a fulminant development – the cepacia syndrome. To evaluate the relationship between colonisation/ infection by the different Bcc species and the clinical course, the authors carried out a retrospective study of 31 CF patients with Bcc bacteria isolations followed at Hospital de Santa Maria from January 1995 to March 2006. Patients were categorised into two groups: Group I, with intermittent isolations and Group II with chronic isolations. The prevalence of Bcc species was as follows: B. cepacia 57%, B. cenocepacia 43%, B. multivorans 7%, B. stabilis 13%. Three of the patients died of cepacia syndrome. The species B. cepacia and B. stabilis, usually less frequent in CF populations of Europe and America, were isolated in a considerable percentage of the patients examined. No correlation could be established between the species and the clinical outcome. Deteriorated but not stable patients from group II, whose lung function and pulmonary exacerbationcaused hospitalisation could be retrospectively analysed, exhibited significant differences in the number of hospitalisations and pulmonary function (FEV1) in the year prior to and the years following Bcc isolation. Based on the available data, it is not currently possible to outline preventive measures through the molecular characterisation of Bcc isolates, reinforcing the notion that the recommended control measures must be followed. Rev Port Pneumol 2008; XIV (1): 5-26

Cystic fibrosis-related liver disease: a single-center experience

Prospective studies concerning liver disease in pediatric cystic fibrosis patients are scarce. The present study aimed to describe the prevalence and clinical expression of cystic fibrosis - related liver disease, in a cohort of 62 pediatric patients. Descriptive study, resulting from the prospective evaluation, between 1994 and 2009, of 62 pediatric patients (age <18 years) with cystic fibrosis. The follow-up protocol included a clinical assessment every 2 months, liver function tests every 6 months and annual liver ultrasonography. The cumulative prevalence of liver disease was 11.2% (7/62 cases). All patients had ΔF508 mutation and pancreatic insufficiency, none had meconium ileus. The liver involvement became clinically evident at a mean age of 8 years (3–15 years), revealed by hepatomegaly or hepatosplenomegaly (3 cases) and/ or abnormalities of liver function tests (3 cases) changes of liver ultrasound (7 cases) with evidence of portal hypertension (2 cases). Four patients were submitted to liver biopsy; biliary fibrosis was documented in one case, focal biliary cirrhosis in 2 cases and multilobular cirrhosis in another case. Within a median 11.6 years follow-up period (all patients under UDCA therapy after liver disease diagnosis), progression of liver disease was observed in 2 patients; one patient developed refractory variceal bleeding and progressive hepatic failure, requiring liver transplant. The results of the present study agree with those of previous pediatric studies, further documenting clinical expression of liver disease in CF patients, which is usually detected in the first decade of life and emphasize the contribution of ultrasound to early diagnosis of liver involvement. Moreover, although advanced liver disease is a relatively rare event, early isolated liver transplantation may have to be considered at this age group.

Perfil epidemiológico das infecções bacterianas do aparelho respiratório em doentes com fibrose quística

RESUMO Com o intuito de caracterizar a evolucao do perfil epidemiologico das infeccoes bacterianas do aparelho respiratorio dos doentes com Fibrose Quistica (FQ), os autores realizaram um estudo retrospectivo da prevalencia e incidencia das mesmas em 78 doentes com FQ seguidos no Centro Especializado de FQ da Clinica Universitaria de Pediatria do Hospital de Santa Maria, Lisboa durante um periodo de 5 anos (1995-1999). A Pseudomonas aeruginosa foi a bacteria mais frequentemente isolada nos tres primeiros anos do estudo (60-73%), sendo ultrapassada nos dois anos seguintes pelo Staphylococcus aureus . No entanto, a Pseudomonas aeruginosa constituiu sempre o principal agente de colonizacao cronica (44-59%), com um pico de inicio da mesma entre os 0 e os 5 anos (34%). Verificou-se ao longo dos 5 anos um aumento significativo da prevalencia de colonizacao intermitente e cronica por Staphylococcus aureus (48% para 83% e 32% para 54%). A prevalencia de isolamentos de Staphylococcus aureus resistente a meticilina e de Burkholderia cepacia quase que duplicou neste periodo. As taxas de isolamento e de colonizacao cronica por Alcaligenes xylosoxidans aumentaram bruscamente a partir de 1997 (de 3% e 0% em 1996 para 7% e 5% em 1997 e 10% e 7% em 1999). A colonizacao cronica por Haemophilus influenzae manteve uma prevalencia media de 22%, apesar dum aumento dos isolamentos (de 42% para 61%). Em 55% dos doentes observou-se colonizacao cronica por dois ou mais agentes. Em funcao destes resultados sao discutidos os esquemas terapeuticos e as medidas de prevencao de contagios que tem sido preconizados nos doentes com FQ do nosso centro. REV PORT PNEUMOL 2003; IX (4): 337-352

Estarão diferentes as pneumonias agudas adquiridas na comunidade com internamento hospitalar em idade pediátrica na última década

Resumo Nos ultimos anos tem sido descrita, no mundo ocidental, uma reducao da incidencia da pneumonia aguda da comunidade (PAC) nas criancas, parodoxalmente associada a maior gravidade dos casos internados. O presente estudo pretendeu caracterizar os casos de PAC internados e compara-los com um estudo anterior a 2001. Recolhemos dados referentes a 63 internamentos, durante seis meses. Houve predominio do grupo dos 0-2 anos. Na radiografia toracica, em 58 casos (92,1%) detectou-se condensacao/atelectasia e em 17 (27,0%) derrame pleu ral (DP). Onze dos DP corresponderam a empiema (17,4% dos internamentos). Isolou-se agente bacteriano em cinco casos: Streptococcus pyogenes (dois, liquido pleural), Streptococcus pneumoniae (dois, hemocultura) e Haemophilus influenzae (um, hemocultura). Foi prescrita antibioticoterapia em 61 (96,8%) criancas. A duracao mediana de internamento foi de cinco dias. Constatou-se, nos casos de DP, idade superior, maior duracao de febre, proteina C reactiva mais alta e maior duracao de internamento e de antibioticoterapia endovenosa. Comparativamente com o estudo anterior, constatou-se haver maior gravidade dos casos internados, traduzida por maior incidencia de DP e empiema; paradoxalmente, registou-se menor duracao da febre em meio hospitalar e menor duracao do internamento. No estudo actual houve menor prescricao antibiotica previa a admissao e maior prescricao de ampicilina durante o internamento. Na literatura, a maior gravidade das pneumonias internadas nos ultimos anos tem sido associada a emergencia de serotipos mais agressivos de Stretococcus pneumoniae nao integrados na vacina heptavalente, assumindo interesse crescente a introducao de vacinas que os incluam. As pneumonias complicadas devem ser orientadas para centros de referencia com experiencia no seu diagnostico e tratamento. Rev Port Pneumol 2010; XVI (2): 287-305

Complicated pleural effusion in children – Therapeutical approach

Pediatric management of complicated pleural effusion (CPE) remains controversial. Different approaches include antibiotics and chest tube drainage alone or the use of fibrinolitics, videothorascoscopy (VTC) and surgical decortication through thoracotomy. The aim of the present study was to review, evaluate and update technical approach to CPE. We retrospectively reviewed the clinical files of children admitted to the Pediatric Respiratory Ward between 1992 and 2003 with the diagnosis of CPE. Twenty-five patients were included [15 male (60%)]. Mean (+/-SD) age was 37,4 (+/-37,0) months. Bacteria were identified in 17/25 (68%) [S. aureus in 6/17 (35%), St. pneumoniae in 5/17 (29%)], 16/17 (94%)in the pleural fluid. Twenty-five children were treated with antibiotics and thoracocentesis (100%). Chest tube drainage was required in 22/25 (88%) with mean (+/-DP) duration of 14,2 (+/-7,8) days. Fibrinolitics were employed in 1 only case and surgical decortication in 11/25 (44%). One patient (4%) was submitted to primary VTC. Median length of stay was 30,4 (+/-15,1) days and no deaths were recorded. Center skills in CPE management are critical on the choice of the technique and the timing of approach. This seems to influence immediate prognosis.

Respiratory sleep disturbance in children and adolescents with cystic fibrosis.

UNLABELLED Sleep disturbance has been described in cystic fibrosis (CF) patients as relevant to clinical and lung function predictive factors helping to improve the diagnosis and early intervention. Related paediatric studies are scarce. OBJECTIVE To describe respiratory sleep disturbance (RSD) and its association with spirometric indices in a population of CF children. A second aim was to determine if spirometric indices and wake-time SpO2 are predictors of sleep disturbance. METHODS A cross-sectional study involving 33CF paediatric patients. All participants underwent in-lab polysomnography (PSG), pulse oximetry and spirometry. A standardized sleep questionnaire was completed for each patient. Two subgroups were considered: I - Normal (FEV1>-1.64 z-score); II - Obstructed (FEV1≤-1.64 z-score). RESULTS Participants median age was 12 (6-18) years, 16 (48.5%) were male. Twenty-nine patients (87.9%) presented sleep complaints. Sleep efficiency was reduced; sleep latency and waking after sleep onset (WASO) increased. N1 increased, N2, N3, REM and awakenings were normal. The apnoea-hypopnoea index was 0.6/h (sd 0.9); respiratory disturbance index (RDI) was 6.6/h (sd 5.2). Mean awaking (97% (sd 1.1)) and sleep SpO2 (95% (sd 2.7)) were normal; mean nocturnal oximetry desaturation index was 2.36/h; minimal nocturnal SpO2 was 89% (sd 4.1). We found associations between mean nocturnal SPO2 and mean values of FEV1 (r=0.528; p=0.002) and FEF25-75 (r=0.426; p=0.013). There were significant differences in nocturnal SpO2 between normal and obstructed patients (p<0.000). PSG data correlated with the questionnaire answers for night awakenings and WASO (p=0.985) and difficult breathing during sleep and RDI (p=0.722). This study points to most CF children having sleep complaints, and highlights the correlation between subjective assessment of sleep and PSG and spirometric results. Awake-time SpO2 and spirometric values are possible risk predictors for nocturnal desaturation.

Colonização por Staphylococcus aureus resistente à meticilina: Que impacto na morbilidade de doentes pediátricos com fibrose quística?

Resumo Introducao: Ao Staphylococcus aureus resistente a meticilina (MRSA) e classicamente reconhecido um papel patogenico no âmbito da fibrose quistica (FQ). Objectivos: Avaliacao da evolucao da prevalencia e incidencia da colonizacao por MRSA, impacto clinico no ano apos o primeiro isolamento, factores de risco e padrao de resistencia antimicrobiana. Metodos: Estudo retrospectivo dos doentes pediatricos colonizados por MRSA seguidos no centro de FQ do Hospital de Santa Maria de 2003 a 2007. Resultados: O MRSA foi isolado em secrecoes respiratorias de 12 dos 60 doentes seguidos durante este periodo (colonizacao cronica em 3 doentes). A idade media a data do primeiro isolamento foi de 9 anos e 10 meses e o tempo medio entre o diagnostico de FQ e a aquisicao de MRSA de 5 anos e 7 meses. Verificou-se um aumento da prevalencia e incidencia de colonizacao por MRSA, com um maximo atingido em 2007 (prevalencia 14,3% e incidencia 8,9%). Quatro doentes cumpriram antibioticoterapia profilactica antiestafilococica com flucloxacilina. No ano apos o primeiro isolamento de MRSA, constatou-se um aumento do numero de dias de internamento em 4 doentes (2 com colonizacao cronica) e deterioracao da funcao pulmonar em 5, incluindo a totalidade dos doentes com colonizacao cronica. Apenas um doente apresentou diminuicao de percentil de indice de massa corporal. As resistencias mais frequentemente encontradas foram a rifampicina e a clindamicina. Conclusoes: Este estudo revelou ocorrencia de deterioracao clinica relevante em doentes com colonizacao cronica por MRSA, reforcando a importância da implementacao de estrategias eficazes e precoces de erradicacao. Rev Port Pneumol 2010; XVI (4): 527-542