Spacers and Valved Holding Chambers-The Risk of Switching to Different Chambers.

Spacers are pressurized metered-dose inhaler (pMDI) accessory devices developed to reduce problems of poor inhaler technique with pMDIs. Spacers that feature a 1-way inspiratory valve are termed valved holding chambers (VHCs); they act as aerosol reservoirs, allowing the user to actuate the pMDI device and then inhale the medication in a 2-step process that helps users overcome challenges in coordinating pMDI actuation with inhalation. Both spacers and VHCs have been shown to increase fine particle delivery to the lungs, decrease oropharyngeal deposition, and reduce corticosteroid-related side effects such as throat irritation, dysphonia, and oral candidiasis commonly seen with the use of pMDIs alone. Spacers and VHCs are not all the same, and also are not interchangeable: the performance may vary according to their size, shape, material of manufacture and propensity to become electrostatically charged, their mode of interface with the patient, and the presence or otherwise of valves and feedback devices. Thus, pairing of a pMDI plus a spacer or a VHC should be considered as a unique delivery system. In this Rostrum we discuss the risk potential for a patient getting switched to a spacer or VHC that delivers a reduced dose medication.

New insights into the immunoproteome of B. cenocepacia J2315 using serum samples from cystic fibrosis patients.

Bacteria of the Burkholderia cepacia complex (Bcc) are ubiquitous multidrug resistant organisms and opportunistic pathogens capable of causing life threatening lung infections among cystic fibrosis (CF) patients. No effective therapies are currently available to eradicate Bcc bacteria from CF patients, as these organisms are inherently resistant to the majority of clinically available antimicrobials. An immunoproteomics approach was used to identify Bcc proteins that stimulate the humoral immune response of the CF host, using bacterial cells grown under conditions mimicking the CF lung environment and serum samples from CF patients with a clinical record of Bcc infection. 24 proteins of the Bcc strain B. cenocepacia J2315 were identified as immunoreactive, 19 here reported as immunogenic for the first time. Ten proteins were predicted as extracytoplasmic, 9 of them being conserved in Bcc genomes. The immunogenic Bcc extracytoplasmic proteins are potential targets for development of novel therapeutic strategies and diagnostic tools to protect patients against the onset of chronic Bcc lung infections.

Assessing gastro-intestinal related quality of life in cystic fibrosis: Validation of PedsQL GI in children and their parents.

BACKGROUND: Most patients with cystic fibrosis (CF) suffer from pancreatic insufficiency, leading to fat malabsorption, malnutrition and abdominal discomfort. Until recently, no specific tool was available for assessing gastro-intestinal related quality of life (GI QOL) in patients with CF. As the Horizon2020 project MyCyFAPP aims to improve GI QOL by using a newly designed mobile application, a sensitive and reliable outcome measure was needed. We aimed to study the applicability of the existing child-specific Pediatric Quality of Life Inventory, Gastrointestinal Symptoms Scales and Module (PedsQL GI) in children with CF. METHODS: A multicenter, prospective observational study was performed in 6 European centers to validate the PedsQL GI in children with CF during 3 months. RESULTS: In total, 248 children and their parents were included. Within-patient variability of PedsQL GI was low (24.11), and there was reasonable agreement between children and parents (ICC 0.681). Nine of 14 subscales were informative (no ceiling effect). The PedsQL GI and the median scores for 4 subscales were significantly lower in patients compared to healthy controls. Positive associations were found between PedsQL GI and age (OR = 1.044, p = 0.004) and between PedsQL GI and BMI z-score (OR = 1.127, p = 0.036). PedsQL GI correlated with most CFQ-R subscales (r 0.268 to 0.623) and with a Visual Analogue Scale (r = 0.20). CONCLUSIONS: PedsQL GI is a valid and applicable instrument to assess GI QOL in children with CF. Future research efforts should examine the responsiveness of the CF PedsQL GI to change in the context of clinical interventions and trials.

The effect of premature termination codon mutations on CFTR mRNA abundance in human nasal epithelium and intestinal organoids: a basis for read-through therapies in cystic fibrosis.

A major challenge in cystic fibrosis (CF) research is applying mutation-specific therapy to individual patients with diverse and rare CF transmembrane conductance regulator (CFTR) genotypes. Read-through agents are currently the most promising approach for Class I mutations that introduce premature termination codons (PTCs) into CFTR mRNA. However, variations in degradation of PTC containing transcripts by nonsense mediated decay (NMD) might lower read-through efficacy. Allele specific quantitative real time (qRT)-PCR was used to measure variations in CFTR mRNA abundance for several PTC mutations in respiratory cells and intestinal organoids. The majority of PTC mutations were associated with reduced levels of relative mRNA transcript abundance (∼33% and 26% of total CFTR mRNA in respiratory cells and intestinal organoids, respectively, compared to >50% for non-PTC causing mutations). These levels were generally not affected by PTC mutation type or position, but there could be twofold variations between individuals bearing the same genotype. Most PTC mutations in CFTR are subject to similar levels of NMD, which reduce but do not abolish PTC bearing mRNAs. Measurement of individual NMD levels in intestinal organoids and HNE cells might, therefore, be useful in predicting efficacy of PTC read-through in the context of personalized CFTR modulator therapy.

Cystic Fibrosis Newborn Screening in Portugal: PAP Value in Populations with Stringent Rules for Genetic Studies.

Newborn screening (NBS) for cystic fibrosis (CF) has been shown to be advantageous for children with CF, and has thus been included in most NBS programs using various algorithms. With this study, we intend to establish the most appropriate algorithm for CF-NBS in the Portuguese population, to determine the incidence, and to contribute to elucidating the genetic epidemiology of CF in Portugal. This was a nationwide three-year pilot study including 255,000 newborns (NB) that were also screened for congenital hypothyroidism (CH) and 24 other metabolic disorders included in the Portuguese screening program. Most samples were collected in local health centers spread all over the country, between the 3rd and 6th days of life. The algorithm tested includes immunoreactive trypsinogen (IRT) determination, pancreatitis associated protein (PAP) as a second tier, and genetic study for cases referred to specialized clinical centers. Thirty-four CF cases were confirmed positive, thus indicating an incidence of 1:7500 NB. The p.F508del mutation was found in 79% of the alleles. According to the results presented here, CF-NBS is recommended to be included in the Portuguese NBS panel with a small adjustment regarding the PAP cut-off, which we expect to contribute to the improvement of the CF-NBS performance. According to our results, this algorithm is a valuable alternative for CF-NBS in populations with stringent rules for genetic studies.

Nutritional status, nutrient intake and use of enzyme supplements in paediatric patients with Cystic Fibrosis; a European multicentre study with reference to current guidelines.

BACKGROUND: The New European guidelines have established the most updated recommendations on nutrition and pancreatic enzyme replacement therapy (PERT) in CF. In the context of MyCyFAPP project - a European study in children with CF aimed at developing specific tools for improvement of self-management - the objective of the current study was to assess nutritional status, daily energy and macronutrient intake, and PERT dosing with reference to these new guidelines. METHODS: Cross sectional study in paediatric patients with CF from 6 European centres. SD-scores for weight-for-age (WFA), height-for-age (HFA) and body mass index-for-age (BMI) were obtained. Through a specific 4-day food and enzyme-dose record, energy and macronutrients intake and PERT-use (LU/g lipids) were automatically calculated by the MyCyFAPP system. Comparisons were made using linear regression models. RESULTS: The lowest quartiles for BMI and HFA were between 0 and -1SD in all the centres with no significant differences, and 33.5% of the patients had a SD-score <0 for all three parameters. The minimum energy intake recommendation was not reached by 40% of the children and mean nutrients intake values were 14%, 51% and 34% of the total energy for protein, carbohydrates and lipids respectively. When assessed per centre, reported PERT doses were in the recommended range in only 13.8% to 46.6% of the patients; from 5.6% up to 82.7% of children were above the recommended doses and 3.3% to 75% were below. CONCLUSION: Among the 6 centres, a large variability and inconsistency with new guidelines on nutrition and PERT-use was found. Our findings document the lack of a general criterion to adjust PERT and suggest the potential benefit of educational and self-managerial tools to ensure adherence to therapies, both for clinical staff and families. They will be taken into account when developing these new tools during the next stages of MyCyFAPP Project.

Innovative approach for self-management and social welfare of children with cystic fibrosis in Europe: development, validation and implementation of an mHealth tool (MyCyFAPP).

INTRODUCTION: For the optimal management of children with cystic fibrosis, there are currently no efficient tools for the precise adjustment of pancreatic enzyme replacement therapy, either for advice on appropriate dietary intake or for achieving an optimal nutrition status. Therefore, we aim to develop a mobile application that ensures a successful nutritional therapy in children with cystic fibrosis. METHODS AND ANALYSIS: A multidisciplinary team of 12 partners coordinate their efforts in 9 work packages that cover the entire so-called 'from laboratory to market' approach by means of an original and innovative co-design process. A cohort of 200 patients with cystic fibrosis aged 1-17 years are enrolled. We will develop an innovative, clinically tested mobile health application for patients and health professionals involved in cystic fibrosis management. The mobile application integrates the research knowledge and innovative tools for maximising self-management with the aim of leading to a better nutritional status, quality of life and disease prognosis. Bringing together different and complementary areas of knowledge is fundamental for tackling complex challenges in disease treatment, such as optimal nutrition and pancreatic enzyme replacement therapy in cystic fibrosis. Patients are expected to benefit the most from the outcomes of this innovative project. ETHICS AND DISSEMINATION: The project is approved by the Ethics Committee of the coordinating organisation, Hospital Universitari La Fe (Ref: 2014/0484). Scientific findings will be disseminated via journals and conferences addressed to clinicians, food scientists, information and communications technology experts and patients. The specific dissemination working group within the project will address the wide audience communication through the website (http://www.mycyfapp.eu), the social networks and the newsletter.

The Burkholderia cenocepacia OmpA-like protein BCAL2958: identification, characterization, and detection of anti-BCAL2958 antibodies in serum from B. cepacia complex-infected Cystic Fibrosis patients.

Respiratory infections by bacteria of the Burkholderia cepacia complex (Bcc) remain an important cause of morbidity and mortality among cystic fibrosis patients, highlighting the need for novel therapeutic strategies. In the present work we have studied the B. cenocepacia protein BCAL2958, a member of the OmpA-like family of proteins, demonstrated as highly immunogenic in other pathogens and capable of eliciting strong host immune responses. The encoding gene was cloned and the protein, produced as a 6× His-tagged derivative, was used to produce polyclonal antibodies. Bioinformatics analyses led to the identification of sequences encoding proteins with a similarity higher than 96 % to BCAL2958 in all the publicly available Bcc genomes. Furthermore, using the antibody it was experimentally demonstrated that this protein is produced by all the 12 analyzed strains from 7 Bcc species. In addition, results are also presented showing the presence of anti-BCAL2958 antibodies in sera from cystic fibrosis patients with a clinical record of respiratory infection by Bcc, and the ability of the purified protein to in vitro stimulate neutrophils. The widespread production of the protein by Bcc members, together with its ability to stimulate the immune system and the detection of circulating antibodies in patients with a documented record of Bcc infection strongly suggest that the protein is a potential candidate for usage in preventive therapies of infections by Bcc.

Comparative ex vivo, in vitro and in silico analyses of a CFTR splicing mutation: Importance of functional studies to establish disease liability of mutations.

The Cystic Fibrosis p.Ile1234Val missense mutation actually creates a new dual splicing site possibly used either as a new acceptor or donor. Here, we aimed to test the accuracy of in silico predictions by comparing them with in vitro and ex vivo functional analyses of this mutation for an accurate CF diagnosis/prognosis. To this end, we applied a new in vitro strategy using a CFTR mini-gene which includes the complete CFTR coding sequence plus intron 22 (short version) which allows the assessment of alternatively spliced mRNA levels as well as the properties of the resulting abnormal CFTR protein regarding processing, intracellular localization and function. Our data demonstrate that p.Ile1234Val leads to usage of the alternative splicing donor (but not acceptor) resulting in alternative CFTR transcripts lacking 18 nts of exon 22 which produce a truncated CFTR protein with residual Cl- channel function. These results recapitulate data from native tissues of a CF patient. In conclusion, the existing in silico prediction models have limited application and ex vivo functional assessment of mutation effects should be made. Alternatively the in vitro strategy adopted here can be applied to assess the disease liability of mutations for an accurate CF diagnosis/prognosis.

Incidence of Burkholderia contaminans at a cystic fibrosis centre with an unusually high representation of Burkholderia cepacia during 15 years of epidemiological surveillance.

The Burkholderia cepacia complex (Bcc) is a heterogeneous group of bacteria comprising around 20 related species. These bacteria are important opportunistic pathogens, especially in cystic fibrosis (CF) patients, and are associated with a worse prognosis and decreased life expectancy. The taxonomic position of 20 Bcc isolates retrieved from CF patients receiving care at Hospital Santa Maria (HSM), in Lisbon, from 1995 to 2006, was re-examined in the present work. These isolates, formerly classified as Burkholderia cepacia (taxon K), are here reclassified as Burkholderia contaminans, including the former B. cepacia IST408, which was the focus of previous studies regarding the biosynthesis of the exopolysaccharide 'cepacian'. The CF population examined has been previously described as having an exceptionally high representation of B. cepacia, presumably due to a contamination arising from saline solutions for nasal application. Twenty-one additional isolates, obtained from a chronically infected patient, from 2006 to 2010, were also identified as B. contaminans. This study also provides insight into the potential clinical impact of B. contaminans, a species that is rarely associated with CF infections. Isolates belonging to this species were shown to be involved in chronic and transient respiratory infections, and were associated with severe lung function deterioration and with a case of death with cepacia syndrome. However, since the patients were co-infected with Burkholderia cenocepacia and other non-Burkholderia bacteria, the role played by B. contaminans is unclear. Nevertheless, B. contaminans isolates were found to prevail over B. cenocepacia isolates during co-infection of at least one chronically infected patient.

Changes in transcriptome of native nasal epithelium expressing F508del-CFTR and intersecting data from comparable studies.

BACKGROUND: Microarray studies related to cystic fibrosis (CF) airway gene expression have gone some way in clarifying the complex molecular background of CF lung diseases, but have made little progress in defining a robust "molecular signature" associated with mutant CFTR expression. Disparate methodological and statistical analyses complicate comparisons between independent studies of the CF transcriptome, and although each study may be valid in isolation, the conclusions reached differ widely. METHODS: We carried out a small-scale whole genome microarray study of gene expression in human native nasal epithelial cells from F508del-CFTR homozygotes in comparison to non-CF controls. We performed superficial comparisons with other microarray datasets in an attempt to identify a subset of regulated genes that could act as a signature of F508del-CFTR expression in native airway tissue samples. RESULTS: Among the alterations detected in CF, up-regulation of genes involved in cell proliferation, and down-regulation of cilia genes were the most notable. Other changes involved gene expression changes in calcium and membrane pathways, inflammation, defence response, wound healing and the involvement of estrogen signalling. Comparison of our data set with previously published studies allowed us to assess the consistency of independent microarray data sets, and shed light on the limitations of such snapshot studies in measuring a system as subtle and dynamic as the transcriptome. Comparison of in-vivo studies nevertheless yielded a small molecular CF signature worthy of future investigation. CONCLUSIONS: Despite the variability among the independent studies, the current CF transcriptome meta-analysis identified subsets of differentially expressed genes in native airway tissues which provide both interesting clues to CF pathogenesis and a possible CF biomarker.

HGF stimulation of Rac1 signaling enhances pharmacological correction of the most prevalent cystic fibrosis mutant F508del-CFTR.

Cystic fibrosis (CF), a major life-limiting genetic disease leading to severe respiratory symptoms, is caused by mutations in CF transmembrane conductance regulator (CFTR), a chloride (Cl(-)) channel expressed at the apical membrane of epithelial cells. Absence of functional CFTR from the surface of respiratory cells reduces mucociliary clearance, promoting airways obstruction, chronic infection, and ultimately lung failure. The most frequent mutation, F508del, causes the channel to misfold, triggering its premature degradation and preventing it from reaching the cell surface. Recently, novel small-molecule correctors rescuing plasma membrane localization of F508del-CFTR underwent clinical trials but with limited success. Plausibly, this may be due to the mutant intrinsic plasma membrane (PM) instability. Herein, we show that restoration of F508del-CFTR PM localization by correctors can be dramatically improved through a novel pathway involving stimulation of signaling by the endogenous small GTPase Rac1 via hepatocyte growth factor (HGF). We first show that CFTR anchors to apical actin cytoskeleton (via Ezrin) upon activation of Rac1 signaling through PIP5K and Arp2/3. We then found that such anchoring retains pharmacologically rescued F508del-CFTR at the cell surface, boosting functional restoration by correctors up to 30% of wild-type channel levels in human airway epithelial cells. Our findings reveal that surface anchoring and retention is a major target pathway for CF pharmacotherapy, namely, to achieve maximal restoration of F508del-CFTR in patients in combination with correctors. Moreover, this approach may also translate to other disorders caused by trafficking-deficient surface proteins.

Reference percentiles for FEV(1) and BMI in European children and adults with cystic fibrosis.

BACKGROUND: The clinical course of Cystic Fibrosis (CF) is usually measured using the percent predicted FEV(1) and BMI Z-score referenced against a healthy population, since achieving normality is the ultimate goal of CF care. Referencing against age and sex matched CF peers may provide valuable information for patients and for comparison between CF centers or populations. Here, we used a large database of European CF patients to compute CF specific reference equations for FEV(1) and BMI, derived CF-specific percentile charts and compared these European data to their nearest international equivalents. METHODS: 34859 FEV(1) and 40947 BMI observations were used to compute European CF specific percentiles. Quantile regression was applied to raw measurements as a function of sex, age and height. Results were compared with the North American equivalent for FEV(1) and with the WHO 2007 normative values for BMI. RESULTS: FEV(1) and BMI percentiles illustrated the large variability between CF patients receiving the best current care. The European CF specific percentiles for FEV(1) were significantly different from those in the USA from an earlier era, with higher lung function in Europe. The CF specific percentiles for BMI declined relative to the WHO standard in older children. Lung function and BMI were similar in the two largest contributing European Countries (France and Germany). CONCLUSION: The CF specific percentile approach applied to FEV(1) and BMI allows referencing patients with respect to their peers. These data allow peer to peer and population comparisons in CF patients.

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.

The impact of methicillin-resistant Staphylococcus aureus colonisation on paediatric cystic fibrosis patients' morbidity.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) plays a well-recognised pathogenic role in cystic fibrosis (CF). AIMS: To evaluate the prevalence and incidence of colonisation by MRSA, clinical impact of MRSA colonisation (year after first MRSA isolation), risk factors and pattern of antimicrobial resistance. METHODS: Retrospective review of paediatric CF patients colonised with MRSA followed-up at the CF Unit of Hospital de Santa Maria 2003-2007. RESULTS: Twelve of the 60 patients followed-up during this period were MRSA-positive at some time (chronic colonisation in 3 patients). Mean age at acquisition was 9 years 10 months and mean time interval between CF diagnosis and MRSA acquisition 5 years 7 months. An important rise in MRSA colonisation prevalence and incidence was observed, with the highest rate seen in 2007 (prevalence 14.3% and incidence 8.9%). Four patients had received anti-staphylococcal prophylaxis with flucloxacillin. An increase in the total number of in-patient days was observed in four patients (two with chronic colonisation). Deterioration in lung function was seen in five patients (including the three patients with chronic colonisation). Only one patient had a decrease in body mass index percentile. Resistance to clindamycin and rifampin was the most frequently seen. CONCLUSIONS: This study revealed significant clinical deterioration in patients with chronic colonisation by MRSA, reinforcing the importance of effective and timely decolonisation strategies.

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.

Deletion of CFTR translation start site reveals functional isoforms of the protein in CF patients.

BACKGROUND/AIMS: Mutations in the CFTR gene cause Cystic Fibrosis (CF) the most common life-threatening autosomal recessive disease affecting Caucasians. We identified a CFTR mutation (c.120del23) abolishing the normal translation initiation codon, which occurs in two Portuguese CF patients. This study aims at functionally characterizing the effect of this novel mutation. METHODS: RNA and protein techniques were applied to both native tissues from CF patients and recombinant cells expressing CFTR constructs to determine whether c.120del23 allows CFTR protein production through usage of alternative internal codons, and to characterize the putative truncated CFTR form(s). RESULTS: Our data show that two shorter forms of CFTR protein are produced when the initiation translation codon is deleted indicating usage of internal initiation codons. The N-truncated CFTR generated by this mutation has decreased stability, very low processing efficiency, and drastically reduced function. Analysis of mutants of four methionine codons downstream to M1 (M82, M150, M152, M156) revealed that each of the codons M150/M152/M156 (exon 4) can mediate CFTR alternative translation. CONCLUSIONS: The CFTR N-terminus has an important role in avoiding CFTR turnover and in rendering effective its plasma membrane traffic. These data correlate well with the severe clinical phenotype of CF patients bearing the c.120del23 mutation.

[Spontaneous pneumothorax - a clue to another diagnosis]. / Pneumotórax espontâneo - A pista para outro diagnóstico.

Marfan syndrome is an autosomal dominant illness of the connective tissue, with typical skeletal, ocular and cardiovascular manifestations. Less frequently, pulmonary involvement occurs, namely spontaneous pneumothorax, which generally is recurrent and occurs in 4 -11% of cases. The authors describe a 14 -year -old boy, previously healthy, admitted with a unilateral spontaneous pneumothorax, and clinical phenotype of Marfan syndrome. The subsequent investigation led to the diagnosis of mitral valve prolapse and dilatation of the root of aorta. Pneumothorax resolved through active drainage and a computerised tomography scan excluded subpleural blebs. The patient was readmitted two months later with a new spontaneous pneumothorax, with an identical localization. Surgical resection of a newly identified enfisematous bleb and pleurodesis were performed. Two years later he is asymptomatic. We highlight the importance of an early diagnosis of and a multidisciplinary approach to these patients. Monitoring illness progression and prevention of serious complications, namely cardiovascular, are essential.

[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.