Cystic fibrosis with normal sweat chloride concentration: case report

Cystic fibrosis is a genetic disease usually diagnosed by abnormal sweat testing. We report a case of an 18-year-old female with bronchiectasis, chronic P. aeruginosa infection, and normal sweat chloride concentrations who experienced rapid decrease of lung function and clinical deterioration despite treatment. Given the high suspicion ofcystic fibrosis, broad genotyping testing was performed, showing a compound heterozygous with deltaF508 and 3849+10kb C->T mutations, therefore confirming cystic fibrosis diagnosis. Although the sweat chloride test remains the gold standard for the diagnosis of cystic fibrosis, alternative diagnostic tests such as genotyping and electrophysiologic measurements must be performed if there is suspicion of cystic fibrosis, despite normal or borderline sweat chloride levels.

The cystic fibrosis microbiome in an ecological perspective and its impact in antibiotic therapy

The recent focus on the cystic fibrosis (CF) complex microbiome has led to the recognition that the microbes can interact between them and with the host immune system, affecting the disease progression and treatment routes. Although the main focus remains on the interactions between traditional pathogens, growing evidence supports the contribution and the role of emergent species. Understanding the mechanisms and the biological effects involved in polymicrobial interactions may be the key to improve effective therapies and also to define new strategies for disease control. This review focuses on the interactions between microbe-microbe and host-microbe, from an ecological point of view, discussing their impact on CF disease progression. There are increasing indications that these interactions impact the success of antimicrobial therapy. Consequently, a new approach where therapy is personalized to patients by taking into account their individual CF microbiome is suggested.

Pseudomonas aeruginosa diversification during infection development in cystic fibrosis lungs

Dissertação de mestrado integrado em Engenharia Biomédica (área de especialização em Engenharia Clínica)

Isolation of Pseudomonas cepacia in cystic fibrosis patient

Pulmonary infection on cystic fibrosis (CF) patients are associated with a limited qualitative number of microorganisms. During the colonization process, Staphylococcus aureus usually preceedes Pseudomonas aeruginosa. This latter is at first non-mucoid, being replaced or associated to a mucoid morphotype which is rare in other diseases. In 1980, Pseudomonas cepacia appeared as an important agent in CF pulmonary infections with a mean frequency of about 6.1% isolations in different parts of the world. The primus colonization mainly occurs in the presence of pre-existent tissue lesions and the clinical progress of the disease is variable. In some patients it can be fulminant; in others it can cause a gradual and slow decrease in their pulmonary functions. The concern with this germ isolation is justified by its antibiotic multiple resistence and the possibility of direct transmission from a colonized patient to a non-colonized one. We reported the first case of P. cepacia infection in a CF patient in our area. The microbiological attendance to this patient had been made from 1986 to 1991 and the first positive culture appeared in 1988. The sensitivity profile showed that the primus colonization strain was sensitive to 9 of 17 tested antibiotics, however in the last culture the strain was resistent to all antibiotics. These data corroborate the need for monitoring the bacterial flora on CF patients respiratory system.

[R74W;R1070W;D1270N]: a new complex allele responsible for cystic fibrosis.

Since the beginning of population screening for CF carriers, it has become apparent that complex CFTR alleles are not uncommon. Deciphering their impact in disease pathogenesis remains a challenge for both clinicians and researchers. We report the observation of a new complex allele p.[R74W+R1070W+D1270N] found in trans with a type 1 mutation and associated with clinical diagnosis of cystic fibrosis in a one year-old Moroccan patient. This case underlines the difficulties in counseling patients with uncommon mutations and the necessity of functional studies to evaluate the structure-function relationships, since the association of several variations in cis can dramatically alter CFTR function.

Assessment of total energy expenditure in free-living patients with cystic fibrosis.

The increase in resting energy expenditure (REE) reported in patients with cystic fibrosis (CF) does not necessarily imply an increase in total energy expenditure (TEE). In this study REE was assessed with open-circuit indirect calorimetry, and free-living 24-hour TEE with the heart rate method. Thirteen patients with CF, aged 8 to 24 years, with adequate nutritional status and moderately decreased pulmonary function, were studied. They were compared with 13 healthy control subjects matched for gender, age, height, and nutritional status. Resting energy expenditure was higher in patients with CF (1512 +/- 88 kcal/day) than in control subjects (1339 +/- 76 kcal/day; p less than 0.01), whereas free-living 24-hour TEE (2345 +/- 127 kcal/day and 2358 +/- 256 kcal/day, respectively) and net mechanical work efficiency of walking on a treadmill (20.4 +/- 0.7% and 19.8 +/- 0.6%, respectively) were similar. Respiratory quotient was higher in patients with CF than in control subjects at rest (0.834 +/- 0.009 vs 0.797 +/- 0.008; p less than 0.05), and tended to remain so during physical exercise, indicating a higher contribution of carbohydrate oxidation to energy expenditure. We conclude that in free living conditions, patients with CF can compensate for their increase in REE by a reduction in spontaneous physical activities or other yet undefined mechanisms.

Serum phospholipid fatty acid profile and dietary intake in an adult Mediterranean population with cystic fibrosis.

The relative importance of the usual diet in serum phospholipids in subjects with cystic fibrosis (CF) has been poorly studied. To compare the fatty acid profile in serum phospholipids from adult CF subjects with that of healthy subjects, and determine the role of the normal diet in this profile, we studied thirty-seven adult CF subjects with stable pulmonary disease and thirty-seven healthy controls matched for age, sex and nutritional status. A dietary questionnaire was obtained, anthropometric data were recorded, and the fatty acid profile measured by GLC. Compared with the controls, the percentages of myristic, palmitoleic and stearic acids and total MUFA were significantly higher in the CF group, and DHA, linoleic acid, total PUFA and n-6 fatty acids were significantly lower in the CF group. The CF subjects with worse pulmonary function and with pancreatic insufficiency had significantly lower levels of linoleic and n-6 fatty acids. The total energy intake was significantly higher in the CF subjects, although the energy distribution in the CF subjects and the controls was not different for the carbohydrates, lipids and proteins. No differences were detected in fat intake for MUFA (51 (SD 4) v. 52 (SD 4) %) or saturated fatty acids (33.5 (SD 5) v. 31.2 (SD 3.8) %), but the PUFA were slightly lower in the CF subjects (15.4 (SD 4.5) v. 17.4 (SD 4.2) %; P=0.02). The usual dietary intake of fatty acids by adult CF subjects does not appear to explain the difference in the fatty acid profile compared with controls. This suggests an abnormal fatty acid metabolism in CF subjects.

Polyphasic characterisation of Burkholderia cepaciacomplex species isolated from children with cystic fibrosis

Cystic fibrosis (CF) patients with Burkholderia cepacia complex (Bcc) pulmonary infections have high morbidity and mortality. The aim of this study was to compare different methods for identification of Bcc species isolated from paediatric CF patients. Oropharyngeal swabs from children with CF were used to obtain isolates of Bcc samples to evaluate six different tests for strain identification. Conventional (CPT) and automatised (APT) phenotypic tests, polymerase chain reaction (PCR)-recA, restriction fragment length polymorphism-recA, recAsequencing, and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) were applied. Bacterial isolates were also tested for antimicrobial susceptibility. PCR-recA analysis showed that 36 out of the 54 isolates were Bcc. Kappa index data indicated almost perfect agreement between CPT and APT, CPT and PCR-recA, and APT and PCR-recA to identify Bcc, and MALDI-TOF and recAsequencing to identify Bcc species. The recAsequencing data and the MALDI-TOF data agreed in 97.2% of the isolates. Based on recA sequencing, the most common species identified were Burkholderia cenocepacia IIIA (33.4%),Burkholderia vietnamiensis (30.6%), B. cenocepaciaIIIB (27.8%), Burkholderia multivorans (5.5%), and B. cepacia (2.7%). MALDI-TOF proved to be a useful tool for identification of Bcc species obtained from CF patients, although it was not able to identify B. cenocepacia subtypes.

Dietary supplementation with omega-3 in cystic fibrosis patients

Accumulation of neutr ophils releasing proteolytic enzymes and free radicals induceprogressive lung tissue destruction in CF. Among several hfflammatory mediatorsimplicated in this process, leukotriene B 4 (LTB4) product of arachidonic (AA;20:4n 6) omega 6 polytmsaturated fatty acid (PUFA) plays an important role.Various anti inflammatory strategies including dietary supplementation of omega 3PUFA, known to favor the synthesis of less active leukotriene B 5 (LTBs), have beeninvestigated. To further explore this nutritional approach, biological effects of anomega 3 PUFA oral supplementation (n 3 OS) were measured in 17 CF patients haa prospective, randomized, double blind, crossover study. CF patients (mean age:18 + 9 years, FEVI: 66 + 29 %) received a dietary supplementation enriched, or not,ha omega 3 PUFA during a 2 x 6 months period. A modification in neutrophilmembrane PUFA composition was observed under n 3 OS with an increase in EPA(20:5n 3) PUFA (from 0.66 ± 0.56 to 1.60 ± 0.61 ~tmol %, P< 0.01). The LTB jLTB 5ratio was decreased (from 72 + 27 to 24 + 7, P< 0.C~31), in CF patients taking n 3OS. However, n 3 OS supplementation did neither affect the internalization of bothIL 8 receptors following IL 8 exposure, nor IL 8 induced neutrophil chemotaxis.Our results show that n 3 PUFA are absorbed and incorporated in neutrophilmembrmae. The consecutive decrease ha LTBjLTB 5 ratio suggests that, ha theseconditions, neutr ophils may produce less toxic mediators from the AA pathway. Thepotential clinical benefit for CF patients still needs to be assessed with furtherstudies of longer duration and including more patients.

Adaptação cultural e propriedades psicométricas iniciais do instrumento DISABKIDS ® – Cystic Fibrosis Module – versão brasileira

Este estudo objetivou adaptar culturalmente e descrever as propriedades psicométricas iniciais do instrumento de mensuração de qualidade de vida relacionada à saúde DISABKIDS® − Cystic Fibrosis Module para crianças e adolescentes e seus pais/cuidadores. Estudo metodológico de desenvolvimento sequencial, incluindo 126 participantes em quatro estados brasileiros. Envolveu tradução e retrotradução dos itens, equivalência conceitual e semântica, validade de face e descrição das propriedades psicométricas iniciais relacionadas ao construto e fidedignidade . Para equivalência semântica da versão adaptada houve ajustes na redação de um item. O instrumento apresentou consistência interna satisfatória com valores de alfa de Cronbach entre 0,70 e 0,85, validade convergente com valores de correlação acima 0,40 em 85% dos itens e validade divergente com valores de ajuste superiores a 75%. A versão brasileira do DISABKIDS® - CFM certamente se constituirá em um instrumento válido e confiável para a mensuração da qualidade de vida de crianças e adolescentes brasileiros com fibrose cística.

Thérapies inhalées dans la mucoviscidose [Inhaled therapies for cystic fibrosis].

Inhaled therapies play a significant role in the management of cystic fibrosis patients. Mucolytic and airway-rehydrating agents improve mucociliary clearance and respiratory functional status. Nebulized antibiotherapy achieve high local concentration, while reducing systemic toxicity. Tolerance to inhaled treatments is good excepting frequent bronchoconstriction which can usually be prevented by prior administration of beta2-mimetics. The majority of treatments are only available in liquid formulations. Thus, nebulization is the most frequently used inhalation mode. Vibrating-mesh nebulizers have significantly reduced inhalation time.

PCR detection of the pKM.19/ScrfI RFLP (D7S23), a marker closely linked to the cystic fibrosis mutation

Source: Description: pKM-19 is a 1.0 kb EcoRI human genomic fragment inserted in pUC13, that detects a Scrfl (CC/NGG) RFLP (1, 2). We report here the primer sequences suitable for the detection of this RFLP by PCR...

Mspl restriction fragment length polymorphism near exon 10 of cystic fibrosis (CFTR) gene.

Source/Description: The probe used is a 98 bp fragment amplified by PCR from a cDNA clone of the CFTR gene or from genomic DNA corresponding to exon 10, using two primers from this exon (1)...

Using sport to cope with cystic fibrosis

After a relatively normal childhood, people suffering from cystic fibrosis reach a stage where they are progressively confronted with increasingly crippling functional limitations. Some of them nonetheless regularly undertake physical and/or sporting activity. It is then interesting to examine the process of commitment to a practice that is based on the idea of progress and often exceptional performance by the body but which, for these people, makes the decline of their physical capacities particularly salient. The qualitative survey combines participant observation with 35 semi-directive interviews with sportsmen and women with cystic fibrosis. Their commitment to sport, constructed by/with the family is initially first aimed maintaining a form of control over their identity but progressively becomes a means of controlling the illness trajectory. Lung transplant, when possible, relaunches the practice in relation to its initial interests.