The neutrophil-recruiting chemokine GCP-2/CXCL6 is expressed in cystic fibrosis airways and retains its functional properties after binding to extracellular DNA.

Infections in cystic fibrosis (CF), often involving Pseudomonas aeruginosa, result from a dysregulated airway immunity where one hallmark is the accumulation of necrotic and apoptotic immune cells, in particular neutrophils. In addition, neutrophils actively release DNA, forming neutrophil extracellular traps (NETs) that contain antimicrobial proteins. Altogether, free DNA in complex with actin accumulates in the airway lumen, resulting in highly viscous sputum that provides an anionic matrix, binding cationic antimicrobial proteins. In this study, granulocyte chemotactic protein 2 (GCP-2)/CXCL6, a neutrophil-activating chemokine with bactericidal properties, was detected in the airway epithelium of CF patients and was also present in azurophilic and specific granules of neutrophils. Elastase of neutrophils, but not of P. aeruginosa, completely degraded CXCL6 (chemokine (C-X-C motif) ligand 6). In addition, CXCL6 colocalized with extracellular DNA in both CF sputa and in in vitro-formed NETs. In vitro, CXCL6 bound DNA with a KD of 2,500 nM. Interestingly, both the bactericidal and the receptor-activating properties of CXCL6 (against neutrophils) remained largely unaffected in the presence of DNA. However, the chemotactic properties of CXCL6 were reduced by the presence of DNA. Taken together, CXCL6 is expressed in CF, retaining its functional properties even after binding to the anionic scaffold that extracellular DNA provides in CF.

Guidelines for the management of pregnancy in women with cystic fibrosis.

Women with cystic fibrosis (CF) now regularly survive into their reproductive years in good health and wish to have a baby. Many pregnancies have been reported in the literature and it is clear that whilst the outcome for the baby is generally good and some mothers do very well, others find either their CF complicates the pregnancy or is adversely affected by the pregnancy. For some, pregnancy may only become possible after transplantation. Optimal treatment of all aspects of CF needs to be maintained from the preconceptual period until after the baby is born. Clinicians must be prepared to modify their treatment to accommodate the changing physiology during pregnancy and to be aware of changing prescribing before conception, during pregnancy, after birth and during breast feeding. This supplement offers consensus guidelines based on review of the literature and experience of paediatricians, adult and transplant physicians, and nurses, physiotherapists, dietitians, pharmacists and psychologists experienced in CF and anaesthetist and obstetricians with experience of CF pregnancy. It is hoped they will provide practical guidelines helpful to the multidisciplinary CF teams caring for pregnant women with CF.

Demographic transition of the Swedish cystic fibrosis community--results of modern care.

Assessing the results of modern cystic fibrosis (CF)-care and estimating the future population and its demography is important to evaluate the treatment regimens and to calculate the future needs of health-care resources. This paper updates previous incidence calculations. It assesses the results of modern CF-care in terms of survival and changing demography in Sweden. The incidence of CF in Sweden was calculated as 1/5600 live-births. Of the CF-population alive in 1999, 45% were > or = 18 years old. The mean annual mortality rate since 1991 was 0.9% (+/-0.4) and the median age at death 26 years (range 0-72). Of those born > or = 1991, 95% were estimated to survive their 25th birthday. The incidence of CF in Sweden is low. Modern CF-care in Sweden shows good results. The CF-population is growing rapidly and the adult part of the population will soon be larger than the paediatric. Continuously adapted resources are required to assure the future treatment quality especially for the growing adult CF-population.

Identification of MUC5B, MUC5AC and small amounts of MUC2 mucins in cystic fibrosis airway secretions.

To investigate the genetic identities of the mucins secreted in cystic fibrosis (CF) airways, sputum was collected from five individuals. Samples were separated into gel and sol phases by high-speed centrifugation and the gel phase was extracted in 6 M guanidinium chloride. The 'insoluble' residue remaining after extraction of the gel phase was brought into solution by reduction/alkylation. Density-gradient centrifugation in CsCl revealed polydisperse distributions of sialic acid-containing mucins in the gel phase, insoluble residue and sol phase fractions and the degree of variation between the different individuals was low. Antibodies recognizing MUC5AC and MUC5B identified these mucins in each of the fractions. MUC2, however, was present only as a component of the insoluble residue from the gel which accounted for less than 4% by mass of the total mucins. MUC5B and MUC5AC from the gel phase were large oligomeric species composed of disulphide-bond linked subunits and MUC5B was present as two populations with different charge densities which are likely to correspond to MUC5B 'glycoforms'. The sol phase contained, in addition to MUC5AC and MUC5B, mainly smaller mucins which did not react with the antisera and which were probably degraded. MUC5AC appeared to be enriched in the sol, suggesting that this mucin may be more susceptible to proteolytic degradation than MUC5B. The mucins present in sputum remained broadly similar during acute exacerbation and following antibiotic treatment, although the relative amount of an acidic MUC5B glycoform was decreased during infection.

Mild cystic fibrosis mutations in Southern Sweden with special reference to S549I and T338I.

In this study of cystic fibrosis (CF) gene mutations in Southern Sweden we found missense mutations in 12 out of 110 patients. These patients, as a group, differed from deltaF508 homozygotes by a higher frequency of pancreatic sufficiency and an older age at diagnosis as has been indicated in previous studies. In addition, lung function (vital capacity (VC) and forced expiratory volume in 1 s (FEV1)) tended to be better although the difference did not reach statistical significance (p = 0.13 for FEV1). For two mutations, S549I and T338I, our results differed from earlier reports. In our experience, S549I confers a milder phenotype and T338I a more severe one than previously reported. We conclude that each mutation should be treated separately when trying to correlate genotype with phenotype.

Mucus clearance with three chest physiotherapy regimes in cystic fibrosis: a comparison between postural drainage, PEP and physical exercise.

The effects of three different regimes of chest physiotherapy were compared in this cross-over study. Mucus clearance was monitored in nine clinically stable cystic fibrosis (CF) patients. The patients performed: 1) postural drainage with thoracic expansion exercises + forced expiration technique (FET) in the left decubitus position; 2) positive expiratory pressure (PEP)-mask breathing + FET; and 3) physical exercise on a bicycle ergometer + FET. All treatments had the same duration and FET was standardized. Mucus clearance was assessed using a technique based on measurement of the elimination of inhaled radiolabelled particles. Mean clearance of tracer from the right lung by postural drainage, PEP and physical exercise was 18% (range 10-29%), 20% (12-43%), 16% (8-25%), respectively, and from the left lung 20% (8-42%), 15% (5-23%) and 13% (5-17%), respectively. The differences were not statistically significant. Surprisingly, postural drainage (PD) was the most effective technique in the left, dependent lung in 7 of the 9 patients.