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At least 19 recordsLinked to original sources
PubMed1995

The risk of cancer among patients with cystic fibrosis. Cystic Fibrosis and Cancer Study Group.

BACKGROUND: Anecdotal reports suggest an increased frequency of certain cancers in patients with cystic fibrosis, the commonest genetic disorder of whites. One third of patients with cystic fibrosis now reach adulthood, when cancer is more frequent, implying that cancer rates in these patients will increase over time. We investigated the relation between cystic fibrosis and cancer in North American and European patients with cystic fibrosis. Methods. We performed a retrospective cohort study of the occurrence of cancer in 28,511 patients with cystic fibrosis from 1985 through 1992 in the United States and Canada. The number of cases observed was compared with the number expected, calculated from population-based data on the incidence of cancer. We also analyzed proportional incidence ratios to assess the association between specific cancers and cystic fibrosis in Europe. RESULTS: Thirty-seven cancers were observed in the North American cohort during 164,764 person-years of follow-up, as compared with an expected number of 45.6, yielding a ratio of observed to expected cancers of 0.8 (95 percent confidence interval, 0.6 to 1.1). Thirteen digestive tract tumors were observed, as compared with an expected number of two, for a ratio of observed to expected cancers of 6.5 (95 percent confidence interval, 3.5 to 11.1). In Europe, 11 of 39 cancers originated in the digestive tract, yielding a positive association between digestive tract tumors and cystic fibrosis (odds ratio, 6.4; 95 percent confidence interval, 2.9 to 14.0). CONCLUSIONS: Although the overall risk of cancer in patients with cystic fibrosis is similar to that of the general population, there is an increased risk of digestive tract cancers. Persistent or unexplained gastrointestinal symptoms in these patients should be carefully investigated.

Adolescent↗
PubMed1995

A multicenter study of alternate-day prednisone therapy in patients with cystic fibrosis. Cystic Fibrosis Foundation Prednisone Trial Group.

The purpose of this study was to evaluate the efficacy and safety of alternate-day prednisone therapy in treating patients with mild-to-moderate cystic fibrosis during a 4-year period. In 15 North American cystic fibrosis centers, we screened 320 patients and enrolled 285 patients from April 1986 to December 1987. Patients were randomly assigned to take prednisone, 1 mg/kg per dose or 2 mg/kg per dose, or a matching placebo given on alternate days. Lung function, clinical status, hospitalizations, growth, and steroid side effects were monitored. During the first 24 months the percentage of the predicted forced vital capacity was greater in the 1 mg/kg group (p < 0.0001) and the 2 mg/kg group (p < 0.01) when each was compared with placebo. Patients in the 1 mg/kg group had a higher percentage of predicted forced vital capacity than placebo patients during the entire 48 months (p < 0.0025), but only in the group of patients who were colonized with Pseudomonas aeruginosa at baseline. For 48 months, the 1 mg/kg group had a higher percentage of predicted forced expiratory volume in 1 second than patients given placebo (p < 0.02). The prednisone-treated groups had a reduction in serum IgG concentrations (1 mg/kg vs placebo, p < 0.007; 2 mg/kg vs placebo, p < 0.003). From 6 months onward, height z scores fell in the 2 mg/kg group compared with those given placebo (p < 0.001). For the 1 mg/kg group, height z scores were lower from 24 months. An excess of abnormalities in glucose metabolism was seen in the 2 mg/kg group compared with the placebo group (p < 0.005). Our findings suggest a role for alternate-day prednisone therapy at a dose of 1 mg/kg in patients with mild to moderate cystic fibrosis. The benefit of improved lung function appears to outweigh the potential for adverse effects when the treatment period is less than 24 months.

Adolescent↗
PubMed2006

Targeted therapy for cystic fibrosis: cystic fibrosis transmembrane conductance regulator mutation-specific pharmacologic strategies.

Cystic fibrosis (CF) results from the absence or dysfunction of a single protein, the CF transmembrane conductance regulator (CFTR). CFTR plays a critical role in the regulation of ion transport in a number of exocrine epithelia. Improvement or restoration of CFTR function, where it is deficient, should improve the CF phenotype. There are >1000 reported disease-causing mutations of the CFTR gene. Recent investigations have afforded a better understanding of the mechanism of dysfunction of many of these mutant CFTRs, and have allowed them to be classified according to their mechanism of dysfunction. These data, as well as an enhanced understanding of the role of CFTR in regulating epithelial ion transport, have led to the development of therapeutic strategies based on pharmacologic enhancement or repair of mutant CFTR dysfunction. The strategy, termed 'protein repair therapy', is aimed at improving the regulation of epithelial ion transport by mutant CFTRs in a mutation-specific fashion. The grouping of CFTR gene mutations, according to mechanism of dysfunction, yields some guidance as to which pharmacologic repair agents may be useful for specific CFTR mutations. Recent data has suggested that combinations of pharmacologic repair agents may be necessary to obtain clinically meaningful CFTR repair. Nevertheless, such strategies to improve mutant CFTR function hold great promise for the development of novel therapies aimed at correcting the underlying pathophysiology of CF.

Cystic Fibrosis↗
PubMed1999

Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. Cystic Fibrosis Inhaled Tobramycin Study Group.

BACKGROUND AND METHODS: We conducted two multicenter, double-blind, placebo-controlled trials of intermittent administration of inhaled tobramycin in patients with cystic fibrosis and Pseudomonas aeruginosa infection. A total of 520 patients (mean age, 21 years) were randomly assigned to receive either 300 mg of inhaled tobramycin or placebo twice daily for four weeks, followed by four weeks with no study drug. Patients received treatment or placebo in three on-off cycles for a total of 24 weeks. The end points included pulmonary function, the density of P. aeruginosa in sputum, and hospitalization. RESULTS: The patients treated with inhaled tobramycin had an average increase in forced expiratory volume in one second (FEV1) of 10 percent at week 20 as compared with week 0, whereas the patients receiving placebo had a 2 percent decline in FEV1 (P<0.001). In the tobramycin group, the density of P. aeruginosa decreased by an average of 0.8 log10 colony-forming units (CFU) per gram of expectorated sputum from week 0 to week 20, as compared with an increase of 0.3 log10 CFU per gram in the placebo group (P<0.001). The patients in the tobramycin group were 26 percent (95 percent confidence interval, 2 to 43 percent) less likely to be hospitalized than those in the placebo group. Inhaled tobramycin was not associated with detectable ototoxic or nephrotoxic effects or with accumulation of the drug in serum. The proportion of patients with P. aeruginosa isolates for which the minimal inhibitory concentration of tobramycin was 8 microg per milliliter or higher increased from 25 percent at week 0 to 32 percent at week 24 in the tobramycin group, as compared with a decrease from 20 percent at week 0 to 17 percent at week 24 in the placebo group. CONCLUSIONS: In a 24-week study of patients with cystic fibrosis, intermittent administration of inhaled tobramycin was well tolerated and improved pulmonary function, decreased the density of P. aeruginosa in sputum, and decreased the risk of hospitalization.

Administration, Inhalation↗
PubMed1997

Nutritional benefits of neonatal screening for cystic fibrosis. Wisconsin Cystic Fibrosis Neonatal Screening Study Group.

BACKGROUND: Many patients with cystic fibrosis are malnourished at the time of diagnosis. Whether newborn screening and early treatment may prevent the development of a nutritional deficiency is not known. METHODS: We compared the nutritional status of patients with cystic fibrosis identified by neonatal screening or by standard diagnostic methods. A total of 650,341 newborn infants were screened by measuring immunoreactive trypsinogen on dried blood spots (from April 1985 through June 1991) or by combining the trypsinogen test with DNA analysis (from July 1991 through June 1994). Of 325,171 infants assigned to an early-diagnosis group, cystic fibrosis was diagnosed in 74 infants, including 5 with negative screening tests. Excluding infants with meconium ileus, we evaluated nutritional status for up to 10 years by anthropometric and biochemical methods in 56 of the infants who received an early diagnosis and in 40 of the infants in whom the diagnosis was made by standard methods (the control group). Pancreatic insufficiency was managed with nutritional interventions that included high-calorie diets, pancreatic-enzyme therapy, and fat-soluble vitamin supplements. RESULTS: The diagnosis of cystic fibrosis was confirmed by a positive sweat test at a younger age in the early-diagnosis group than in the control group (mean age, 12 vs. 72 weeks). At the time of diagnosis, the early-diagnosis group had significantly higher height and weight percentiles and a higher head-circumference percentile (52nd, vs. 32nd in the control group; P=0.003). The early-diagnosis group also had significantly higher anthropometric indexes during the follow-up period, especially the children with pancreatic insufficiency and those who were homozygous for the deltaF508 mutation. CONCLUSIONS: Neonatal screening provides the opportunity to prevent malnutrition in infants with cystic fibrosis.

Body Height↗
PubMed1992

Double-lung transplantation for cystic fibrosis. The Cystic Fibrosis Transplant Study Group.

One hundred twenty cystic fibrosis patients were accepted for transplantation. Twenty-five patients underwent double-lung transplantation. Twenty-five patients died awaiting transplantation (20.6%). There were 13 female and 12 male patients. Their mean age was 28 years (range, 7 to 34 years), and mean percentage ideal body weight was 76% (range, 58.5% to 91.9%). Most patients were hypoxic and hypercarbic. Two patients underwent tracheal anastomosis, 15 had en bloc bronchial anastomoses, and 8 had sequential single-lung transplants. Operative mortality was 16%; all deaths were related to bleeding from extensive adhesions. Actuarial survival at 1 year was 64%. Rejection and infection were frequent during the first month and decreased thereafter. Airway complications occurred in 5 patients but were amenable to laser therapy and stenting. We conclude that double-lung transplantation is an acceptable modality for the treatment of cystic fibrosis patients with end-stage lung disease. It may be a better alternative to heart-lung transplantation considering the paucity of thoracic organ donors.

Adolescent↗
PubMed1999

Minor role of Cl- secretion in non-cystic fibrosis and cystic fibrosis human nasal epithelium.

Na+ and Cl- currents were studied in primary cultures of human nasal epithelium derived from non-cystic fibrosis (non-CF) and cystic fibrosis (CF) patients. We found that Na+ absorption dominates transepithelial transport and the Na+ current contains an amiloride-sensitive and amiloride-insensitive component. In non-CF tissue both components contribute about equally to the entire short-circuit current (ISC), whereas in CF tissues the major part of the current is amiloride-sensitive. Na+ removal reduced ISC to values close to zero. Several Cl- channel blockers were used to identify the remaining tiny Na+-independent current. Under unstimulated, physiological conditions in the presence of Cl- on both sides and amiloride on the apical side of the epithelium diphenylamine-2-carboxic acid (DPC), 4,4'-diisothiocyanatostilbene-2, 2'- disulfonic acid (DIDS) and 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) failed to induce clearcut inhibition of ISC. cAMP as well as ATP did not affect ISC either in CF or in non-CF epithelia. Reduction of apical Cl- increased ISC and depolarized transepithelial potential; however, the observed increase was insensitive to DIDS, DPC and NPPB. From these data we conclude that Cl- conductances in primary cultures of human nasal epithelium derived from CF patients as well as from non-CF patients are present only in low numbers or do not contribute significantly to transepithelial ion transport.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1995

Cystic fibrosis.

Cystic fibrosis has only been recognized as a distinct clinical entity for less than 60 years. In that period of time, the median survival has improved from a few months to 29 years. This editorial review outlines the clinical multiorgan involvement of cystic fibrosis and current management strategies and introduces the comprehensive articles by the contributing authors of this section on the most rapidly evolving areas in cystic fibrosis. The discussion includes how the cystic fibrosis gene product, the cystic fibrosis transmembrane conductance regulator, produces lung disease; the relationship between genotype and phenotype; the factors that determine prognosis in cystic fibrosis; new treatment modalities for cystic fibrosis; lung transplantation; and the prospects for gene therapy in cystic fibrosis. With rapid advances in our clinical and genetic understanding of cystic fibrosis, it is projected that individuals born with cystic fibrosis today will live into their 40s.

Cystic Fibrosis↗
PubMed2002

Anaesthesia in patients with cystic fibrosis.

Cystic fibrosis is an autosomal-recessive disorder. In 1989 the gene mutation that causes cystic fibrosis was localized on the long arm of chromosome 7. Cystic fibrosis occurs in 1/2000 children and the majority now reach adulthood. In view of numerous clinical manifestations of cystic fibrosis, these patients frequently require surgery. Cystic fibrosis is therefore of increasing interest to anaesthesiologists. Preoperative assessment is reviewed. Pre-, intra- and postoperative care must be directed toward optimal clearance of viscous respiratory secretions, and should minimize the risk of postoperative respiratory complications. All procedures should be planned but it is very important to prepare patients for surgery, with daily physiotherapy, administration of therapeutic agents using aerosols, management of nutrition and pancreatic enzymes, and administration of vitamins and antibiotics if indicated. Currently, anaesthesia can safely be carried out in cystic fibrosis patients undergoing minor surgery, with very low incidence of postoperative respiratory complications. Finally, organ transplantation, and in particular lung transplantation, with all its attendant anaesthesiological implications, has improved the outcome for many patients with cystic fibrosis.

Journal Article↗
PubMed1989

Prenatal diagnosis of cystic fibrosis.

Cystic fibrosis is the most common autosomal recessive genetic disorder in the Caucasian population (1:2000-1:4000) (Warwick, W. J. (1978) Helv. Paediatr. Acta 33, 117-125). This defect is characterized by chronic obstructive pulmonary disease, pancreatic exocrine insufficiency and abnormally high perspiration electrolytes in most patients (Talamo et al. (1985) In: The metabolic basis of inherited diseases, pp. 1887-1917). The elevated electrolyte level provides the most reliable diagnostic test for cystic fibrosis homozygotes. Although prospects for cystic fibrosis patients have improved, genetically homozygous cystic fibrosis is effectively a lethal disease. Because of the seriousness of the disease, many families with one affected child desire a prenatal diagnosis when a second pregnancy occurs. Despite extensive research, the biochemical basis of cystic fibrosis remains unknown. Secondary effects on microvillar enzymes allow second trimester diagnosis (17-18 weeks of gestation (Brock, D. H. J. (1983) Lancet II, 941-943). First trimester prenatal diagnosis for cystic fibrosis became possible with DNA technology. Application of polymorphic marker loci to problems of prenatal diagnosis and carrier-testing is discussed.

Alkaline Phosphatase↗
PubMed1995

Anaesthesia for adults with cystic fibrosis.

Cystic fibrosis is an autosomal recessive disorder which affects one in 2500 live births. It is a multisystem disease and has a variety of presentations. The major clinical features affect the gastrointestinal and respiratory tracts. Severe respiratory disease, diabetes and gastroesophageal reflux are common features of concern to anaesthetists. Improved care of young patients has allowed many to survive into adulthood. Lung transplantation has significantly improved the outlook for many patients. At Alfred Hospital, 74 patients with cystic fibrosis underwent 149 procedures from January 1978 to January 1994, with a mortality of 0.6% (95% CI 0.4%-0.8%). This retrospective cohort study describes the anaesthetic management and perioperative care of these patients. Most of the anaesthetics were for procedures related to cystic fibrosis but 12% were for unrelated conditions. Cystic fibrosis related procedures include diagnostic, venous access, enteral feeding procedures, treatment of complications of cystic fibrosis and lung transplantation. Despite extremely poor respiratory function, these patients can be managed with acceptably low postoperative mortality (1%). Pre- and postoperative care must be directed towards optimal clearance of viscous respiratory secretions. Procedures need to be planned so that optimal care can be given by each member of the team caring for cystic fibrosis patients.

Adolescent↗
PubMed1990

Guidance of children and adolescents with cystic fibrosis.

Cystic fibrosis is the most common serious genetic disorder in people of European descent. Treatment of these patients is ongoing throughout life and until now has been aimed at the consequences and is still not curative. Over the past 10-20 years, there has been a dramatic improvement of mortality rates for cystic fibrosis, due in large part to advances in medical care. The average age of survival for young people with cystic fibrosis is pushing well into the 20s with one third living into their 30s. Consequently, education plays a major role in management of patients with cystic fibrosis, and starts directly after being sure of the diagnosis. Growing up, these patients experience a lot of problems, and these are especially marked in the adolescent. A special problem, for many cystic fibrosis patients is becoming an adult. Continuity in care for these patients from the pediatric to the adult department is not always guaranteed. It is concluded that patients with cystic fibrosis should be treated in specialized centers, and such treatment cannot be carried out sufficiently by one person, but has to be embedded in a team of caregivers.

Adolescent↗