Cystic Fibrosis Status Research Articles

The association between cystic fibrosis-related diabetes and periodontitis in adults: A pilot cross-sectional study.

Periodontitis is a highly prevalent complication of diabetes. However, the association between cystic fibrosis-related diabetes (CFRD) and periodontitis has not yet been evaluated. The objective of this study was to assess if: 1) CFRD is associated with periodontitis among adults with CF, and 2) periodontitis prevalence differs by CF and diabetes status. This was a pilot cross-sectional study of the association between CFRD and periodontitis in adults with cystic fibrosis (CF) (N = 32). Historical non-CF controls (N = 57) from the U.S. National Health and Nutrition Examination Survey (NHANES) dataset were frequency matched to participants with CF on age, sex, diabetes status, and insulin use. We defined periodontitis using the U.S. Centers for Disease Control and Prevention and the American Academy of Periodontology (CDC/AAP) case definition, as the presence of two or more interproximal sites with CAL ≥3 mm and two or more interproximal sites with PD ≥4 mm (not on the same tooth) or one site with PD ≥5 mm. Because NHANES periodontal data were only available for adults ages ≥30 years, our analysis that included non-CF controls focused on this age group (CF N = 19, non-CF N = 57). Based on CF and diabetes status, we formed four groups: CFRD, CF and no diabetes, non-CF with diabetes, and non-CF and no diabetes (healthy). We used the Fisher's exact test for hypotheses testing. There was no association between CFRD and periodontitis for participants with CF ages 22-63 years (CFRD 67% vs. CF no diabetes 53%, P = 0.49), this was also true for those ages ≥30 years (CFRD 78% vs. CF no diabetes 60%, P = 0.63). For the two CF groups, the prevalence of periodontitis was significantly higher than for healthy controls (CFRD 78% vs. healthy 7%, P<0.001; CF no diabetes 60% vs. healthy 7%, P = 0.001) and not significantly different than the prevalence for non-CF controls with diabetes (CFRD 78% vs. non-CF with diabetes 56%, P = 0.43; CF no diabetes 60% vs. non-CF with diabetes 56%, P = 0.99). Among participants with CF, CFRD was not associated with periodontitis. However, regardless of diabetes status, participants with CF had increased prevalence of periodontitis compared to healthy controls.

Network Analysis to Identify Multi-Omic Correlations in the Lower Airways of Children With Cystic Fibrosis.

The leading cause of morbidity and mortality in cystic fibrosis (CF) is progressive lung disease secondary to chronic airway infection and inflammation; however, what drives CF airway infection and inflammation is not well understood. By providing a physiological snapshot of the airway, metabolomics can provide insight into these processes. Linking metabolomic data with microbiome data and phenotypic measures can reveal complex relationships between metabolites, lower airway bacterial communities, and disease outcomes. In this study, we characterize the airway metabolome in bronchoalveolar lavage fluid (BALF) samples from persons with CF (PWCF) and disease control (DC) subjects and use multi-omic network analysis to identify correlations with the airway microbiome. The Biocrates targeted liquid chromatography mass spectrometry (LC-MS) platform was used to measure 409 metabolomic features in BALF obtained during clinically indicated bronchoscopy. Total bacterial load (TBL) was measured using quantitative polymerase chain reaction (qPCR). The Qiagen EZ1 Advanced automated extraction platform was used to extract DNA, and bacterial profiling was performed using 16S sequencing. Differences in metabolomic features across disease groups were assessed univariately using Wilcoxon rank sum tests, and Random forest (RF) was used to identify features that discriminated across the groups. Features were compared to TBL and markers of inflammation, including white blood cell count (WBC) and percent neutrophils. Sparse supervised canonical correlation network analysis (SsCCNet) was used to assess multi-omic correlations. The CF metabolome was characterized by increased amino acids and decreased acylcarnitines. Amino acids and acylcarnitines were also among the features most strongly correlated with inflammation and bacterial burden. RF identified strong metabolomic predictors of CF status, including L-methionine-S-oxide. SsCCNet identified correlations between the metabolome and the microbiome, including correlations between a traditional CF pathogen, Staphylococcus, a group of nontraditional taxa, including Prevotella, and a subnetwork of specific metabolomic markers. In conclusion, our work identified metabolomic characteristics unique to the CF airway and uncovered multi-omic correlations that merit additional study.

A doggy tale: Risk of zoonotic infection with Bordetella bronchiseptica for cystic fibrosis (CF) patients from live licenced bacterial veterinary vaccines for cats and dogs.

Live-attenuated bacterial veterinary vaccines can constitute an infection risk for individuals with any defect in their phagocytic function, including chronic granulomatous disease, leukocyte adhesion deficiency, myeloperoxidase deficiency, as well as Chediak-Higashi syndrome, from accidental acquisition of licenced attenuated live bacterial vaccine, at vaccination or from their vaccinated pet. Ownership of small companion animals, including cats and dogs, is popular within the cystic fibrosis (CF) community. These animals require vaccines as part of their routine care, which may involve live viral and bacterial vaccines, with potential for infection in the CF owner. This report examines the scope of current canine and feline vaccines, with particular emphasis on veterinary vaccination strategies against the Gram-negative pathogen, Bordetella bronchiseptica and describes new vaccine innovations offering protection to both pet and CF owner. The Gram-negative bacterium, Bordetella bronchoseptica, may cause respiratory disease in small companion animals, as well as in certain human vulnerable groups, including those with CF. Live licenced veterinary bacterial vaccines for Bordetella bronchiseptica (Kennel Cough) are available for cats and dogs, which are an infection concern for humans with CF who may come into contact with vaccinated animals. Live licenced veterinary bacterial vaccines for Bordetella bronchiseptica (Kennel Cough) are available for intranasal administration to cats and dogs. These vaccines require a withdrawal period of vaccinated animal from vulnerable owner, ranging from 35days - 11weeks. Recently, a new dead IM vaccine is now available not requiring exclusion of the vaccinated pet from CF owner. CF pharmacists, hospital pharmacists and community pharmacists are important custodians of vaccine-related advice to people with CF, who are frequently consulted for such advice. Pharmacists should be aware of the recent innovations in veterinary medicines, so that they can give appropriate advice to people with CF when asked. Immunocompromised patients, that is those with CF or those with any defect in their phagocytic function (chronic granulomatous disease, leukocyte adhesion deficiency, myeloperoxidase deficiency, Chediak-Higashi syndrome) should avoid exposure to live veterinary bacterial vaccines and seek animal vaccination utilising non-live vaccines. Most importantly, this manuscript highlights the development of a new veterinary vaccine for dogs, which we want to make the CF healthcare community aware of, which is an acellular dead vaccine, so that those patients with dogs needing annual vaccination can select this vaccine pathway, thereby minimising risk of infection from the vaccine strains and avoiding the social exclusion between CF patient and their pet. CF patients should understand the potential infection implications of live-attenuated viral and bacterial strains as vaccines, whether these are small companion animals, exotic animals or large farm animals. Patients should make their veterinarian aware of their CF status, so that a safe and efficacious vaccine strategy is used, both mitigating the potential infection risks from live vaccine components with the CF patient, but simultaneously offering maximum immunological protection to the animal.

Untreated dental disease and lung transplant waitlist evaluation time for individuals with cystic fibrosis.

Dental clearance is typically part of the evaluation process prior to placement on the lung transplant waiting list. Individuals with cystic fibrosis (CF) are thought to be at low risk for dental disease. We hypothesized that individuals with CF in need of lung transplantation would have lower dental disease prevalence and shorter waitlist evaluation time than individuals with non-CF lung diseases. We conducted a retrospective study of individuals who received a lung transplant between 2011 and 2017 at the University of Washington (Seattle, WA, USA) (N=280). Untreated dental disease was assessed by the individual's dentist. Waitlist evaluation time was defined as the time, in days, from the initial evaluation by a transplant pulmonologist to placement on the lung transplant waiting list. We used logistic and linear regression models for hypothesis testing. The prevalence of untreated dental disease did not differ by CF status (p=0.99). There was no difference in waitlist evaluation time for transplant recipients by CF status (p=0.78) or by dental disease status (p=0.93). Our findings provide further evidence that individuals with CF are not at low risk for dental disease. Ensuring optimal oral health is important for all individuals with lung diseases.

Should the dosage of propofol be higher and independent of immunosuppressive therapy in adult cystic fibrosis patients undergoing sedation during flexible video bronchoscopy?

Flexible video bronchoscopy (FVB) performed under sedation is a useful procedure in adults with cystic fibrosis (CF). Propofol dosage for CF is poorly described, although it is of high importance for professionals. The study aimed to assess whether propofol dosage should be higher in adults CF undergoing sedation during FVB. 50 adult CF and non-CF patients undergoing sedation during FVB were included. Clinical features of studied patients were assessed. In CF group spirometry, liver enzymes, inflammatory biomarkers, albumin, protein concentration, WBC were estimated. Propofol and fentanyl dosage was calculated. Multiple regression model was performed. CF patients were characterized by a lower mean value of body weight and lower mean requirement of total propofol (135 mg in CF vs. 145 mg in non-CF). Calculated propofol dose per kg of body weight was significantly higher in CF (2.43 mg/kg vs. 2.04 mg/kg) and did not depend on the bronchopulmonary disease stage. Propofol dose per kg of body weight was predicted by CF status (CF vs. non-CF), sex, and age. Adult CF patients not receiving immunosuppressive therapy require higher propofol dose per kg of body weight compared to non-CF, independently on bronchopulmonary disease stage showing a narrow therapeutic window for propofol in CF group.

Decreased Immune Activation in Cystic Fibrosis Airway Epithelium Following Lung Transplant

End-stage cystic fibrosis (CF) can be managed by lung transplantation (LT), but chronic allograft dysfunction (CLAD) limits long-term survival. While Pseudomonas aeruginosa airway infection (PsA) is a risk factor for CLAD for most lung allograft recipients, this association does not hold for CF recipients. We hypothesized that differences in host epithelial immune responses and the composition of airway microbial communities could contribute to protection from CLAD in CF recipients with PsA. We compared transcriptomes from clinical airway brushes following LT for 28 subjects, grouped by CF status and PsA culture result (CF+PsA+, n=8; CF+PsA-, n=6; CF-PsA+, n=5; and CF-PsA-, n=9) using DEseq2. For in vitro analysis of immune responses, airway epithelial cells (AEC) were isolated from lung explants (pre-LT) or surveillance airway brushes (post-LT) and grown at air-liquid interface until polarized and differentiated. Gene expression differences and DNA methylation were compared by CF status using quantitative PCR and DNA methylation array. For subjects with a positive PsA culture following LT, there were 193 differentially expressed genes between CF and non-CF airways. Pathway analysis demonstrated suppression of interferon response in CF airways. Relative to non-CF referents, CF AEC in vitro transitioned from increased expression of neutrophil-associated genes (Cxcl8 and Lcn2) pre-LT, to decreased expression of interferon-associated genes (Mx1 and Oas1) post-LT. DNA methylation analysis showed hypermethylation of promoters in type I interferon responsive genes (p = 0.002). All CF+PsA+ subjects had mucoid PsA strains while 72% of non-CF subjects had non-mucoid PsA (p <0.001). The combination of attenuated interferon responses and prevalence of mucoid strains may explain the differential outcomes in CF LT recipients with PsA.

Age-related heterogeneity in dental caries and associated risk factors in individuals with cystic fibrosis ages 6–20 years: A pilot study

BackgroundThe literature conflicts regarding dental caries risk in cystic fibrosis (CF) relative to controls. MethodsProspective, observational study of age-related heterogeneity in caries rates and potential risk factors in individuals with CF ages 6-20 at a single clinic in Washington state (N=85). Caries rates for enrolled CF participants and historical controls from NHANES were compared using cubic spline regression models. Generalized linear regression models identified correlates of age and caries in CF. ResultsChildren ages 6-9 with CF had significantly lower caries than controls (Holm’s P<0.05). There was no difference for ages 10-20 by CF status (Holm’s P>0.05). Various biological/intraoral, medical, and behavioral factors were associated with caries and age in CF. ConclusionsYounger children with CF may be protected from caries, but there is apparent loss of protection in early adolescence associated with multiple risk factors. Additional studies are needed to confirm these findings.

Activity of Bacteriophages in Removing Biofilms of Pseudomonas aeruginosa Isolates from Chronic Rhinosinusitis Patients.

Introduction: Pseudomonas aeruginosa infections are prevalent amongst chronic rhinosinusitis (CRS) sufferers. Many P. aeruginosa strains form biofilms, leading to treatment failure. Lytic bacteriophages (phages) are viruses that infect, replicate within, and lyse bacteria, causing bacterial death.Aim: To assess the activity of a phage cocktail in eradicating biofilms of ex vivo P.aeruginosa isolates from CRS patients.Methods: P. aeruginosa isolates from CRS patients with and without cystic fibrosis (CF) across three continents were multi-locus sequence typed and tested for antibiotic resistance. Biofilms grown in vitro were treated with a cocktail of four phages (CT-PA). Biofilm biomass was measured after 24 and 48 h, using a crystal violet assay. Phage titrations were performed to confirm replication of the phages. A linear mixed effects model was applied to assess the effects of treatment, time, CF status, and multidrug resistance on the biomass of the biofilm.Results: The isolates included 44 strain types. CT-PA treatment significantly reduced biofilm biomass at both 24 and 48 h post-treatment (p < 0.0001), regardless of CF status or antibiotic resistance. Biomass was decreased by a median of 76% at 48 h. Decrease in biofilm was accompanied by a rise in phage titres for all except one strain.Conclusion: A single dose of phages is able to significantly reduce biofilms formed in vitro by a range of P.aeruginosa isolates from CRS patients. This represents an exciting potential and novel targeted treatment for P. aeruginosa biofilm infections and multidrug resistant bacteria.

Influenza Virus Detection Following Administration of Live-Attenuated Intranasal Influenza Vaccine in Children With Cystic Fibrosis and Their Healthy Siblings.

Background. We aimed to explore the detection profile of influenza viruses following live-attenuated intranasal influenza vaccination (LAIV) in children aged 2–19 years with and without cystic fibrosis (CF). Methods. Before the 2013–2014 influenza season, flocked nasal swabs were obtained before vaccination and 4 times in the week of follow-up from 76 participants (nCF: 57; nhealthy: 19). Influenza was detected by reverse transcription polymerase chain reaction (RT-PCR) assays. A Bayesian hierarchical logistic regression model was used to estimate the effect of CF status and age on influenza detection. Results. Overall, 69% of the study cohort shed influenza RNA during follow-up. The mean duration of RT-PCR detection was 2.09 days (95% credible interval [CrI]: 1.73–2.48). The odds of influenza RNA detection on day 1 following vaccination decreased with age in years (odds ratio [OR]: 0.82 per year; 95% CrI: 0.70–0.95), and subjects with CF had higher odds of influenza RNA detection on day 1 of follow-up (OR: 5.09; 95% CrI: 1.02–29.9). Conclusion. Despite the small sample size, our results indicate that LAIV vaccine strains are detectable during the week after LAIV, mainly in younger individuals and vaccinees with CF. It remains unclear whether recommendations for avoiding contact with severely immunocompromised patients should differ for these groups.

Dental utilization for Medicaid-enrolled children with cystic fibrosis.

Despite a multitude of risk factors, children with cystic fibrosis (CF) have lower reported dental caries prevalence. A potential explanation is preventive dental care use, but no studies to date have examined dental use for children with CF. Iowa Medicaid data were analyzed for children age 3 to 17 years (N = 156,268). Poisson regression models were used to compare utilization rates for any dental care and also for specific categories of dental care, by CF status. Children with CF were significantly less likely to use any dental care than children without CF (incident rate ratio: 0.819, 95% CI: 0.80 to 0.84, p < .001). There were no significant differences in use across specific categories of dental care. Medicaid-enrolled children with CF are less likely to use dental care than children without CF. These findings suggest that use of dental care use is an unlikely explanation for lower purported caries rates among children with CF.

Analysis of pediatric airway morphology using statistical shape modeling.

Traditional studies of airway morphology typically focus on individual measurements or relatively simple lumped summary statistics. The purpose of this work was to use statistical shape modeling (SSM) to synthesize a skeleton model of the large bronchi of the pediatric airway tree and to test for overall airway shape differences between two populations. Airway tree anatomy was segmented from volumetric chest computed tomography of 20 control subjects and 20 subjects with cystic fibrosis (CF). Airway centerlines, particularly bifurcation points, provide landmarks for SSM. Multivariate linear and logistic regression was used to examine the relationships between airway shape variation, subject size, and disease state. Leave-one-out cross-validation was performed to test the ability to detect shape differences between control and CF groups. Simulation experiments, using tree shapes with known size and shape variations, were performed as a technical validation. Models were successfully created using SSM methods. Simulations demonstrated that the analysis process can detect shape differences between groups. In clinical data, CF status was discriminated with good accuracy (precision=0.7, recall=0.7) in leave-one-out cross-validation. Logistic regression modeling using all subjects showed a good fit (ROC AUC=0.85) and revealed significant differences in SSM parameters between control and CF groups. The largest mode of shape variation was highly correlated with subject size (R=0.95, p<0.001). SSM methodology can be applied to identify shape differences in the airway between two populations. This method suggests that subtle shape differences exist between the CF airway and disease control.

Dental caries prevalence in children and adolescents with cystic fibrosis: a qualitative systematic review and recommendations for future research

Children and adolescents with cystic fibrosis (CF) are believed to be at low risk for dental caries, but this paradigm has not been critically evaluated. To conduct a qualitative systematic review of the international literature on dental caries prevalence in children and adolescents with CF and make recommendations on future CF-related oral health research priorities. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement was used to identify relevant studies published between 1960 and 2013. The search resulted in 696 studies. Fifteen publications were included in the qualitative systematic review. Ten studies concluded that children with CF had significantly lower caries prevalence than control children, three studies reported that children with CF had higher caries prevalence, and two studies found no difference by CF status. Of the seven studies including age-based subgroup analyses, only one study supported the current paradigm. All studies had limitations that may bias study results. While children with CF may be a lower risk for dental caries, adolescents with CF may not be at lower caries than those without CF. Additional research is needed to evaluate a potentially flawed paradigm regarding caries risk in children and adolescents with CF.

Aquagenic wrinkling of the palms in cystic fibrosis and the cystic fibrosis carrier state: a case-control study

Aquagenic wrinkling of the palms (AWP) is hyperwrinkling occurring within 3 min of exposure to water. It is associated with cystic fibrosis (CF) and has been reported in a CF carrier. To ascertain if AWP is a sign of the CF carrier state and to test for an association between cystic fibrosis transmembrane regulator (CFTR) protein function and time to wrinkling. Twenty-one patients, 13 carriers and 15 controls were recruited. Hands were immersed in water and time to wrinkling was measured. An analysis of variance was performed with mean time to wrinkling as the dependent variable and CF status as the independent variable. Patients with a time to wrinkling of ≤ 3 min were defined as having AWP. A test of proportions was performed to assess if the proportion of patients with AWP varied between groups. Mean time to wrinkling was 11 min in controls, 7 min in carriers and 2 min in patients with CF. AWP was not seen in controls, but occurred in 80% of patients with CF and 25% of carriers. There was a significant difference between groups (P < 0·001). The study demonstrated that AWP is a sign of both CF and the carrier state. It suggests that time to wrinkling decreases with decreased CFTR protein function. Patients presenting with AWP should be offered screening for both CF and the carrier state.

Amniotic Fluid Digestive Enzyme Analysis Is Useful for Identifying CFTR Gene Mutations of Unclear Significance

The large number of CFTR [cystic fibrosis transmembrane conductance regulator (ATP-binding cassette sub-family C, member 7)] mutations and the existence of variants of unclear significance complicate the prenatal diagnosis of cystic fibrosis (CF). The aim of this study was to determine whether the pattern of amniotic fluid digestive enzymes (AF-DEs) could be correlated with the severity of CFTR mutations. The AF-DE pattern (gamma-glutamyltranspeptidase, aminopeptidase M, and the intestinal isoform of alkaline phosphatase) was retrospectively analyzed in 43 AF samples. All fetuses presented 2 CFTR mutations, which were classified according to the severity of the disease: CF/CF (n = 38); CF/CFTR-related disorders (n = 1); and CF/unknown variant (n = 4). The relationships between clinical CF status, CFTR mutations, and AF-DE pattern were studied. Of 38 severely affected CF fetuses, an "obstructive" AF-DE pattern was observed in 15 of 15 samples collected before 22 weeks, irrespective of the CFTR mutation (diagnostic sensitivity, 100%; diagnostic specificity, 99.8%). In the 23 fetuses evaluated after 22 weeks, the AF-DE pattern was abnormal in 7 cases and noncontributive in 16 (diagnostic sensitivity, 30.4%; diagnostic specificity, 99.8%). Of the 5 questionable cases (F508del/N1224K, F508del/L73F, 3849+10kbC>T/G1127E, F508del/S1235R, F508del/G622D), all were CF symptom free at 2-4 years of follow-up. The AF-DE pattern (<22 weeks) was typical in 3 cases but abnormal in the last 2 cases. AF-DE analysis is of value for prenatal CF diagnosis in classic forms of CF and could be helpful in nonclassic CF.

Polyunsaturated Fatty Acids in Cystic Fibrosis Are Related to Nutrition and Clinical Expression of the Disease

Polyunsaturated Fatty Acids in Cystic Fibrosis Are Related to Nutrition and Clinical Expression of the Disease

X chromosome transmission ratio distortion in Cftr +/- intercross-derived mice

BackgroundCystic fibrosis (CF) mice, created with a genetically engineered mutation in the Cystic fibrosis transmembrane conductance regulator (Cftr) gene, may develop intestinal plugs which limit their survival past weaning. In a studied population of genetically mixed CF mice differences in allelic ratios at particular loci, between surviving CF mice and mice with the lethal intestinal defect, were used to map cystic fibrosis modifier gene one, Cfm1. Using this approach, we previously identified an X chromosome locus which may influence the survival to weaning of C57BL/6J × BALB/cJ F2 CF mice. We also detected two regions of transmission ratio distortion, independent of Cftr genotype, in a limited dataset. To investigate these findings, in this study we have genotyped 1208 three-week old F2 mice, and 186 day E15.5 embryos, derived from a congenic (C57BL/6J × BALB/cJ) F1 Cftr +/- intercross, for the putative distortion regions.ResultsAn excess of homozygous BALB genotypes, compared to Mendelian expectations, was detected on chromosomes 5 (p = 5.7 × 10-15) and X (p = 3.0 × 10-35) in three-week old female mice but transmission ratio distortion was not evident in the tested region of chromosome 3 (p = 0.39). Significant pre-weaning lethality of CF mice occurred as 11.3% (137/1208) of the three-week old offspring were identified as CF mice. X chromosome genotypes were not, however, distorted in the female CF mice (p = 0.62), thus the significant non-Mendelian inheritance of this locus was dependent on CF status. The survival of CF embryos to day E15.5 was consistent with Mendelian expectations (42/186 = 23%), demonstrating the loss of CF mice to have occurred between E15.5 and three weeks of age. The excess of X chromosome homozygous BALB genotypes was recorded in female embryos (p = 0.0048), including CF embryos, indicating the distortion to be evident at this age.ConclusionTwo of three previously suggested loci of transmission ratio distortion were replicated as distorted in this mouse cross. The non-Mendelian inheritance of X chromosome genotypes implicates this region in the survival to weaning of non-CF mice.

A Pilot Study of the Effect of Inhaled Buffered Reduced Glutathione on the Clinical Status of Patients With Cystic Fibrosis

To assess the impact of inhaled, buffered reduced glutathione (GSH) on clinical indicators of cystic fibrosis (CF) pathophysiology. A randomized, double-blind, placebo-controlled pilot study was conducted over an 8-week period. Nineteen subjects, age 6 to 19 years, with CF status documented by positive sweat chloride test results (> 60 mEq/L) were recruited for the trial. After matching on age and sex, 10 patients were randomly assigned to the treatment group and 9 patients to the placebo group. Primary outcomes were FEV1, FVC, forced expiratory flow at 25 to 75% of vital capacity, and peak flow; secondary outcomes were body mass index, 6-min walk distance, and self-reported cough frequency, mucus production/viscosity/color, wellness, improvement, and stamina. INTERVENTIONS AND ANALYSIS: Treatment was buffered GSH, and placebo was sodium chloride with a hint of quinine. The total daily dose of buffered GSH was approximately 66 mg/kg of body weight, and the total daily dose of placebo was approximately 15 mg/kg of body weight (quinine, 25 to 30 microg/kg). Doses were distributed across four inhalation sessions per day and spaced 3- to 4-h apart. General linear mixed models were used to analyze the data. The final sample size was nine subjects in the treatment group and seven subjects in the placebo group. Mean change for peak flow was -6.5 L/min for the placebo group and +33.7 L/min for the GSH group (p = 0.04), and self-reported average improvement on a scale from 1 to 5 (1 being much worse and 5 being much better) was 2.8 for placebo and 4.7 for GSH (p = 0.004). Of the 13 primary and secondary outcomes examined, 11 outcomes favored the treatment group over the placebo group (p = 0.002), indicating a general tendency of improvement in the GSH group. No adverse events in the treatment group were noted. This pilot study indicates the promise of nebulized buffered GSH to ameliorate CF disease, and longer, larger, and improved studies of inhaled GSH are warranted.

Glucose intolerance in cystic fibrosis patients.

Diabetes mellitus has evolved as a complication because of increased longevity of patients with cystic fibrosis (CF). CF-related diabetes (CFRD) is associated with increased morbidity and mortality, therefore, prompt diagnosis and aggressive management are important. The prevalence of CFRD increases with age with an age-dependent incidence rate of 5% per year; at 30 years 50% of patients are diabetic. CFRD develops insidiously. Screening by measurements of fasting, random plasma glucose or glycated haemoglobin A(1c), alone or in combination, do not reliably identify CFRD as compared with the 2-hour plasma glucose value measured during an oral glucose tolerance test. Reasons for the development of CFRD are not fully understood. Generally, patients are characterised by the presence of a class I, II or III CF mutation, exocrine pancreatic insufficiency, impaired and delayed insulin secretion, impaired glucagon secretion, normal insulin sensitivity and an increased insulin clearance rate. One can speculate that for endocrine dysfunction to deteriorate from normal to impaired glucose tolerance and then to CFRD, there must be an additional diabetes mellitus-related genetic defect.CFRD leads to deterioration of overall clinical CF status but insulin therapy can revert this. Late diabetic complications may develop as in other types of diabetes although macrovascular complications are rare. CFRD patients have an increased mortality compared to non-diabetic CF patients. Insulin therapy is the preferred treatment.

Counseling and screening for cystic fibrosis in patients with congenital bilateral absence of the vas deferens: Patient perceptions

Congenital bilateral absence of the vas deferens (CBAVD) occurs in approximately 1.3% of infertile males and is thought to be, in most cases, a primarily genital form of cystic fibrosis (CF). Fourteen males with CBAVD considering microsurgical sperm aspiration from the epididymis (MESA) and in vitro fertilization were seen for genetic counseling and screening for CF. To retrospectively evaluate these patients' perceptions of the counseling and screening information, we conducted structured telephone interviews to assess their recall of information about CF and its impact on their health concerns and reproductive plans. We found that, as the health implications of CF are abstract and not as important to patients as the diagnosis of CBAVD itself, patients tend to view their CF status primarily in terms of their reproductive potential. Retrospective analysis afforded us an opportunity to identify the psychosocial issues of most concern to this unique patient population.

Prognostic implications of fetal echogenic bowel

Summary Background An increased frequency of hyperechogenic bowel on ultrasound has been reported in fetuses with cystic fibrosis (CF) and trisomy-21. However, the diagnostic application of this observation has been hampered by the absence of a means of measuring echogenicity. Methods We devised an ultrasonic grading system in which echogenicity was quantified by linear gain reduction and comparison with fetal iliac crest. From 7400 second-trimester ultrasound referrals, 145 patients were identified as having a fetus with abnormally echogenic bowel. They were offered genetic counselling, parental and (if appropriate) CF carrier testing, and amniocentesis for karyotype and CF status if parents were informative. Follow-up was to 4 months of age. Findings Of 40 fetuses with mild increase in bowel sonodensity (grade 1), none had CF or aneuploidy. Of 81 patients identified with a moderate increase (grade 2), 2 had trisomy 21 and 2 had CF. And of 24 pregnancies with a pronounced increase (grade 3), 5 had CF and 6 had trisomy-21. Interpretation Parental CF carrier testing and amniocentesis to identify aneuploidy or fetal CF status has a high positive ascertainment rate in fetuses with echogenic bowel grades 2 and 3.