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The impact of evolving treatment regimens, airway clearance strategies, and antibiotic combinations on the incidence and prevalence of respiratory infection in cystic fibrosis (CF) in children and adolescents remains unclear. The incidence, prevalence, and prescription trends from 2002 to 2019 with 18,339 airway samples were analysed. Staphylococcus aureus [- 3.86% (95% CI - 5.28-2.43)] showed the largest annual decline in incidence, followed by Haemophilus influenzae [- 3.46% (95% CI - 4.95-1.96)] and Pseudomonas aeruginosa [- 2.80%95% CI (- 4.26-1.34)]. Non-tuberculous mycobacteria and Burkholderia cepacia showed a non-significant increase in incidence. A similar pattern of change in prevalence was observed. No change in trend was observed in infants < 2 years of age. The mean age of the first isolation of S. aureus (p < 0.001), P. aeruginosa (p < 0.001), H. influenza (p < 0.001), Serratia marcescens (p = 0.006) and Aspergillus fumigatus (p = 0.02) have increased. Nebulised amikacin (+ 3.09 ± 2.24 prescription/year, p = 0.003) and colistin (+ 1.95 ± 0.3 prescriptions/year, p = 0.032) were increasingly prescribed, while tobramycin (- 8.46 ± 4.7 prescriptions/year, p < 0.001) showed a decrease in prescription. Dornase alfa and hypertonic saline nebulisation prescription increased by 16.74 ± 4.1 prescriptions/year and 24 ± 4.6 prescriptions/year (p < 0.001). There is a shift in CF among respiratory pathogens and prescriptions which reflects the evolution of cystic fibrosis treatment strategies over time., (© 2024. Crown.)

Highly effective modulator therapies (HEMTs) have revolutionised the management approach of most patients living with cystic fibrosis (CF) who have access to these therapies. Clinical trials have reported significant improvements across multiorgan systems, with patients surviving longer. However, there are accumulating case reports and observational data describing various adverse events following initiation of HEMTs including drug-to-drug interactions, drug induced liver injury, Stevens-Johnson syndrome, and neurocognitive symptoms including psychosis and depression, which have required discontinuation of therapy. Current clinical trials are assessing efficacy in younger patients with CF, yet long-term studies are also required to better understand the safety profile in the real-world setting across all ages and the impact of HEMT dose alteration or discontinuation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2023. Published by Elsevier Ltd. All rights reserved.)

Background: Respiratory infections caused by Staphylococcus aureus and Pseudomonas aeruginosa are a major concern for cystic fibrosis (CF) patients due to increasing antibiotic resistance. Bacteriophages, which are viruses that selectively target and kill bacteria, are being studied as an alternative treatment for these infections. This systematic review evaluates the safety and effectiveness of bacteriophages for the treatment of CF-related infections caused by S. aureus and/or P. aeruginosa. We conducted a search for original, published articles in the English language up to March 2023. Studies that administered bacteriophages via intravenous, nebulised, inhaled, or intranasal routes were included, with no comparators required. In vitro and in vivo studies were eligible for inclusion, and only animal in vivo studies that utilised a CF transmembrane conductance regulator (CFTR) animal model were included. Bacteriophage treatment resulted in a decrease in bacterial load in both humans and animals infected with P. aeruginosa. Complete eradication of P. aeruginosa was only observed in one human subject. Additionally, there was a reduction in biofilm, improvement in resistance profile, and reduced pulmonary exacerbations in individual case reports. Evidence suggests that bacteriophage therapy may be a promising treatment option for CF-related infections caused by P. aeruginosa and S. aureus. However, larger and more robust trials are needed to establish its safety and efficacy and create necessary evidence for global legislative frameworks., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

This review summarises the experiences of young children and their families living with CF during the first five years of life following NBS diagnosis, as well as the options of psychosocial support available to them. We present strategies embedded within routine CF care that focus on prevention, screening, and intervention for psychosocial health and wellbeing that constitute essential components of multidisciplinary care in infancy and early childhood., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Haemoptysis occurs in up to 25 % of young people with Cystic fibrosis (CF) [1]. We undertook a literature review and described the management approach to haemoptysis in CF between 2010 and 2020 at an Australian tertiary paediatric centre, The Children's Hospital Westmead, Sydney, New South Wales, using a retrospective review of the medical records which identified 67 episodes. Sixty episodes met inclusion criteria, including 31 patients. Using the US CF Foundation guidelines, episodes were classified as scant (53.3 %), moderate (38.3 %) or massive (8.3 %). Fifty-two percent of patients were female, mean age at presentation was 15.4 years (SD+/- 2.4) and 58 % were homozygous for the Fdel508 genotype. Twelve episodes (9 patients) required bronchial artery embolization (BAE). BAE was used in all cases of massive haemoptysis 5/5 (100 %), 6/23 (22 %) episodes of moderate and 1/32 (3 %) episode of scant haemoptysis as an elective procedure for recurrent haemoptysis. Our literature review and institutional experience highlights the need for up-to-date management guidelines in the management of haemoptysis in Cystic Fibrosis. Based on our experience, we provide a proposed algorithm to help guide the management of haemoptysis in CF., Competing Interests: Conflict of Interest The authors have no conflict of interest to disclose., (Copyright © 2022. Published by Elsevier Ltd.)

Introduction: Cystic fibrosis (CF) is a multisystem condition that is complicated by recurrent pulmonary infections requiring aggressive antibiotic treatment. This predisposes the patient to complications such as sensorineural hearing loss, renal impairment, hypersensitivity and the development of antibiotic resistance. Pseudomonas aeruginosa is one of the more common organisms which cause recurrent infections and result in greater morbidity and mortality in people living with CF. Bacteriophages have been identified as a potential alternative or adjunct to antibiotics. We hypothesise that bacteriophage therapy is a safe and well-tolerated treatment in children with CF infected with P. aeruginosa infection in their airways., Methods: This single-arm, open-labelled, non-randomised trial will run for a maximum period of 36 months with up to 10 participants. Adolescents (≥12 years and <18 years of age) who continue to shed P.aeruginosa (within 3 months of enrolment) despite undergoing eradication therapy previously, will be considered for this trial. Non-genetically modified bacteriophages that have demonstrated obligate lytic activity against each of the study participants' P. aeruginosa strains will be selected and prepared according to a combination of established protocols (isolation, purification, sterility testing and packaging) to achieve close to good manufacturing practice recommendations. The selected bacteriophage will be administered endo-bronchially first under direct vision, followed by two times a day nebulisation for 7 days in addition to standard CF treatment (intravenous antibiotics, physiotherapy to be completed as inpatient for 10-14 days). Safety and tolerability will be defined as the absence of (1) fever above 38.5°C occurring within 1 hour of the administration of the nebulised bacteriophage, (2) a 10% decline in spirometry (forced expiratory volume in 1 s %) measured preadministration and postadministration of the first dose of nebulised bacteriophage. Clinical reviews including repeat sputum cultures and spirometry will be performed at 3, 6, 9 and 12 months following bacteriophage treatment., Ethics and Dissemination: Our clinical trial is conducted in accordance with (1) good clinical practice, (2) Australian legislation, (3) National Health and Medical Research Council guidelines for the ethical conduct of research., Trial Registration Number: Australia and New Zealand Clinical Trial Registry (ACTRN12622000767707)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Children with cystic fibrosis (CF) pulmonary exacerbations receive IV tobramycin therapy, with dosing guided by either log-linear regression (LLR) or Bayesian forecasting (BF)., Objectives: To compare clinical and performance outcomes for LLR and BF., Patients and Methods: A quasi-experimental intervention study was conducted at a tertiary children's hospital. Electronic medical records were extracted (from January 2015 to September 2021) to establish a database consisting of pre-intervention (LLR) and post-intervention (BF) patient admissions and relevant outcomes. All consecutive patients treated with IV tobramycin for CF pulmonary exacerbations guided by either LLR or BF were eligible., Results: A total of 376 hospital admissions (LLR = 248, BF = 128) for CF pulmonary exacerbations were included. Patient demographics were similar between cohorts. There were no significant differences found in overall hospital length of stay, rates of re-admission within 1 month of discharge or change in forced expiratory volume in the first second (Δ FEV1) at the end of tobramycin treatment. Patients treated with LLR on average had twice the number of therapeutic drug monitoring (TDM) blood samples collected during a single hospital admission. The timeframe for blood sampling was more flexible with BF, with TDM samples collected up to 16 h post-tobramycin dose compared with 10 h for LLR. The tobramycin AUC0-24 target of ≥100 mg/L·h was more frequently attained using BF (72%; 92/128) compared with LLR (50%; 124/248) (P < 0.001). Incidence of acute kidney injury was rare in both groups., Conclusions: LLR and BF result in comparable clinical outcomes. However, BF can significantly reduce the number of blood collections required during each admission, improve dosing accuracy, and provide more reliable target concentration attainment in CF children., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In developed countries, it is projected that there will be a 70% increase in the number of adults living with Cystic Fibrosis (CF) between 2010 and 2025. This shift in demographics highlights the importance of high-quality transition programmes with developmentally appropriate integrated health care services as the individual moves through adolescence to adulthood. Adolescents living with CF face additional and unique challenges that may have long-term impacts on their health, quality of life and life-expectancy. CF specific issues around socially challenging symptoms, body image, reproductive health and treatment burden differentiate people with CF from their peers and require clinicians to identify and address these issues during the transition process. This review provides an overview of the health, developmental and psychosocial challenges faced by individuals with CF, their guardians and health care teams considering the fundamental components and tools that are required to build a transition programme that can be tailored to suit individual CF clinics., (Crown Copyright © 2020. Published by Elsevier Ltd. All rights reserved.)

This article advocates for a universal approach to infection control measures in cystic fibrosis. The central tenets of infection control include hand hygiene, contact precautions, regular microbiological surveillance and adopting inpatient, outpatient, domestic and social practices to minimise acquisition of common CF pathogens. Infection control measures should be proactive and prospective, assuming all patients harbour aggressive pathogens, and not relying on past culture results. The challenges of implementing these policies include cost, equipment, education, consistency, meticulousness all whilst balancing additional procedures to a busy clinical workload., (Crown Copyright © 2020. Published by Elsevier Ltd. All rights reserved.)

Background: Clinical and prognostic value of preschool Multiple Breath Washout (MBW) remains unclear., Methods: Initial MBW results (Exhalyzer® D, EcoMedics AG) in preschool Cystic Fibrosis (CF) subjects (age 2-6 years) at a time of clinical stability were compared to (1) concurrent clinical status measures and (2) later spirometry outcomes. Abnormal Lung Clearance Index (LCI) was defined using published reference data (ULN for LCI 8.0)., Results: LCI was abnormal in 56% (28/50), with mean (SD) LCI 8.61(1.85) at age 4.71(1.3) years. Abnormal LCI was associated with higher dornase alfa use, previous positive bacterial cultures and pF508.del homozygous genotype. Later spirometry (n = 44; mean (SD) 2.3(0.5) years after MBW) demonstrated that abnormal initial preschool LCI was a strong predictor of lower later spirometry outcomes., Conclusion: Abnormal preschool LCI was associated with concurrent measures of clinical status and later spirometry deficits, suggesting early prognostic utility of MBW testing in this age range., (Copyright © 2019. Published by Elsevier B.V.)

Non-tuberculous mycobacterial (NTM) (especially M. abscessus complex) infections pose a considerable challenge in the management of lung disease in patients with cystic fibrosis (CF). The apparent increase in prevalence is likely multifactorial. Emergent evidence of patient-to-patient transmission and isolation of highly resistant strains is a concern for all CF centers around the world. Treatment is often long and burdensome with multiple agents. Treatment side effects are frequent and can cause significant morbidity. Although consensus guidelines provide some direction, many units are faced with the challenges of: finding drug combinations for highly resistant strains; dealing with interruptions of treatment; discussing additional facilitating procedures in the form of gastrostomy and long-term vascular access devices; as well as supporting families emotionally and psychologically through the process., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Pseudomonas aeruginosa is a common bacterial pathogen in the evolution of bronchiectasis in cystic fibrosis. The appearance of resistant strains of pseudomonas is increasing with the earlier and more liberal use of a range of anti-pseudomonal antibiotics for the treatment of bacterial chest infections. The rationale for treatment and potential benefits of aggressive treatment of resistant strains of Pseudomonas aeruginosa from early in life are discussed., (Copyright © 2017. Published by Elsevier Ltd.)

Objective: To describe the clinical course of children who have intermediate sweat chloride values on initial screening for cystic fibrosis (CF)., Study Design: We performed a retrospective review of children with intermediate sweat chloride values (raised immunoreactive trypsinogen/1 copy of p.F508del CF mutation on newborn screening (NBS)/sweat chloride value of 30-59 mmol/L) presenting to The Children's Hospital at Westmead over 15 years. Patients with an intermediate sweat chloride evolving to a formal diagnosis of CF (termed "delayed CF") were matched (2:1) with NBS positive patients with CF (termed "NBS positive CF"). Clinical outcomes were compared., Results: Fourteen of 29 (48%, 95% CI 0.3-0.66) patients with intermediate sweat chloride value evolved to a diagnosis of CF and were matched with 28 NBS positive patients with CF. Delayed CF had less pancreatic insufficiency (OR 0.06, 95% CI 0.01-0.44, P = .006), less colonization with nonmucoid Pseudomonas aeruginosa (OR 0.04, 95% CI 0.01-0.38, P = .005), milder obstructive lung disease (forced expiratory volume in 1 second/forced vital capacity ratio), and overall disease severity (Shwachman scores) at 10 years (mean difference 5.93, 95% CI 0.39-11.46, P = .04; mean difference 4.72, 95% CI 0.9-8.53, P = .015, respectively). Nutritional outcomes were better at 2 years for delayed CF but did not persist to later ages., Conclusions: In this cohort, approximately one-half of infants with intermediate sweat chloride value were later diagnosed with CF. The clinical course of delayed CF was milder in some aspects compared with NBS positive CF. These results emphasize the importance of ongoing follow-up of infants with intermediate sweat chloride values., (Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.)

Rationale: A decrease in diffusion capacity for carbon monoxide (DLCO) after exercise has been reported in healthy adults. There is limited information for post-exercise DLCO available in children either in health or in disease., Objectives: To evaluate (1) reproducibility of DLCO measures in children, (2) differences in DLCO between elite athletic swimmers (AS), stable cystic fibrosis patients (CF), and healthy controls (Con) at rest; and (3) after a maximal treadmill exercise test., Methods: Participants performed spirometry and DLCO at baseline, a maximal treadmill exercise test and repeated DLCO measures for 2 hr after cessation of exercise., Results: The mean (SD) co-efficient of variation between baseline DLCO tests was 2.49% (1.86%). In girls, the mean baseline DLCO (ml/min/mmHg) was 18.61 (4.15) in CF, 22.32 (4.79) in controls and 27.18 (5.33) in AS. In boys: 23.68 (5.31) in CF, 28.09 (9.95) in controls and 37.75 (9.46) in AS. Baseline DLCO was significantly higher in AS than in CF patients (P < 0.01). In girls post-exercise, the greatest mean decrease in DLCO from baseline was -7.50% to -12.83% and in boys -6.92% to -17.71%. The decline in DLCO was less important in the athletes than the other groups (P < 0.05)., Conclusions: DLCO is highly repeatable in children. AS have an increased DLCO at rest compared to both children with CF and controls. There is a decline from baseline to post-exercise DLCO and while there are disease-specific differences, the general pattern of change in DLCO measures after exercise is similar in children to adults., (© 2013 Wiley Periodicals, Inc.)

Objective: To identify the incidence and outcomes of cholestasis and meconium ileus (MI) in infants with cystic fibrosis (CF)., Design: Retrospective cohort study., Setting: Single-centre study., Patients: From January 1986 to December 2011, 401 infants with CF (69 with MI) presented to our centre., Main Outcome Measurements: (1) incidence of cholestasis, (2) identification of risk factors for cholestasis, (3) association between the presence of cholestasis and MI and the development of clinically significant CF-associated liver disease (CFLD) defined as multilobular cirrhosis with portal hypertension., Results: Cholestasis occurred in 23 of 401 infants (5.7%). There was a significantly higher incidence of cholestasis in infants with MI (27.1%) compared to those without MI (1.2%) (p<0.001). Infants with MI had a 30.36-fold increased risk of developing cholestasis compared to those without MI (p<0.001). Cholestasis resolved in all children, at a median (range) age of 9.2 (0.8-53.2) months in the MI group and 10.2 (2.0-19.4) months in the non-MI group. The majority of cholestatic infants (87.0%) and infants with MI (92.8%) did not develop clinically significant CFLD, not significantly different than either the 93.9% of non-cholestatic infants nor the 93.7% infants without MI., Conclusions: Cholestasis is an uncommon condition in CF affecting only 5.7% of the screened newborn CF population. The greatest risk factor for developing cholestasis is the presence of MI. However, the presence of MI appears not to be associated with the development of CFLD. An effect of neonatal cholestasis on the development of CFLD cannot be excluded by this study.

The survival of patients with cystic fibrosis (CF) has progressively increased over recent decades, largely attributable to early diagnosis through newborn screening and advances in nutritional and respiratory care. As the life expectancy of patients with CF has improved, non-respiratory complications such as liver disease have become increasingly recognized. Biochemical derangements of liver enzymes in CF are common and may be attributed to a number of specific hepatobiliary abnormalities. Among them, Cystic Fibrosis-associated Liver Disease (CFLD) is clinically the most significant hepatic complication and is believed to have a significant impact on morbidity and mortality. However, there remains much conjecture about the extent of the adverse prognostic implications that a diagnosis of CFLD has on clinical outcomes. The purpose of this review is to give an overview of the current knowledge regarding liver disease in children with CF., (Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.)

There is comparatively little data on diffusion capacity in children during exercise. With the advent of improved technology, there is an increasing interest in exercise testing of children in order to predict the evolution of lung disease. In addition to the standard measure of exercise capacity, the VO(2max), interest is evolving in the consequences of alterations in diffusion capacity which may be unmasked with exercise. This review will consider what is known about diffusion capacity with exercise in children with well documented lung disease in the form of cystic fibrosis, healthy controls and swimmers as elite athletes with the largest lung volumes., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Cystic fibrosis is a life-limiting condition which is readily diagnosed in the vast majority of cases on newborn screening [NBS]. A diagnosis made on newborn screening translates into earlier initiation of therapies, improved growth, better lung function into the adult years and culminates in better survival., (Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.)

Background: Newborn screening (NBS) for cystic fibrosis (CF) is associated with improved early nutritional outcomes and improved spirometry in children. The aim of this study was to determine whether early diagnosis and treatment of CF with NBS in New South Wales in 1981 led to better clinical outcomes and survival into early adulthood., Methods: Retrospective observational study comprising two original cohorts born in the 3 years before ('non-screened cohort', n=57) and after ('screened'; n=60) the introduction of NBS. Patient records were assessed at transfer from paediatric to adult care by age 19 years and survival was documented to age 25 years., Results: Non-screened patients (n=38) when compared with screened patients (n=41) had a higher rate and lower age of Pseudomonas aeruginosa acquisition at age 18 years (p ≤ 0.01). Height, weight and body mass index (BMI) z scores (all p<0.01) and forced expiratory volume in 1 s (FEV(1))% were better in the screened group (n=41) (difference: 16.7 ± 6.4%; p=0.01) compared to non-screened (n=38) subjects on transfer to adult care. Each 1% increase in FEV(1)% was associated with a 3% (95% CI 1% to 5%; p=0.001) decrease in risk of death and each 1.0 kg/m(2) increase in BMI contributed to a 44% (95% CI 31% to 55%; p<0.001) decrease in risk of death. This accumulated in a significant survival difference at age 25 years (25 vs 13 deaths or lung transplants; p=0.01)., Conclusion: NBS for CF leads to better lung function, nutritional status and improved survival in screened patients in early adulthood.

Objective: Although dornase alfa is a widely used, aerosolized, mucolytic agent in patients with cystic fibrosis (CF), its efficacy in relation to the timing of physiotherapy has not been tested. We sought to determine whether dornase alfa is more efficacious when it is administered 30 minutes before versus 30 minutes after physiotherapy/positive expiratory pressure (PEP) therapy in clinically stable children., Methods: Using a crossover, randomized, double-blind, and placebo-controlled trial, we undertook a 6-week study of the efficacy of dornase alfa in relation to the timing of physiotherapy at home. There were 2 treatment orders. Dornase alfa before + placebo after physiotherapy/PEP for 2 weeks was followed by a 2-week washout and then the reverse order placebo before and dornase alfa after physiotherapy/PEP for the final 2 weeks. The second treatment order reversed the placebo and dornase alfa therapy for the first and last 2-week blocks. The main outcome measures used included the change in predicted percentage of forced expiratory volume in 1 second (FEV1), a composite quality of well-being score (QWB), and a measure of aerobic fitness (maximal oxygen consumption, [VO2max]), determined using shuttle testing., Results: Fifty-two patients who had CF (27 female) with mild to moderate suppurative lung disease, were a mean +/- SD age of 10.7 +/- 3.2 years, had Shwachman scores of 86 +/- 11.8, had predicted FEV1 of 83% +/- 18%, had quality of well-being score of 0.76 +/- 0.08, and had VO2max of 42.6 +/- 6.3 ml/kg per min were enrolled. Fifty patients completed the study. Intention-to-treat analysis was used. Nonsignificant mean (95% confidence interval) differences in FEV1 (0.02 L [-0.05 to 0.10]), VO2max (-0.75 ml/kg per min [-1.85 to 0.35]), and QWB (0.005 [-0.94 to 0.0028]) for dornase alfa after physiotherapy/PEP were detected. A post hoc analysis showed that patients who were colonized persistently with Pseudomonas aeruginosa had a significantly greater improvement in FEV1 (0.12 L [0.23 to 0.01] vs -0.04 L [0.05 to -0.13]) when dornase alfa was administered after physiotherapy/PEP., Conclusions: Dornase alfa is equally efficacious when delivered before or after physiotherapy/PEP in patients with CF. Patients who are colonized persistently with P aeruginosa may derive more improvement in FEV1 when dornase alfa is delivered after physiotherapy/PEP.

Allergic bronchopulmonary aspergillosis (ABPA) is an uncommon condition which may complicate asthma and cystic fibrosis; it is seldom considered life-threatening. We report a well 8-year-old boy with cystic fibrosis and normal lung function who progressed to respiratory failure over several days, attributable to ABPA. He recovered with non-invasive ventilation and oral corticosteroid and antifungal medications, regaining normal lung function within 2 months. To our knowledge, such an acute severe presentation of ABPA in a previously well child has not been reported before.

While several studies have demonstrated essential fatty acid (EFA) deficiency in plasma and tissue lipids of cystic fibrosis (CF) patients, the reasons for this deficiency are not well established. It is believed that reduced EFA intake, malabsorption of fat, altered desaturase/lipase activity and defective cystic fibrosis transmembrane conductance regulator (CFTR) altering utilisation of EFA in epithelial cells contribute to the development of EFA deficiency in CF. It is likely that increased metabolism of arachidonic acid to eicosanoids such as leukotrienes, thromboxane and prostaglandins may also be a contributing factor. Evidence is presented that elevated oxidative damage to EFA and impaired antioxidant defences, in particular vitamin E, may contribute to the development of EFA deficiency in CF. Furthermore, antioxidant supplementation in CF may improve EFA status.

Background: Oxidative stress, as measured by 8-iso-prostaglandin F(2)(alpha) (8-iso-PGF(2)(alpha)), and depleted antioxidant defenses were shown in stable cystic fibrosis (CF) patients. The plasma fatty acid status of CF patients was linked to oxidative stress after respiratory exacerbations., Objective: We examined changes in plasma 8-iso-PGF(2)(alpha), antioxidant defenses, plasma fatty acid status, and clinical markers resulting from short-term antioxidant supplementation., Design: Forty-six CF patients were randomly assigned to either group A [low dose of supplement (10 mg vitamin E and 500 micro g vitamin A)] or group B [high dose of supplement (200 mg vitamin E, 300 mg vitamin C, 25 mg beta-carotene, 90 micro g Se, and 500 micro g vitamin A)]. Plasma concentrations of 8-iso-PGF(2)(alpha), vitamins E and C, beta-carotene, zinc, selenium, and copper; plasma fatty acid composition; erythrocyte glutathione peroxidase (EC 1.11.1.9) and superoxide dismutase (EC 1.15.1.1) activities; lung function; and dietary intake were measured before and after 8 wk of supplementation., Results: Antioxidant defenses in group B improved, whereas those in group A did not: in groups B and A, the mean (+/- SEM) changes (Delta) in vitamin E were 10.6 +/- 1.5 and -1.9 +/- 0.9 micro mol/L, respectively (P < 0.001), (Delta)beta-carotene were 0.1 +/- 0.04 and -0.01 +/- 0.02 micro mol/L, respectively (P = 0.007), (Delta)selenium were 0.51 +/- 0.10 and -0.09 +/- 0.04 micro mol/L, respectively (P < 0.001), and (Delta)glutathione peroxidase activity were 1.3 +/- 0.3 and -0.3 +/- 0.6 U/g hemoglobin, respectively (P = 0.016). There were no significant differences between the groups in Delta8-iso-PGF(2)(alpha), (Delta)vitamin C, (Delta)fatty acid composition, (Delta)superoxide dismutase activity, (Delta)lung function, or (Delta)white cell count. Within group B, (Delta)beta-carotene correlated with (Delta)percentage of forced vital capacity (r = 0.586, P = 0.005), (Delta)selenium correlated with (Delta)percentage of forced expiratory volume in 1 s (r = 0.440, P = 0.046), and (Delta)plasma fatty acid concentrations correlated with (Delta)percentage of forced expiratory volume in 1 s (r = 0.583, P = 0.006) and Delta8-iso-PGF(2)(alpha) (r = 0.538, P = 0.010)., Conclusions: Whereas increased beta-carotene, selenium, and fatty acid concentrations are linked to improved lung function, increased plasma fatty acid concentrations are linked to oxidative stress. If oxidative stress is deemed to be important to the clinical outcome of CF patients, means of reducing oxidative stress while maintaining a high-fat, high-energy diet must be investigated.

Background: Oxidative stress and depleted antioxidant defenses occur in stable cystic fibrosis patients. During acute infection, the balance between oxidants and antioxidants may be further disturbed., Objective: We examined the oxidative stress during acute infection in cystic fibrosis patients by measuring 8-iso-prostaglandin F(2 alpha) (8-iso-PGF(2 alpha)) and antioxidant defenses in relation to dietary intake, fatty acid status, immune function, and clinical status., Design: Plasma concentrations of total 8-iso-PGF(2 alpha), vitamins E and C, beta-carotene, zinc, selenium, and copper; plasma fatty acid compositions; erythrocyte glutathione concentrations; glutathione peroxidase and superoxide dismutase activity; sputum glutathione and 8-iso-PGF(2 alpha) concentrations; lung function; clinical symptoms; and dietary intake were measured in 15 cystic fibrosis patients before and after 10-14 d of intravenous antibiotic treatment for a pulmonary exacerbation., Results: After treatment, respiratory status improved (percentage of forced expiratory volume in 1 s: 60 +/- 6% at baseline compared with 74 +/- 7% after treatment, P = 0.01), quality of well-being improved (P = 0.001), and total plasma 8-iso-PGF(2 alpha) concentrations increased from 469 nmol/L at baseline (interquartile range: 373-554 nmol/L) to 565 nmol/L after treatment (interquartile range: 429-689 nmol/L; P = 0.008). Total energy, fat, carbohydrate, and protein intakes per kilogram body weight also increased; however, dietary antioxidant intake was unchanged. Plasma fatty acid concentrations increased after treatment, strongly correlating with plasma 8-iso-PGF(2 alpha) concentrations (r = 0.768, P = 0.001). There were no significant changes in white cell counts or plasma concentrations of vitamins E and C or beta-carotene. Erythrocyte glutathione peroxidase activity was reduced after treatment, whereas there was no significant change in superoxide dismutase activity., Conclusions: Oxidative stress increased after treatment for pulmonary exacerbations and was strongly linked to increased concentrations of plasma fatty acids. Although intravenous antibiotic therapy and physiotherapy improved lung function within 10-14 d of treatment, the biochemical effects of oxidation continued further. Thus, antioxidant intervention during treatment for and recovery from acute infection in cystic fibrosis should be considered.

The present study was designed to compare the clinical course of children diagnosed with cystic fibrosis (CF) in infancy due to the presence of meconium ileus (MI) with children diagnosed by way of a newborn screening programme (non-MI). A matched case-control study design was used. Matching was performed on the basis of sex and date of birth. All children born in New South Wales, Australia after 1980 and who had attended the CF clinic at The Children's Hospital at Westmead since diagnosis were included as possible cases or controls. Parameters pertaining to the clinical course were compared in 39 matched pairs. MI children had a significantly worse pulmonary status. The forced expiratory volume in one second was 16.3 +/- 5.2% higher (p<0.001, n=21 pairs) and the forced vital capacity value 10.5 +/- 4.7%, higher (p<0.05, n=21 pairs) in non-MI children. The difference between the pairs (18.6 +/- 4.4 MI and 20.5 +/- 3.4 non-MI) in the Shwachman chest radiograph score was statistically significant (p<0.05, n=39 pairs). There were no significant differences in any other assessed parameters, such as height, weight, the presence of liver function abnormalities, the frequency of hospitalization or airway microbial colonization. Meconium ileus may be an early indication of a more severe phenotype of cystic fibrosis. This was suggested by the significantly lower pulmonary function found in children with a history of meconium ileus compared to age- and sex-matched children who did not have meconium ileus.

Objective: To examine oxidative stress in CF by measuring 8-iso-PGF2alpha and antioxidant defenses, in relation to dietary intake, immune function and clinical status., Methods: We measured total plasma concentrations of 8-iso-PGF2alpha and dietary antioxidants (vitamin E, vitamin C, beta-carotene), erythrocyte antioxidant enzyme activities (glutathione peroxidase and superoxide dismutase), lung function and dietary intake in 21 CF subjects and 21 healthy age- and gender-matched controls., Results: Total plasma 8-iso-PGF2alpha concentration (median [quartile 1-quartile 3]) was significantly higher in CF subjects compared to controls (214 pg/mL (155-331) vs. 135 pg/mL (101-168), p = 0.001). Neutrophil, monocyte and total white cell counts were elevated in the CF group and these correlated with 8-iso-PGF2alpha concentration. Despite similar dietary intake, lower plasma antioxidant concentrations were observed in the CF group (vitamin E, p < 0.001, vitamin C, p = 0.004, beta-carotene, p = 0.001). 8-iso-PGF2alpha correlated negatively with plasma vitamin E, C and beta-carotene concentrations., Conclusion: Oxidative stress is increased in CF patients, despite normal dietary antioxidant intake. The immune response appears to be a key factor causing oxidative stress. Antioxidant intervention aimed at reducing oxidative stress in CF needs to be assessed.

Objective: To determine whether 4 years of colonization with a novel Australian cluster strain (The 'Hunter' strain) of Burkholderia cepacia (B. cepacia) in cystic fibrosis (CF) patients was associated with more rapid decline in nutritional status and pulmonary function than in non-colonized contemporaries from the same CF clinic., Methodology: A retrospective review of respiratory function and nutritional data from a single multidisciplinary paediatric CF clinic over 4 years (1993-97)., Results: Paired spirometry data for 1993 and 1997 were available in 47 patients without (n = 31) and with B. cepacia (n = 16) colonization (mean (+/- SD) ages in 1993: 12.1 years +/- 4.0 vs 12.6 years +/- 6.5; P = 0.83). Their percentage predicted forced expiratory volume in 1 s (FEV1) (94.2% +/- 16.7 vs 85.9% +/- 21.2; P = 0.19) were not significantly different. The averaged annual fall in FEV1 over 4 years was also not significantly different (3.8% +/- 3.8 vs 3.6% +/- 3.7; P = 0.82). Weight percentile (Wt%), height percentile (Ht%) and percentage age weight for height (%WFH) were not significantly different between groups in 1993. By 1997, Wt% (36.7% +/- 25.1 vs 22.3% +/- 19.6; P = 0.04) and Ht% (42.5% +/- 29.6 vs 17.6% +/- 19.4; P = 0.002) but not %WFH (102% +/- 10.0 vs 106% +/- 11.2; P > 0.10) were lower in subjects with B. cepacia., Conclusions: In adolescent CF patients, colonization with the Hunter strain of B. cepacia was associated with a deterioration in some nutritional parameters but not with an accelerated decline in FEV1 over 4 years. As varying pathogenicity of B. cepacia strains may account for differing rates of pulmonary decline, further assessment of the consequences of colonization with certain strains of B. cepacia in CF is needed.