Probiotic knowledge of adults with cystic fibrosis is limited but is associated with probiotic use: A cross-sectional survey study.

Background: Probiotics are used by people with cystic fibrosis (CF) and other chronic diseases to manage gastrointestinal symptoms. Aim: To describe probiotic knowledge; its relationship with probiotic use, probiotic information sources and factors influencing choice in adults with CF and a general population control group. Methods: A cross-sectional questionnaire study was conducted in adults with CF (n = 205) and Controls (n = 158). Probiotic knowledge was compared between CF and Controls using a knowledge score (maximum 5) based on predefined criteria: (1a) bacteria/microorganism; (1b) live; (2a) administered; (2b) adequate dose and (3) health benefit, using independent samples t-test. Two-way analysis of variance explored knowledge scores between CF and Control and between Ever User and Never User groups. Chi-square and Fisher's exact tests compared knowledge criterion, probiotic sources and influences on probiotic choice between groups. Thematic analysis of open-text responses explored probiotic-related knowledge and influences on probiotic decision making. Results: Knowledge scores (mean ± SD) did not differ between CF (1.70 ± 1.12) and Controls (1.89 ± 0.99), p = 0.13. Probiotic use was associated with knowledge score (p < 0.001). More CF Ever Users than Never Users correctly identified criteria 1a (65% vs. 38%), 1b (16% vs. 0%), 2a (45% vs. 22%) and 3 (73% vs. 42%) (all p < 0.005). CF participants considered 'dairy yoghurt' (69%), 'live cultures' (64%) and 'fermented foods' (37%) as 'all/mostly' probiotic sources. The internet was the commonest source of probiotic-related information. Conclusion: Probiotic knowledge and use were associated in adults with CF. Understanding of probiotic characteristics and sources were limited. Education is needed to help guide patient probiotic decision making.

Probiotic use in adults with cystic fibrosis is common and influenced by gastrointestinal health needs: A cross-sectional survey study.

BACKGROUND: Cystic fibrosis (CF) primarily affects the lung, however, gastrointestinal disorders and symptoms, including dysbiosis, also impact on morbidity and quality of life. There is interest in strategies to modulate the gastrointestinal microbiota, including probiotics, although the evidence remains inadequate to guide practice, and information on use is limited. The present study aimed to characterise probiotic use, beliefs and experiences of adults with CF. METHODS: A cross-sectional questionnaire study was conducted in adults with CF (n = 205) and a general population Control group (n = 158), recruited from Victoria, Australia. Participants were classified as probiotic 'Ever Users' or 'Never Users'. Outcomes included self-reported probiotic use and factors associated with probiotic use, which were analysed using logistic regression analysis. Open-ended questionnaire responses were thematically analysed. RESULTS: In total, 70% of adults with CF had ever used probiotics (supplements and/or foods), comparable to Controls (80%) (p = 0.03). Key reasons for CF probiotic use were gastrointestinal- and antibiotic-related (75%). Most CF Ever Users (73%) did not discuss probiotic use with CF clinicians and 33% were uncertain if probiotics had been helpful. Female gender (odds ratio [OR] = 2.82; 95% confidence interval [CI] = 1.36-5.87; p = 0.005), university-level education (OR = 2.73; 95% CI = 1.24-6.01; p = 0.01) and bloating on antibiotics (OR = 2.14; 95% CI = 1.04-4.40; p = 0.04) were independently associated with probiotic use in CF; as was female gender in Controls (OR = 2.84; 95% CI = 1.20-6.71; p = 0.02). CONCLUSIONS: Probiotics were used by adults with CF for gastrointestinal- and antibiotic-related reasons often without informing clinicians and despite uncertainty about perceived helpfulness. Further research investigating gastrointestinal outcomes of probiotics will inform practice recommendations guiding their use in CF and other chronic diseases.

Lumacaftor/ivacaftor-associated health stabilisation in adults with severe cystic fibrosis.

INTRODUCTION: Lumacaftor/ivacaftor (LUM/IVA) has been shown to improve clinical outcomes in cystic fibrosis (CF) patients homozygous for Phe508del with forced expiratory volume in 1 s (FEV1) % pred >40%. We assessed the clinical utility of LUM/IVA in all eligible adult CF patients with FEV1 % pred <40% treated for at least 1 year under a single-centre managed access programme. METHODS: Following clinical optimisation, eligible patients (n=40) with FEV1 % pred <40% were commenced on LUM/IVA and monitored for tolerance and clinical outcomes, including health service utilisation, pulmonary function, weight and body composition. 24 patients reached 1 year of treatment by the time of evaluation. Six patients discontinued due to adverse events (five for increased airways reactivity) and three underwent lung transplantation. RESULTS: In comparison with the year prior to LUM/IVA commencement, significant reductions (median per year) were observed in the treatment year in the number of pulmonary exacerbations requiring hospitalisation (from 3 to 1.5; p=0.0002), hospitalisation days (from 27 to 17; p=0.0002) and intravenous antibiotic (IVAB) usage days (from 45 to 27; p=0.0007). Mean±sd change in FEV1 % pred was -2.10±1.18% per year in the year prior, with the decline reversed in the year following (+1.45±1.13% per year; p=0.035), although there was significant heterogeneity in individual responses. Mean±sd weight gain at 1 year was 2.5±4.1 kg (p=0.0007), comprising mainly fat mass (mean 2.2 kg). The proportion of patients severely underweight (body mass index <18.5 kg·m-2) decreased from 33% at baseline to 13% at 1 year (p=0.003). CONCLUSION: This real-world evaluation study demonstrated benefits over several clinical domains (infective exacerbations requiring hospitalisation, IVABs, pulmonary function decline and nutritional parameters) in CF patients with severe lung disease.

Body composition and weight changes after ivacaftor treatment in adults with cystic fibrosis carrying the G551 D cystic fibrosis transmembrane conductance regulator mutation: A double-blind, placebo-controlled, randomized, crossover study with open-label extension.

OBJECTIVES: In patients with cystic fibrosis (CF) who carry the G551D mutation, treatment with ivacaftor improves lung function and weight; however, short- and long-term impacts on body composition have not been well studied. METHODS: Twenty adults with CF carrying the G551D mutation (mean ± standard deviation body mass index [BMI] 23.3 ± 4.3 kg/m2) were recruited for a single-center, double-blind, placebo-controlled, 28-d, crossover study of ivacaftor, followed by an open-label extension (OLE) for 5 mo. Eleven patients underwent measurements 2 y later. The study variables included weight, BMI, and body composition (including fat-free mass [FFM] and fat mass). RESULTS: After 28 d of treatment with ivacaftor, weight increased by 1.1 ± 1.3 kg, BMI by 0.4 ± 0.5 kg/m2, and FFM by 1.1 ± 1.2 kg (all P < .005) with no change in fat mass. Differences between 28-d changes on ivacaftor and placebo were not statistically significant. In the following 5 mo of the OLE, there were significant increases in weight (1.2 ± 1.9 kg; P < .05) and fat mass (1.5 ± 1.9 kg; P < .01), but not in FFM. Between baseline and the end of the OLE, the total weight gain was 2.5 ± 2.4 kg (P < .005), comprised of 0.9 ± 1.5 kg FFM (P < .05) and 1.6 ± 1.8 kg fat mass (P < .005). For the 11 participants who were followed for a further 2 y, no further changes in mean weight, BMI, or body composition parameters between 6 mo and 2 y later were observed. CONCLUSIONS: Small gains were seen in FFM in the first month of ivacaftor treatment. Weight, BMI, and fat-mass gains in the first 6 mo on ivacaftor plateaued by 2.5 y. The metabolic and clinical consequences of weight and fat-mass gains remain to be determined.

Highlights from the nutrition guidelines for cystic fibrosis in Australia and New Zealand.

Optimal nutrition care is important in the management of cystic fibrosis (CF). This paper summarises the '2017 Nutrition Guidelines for Cystic Fibrosis in Australia and New Zealand (NZ)'. CF dietitians formulated 68 practice questions which were used to guide a systematic literature search and review of the evidence for nutrition in CF. Identified papers underwent quality and evidence assessment using the American Dietetic Association quality criteria checklist and the National Health and Medical Research Council of Australia (NHMRC) rankings. Evidence statements, graded recommendations and practice points were developed covering core nutrition topics (assessment and nutrition interventions including oral, enteral and micronutrient supplementation); nutrition-related co-morbidities (including pancreatic insufficiency, CF-related diabetes, bone health and distal intestinal obstruction syndrome); and key new topic areas (genetic modulator therapies, overweight/obesity and complementary therapies). This paper showcases highlights from the guidelines, focussing on new topic areas and geographic and climate considerations for vitamin D, salt and hydration.

Predictive energy equations are inaccurate for determining energy expenditure in adult burn injury: a retrospective observational study.

BACKGROUND: Severe burn injuries are associated with hypermetabolism. This study aimed to compare the measured energy expenditure (mEE) with predicted energy requirements (pERs), and to correlate energy expenditure (EE) with clinical parameters in adults with severe burn injury. METHODS: Data were retrospectively analysed on 29 burn patients (median (interquartile range) age: 46 (28-61) years, % total body surface area burn: 37% (18-46%)) admitted to an intensive care unit. Indirect calorimetry was performed on 1-4 occasions per patient to measure EE. mEE was compared with pER calculated using four prediction equations. Bland-Altman and correlation analyses were performed. RESULTS: Mean ± SD mEE was 9752 ± 2089 kJ/day (143 ± 32% of predicted basal metabolic rate). Bland-Altman analysis demonstrated clinically important overestimation for three of the four prediction equations and wide 95% limits of agreement for all equations. Overestimation of EE was more marked early post-burn. mEE correlated with day post-burn (r = 0.42, P = 0.004) and number of operations prior to first EE measurement (r = 0.34, P = 0.016), but not with % total body surface area (r = 0.02, P = 0.9). CONCLUSIONS: Patients with severe burn injury exhibit hypermetabolism. The observed poor agreement between pER and mEE at an individual level indicates the value of indirect calorimetry in determining EE in burn injury.

The activin A antagonist follistatin inhibits cystic fibrosis-like lung inflammation and pathology.

Cystic fibrosis (CF) is the most common life-limiting genetically acquired respiratory disorder. Patients with CF have thick mucus obstructing the airways leading to recurrent infections, bronchiectasis and neutrophilic airway inflammation culminating in deteriorating lung function. Current management targets airway infection and mucus clearance, but despite recent advances in care, life expectancy is still only 40 years. We investigated whether activin A is elevated in CF lung disease and whether inhibiting activin A with its natural antagonist follistatin retards lung disease progression. We measured serum activin A levels, lung function and nutritional status in CF patients. We studied the effect of activin A on CF lung pathogenesis by treating newborn CF transgenic mice (ß-ENaC) intranasally with the natural activin A antagonist follistatin. Activin A levels were elevated in the serum of adult CF patients, and correlated inversely with lung function and body mass index. Follistatin treatment of newborn ß-ENaC mice, noted for respiratory pathology mimicking human CF, decreased the airway activin A levels and key features of CF lung disease including mucus hypersecretion, airway neutrophilia and levels of mediators that regulate inflammation and chemotaxis. Follistatin treatment also increased body weight and survival of ß-ENaC mice, with no evidence of local or systemic toxicity. Our findings demonstrate that activin A levels are elevated in CF and provide proof-of-concept for the use of the activin A antagonist, follistatin, as a therapeutic in the long-term management of lung disease in CF patients.

Loss of fat-free mass over four years in adult cystic fibrosis is associated with high serum interleukin-6 levels but not tumour necrosis factor-alpha.

BACKGROUND & AIMS: Malnutrition is associated with poorer outcome in cystic fibrosis (CF). This follow-up study aimed to document nutritional status changes, including fat-free mass (FFM), in adults with CF; and to identify predictors of FFM loss. METHODS: Fifty-eight non-transplanted CF adults (mean ± SD forced expiratory volume in one second (FEV1) 63.7 ± 21.4%predicted; mean ± SD age 30.3 ± 7.7years at baseline) were studied at baseline and 3.6 ± 0.4 years later. Body composition was measured using dual-energy X-ray absorptiometry. At follow-up, blood was analysed for interleukin-6 and tumour necrosis factor-α (TNF-α) on three occasions over six months and averaged for each participant. Associations with annual percentage change in FFM (ann%ΔFFM), including cytokines, CF genotype and annual change in FEV1%predicted (annΔFEV1%), were determined. RESULTS: Mean FFM was 49.5 ± 8.8 kg at baseline and 49.6 ± 8.9 kg at follow-up (p = 0.66). Ann%ΔFFM ranged from -2.0 to +3.6%. FEV1%predicted declined by 1.2 ± 2.4% per year. Forty percent of participants had elevated average interleukin-6 levels. Ann%ΔFFM was negatively correlated with interleukin-6 levels (rho -0.34, p = 0.008), but not TNF-α or annΔFEV1%. F508DEL homozygote or heterozygote participants had greater FFM loss than those carrying no F508DEL allele (p = 0.01). CONCLUSION: Higher serum interleukin-6 and presence of the F508DEL mutation, but not TNF-α, were associated with FFM loss in adults with CF.

Fat-free mass depletion in cystic fibrosis: associated with lung disease severity but poorly detected by body mass index.

OBJECTIVE: Malnutrition in cystic fibrosis (CF) is associated with poorer survival, but the determinants of fat-free mass (FFM) depletion are not well-characterized. It is unknown whether routine nutritional indicators, including body mass index (BMI), are adequate for detecting FFM depletion. This study aimed to determine the prevalence of FFM depletion in adults with CF, to compare fat-free mass index (FFMI) with BMI, and to identify predictors of FFM depletion. METHODS: This was a prospective cross-sectional study of 86 adults with CF (19-59 y old). Body composition was assessed using dual-energy X-ray absorptiometry to determine FFMI and BMI. FFMI percentiles and Z-scores were derived from a reference population of 156 healthy adults. FFM depletion was defined as an FFMI below the fifth percentile for age and gender and low BMI as <18.5 kg/m(2). Univariate and multivariate analyses identified predictors of FFMI and FFMI Z-score. RESULTS: Mean FFMIs were 18.3+/-1.9 kg/m(2) in men with CF and 15.8+/-1.1 kg/m(2) in women with CF (P<0.0005). FFM depletion was found in 14% of adults with CF, and low BMI was found in 18.6%. The sensitivity of BMI for detecting FFM depletion was 42%. Forced expiratory volume in 1 s as a percentage of predicted was independently associated with FFMI in women (r=0.62, P<0.0001) and men (r=0.28, P=0.045) and FFMI Z-score (r=0.41, P<0.0001). CONCLUSION: FFM depletion was found in 14% of adults with CF, but was undetectable by BMI in 58% of these patients. These findings, together with the association of FFMI with forced expiratory volume in 1 s predicted, suggest a role for body composition assessment in adult CF care.

Intravenous zoledronate improves bone density in adults with cystic fibrosis (CF).

OBJECTIVE: Reduced bone mineral density (BMD) and increased rates of atraumatic fracture are observed in cystic fibrosis (CF) patients, causing increasing morbidity as this population ages. The study aimed to assess the safety, tolerability and effect on BMD of intravenous zoledronate in adults with CF and osteopaenia. DESIGN: Randomized, double-blind, placebo-controlled clinical trial. SETTING: Adult CF outpatient clinics at two hospitals. PATIENTS: Twenty-two non-transplanted CF patients aged > or = 18 years with a bone densitometry T-score of < -1.5 at one of three sites (lumbar spine, femoral neck, distal forearm) were studied. Participants were randomized to receive either 2 mg zoledronate i.v. (n = 10) or normal saline (placebo, n = 12) every 3 months for 2 years (8 infusions). All participants received calcium and vitamin D supplements twice daily. MEASUREMENTS: Percentage change in areal BMD from baseline. RESULTS: Lumbar spine BMD increased from baseline more with zoledronate than placebo at 6 months (5.35 +/- 0.76 vs. 1.19 +/- 1.20%, P = 0.012), 12 months (6.6 +/- 1.5 vs. 0.35 +/- 1.55%, P = 0.011) and 24 months (6.14 +/- 1.86 vs. 0.44 +/- 0.10, P = 0.021). Femoral neck BMD increased more after zoledronate than placebo at 6 months (3.2 +/- 1.6 vs.-1.43 +/- 0.43%, P = 0.019), 12 months (4.12 +/- 1.8 vs.-1.59 +/- 1.4%, P = 0.024) and 24 months (4.23 +/- 1.3 vs.-2.5 +/- 1.41%, P = 0.0028). Forearm BMD did not change. Zoledronate was associated with flu-like and musculoskeletal side effects, particularly after the first infusion. There were no fractures in either group. CONCLUSION: Intravenous zoledronate was significantly more effective than placebo for increasing BMD in adults with CF and osteopaenia, but side effects limited its tolerability.