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Vitamin D supplementation in patients with cystic fibrosis: A systematic review and meta-analysis.
Juhász, MF, Varannai, O, Németh, D, Szakács, Z, Kiss, S, Izsák, VD, Martonosi, ÁR, Hegyi, P, Párniczky, A
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society. 2021;(5):729-736
Abstract
Despite routine supplementation, vitamin D insufficiency is often seen in cystic fibrosis (CF) patients on account of pancreatic insufficiency. Vitamin D is a crucial component of bone health and affects nearly all cells of the immune system. However, clinical benefits or harms associated with supplementation are poorly documented. In this systematic review, we included randomized controlled trials (RCTs) that compared vitamin D supplementation with placebo (i.e. 'non-increased dose') in CF patients. Analysing the 8 included RCTs, the intervention group had significantly higher serum 25-hydroxyvitamin D (se25OHD) levels, but there were no significant differences found in the quantitative synthesis of clinical outcomes, including bone disease-, respiratory status- and immunological status-related outcomes. Based on our current results, while a higher vitamin D dose elevates se25OHD, it does not seem to influence clinical outcomes. Future RCTs should include outcomes of past studies and apply longer follow-up periods to document long-term patient-important outcomes.
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2.
Antibiotic adjuvant therapy for pulmonary infection in cystic fibrosis.
Hurley, MN, Smith, S, Forrester, DL, Smyth, AR
The Cochrane database of systematic reviews. 2020;(7):CD008037
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Abstract
BACKGROUND Cystic fibrosis is a multi-system disease characterised by the production of thick secretions causing recurrent pulmonary infection, often with unusual bacteria. This leads to lung destruction and eventually death through respiratory failure. There are no antibiotics in development that exert a new mode of action and many of the current antibiotics are ineffective in eradicating the bacteria once chronic infection is established. Antibiotic adjuvants - therapies that act by rendering the organism more susceptible to attack by antibiotics or the host immune system, by rendering it less virulent or killing it by other means, would be a significant therapeutic advance. This is an update of a previously published review. OBJECTIVES To determine if antibiotic adjuvants improve clinical and microbiological outcome of pulmonary infection in people with cystic fibrosis. SEARCH METHODS We searched the Cystic Fibrosis Trials Register which is compiled from database searches, hand searches of appropriate journals and conference proceedings. Date of most recent search: 16 January 2020. We also searched MEDLINE (all years) on 14 February 2019 and ongoing trials registers on 06 April 2020. SELECTION CRITERIA Randomised controlled trials and quasi-randomised controlled trials of a therapy exerting an antibiotic adjuvant mechanism of action compared to placebo or no therapy for people with cystic fibrosis. DATA COLLECTION AND ANALYSIS Two of the authors independently assessed and extracted data from identified trials. MAIN RESULTS We identified 42 trials of which eight (350 participants) that examined antibiotic adjuvant therapies are included. Two further trials are ongoing and five are awaiting classification. The included trials assessed β-carotene (one trial, 24 participants), garlic (one trial, 34 participants), KB001-A (a monoclonal antibody) (two trials, 196 participants), nitric oxide (two trials, 30 participants) and zinc supplementation (two trials, 66 participants). The zinc trials recruited children only, whereas the remaining trials recruited both adults and children. Three trials were located in Europe, one in Asia and four in the USA. Three of the interventions measured our primary outcome of pulmonary exacerbations (β-carotene, mean difference (MD) -8.00 (95% confidence interval (CI) -18.78 to 2.78); KB001-A, risk ratio (RR) 0.25 (95% CI 0.03 to 2.40); zinc supplementation, RR 1.85 (95% CI 0.65 to 5.26). β-carotene and KB001-A may make little or no difference to the number of exacerbations experienced (low-quality evidence); whereas, given the moderate-quality evidence we found that zinc probably makes no difference to this outcome. Respiratory function was measured in all of the included trials. β-carotene and nitric oxide may make little or no difference to forced expiratory volume in one second (FEV1) (low-quality evidence), whilst garlic probably makes little or no difference to FEV1 (moderate-quality evidence). It is uncertain whether zinc or KB001-A improve FEV1 as the certainty of this evidence is very low. Few adverse events were seen across all of the different interventions and the adverse events that were reported were mild or not treatment-related (quality of the evidence ranged from very low to moderate). One of the trials (169 participants) comparing KB001-A and placebo, reported on the time to the next course of antibiotics; results showed there is probably no difference between groups, HR 1.00 (95% CI 0.69 to 1.45) (moderate-quality evidence). Quality of life was only reported in the two KB001-A trials, which demonstrated that there may be little or no difference between KB001-A and placebo (low-quality evidence). Sputum microbiology was measured and reported for the trials of KB001-A and nitric oxide (four trials). There was very low-quality evidence of a numerical reduction in Pseudomonas aeruginosa density with KB001-A, but it was not significant. The two trials looking at the effects of nitric oxide reported significant reductions in Staphylococcus aureus and near-significant reductions in Pseudomonas aeruginosa, but the quality of this evidence is again very low. AUTHORS' CONCLUSIONS We could not identify an antibiotic adjuvant therapy that we could recommend for treating of lung infection in people with cystic fibrosis. The emergence of increasingly resistant bacteria makes the reliance on antibiotics alone challenging for cystic fibrosis teams. There is a need to explore alternative strategies, such as the use of adjuvant therapies. Further research is required to provide future therapeutic options.
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Vitamin D deficiency and its treatment in cystic fibrosis.
Daley, T, Hughan, K, Rayas, M, Kelly, A, Tangpricha, V
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society. 2019;:S66-S73
Abstract
Vitamin D deficiency is a common finding in individuals with cystic fibrosis (CF), despite routine supplementation. Hypovitaminosis D is often the result of fat malabsorption, but other contributors include increased latitude, poor nutritional intake, decreased sun exposure, impaired hydroxylation of vitamin D, and non-adherence to the prescribed vitamin D regimen. Vitamin D is critical for calcium homeostasis and optimal skeletal health, and vitamin D deficiency in CF can lead to skeletal complications of osteopenia and osteoporosis. Over time, our understanding of treatment regimens for vitamin D deficiency in CF has evolved, leading to recommendations for higher doses of vitamin D to achieve target levels of circulating 25-hydroxyvitamin D. There is also some evidence that vitamin D deficiency may have non-skeletal consequences such as an increase in pulmonary exacerbations. The exact mechanisms involved in the non-skeletal complications of vitamin D deficiency are not clearly understood, but may involve the innate immune system. Future clinical studies are needed to help address whether vitamin D has a role in CF beyond skeletal health.
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The Impact of Secondhand Smoke Exposure on Children with Cystic Fibrosis: A Review.
Kopp, BT, Ortega-García, JA, Sadreameli, SC, Wellmerling, J, Cormet-Boyaka, E, Thompson, R, McGrath-Morrow, S, Groner, JA
International journal of environmental research and public health. 2016;(10)
Abstract
Secondhand smoke exposure (SHSe) has multiple adverse effects on lung function and growth, nutrition, and immune function in children; it is increasingly being recognized as an important modifier of disease severity for children with chronic diseases such as cystic fibrosis (CF). This review examines what is known regarding the prevalence of SHSe in CF, with the majority of reviewed studies utilizing parental-reporting of SHSe without an objective biomarker of exposure. A wide range of SHSe is reported in children with CF, but under-reporting is common in studies involving both reported and measured SHSe. Additionally, the impact of SHSe on respiratory and nutritional health is discussed, with potential decreases in long-term lung function, linear growth, and weight gain noted in CF children with SHSe. Immunologic function in children with CF and SHSe remains unknown. The impact of SHSe on cystic fibrosis transmembrane conductance regulator (CFTR) function is also examined, as reduced CFTR function may be a pathophysiologic consequence of SHSe in CF and could modulate therapeutic interventions. Finally, potential interventions for ongoing SHSe are delineated along with recommended future areas of study.
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5.
Antibiotic adjuvant therapy for pulmonary infection in cystic fibrosis.
Hurley, MN, Forrester, DL, Smyth, AR
The Cochrane database of systematic reviews. 2013;(6):CD008037
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Free full text
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Abstract
BACKGROUND Cystic fibrosis is a multi-system disease characterised by the production of thick secretions causing recurrent pulmonary infection, often with unusual bacteria. This leads to lung destruction and eventually death through respiratory failure. There are no antibiotics in development that exert a new mode of action and many of the current antibiotics are ineffective in eradicating the bacteria once chronic infection is established. Antibiotic adjuvants - therapies that act by rendering the organism more susceptible to attack by antibiotics or the host immune system, by rendering it less virulent or killing it by other means, are urgently needed. OBJECTIVES To determine if antibiotic adjuvants improve clinical and microbiological outcome of pulmonary infection in people with cystic fibrosis. SEARCH METHODS We searched the Cystic Fibrosis Trials Register which is compiled from database searches, hand searches of appropriate journals and conference proceedings.Date of most recent search: 26 July 2012.We also searched MEDLINE (all years) on 23 February 2013 and ongoing trials registers on 13 February 2013. SELECTION CRITERIA Randomised controlled trials and quasi-randomised controlled trials of a therapy exerting an antibiotic adjuvant mechanism of action compared to placebo or no therapy for people with cystic fibrosis. DATA COLLECTION AND ANALYSIS The authors independently assessed and extracted data from identified studies. MAIN RESULTS We identified eighteen studies of which four are included that examined antibiotic adjuvant therapies, three studies are ongoing. The included studies involve the assessment of β-carotene, garlic and zinc supplementation and KB001 (a biological agent). No therapy demonstrated a significant effect upon pulmonary function, pulmonary exacerbations or quality of life. The study of zinc supplementation reports a reduction in the requirement of oral antibiotics but not of intravenous antibiotics, an effect that is difficult to understand. AUTHORS' CONCLUSIONS We could not identify an antibiotic adjuvant therapy that could be recommended for the treatment of lung infection in those with cystic fibrosis. The emergence of increasingly resistant bacteria makes the reliance on antibiotics alone challenging for cystic fibrosis teams. There is a need to explore alternative strategies, such as the use of adjuvant therapies. Further research is required to provide future therapeutic options.
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Adaptation of Pseudomonas aeruginosa to the cystic fibrosis airway: an evolutionary perspective.
Folkesson, A, Jelsbak, L, Yang, L, Johansen, HK, Ciofu, O, Høiby, N, Molin, S
Nature reviews. Microbiology. 2012;(12):841-51
Abstract
The airways of patients with cystic fibrosis (CF) are nearly always infected with many different microorganisms. This environment offers warm, humid and nutrient-rich conditions, but is also stressful owing to frequent antibiotic therapy and the host immune response. Pseudomonas aeruginosa is commonly isolated from the airways of patients with CF, where it most often establishes chronic infections that usually persist for the rest of the lives of the patients. This bacterium is a major cause of mortality and morbidity and has therefore been studied intensely. Here, we discuss how P. aeruginosa evolves from a state of early, recurrent intermittent colonization of the airways of patients with CF to a chronic infection state, and how this process offers opportunities to study bacterial evolution in natural environments. We believe that such studies are valuable not only for our understanding of bacterial evolution but also for the future development of new therapeutic strategies to treat severe chronic infections.
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7.
Antibiotic adjuvant therapy for pulmonary infection in cystic fibrosis.
Hurley, MN, Forrester, DL, Smyth, AR
The Cochrane database of systematic reviews. 2010;(10):CD008037
Abstract
BACKGROUND Cystic fibrosis is a multi-system disease characterised by the production of thick secretions causing recurrent pulmonary infection, often with unusual bacteria. This leads to lung destruction and eventually death through respiratory failure. There are no antibiotics in development that exert a new mode of action and many of the current antibiotics are ineffective in eradicating the bacteria once chronic infection is established. Antibiotic adjuvants - therapies that act by rendering the organism more susceptible to attack by antibiotics or the host immune system, by rendering it less virulent or killing it by other means, are urgently needed. OBJECTIVES To determine if antibiotic adjuvants improve clinical and microbiological outcome of pulmonary infection in people with cystic fibrosis. SEARCH STRATEGY We searched the Cystic Fibrosis Trials Register which is compiled from database searches, hand searches of appropriate journals and conference proceedings.Date of most recent search: 26 August 2010.We also searched MEDLINE (all years) on 21 July 2010. SELECTION CRITERIA Randomised controlled trials and quasi-randomised controlled trials of a therapy exerting an antibiotic adjuvant mechanism of action compared to placebo or no therapy for people with cystic fibrosis. DATA COLLECTION AND ANALYSIS The authors independently assessed and extracted data from identified studies. MAIN RESULTS We identified eighteen studies of which three are included that examined antibiotic adjuvant therapies, five studies are ongoing. The included studies involve the assessment of β-carotene, garlic and zinc supplementation. No therapy demonstrated a significant effect upon pulmonary function, pulmonary exacerbations or quality of life. The study of zinc supplementation reports a reduction in the requirement of oral antibiotics but not of intravenous antibiotics, an effect that is difficult to understand. AUTHORS' CONCLUSIONS We could not identify an antibiotic adjuvant therapy that could be recommended for the treatment of lung infection in those with cystic fibrosis. The emergence of increasingly resistant bacteria makes the reliance on antibiotics alone challenging for cystic fibrosis teams. There is a need to explore alternative strategies, such as the use of adjuvant therapies. Further research is required to provide future therapeutic options.