Omega‐3 fatty acid supplementation for cystic fibrosis
Information
- DOI:
- https://doi.org/10.1002/14651858.CD002201.pub6Copy DOI
- Database:
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- Cochrane Database of Systematic Reviews
- Version published:
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- 10 April 2020see what's new
- Type:
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- Intervention
- Stage:
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- Review
- Cochrane Editorial Group:
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Cochrane Cystic Fibrosis and Genetic Disorders Group
- Copyright:
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- Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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Authors
Contributions of authors
Original review
NBW formulated the question, was primarily responsible for development of the protocol and writing the original review. NBW and TN'D selected the studies, graded the quality and extracted the data.
ME was consulted at all stages of the review, providing advice and support when needed.
Updates from 2007
Following the death of the lead author NBW, CO has taken on the lead and acts as guarantor of the review from 2007. The methodological quality of the included studies was re‐assessed by CO using the criteria described by Jüni (Jüni 2001) and then again to reflect the current Cochrane guidelines with regards to risk of bias.
At the update in 2011, ME stepped down from the review team and a new author, NJ joined the team. For this update also, TN'D has not been actively involved and her name does not currently appear on the citation.
At the update in 2013, NJ stepped down from the review team and a new author, HW, joined the team.
At the update in 2016, CO stepped down as lead author, but remained as a co‐author. HW became lead author.
At the update in 2020 CO stepped down as co‐author. HW remained as lead author. CS joined as co‐author.
Sources of support
Internal sources
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Sheffield Children's Hospital Appeal, UK.
External sources
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National Institute for Health Research, UK.
This systematic review was supported by the National Institute for Health Research, via Cochrane Infrastructure funding to the Cochrane Cystic Fibrosis and Genetic Disorders Group.
Declarations of interest
Both authors: none known.
Acknowledgements
We gratefully acknowledge the assistance of Sheffield Children's Hospital Appeal funding, which supported the undertaking of the initial version of this review.
We acknowledge the considerable input into the production of the protocol and initial review of the former lead author, Naomi Beckles‐Wilson, and co‐authors Dr Mark Everard and Tracy N'Diaye. In addition the contribution by the previous lead author Coleen Oliver.
This project was supported by the National Institute for Health Research, via Cochrane Infrastructure funding to the Cochrane Cystic Fibrosis and Genetic Disorders Group. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, NHS or the Department of Health.
Version history
| Published | Title | Stage | Authors | Version |
| 2020 Apr 10 | Omega‐3 fatty acid supplementation for cystic fibrosis | Review | Helen Watson, Caroline Stackhouse | |
| 2016 Jan 05 | Omega‐3 fatty acids for cystic fibrosis | Review | Colleen Oliver, Helen Watson | |
| 2013 Nov 27 | Omega‐3 fatty acids for cystic fibrosis | Review | Colleen Oliver, Helen Watson | |
| 2011 Aug 10 | Omega‐3 fatty acids for cystic fibrosis | Review | Colleen Oliver, Nikki Jahnke | |
| 2007 Oct 17 | Omega‐3 fatty acids (from fish oils) for cystic fibrosis | Review | Colleen Oliver, Mark Everard, Tracy N'Diaye | |
| 2002 Jul 22 | Omega‐3 fatty acids (from fish oils) for cystic fibrosis | Review | Naomi R Beckles‐Willson, T Elliott, Mark Everard, Tracy N'Diaye | |
Differences between protocol and review
The former secondary outcome "number of courses of antibiotics given (oral and intravenous)" has been moved to a sub‐outcome of the primary outcome "Number of respiratory exacerbations" as often respiratory exacerbations are defined by the courses of antibiotics prescribed.
Keywords
MeSH
Medical Subject Headings (MeSH) Keywords
- *Dietary Supplements;
- Bias;
- Cystic Fibrosis [blood, *diet therapy];
- Disease Progression;
- Fatty Acids, Omega‐3 [*administration & dosage, adverse effects];
- Fatty Acids, Omega‐6 [administration & dosage];
- Forced Expiratory Volume;
- Olive Oil [administration & dosage];
- Randomized Controlled Trials as Topic;
- Vital Capacity;
Medical Subject Headings Check Words
Adult; Child; Humans;
PICOs
Study flow (PRISMA) diagram
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Comparison 1 Omega‐3 fatty acids versus placebo, Outcome 1 Adverse events.
Comparison 1 Omega‐3 fatty acids versus placebo, Outcome 2 FEV1 % predicted (post‐treatment).
Comparison 1 Omega‐3 fatty acids versus placebo, Outcome 3 FVC % predicted (post treatment).
Comparison 1 Omega‐3 fatty acids versus placebo, Outcome 4 BMI (SD score) (post treatment).
Comparison 1 Omega‐3 fatty acids versus placebo, Outcome 5 EPA and DHA % content of neutrophil membrane (post treatment).
Comparison 1 Omega‐3 fatty acids versus placebo, Outcome 6 Leukotriene B4 to leukotriene B5 ratio (post treatment).
Comparison 1 Omega‐3 fatty acids versus placebo, Outcome 7 EPA and DHA content of serum phospholipids (change from baseline).
Comparison 1 Omega‐3 fatty acids versus placebo, Outcome 8 N6/N3 ratio content of serum phospholipids (change from baseline).
| Omega‐3 fatty acid supplementation compared with placebo for cystic fibrosis | ||||||
| Patient or population: children and adults with cystic fibrosis Settings: outpatients Intervention: oral omega‐3 supplementation (EPA or DHA, or both) Comparison: placebo | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | No of Participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| Placebo | Omega‐3 supplementation | |||||
| Number of pulmonary exacerbations (median number of exacerbations during the study) Follow‐up: 12 months | The number of exacerbations in the placebo group was greater than in the omega‐3 group (3.5 versus 1.7 (range 1 ‐ 3)). | N/A | 13 | ⊕⊝⊝⊝ | The authors only report the number of exacerbations in the supplemented group compared to the 12 months prior to the trial. Extra data was provided by the study authors to allow a between group comparison. This outcome was not included in the study protocol. | |
| Adverse events: diarrhoea Follow‐up: 6 weeks | 1 study reported drop out due to diarrhoea. 2 out of 7 participants in the fish oil group dropped out and 2 out of 5 participants in the placebo group, OR 0.6 (0.05 to 6.79). | OR 0.6 (0.05 to 6.79) | 12 | ⊕⊝⊝⊝ | Other adverse events included stomach pains (5/35 participants) but the intervention arm wasn't specified (Keen 2010). | |
| FEV1 % predicted Follow‐up: 6 months | The mean FEV1 % predicted was 64% in the control group. | The mean FEV1 % predicted in the intervention group was 2% higher (19.1% lower to 23.11% higher) | MD 2.00 (19.11 to 23.11) | 17 | ⊕⊝⊝⊝ | A further study (n = 16) reported a significant increase from baseline in the EPA group compared to the control group measured in L compared to the placebo group (P = 0.06) (Lawrence 1993). Two studies reported no difference in FEV1 % predicted or lung function (measurement not stated) between groups (Hanssens 2016; Keen 2010) |
| FVC % predicted Follow‐up: 6 months | The mean FVC % predicted in the control group was 81%. | The mean FVC % predicted in the intervention group was 1% lower (16.65 % lower to 14.65 % higher). | MD ‐1.00 (‐16.65 to 14.65) | 17 | ⊕⊝⊝⊝ | 1 study reported a significant rise in FVC (L) in the EPA group (P = 0.01) (Lawrence 1993). 2 studies reported no difference in FVC between groups, but no data were available for analysis (Hanssens 2016; Keen 2010). |
| Growth and nutrition: BMI SD score Follow‐up: 6 months | No significant difference was seen between the PUFA group and the placebo group after 6 months. | MD 0.00 (95 % CI ‐0.64 to 0.64) | 29 | ⊕⊝⊝⊝ | A further study reported on BMI but reported only that BMI z scores remained stable throughout the study (Hanssens 2016). | |
| Biochemical markers of essential fatty acid status: EPA and DHA % content of neutrophil membrane Follow‐up: 6 months | 1 study reported a higher EPA content of the neutrophil membrane in the omega‐3 PUFA‐supplemented group compared to the placebo group, MD 0.90 (95% CI 0.46 to 1.34). In the same study, no difference was observed in DHA membrane concentration between groups, MD 0.10 (95% CI ‐0.45 to 0.65) | 29 | ⊕⊝⊝⊝ | At 6 months, Keen reported a significant increase from baseline in both EPA and DHA content of serum phospholipids in the omega‐3 supplemented group compared to placebo, MD 0.70 (95% CI 0.42 to 0.98) and MD 1.10 (95% CI 0.39 to 1.81), respectively (Keen 2010). | ||
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| aDowngraded twice due to risk of bias within the included study for this outcome. There was uncertainty around allocation concealment and blinding and a high risk of bias due to selective reporting. bDowngraded once due to imprecision from very low participant numbers and low event rates. cDowngraded once due to risk of bias within the included study. It was unclear whether allocation was concealed and whether the outcomes were predefined as there was no protocol available. dDowngraded twice due to very low participant numbers (n = 12) and low event rates. eDowngraded twice due to risk of bias within the trial. The risk of bias was unclear across several domains including; randomisation, allocation concealment, incomplete outcome assessment and selective reporting. | ||||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Adverse events Show forest plot | 1 | Odds Ratio (M‐H, Fixed, 95% CI) | Totals not selected | |
| 1.1 Diarrhoea and eructation | 1 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.0 [0.0, 0.0] | |
| 2 FEV1 % predicted (post‐treatment) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 2.1 At 6 months | 1 | Mean Difference (IV, Fixed, 95% CI) | 0.0 [0.0, 0.0] | |
| 3 FVC % predicted (post treatment) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 3.1 At 6 months | 1 | Mean Difference (IV, Fixed, 95% CI) | 0.0 [0.0, 0.0] | |
| 4 BMI (SD score) (post treatment) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 4.1 At 6 months | 1 | Mean Difference (IV, Fixed, 95% CI) | 0.0 [0.0, 0.0] | |
| 5 EPA and DHA % content of neutrophil membrane (post treatment) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 5.1 EPA at 6 months | 1 | Mean Difference (IV, Fixed, 95% CI) | 0.0 [0.0, 0.0] | |
| 5.2 DHA at 6 months | 1 | Mean Difference (IV, Fixed, 95% CI) | 0.0 [0.0, 0.0] | |
| 6 Leukotriene B4 to leukotriene B5 ratio (post treatment) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 6.1 At 6 months | 1 | Mean Difference (IV, Fixed, 95% CI) | 0.0 [0.0, 0.0] | |
| 7 EPA and DHA content of serum phospholipids (change from baseline) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 7.1 EPA At 6 months | 1 | Mean Difference (IV, Fixed, 95% CI) | 0.0 [0.0, 0.0] | |
| 7.2 DHA at 6 months | 1 | Mean Difference (IV, Fixed, 95% CI) | 0.0 [0.0, 0.0] | |
| 8 N6/N3 ratio content of serum phospholipids (change from baseline) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Totals not selected | |
| 8.1 At 3 months | 1 | Mean Difference (IV, Fixed, 95% CI) | 0.0 [0.0, 0.0] | |
