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. 2019 Sep 9;9(9):CD001505.
doi: 10.1002/14651858.CD001505.pub5.

Oral non-steroidal anti-inflammatory drug therapy for lung disease in cystic fibrosis

Larry C Lands  1 , Sanja Stanojevic
Affiliations

Oral non-steroidal anti-inflammatory drug therapy for lung disease in cystic fibrosis

Larry C Lands et al. Cochrane Database Syst Rev. .

Abstract

Background: Progressive lung damage causes most deaths in cystic fibrosis. Non-steroidal anti-inflammatory drugs (such as ibuprofen) may prevent progressive pulmonary deterioration and morbidity in cystic fibrosis. This is an update of a previously published review.

Objectives: To assess the effectiveness of treatment with oral non-steroidal anti-inflammatory drugs in cystic fibrosis.

Search methods: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, hand searches of relevant journals and abstract books of conference proceedings. We contacted manufacturers of non-steroidal anti-inflammatory drugs and searched online trials registries.Latest search of the Group's Trials Register: 21 November 2018.

Selection criteria: Randomized controlled trials comparing oral non-steroidal anti-inflammatory drugs, at any dose for at least two months, to placebo in people with cystic fibrosis.

Data collection and analysis: Two authors independently assessed trials for inclusion the review and their potential risk of bias. Two authors independently rated the quality of the evidence for each outcome using the GRADE guidelines.

Main results: The searches identified 17 trials; four are included (287 participants aged five to 39 years; maximum follow-up of four years) and one is currently awaiting classification pending publication of the full trial report and two are ongoing. Three trials compared ibuprofen to placebo (two from the same center with some of the same participants); one trial assessed piroxicam versus placebo.The three ibuprofen trials were deemed to have good or adequate methodological quality, but used various outcomes and summary measures. Reviewers considered measures of lung function, nutritional status, radiological assessment of pulmonary involvement, intravenous antibiotic usage, hospital admissions, survival and adverse effects. Combined data from the two largest ibuprofen trials showed a lower annual rate of decline for lung function, % predicted forced expiratory volume in one second (FEV1), mean difference (MD) 1.32 (95% confidence interval (CI) 0.21 to 2.42) (moderate-quality evidence); forced vital capacity (FVC), MD 1.27 (95% CI 0.26 to 2.28) (moderate-quality evidence); forced expiratory flow (FEF25%-75%), MD 1.80 (95% CI 0.15 to 3.45). The post hoc analysis of data from two trials split by age showed a slower rate of annual decline of FEV1 % predicted and FVC in the ibuprofen group in younger children, MD 1.41% (95% CI 0.03 to 2.80) (moderate-quality evidence) and MD 1.32% (95% CI 0.04 to 2.60) (moderate-quality evidence) respectively. Data from four trials demonstrated the proportion of participants with at least one hospitalization may be slightly lower in the ibuprofen group compared to placebo, Peto odds ratio 0.61 (95% CI 0.37 to 1.01) (moderate-quality evidence). In one trial, long-term use of high-dose ibuprofen was associated with reduced intravenous antibiotic usage, improved nutritional and radiological pulmonary status. No major adverse effects were reported, but the power of the trials to identify clinically important differences in the incidence of adverse effects was low.We did not have any concerns with regards to risk of bias for the trial comparing piroxicam to placebo. However, the trial did not report many data in a form that we could analyze in this review. No data were available for the review's primary outcome of lung function; available data for hospital admissions showed no difference between the groups. No analyzable data were available for any other review outcome.

Authors' conclusions: High-dose ibuprofen can slow the progression of lung disease in people with cystic fibrosis, especially in children, which suggests that strategies to modulate lung inflammation can be beneficial for people with cystic fibrosis.

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Conflict of interest statement

Dr Larry Lands was the lead investigator in the Trans‐Canadian Trial (Lands 2007). He is also the chief medical advisor for a phase II trial currently underway of fenretinide for CF adults as an anti‐inflammatory therapy; this drug is not eligible for inclusion in this review.

Dr Sanja Stanojevic declares no known conflict of interest.

Figures

1.1
1.1. Analysis
Comparison 1 Oral nonsteroidal anti‐inflammatory drug versus placebo, Outcome 1 Annual rate of change in % predicted FEV1.
1.2
1.2. Analysis
Comparison 1 Oral nonsteroidal anti‐inflammatory drug versus placebo, Outcome 2 Annual rate of change in % predicted FEV1 (split by age).
1.3
1.3. Analysis
Comparison 1 Oral nonsteroidal anti‐inflammatory drug versus placebo, Outcome 3 Annual rate of change in % predicted FVC.
1.4
1.4. Analysis
Comparison 1 Oral nonsteroidal anti‐inflammatory drug versus placebo, Outcome 4 Annual rate of change in % predicted FVC (split by age).
1.5
1.5. Analysis
Comparison 1 Oral nonsteroidal anti‐inflammatory drug versus placebo, Outcome 5 Annual rate of change in % predicted FEF25%‐75%.
1.6
1.6. Analysis
Comparison 1 Oral nonsteroidal anti‐inflammatory drug versus placebo, Outcome 6 Annual rate of change in % predicted FEF25%‐75% (split by age).
1.7
1.7. Analysis
Comparison 1 Oral nonsteroidal anti‐inflammatory drug versus placebo, Outcome 7 Proportion with at least one respiratory hospitalisation.
1.8
1.8. Analysis
Comparison 1 Oral nonsteroidal anti‐inflammatory drug versus placebo, Outcome 8 Proportion with at least one hospital admission.
1.9
1.9. Analysis
Comparison 1 Oral nonsteroidal anti‐inflammatory drug versus placebo, Outcome 9 Number of deaths.
1.10
1.10. Analysis
Comparison 1 Oral nonsteroidal anti‐inflammatory drug versus placebo, Outcome 10 Annual rate of change in % ideal body weight.
1.11
1.11. Analysis
Comparison 1 Oral nonsteroidal anti‐inflammatory drug versus placebo, Outcome 11 Annual rate of change in % ideal body weight (split by age).
1.12
1.12. Analysis
Comparison 1 Oral nonsteroidal anti‐inflammatory drug versus placebo, Outcome 12 Chest X‐ray score.
1.13
1.13. Analysis
Comparison 1 Oral nonsteroidal anti‐inflammatory drug versus placebo, Outcome 13 Chest X‐ray score (split by age).
1.14
1.14. Analysis
Comparison 1 Oral nonsteroidal anti‐inflammatory drug versus placebo, Outcome 14 Increase in abdominal pain.
1.15
1.15. Analysis
Comparison 1 Oral nonsteroidal anti‐inflammatory drug versus placebo, Outcome 15 Decrease in abdominal pain.
1.16
1.16. Analysis
Comparison 1 Oral nonsteroidal anti‐inflammatory drug versus placebo, Outcome 16 Proportion with at least one gastrointestinal hospitalisation.
1.17
1.17. Analysis
Comparison 1 Oral nonsteroidal anti‐inflammatory drug versus placebo, Outcome 17 Stool frequency.
1.18
1.18. Analysis
Comparison 1 Oral nonsteroidal anti‐inflammatory drug versus placebo, Outcome 18 Occult blood.
1.19
1.19. Analysis
Comparison 1 Oral nonsteroidal anti‐inflammatory drug versus placebo, Outcome 19 Increase in epistaxis.
1.20
1.20. Analysis
Comparison 1 Oral nonsteroidal anti‐inflammatory drug versus placebo, Outcome 20 Decrease in epistaxis.
1.21
1.21. Analysis
Comparison 1 Oral nonsteroidal anti‐inflammatory drug versus placebo, Outcome 21 Increase in conjunctivitis.
1.22
1.22. Analysis
Comparison 1 Oral nonsteroidal anti‐inflammatory drug versus placebo, Outcome 22 Decrease in conjunctivitis.
1.23
1.23. Analysis
Comparison 1 Oral nonsteroidal anti‐inflammatory drug versus placebo, Outcome 23 Increase in nausea.
1.24
1.24. Analysis
Comparison 1 Oral nonsteroidal anti‐inflammatory drug versus placebo, Outcome 24 Increase in diarrhoea.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

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