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The Cochrane Database of Systematic... 2003The lung disease in cystic fibrosis is characterised by impaired mucociliary clearance. Hypertonic saline (HS) has been shown to enhance mucociliary clearance in-vitro... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The lung disease in cystic fibrosis is characterised by impaired mucociliary clearance. Hypertonic saline (HS) has been shown to enhance mucociliary clearance in-vitro and this may act to lessen the destructive inflammatory process in the airways.
OBJECTIVES
To investigate the effects of treatment with nebulised hypertonic saline on people with CF compared to placebo and or other treatments that enhance mucociliary clearance.
SEARCH STRATEGY
'We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group trials register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and handsearching abstract books of conference proceedings. Date of the most recent search of the Group's register: October 2001.
SELECTION CRITERIA
All controlled trials (any language) assessing the effect of hypertonic saline compared to placebo or other mucolytic therapy, for any duration or dose regimen in people with cystic fibrosis of any age or severity.
DATA COLLECTION AND ANALYSIS
All identified trials were independently reviewed by both reviewers & all data collected. Trial quality was assessed along with allocation concealment.
MAIN RESULTS
Fourteen controlled trials were identified. Nine trials met the inclusion criteria; these involved 235 participants with an age range of 6 to 46 years. Two short-term trials of immediate effect on mucociliary clearance demonstrated that HS increased isotope clearance compared to control. Lung function as measured by improvement in Forced Expiratory Volume at one second (FEV1 l/min) was observed in four trials. When 3% to 7% saline was used in a volume of 10mls twice a day, in comparison to placebo, HS led to a significant increase in FEV1, WMD 12.20 (95%CI 4.30 to 20.10). In comparison to deoxyribonuclease (DNase) two trials used a similar concentration and volume of HS. Over a three week period the groups showed a similar increase in FEV1, WMD -1.60 (95%CI -11.16 to 7.96). However after 12 weeks treatment in participants with moderate to severe lung disease compared to DNase, HS 5mls twice a day showed less benefit to FEV1, WMD -13.00 (95%CI -22.46 to -3.54). No serious adverse events were noted.
REVIEWER'S CONCLUSIONS
Nebulised hypertonic saline improves mucociliary clearance in short term clinical trials and appears to increase lung function compared to control. In comparison to DNase it may be less effective at improving lung function, after three months. At this stage there is insufficient evidence to support the use of hypertonic saline as routine treatment for people with cystic fibrosis.
Topics: Administration, Inhalation; Controlled Clinical Trials as Topic; Cystic Fibrosis; Humans; Mucociliary Clearance; Nebulizers and Vaporizers; Randomized Controlled Trials as Topic; Saline Solution, Hypertonic
PubMed: 12535409
DOI: 10.1002/14651858.CD001506 -
Scientific Reports Jul 2016An increasing number of studies have highlighted the potential link between EXO1 polymorphisms and cancer risk, although no consensus has yet been obtained. Thus, we... (Meta-Analysis)
Meta-Analysis
An increasing number of studies have highlighted the potential link between EXO1 polymorphisms and cancer risk, although no consensus has yet been obtained. Thus, we aimed to obtain a thorough and current assessment of EXO1 polymorphisms and cancer susceptibility by performing a meta-analysis. A comprehensive literature retrieval was performed on PubMed, EMbase, Web of Science and Wanfang databases. The odds ratio (OR) and 95% confidence interval (CI) were applied to assess the results. Finally, 39 case-control studies of the nine EXO1 polymorphisms that involved 21,651 cases and 21,348 controls met our inclusion criteria. The pooled analysis indicated that the rs1047840 polymorphism conferred a significantly increased susceptibility to cancer in an allelic model. Similarly, the rs3754093, rs1776177, rs9350, rs10802996, rs1635498, rs1776148 and rs851797 polymorphisms were also associated with an increased susceptibility to cancer in an allelic model, respectively, while no significant association was identified for rs1635517 polymorphism. For the rs1047840 polymorphism, in an ethnicity subgroup analysis, a significantly increased susceptibility to cancer for Asians was identified in all the genetic models, and for Caucasians in an allelic model. Our findings provide the evidence that the rs1047840, rs9350, rs10802996, rs1635498, rs1776148, rs1776177, rs3754093 and rs851797 polymorphisms may act as risk factors for cancer.
Topics: Case-Control Studies; DNA Repair Enzymes; Ethnicity; Exodeoxyribonucleases; Genetic Predisposition to Disease; Humans; Neoplasms; Polymorphism, Single Nucleotide
PubMed: 27387683
DOI: 10.1038/srep29270 -
The Cochrane Database of Systematic... Apr 2013Nebuliser systems are used to deliver medications to control the symptoms and the progression of lung disease in people with cystic fibrosis. Many types of nebuliser... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Nebuliser systems are used to deliver medications to control the symptoms and the progression of lung disease in people with cystic fibrosis. Many types of nebuliser systems are available for use with various medications; however, there has been no previous systematic review which has evaluated these systems.
OBJECTIVES
To evaluate effectiveness, safety, burden of treatment and adherence to nebulised therapy using different nebuliser systems for people with cystic fibrosis.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching of relevant journals and abstract books of conference proceedings. We searched the reference lists of each study for additional publications and approached the manufacturers of both nebuliser systems and nebulised medications for published and unpublished data. Date of the most recent search: 15 Oct 2012.
SELECTION CRITERIA
Randomised controlled trials or quasi-randomised controlled trials comparing nebuliser systems including conventional nebulisers, vibrating mesh technology systems, adaptive aerosol delivery systems and ultrasonic nebuliser systems.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed studies for inclusion. They also independently extracted data and assessed the risk of bias. A third author assessed studies where agreement could not be reached.
MAIN RESULTS
The search identified 40 studies with 20 of these (1936 participants) included in the review. These studies compared the delivery of tobramycin, colistin, dornase alfa, hypertonic sodium chloride and other solutions through the different nebuliser systems. This review demonstrates variability in the delivery of medication depending on the nebuliser system used. Conventional nebuliser systems providing higher flows, higher respirable fractions and smaller particles decrease treatment time, increase deposition and may be preferred by people with CF, as compared to conventional nebuliser systems providing lower flows, lower respirable fractions and larger particles. Nebulisers using adaptive aerosol delivery or vibrating mesh technology reduce treatment time to a far greater extent. Deposition (as a percentage of priming dose) is greater than conventional with adaptive aerosol delivery. Vibrating mesh technology systems may give greater deposition than conventional when measuring sputum levels, but lower deposition when measuring serum levels or using gamma scintigraphy. The available data indicate that these newer systems are safe when used with an appropriate priming dose, which may be different to the priming dose used for conventional systems. There is an indication that adherence is maintained or improved with systems which use these newer technologies, but also that some nebuliser systems using vibrating mesh technology may be subject to increased failures.
AUTHORS' CONCLUSIONS
Clinicians should be aware of the variability in the performance of different nebuliser systems. Technologies such as adaptive aerosol delivery and vibrating mesh technology have advantages over conventional systems in terms of treatment time, deposition as a percentage of priming dose, patient preference and adherence. There is a need for long-term randomised controlled trials of these technologies to determine patient-focused outcomes (such as quality of life and burden of care), safe and effective dosing levels of medications and clinical outcomes (such as hospitalisations and need for antibiotics) and an economic evaluation of their use.
Topics: Aerosols; Albuterol; Anti-Bacterial Agents; Bronchodilator Agents; Carbenicillin; Colistin; Cromolyn Sodium; Cystic Fibrosis; Deoxyribonuclease I; Drug Delivery Systems; Humans; Medication Adherence; Nebulizers and Vaporizers; Randomized Controlled Trials as Topic; Recombinant Proteins; Saline Solution, Hypertonic; Tobramycin
PubMed: 23633344
DOI: 10.1002/14651858.CD007639.pub2 -
The Cochrane Database of Systematic... Jun 2013Inhalation of the enzyme dornase alfa reduces sputum viscosity and improves clinical outcomes of people with cystic fibrosis. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Inhalation of the enzyme dornase alfa reduces sputum viscosity and improves clinical outcomes of people with cystic fibrosis.
OBJECTIVES
To determine the effect of timing of dornase alfa inhalation on measures of clinical efficacy in people with cystic fibrosis (in relation to airway clearance techniques or time of day).
SEARCH METHODS
Relevant randomised and quasi-randomised controlled trials were identified from the Cochrane Cystic Fibrosis Trials Register, Physiotherapy Evidence Database (PEDro), and international CF conference proceedings.Date of the most recent search: 22 February 2013.
SELECTION CRITERIA
Any trial of dornase alfa in people with cystic fibrosis where timing of inhalation was the randomised element in the study with either: inhalation before compared to after airway clearance techniques; or morning compared to evening inhalation.
DATA COLLECTION AND ANALYSIS
Both authors independently selected trials, assessed risk of bias and extracted data with disagreements resolved by discussion. Relevant data were extracted and, where possible, meta-analysed.
MAIN RESULTS
We identified 99 trial reports representing 48 studies, of which five studies (providing data on 122 participants) met our inclusion criteria. All five studies used a cross-over design. Intervention periods ranged from two to eight weeks. Four trials compared dornase alfa inhalation before versus after airway clearance techniques. Inhalation after instead of before airway clearance did not significantly change FEV1. Similarly, FVC and quality of life were not significantly affected; FEF25 was significantly worse with dornase alfa inhalation after airway clearance, MD -0.17 litres (95% CI -0.28 to -0.05), based on the pooled data from two small studies in children (7 to 19 years) with well-preserved lung function. All other secondary outcomes were statistically non-significant.In one trial, morning versus evening inhalation had no impact on lung function or symptoms.
AUTHORS' CONCLUSIONS
The current evidence derived from a small number of participants does not indicate that inhalation of dornase alfa after airway clearance techniques is more or less effective than the traditional recommendation to inhale nebulised dornase alfa 30 minutes prior to airway clearance techniques, for most outcomes. For children with well-preserved lung function, inhalation before airway clearance may be more beneficial for small airway function than inhalation after. However, this result relied on a measure with high variability and studies with variable follow up. In the absence of strong evidence to indicate that one timing regimen is better than another, the timing of dornase alpha inhalation can be largely based on pragmatic reasons or individual preference with respect to the time of airway clearance and time of day. Further research is warranted.
Topics: Administration, Inhalation; Adolescent; Child; Combined Modality Therapy; Cystic Fibrosis; Deoxyribonuclease I; Drug Administration Schedule; Humans; Quality of Life; Randomized Controlled Trials as Topic; Respiratory Therapy; Time Factors; Young Adult
PubMed: 23737088
DOI: 10.1002/14651858.CD007923.pub3 -
Journal of Assisted Reproduction and... May 2014Estrogens play an important role in male reproduction via interacting with estrogen receptors (ERs), whose expression can be regulated by the polymorphisms in different... (Meta-Analysis)
Meta-Analysis
PURPOSE
Estrogens play an important role in male reproduction via interacting with estrogen receptors (ERs), whose expression can be regulated by the polymorphisms in different regions of ESR1 and ESR2 genes. However, results from published studies on the association between four well-characterized polymorphisms (PvuII, XbaI, RsaI, and AluI) in the gene of ERs (ESR1 and ESR2) and male infertility risk are inconclusive.
METHODS
To investigate the strength of relationship of PvuII and XbaI in ESR1 and RsaI and AluI in ESR2 with male infertility, we conducted a meta-analysis of 12 eligible studies with odds ratio (OR) and its corresponding 95 % confidence intervals (95 % CI).
RESULTS
Overall, ESR1 PvuII and ESR2 RsaI polymorphisms were significantly associated with male infertility risk. The subgroup analyses by ethnicities demonstrated that in Asians, ESR1 PvuII, XbaI and ESR2 RsaI polymorphisms were significantly associated with a decreased infertility risk, while in Caucasians both ESR1 PvuII and ESR2 RsaI polymorphisms increased the susceptibility to male infertility. As for ESR2 AluI polymorphism, no significant association was detected in either overall analysis or subgroup analyses by ethnicities/genotyping methods.
CONCLUSIONS
This meta-analysis suggested that polymorphisms in the genes of ERs (ESR1 and ESR2) may have differential roles in the predisposition to male infertility according to the different ethnic backgrounds. Further well-designed and unbiased studies with larger sample size and diverse ethnic backgrounds should be conducted to verify our findings.
Topics: Asian People; Deoxyribonucleases, Type II Site-Specific; Estrogen Receptor alpha; Estrogen Receptor beta; Genetic Predisposition to Disease; Humans; Infertility, Male; Male; Odds Ratio; Polymorphism, Genetic; White People
PubMed: 24647635
DOI: 10.1007/s10815-014-0212-5 -
The Cochrane Database of Systematic... Nov 2012Bronchiolitis is one of the most common respiratory problems in the first year of life. The sputum of infants with bronchiolitis has increased deoxyribonucleic acid... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Bronchiolitis is one of the most common respiratory problems in the first year of life. The sputum of infants with bronchiolitis has increased deoxyribonucleic acid (DNA) content, leading to mucous plugging and airway obstruction. Recombinant human deoxyribonuclease (rhDNase), an enzyme that digests extracellular DNA, might aid the clearance of mucus and relieve peripheral airway obstruction.
OBJECTIVES
To determine the effect of nebulised rhDNase on the severity and duration of viral bronchiolitis in children younger than 24 months of age in the hospital setting.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) 2012, Issue 7 which includes the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to July Week 4, 2012), EMBASE (1974 to August 2012) and LILACS (1982 to August 2012).
SELECTION CRITERIA
Randomised controlled trials (RCTs) using nebulised rhDNase alone or with concomitant therapy in children younger than 24 months of age hospitalised with acute bronchiolitis.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed literature searches, assessed trial quality and extracted data. We obtained unpublished data from trial authors. We used Review Manager 5.1 to pool treatment effects expressed as the mean difference (MD) or standardised mean difference (SMD) with 95% confidence intervals (CI).
MAIN RESULTS
Three RCTs (333 participants) were identified, two of which were multicentre trials comprising only participants positive for respiratory syncytial virus (RSV). The other trial enrolled participants clinically diagnosed with bronchiolitis from a hospital in Italy. All studies used 2.5 mL (1 mg/mL) of nebulised rhDNase compared with placebo either as a daily or a twice daily dose. Adjunctive therapy included nebulised salbutamol, steroids, supplemental oxygen, intravenous fluids or tube feeding, nasal washing, nasal decongestants and antibiotics.Overall, nebulised rhDNase showed no benefit in clinically meaningful outcomes. Meta-analysis favoured the control group with a shorter duration of hospital stay (MD 0.50; 95% CI 0.10 to 0.90, P = 0.01) and better clinical score improvement (SMD -0.24; 95% CI -0.50 to 0.01, P = 0.06). The largest trial showed no difference in supplemental oxygen use or intensive care unit (ICU) admission.In one RCT, four out of 11 patients in the treatment group had atelectasis. Two of these patients showed distinctive clinical improvement after nebulised rhDNase.There was no significant difference in adverse events. These included temporary desaturation, temporary coughing, increased coughing, facial rash, hoarseness, dyspnoea and bad taste, reported in a total of 11 patients from both treatment groups.
AUTHORS' CONCLUSIONS
The results based on the three included studies in this review did not support the use of nebulised rhDNase in children under 24 months of age hospitalised with acute bronchiolitis. In these patients, treatment did not shorten the length of hospitalisation or improve clinical outcomes. It might have a role in severe bronchiolitis complicated by atelectasis, but further clinical studies would need to be performed.
Topics: Administration, Inhalation; Bronchiolitis, Viral; Deoxyribonucleases; Humans; Infant; Nebulizers and Vaporizers; Pulmonary Atelectasis; Randomized Controlled Trials as Topic
PubMed: 23152257
DOI: 10.1002/14651858.CD008395.pub2 -
Modern Pathology : An Official Journal... Dec 2022Reflex mismatch repair immunohistochemistry (MMR IHC) testing for MLH1, PMS2, MSH2 and MSH6 is used to screen for Lynch syndrome. Recently MMR-deficiency (MMRd) has been... (Meta-Analysis)
Meta-Analysis
Reflex mismatch repair immunohistochemistry (MMR IHC) testing for MLH1, PMS2, MSH2 and MSH6 is used to screen for Lynch syndrome. Recently MMR-deficiency (MMRd) has been approved as a pan-cancer predictive biomarker for checkpoint inhibitor therapy, leading to a vast increase in the use of MMR IHC in clinical practice. We explored whether immunohistochemical staining with PMS2 and MSH6 can be used as a reliable substitute. This two-antibody testing algorithm has the benefit of saving tissue, cutting costs and saving time. PubMed, Embase and Cochrane library were systematically searched for articles reporting on MMR IHC. The weighed percentage of cases with isolated MLH1 or MSH2 loss or combined MLH1/MSH2 loss alone was analyzed using a random effects model meta-analysis in R. The search yielded 1704 unique citations, of which 131 studies were included, describing 9014 patients. A weighed percentage of 1.1% (95% CI 0.53-18.87, I = 87%) of cases with isolated MLH1 or MSH2 loss or combined MLH1/MSH2 loss alone was observed. In the six articles with the main aim of investigating the two-antibody testing algorithm all MMRd cases were detected with the two-antibody testing algorithm, there were no cases with isolated MLH1 or MSH2 loss or combined MLH1/MSH2 loss alone. This high detection rate of MMRd of the two-antibody testing algorithm supports its use in clinical practice by specialized pathologists. Staining of all four antibodies should remain the standard in cases with equivocal results of the two-antibody testing algorithm. Finally, educational sessions in which staining pattern pitfalls are discussed will continue to be important.
Topics: Humans; Mismatch Repair Endonuclease PMS2; MutL Protein Homolog 1; MutS Homolog 2 Protein; DNA-Binding Proteins; Colorectal Neoplasms; DNA Mismatch Repair; Biomarkers, Tumor; Algorithms
PubMed: 36104536
DOI: 10.1038/s41379-022-01149-w -
The Laryngoscope Jun 2014To systematically review existing literature on the effectiveness of medical management of chronic rhinosinusitis (CRS) in cystic fibrosis (CF) patients. (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVES/HYPOTHESIS
To systematically review existing literature on the effectiveness of medical management of chronic rhinosinusitis (CRS) in cystic fibrosis (CF) patients.
STUDY DESIGN
Systematic review.
METHODS
We performed a literature search of PubMed, Embase, and Cochrane CENTRAL from 1987 to 2012. Inclusion criteria included English language as containing original data, with five or more subjects, measurable clinical outcomes, and readily available interventions. Data were systematically collected on study design, patient demographics, clinical characteristics and outcomes, and level of evidence. Two investigators independently reviewed all manuscripts and performed a comprehensive quality assessment.
RESULTS
Of 415 abstracts identified, 12 articles were included. These 12 studies reported on 701 adult and pediatric CF patients who underwent medical therapy. Medical treatment included antibiotics (4/12), topical steroids (4/12), dornase alfa (3/12), and ibuprofen (1/12). Outcome measures included symptom scores (7/12), endoscopic findings (7/12), radiographic findings (4/12), pulmonary function testing (4/12), and rhinomanometry (2/12). Most studies found improvement in at least one of the outcome measures. There was statistical significance in clinical outcomes with dornase alfa, beclomethasone, and betamethasone. Most studies were level 3 or 4 evidence (9/12), but three studies were level 1 or 2 evidence (two dornase alfa studies, one betamethasone study).
CONCLUSIONS
Dornase alfa and, to a lesser extent, topical steroids demonstrated significant benefits in the medical treatment CRS in CF. There was a lack of evidence to support antibiotic therapy in the outcomes assessed. Further high-quality studies should be carried out to determine the efficacy of various medical therapies for CRS in CF.
LEVEL OF EVIDENCE
NA.
Topics: Administration, Oral; Administration, Topical; Adult; Anti-Bacterial Agents; Child; Child, Preschool; Chronic Disease; Cystic Fibrosis; Deoxyribonuclease I; Drug Therapy, Combination; Female; Humans; Magnetic Resonance Imaging; Prognosis; Randomized Controlled Trials as Topic; Recombinant Proteins; Retrospective Studies; Rhinitis; Risk Assessment; Severity of Illness Index; Sinusitis; Steroids; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 24338982
DOI: 10.1002/lary.24503 -
The Cochrane Database of Systematic... May 2011Surgical wounds that become infected are often debrided because clinicians believe that removal of this necrotic or infected tissue will expedite wound healing. There... (Review)
Review
BACKGROUND
Surgical wounds that become infected are often debrided because clinicians believe that removal of this necrotic or infected tissue will expedite wound healing. There are numerous methods available but no consensus on which one is most effective for surgical wounds.
OBJECTIVES
To determine the effect of different methods of debridement on the rate of debridement and healing of surgical wounds.
SEARCH STRATEGY
For this second update we searched the Cochrane Wounds Group Specialised Register (searched 13 April 2011); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1); Ovid MEDLINE (2007 to March Week 5 2011); Ovid MEDLINE (In-Process & Other Non-Indexed Citations, April 11, 2011); Ovid EMBASE (2007 to 2011 Week 14); and EBSCO CINAHL (2007 to 8 April 2011).
SELECTION CRITERIA
We included randomised controlled trials (RCTs) with outcomes including at least one of the following: time to complete debridement or time to complete healing.
DATA COLLECTION AND ANALYSIS
Two review authors independently reviewed the abstracts and titles obtained from the search, extracted data independently using a standardised extraction sheet and independently assessed methodological quality. One review author was involved in all stages of the data collection and extraction process, thus ensuring continuity.
MAIN RESULTS
Five RCTs (159 participants) were eligible for inclusion; all compared treatments for infected surgical wounds and reported time required to achieve a clean wound bed (complete debridement). One trial compared an enzymatic agent (streptokinase/streptodornase) with saline-soaked dressings. Four trials compared the effectiveness of dextranomer beads or paste with other products (different comparator in each trial) to achieve complete debridement. Meta-analysis was not possible due to the unique comparisons within each trial. One trial reported that dextranomer achieved a clean wound bed significantly more quickly than Eusol, and one trial comparing enzymatic debridement with saline-soaked dressings reported that the enzyme-treated wounds were cleaned more quickly. However, methodological quality was poor in these two trials.
AUTHORS' CONCLUSIONS
There is a lack of large, high-quality published RCTs evaluating debridement per se, or comparing different methods of debridement for surgical wounds, to guide clinical decision-making.
Topics: Debridement; Dextrans; Humans; Randomized Controlled Trials as Topic; Streptodornase and Streptokinase; Surgical Wound Infection; Wound Healing
PubMed: 21563150
DOI: 10.1002/14651858.CD006214.pub3 -
The Cochrane Database of Systematic... Mar 2021Inhalation of the enzyme dornase alfa reduces sputum viscosity and improves clinical outcomes of people with cystic fibrosis. This is an update of a previously published... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Inhalation of the enzyme dornase alfa reduces sputum viscosity and improves clinical outcomes of people with cystic fibrosis. This is an update of a previously published Cochrane Review.
OBJECTIVES
To determine whether the timing of dornase alfa inhalation (in relation to airway clearance techniques or morning versus evening inhalation) has an impact on objective and subjective measures of clinical efficacy in people with cystic fibrosis.
SEARCH METHODS
Relevant randomised and quasi-randomised controlled trials were identified from the Cochrane Cystic Fibrosis Trials Register, the Physiotherapy Evidence Database (PEDro), clinical trial registries and international cystic fibrosis conference proceedings. Date of the most recent search: 12 October 2020.
SELECTION CRITERIA
Any trial of dornase alfa in people with cystic fibrosis where timing of inhalation was the randomised element in the trial with either: inhalation before compared to after airway clearance techniques; or morning compared to evening inhalation. DATA COLLECTION AND ANALYSIS: Both authors independently selected trials, assessed risk of bias and extracted data with disagreements resolved by discussion. Relevant data were extracted and, where possible, meta-analysed. We assessed the quality of the evidence using GRADE.
MAIN RESULTS
We identified 115 trial reports representing 55 trials, of which five trials (providing data on 122 participants) met our inclusion criteria. All five trials used a cross-over design. Intervention periods ranged from two to eight weeks. Four trials (98 participants) compared dornase alfa inhalation before versus after airway clearance techniques. Inhalation after instead of before airway clearance did not significantly change forced expiratory volume at one second (very-low quality evidence). Similarly, forced vital capacity (low-quality evidence) and quality of life (very-low quality evidence) were not significantly affected; forced expiratory flow at 25% was significantly worse with dornase alfa inhalation after airway clearance, mean difference -0.17 litres (95% confidence interval -0.28 to -0.05), based on the pooled data from two small trials in children (7 to 19 years) with well-preserved lung function. All other secondary outcomes were statistically non-significant. In one trial (25 participants), morning versus evening inhalation had no impact on lung function or symptoms (low-quality evidence).
AUTHORS' CONCLUSIONS
The current evidence derived from a small number of participants does not indicate that inhalation of dornase alfa after airway clearance techniques is more or less effective than the traditional recommendation to inhale nebulised dornase alfa 30 minutes prior to airway clearance techniques, for most outcomes. For children with well-preserved lung function, inhalation before airway clearance may be more beneficial for small airway function than inhalation after. However, this result relied on a measure with high variability and trials with variable follow-up. In the absence of strong evidence to indicate that one timing regimen is better than another, the timing of dornase alfa inhalation can be largely based on pragmatic reasons or individual preference with respect to the time of airway clearance and time of day. Further research is warranted.
Topics: Administration, Inhalation; Adolescent; Child; Combined Modality Therapy; Cystic Fibrosis; Deoxyribonuclease I; Drug Administration Schedule; Forced Expiratory Volume; Humans; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins; Respiratory Therapy; Time Factors; Vital Capacity; Young Adult
PubMed: 33686652
DOI: 10.1002/14651858.CD007923.pub6