Alpha-1 Antitrypsin Deficiency (AATD) is a rare genetic condition predisposing individuals to COPD. The majority of treatment for AATD is similar to non-AATD related COPD; intravenous augmentation of Alpha-1 Antitrypsin is a specific treatment but is inequitably used across Europe and not used in the UK. There is a pressing need to systematically investigate efficacy since the publication of a new placebo controlled RCT and to identify patient centred, clinically meaningful outcomes.1
Methods
A systematic review was conducted using standard review methodology with meta-analysis and narrative synthesis (registered with PROSPERO-CRD42015019354). Eligible studies were those of any treatment used in severe AATD. RCT’s were the primary focus however case series and uncontrolled studies (n > 10 patients receiving treatment or usual care, with baseline and follow-up data >3 months), were eligible for inclusion to ensure natural history of disease outside RCT’s could be determined.
Results
7296 unique records were reviewed with 51 trials analysed on 5632 participants: 26 AAT-augmentation (3 for meta-analysis); 17 surgical intervention (5 Lung volume reduction (LVR) surgery, 1 Bronchoscopic valve LVR and 11 Lung transplantation); 3 medical interventions and 3 trials completed but not published. Meta-analysis of AAT-Augmentation demonstrated slower lung CT density decline, difference 0.79 g/l/year (95% CI: 0.29–1.29; p = 0.002), and a small increase in annual exacerbations 0.29/year (95% CI: 0.04–0.54; p = 0.02) compared to placebo (Figure 1). Survival benefit of transplant was observed in one study (p = 0.006) but not in a second with more stringent matching for groups; however significant improvements in health status, total SGRQ and all domain scores, at one year (p < 0.01) were observed. Mortality post lung transplant was comparable between AATD and non-AATD related COPD cohorts. Surgical lung volume reduction demonstrated inferior outcomes when compared to non-AATD related emphysema.
Conclusion
CT density, FEV1, DLCO, health status and exacerbation rates were frequently used as outcomes in AATD related treatment trials. AAT-Augmentation is able to slow the progression of severity of emphysema when measured by CT density change compared to placebo. This systematic review will help assist in the improved monitoring and management of patients with AATD.
Reference
1 Chapman KR, et al. Intravenous augmentation treatment and lung density in severe α1 antitrypsin deficiency (RAPID): a randomised, double-blind, placebo-controlled trial. The Lancet 2015;386(9991):360–368.
BACKGROUND: Oxygen (O2) is widely recommended for patients with myocardial infarction yet a narrative review has suggested it may do more harm than good. Systematic reviews have concluded that there was insufficient evidence to know whether oxygen reduced, increased or had no effect on the heart ischaemia or infarct size. OBJECTIVE: To review the evidence from randomized controlled trials to establish whether routine use of inhaled oxygen in acute myocardial infarction (AMI) improves patient-centered outcomes, in particular pain and death. CRITERIA FOR CONSIDERING STUDIES FOR THIS REVIEW: The following bibliographic databases were searched (to the end of February 2010): Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), Medline, Medline In-Process, Embase, CINAHL, Lilacs and PASCAL, British Library ZETOC, Web of Science ISI Proceedings. Experts were also contacted to identify any studies. No language restrictions were applied. SELECTION CRITERIA: Randomized controlled trials of people with suspected or proven AMI, less than 24 hours after onset, in which the intervention was inhaled oxygen (at normal pressure) compared to air and regardless of co-therapies provided these were the same in both arms of the trial. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed the titles and abstracts of identified studies to see if they met the inclusion criteria and independently undertook the data extraction. The quality of studies and the risk of bias were assessed according to guidance in the Cochrane Handbook. The primary outcomes were death, pain and complications. The measure of effect used was the relative risk (RR). MAIN RESULTS: Three trials involving 387 patients were included and 14 deaths occurred. The pooled RR of death was 2.88 (95% CI 0.88 to 9.39) in an intention-to-treat analysis and 3.03 (95% CI 0.93 to 9.83) in patients with confirmed AMI. While suggestive of harm, the small number of deaths recorded meant that this could be a chance occurrence. Pain was measured by analgesic use. The pooled RR for the use of analgesics was 0.97 (95% CI 0.78 to 1.20). AUTHORS' CONCLUSIONS: There is no conclusive evidence from randomized controlled trials to support the routine use of inhaled oxygen in patients with acute AMI. A definitive randomized controlled trial is urgently required given the mismatch between trial evidence suggestive of possible harm from routine oxygen use and recommendations for its use in clinical practice guidelines.
Children with epidermolysis bullosa (EB) comprise a rare population with high morbidity and mortality. An improved understanding of the clinical trajectory of patients with EB, including age at time of clinical diagnosis and major clinical events, is needed to refine best practices and improve quality of life and clinical outcomes for patients with EB.
Objectives
To describe demographics, clinical characteristics, milestone diagnostic and clinical events (such as initial esophageal dilation), and outcomes in patients with EB using the Epidermolysis Bullosa Clinical Characterization and Outcomes Database and to determine what characteristics may be associated with overall EB severity and/or disease progression.
Design, Setting, and Participants
This cohort study included data on patients with EB who were enrolled in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database from January 1, 2011, to June 30, 2017; 17 participating EB centers in the United States and Canada contributed data to this study.
Exposures
Type of EB, including recessive dystrophic epidermolysis bullosa (RDEB), junctional epidermolysis bullosa (JEB), dominant dystrophic epidermolysis bullosa (DDEB), and epidermolysis bullosa simplex (EBS).
Main Outcomes and Measures
Demographic information, clinical characteristics (including age at onset of signs of EB and subsequent clinical diagnosis), types of diagnostic testing performed, and milestone clinical events for patients with RDEB.
Results
Of 644 enrolled patients from 17 sites included in this study, 323 were male (50.2%), with a mean (SD) age of 14.4 (11.7) years; 283 (43.9%) had RDEB, 194 (30.1%) had EBS, 104 (16.2%) had DDEB, and 63 (9.8%) had JEB. Signs of disease were present at birth in 202 patients with RDEB (71.4%), 39 with JEB (61.9%), 60 with DDEB (57.7%), and 74 with EBS (38.1%). For those with signs of disease at birth, a clinical diagnosis was made at the time of birth in 135 patients with RDEB (67.0%), 31 with DDEB (52.6%), 35 with EBS, (47.3%) and 18 with JEB (46.2%). Patients with JEB had the highest rate of any confirmatory testing (51 of 63 [81.0%]), followed by RDEB (218 of 283 [77.0%]), DDEB (71 of 104 [68.3%]), and EBS (100 of 194 [51.5%]). For all types of EB, both electron microscopy and immunofluorescence microscopy were performed at younger ages than genetic analysis. Among 283 patients with RDEB, 157 (55.5%) had esophageal dilation, 104 (36.7%) had gastrostomy tube placement, 62 (21.9%) had hand surgery, 18 (6.4%) developed squamous cell carcinoma, and 19 (6.7%) died.
Conclusions and Relevance
The findings suggest that diagnostic testing for EB is more common for patients with severe phenotypes. Earlier diagnostic testing may enable improved characterizations of patients so that appropriate counseling and clinical care may be offered, especially pertaining to milestone events for those with RDEB.
Research data used in the paper 'Treatment of lung disease in alpha-1 antitrypsin deficiency: a systematic review.', Edgar RG, Patel M, Bayliss S, Crossley D, Sapey E, Turner AM, forthcoming in The International Journal of Chronic Obstructive Pulmonary Disease (2017)
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