Therapeutic efficacy of alpha-1 antitrypsin augmentation therapy on the loss of lung tissue: an integrated analysis of 2 randomised clinical trials using computed tomography densitometry

Stockley, Robert A.; Parr, David; Piitulainen, Eeva; Stolk, Jan; Stoel, Berend C.; Dirksen, Asger

doi:10.1186/1465-9921-11-136

Cited by 164 publications

(114 citation statements)

References 28 publications

(57 reference statements)

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“…It is associated with lower zone dominant emphysema [58], although significant heterogeneity exists, possibly due to genetic modifiers, as in usual COPD [59]. Augmentation therapy for AATD has been routinely used in some countries since the first trials were completed; a meta-analysis has demonstrated that it may reduce emphysema progression [15]. Further trials, including inhaled α 1 -antitrypsin, are due to be published soon and other specific therapies may become available in due course [60].…”

Section: Subgroups With Implications For Treatmentmentioning

confidence: 99%

Clinically relevant subgroups in COPD and asthma

Turner

Tamási

Schleich³

et al. 2015

Eur Respir Rev

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As knowledge of airways disease has grown, it has become apparent that neither chronic obstructive pulmonary disease (COPD) nor asthma is a simple, easily defined disease. In the past, treatment options for both diseases were limited; thus, there was less need to define subgroups. As treatment options have grown, so has our need to predict who will respond to new drugs. To date, identifying subgroups has been largely reported by detailed clinical characterisation or differences in pathobiology. These subgroups are commonly called "phenotypes"; however, the problem of defining what constitutes a phenotype, whether this should include comorbid diseases and how to handle changes over time has led to the term being used loosely.In this review, we describe subgroups of COPD and asthma patients whose clinical characteristics we believe have therapeutic or major prognostic implications specific to the lung, and whether these subgroups are constant over time. Finally, we will discuss whether the subgroups we describe are common to both asthma and COPD, and give some examples of how treatment might be tailored in patients where the subgroup is clear, but the label of asthma or COPD is not. @ERSpublications Summary of subgroups of airways disease that can be found in COPD and asthma, and their management

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Section: Subgroups With Implications For Treatmentmentioning

confidence: 99%

Clinically relevant subgroups in COPD and asthma

Turner

Tamási

Schleich³

et al. 2015

Eur Respir Rev

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“…46 Combined analysis of 2 clinical trials of intravenous alpha-1 antitrypsin augmentation showed that this medication significantly reduces the decline in lung density in individuals with alpha-1 antitrypsin deficiency. 47 In individuals with smoking-related emphysema, Gietema, et al, evaluated 157 individuals enrolled in a lung cancer screening study, who underwent repeat CT scans within 3 months, and found that the limits of agreement for %LAA -950 were from -1.3% to +1.1%, suggesting that CT can detect a change of 1.1% in extent of emphysema with 95% probability. In 1,928 individuals enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE study) Coxson, et al, found an average annual decline in lung density of 1.13g/L, after correction for lung volume, in a group of 1,928 current and former smokers.…”

Section: Longitudinal Evaluationmentioning

confidence: 99%

Progress in Imaging COPD, 2004 - 2014

Lynch¹

2014

J COPD F

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Abbreviations: computed tomography, CT; magnetic resonance imaging, MRI; positron emission tomography, PET; Global Initiative for chronic Obstructive Lung Disease, GOLD; quantitative CT, QCT; Hounsfield Units, HU; percentage of low attenuation area, %LAA; relative area of lung less than -950 HU, RA950; Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints, ECLIPSE; forced expiratory volume in 1 second, FEV1; forced vital capacity, FVC. Journal of the COPD Foundation(GOLD) stage may have substantial, little, or no emphysema. Discrete subphenotypes of COPD include emphysema of varying morphologic appearance, large airway abnormality and small airway obstruction. Increasing awareness of the heterogeneity of COPD has led to increased use of CT to characterize COPD for purposes of genetic evaluation and identification of specific subgroups which may be amenable to therapeutic trials. 1-3 While visual assessment is important in determining the presence and character of emphysema, the last decade has been characterized by increasing use of quantitative imaging to provide precise estimates of the severity and distribution of emphysema, gas trapping and airway wall thickening. Several large cohorts of cigarette smokers have now been quite extensively characterized by CT, resulting in increased knowledge of the clinical correlates of quantitative CT parameters. [4][5][6] The purpose of this paper is to present the substantial contribution that imaging has made to our understanding of COPD over the past 10 years. AbstractComputed tomography (CT) has contributed substantially to our understanding of COPD over the past decade. Visual and quantitative assessments of CT in COPD are complementary. Visual assessment should provide assessment of centrilobular, panlobular and paraseptal emphysema, airway wall thickening, bronchiectasis, findings of respiratory bronchiolitis, and enlargement of the pulmonary artery. Quantitative CT permits evaluation of severity of emphysema, airway wall thickening, and expiratory air trapping, and is now being used for longitudinal evaluation of the progression of COPD. Innovative techniques are being developed to use CT to characterize the pattern of emphysema and smoking-related respiratory bronchiolitis. Magnetic resonance imaging (MRI) and positron emission tomography PET-CT are useful research tools in the evaluation of COPD.

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“…The mean change in lung density from baseline to last CT scan was −4.082 g·L −1 for AAT therapy and −6.379 g·L −1 for placebo, with a treatment difference of 2.297 (95% CI 0.669-3.926; p=0.006). The corresponding annual declines in lung density were −1.73 g·L , respectively [14].…”

Section: Delaying the Progression Of Emphysemamentioning

confidence: 97%

“…Data from two similar randomised, double-blind, placebo-controlled trials (the EXACTLE study and a Danish-Dutch study), both of which investigated the efficacy of AAT augmentation therapy on emphysema progression using CT densitometry, were pooled (to increase the statistical power) [14]. Mean follow-up was ∼2.5 years.…”

Section: Delaying the Progression Of Emphysemamentioning

confidence: 99%

Long-term experience in the treatment of α₁-antitrypsin deficiency: 25 years of augmentation therapy

Teschler

2015

Eur Respir Rev

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Although it is often under-recognised, α 1 -antitrypsin deficiency (AATD) represents one of the most common genetic respiratory disorders worldwide. Since the publication of studies in the late 1980s, which demonstrated that plasma-derived augmentation therapy with intravenous α 1 -antitrypsin (AAT) can reverse the biochemical deficiencies in serum and lung fluid that characterise emphysema, augmentation therapy has become the cornerstone of patient management. This article, with a focus on experience gained in clinical practice in Germany, provides an overview of some of the research highlights and clinical experience gained in the use of augmentation therapy for AATD during the past 25 years, and briefly discusses the potential role of AAT augmentation therapy in lung transplant recipients. Additionally, the goals of AAT augmentation therapy will be discussed, namely to delay the progression of emphysema, reduce the frequency of exacerbations and improve health-related quality of life. Beyond pulmonary disease, there is recent growing evidence to indicate that AATD could also play a role in rare disorders such as panniculitis, granulomatosis with polyangiitis and ulcerative colitis. @ERSpublications Overview of long-term experience gained with AAT augmentation therapy for the treatment of AATD http://ow.ly/HmJLR

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Therapeutic efficacy of alpha-1 antitrypsin augmentation therapy on the loss of lung tissue: an integrated analysis of 2 randomised clinical trials using computed tomography densitometry

Cited by 164 publications

References 28 publications

Clinically relevant subgroups in COPD and asthma

Clinically relevant subgroups in COPD and asthma

Progress in Imaging COPD, 2004 - 2014

Long-term experience in the treatment of α₁-antitrypsin deficiency: 25 years of augmentation therapy

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Therapeutic efficacy of alpha-1 antitrypsin augmentation therapy on the loss of lung tissue: an integrated analysis of 2 randomised clinical trials using computed tomography densitometry

Cited by 164 publications

References 28 publications

Clinically relevant subgroups in COPD and asthma

Clinically relevant subgroups in COPD and asthma

Progress in Imaging COPD, 2004 - 2014

Long-term experience in the treatment of α1-antitrypsin deficiency: 25 years of augmentation therapy

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Product

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Long-term experience in the treatment of α₁-antitrypsin deficiency: 25 years of augmentation therapy