Long-term evolution of lung function in individuals with alpha-1 antitrypsin deficiency from the Spanish registry (REDAAT)

Esquinas, Cristina; Serreri, Sonia; Barrecheguren, Miriam; Rodrı́guez, Esther; Núñez, Alexa; Maldonado, Francisco Casas; Blanco, Ignacio; Pirina, Pietro; Lara, Beatríz; Miravitlles, Marc

doi:10.2147/copd.s155226

Cited by 20 publications

(15 citation statements)

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“…In clinical practice, lung emphysema and chronic bronchitis are the most common clinical phenotypes of COPD associated with PiZZ deficiency [4]. Environmental factors, particularly cigarette smoke, greatly increase the risk of COPD development [2], and while the onset of respiratory disease in smokers occurs in the third or fourth decades of life, in nonsmokers the onset can be delayed to the fifth or sixth decades, and even some nonsmokers may have a normal life span without developing COPD or other diseases associated with AAT deficiency [5][6][7][8][9]. This striking variability of clinical expression suggests that in a number of cases AAT deficiency alone is not enough to induce COPD, and that, in addition to smoking and other environmental pollutants, genetic modifiers not yet definitively identified likely influence this clinical variability [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Prevalence of α₁-antitrypsin PiZZ genotypes in patients with COPD in Europe: a systematic review

et al. 2020

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The percentage of α1-antitrypsin protease inhibitor ZZ (PiZZ) genotypes in patients with COPD is controversial, with large differences among various studies. We aimed to estimate the prevalence of PiZZ in COPD patients from 20 European countries with available data, according to the number of PiZZ and COPD individuals in each country.A systematic review was conducted to select European countries with reliable data on the prevalence of PiZZ and COPD. We created a database with the following data: 1) total population and population aged ≥40 years according to the Eurostat database; 2) number and 95% CI of PiZZ patients aged ≥40 years; 3) application of a conversion factor of genetic penetrance of 60%; 4) number of COPD individuals, with 95% CI, aged ≥40 years; and 5) calculation of the PiZZ/COPD ratio. Finally, results were presented using an Inverse Distance Weighted Interpolation map.We found 36 298 (95% CI 23 643–56 594) PiZZ individuals at high risk and 30 849 709 (95% CI 21 411 293–40 344 496) COPD patients, with a PiZZ/COPD ratio of 0.12% (range 0.08–0.24%), and a prevalence of 1 out of 408 in Northern, 1 out of 944 in Western, 1 out of 1051 in Central, 1 out of 711 in Southern, and 1 out of 1274 in Eastern Europe.These data may be useful to plan strategies for future research and diagnosis, and to rationalise the available therapeutic resources.

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Section: Introductionmentioning

confidence: 99%

Prevalence of α₁-antitrypsin PiZZ genotypes in patients with COPD in Europe: a systematic review

et al. 2020

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“…The national German registry analysis with patients who had not received augmentation therapy (n=15) and patients who did receive therapy (n=85) over a mean follow-up of 4.89 years [ 22 ] showed no difference in FEV 1 decline between groups. Neither did the analysis of the Spanish national database of patients who did not receive augmentation therapy (n=45) and patients who did receive augmentation therapy (n=77) over an average of >8 years [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Long-term effect of α₁-antitrypsin augmentation therapy on the decline of FEV₁in deficient patients: an analysis of the AIR database

et al. 2021

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BackgroundPatients with ZZ (Glu342Lys) alpha-1-antitrypsin deficiency (ZZ-AATD) who received augmentation therapy with alpha-1-antitrypsin (AAT) in randomised controlled trials over 2–3 years, failed to show a significant reduction of the annual decline of FEV1.MethodsTo compare the trajectory of FEV1 change during 4 or more years in ZZ-AATD patients with emphysema receiving or not receiving intravenous augmentation therapy, a retrospective analysis of FEV1 values entered in the Alpha-1 International Registry (AIR) of ZZ-AATD patients from five different European countries: Germany, UK, Spain, Italy and The Netherlands was performed. The post-bronchodilator FEV1%predicted values for baseline and follow-up over time from patients were analysed using linear mixed effects models.ResultsData of 374 patients were analysed: 246 untreated and 128 treated with intravenous AAT augmentation therapy. The mean follow-up duration of the untreated group was 8.60 (sd±3.34) years and 8.59 (±2.62) years for the treated group. The mixed effects model analysis showed a mean FEV1 decline of −0.931% predicted per year (95% confidence interval −1.144 to −0.718) in the untreated group and a decline of −1.016% predicted per year (−1.319 to −0.7145) in the treated group. The likelihood ratio test showed no difference between the two groups (p=0.71).ConclusionIn our study population, we could not detect a significant difference in the annual decline of FEV1 by AAT augmentation treatment over an average period of 8.6 years. Other approaches are needed to validate any benefit of augmentation therapy.

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“…Although the decline in FEV 1 did not differ significantly between never‐ and ex‐smokers in an UK study, there was substantial inter‐individual variability and the progression of emphysema assessed by lung density in computed tomography (CT) scans appeared to continue even when FEV 1 remains stable 92 . Recent work from a large Spanish A1AT registry confirmed great inter‐individual variability regarding lung function decline, but reported values comparable to usually observed in COPD 93 . Once clinical lung disease has developed survival is poor, whereas it seems that never‐smokers with A1AT‐deficiency need not have an increased mortality 94 …”

Section: Natural History Of Copdmentioning

confidence: 90%

“…92 Recent work from a large Spanish A1AT registry confirmed great inter-individual variability regarding lung function decline, but reported values comparable to usually observed in COPD. 93 Once clinical lung disease has developed survival is poor, whereas it seems that never-smokers with A1AT-deficiency need not have an increased mortality. 94…”

Section: Natural History Of Copd Associated With A1at Deficiencymentioning

confidence: 99%

Natural history and mechanisms of COPD

et al. 2021

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The natural history of COPD is complex, and the disease is best understood as a syndrome resulting from numerous interacting factors throughout the life cycle with smoking being the strongest inciting feature. Unfortunately, diagnosis is often delayed with several longitudinal cohort studies shedding light on the long ‘preclinical’ period of COPD. It is now accepted that individuals presenting with different COPD phenotypes may experience varying natural history of their disease. This includes its inception, early stages and progression to established disease. Several scenarios regarding lung function course are possible, but it may conceptually be helpful to distinguish between individuals with normal maximally attained lung function in their early adulthood who thereafter experience faster than normal FEV1 decline, and those who may achieve a lower than normal maximally attained lung function. This may be the main mechanism behind COPD in the latter group, as the decline in FEV1 during their adult life may be normal or only slightly faster than normal. Regardless of the FEV1 trajectory, continuous smoking is strongly associated with disease progression, development of structural lung disease and poor prognosis. In developing countries, factors such as exposure to biomass and sequelae after tuberculosis may lead to a more airway‐centred COPD phenotype than seen in smokers. Mechanistically, COPD is characterized by a combination of structural and inflammatory changes. It is unlikely that all patients share the same individual or combined mechanisms given the heterogeneity of resultant phenotypes. Lung explants, bronchial biopsies and other tissue studies have revealed important features. At the small airway level, progression of COPD is clinically imperceptible, and the pathological course of the disease is poorly described. Asthmatic features can further add confusion. However, the small airway epithelium is likely to represent a key focus of the disease, combining impaired subepithelial crosstalk and structural/inflammatory changes. Insufficient resolution of inflammatory processes may facilitate these changes. Pathologically, epithelial metaplasia, inversion of the goblet to ciliated cell ratio, enlargement of the submucosal glands and neutrophil and CD8‐T‐cell infiltration can be detected. Evidence of type 2 inflammation is gaining interest in the light of new therapeutic agents. Alarmin biology is a promising area that may permit control of inflammation and partial reversal of structural changes in COPD. Here, we review the latest work describing the development and progression of COPD with a focus on lung function trajectories, exacerbations and survival. We also review mechanisms focusing on epithelial changes associated with COPD and lack of resolution characterizing the underlying inflammatory processes.

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Long-term evolution of lung function in individuals with alpha-1 antitrypsin deficiency from the Spanish registry (REDAAT)

Cited by 20 publications

References 40 publications

Prevalence of α₁-antitrypsin PiZZ genotypes in patients with COPD in Europe: a systematic review

Prevalence of α₁-antitrypsin PiZZ genotypes in patients with COPD in Europe: a systematic review

Long-term effect of α₁-antitrypsin augmentation therapy on the decline of FEV₁in deficient patients: an analysis of the AIR database

Natural history and mechanisms of COPD

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Long-term evolution of lung function in individuals with alpha-1 antitrypsin deficiency from the Spanish registry (REDAAT)

Cited by 20 publications

References 40 publications

Prevalence of α1-antitrypsin PiZZ genotypes in patients with COPD in Europe: a systematic review

Prevalence of α1-antitrypsin PiZZ genotypes in patients with COPD in Europe: a systematic review

Long-term effect of α1-antitrypsin augmentation therapy on the decline of FEV1in deficient patients: an analysis of the AIR database

Natural history and mechanisms of COPD

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Product

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Prevalence of α₁-antitrypsin PiZZ genotypes in patients with COPD in Europe: a systematic review

Prevalence of α₁-antitrypsin PiZZ genotypes in patients with COPD in Europe: a systematic review

Long-term effect of α₁-antitrypsin augmentation therapy on the decline of FEV₁in deficient patients: an analysis of the AIR database