Comparing Patients with ZZ Versus SZ Alpha-1 Antitrypsin Deficiency: Findings from AlphaNet’s Disease Management Program

Choate, Radmila; Mannino, David M.; Holm, Kristen E.; Sandhaus, Robert A.

doi:10.15326/jcopdf.6.1.2018.0134

Cited by 13 publications

(19 citation statements)

References 27 publications

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“…In national and international AATD registries, patients with the PI*SZ genotype generally constitute a smaller proportion of the total number of patients (from 1.0 to 21.3%), with the highest number of PI*SZ individuals reported by the Spanish registry (Table 1) [15][16][17][18][19][20][21][22][23][24][25]. However, not all of these individuals have symptomatic disease (index cases), as some registries, e.g., the Danish and Irish targeted detection programmes, conduct screening of family members of diagnosed individuals specifically to identify non-index cases [24,26].…”

Section: Prevalence Of the Pi*sz Genotypementioning

confidence: 99%

“…Smoking is a key risk factor for the development of lung disease in patients with AATD and disease progression and survival are both significantly worse in smokers than never-smokers [4,42]. Recent studies have shown that identified PI*SZ individuals are more likely to have a history of tobacco smoking, and generally worse health than PI*ZZ individuals, and also demonstrate worse behaviours associated with poor health (such as lack of exercise) [16,17]. However, there are conflicting reports as to the individual impact of smoking on the development of lung disease in PI*SZ individuals.…”

Section: Influence Of Smokingmentioning

confidence: 99%

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Clinical considerations in individuals with α₁-antitrypsin PI*SZ genotype

et al. 2020

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α1-Antitrypsin deficiency (AATD), characterised by reduced levels or functionality of α1-antitrypsin (AAT), is a significantly underdiagnosed genetic condition that predisposes individuals to lung and liver disease. Most of the available data on AATD are based on the most common, severe deficiency genotype (PI*ZZ); therefore, treatment and monitoring requirements for individuals with the PI*SZ genotype, which is associated with a less severe AATD, are not as clear. Recent genetic data suggest the PI*SZ genotype may be significantly more prevalent than currently thought, due in part to less frequent identification in the clinic and less frequent reporting in registries. Intravenous AAT therapy, the only specific treatment for patients with AATD, has been shown to slow disease progression in PI*ZZ individuals; however, there is no specific evidence for AAT therapy in PI*SZ individuals, and it remains unclear whether AAT therapy should be considered in these patients. This narrative review evaluates the available data on the PI*SZ genotype, including genetic prevalence, the age of diagnosis and development of respiratory symptoms compared with PI*ZZ individuals, and the impact of factors such as index versus non-index identification and smoking history. In addition, the relevance of the putative 11 µM “protective threshold” for AAT therapy and the risk of liver disease in PI*SZ individuals is explored. The purpose of this review is to identify open research questions in this area, with the aim of optimising the future identification and management of PI*SZ individuals.

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Section: Prevalence Of the Pi*sz Genotypementioning

confidence: 99%

Section: Influence Of Smokingmentioning

confidence: 99%

Clinical considerations in individuals with α₁-antitrypsin PI*SZ genotype

et al. 2020

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“…Whilst their milder genetic profile when compared with PiZZ makes PiSZ, SS, and MZ patients less likely to develop adverse effects linked to AATD, such genotypes are much more prevalent than ZZ in the world 5 – 7 , and in the presence of unhealthy behaviors they become big risk groups for the development of lung disease. This enhances public health need to increase diagnosis and implement preventive measures in these patients 7 , 8 .…”

Section: Which Patients Develop Clinically Relevant Disease?mentioning

confidence: 99%

“…The major clinical risk in PiSZ is the development of COPD, which is three times higher compared with PiMM 9 , less so in never-smoking patients 10 . When PiSZ patients develop emphysema, usually it has an apical dominance 5 ; physicians’ cognitive bias to screen for AATD mainly in basal emphysema may exclude them from testing and follow-up, thus leading to a greater proportion of undiagnosed patients relative to PiZZ. Reversibility has also been observed in a large number of patients, which is frequently associated with more severe airflow obstruction 10 .…”

Section: Which Patients Develop Clinically Relevant Disease?mentioning

confidence: 99%

Alpha-1 antitrypsin deficiency: an update on clinical aspects of diagnosis and management

Santos¹,

Turner²

2020

Fac Rev

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Clinical heterogeneity has been demonstrated in alpha-1 antitrypsin deficiency (AATD), such that clinical suspicion plays an important role in its diagnosis. The PiZZ genotype is the most common severe deficiency genotype and so tends to result in the worst clinical presentation, hence it has been the major focus of research. However, milder genotypes, especially PiSZ and PiMZ, are also linked to the development of lung and liver disease, mainly when unhealthy behaviors are present, such as smoking and alcohol use. Monitoring and managing AATD patients remains an area of active research. Lung function tests or computed tomography (CT) densitometry may allow physicians to identify progressive disease during follow up of patients, with a view to decision making about AATD-specific therapy, like augmentation therapy, or eventually surgical procedures such as lung volume reduction or transplant. Different types of biological markers have been suggested for disease monitoring and therapy selection, although most need further investigation. Intravenous augmentation therapy reduces the progression of emphysema in PiZZ patients and is available in many European countries, but its effect in milder deficiency is less certain. AATD has also been suggested to represent a risk factor and trigger for pulmonary infections, like those induced by mycobacteria. We summarize the last 5–10 years’ key findings in AATD diagnosis, assessment, and management, with a focus on milder deficiency variants.

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“…In terms of genotype frequencies, two subjects were PiZZ and were already confirmed AATD cases. Another two subjects were identified as PiSZ and were also counted as severely deficient, though this may not be appropriate, since there is debate in the literature about whether the clinical risk attributable solely to the genetic mutation is similar [11,12]. In terms of heterozygosity of deficient alleles, 40 subjects carried a single Z and 143 a single S allele.…”

mentioning

confidence: 99%

Modernising case finding for α₁-antitrypsin deficiency by DNA sequencing of COPD patients

Quinn

Turner

2020

Eur Respir J

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Alpha-1-antitrypsin deficiency (AATD) is a hereditary metabolic disorder caused by mutations in the SERPINA1 gene that result in a reduction in the serum concentration of the protein alpha-1-antitrypsin (AAT), and a predisposition to COPD [1]. AAT functions as an inhibitor of neutrophil elastase (and other proteases) and is essential in maintaining a balance of protease and antiprotease activity in the lungs [2]. Imbalance causes an escalating cycle of inflammation and degradation of lung tissue that, over time, leads to COPD [3].

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Comparing Patients with ZZ Versus SZ Alpha-1 Antitrypsin Deficiency: Findings from AlphaNet’s Disease Management Program

Abstract: For personal use only. Permission required for all other uses.

Cited by 13 publications

References 27 publications

Clinical considerations in individuals with α₁-antitrypsin PI*SZ genotype

Clinical considerations in individuals with α₁-antitrypsin PI*SZ genotype

Alpha-1 antitrypsin deficiency: an update on clinical aspects of diagnosis and management

Modernising case finding for α₁-antitrypsin deficiency by DNA sequencing of COPD patients

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Comparing Patients with ZZ Versus SZ Alpha-1 Antitrypsin Deficiency: Findings from AlphaNet’s Disease Management Program

Abstract: For personal use only. Permission required for all other uses.

Cited by 13 publications

References 27 publications

Clinical considerations in individuals with α1-antitrypsin PI*SZ genotype

Clinical considerations in individuals with α1-antitrypsin PI*SZ genotype

Alpha-1 antitrypsin deficiency: an update on clinical aspects of diagnosis and management

Modernising case finding for α1-antitrypsin deficiency by DNA sequencing of COPD patients

Contact Info

Product

Resources

About

Clinical considerations in individuals with α₁-antitrypsin PI*SZ genotype

Clinical considerations in individuals with α₁-antitrypsin PI*SZ genotype

Modernising case finding for α₁-antitrypsin deficiency by DNA sequencing of COPD patients