Longitudinal lung function study in heterozygous PiMZ phenotype subjects

Tarján, É.; Magyar, P.; Váczi, Z.; Lantos, A; Vaszar, Laszlo T.

doi:10.1183/09031936.94.07122199

Cited by 48 publications

(16 citation statements)

References 26 publications

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“…In a prospective cohort that followed iron-ore miners for 5 years, MZ individuals had more decline in FEV1/FVC than MM ones, but there was no difference in respiratory symptoms [61]. In another 10-year longitudinal study among a cohort of nonsmokers matched for age, height and body weight, pulmonary elasticity was measured and was found to decrease significantly over time in the MZ group when compared to the MM group [62]. In smokers there was a significant difference in FEV1, with annual decline of 75 mL in MZ versus 53 mL in MM subjects [63].…”

Section: Progression Of Obstructive Lung Disease In Mz Individualsmentioning

confidence: 94%

COPD in individuals with the PiMZ alpha-1 antitrypsin genotype

Ashry

Strange

2017

Eur Respir Rev

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Since the discovery of severe alpha-1 antitrypsin deficiency as a genetic risk factor for emphysema, there has been ongoing debate over whether individuals with intermediate deficiency with one protease inhibitor Z allele (PiMZ, or MZ) are at some risk for emphysema. This is important, because MZ individuals comprise 2-5% of the general population. In this review we summarise the evidence about the risks of the MZ population to develop emphysema or asthma. We discuss the different study designs that have tried to answer this question. The risk of emphysema is more pronounced in case-control than in population-based studies, perhaps due to inadequate power. Carefully designed family studies show an increased risk of emphysema in MZ smokers. This is supported by the rapid decline in lung function of MZ individuals when compared to the general population after massive environmental exposures. The risk of asthma in MZ subjects is less studied, and more literature is needed before firm conclusions can be made. Augmentation therapy in MZ individuals is not supported by any objective studies. MZ smokers are at increased risk for emphysema that is more pronounced when other environmental challenges are present.

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Section: Progression Of Obstructive Lung Disease In Mz Individualsmentioning

confidence: 94%

COPD in individuals with the PiMZ alpha-1 antitrypsin genotype

Ashry

Strange

2017

Eur Respir Rev

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“…However, because the low prevalence of the relevant AAT variants, the proportion of COPD attributable to this gene was only y1%. A few studies assessing the association between different genotypes and the development of COPD suggested that those with an MZ genotype could be at higher risk of COPD than those with an MM genotype [69,70]. Other recent findings include studies showing an association between the presence of deoxyribonucleic acid (DNA) instability and COPD in smokers [71] and a higher frequency of the glutathione S-transferase (GSTP1) polymorphism in patients with COPD [72].…”

Section: Genetic Determinantsmentioning

confidence: 98%

Epidemiology of chronic obstructive pulmonary disease

Antó¹,

Vermeire²,

Vestbo³

et al. 2001

Eur Respir J

344

208

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Epidemiology of chronic obstructive pulmonary disease. J.M. Antó, P. Vermeire, J. Vestbo, J. Sunyer. #ERS Journals Ltd 2001. ABSTRACT: Chronic obstructive pulmonary disease (COPD) is a leading cause of world-wide mortality and disability. On average y5-15% of adults in industrialized countries have COPD defined by spirometry. In 1990, COPD was considered to be at the twelfth position world-wide as a cause of combined mortality and disability but is expected to become the fifth cause by the year 2020.COPD has a chronic long-lasting course characterized by irreversible decline of forced expiratory volume in one second (FEV1), increasing presence of dyspnoea and other respiratory symptoms, and progressive deterioration of health status. After diagnosis the 10-yr survival rate is y50% with more than one-third of patients dying due to respiratory insufficiency.Several environmental exposures such as air pollution increase the risk of death in COPD patients. The aetiology of COPD is overwhelmingly dominated by smoking although many other factors could play a role. Particular genetic variants are likely to increase the susceptibility to environmental factors although little is known about which are the relevant genes. There is clear evidence about the role of the a-1-antitrypsin but the fraction of COPD attributable to the relevant variants is only 1%. Phenotypic traits that are considered to play a role in the development of COPD include sex, with females being at a higher risk, bronchial responsiveness and atopy. There is strong causal evidence regarding the relationship between smoking and COPD with decline in FEV1 levelling off after smoking cessation. Passive smoking has been found to be associated with a small though statistically significant decline in FEV1. Other risk factors that are likely to be relevant in the development of COPD are occupation, low socioeconomic status, diet and possibly some environmental exposures in early life.Although there is accumulating evidence that oxygen therapy, pharmacological treatment and rehabilitation may improve the course of chronic obstructive pulmonary disease, preventing smoking continues to be the most relevant measure, not only to prevent chronic obstructive pulmonary disease, but also to arrest its development. Eur Respir J 2001; 17: 982-994.

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“…Heterozygous, PiMZ individuals have moderately reduced serum levels A1AT, but whether they have increased risk of COPD is uncertain. Tarjan et al (Tarjan et al, 1994) in longitudinal lung function study in heterozygous PiMZ subjects observed a decrease in elasticity and deterioration lung function parameters in comparison to those without A1ATD, which supports the concept of PiMZ phenotype being a risk factor for pulmonary emphysema development at a younger age. Dahl et al (Dahl et al, 2002) found that PiMZ heterozygotes had a slightly greater rate of decrease in FEV 1 .…”

Section: Hereditary Alpha-1-antitrypsin Deficiency and Emphysemamentioning

confidence: 59%