Is PiSS Alpha-1 Antitrypsin Deficiency Associated with Disease?

McGee, Dawn; Schwarz, L; McClure, Rebecca; Peterka, Lauren; Rouhani, Farshid N.; Brantly, Mark; Strange, Charlie

doi:10.1155/2010/570679

Cited by 9 publications

(6 citation statements)

References 17 publications

(12 reference statements)

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“…Eden et al [ 16 ] showed that 44% of patients with AATD (20–25% of them with an allergy) had asthma, which was three times more prevalent in PI*MZ subjects than in PI*ZZ individuals. Other investigators have found an even higher percentage of asthmatics among PI*SS population when compared to subjects without deficient alleles [ 25 ]. We have not found any clinical association between AATD and AAT genotypes and severity of asthma among HDM sensitized patients.…”

Section: Discussionmentioning

confidence: 99%

Alpha 1 antitrypsin distribution in an allergic asthmatic population sensitized to house dust mites

Suárez-Lorenzo

Castro

Cruz-Niesvaara³

et al. 2018

Clin Transl Allergy

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Background and objectiveSevere alpha1 antitrypsin deficiency has been clearly associated with pulmonary emphysema, but its relationship with bronchial asthma remains controversial. Some deficient alpha 1 antitrypsin (AAT) genotypes seem to be associated with asthma development. The objective of this study was to analyze the distribution of AAT genotypes in asthmatic patients allergic to house dust mites (HDM), and to asses a possible association between these genotypes and severe asthma.MethodsA cross-sectional cohort study of 648 patients with HDM allergic asthma was carried out. Demographic, clinical and analytical variables were collected. PI*S and PI*Z AAT deficient alleles of the SERPINA1 gene were assayed by real-time PCR.ResultsAsthma was intermittent in 253 patients and persistent in 395 patients (246 mild, 101 moderate and 48 severe). One hundred and forty-five asthmatic patients (22.4%) with at least one mutated allele (S or Z) were identified. No association between the different genotypes and asthma severity was found. No significant differences in all clinical and functional tests, as well as nasal eosinophils, IgA and IgE serum levels were observed. Peripheral eosinophils were significantly lower in patients with the PI*MS genotype (p = 0.0228). Neither association between deficient AAT genotypes or serum ATT deficiency (AATD) and development of severe asthma, or correlation between ATT levels and FEV1 was observed.ConclusionIn conclusion, the distribution of AAT genotypes in HDM allergic asthmatic patients did not differ from those found in Spanish population. Neither severe ATTD or deficient AAT genotypes appear to confer different clinical expression of asthma.

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Section: Discussionmentioning

confidence: 99%

Alpha 1 antitrypsin distribution in an allergic asthmatic population sensitized to house dust mites

Suárez-Lorenzo

Castro

Cruz-Niesvaara³

et al. 2018

Clin Transl Allergy

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“…Regarding asthma, several investigators have suggested an increased risk of asthma among certain genotypes of AATD whereas others did not find an association. [10][11][12][13] Nevertheless, few studies suggested that AATD patients with concomitant asthma have a worse prognosis. 14,15 The recent ERS Statement of few years ago refer to the WHO recommendation to test all patients with COPD and all patients with adult-onset asthma.…”

Section: Introductionmentioning

confidence: 99%

<p>The Distribution of Alpha-1 Antitrypsin Genotypes Between Patients with COPD/Emphysema, Asthma and Bronchiectasis</p>

Veith¹,

Tüffers²,

Peychev³

et al. 2020

COPD

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Alpha-1-antitrypsin deficiency (AATD) is a rare hereditary condition characterized by low circulating levels of alpha-1antitrypsin (AAT). While the association between AATD and COPD/emphysema is undisputed, the association between AATD and asthma or bronchiectasis is still a matter of debate. Aims and Objectives: Our study aimed to investigate the distribution of AAT genotypes between patients with COPD/emphysema, asthma and bronchiectasis. To back up the diagnostic labels, we described symptoms associated with the diagnosis. Methods: Between September 2003 and March 2020, 29,465 testing kits (AlphaKit®) were analyzed in the AAT laboratory, University of Marburg, Germany. The diagnosis of AATD has been made based on the measurements of AAT serum levels, followed by genotyping, phenotyping or whole gene sequencing depending on the availability and/or the need for more detailed interpretation of the results. The respiratory symptoms were recorded as well. Results: Regarding the distribution of the wild type allele M and the most frequent mutations S (E264V) and Z (E342K), no significant differences could be found between COPD/emphysema [Pi*MM (58.24%); Pi*SZ (2.49%); Pi*ZZ (9.12%)] and bronchiectasis [Pi*MM (59.30%) Pi*SZ (2.81%); Pi*ZZ (7.02%)]. When COPD/emphysema and bronchiectasis were recorded in the same patient, the rate of Pi* ZZ (14.78%) mutations was even higher. Asthma patients exhibited significantly less deficient genotypes [Pi*MM (54.81%); Pi*SZ (2%); Pi*ZZ (2.77%)] than two other groups. Associated respiratory symptoms confirmed the diagnosis. Conclusion: COPD/emphysema and bronchiectasis, but not asthma patients, exhibit higher frequency of AATD genotypes. Our data suggest that AATD testing should be offered to patients with COPD/emphysema and bronchiectasis.

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“…Moreover, studies that measured pulmonary function did not find a difference between MS and MM individuals. Another study did attempt to address the risk of COPD in SS individuals but found no increased risk of obstructive lung disease and was limited by small sample size (McGee et al 2010). The effect of the I and F mutations on the AAT molecule has been described earlier, but to date any mention of COPD risk associated with these mutations is limited to case reports describing compound heterozygotes (Kelly et al 1989;Baur and Bencze 1987).…”

Section: Other Aatd Phenotypes As Genetic Risk Factors For Copdmentioning

confidence: 99%