The IDDEA project: a strategy for the detection of alpha-1 antitrypsin deficiency in COPD patients in the primary care setting

Abstract

Abstract:Objective: Primary care provides the main route for access to health care for patients with common chronic illnesses such as chronic obstructive pulmonary disease (COPD). Alpha-1 antitrypsin (AAT) deficiency is an underdiagnosed pathology associated with COPD risk which has a very low prevalence. The Information and Detection of the Deficiency of AAT (IDDEA) project was developed to identify AAT-deficient patients at primary care centres by providing adequate diagnostic tools to family doctors. Methods: Patients with COPD were identified and registered on a specially designed website. Dried blood samples were collected on filter papers and sent to the laboratory for AAT levels and AAT deficiency-related genotype determinations. Results were uploaded to the website and analysed. Results: Between January 2008 and April 2009, 596 patients were identified by 90 participating physicians. The number of patients who did not have AAT deficiency (serum concentrations 60 mg AAT/dl) was 549 (98.9%). Nineteen patients (3.2%) were carriers of the allelic variant Pi*Z among which two were homozygous PiZZ (one of them was an index case) and one was heterozygous PiSZ. These three newly detected cases were registered in the Spanish Registry of Patients with AAT Deficiency. An estimate of the gene frequency of the S allele was 7.65% and the severe deficiency Z allele was 1.76%. Conclusions: Results confirm that ATT deficiency is still underdiagnosed. The IDDEA system appears to be a useful tool for the detection of AAT deficiency in the primary care setting.

Clinical phenotypes of Italian and Spanish patients with α1-antitrypsin deficiency

“…Unfortunately, the situation in Spain and Italy is worse with a mean delay of 9 years. More awareness campaigns are needed, especially among primary care physicians who care for most patients with COPD, particularly in early stages of the disease [23]. Another interesting difference is the higher prevalence of rare genotypes in Italy compared with Spain, which is in accordance with previous reports [24,25] and could be related to the differences between the two nationwide diagnostic algorithms [19].…”

Rare alpha-1-antitrypsin variants: are they really so rare?

“…In this last study, 20% of rare α1-AT genotypes corresponded to four previously uncharacterized variants, such as allele Lys259Ile in four cases (10% of rare alleles). α1-AT deficiency detection programs performed with dried blood spot (DBS) technology are based on detection of the major P*IS and PI*Z alleles [Molina et al 2011]. However, they can be interpreted as indirect evidence of the prevalence of rare α1-AT alleles.…”

“…null alleles which do not express the protein). Owing to their low frequency, these non-S and non-Z deficient variants are called 'rare' and most of them are difficult or even impossible to characterize using the isoelectrofocusing (IEF) method for α1-AT phenotyping or the usual allele-specific genotyping assay included in largescale screening programs for detecting P*IS and PI*Z alleles [Molina et al 2011]. This may have contributed to misclassification of many of these cases, which would misrepresent their true frequency.…”

Medical Costs of Alpha-1 Antitrypsin Deficiency-Associated COPD in the United States

“…57 This analysis detected signi cant delays in getting an AATD diagnosis after the initial COPD diagnosis. 51,58,59 This nding is important to patients and payers, as a timely diagnosis of AATD status would facilitate more personalized care, through a reduction in the number of unscheduled physician visits. 55 Building upon the premise that enrollment into a disease management program could potentially mitigate excess healthcare expenditures, earlier detection may lead to earlier bene t from ADMAPP.…”