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Alpha-1 Antitrypsin Deficiency in a French General Hospital: Fortuitous Detection Rather Than Efficient Screening

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Alpha-1 Antitrypsin Deficiency in a French General Hospital: Fortuitous Detection Rather Than Efficient Screening Alpha-1 antitrypsin deficiency in a French General Hospital: fortuitous detection rather than efficient screening. Hakim Kherouf, Geoffroy de Faverges, Pierre J.J. Dumont, Evelyne Bourgerette, Tu N’Guyen, Olivier Moquet To cite this version: Hakim Kherouf, Geoffroy de Faverges, Pierre J.J. Dumont, Evelyne Bourgerette, Tu N’Guyen, et al.. Alpha-1 antitrypsin deficiency in a French General Hospital: fortuitous detection rather than efficient screening.. Advances in Respiratory Medicine, Via Medica, 2018, 86 (4), pp.179-182. 10.5603/ARM.a2018.0027. hal-01382807v3 HAL Id: hal-01382807 https://hal.archives-ouvertes.fr/hal-01382807v3 Submitted on 11 Dec 2018 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. ORIGINAL RESEARCH Hakim Kherouf1, Geoffroy De Faverges2, Pierre Dumont1, Evelyne Bourgerette1, Tu Nguyen3, Olivier Moquet1 1Laboratoire de Biologie Medicale, Centre Hospitalier de l’Agglomération de Nevers, France 2Service de Pneumologie, Centre Hospitalier de l’Agglomération de Nevers, France 3Département de l’Information Medicale, Centre Hospitalier de l’Agglomération de Nevers, France Alpha-1 antitrypsin deficiency in a French General Hospital: fortuitous detection rather than efficient screening The authors declare no financial disclosure Abstract Introduction: We studied the characteristics of the screening procedure for alpha-1 antitrypsin at Nevers Hospital (France), together with the performance of serum protein gel electrophoresis for the fortuitous detection of patients with deficiency. Material and methods: We carried out a retrospective study of requests for alpha-1 antitrypsin determination referred to the laboratory during 3 years. We compared these requests with the numbers of patients seen at the hospital and requiring screening according to international recommendations. In parallel, we reviewed all the serum protein gel electrophoresis results obtained during the same period. Results: The laboratory received 102 direct requests for alpha-1 antitrypsin determination, whereas more than 1397 patients presented an indication for screening. No case of alpha-1 antitrypsin deficiency was detected among the 102 patients screened. In parallel, 5551 serum protein gel electrophoresis analyses were carried out at the laboratory. A decrease in the size of the alpha-1 globulin fraction was detected in 68 patients. Seventeen of these patients underwent alpha-1 antitrypsin determinations and 14 were found to have alpha-1 antitrypsin deficiency. Conclusion: Alpha-1 antitrypsin deficiency was more frequently detected fortuitously, by electrophoresis, than through efficient screening. The exploration of alpha-1 globulin deficiencies by serum protein gel electrophoresis thus appears to be still a particu- larly efficient approach to the detection of alpha-1 antitrypsin deficiency and should be carried out systematically. Furthermore, the testing of all patients with an indication for screening according to international recommendations should be encouraged. Key words: alpha-1 antitrypsin deficiency, serum protein electrophoresis, agar gel electrophoresis, PI phenotype, screening Adv Respir Med. 2018; 86: 179–182 Introduction cies of alpha-1 antitrypsin (AAT), the principal plasma protease inhibitor, based on the absence of Carl-Bertil Laurell, a biochemist at the Uni- a serum alpha-1 fraction on SPE. In collaboration versity of Malmö, was one of the pioneers of the with Sten Erikson, he subsequently demonstrated development of serum protein electrophoresis the relationship between AAT deficiency and the (SPE) as a diagnostic tool in medicine. In 1961, development of emphysema [1]. he introduced the use of agarose gels, in place Today, the biological diagnosis of AAT defi- of paper, as a support for the migration and se- ciency is based on sensitive and specific quanti- paration of proteins, a “standard” technique still fications of plasma AAT by immunoturbidimetry widely used in medical laboratories. In 1963, he or nephelometry, which is then followed by identified the first patients with severe deficien- isoelectric focusing to phenotype the most com- Address for correspondence: Olivier Moquet, Laboratoire de Biologie Médicale, Centre Hospitalier de l’Agglomération de Nevers 1, Boulevard de l’Hôpital 58 000 Nevers, France, Tel. +33 (0)3 86 93 73 67, Fax : +33 (0)3 86 93 73 61, e-mail: [email protected] DOI: 10.5603/ARM.a2018.0027 Received: 21.06.2018 Copyright © 2018 PTChP ISSN 2451–4934 www.journals.viamedica.pl 179 Advances in Respiratory Medicine 2018, vol. 86, no. 4, pages 179–182 mon variants, or genotyping [2]. In France, these This study has been declared to the CNIL, the examinations are carried out by a few specialized French Commission for Data Protection & Civil laboratories, but testing is accessible nationwide, Liberties (No. 1860860). via subcontracting through a network of hospital and private medical laboratories. Nevertheless, Results AAT deficiency remains underdiagnosed in Fran- ce and worldwide, despite the existence of inter- The laboratory received 119 requests, inclu- national recommendations for screening [2]. It is ding 102 direct requests for AAT determination, estimated, for example, that only 5 to 10% of the during the study period. Overall, 28 of the tests 7,500 to 10,000 patients with the PiZ phenotype, were performed for the exploration of liver di- the most severe form of this deficiency, have been sorders, 70 for respiratory disorders (32 for em- identified in France [3, 4], and that this condition physema, 28 for chronic obstructive pulmonary is diagnosed on average 10 years after the appe- disease (COPD), 5 for asthma, 5 for sleep apnea, arance of the first symptoms [5]. In Poland, the and 2 for pneumothorax), 1 in the context of number of patients with the PiZ phenotype is vasculitis, and 3 for unknown indications (not estimated to be between 4,189 and 7,000 [6]. recorded). No cases of AAT deficiency were de- Serum protein electrophoresis remains as re- tected in the 102 directly requested AAT deter- levant as ever and is still widely prescribed for the minations. Over the same period, 1,397 patients exploration of various diseases (hematological, li- admitted to the hospital had an indication for ver, renal and inflammatory diseases, for example). screening: 1,180 had COPD, 147 had pulmonary The widespread use of this technique may emphysema, 38 had partially irreversible asth- still allow the fortuitous discovery of patients ma, 27 had bronchiectasis of unknown etiology, with AAT deficiency. We studied the characteri- four had anti-PR3 antibody-positive vasculitis stics of screening for AAT deficiency at Nevers and one had panniculitis. It was not possible to Hospital (NH), and the performance of SPE for determine the number of patients with unexpla- the incidental discovery of AAT deficiency in ined liver disease or bronchial obstruction. One patients. patient had already been diagnosed with AAT deficiency (PiMZ). Material and methods In parallel, 5,551 SPE tests were performed at the laboratory, on serum samples from 4,406 We retrospectively reviewed all requests for patients. The alpha-1 globulin fraction was ab- AAT determination (± typing) received by the normally small in 68 patients. In response to the laboratory during 3 years (May 2012 to May 2015) comment added to the results concerning the pos- (subcontracted tests), noting the reasons for the sibility of a deficiency, 17 subjects underwent AAT prescription of the tests and their results. We assays (and typing by isoelectric focusing in cases compared the number of tests performed with the of confirmed deficiency; Fig. 1). AAT deficiency number of patients hospitalized at the NH eligible (AAT concentration < 0.93 g/L, the reference value for screening in accordance with international of the subcontractor laboratory) was confirmed in recommendations or already diagnosed as having 14 of the 17 patients (82%; Fig. 1). The deficiency AAT deficiency, by performing statistical queries phenotypes were as follows: two PiZZ, four PiSZ, in the PMSI of the hospital (PMSI, programme de one PiSS, five PiMZ, and two PiMS. The results médicalisation des systèmes d’information; the for the alpha-1 globulin fraction and AAT deter- hospital medico-administrative database). mination for these 17 patients are summarized in In parallel, we reviewed all SPE tests perfor- Figure 1, and the characteristics of the 14 subjects med in the laboratory over the same period. Gel with AAT deficiencies are presented in Table 1. electrophoresis was performed on a Hydrasys -Hyrys device (Sebia). For all tests in which the Discussion alpha-1 globulin fraction was smaller than the value considered normal according to laboratory Screening characteristics standards (< 1 g/L, rounded to the nearest decimal The lack of detection of AAT deficiency in place), in the absence of an obvious cause (he- any of the 102 patients directly referred for testing patocellular insufficiency, severe undernutrition, is not entirely surprising. Despite the widespread protein leakage), a comment
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