Alpha-1 Antitrypsin Deficiency and Bronchial Asthma: Current Challenges
Abstract
:1. Introduction
2. Prevalence of AATD in Patients with Asthma
Study | Size | Origin of Data | Asthma Diagnosis | Diagnosis of AATD | Prevalence |
---|---|---|---|---|---|
Northern Europe | |||||
Fagerhol MK, Hauge HE. Acta Allergol 1969 [18] | 39 | Norway | Physician diagnosed. Exacerbated | AAT phenotyping | 8 cases (20.5%) |
von Ehrenstein OS et al. Arch Dis Child 2004 [21] | 2747 | Germany ISAAC study [31] | Physician diagnosed or suggestive symptoms in children 9–11 yr | AAT plasma levels by nephelometry and PI*S and PI*Z genotypes by PCR | Not specified |
van Veen IH et al. Respir Med 2006 [32] | 122 | The Netherlands | Severe asthma | AAT phenotypes by isoelectrofocusing | 6 cases (4.9%) |
Southern Europe | |||||
Miravitlles M et al. Respir Med 2002 [33] | 111 | Spain | Symptomatic in the previous year >14 yr. | All cases with both: Hematic AAT levels by nephelometry AAT phenotypes by isoelectrofocusing | 22 cases (19.8%) |
Suarez-Lorenzo I et al. Clin Transl Allergy. 2018 [34] | 648 | Spain | Allergic asthma | AAT serum levels by nephelometry AAT genotypes by PCR | 145 cases (22.3%) |
Suarez-Lorenzo I et al. J Asthma 2022 [22] | 648 | Spain | Allergic asthma | AAT genotypes by PCR for the PI*Mmalton mutation | 145 cases (22.3%) |
Hernández-Pérez JM et al. Pulmonology. 2023 [35] | 485 | Spain | Physician diagnosed | AAT serum levels by nephelometry AAT genotypes by PCR + sequencing if discrepancy | 117 cases (24.2%) |
Aiello M et al. Respiration 2021 [36] | 600 | Italy | Mild to moderate asthma | AAT serum levels by nephelometry and AAT phenotypes by isoelectrofocusing if AAT < 113 mgr/dL or symptom/family history of AATD + sequencing if discrepancy | 22 cases (3.6%) |
Vianello A et al. J Allergy Clin Immunol Pract 2021 [37] | 143 | Italy | Severe asthma with biologics | AAT level < 1.1 g/L followed by phenotype by isoelectrofocusing or genotype by PCR. | 10 cases (6.9%) |
Aiello M et al. J Asthma 2022 [25] | 735 | Italy | Mild to moderate asthma | AAT serum levels by nephelometry and AAT phenotypes by isoelectrofocusing if AAT < 113 mgr/dL or symptom/family history of AATD + sequencing if discrepancy | 22 cases (2.9%) |
Northern America | |||||
Hyde JS et al. Ann Allergy 1979 [38] | 46 | USA | Physician diagnosed | Serum AAT by electroimmunodiffusion and phenotypes | 10 cases (21.7%) |
Eden E et al. J Asthma 2007 [39] | 285 | USA LODO trial [40] | Physician diagnosed, >15 yr. Uncontrolled | Hematic AAT levels AAT phenotypes by isoelectrofocusing | 35 cases (12.2%) |
Ortega VE et al. J Allergy Clin Immunol Pract. 2025 [23] | 1293 | USA NHLBI SARP | Asthma symptoms confirmed by either: Methacholine test Bronchodilator reversibility | Gene sequencing | Not disclosed |
Townley RG et al. Chest 1990 [41] | 486 | USA | Clinical presentation + spirometry reversibility | Serum AAT by radioimmunodiffusion + phenotype | 70 cases (14.4%) |
Other geographical areas | |||||
Mousavi SA et al. Tanaffos 2013 [42] | 43 | Iran | Persistent asthma, >14 yr. | AAT serum levels by turbidimetry < 90 mg/dL | 2 cases (4.6%) |
Montealegre F et al. P R Health Sci J. 2006 [43] | 105 | Puerto Rico | Asthma exacerbation Physician diagnosed | Both: AAT serum levels by a fluorescence immunoassay AAT phenotypes by isoelectrofocusing | 14 cases (13.3%) |
Colp C et al. Arch Intern Med. 1990 [26] | 55 | Puerto Rico | Respiratory symptoms of asthma or COPD | AAT phenotypes | 14 cases (25.4%) |
Tural Onur S et al. Int J Chron Obstruct Pulmon Dis. 2023 [24] | 209 | Turkey | Physician diagnosed | AAT hematic levels by nephelometry + AAT genotype by Progenika on dried blood spots. | Not specified for asthma |
3. Prevalence of Asthma in Patients with AATD
4. AATD as a Risk Factor for Developing Asthma
5. Impact of AATD on Asthma
6. Augmentation Therapy for AATD and Bronchial Asthma
7. Summary and Research Questions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
AATD | alpha-1 antitrypsin deficiency |
AAT | alpha-1 antitrypsin |
EARCO | European Alpha-1 Research Collaboration |
References
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Study | Size | Origin of Data | Type of AATD | Asthma Diagnosis | Prevalence |
---|---|---|---|---|---|
Northern Europe | |||||
Fähndrich S et al. COPD 2015 [49] | 1066 | Germany AATD registry | Severe AATD: AAT < 50 mg/dL with PI*ZZ or other deficient allelic variants | Physician diagnosed | 170 cases (15.9%) |
Chorostowska-Wynimko J et al. COPD 2015 [50] | 55 | Poland AATD registry | Severe AATD PiZ phenotype | Physician diagnosed | 9 cases (16.3%) |
Larsson et al. Acta Med Scand 1978 [46] | 246 | Sweden | Severe AATD PiZ phenotype | According to the WHO 1961 definition | 8 cases (3.2%) |
Piitulainen E, Sveger T. Thorax 2002 [51] | 98 | Sweden | PiZ phenotype | Physician diagnosed | 15 cases (15.3%) |
Piitulainen E, Tanash HA. COPD 2015 [52] | 1553 | Sweden AATD registry | PiZZ, PiZNull, or PNullNull phenotypes | Physician diagnosed | 176 cases (11.3%) |
Tobin MJ et al. Br J Dis Chest 1983 [47] | 129 | United Kingdom | PiZ phenotype | Physician diagnosed | 14 cases (10.8%) |
Southern Europe | |||||
Luisetti M et al. COPD 2015 [53] | 422 | Italy AATD registry | Pi*ZZ, Pi*SZ, and carriers of rare deficient variants. | Physician diagnosed | 21 cases (4.9%) |
Ferrarotti I et al. Pulmonology 2025 [54] | 281 | Italy AATD registry | Pi*ZZ, Pi*SZ, and carriers of rare deficient variants. | Physician diagnosed | 15 cases (5.3%) |
Lara B, Miravitlles M. COPD 2015 [48] | 448 | Spain AATD registry | Pi*ZZ, Pi*SZ, and carriers of rare deficient variants. | Physician diagnosed | 80 cases (17.8%) |
Lara B et al. Arch Bronconeumol 2017 [55] | 511 | Spain AATD registry | Pi*ZZ, Pi*SZ, and carriers of rare deficient variants. | Physician diagnosed | 57 cases (11.1%) |
Torres-Duran M et al. ERJ Open Res 2022 [56] | 405 | Spain EARCO registry [57] | Any mutation not carrying a PI*M allele | Physician diagnosed | 55 cases (13.5%) |
Northern America | |||||
Eden E et al. AJRCCM 1997 [58] | 43 | USA NHLBI registry | AAT < 11 µM PI*ZZ or PI*ZNull | One of: History of attacks of wheezing associated with shortness of breath Spirometric evidence of a bronchodilator response Presence of atopy upon skin testing Total serum IgE above 100 IU/mL | 11 cases (25.5%) |
McElvaney NG et al. Chest 1997 [59] | 1129 | USA NHLBI registry | AAT < 11 µM PI*ZZ or PI*ZNull | Not specified | 350 cases (31.0%) |
Eden E et al. Chest 2003 [60] | 1052 | USA NHLBI registry | AAT < 11 µM PI*ZZ or PI*ZNull | All of: A ≥ 12% improvement in FEV1 of at least 200 mL after bronchodilator on any visit Had a history of more than one attack of wheezing with shortness of breath Reported a doctor’s diagnosis of asthma or allergy | 220 cases (20.9%) |
Eden E et al. Respir Med 2006 [45] | 757 | USA Alpha1 Foundation registry | Any mutation | Physician diagnosed | 338 (44.6%) |
DeMeo DL et al. Thorax 2007 [61] | 378 | USA | PI*ZZ | Physician diagnosed | 140 cases (37.0%) |
Kelbel T et al. J Allergy Clin Immunol Pract 2017 [62] | 226 | USA | Severe AATD: ZZ, SZ, ZNull, and FZ | Physician diagnosed | 64 cases (29.6%) |
Other geographical areas | |||||
Miravitlles M et al. Respir Res 2022 [63] | 1044 | International EARCO registry [57] | Any mutation not carrying a PI*M allele | Physician diagnosed | 158 cases (15.1%) |
Miravitlles M et al. Eur Respir J 2023 [64] | 629 | International EARCO registry [57] | PI*ZZ | Physician diagnosed | 88 cases (14.1%) |
Martin T et al. Respir Res 2024 [65] | 634 | International EARCO registry [57] | PI*SS and PI*ZZ | Physician diagnosed | 109 cases (17.1%) |
Janus ED et al. Lancet 1985 [44] | 69 | New Zealand | PiZ phenotype | Not specified | 1 case (1.4%) |
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Lopez-Campos, J.L.; Muñoz-Sánchez, B.; Ferrer-Galván, M.; Quintana-Gallego, E. Alpha-1 Antitrypsin Deficiency and Bronchial Asthma: Current Challenges. Biomolecules 2025, 15, 807. https://doi.org/10.3390/biom15060807
Lopez-Campos JL, Muñoz-Sánchez B, Ferrer-Galván M, Quintana-Gallego E. Alpha-1 Antitrypsin Deficiency and Bronchial Asthma: Current Challenges. Biomolecules. 2025; 15(6):807. https://doi.org/10.3390/biom15060807
Chicago/Turabian StyleLopez-Campos, José Luis, Belén Muñoz-Sánchez, Marta Ferrer-Galván, and Esther Quintana-Gallego. 2025. "Alpha-1 Antitrypsin Deficiency and Bronchial Asthma: Current Challenges" Biomolecules 15, no. 6: 807. https://doi.org/10.3390/biom15060807
APA StyleLopez-Campos, J. L., Muñoz-Sánchez, B., Ferrer-Galván, M., & Quintana-Gallego, E. (2025). Alpha-1 Antitrypsin Deficiency and Bronchial Asthma: Current Challenges. Biomolecules, 15(6), 807. https://doi.org/10.3390/biom15060807