{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:21:11Z","timestamp":1792023671247,"version":"4.4.0"},"reference-count":56,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Introduction: Alpha-1 antitrypsin deficiency (AATD) is a genetic condition caused by SERPINA1 variants with variable severity. Current international guidelines do not recommend augmentation therapy for intermediate AATD; nevertheless, some patients show clinically severe phenotypes in real-world practice. We aimed to evaluate, in an exploratory manner, the potential effects of augmentation therapy on exacerbations, quality of life, and lung function in this subgroup. Methods: In this multicenter retrospective study, we included 27 heterozygous patients with intermediate AATD (serum AAT 50\u2013110 mg\/dL), Chronic Obstructive Pulmonary Disease (COPD), and\/or emphysema. Clinical phenotypes included emphysema-predominant disease, COPD with frequent exacerbations, and overlap with bronchiectasis\/asthma; HRCT patterns were recorded. We assessed the annual number of exacerbations (moderate: steroids\/antibiotics; severe: hospitalization\/including pneumothorax), St. George\u2019s Respiratory Questionnaire (SGRQ), and lung function before and after 12 months of therapy. Results: Augmentation therapy was associated with a reduction in annual exacerbations from a median (IQR) of 2 (1.5\u20133) to 1 (0\u20131) (p &lt; 0.0001) and an improvement in SGRQ total score (58.89 \u00b1 16.83 to 48.34 \u00b1 21.20; p = 0.0039). The mean SGRQ change exceeded the 4-point MCID for COPD. No significant changes were observed in spirometry or Diffusing Capacity of the Lung for Carbon Monoxide (DLCO). Conclusions: These exploratory findings suggest that augmentation therapy may reduce exacerbations and improve quality of life in selected patients with intermediate AATD and COPD\/emphysema. Given the retrospective design, small sample, and lack of a control group, the results should be interpreted as hypothesis-generating and warrant confirmation in prospective studies.<\/jats:p>","DOI":"10.3390\/medicina61101747","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T12:05:13Z","timestamp":1758801913000},"page":"1747","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Phenotypic Expression of Respiratory Diseases and Tailored Treatment in Patients with Intermediate Alpha-1 Antitrypsin Deficiency: Evidence from a Retrospective Analysis of a Selected Cohort of Patients"],"prefix":"10.3390","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2404-3545","authenticated-orcid":false,"given":"Anna","family":"Annunziata","sequence":"first","affiliation":[{"name":"Respiratory Pathophysiology and Rehabilitation Unit, Azienda Ospedaliera di Rilievo Nazionale dei Colli, Monaldi Hospital, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Fiorentino","sequence":"additional","affiliation":[{"name":"Respiratory Pathophysiology and Rehabilitation Unit, Azienda Ospedaliera di Rilievo Nazionale dei Colli, Monaldi Hospital, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9457-6558","authenticated-orcid":false,"given":"Francesca","family":"Simioli","sequence":"additional","affiliation":[{"name":"Respiratory Pathophysiology and Rehabilitation Unit, Azienda Ospedaliera di Rilievo Nazionale dei Colli, Monaldi Hospital, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidia","family":"Atripaldi","sequence":"additional","affiliation":[{"name":"Respiratory Pathophysiology and Rehabilitation Unit, Azienda Ospedaliera di Rilievo Nazionale dei Colli, Monaldi Hospital, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Balestrino","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Campania \u201cLuigi Vanvitelli\u201d, Azienda Ospedaliera di Rilievo Nazionale dei Colli, Monaldi Hospital, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Zuccarini","sequence":"additional","affiliation":[{"name":"Respiratory Diseases Unit, Ospedale Santo Spirito, 65124 Pescara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5320-5809","authenticated-orcid":false,"given":"Barbara","family":"Piras","sequence":"additional","affiliation":[{"name":"Respiratory Unit, Department of Medical, Surgical and Experimental Sciences, University of Sassari, Via San Pietro, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7621-3217","authenticated-orcid":false,"given":"Alessandro","family":"Libra","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Policlinico \u201cG. Rodolico-San Marco\u201d, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Pino","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Policlinico \u201cG. Rodolico-San Marco\u201d, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8484-4598","authenticated-orcid":false,"given":"Pierpaolo","family":"Di Micco","sequence":"additional","affiliation":[{"name":"UOC Medicina Interna, P.O. Santa Maria delle Grazie, Pozzuoli, ASL Napoli2 Nord, 80076 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0613-1074","authenticated-orcid":false,"given":"Carmine","family":"Siniscalchi","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Parma University Hospital, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Ferrarotti","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Therapeutics, Pulmonology Unit, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Aronne","sequence":"additional","affiliation":[{"name":"Respiratory Pathophysiology and Rehabilitation Unit, Azienda Ospedaliera di Rilievo Nazionale dei Colli, Monaldi Hospital, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaella","family":"Manzo","sequence":"additional","affiliation":[{"name":"Respiratory Pathophysiology and Rehabilitation Unit, Azienda Ospedaliera di Rilievo Nazionale dei Colli, Monaldi Hospital, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Vancheri","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Policlinico \u201cG. Rodolico-San Marco\u201d, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4293-4461","authenticated-orcid":false,"given":"Cecilia","family":"Calabrese","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Campania \u201cLuigi Vanvitelli\u201d, Azienda Ospedaliera di Rilievo Nazionale dei Colli, Monaldi Hospital, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.amjms.2024.04.002","article-title":"Pulmonary manifestations of alpha 1 antitrypsin deficiency","volume":"368","author":"Mulkareddy","year":"2024","journal-title":"Am. J. Med Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1700610","DOI":"10.1183\/13993003.00610-2017","article-title":"European Respiratory Society statement: Diagnosis and treatment of pulmonary disease in \u03b11-antitrypsin deficiency","volume":"50","author":"Miravitlles","year":"2017","journal-title":"Eur. Respir. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"173","DOI":"10.2147\/TACG.S257511","article-title":"Known Mutations at the Cause of Alpha-1 Antitrypsin Deficiency an Updated Overview of SERPINA1 Variation Spectrum","volume":"14","author":"Seixas","year":"2021","journal-title":"Appl. Clin. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1164\/rccm.201911-2209ED","article-title":"Alpha-1 Antitrypsin Mutations: Is One Too Many?","volume":"201","author":"Sandford","year":"2020","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.mrrev.2017.03.001","article-title":"Alpha-1-antitrypsin deficiency: Genetic variations, clinical manifestations and therapeutic interventions","volume":"773","author":"Hazari","year":"2017","journal-title":"Mutat. Res. Rev. Mutat. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"65","DOI":"10.2174\/0929867324666161118125827","article-title":"Alpha-1 Antitrypsin Deficiency: Current Perspective from Genetics to Diagnosis and Therapeutic Approaches","volume":"24","author":"Santangelo","year":"2017","journal-title":"Curr. Med. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1111\/joim.12239","article-title":"Role of alpha-1 antitrypsin in human health and disease","volume":"276","author":"Blanco","year":"2014","journal-title":"J. Intern. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.trsl.2010.12.014","article-title":"C reactive protein and alpha1-antitrypsin: Relationship between levels and gene variants","volume":"157","author":"Ottaviani","year":"2011","journal-title":"Transl. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2429911","DOI":"10.1080\/25310429.2024.2429911","article-title":"Clinical features in patients with severe Alpha-1 antitrypsin deficiency due to rare genotypes","volume":"31","author":"Ferrarotti","year":"2025","journal-title":"Pulmonology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e00528","DOI":"10.1002\/rcr2.528","article-title":"Clinical manifestations in patients with PI*MMMalton genotypes. A matter still unsolved in alpha-1 antitrypsin deficiency","volume":"8","author":"Aiello","year":"2020","journal-title":"Respirol. Case Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1378\/chest.98.3.522","article-title":"A role for intermediate, heterozygous alpha 1-antitrypsin deficiency in obstructive lung disease","volume":"98","author":"Lieberman","year":"1990","journal-title":"Chest"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"170068","DOI":"10.1183\/16000617.0068-2017","article-title":"COPD in individuals with the PiMZ alpha-1 antitrypsin genotype","volume":"26","author":"Strange","year":"2017","journal-title":"Eur. Respir. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1164\/rccm.201311-1984OC","article-title":"Clarification of the risk of chronic obstructive pulmonary disease in \u03b11-antitrypsin deficiency PiMZ heterozygotes","volume":"189","author":"Molloy","year":"2014","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1513\/AnnalsATS.201611-838OC","article-title":"Genetic Epidemiology of COPD (COPDGene) Investigators. Alpha-1 Antitrypsin PiMZ Genotype Is Associated with Chronic Obstructive Pulmonary Disease in Two Racial Groups","volume":"14","author":"Foreman","year":"2017","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1164\/rccm.202106-1404OC","article-title":"COPDGeneInvestigators. Alpha-1 Antitrypsin MZ Heterozygosity Is an Endotype of Chronic Obstructive Pulmonary Disease","volume":"205","author":"Ghosh","year":"2022","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Annunziata, A., Fiorentino, G., Balestrino, M., Rega, R., Spinelli, S., Atripaldi, L., Sola, A., Massaro, F., and Calabrese, C. (2024). Alpha-1 Antitrypsin PI M Heterozygotes with Rare Variants: Do They Need a Clinical and Functional Follow-Up?. J. Clin. Med., 13.","DOI":"10.3390\/jcm13041084"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.rmed.2017.05.011","article-title":"Exacerbations and duration of smoking abstinence are associated with the annual loss of FEV1 in individuals with PiZZ alpha-1-antitrypsin deficiency","volume":"129","author":"Bernhard","year":"2017","journal-title":"Respir. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/S0140-6736(15)60860-1","article-title":"Intravenous augmentation treatment and lung density in severe \u03b11 antitrypsin deficiency (RAPID): A randomised, double-blind, placebo-controlled trial","volume":"386","author":"Chapman","year":"2015","journal-title":"Lancet"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/S2213-2600(16)30430-1","article-title":"Long-term efficacy and safety of \u03b11 proteinase inhibitor treatment for emphysema caused by severe \u03b11 antitrypsin deficiency: An open-label extension trial (RAPID-OLE)","volume":"5","author":"McElvaney","year":"2017","journal-title":"Lancet Respir. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1164\/rccm.202305-0863OC","article-title":"Augmentation therapy for severe Alpha-1 antitrypsin deficiency improves survival and is decoupled from Spirometric decline-a multinational registry analysis","volume":"208","author":"Fraughen","year":"2023","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.rmed.2017.07.004","article-title":"Intensive smoking diminishes the differences in quality of life and exacerbation frequency between the alpha-1-antitrypsin deficiency genotypes PiZZ and PiSZ","volume":"130","author":"Bernhard","year":"2017","journal-title":"Respir. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"230170","DOI":"10.1183\/16000617.0170-2023","article-title":"Nine controversial questions about augmentation therapy for alpha-1 antitrypsin deficiency: A viewpoint","volume":"32","author":"Miravitlles","year":"2023","journal-title":"Eur. Respir. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1515\/cclm-2020-1881","article-title":"Comparison of different algorithms in laboratory diagnosis of alpha1-antitrypsin deficiency","volume":"59","author":"Balderacchi","year":"2021","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"196","DOI":"10.7326\/0003-4819-106-2-196","article-title":"Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease","volume":"106","author":"Anthonisen","year":"1987","journal-title":"Ann. Intern. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2251519","DOI":"10.1183\/13993003.01519-2022","article-title":"European Respiratory Society\/American Thoracic Society technical statement: Standardisation of the measurement of lung volumes, 2023 update","volume":"62","author":"Bhakta","year":"2023","journal-title":"Eur. Respir. J."},{"key":"ref_26","first-page":"178","article-title":"Long-term augmentation therapy with alpha-1 antitrypsin in an MZ-AAT severe persistent asthma","volume":"69","author":"Blanco","year":"2008","journal-title":"Monaldi. Arch. Chest. Dis."},{"key":"ref_27","first-page":"115","article-title":"Alpha 1 antitrypsin deficiency and intermediate risk: Case of a heterozygote for the MWurzburg allele","volume":"35","author":"Annunziata","year":"2020","journal-title":"Rass. Patol. Dell\u2019apparato Respir."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.12974\/2312-5470.2021.07.01","article-title":"Intermediate Alpha-1 Antitrypsin Deficiency Can Play a Role in Pulmonary Exacerbation?","volume":"7","author":"Annunziata","year":"2021","journal-title":"Glob. J. Respir. Care"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Barjaktarevic, I., and Miravitlles, M. (2021). Alpha-1 antitrypsin (AAT) augmentation therapy in individuals with the PI*MZ genotype: A pro\/con debate on a working hypothesis. BMC Pulm. Med., 21.","DOI":"10.1186\/s12890-021-01466-x"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.arbres.2023.02.016","article-title":"Alpha-1 Antitrypsin Deficiency and SERPINA1 Variants Could Play a Role in Asthma Exacerbations","volume":"59","year":"2023","journal-title":"Arch. Bronc."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2416870","DOI":"10.1016\/j.pulmoe.2023.05.002","article-title":"Alpha-1 antitrypsin deficiency and Pi*S and Pi*Z SERPINA1 variants are associated with asthma exacerbations","volume":"31","year":"2025","journal-title":"Pulmonology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1016\/j.rmed.2009.04.008","article-title":"Exacerbations in subjects with alpha-1 antitrypsin deficiency receiving augmentation therapy","volume":"103","author":"Campos","year":"2009","journal-title":"Respir. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1378\/chest.118.5.1480","article-title":"Augmentation therapy reduces frequency of lung infections in antitrypsin deficiency: A new hypothesis with supporting data","volume":"118","author":"Lieberman","year":"2000","journal-title":"Chest"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1177\/1753465812438387","article-title":"Investigators of the rEXA study group. Reduction of severe exacerbations and hospitalization-derived costs in alpha-1-antitrypsin-deficient patients treated with alpha-1-antitrypsin augmentation therapy","volume":"6","author":"Torres","year":"2012","journal-title":"Ther. Adv. Respir. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1183\/09031936.00159408","article-title":"Exploring the role of CT densitometry: A randomised study of augmentation therapy in alpha1-antitrypsin deficiency","volume":"33","author":"Dirksen","year":"2009","journal-title":"Eur. Respir. J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"270","DOI":"10.7326\/0003-4819-136-4-200202190-00006","article-title":"Change in lung function and morbidity from chronic obstructive pulmonary disease in alpha1-antitrypsin MZ heterozygotes: A longitudinal study of the general population","volume":"136","author":"Dahl","year":"2002","journal-title":"Ann. Intern. Med."},{"key":"ref_37","first-page":"162","article-title":"Exacerbations of Lung Disease in Alpha-1 Antitrypsin Deficiency","volume":"8","author":"Smith","year":"2021","journal-title":"Chronic Obstr. Pulm. Dis."},{"key":"ref_38","first-page":"549","article-title":"Patient-Reported Pulmonary Symptoms, Exacerbations, and Management in a Cohort of Patients with Alpha-1 Antitrypsin Deficiency","volume":"9","author":"Choate","year":"2022","journal-title":"Chronic Obstr. Pulm. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejim.2019.12.014","article-title":"Understanding the impact of chronic obstructive pulmonary disease exacerbations on patient health and quality of life","volume":"73","author":"Hurst","year":"2020","journal-title":"Eur. J. Intern. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.ijsu.2020.04.010","article-title":"Moderate and severe exacerbations have a significant impact on health-related quality of life, utility, and lung function in patients with chronic obstructive pulmonary disease: A meta-analysis","volume":"78","author":"Guo","year":"2020","journal-title":"Int. J. Surg."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1111\/resp.14041","article-title":"Chronic obstructive pulmonary disease exacerbation fundamentals: Diagnosis, treatment, prevention and disease impact","volume":"26","author":"MacLeod","year":"2021","journal-title":"Respirology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"107437","DOI":"10.1016\/j.rmed.2023.107437","article-title":"Physical status, symptoms and health-related quality of life during a severe exacerbation of COPD: Recovery and discriminative capacity for future events","volume":"220","author":"Quadflieg","year":"2023","journal-title":"Respir. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"107452","DOI":"10.1016\/j.rmed.2023.107452","article-title":"Clinical phenotypes of COPD and their impact on quality of life: A cross-sectional study","volume":"220","author":"Anandan","year":"2023","journal-title":"Respir. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1136\/thoraxjnl-2011-201518","article-title":"Long-term natural history of chronic obstructive pulmonary disease: Severe exacerbations and mortality","volume":"67","author":"Suissa","year":"2012","journal-title":"Thorax"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"653","DOI":"10.2147\/COPD.S34186","article-title":"Exacerbation frequency and course of COPD","volume":"7","author":"Halpin","year":"2012","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"313","DOI":"10.2147\/COPD.S121389","article-title":"Seasonality, risk factors and burden of community-acquired pneumonia in COPD patients: A population database study using linked health care records","volume":"12","author":"Williams","year":"2017","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"427","DOI":"10.2147\/COPD.S346591","article-title":"Frequency and severity of exacerbations of COPD associated with future risk of exacerbations and mortality: A UK routine health care data study","volume":"17","author":"Whittaker","year":"2022","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Negro, R.W.D. (2019). COPD: The annual cost-of-illness during the last two decades in Italy, and its mortality predictivity power. Healthcare, 7.","DOI":"10.3390\/healthcare7010035"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"S332","DOI":"10.1513\/AnnalsATS.201507-436KV","article-title":"Alpha-1 Antitrypsin Deficiency: Phenotypes and Quality of Life","volume":"13","author":"Stockley","year":"2016","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"46","DOI":"10.3109\/15412555.2015.1022645","article-title":"Health-related quality of life in patients with alpha-1 antitrypsin deficiency: The French experience","volume":"12","author":"Gauvain","year":"2015","journal-title":"COPD"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.2147\/COPD.S130925","article-title":"Deterioration of quality of life is associated with the exacerbation frequency in individuals with alpha-1-antitrypsin deficiency-analysis from the German Registry","volume":"12","author":"Bernhard","year":"2017","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1183\/09031936.05.00074704","article-title":"Exacerbations in \u03b11-antitrypsin deficiency","volume":"25","author":"Needham","year":"2005","journal-title":"Eur. Respir. J."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1186\/s12931-018-0844-6","article-title":"Health status decline in \u03b1-1 antitrypsin deficiency: A feasible outcome for disease modifying therapies?","volume":"19","author":"Stockley","year":"2018","journal-title":"Respir. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"63","DOI":"10.23736\/S2784-8477.22.01995-7","article-title":"Diagnosis and management of patients with \u03b11-antitrypsin deficiency: An Italian perspective","volume":"61","author":"Aliberti","year":"2022","journal-title":"Minerva Respir. Med."},{"key":"ref_55","first-page":"101345","article-title":"Clinical presentations of four patients with rare Alpha 1 Antitrypsin variants identified in a single US center","volume":"32","author":"Kueppers","year":"2021","journal-title":"Respir. Med. Case Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"53","DOI":"10.2147\/COPD.S346051","article-title":"Opinions and Attitudes of Pulmonologists About Augmentation Therapy in Patients with Alpha-1 Antitrypsin Deficiency. A Survey of the EARCO Group","volume":"17","author":"Greulich","year":"2022","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/61\/10\/1747\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:49:37Z","timestamp":1760035777000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/61\/10\/1747"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,25]]},"references-count":56,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["medicina61101747"],"URL":"https:\/\/doi.org\/10.3390\/medicina61101747","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,25]]}}}