Effect Of Pulmonary Rehabilitation in Patients With Alpha-1 Antitrypsin Deficiency (RRALFA1)

Effect of Pulmonary Rehabilitation and Physical Activity in Patients With Alpha-1 Antitrypsin Deficiency

This single-center, longitudinal, observational, prospective study aims to assess the applicability, adherence, and clinical impact of the Active Cycle of Breathing Technique (ACBT) with augmented reality support in patients with alpha-1 antitrypsin deficiency (AATD).

A total of 50 adult AATD patients will be recruit from the Lung Function Unit of the University Hospital of Parma, meeting specific inclusion criteria. Participants will perform ACBT twice daily and walk at least 5000 steps per day. Clinical and functional outcomes including dyspnea perception, lung function, and quality of life, will be assessed before and after a six-week ACBT program.

The study explores whether augmented reality enhance adherence and efficacy compared to conventional pulmonary rehabilitation (PR) methods. The expected outcome is improved adherence to PR.

Study Overview

• Status: Completed
• Conditions: Alpha-1 Antitrypsin Deficiency (AATD)
• Intervention / Treatment: Other: Pulmonary Rehabilitation

Detailed Description

Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder caused by mutations in the SERPINA1 gene, located on chromosome 14. The condition is characterized by low circulating levels of alpha-1 antitrypsin (AAT), a glycoprotein primarily produced by hepatocytes, which plays a crucial role in inhibiting neutrophil elastase (NE). Without adequate AAT, unregulated NE activity damages the lung parenchyma, leading to progressive emphysema. AATD presents with variable phenotypic expression, ranging from asymptomatic individuals to those with severe pulmonary and hepatic complications.

Treatment includes intravenous AAT replacement therapy, vaccination and guideline-recommended pulmonary rehabilitation (PR) based on the patient's clinical condition.

PR consists of a structured program combining breathing exercises, physical training, education, and psychological support to optimize respiratory function and improve patients' quality of life. One of the most effective techniques within PR is the Active Cycle of Breathing Technique (ACBT), which enhances airway clearance and lung function. ACBT is a simple, standardized, and home-based technique that patients can perform with or without digital tools. ACBT has already been shown to improve forced vital capacity, peak expiratory flow, arterial oxygenation and exercise capacity.

A tendency towards poor adherence to PR has been reported in the literature. To facilitate the performance of PR procedures, technological evolution in recent decades has brought new complementary techniques such as active video games, virtual reality and augmented reality.

ThIs study aims to assess satisfaction, adherence, and usability of pulmonary rehabilitation techniques in AATD patients, both with and without technological support, through relevant questionnaires (VAS, RAI, USE, TAM). Additionally, it aims to describe changes in the perception of dyspnea (mMRC), quality of life (EuroQol 5), impact of the pathology on daily life, and some functional parameters (FEV1, FVC, R5-R20, LCI, metres walked assessed by the six-minute walking test) at baseline and at the end of the rehabilitation program.

Data will be collected in a dedicated electronic Clinical Records Form (CRF). The database will be saved on a password-protected company Personal Computer (PC) which will be updated at each visit and used exclusively for scientific research purposes. At the time of enrollment, each patient will receive an alphanumeric code so that any information collected during the study, and in particular sensitive data, is treated in an anonymous manner. Data reporting patients' identifications will only be used to file patients and collect informed consent.

• Study Type: Observational
• Enrollment (Actual): 50

Contacts and Locations

Study Locations

• Italy
  • Italy
    • Parma, Italy, Italy, 43126
      • University of Parma

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The population will consist of 50 adult patients, referred at outpatient clinic of the Respiratory Disease Unit of the University Hospital of Parma (Italy)

Description

Inclusion Criteria:

• Male or female adults aged ≥18 years;
• Signed informed consent;
• All AATD patients, regardless of nephelometric alpha-1 antitrypsin dose and clinical phenotype, who require PR according to guidelines

Exclusion Criteria:

• Subjects unable to perform the lung function tests and rehabilitation program required by the protocol

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with alpha-1 antitrypsin deficiency (AATD); Adults with a confirmed diagnosis of alpha-1 antitrypsin deficiency (AATD) with asthma and/or COPD.	Other: Pulmonary Rehabilitation; the Active Cycle of Breathing Technique (ACBT) is a simple, standardized, and home-based technique that patients can perform with or without digital tools. ACBT has already been shown to improve forced vital capacity, peak expiratory flow, arterial oxygenation and exercise capacity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient satisfaction with PR techniques using Technology Acceptance Model (TAM) questionnaire.	Satisfaction will be assessed using the Technology Acceptance Model (TAM) questionnaire, with scores ranging from 1 to 7, where lower scores indicate more satisfaction.	six weeks
Patient adherence to the PR techniques using the Rehabilitation Adherence Index (RAI) questionnaire.	Adherence will be assessed using the Rehabilitation Adherence Index (RAI) questionnaire, with scores ranging from 1 to 7, where higher scores indicate better adherence.	six weeks
Usability of pulmonary rehabilitation techniques using the Usefulness, Satisfaction and Ease of Use (USE) questionnaire	Usability will be measured using the Usefulness, Satisfaction and Ease of Use (USE) questionnaire, with scores ranging from 1 to 7, where higher scores indicate better usability.	six weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To describe the change in perception of dyspnea at baseline and at the end of the PR using Modified Medical Research Council (mMRC) questionnaire.	The Modified Medical Research Council (mMRC) questionnaire assesses the perception of dyspnea with scores ranging from 0 to 4, with higher scores indicating greater severity.	six weeks
To describe the change in quality of life at baseline and at the end of the PR using EuroQol-5D (EQ-5D) questionnaire.	The EQ-5D questionnaire assesses health-related quality of life across five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has five levels of severity: no problems, slight problems, moderate problems, severe problems, and unable to perform/extreme problems. Additionally, the EQ-5D includes a visual analogue scale (VAS) where respondents rate their overall health on a scale from 0 to 100, with 0 being the worst imaginable health and 100 being the best.	six weeks
To assess the impact of Chronic Obstructive Pulmonary Disease (COPD) on AATD- related COPD patients using COPD Assessment Test (CAT)	The COPD Assessment Test (CAT) is assess the impact of Chronic Obstructive Pulmonary Disease (COPD) on a person's daily life. It ranges from 0 to 5, where higher scores indicate a greater impact of COPD on daily life	six weeks
To assess the impact of asthma on AATD patients with asthma using the Asthma Control Test (ACT)	The Asthma Control Test (ACT) is a questionnaire used to assess asthma control, with scores ranging from 5 to 25. Higher scores indicate better asthma control, meaning the asthma is well-managed and less likely to interfere with daily activities.	six weeks
To describe the change in functional respiratory parameters at baseline and at the end of the PR program using spirometry.	Spirometry will be performed according to ATS/ERS standards to obtain Forced Expiratory Volume in 1 second (FEV₁, % predicted), Forced Vital Capacity (FVC, % predicted), and FEV₁/FVC, %.	six weeks

Collaborators and Investigators

• Sponsor: University of Parma
• Collaborators: Chiesi Farmaceutici S.p.A.

Publications and helpful links

General Publications

• Conrad A, Janciauskiene S, Köhnlein T, Fuge J, Ivanyi P, Tudorache I, Gottlieb J, Welte T, Fuehner T. Impact of alpha 1-antitrypsin deficiency and prior augmentation therapy on patients' survival after lung transplantation. Eur Respir J. 2017 Sep 10;50(3):1700962. doi: 10.1183/13993003.00962-2017.
• Cerdán de Las Heras J, Tulppo M, Kiviniemi AM, et al. Augmented reality glasses as a new tele-rehabilitation tool for home use: patients' perception and expectations. Disabil Rehabil Assist Technol. 2022 May;17(4):480-486.
• Patsaki I, Avgeri V, Rigoulia T, et al. Benefits from Incorporating Virtual Reality in Pulmonary Rehabilitation of COPD Patients: A Systematic Review and Meta-Analysis. Adv Respir Med. 2023 Aug 10;91(4):324-336.
• Hayton C, Clark A, Olive S, et al. Barriers to pulmonary rehabilitation: characteristics that predict patient attendance and adherence. Respir Med. 2013 Mar;107(3):401-7.
• Depew ZS, Novotny PJ, Benzo RP. How many steps are enough to avoid severe physical inactivity in patients with chronic obstructive pulmonary disease? Respirology. 2012 Aug;17(6):1026-7. doi: 10.1111/j.1440-1843.2012.02207.x.
• Savci S, Ince DI , Arikan H. A comparison of autogenic drainage and the active cycle of breathing techniques in patients with chronic obstructive pulmonary diseases. Journal of Cardiopulmonary Rehabilitation, 01 Jan 2000, 20(1):37-43
• Zisi D, Chryssanthopoulos C, Nanas S, et al. The effectiveness of the active cycle of breathing technique in patients with chronic respiratory diseases: A systematic review. Heart Lung. 2022 May-Jun;53:89-98
• Barjaktarevic I, Campos M. Management of lung disease in alpha-1 antitrypsin deficiency: what we do and what we do not know. Ther Adv Chronic Dis. 2021 Jul 29;12 suppl:20406223211010172.
• Alwadani FA, Wheeler K, Pittaway H, et al. Pulmonary Rehabilitation for Chronic Obstructive Pulmonary Disease Patients with Underlying Alpha-1 Antitrypsin Deficiency: A Systematic Review and Practical Recommendations. Chronic Obstr Pulm Dis. 2024 Jan 25;11(1):121-132
• Nici L, Donner C, Wouters E, Zuwallack R, Ambrosino N, Bourbeau J, Carone M, Celli B, Engelen M, Fahy B, Garvey C, Goldstein R, Gosselink R, Lareau S, MacIntyre N, Maltais F, Morgan M, O'Donnell D, Prefault C, Reardon J, Rochester C, Schols A, Singh S, Troosters T; ATS/ERS Pulmonary Rehabilitation Writing Committee. American Thoracic Society/European Respiratory Society statement on pulmonary rehabilitation. Am J Respir Crit Care Med. 2006 Jun 15;173(12):1390-413.
• Crystal RG. Alpha 1-antitrypsin deficiency, emphysema, and liver disease. Genetic basis and strategies for therapy. J Clin Invest. 1990 May;85(5):1343-52. doi: 10.1172/JCI114578. No abstract available.
• Nukiwa T, Brantly M, Ogushi F, Fells G, Satoh K, Stier L, Courtney M, Crystal RG. Characterization of the M1(Ala213) type of alpha 1-antitrypsin, a newly recognized, common "normal" alpha 1-antitrypsin haplotype. Biochemistry. 1987 Aug 25;26(17):5259-67. doi: 10.1021/bi00391a008.
• Brantly M, Nukiwa T, Crystal RG. Molecular basis of alpha-1-antitrypsin deficiency. Am J Med. 1988 Jun 24;84(6A):13-31.
• DeMeo DL, Silverman EK. Alpha1-antitrypsin deficiency. 2: genetic aspects of alpha(1)-antitrypsin deficiency: phenotypes and genetic modifiers of emphysema risk. Thorax. 2004 Mar;59(3):259-64. doi: 10.1136/thx.2003.006502.
• Long GL, Chandra T, Woo SL, Davie EW, Kurachi K. Complete sequence of the cDNA for human alpha 1-antitrypsin and the gene for the S variant. Biochemistry. 1984 Oct 9;23(21):4828-37.
• Lai EC, Kao FT, Law ML, Woo SL. Assignment of the alpha 1-antitrypsin gene and a sequence-related gene to human chromosome 14 by molecular hybridization. Am J Hum Genet. 1983 May;35(3):385-92.
• Luisetti M, Seersholm N. Alpha1-antitrypsin deficiency. 1: epidemiology of alpha1-antitrypsin deficiency. Thorax. 2004 Feb;59(2):164-9. doi: 10.1136/thorax.2003.006494.

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2024
• Primary Completion (Actual): June 24, 2025
• Study Completion (Actual): June 24, 2025

Study Registration Dates

• First Submitted: June 27, 2025
• First Submitted That Met QC Criteria: November 18, 2025
• First Posted (Actual): November 21, 2025

Study Record Updates

• Last Update Posted (Actual): November 21, 2025
• Last Update Submitted That Met QC Criteria: November 18, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Pulmonary rehabilitation; Alpha-1 antitrypsin deficiency; Active Cycle of Breathing Technique
• Additional Relevant MeSH Terms: Pathologic Processes; Genetic Diseases, Inborn; Respiratory Tract Diseases; Digestive System Diseases; Lung Diseases; Liver Diseases; Subcutaneous Emphysema; Emphysema; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; alpha 1-Antitrypsin Deficiency
• Other Study ID Numbers: 31276

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be collected in a dedicated electronic Clinical Records Form (CRF). The database will be saved on a password- protected company personal computer which will be updated at each visit and used exclusively for scientific research purposes. At the time of enrolment, each patient will receive an alphanumeric code so that any information collected during the study, and in particular sensitive data, will be treated in an anonymous manner. Data reporting patients' identifications will only be used to file patients and collect informed consent.
• IPD Sharing Time Frame: Data will be available during the course of the study. The Investigator will keep paper and electronic copies of all documentation at the Center for a period of at least 7 years after the completion of the study and then he will arrange for its destruction.
• IPD Sharing Access Criteria: Only the personal delegated to collaborate with this study will be able to access to the database using a password to login.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No