Alpha-1 Antitrypsin Deficiency Patients Research Articles

A Multimodal Intervention to Improve Guideline-Based Screening for Alpha-1 Antitrypsin Deficiency in a Community Health Setting.

Evidence-based guidelines recommend screening all individuals with chronic obstructive pulmonary disease (COPD) for the genetic disorder alpha-1 antitrypsin deficiency (AATD). However, it is estimated that only 5% of people with COPD have been tested for AATD, and a large fraction of the estimated 70,000 to 100,000 Americans with AATD have not yet been diagnosed. Low familiarity with AATD and limited knowledge about diagnostic tests and available treatments contribute to suboptimal screening rates. To address barriers to and improve rates of guideline-based AATD diagnostic testing among racially and ethnically diverse patients with COPD at a large community health center. A quality improvement initiative consisting of educational sessions and electronic health record (EHR) system interventions was implemented to improve the adoption of guideline-based screening for AATD in patients with COPD. An analysis of EHR data demonstrated that of patients with a COPD diagnosis (N = 1,030), 22.2% (n = 229) were screened for AATD in the 12 months following the start of the quality improvement initiative compared with 1.3% (n = 13) of patients with a COPD diagnosis (N = 972) seen in the 12 months prior to the start of the quality improvement initiative (P < 0.001). A quality improvement initiative consisting of educational sessions and EHR system modifications was successful in increasing clinicians' knowledge and diagnostic screening rates for AATD in patients with COPD at a large community health center.

Berberine potentiates liver inflammation and fibrosis in the PI*Z hAAT transgenic murine model.

Alpha-1 antitrypsin deficiency (AATD) is an inherited disease, the common variant caused by a Pi*Z mutation in the SERPINA1 gene. Pi*Z AAT increases the risk of pulmonary emphysema and liver disease. Berberine (BBR) is a nature dietary supplement and herbal remedy. Emerging evidence revealed that BBR has remarkable liver-protective properties against various liver diseases. In the present study, we investigated the therapeutic effects and toxicities of BBR in Pi*Z hepatocytes and Pi*Z transgenic mice. Huh7.5 and Huh7.5Z (which carries the Pi*Z mutation) cells were treated with different concentrations of BBR for 48 hours. MTT was performed for cell viability assay. Intracellular AAT levels were evaluated by western blot. In vivo studies were carried out in wild type, native phenotype AAT (Pi*M), and Pi*Z AAT transgenic mice. Mice were treated with 50 mg/kg/day of BBR or solvent only by oral administration for 30 days. Western blot and liver histopathological examinations were performed to evaluate therapeutic benefits and liver toxicity of BBR. BBR reduced intracellular AAT levels in Huh7.5Z cells, meanwhile, no Pi*Z-specific toxicity was observed. However, BBR did not reduce liver AAT load but significantly potentiated liver inflammation and fibrosis accompanying the activation of unfolded protein response and mTOR in Pi*Z mice, but not in wild type and Pi*M mice. BBR exacerbated liver inflammation and fibrosis specifically in Pi*Z mice. This adverse effect may be associated with the activation of unfolded protein response and mTOR. This study implicates that BBR should be avoided by AATD patients.

Liver Characterization of a Cohort of Alpha-1 Antitrypsin Deficiency Patients with and without Lung Disease.

Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder characterized by the misfolding and accumulation of the mutant variant of alpha-1 antitrypsin (AAT) within hepatocytes, which limits its access to the circulation and exposes the lungs to protease-mediated tissue damage. This results in progressive liver disease secondary to AAT polymerization and accumulation, and chronic obstructive pulmonary disease (COPD) due to deficient levels of AAT within the lungs. Our goal was to characterize the unique effects of COPD secondary to AATD on liver disease and gene expression. A subcohort of AATD individuals with COPD (n = 33) and AATD individuals without COPD (n = 14) were evaluated in this study from our previously reported cross-sectional cohort. We used immunohistochemistry to assess the AATD liver phenotype, and RNA sequencing to explore liver transcriptomics. We observed a distinct transcriptomic profile in liver tissues from AATD individuals with COPD compared to those without. A total of 339 genes were differentially expressed. Canonical pathways related to fibrosis, extracellular matrix remodeling, collagen deposition, hepatocellular damage, and inflammation were significantly upregulated in the livers of AATD individuals with COPD. Histopathological analysis also revealed higher levels of fibrosis and hepatocellular damage in these individuals. Our data supports a relationship between the development of COPD and liver disease in AATD and introduces genes and pathways that may play a role in AATD liver disease when COPD is present. We believe addressing lung impairment and airway inflammation may be an approach to managing AATD-related liver disease.

Impact of Hypoxia on Neutrophil Degranulation and Inflammatory Response in Alpha-1 Antitrypsin Deficiency Patients.

Alpha-1 antitrypsin deficiency (AATD) is an inflammatory disorder where neutrophils play a key role. Excessive neutrophil activation leads to local hypoxia and tissue damage. Most research on neutrophil function has been conducted under atmospheric conditions (21% O2), which may not represent physiological or pathological conditions. This study aimed to determine the effects of hypoxia on neutrophil degranulation and cytokine production in AATD patients. Neutrophils isolated from 54 AATD patients (31 MZ; 8 SZ; 15 ZZ) and 7 controls (MM) were exposed to hypoxia (1% O2) for 4 h. Neutrophil degranulation was assessed by measuring elastase (NE), myeloperoxidase (MPO), lactoferrin, and matrix metalloproteinase-9 (MMP-9) levels using immunoassay-based methods. Pro-inflammatory (IL-8, IL-1 beta, IL-6, and TNF-alpha) and anti-inflammatory (IL-4 and IL-10) cytokine levels were assessed by a Luminex-based method. Our results indicate a significantly increased release of NE (p = 0.015), MPO (p = 0.042), lactoferrin (p = 0.015), and MMP-9 (p = 0.001) compared to controls. Pro-inflammatory cytokines show a significant rise in IL-8 (p = 0.019), a trend towards increased IL-1 beta (p = 0.3196), no change in IL-6 (p = 0.7329), and reduced TNF-alpha (p = 0.006). Anti-inflammatory cytokines show increased IL-4 (p = 0.057) and decreased IL-10 (p = 0.05703). Increased neutrophil degranulation and inflammatory phenotype are observed in AATD neutrophils under physiological hypoxia.

Alpha-1 antitrypsin deficiency and Pi*Z allele as important co-factors in the development of liver fibrosis.

Alpha-1 antitrypsin deficiency (AATD) is a codominant autosomal hereditary condition that predisposes patients to the development of lung and/or liver disease, and Pi*Z allele is the most clinically relevant mutation. To evaluate the impact of clinical parameters and AATD phenotypes, particularly the Pi*Z allele, in liver fibrosis. Cross-sectional cohort study including consecutive patients with AATD followed in Pulmonology or Hepatology consultation. Included 69 patients, 49.3% had Pi*MZ phenotype and 10.1% Pi*ZZ. An age ≥ 55 years, age at diagnosis ≥ 41 years and AAT at diagnosis < 77 mg/dL predicted a nonalcoholic fatty liver disease fibrosis score (NFS) not excluding advanced fibrosis [area under the curve (AUC) = 0.840, P < 0.001; AUC = 0.836, P < 0.001; AUC = 0.681, P = 0.025]. An age ≥ 50 years and age at diagnosis ≥ 41 years predicted a fibrosis-4 index of moderate to advanced fibrosis (AUC = 0.831, P < 0.001; AUC = 0.795, P < 0.001). Patients with hypertension, type 2 diabetes mellitus (DM), dyslipidaemia, metabolic syndrome, and regular alcohol consumption were more likely to have a NFS not excluding advanced fibrosis (P < 0.001, P = 0.002, P = 0.008, P < 0.001, P = 0.033). Patients with at least one Pi*Z allele and type 2 DM were 8 times more likely to have liver stiffness measurement ≥ 7.1 kPa (P = 0.040). Risk factors for liver disease in AATD included an age ≥ 50 years, age at diagnosis ≥ 41 years, metabolic risk factors, regular alcohol consumption, at least one Pi*Z allele, and AAT value at diagnosis < 77 mg/dL. We created an algorithm for liver disease screening in AATD patients to use in primary care, selecting those to be referred to Hepatology consultation.

Prevalence of alpha-1 antitrypsin deficiency in patients with acute exacerbation of chronic obstructive pulmonary disease: Insights from a prospective study.

Alpha-1 antitrypsin (AAT) deficiency is a genetic risk factor for chronic obstructive pulmonary disease (COPD) but prevalence data in acutely exacerbated Indian patients is limited. This study determined AAT deficiency rates and correlations with inflammation and lung function among hospitalized patients with COPD. A total of 106 patients hospitalized for acute COPD exacerbations were prospectively enrolled from June 2016 to February 2018 in Kerala, India, excluding any with known AAT deficiency. Serum AAT levels were quantified and correlated with C-reactive protein (CRP) levels as well as postbronchodilator spirometry. Mean serum AAT level was 1.48 ± 0.27 g/L. No AAT deficiency cases were identified, although AAT and CRP both significantly increased during flares. AAT levels positively correlated with FEV1, FVC, and FEV1/FVC ratios. Patients with lower AAT had worse pulmonary status. Despite finding no AAT deficiency in this regional Indian cohort, further studies across expanded, more diverse populations are warranted to definitively establish prevalence nationwide. Temporal monitoring of AAT kinetics could help gauge exacerbation trajectories.

Technoeconomic Analysis of Intensified PEGylated Biopharmaceutical Recombinant Protein Production: Alpha Antitrypsin as a Model Case

Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder characterized by the insufficient production of the AAT protein. Due to availability limitations, not all AATD patients receive protein therapy treatment. In this study, the technoeconomic analysis of different processes (conventional and intensified) producing 200 kg/year of PEGylated recombinant AAT (PEG-AAT) using a Chinese hamster ovary cell line was investigated. All bioprocesses consist of upstream, downstream, and PEGylation sections. A base-case model (process A) of the conventional fed-batch production bioreactor was developed using SuperPro Designer software (Version 13) to evaluate the economic feasibility of the process. The cost of goods (COG) was estimated to be approximately USD 387.6/g. Furthermore, an intensified process (B) was modeled and evaluated to reduce the COG. Process intensification was implemented in the process (N-1 perfusion bioreactor). The specific operating COG for process B was found to be 10% less than that of process A. Scenario analysis was performed to assess the impact of process capacity (100–1000 kg/year) and cell-specific productivity (30–90 pg/cell/day). With an increase in process capacity, the specific operating COG was reduced for all processes. Increasing cell-specific productivity decreases the specific operating COG at different rates for each process, depending on the titer level. Future investigations into the PEGylation section are required since it has the highest COG of all the sections.

Predicting Exacerbations in Alpha-1 Antitrypsin Deficiency Using Clinical and Pulmonary Function Tests: Portuguese EARCO Registry

Introduction: Exacerbations are common in individuals with alpha-1 antitrypsin deficiency (AATD)-related lung disease. This study intended to identify independent predictive factors for exacerbations in AATD using the Portuguese European Alpha-1 Research Collaboration (EARCO) registry. Methods: This study includes patients from the Portuguese EARCO registry, a prospective multicenter cohort (NCT04180319). From October 2020 to April 2023, this registry enrolled 137 patients, 14 of whom were excluded for analysis for either missing 12 months of follow-up or baseline pulmonary function. Results: Among the 123 AATD patients, 27 (22.0%) had at least one exacerbation in the last 12 months of follow-up. Patients with Pi*ZZ phenotype were three times more likely than the rest of the population to experience any exacerbation (32.7 vs. 14.1%, p = 0.014; OR 3.0). BODE index was significantly higher in exacerbators than in non-exacerbators (3.9 ± 2.4 vs. 1.3 ± 1.2; p < 0.001), including on multivariate analysis (p = 0.002). Similar results were found for BODEx (multivariate p < 0.001). DLCO was the only functional parameter independently associated with exacerbations (p = 0.024). Conclusions: DLCO, BODE, and BODEx were independent predictors of exacerbations at 12 months in AATD patients. Understanding these risk factors can aid decision-making on AATD-related lung disease management and improve patient outcomes.

Pulmonary Rehabilitation for Chronic Obstructive Pulmonary Disease Patients with Underlying Alpha-1 Antitrypsin Deficiency: A Systematic Review and Practical Recommendations.

Alpha-1 antitrypsin deficiency (AATD) is an often-overlooked genetic condition that makes individuals susceptible to early onset of chronic obstructive pulmonary disease (COPD). The established benefits of exercise-based pulmonary rehabilitation (PR) for usual COPD patients are unclear for those with underlying AATD, especially given potentially differing muscle adaptations to exercise. This review seeks to compare PR outcomes between AATD and usual COPD patients and to consolidate current knowledge on exercise intervention outcomes for the AATD population. A thorough search of 4 databases (Ovid, Medline, CINAHL, CENTRAL) was conducted based on 3 search concepts: (1) alpha-1 antitrypsin deficiency, (2) pulmonary rehabilitation OR exercise, and (3) muscle morphology. A dual review process and quality assessment were independently implemented throughout all stages of the review. Four studies highlighted modest exercise capacity and quality of life in AATD patients undergoing PR. However, one study reported unique muscle and mitochondrial responses compared to usual COPD patients. Additionally, a moderate exercise session did not alter pro-inflammatory cytokine levels in AATD patients, despite higher levels of tumor necrosis factor-α levels in muscle biopsies compared to usual COPD patients. The current literature base insufficiently addresses the efficacy of PR on AATD, with indications that exercise adaptation may deviate from that of usual COPD patients. Further research is needed to optimize PR, particularly in identifying the most suitable exercise intensity, and delivery setting, and addressing specific educational needs for individuals with AATD.

Bronchiectasis Occurs Independently of Chronic Obstructive Pulmonary Disease in Alpha-1 Antitrypsin Deficiency.

Bronchiectasis occurs in patients with alpha-1 antitrypsin deficiency (AATD), but it is unknown whether an association exists independently of chronic obstructive pulmonary disease (COPD). We assessed whether bronchiectasis was associated with COPD in our cohort, and whether it has clinical significance for lung function decline, exacerbation rate, or symptoms. PiZZ, PiSZ, and PiMZ patients from the Birmingham AATD Research Database were studied. Demographics were recorded, along with the outcomes of symptoms, forced expiratory volume in 1 second (FEV1), transfer factor of carbon monoxide (TLCO), carbon monoxide transfer coefficient (KCO), and annualized exacerbation rate. Lung function decline was calculated for those with ≥3 measurements. Multivariate regression analyses were conducted to assess for associations of bronchiectasis with each outcome. A further binomial logistic regression model assessed for predictors of bronchiectasis diagnosis, including COPD. Those with alternative bronchiectasis causes were excluded from statistical models. A total of 1290 patients were eligible. PiZZ patients with bronchiectasis were older at presentation (54 versus 49 years, p<0.001), less likely to have smoked (65% versus 76.1%, p=0.001), and had higher modified Medical Research Council scores (mMRC) (mMRC 2 versus 0 odds ratio [OR] 1.97, 95% constant interval [CI] 1.20-3.25, p=0.008; mMRC 3 versus 0 OR 2.58 95% CI 1.59-4.19, p<0.001; mMRC 4 versus 0 OR 2.2 95% CI 1.23-3.92; p=0.008) than those without. The OR of bronchiectasis diagnosis was not associated with COPD diagnosis in any phenotype. Bronchiectasis was associated with lower serum alpha-1 antitrypsin levels in PiZZ patients (p=0.012). Bronchiectasis was not associated with a difference in FEV1 percentage predicted (pp)/year decline, KCO pp/year, TLCO pp/year decline, or exacerbation rate in multivariate analysis. Bronchiectasis exists in a significant minority of AATD patients independently of COPD and is associated with more severe shortness of breath. Appropriate treatment of bronchiectasis in AATD is essential.

Lipoproteins in Negative Feedback with Alpha-1 Antitrypsin.

Alpha-1 antitrypsin deficiency patients (AATD) have lower risk of myocardial infarction, a cardiovascular disease that is related to increased remnant cholesterol levels, but not to low-density lipoprotein (LDL) levels. However, when AAT is knocked out in mice (AAT-KO), inflammatory-related, cholesterol metabolism-related, and lipid metabolism-related gene expression in mouse liver was increased, and these data support previous evidence from clinic patients and from a small clinical trial that AAT is in negative feedback regulation with LDL. Herein is a brief summary to examine the roles of AAT in these overlapping pathways.

Nine controversial questions about augmentation therapy for alpha-1 antitrypsin deficiency: a viewpoint.

Augmentation therapy with intravenous alpha-1 antitrypsin is the only specific treatment for alpha-1 antitrypsin deficiency (AATD)-associated emphysema. This treatment has been available and remained basically unchanged for more than 35 years, but many questions persist regarding its indications, regimen of administration and efficacy. Because AATD is a rare disease, it has not been possible to conduct randomised, placebo-controlled trials that are adequately powered for the usual outcomes analysed in non-AATD-related COPD, such as lung function decline, exacerbations, symptoms or quality of life. New outcomes such as lung densitometry measured by computed tomography are more sensitive for identifying emphysema progression but are not widely accepted by regulatory agencies. In addition, clinical manifestations, severity and the natural history of lung disease associated with AATD are very heterogeneous, which means that individual prediction of prognosis is challenging. Therefore, the indication for augmentation is sometimes a dilemma between initiating treatment in individuals who may not develop significant lung disease or in whom disease will not progress and delaying it in patients who will otherwise rapidly and irreversibly progress.Other areas of debate are the possible indication for augmentation in patients with severe AATD and respiratory diseases other than emphysema, such as bronchiectasis or asthma, and the use of therapy after lung transplant in AATD patients. All these uncertainties imply that the indication for treatment must be personalised in expert reference centres after in-depth discussion of the pros and cons of augmentation with the patient.

Predicting Lung Function Using Biomarkers in Alpha-1 Antitrypsin Deficiency.

Lung disease progression in alpha-1 antitrypsin deficiency (AATD) is heterogenous and manifests in different ways. Blood biomarkers are an attractive method of monitoring diseases as they are easy to obtain and repeatable. In non-AATD COPD, blood biomarker panels have predicted disease severity, progression, and mortality. We measured a panel of seven serum biomarkers in 200 AATD patients and compared levels between those with COPD and those without. We assessed whether biomarkers were associated with baseline lung function parameters (FEV1 and TLco) or absolute change in these parameters. In total, 111 patients with a severely deficient genotype of AATD (PiZZ) and COPD were included in the analyses. Pearson's correlation coefficient was measured for biomarker correlations and models were compared using ANOVA. CRP and CCL18 were significantly higher in the serum of AATD COPD versus AATD with no COPD. Biomarkers were not predictive of cross-sectional lung function measurements, however, CC16 was significantly associated with an absolute change in TLco (p = 0.018). An addition of biomarkers to the predictive model for TLco added significant value over covariates alone (R2 0.13 vs. 0.02, p = 0.028). Our findings suggest that CC16 is predictive of emphysema progression in AATD COPD. Proteomics data may reveal alternative candidate biomarkers and further work should include the use of longitudinal biomarker measurements.

Estimating the Prevalence of AATD Patients in the UK to Identify Underdiagnosis and Determine the Eligibility for Potential Augmentation Therapy.

Alpha 1 antitrypsin deficiency (AATD) is a genetic risk factor for chronic obstructive pulmonary disease (COPD). Whilst testing for the condition is relatively simple, there is a disconnect in published literature between genetic epidemiology and numbers of patients known to specialists. This makes planning services for patients difficult. We aimed to estimate the number of patients likely to have lung disease eligible for specific AATD therapy within the UK. The THIN database was used to determine the prevalence of AATD and symptomatic COPD. This, and published rates of AATD were used to extrapolate THIN data to the population size of the UK to give an indicative population size for symptomatic AATD patients who have lung disease. The Birmingham AATD registry was used to describe age at diagnosis, rate of lung disease and symptomatic lung disease for patients with PiZZ (or equivalent) AATD, together with the time from symptom onset to diagnosis, in order to aid interpretation of the THIN data and improve modeling. THIN data showed COPD prevalence of 3%, and AATD prevalence of 0.005-0.2%, depending on how stringently AATD diagnostic codes were applied. The majority of Birmingham AATD patients were diagnosed between the ages 46-55, whilst patients recorded in THIN tended to be older. The rate of COPD was similar in the THIN and Birmingham patients diagnosed with AATD. Modelling to the size of the UK demonstrated a likely symptomatic AATD population of between 3016 and 9866 people. AATD is likely to be under-diagnosed in the UK. Based on projected patient numbers an expansion to specialist services is desirable, in particular if specific therapy for AATD such as augmentation were to be introduced to the healthcare system.

Hypoxia Enhances Oxidative Stress in Neutrophils from ZZ Alpha-1 Antitrypsin Deficiency Patients.

Alpha-1 antitrypsin deficiency (AATD) is a neutrophilic inflammatory disorder that may result in local hypoxia, reactive oxygen and nitrogen species (ROS/RNS) production, and increased damage in adjacent tissues. This study aims to determine the impact of hypoxia on neutrophil oxidative stress profile in AATD patients. Neutrophils were isolated from AATD patients and control volunteers and exposed to hypoxia (1% O2 for 4 h), ROS/RNS, mitochondrial parameters, and non-enzymatic antioxidant defenses measured by flow cytometry. The expression of enzymatic antioxidant defenses was determined by qRT-PCR. Our results indicate that ZZ-AATD neutrophils produce higher amounts of hydrogen peroxide, peroxynitrite, and nitric oxide and decreased levels of the antioxidant enzymes catalase, superoxide dismutase, and glutathione reductase. Likewise, our results show a decrease in mitochondrial membrane potential, indicating that this organelle could be involved in the production of the reactive species observed. No decrease in glutathione and thiol levels were observed. The accumulation of substances with high oxidative capacity would explain the greater oxidative damage observed in proteins and lipids. In conclusion, our results indicate that, compared to MM control individuals, ZZ-AATD neutrophils show increased ROS/RNS production under hypoxic conditions opening a new rationale for using antioxidant therapies to treat the disease.

Cleaning up alpha-1 antitrypsin deficiency related liver disease.

Alpha-1 antitrypsin deficiency (AATD) is one of the most common genetic disorders arising due to mutations in alpha-1 antitrypsin (AAT) gene affecting primarily the lung and the liver. This review summarizes the pathophysiology and clinical manifestation of different AATD genotypes and discusses the recent therapeutic developments. The focus is on the severe, rare homozygous Pi∗ZZ and the common heterozygous Pi∗MZ genotype. Pi∗ZZ individuals harbor an up to 20 times higher risk of liver fibrosis and cirrhosis than noncarriers and liver transplantation is currently the only available therapeutic option. AATD constitutes a proteotoxic disorder arising from hepatic AAT accumulation and the currently most promising data come from a phase 2, open-label trial of fazirsiran, a hepatocyte-targeted siRNA. Pi∗MZ subjects display an increased risk of advanced liver disease and at the latter stage, a faster deterioration than individuals without AAT mutation. Although the fazirsiran data offer a glimpse of hope to AATD patients, a consensus on appropriate study endpoint, a careful patient selection as well as monitoring of long-term safety will be essential for an approval.

SERPINA1 and More? A Putative Genetic Contributor to Pulmonary Dysfunction in Alpha-1 Antitrypsin Deficiency

Alpha-1 antitrypsin deficiency (AATD) is a common inherited disorder associated with an increased risk of pulmonary disease. Its clinical presentation, including the nature and severity of organ involvement, is highly variable and unpredictable and is not as strongly linked to genotype and environmental exposure (e.g., smoking history) as might be expected. Significant differences were observed within matched populations of severe AATD patients regarding risk of complications, age at onset, and disease course, including the dynamics of lung function decline. Genetic factors are among the putative modifiers contributing to the clinical variability in AATD, yet their role remains elusive. Here, we review and summarise our current understanding of epigenetic and genetic modifiers of pulmonary dysfunction in subjects with AATD.

COVID-19’s impact on care practice for alpha-1-antitrypsin deficiency patients

BackgroundPatients with alpha-1 antitrypsin deficiency (AATD), commonly categorized as a rare disease, have been affected by the changes in healthcare management brought about by COVID-19. This study’s aim was to identify the changes that have taken place in AATD patient care as a result of the COVID-19 pandemic in Spain and to propose experts’ recommendations aimed at ensuring humanized and quality care for people with AATD in the post-pandemic situation.MethodsA qualitative descriptive case study with a holistic single-case design was conducted, using focus groups with experts in AATD clinical management, including 15 health professionals with ties to the Spanish health system (12 pneumologists and 2 hospital pharmacists from 11 different hospitals in Spain) and 1 patient representative.ResultsCOVID-19 has had a major impact on numerous aspects of AATD clinical patient management in Spain, including diagnostic, treatment, and follow-up phases. The experts concluded that there is a need to strengthen coordination between Primary Care and Hospital Care and improve the coordination processes across all the organizations and actors involved in the healthcare system. Regarding telemedicine and telecare, experts have concluded that it is necessary to promote this methodology and to develop protocols and training programs. Experts have recommended developing personalized and precision medicine, and patient participation in decision-making, promoting self-care and patient autonomy to optimize their healthcare and improve their quality of life. The possibility of monitoring and treating AATD patients from home has also been proposed by experts. Another result of the study was the recommendation of the need to ensure that plasma donations are made on a regular basis by a sufficient number of healthy individuals.ConclusionThe study advances knowledge by highlighting the challenges faced by health professionals and changes in AATD patient management in the context of the COVID-19 pandemic. It also proposes experts’ recommendations aimed at ensuring humanized and quality care for people with AATD in the post-pandemic situation. This work could serve as a reference study for physicians on their daily clinical practice with AATD patients and may also provide guidance on the changes to be put in place for the post-pandemic situation.

Quality of Life and Mortality Outcomes for Augmentation Naïve and Augmented Patients with Severe Alpha-1 Antitrypsin Deficiency.

Intravenous alpha-1 antitrypsin (AAT) augmentation therapy is the only specific treatment available for alpha-1 antitrypsin deficiency (AATD)-related lung disease. It is widely used worldwide but remains unavailable to patients with AATD in the United Kingdom. While randomized trials of augmentation therapy have demonstrated biochemical efficacy and lung tissue preservation using computed tomography (CT) densitometry, these studies were not adequately powered to demonstrate effectiveness in well-accepted clinical endpoints such as quality of life (QOL) or survival. We used large, prospectively followed AATD patient populations in the United States and United Kingdom to explore these important clinical endpoints. Our inclusion criterion was adults with severe AATD and associated lung disease. The treatment group was U.S. AATD patients receiving augmentation therapy for lung disease. The control group was augmentation therapy naïve AATD patients. Multivariable regression and survival analyses were used to assess QOL and mortality outcomes respectively. Mean annual deterioration of the St George's Respiratory Questionnaire total score was 1.43 points greater/year in the control group compared to those receiving augmentation therapy (95% confidence interval [CI] 0.47 to 2.39, p=0.003). At 7 years, median survival was 82.7% (95% CI 75.3 to 90.7) for the control group versus 87.8% (95% CI 82.8 to 93.2) in the augmentation group, p=0.66. There was significant heterogeneity between cohorts. A comparison of 2 highly characterized AATD cohorts was not able to reliably determine if AAT augmentation therapy improves QOL or mortality in patients with severe AATD-related lung disease. Alternative surrogate biomarkers of disease progression, such as CT lung density, may be a more pragmatic option.

“Idiopathic Pulmonary Fibrosis and Alpha 1 Antitrypsin Deficiency: A Case Report of a Patient Undergoing Lung Transplantation and Intravenous Augmentation Therapy

Idiopathic Pulmonary Fibrosis (IPF) is a chronic interstitial lung disease characterized by progressive lung scarring and the pathological hallmark of usual interstitial pneumonia (UIP). On the other hand, Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder predisposing individuals to lung and liver diseases. Despite its rarity in literature, the relationship between IPF and AATD remains unclear. While IPF often necessitates lung transplantation in advanced stages, traditional AATD management involves supportive therapy. However, the introduction of supplemental alpha1-antitrypsin (AAT) derived from pooled human plasma has shown promise in retarding lung function decline. Notably, post lung transplantation, the genetic basis of AATD-related lung disease persists, potentially exposing patients to disease recurrence. Here, we present a clinical case of a patient initially diagnosed with IPF who subsequently underwent double lung transplantation and was later diagnosed with AATD. This case study prompts inquiry into critical unresolved questions: the potential benefits of post-transplant augmentation therapy for AATD patients and the potential association between AATD and pulmonary fibrosis. The intricate interplay between these two conditions underscores the need for further investigation to enhance our understanding and improve patient outcomes