Alpha-1 Antitrypsin Levels Research Articles

Abstract 4144560: Phase 2 Open-label, Single-arm, Multi-center Clinical Trial to Evaluate the Efficacy and Safety of Camostat Mesylate in Patients with Protein-losing Enteropathy after Fontan Operation-Preliminary Outcome

Introduction: Protein-losing enteropathy (PLE) is a multifaceted condition that profoundly affects the systemic health and quality of life of Fontan patients. Despite medical progress, the treatment of PLE remains a significant challenge. This study investigates the efficacy and safety of Camostat Mesylate for managing PLE patients who have undergone the Fontan operation. Hypothesis: We hypothesize that Camostat Mesylate will enhance the gut environment, resulting in increase of serum albumin levels and decrease of stool alpha-1 antitrypsin levels in PLE patients following Fontan operation. Methods: This phase 2, multicenter, open-label, single-arm trial included patients over 4 years old diagnosed with PLE following Fontan operation. Camostat Mesylate was added to conventional treatments, with follow-up assessments at 1, 3, and 6 months, and a final evaluation one month after discontinuation. Efficacy was measured by changes in serum albumin, stool alpha-1 antitrypsin levels, and PLE symptoms such as diarrhea, edema, weight changes, and ascites. Results: Nineteen patients were enrolled in the study, of whom fifteen patients completed follow-up as per protocol. The median age was 15 years (interquartile range, 12.0-21.3). The median time between the Fontan operation and PLE diagnosis was 2.4 years. Serum albumin levels increased from 2.5 to 2.6 g/dL (p=0.504), and stool alpha-1 antitrypsin levels decreased significantly from 280.0 to 172.1 mg/dL (p=0.033). Notably, patients with diarrhea at baseline showed substantial improvement in both parameters, with increased serum albumin levels from 1.8 to 2.2 g/dL and decreased stool alpha-1 antitrypsin levels from 220.3 to 80.2 mg/dL. No serious adverse events were reported during study period. Conclusions: Camostat Mesylate demonstrated safety and efficacy, reducing stool alpha-1 antitrypsin in PLE patients after Fontan operation, especially those with diarrhea at baseline. Therefore, Camostat Mesylate could be considered as an additional treatment option for patients with PLE following Fontan operation. Key words: Camostat mesylate; protein-losing enteropathy; Fontan operation Source of Funding: This research was funded by SNUH Lee Kun-hee Child Cancer&Rare Disease Project, Republic of Korea.

The association between alpha-1 antitrypsin and B-type natriuretic peptide blood levels in healthy African Americans

ObjectiveB-type natriuretic peptide (BNP) is a neurohormone primarily secreted from cardiac ventricles in reaction to increased volume and pressure. The plasma level of BNP is used to measure the mechanical function of the heart and the risk of developing chronic obstructive pulmonary disease (COPD). Alpha-1 antitrypsin (AAT) is a glycoprotein that acts as an inhibitor of serine proteases and plays a crucial role in protecting the lungs against potential harm. AAT deficiency also causes COPD. The data on the prevalence of BNP and AAT in African Americans (AA) are limited and inconsistent. No previous studies have investigated whether any association exists between BNP and AAT. We collected fasting blood samples from 114 AA subjects who provided informed consent. The plasma levels of the biomarkers were measured using ELISA.ResultsOur findings revealed a significant negative correlation between AAT and BNP (r=-0.266, p = 0.01) as well as between AAT and TNF-α (r=-0.242, p = 0.01). Sex hormones (estrogen and testosterone) have a significant relationship with the levels of AAT and BNP. Increasing the AAT and reducing the levels of inflammation can lower the levels of BNP, which in turn could help lower the risk of heart disease in the AA population.

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.

Increased Intestinal Inflammation and Permeability in Glaucoma.

Evidence suggests that dysbiosis of the gut microbiota plays a pivotal role in the development of glaucoma. This dysbiosis is commonly associated with chronic intestinal inflammation and increased intestinal permeability. However, the understanding of intestinal inflammation and permeability in glaucoma remains insufficient. This study aims to investigate the potential relationship between fecal inflammation and permeability markers and glaucoma. We recruited 114 glaucoma patients and 75healthy controls. Levels of fecal lactoferrin (Lf) and alpha-1 antitrypsin (AAT) were quantified using enzyme linked immunosorbent assay (ELISA) to compare both biomarkers between groups and across different severity grades of glaucoma. Logistic regression analysis was used to assess the association between these fecal biomarkers and glaucoma. The severity of glaucoma was assessed based on the mean deviation (MD) in the visual field. In this study, we observed elevated levels of fecal Lf and AAT in glaucoma patients. The proportion of glaucoma patients with abnormal fecal Lf levels (≥ 7.25µg/g) was significantly higher than that of the controls (p = 0.012). A positive correlation was noted between fecal Lf and AAT (rho = 0.20, p = 0.006). After adjusting for age and sex, multivariable logistic regression analysis indicated that both fecal Lf (OR = 1.11, 95% CI: 1.01-1.21, p = 0.026) and AAT (OR = 1.01, 95% CI: 1.01-1.02, p < 0.001) positively correlated with glaucoma. These biomarkers might reflect glaucoma severity, with significant differences in fecal Lf levels observed between moderate and severe stages, but not in the early stage. Furthermore, increasing levels of fecal AAT correlated with greater severity of glaucomatous injury and a larger vertical cup-to-disc ratio (VCDR) (p < 0.05). This study suggests an increase in intestinal inflammation and permeability in glaucoma, further indicating the importance of the 'gut-retina axis' in the pathogenesis of the disease and potentially offering new therapeutic avenues.

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.

Heterozygous SERPINA1 Defects and Their Impact on Clinical Manifestations of Patients with Predominantly Antibody Deficiencies.

Patients with predominantly antibody deficiencies (PADs) display hypogammaglobulinemia with a high prevalence of infections, along with autoimmune manifestations, benign and malignant lymphoproliferation and granulomatous disease. It is noteworthy that PAD patients, even those with defects in the same causative genes, display a variable clinical phenotype, suggesting that additional genetic polymorphisms, located in either immune-related or non-immune-related genes, may affect their clinical and laboratory phenotype. In this context, we analyzed 80 PAD patients, including 70 with common variable immunodeficiency (CVID) for SERPINA1 defects, in order to investigate the possible contribution to PAD clinical phenotype. Ten CVID patients carried heterozygous pathogenic SERPINA1 defects with normal alpha-1 antitrypsin levels. Interestingly, the presence of the Z allele (rs28929474), which was found in three patients, was significantly associated with liver disease; hepatic complications were also observed in patients carrying the p.Leu23Gln (rs1379209512) and the p.Phe76del (rs775982338) alleles. Conversely, no correlation of SERPINA1 defective variants with respiratory complications was observed, although patients with pathogenic variants exhibit a reduced probability of developing autoimmune diseases. Therefore, we recommend SERPINA1 genetic analysis in PAD in order to identify patients with a higher risk for liver disease.

Maternal serum alpha-1 antitrypsin levels in spontaneous preterm and term pregnancies

Currently, there are no accurate means to predict spontaneous preterm birth (SPTB). Recently, we observed low expression of alpha-1 antitrypsin (AAT) in SPTB placentas. Present aim was to compare the concentrations of maternal serum AAT in pregnancies with preterm and term deliveries. Serum C-reactive protein (CRP) was used as a reference inflammatory marker. Two populations were studied. The first population comprised women who eventually gave birth spontaneously preterm (SPTB group) or term (control group). The second population included pregnant women shortly before delivery and nonpregnant women. We observed that serum AAT levels were higher in the SPTB group than in the controls, and a similar difference was observed when serum CRP was considered in multivariable analysis. However, the overlap in the AAT concentrations was considerable. No statistical significance was observed in serum AAT levels between preterm and term pregnancies at delivery. However, AAT levels were higher at delivery compared to nonpregnant controls. We did not observe a strong correlation between serum AAT and CRP in early pregnancy samples and at labor. We propose that during early pregnancy, complicated by subsequent SPTB, modest elevation of serum AAT associates with SPTB.

Alpha-1 Antitrypsin Phenotyping: An Unmet Educational Need of Healthcare Providers.

Diagnosing alpha-1 antitrypsin deficiency (A1ATD) involves two-step laboratory testing, determination of serum alpha-1 antitrypsin (A1AT) level and phenotyping if A1AT < 100 mg/dL. Whether these guidelines are effectuated in clinical practice is uncertain. To begin to address this issue, we determined whether A1AT phenotyping is performed in patients with serum A1AT 57 - 99 mg/dL at our institution. We reviewed the medical records of patients seen at Jesse Brown Veterans Affairs Medical Center from January 2019 to October 2022 with serum A1AT between 57 and 99 mg/dL. In each case, pertinent demographic, clinical, and pulmonary function tests data were extracted. Data were presented as means and standard deviation (SD) where appropriate. The Student's t-test was used for statistical analysis. P < 0.05 was considered statistically significant. Thirty patients (90% males; 60 ± 18 years) with serum A1ATD < 100 mg/mL were identified. Fourteen were African Americans, four Hispanics, and 12 non-Hispanic Whites. The majority were current or ex-smokers. Fourteen (47%) patients had lung disease, 14 (47%) liver disease and one had concomitant lung and liver diseases. Mean ± SD forced expiratory volume in 1 s (FEV1) and lung diffusing capacity were 2.57 ± 1.41 L (67±19% predicated) and 18.7 ± 10 mL/min/mm Hg (64±28% predicted), respectively. Only 13 patients (43%) underwent phenotype testing (seven African Americans, five Whites, and one Hispanic). Six patients had MZ phenotype, four MS, and three SZ. One patient died from acute respiratory failure during the study period. Phenotyping of patients with serum A1AT 57 - 99 mg/dL at our institution is inadequate. Accordingly, regular continuous medical educational programs on A1AT phenotyping targeting healthcare providers are warranted.

Effect of alpha-1 antitrypsin and alpha-1-acid glycoprotein levels on prognosis in patients with COPD exacerbation and COPD-community-acquired pneumonia

Aims: Chronic obstructive pulmonary disease (COPD) is the most frequent comorbid condition that is present in patients with pneumonia. An exacerbations of chronic obstructive pulmonary disease (ECOPD) and Comminity-acquired pneumonia (CAP) are associated with high rates of hospitalizations, costs, and morbidity. Plasma levels of orosomucoid and Alpha-1 antitrypsin (AAT), also known as Alpha-1-acid glycoprotein (AGP), increase in response to inflammation and tissue necrosis. The purpose of this study is to evaluate the impact of markers in patients with ECOPD and COPD with pneumonia . Methods: To compare the levels of AAT, and AGP, between patients diagnosed with ECOPD only and patients diagnosed with COPD and pneumonia. Results: The study included 14 female and 22 male volunteers. The mean gender and age of groups 1 and 2 were similar. There was no statistical difference in laboratory values between the groups. Conclusion: Alpha-1-acid glycoprotein and AAT are acute-phase proteins elevated in various inflammatory conditions such as infections, trauma, and chronic diseases such as COPD. More studies are needed on their usefulness for monitoring and/or treatment in daily practice.

Detection of Alpha-1 Antitrypsin Levels in Chronic Obstructive Pulmonary Disease in Respiratory Clinics in Spain: Results of the EPOCONSUL 2021 Audit.

Alpha-1 antitrypsin deficiency (AATD) is an underdiagnosed condition despite being one of the most common inherited disorders in adults that is associated with an increased risk of developing chronic obstructive pulmonary disease (COPD). The aim was to evaluate the frequency of performing AAT levels and associated factors in COPD patients in an audit conducted in 2021-2022, as well as to compare with a previous audit conducted in 2014-2015. EPOCONSUL 2021 is a cross-sectional audit that evaluated the outpatient care provided to COPD patients in respiratory clinics in Spain based on available data from medical registries. 4225 patients with a diagnosis of COPD from 45 centers were audited in 2021. A total of 1670 (39.5%) patients underwent AAT determination. Being treated at a specialized COPD outpatient clinic (OR 1.88, p = 0.007), age ≤ 55 years old (OR 1.84, p = 0.007) and a FEV1 < 50% (OR 1.86, p < 0.001) were associated with a higher likelihood of being tested for AAT, while Charlson index ≥ 3 (OR 0.63, p < 0.001) and genotyping of AATD availability (OR 0.42, p < 0.001) showed a statistically significant negative association. The analysis of cases included in respiratory units that participated in both audits showed an increase in the proportion of cases with AAT serum level testing available (adjusted OR 2.81, p < 0.001). The percentage of individuals with serum AAT levels < 60 mg/dL (a severe AATD) was 4%. Our analysis identifies significant improvements in adherence to the recommendation to test AAT levels in COPD patients, performed in 4 out of 10 patients, being more likely at younger ages and with higher COPD severity, and with a detection of severe AATD of 4% among those tested, suggesting that clinicians still perform AAT testing in COPD patients selectively. Therefore, efforts are still needed to optimize AATD screening and establish new early detection strategies to reduce morbidity and mortality in these patients.

Detection and evaluation of positive acute phase reactant protein markers in neonates and adults with sepsis

. Introduction and Aim: Septicemia is a clinical condition caused due to bacterial infection of the blood. Septicemia leading to sepsis could be life-threatening leading to tissue damage, organ failure, and death. The current study aimed to determine the impact of various biomarkers on patients suffering from sepsis, including Serum amyloid A, C-reactive protein, HS- Troponin, fibrinogen, haptoglobin and alpha1-antitrypsin, as well as identify the common bacterial types associated in septic patients. Materials and Methods: This case-control study conducted during October 2022 to May 2023 involved 100 participants that were divided into groups which included patients diagnosed with septicemia due to bacteria (Group A), patients with septicemia with non-bacterial infection (Group B) and healthy individuals as controls (Group C). Results: Serum amyloid A, C-reactive protein, HS-Troponin, Fibrinogen, Haptoglobin, and Alpha-1 antitrypsin levels in neonates and adults with sepsis were found to be elevated when compared to healthy individuals. No significant difference was observed for these parameters between Group A patients (positive for blood culture) and Group B patients (negative for blood culture) among neonates and adult sepsis patients. Conclusion: Neonates and adult sepsis patients exhibited higher levels of serum amyloid A, C-reactive protein, HS-Troponin, fibrinogen, hemoglobin, and Alpha-1 antitrypsin in comparison to healthy controls. Hence, these biochemical parameters could be used as biomarkers to assess a patient's level of sepsis for further therapeutic action.

Recombinant Alpha-1 Antitrypsin-Fc Fusion Protein INBRX-101 in Adults With Alpha-1 Antitrypsin Deficiency: A Phase 1 Study.

Alpha-1 antitrypsin deficiency (AATD) is characterized by low alpha-1 antitrypsin (AAT) levels, predisposing individuals to lung disease. The standard of care, plasma-derived AAT (pdAAT), is delivered as weekly infusions to maintain serum AAT concentrations ≥11µM (≈50% of those in healthy individuals). INBRX-101, a recombinant human AAT-Fc fusion protein, was designed to have a longer half-life and achieve higher AAT levels than pdAAT. In this phase 1 dose-escalation study (N=31), adults with AATD received 1 dose (part 1) or 3 doses (part 2) of 10 (part 1), 40, 80, or 120mg/kg INBRX-101 every 3 weeks (Q3W) via intravenous infusion. The primary endpoint was safety and tolerability. Secondary endpoints were pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of INBRX-101. INBRX-101 was well tolerated. Most treatment-emergent adverse events were grade ≤2. In part 2 (n=18; each dose, n=6), dose-related increases in serum functional AAT (fAAT) were observed; mean fAAT levels remained above the 21 µM target for up to 4 weeks after the final dose in the 120-mg/kg cohort. Antidrug antibodies had no meaningful impact on PK or PD. INBRX-101 was detected in pulmonary epithelial lining fluid (PELF) from all patients assessed (n=11), and PELF fAAT increased after dosing. PK/PD modeling projected steady-state serum fAAT ≥21µM at 120 mg/kg Q3W (average concentration ≈43µM; trough concentration ≈28µM) and Q4W (≈34µM; ≈21µM). The favorable safety profile and ability to maintain serum fAAT levels >21µM with extended-interval dosing, support a phase 2 trial evaluating Q3W and Q4W dosing of INBRX-101.

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.

Serum Western Blot for the Detection of a c-Myc Protein Tag in Non-human Primates and Mice.

This protocol allows for the detection of a c-Myc tag on alpha-1 antitrypsin (AAT) delivered to species that already have endogenous AAT such as non-human primates allowing reliable and repeatable semi-quantitation of serum levels of AAT.

Neuroinflammation as a Main Etiopathogenetic Factor in the Development of Drug-Resistant Epilepsies and Epileptic Encephalopathies

Background: despite the large number of newly emerging antiepileptic drugs, the frequency of treatment-resistant forms of epilepsy has not decreased, averaging 25–30%. Moreover the number of epileptic encephalopathies of early childhood has increased. One of the reasons of drug resistance is neuroinflammation. Aim: to evaluate the role of neuroinflammation in the pathogenesis of severe forms of childhood epilepsy and resistant adult epilepsy.Patients and methods: the main group 1 — 94 pediatric patients with epileptic encephalopathies, average age 20.4 ± 6.2 months. The control group 1 — 42 pediatric patients in remission of epilepsy, average age 21.3 ± 5.7 months. The main group 2 — 35 adult patients with resistant forms of epilepsy, average age 38.3 ± 7.9 years. The control group 2 — adult patients in remission of epilepsy 47 patients, average age 34.2 ± 8.6 years. The following blood levels were analyzed: neuron-specific enolase, S100 protein, eosinophilic cationic protein, IgE total level, total level of circulating immune complexes, leukocyte elastase and alpha-1 antitrypsin. Results: in the group of children with epileptic encephalopathies, an increase in neuroinflammation indicators was revealed in most patients. The average level of neuron-specific enolase is 27.6 ± 5.3 ng/ml compared to 14.2 ± 3.5 ng/ml in the control group. The average S100 protein level is 0.232 ± 0.041 ng/ml compared to 0.092 ± 0.024 ng/ml in the control group. The average level of eosinophilic cationic protein is 39.7 ± 9.4 ng/ml compared with 18.2 ± 5.3 ng/ml in the control group. The average IgE level is 157.3 ± 64.2 IU/ml compared to 42.2 ± 17.5 IU/ml in the control group. The average level of circulating immune complexes is 265.6 ± 54.4 UE/ml compared to 56.8 ± 16.8 UE/ml in the control group. In the group of adult patients with resistant forms of epilepsy, an increase in neuroinflammation indicators was revealed in most patients. The average level of neuron-specific enolase is 19.2 ± 7.2 ng/ml compared to 13.1 ± 4.1 ng/ml in the control group. The average S100 protein level is 0.115 ± 0.037 ng/ml compared to 0.093 ± 0.018 ng/ml in the control group. The average level of eosinophilic cationic protein is 24.2 ± 6.7 ng/ml compared to 18.8 ± 4.7 ng/ml in the control group. The average level of total IgE is 117.9 ± 32.6 IU/ml compared to 53.4 ± 18.2 IU/ml in the control group. The average level of circulating immune complexes is 235.2 ± 43.7 UE/ml compared to 62.6 ± 20.4 UE/ml in the control group. The level of leukocyte elastase was increased in 32 (91.4%) patients, the average level was 267.2 ± 36.8 nmol/min × ml compared with 175.2 ± 23.8 nmol/min × ml in the control group. The level of alpha-1 antitrypsin was increased in 33 (94.3%) patients, the average level was 55.2 ± 12.1 ng/ml compared with 26.4 ± 15.6 ng/ml in the control group. Conclusion: neuroinflammation is the factor of the development of severe forms of epilepsy and the formation of resistance in epileptic encephalopathies. Epileptic encephalopathies of early childhood according to their etiopathogenesis should be considered as subacute encephalitis, where seizures are only one sign of the pathological inflammatory process. The main clinical aim of the treatment of epileptic encephalopathies is the diagnosis of cumulative antigenic load and the selection of anti-inflammatory therapy.

Prevalence of Soil-Transmitted Helminths at Baseline and after Albendazole Treatment in the School-Age Children of Forcibly Displaced Myanmar Nationals in Bangladesh.

The forcibly displaced Myanmar nationals (FDMNs) known as Rohingya refugees are the largest group of stateless individuals globally. According to the emergencies humanitarian actors at the United Nations Office for the Coordination of Humanitarian Affairs, the worldwide refugee crisis involving FDMNs is intensifying at the fastest rate in history. Growing public health demands are being exacerbated by current difficulties in addressing poor access to health services, severe food shortages, and a lack of adequate housing. Infectious diseases constitute a major public health emergency in this vulnerable population. A study was carried out in FDMN children to investigate common soil-transmitted helminth (STH) infection at the time of enrollment and prospectively followed-up to 12 months after 2 doses albendazole treatment. At baseline, the prevalence of STH infection with at least one species was found to be 91.7% and 87.3% for Kato-Katz (KK) and quantitative polymerase chain reaction (qPCR) methods, respectively. Similarly, for follow-up children, the overall infection rate was 95.3% and 91.5%, respectively. Trichuris trichiura was the most predominant STH infection by both KK (baseline 87%, follow-up 89.1%) and qPCR (baseline 77.5%, follow-up 82.9%). The overall prevalence of stunting in the children was 37.8% at baseline and rose to 51.3% at 12 months. Alpha-1 antitrypsin (r = 0.13, P = 0.01) and myeloperoxidase (r = 0.12, P = 0.01) levels showed a positive correlation with Aascaris lumbricoides egg count per gram at baseline. An in-depth investigation is urgently needed to identify the underlying protective measures and the root cause of STH infections to improve the health of FDMN children.

Initial alpha-1 antitrypsin screening in Turkish patients with chronic obstructive pulmonary disease.

Alpha-1 antitrypsin (AAT) deficiency is associated with several types of pathology, and the reported effects of mutations in the ATT-encoding gene vary worldwide. No Turkish study has yet appeared. We thus explored the AAT status of Turkish patients with chronic obstructive pulmonary disease (COPD). This prospective cross-sectional study included outpatients and inpatients treated from June 2021 to June 2022. Serum AAT levels were checked, and dry blood samples were subjected to genetic analysis. : Genetic mutations were found in 21 (3.52%) of 596 patients with prior and new COPD diagnoses treated in our pneumonology outpatient department. The mean serum AAT level was 114.80 mg/dL (minimum 19, maximum 209; standard deviation 27.86 mg/dL). The most frequent mutation was M/Plowell (23.8%, n = 5), followed by M/S (23.8%, n = 5), M/I (19%, n = 4), M/Malton (14.3%, n = 3), Z/Z (9.5%, n = 2), M/Z (4.8%, n = 1), and Kayseri/Kayseri (4.8%, n = 1). Thoracic computed tomography revealed that 85.7% (n = 18) of all patients had emphysema, 28.5% (n = 6) had bronchiectasis, and 28.5% (n = 6) had mass lesions. Of the emphysema patients, 55% (n = 10) had only upper lobe emphysema, and 83.3% (n = 15) had emphysema in additional areas, but statistical significance was lacking (p > 0.05). In patients with emphysema and normal serum AAT levels, genetic analyses may reveal relevant heterozygous mutations, which are commonly ignored. Most clinicians focus on lower lobe emphysema. Evaluations of such patients might reveal AAT mutations that are presently overlooked because they are not considered to influence COPD status.

Diagnosis and augmentation therapy for alpha-1 antitrypsin deficiency: current knowledge and future potential.

The underdiagnosis of alpha-1 antitrypsin (AAT) deficiency (AATD) has been recognized for many years, yet little progress has been made in treatment of the disease. In this review, we summarize the AATD disease process as well as its diagnosis and treatment by AAT augmentation therapy. AATD is a rare autosomal disease that primarily affects the lungs and liver. AATD is associated with an increased susceptibility to developing pulmonary emphysema. The specific pharmacological treatment for AATD is intravenous administration of exogenous AAT. Augmentation therapy with AAT increases serum and pulmonary epithelial AAT levels, restores anti-elastase capacity, and decreases inflammatory mediators in the lung. Augmentation therapy reduces the loss of lung density over time, thus slowing progression of the disease. The effects of augmentation therapy on outcomes, such as frequency/duration of flare-ups, quality of life, lung function decline and mortality, are assessed. Wider testing for AATD, potentially through primary care physicians, could result in earlier treatment and better outcomes for individuals with AATD-induced lung respiratory disease.

Testing Patterns and Disparities for Alpha-1 Antitrypsin Deficiency

BackgroundAlpha-1 antitrypsin deficiency is an under-recognized genetic cause of chronic lung and liver disease; it remains unclear what the testing frequency and disparities are for alpha-1 antitrypsin deficiency. MethodsThis is a retrospective cohort study of people with newly diagnosed chronic obstructive pulmonary disease and liver disease identified at the University of Florida between January 1, 2012 and December 31, 2021. We performed incidence and prevalence analysis for alpha-1 antitrypsin (AAT) testing and point-biserial correlation analysis for tobacco use and AAT testing. We evaluated characteristics with AAT testing using adjusted multivariable logistic regression. ResultsAmong 75,810 subjects with newly diagnosed chronic obstructive pulmonary disease and liver disease between 2012 and 2021, 4248 (5.6%) were tested for AAT deficiency. All subjects had an AAT level performed, while 1654 (39%) had phenotype testing. Annual incidence of testing increased for subjects with newly diagnosed chronic obstructive pulmonary disease or liver disease from 2.8% and 5.4%, respectively, in 2012 to 4.1% and 11.3%, respectively, in 2021. Adjusted multivariable regression analysis showed factors favoring AAT testing were White race, and concomitant chronic obstructive pulmonary disease and liver disease. Increasing age, non-White race, current tobacco use, and being a male with chronic obstructive pulmonary disease had lower odds of AAT testing. ConclusionAlthough slowly improving, testing for AAT deficiency continues to have a low uptake in the clinical setting despite guidelines recommending broader testing. Individuals of White race and those with concomitant chronic obstructive pulmonary disease and liver disease are more likely to be tested, while older subjects, individuals of non-White race, current tobacco use, and men with chronic obstructive pulmonary disease are less favored to be tested.

FRI-448 - Prognostic role of serum alpha-1 antitrypsin levels for waitlist mortality in patients with alcohol-associated liver disease

FRI-448 - Prognostic role of serum alpha-1 antitrypsin levels for waitlist mortality in patients with alcohol-associated liver disease