scholarly journals α1-Antitrypsin deficiency and chronic respiratory disorders

2020 ◽  
Vol 29 (155) ◽  
pp. 190073 ◽  
Author(s):  
Mario Cazzola ◽  
Daiana Stolz ◽  
Paola Rogliani ◽  
Maria Gabriella Matera
Keyword(s):  
Specific Treatment ◽  
Forced Expiratory Volume ◽  
Response To Therapy ◽  
Gas Transfer ◽  
Respiratory Disorders ◽  
Antitrypsin Deficiency ◽  
Valve Placement ◽  
Regenerative Therapies ◽  
Lung Densitometry

α1-antitrypsin deficiency (AATD) is a hereditary disorder associated with a risk of developing liver disease and pulmonary emphysema, and other chronic respiratory disorders (mainly asthma and bronchiectasis); Z variant is the commonest deficient variant of AAT. Determining AAT concentration in serum or plasma and identifying allelic variants by phenotyping or genotyping are fundamental in the diagnosis of AATD. Initial evaluation and annual follow-up measurement of lung function, including post-bronchodilator forced expiratory volume in 1 s and gas transfer inform on disease progression. Lung densitometry is the most sensitive measure of emphysema progression, but must not be use in the follow-up of patients in routine clinical practice. The exogenous administration of purified human serum-derived AAT is the only approved specific treatment for AATD in PiZZ. AAT augmentation therapy is not recommended in PiSZ, PiMZ or current smokers of any protein phenotype, or in patients with hepatic disease. Lung volume reduction and endoscopic bronchial valve placement are useful in selected patients, whereas the survival benefit of lung transplant is unclear. There are several new lines of research in AATD to improve the diagnosis and evaluation of the response to therapy and to develop genetic and regenerative therapies and other treatments.

A Retrospective Hospital Based Study of 440 Patients of Aplastic Anemia from India: Epidemiology; Response to Therapy; and Possible Significance of Jaundice during Therapy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5299-5299 ◽  
Author(s):  
Rajat Kumar ◽  
Dharma R. Choudhary ◽  
Manoranjan Mahapatra ◽  
Atul Kotwal ◽  
Alka Mathur ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Statistical Significance ◽  
Medical Science ◽  
Specific Treatment ◽  
Complete Response ◽  
Response To Therapy ◽  
Acute Leukemias ◽  
Overall Response ◽  
High Incidence

Abstract All new cases of aplastic anemia (AA) seen in the Hematology out patient department (OPD) of All India Institute of Medical Science (AIIMS) from January 2001 to December 2003 were studied till last follow up. Complete response (CR) was defined as - normalization of blood counts; Partial response (PR) as - improvement in blood counts, transfusion independence and not meeting criteria of CR. Database was created in MS Access and SPSS ver 11 was used for statistical analysis. Descriptive statistics were calculated and appropriate tests of significance carried out. Result- A total of 440 cases of AA were seen during the study period. The total number of new hematology patients seen in the same period was 8605; thus AA comprised 51.13 per thousand (95% CI, 37.9–67.1) new hematology cases. The number of acute leukemias (AML and ALL) diagnosed during this period was 392: the ratio of AA to acute leukemia was 1.1:1. The total number of OPD patients registered in AIIMS for these 3 years was 43,04,849. Thus AA patients comprised 102.23 per million (95% CI, 83.2–123.8) hospital OPD patients. This very high incidence of AA may be due to the tertiary nature of AIIMS. The median age at presentation was 19yr (range 2–84), with males 311 (71%) and females 129 (29%). At presentation the hematological values were: mean hemoglobin (Hb) 5.2 ± 2.03 g/dl; mean total leucocyte count (TLC) 3.1 ± 1.3 x 109/L, mean platelet counts 33.8 ± 19.5 x 109/L. Follow up period was for a median of 3 months (range 0–42). Specific treatment consisted of (a) Androgens - Stanozolol at 2 mg/kg/d (b) Cyclosporine at 3mg/kg/d (c) Antithymocyte globulin at total dose of 75–80mg/kg over 5 to 8 days and (d) combinations of these drugs. The following subgroups were excluded from analysis (i) 14 (3.1%) patients whose records were incomplete and (ii) 38 (8.6%) patients who received only supportive therapy with no response, but whose individual follow up was limited. The overall response to all therapies was 29.7%. The response to different subgroups and statistical significance is given in Table. Jaundice occurred in 23 (5.2%) patients during treatment and HBsAg was positive in two. The course of jaundice was clinically uncomplicated and lasted for 2 to 3 weeks. An interesting finding was a partial or complete response to therapy in 19/23 (82.6%) with CR in 47.8% and PR in 34.8%. The difference in response rate of those who developed jaundice while on therapy and those who did not was statistically significant (P=0.000). Conclusions: The high incidence of AA in India provides a potential for future studies regarding its etiopathogenesis and therapy. Economic limitations make Stanozolol an important drug in developing countries with its response rates of 19.7%. The unexpected high response in those who developed jaundice during therapy suggests that this could be a marker for recovery. Response§ to Different Therapies in 388 Patients of Aplastic Anemia Treatment group Androgen alone Cyclosporin alone Androgen and Cyclosporin ATG + Cyclosporin ±Androgen Test Chi square test. ©Not statistically significant. ®Statistically significant. §Response compared to overall response to other therapies. Total number (%) 172 (39.1) 13 (3) 179 (40.7) 24 (6.3) Overall response, % 19.7 8.3 31.2 62.5 PR, % 8.6 8.3 15.9 33.3 CR, % 11.1 0 15.3 29.2 P value 0.067© not done 0.083© 0.000®

scholarly journals A New Multiplatform Model for Outpatient Prenatal and Postpartum Care in a Cohort of COVID-19-Affected Obstetric Patients

2021 ◽  
Vol 18 (10) ◽  
pp. 5144
Author(s):  
Mar Muñoz-Chápuli Gutiérrez ◽  
Ana Durán-Vila ◽  
Javier Ruiz-Labarta ◽  
Pilar Payá-Martínez ◽  
Pilar Pintado Recarte ◽  
...  
Keyword(s):  
Clinical Manifestations ◽  
Specific Treatment ◽  
Rt Pcr ◽  
Good Adherence ◽  
Major Morbidity ◽  
Reference Hospital ◽  
The Mean ◽  
Discharge From Hospital ◽  
Over Time

Spain was one of the epicenters of the first wave of the COVID-19 pandemic. We describe in this article the design and results of a new telephone-and-telematic multiplatform model of systematic prenatal and postpartum follow-up for COVID-19-affected women implemented in a tertiary reference hospital in Madrid. We included patients with RT-PCR-confirmed COVID-19 during pregnancy or delivery from 10 March 2020 to 15 December 2020. We had a total of 211 obstetric patients: 148 (70.1%) were tested at the onset of suspicious clinical manifestations and 62 (29.4%) were tested in the context of routine screening. Of all the patients, 60 women (28.4%) were asymptomatic and 97 (46%) presented mild symptoms. Fifty-one women (24.2%) were admitted to our hospital for specific treatment because of moderate or severe symptoms. We had no missed cases and a good adherence. The mean number of calls per patient was 2.3. We performed 55 in-person visits. We analyzed the complexity of our program over time, showing a two-wave-like pattern. One patient was identified as needing hospitalization and we did not record major morbidity. Telemedicine programs are a strong and reproducible tool to reach to pregnant population affected by COVID-19, to assess its symptoms and severity, and to record for pregnancy-related symptoms both in an outpatient regime and after discharge from hospital.

scholarly journals Rituximab-Containing Risk-Adapted Treatment Strategy in Nodular Lymphocyte Predominant Hodgkin Lymphoma: 7-Years Follow-Up

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1760
Author(s):  
Novella Pugliese ◽  
Marco Picardi ◽  
Roberta Della Pepa ◽  
Claudia Giordano ◽  
Francesco Muriano ◽  
...  
Keyword(s):  
Side Effects ◽  
Hodgkin Lymphoma ◽  
Prognostic Score ◽  
Single Agent ◽  
Response To Therapy ◽  
Baseline Risk ◽  
Historical Cohort ◽  
Treatment Groups

Background: Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare variant of HL that accounts for 5% of all HL cases. The expression of CD20 on neoplastic lymphocytes provides a suitable target for novel treatments based on Rituximab. Due to its rarity, consolidated and widely accepted treatment guidelines are still lacking for this disease. Methods: Between 1 December 2007 and 28 February 2018, sixteen consecutive newly diagnosed adult patients with NLPHL received Rituximab (induction ± maintenance)-based therapy, according to the baseline risk of German Hodgkin Study Group prognostic score system. The treatment efficacy and safety of the Rituximab-group were compared to those of a historical cohort of 12 patients with NLPHL who received Doxorubicin, Bleomycin, Vinblastine, Dacarbazine (ABVD) chemotherapy followed by radiotherapy (RT), if needed, according to a similar baseline risk. The primary outcome was progression-free survival (PFS) and secondary outcomes were overall survival (OS) and side-effects (according to the Common Terminology Criteria for Adverse Events, v4.03). Results: After a 7-year follow-up (range, 1–11 years), PFS was 100% for patients treated with the Rituximab-containing regimen versus 66% for patients of the historical cohort (p = 0.036). Four patients in the latter group showed insufficient response to therapy. The PFS for early favorable and early unfavorable NLPHLs was similar between treatment groups, while a better PFS was recorded for advanced-stages treated with the Rituximab-containing regimen. The OS was similar for the two treatment groups. Short- and long-term side-effects were more frequently observed in the historical cohort. Grade ≥3 neutropenia was more frequent in the historical cohort compared with the Rituximab-group (58.3% vs. 18.7%, respectively; p = 0.03). Long-term non-hematological toxicities were observed more frequently in the historical cohort. Conclusion: Our results confirm the value of Rituximab in NLPHL therapy and show that Rituximab (single-agent) induction and maintenance in a limited-stage, or Rituximab with ABVD only in the presence of risk factors, give excellent results while sparing cytotoxic agent- and/or RT-related damage. Furthermore, Rituximab inclusion in advanced-stage therapeutic strategy seems to improve PFS compared to conventional chemo-radiotherapy.

scholarly journals Forgiveness Interventions for Older Adults: A Review

2021 ◽  
Vol 10 (9) ◽  
pp. 1866
Author(s):  
Javier López ◽  
Maria Inés Serrano ◽  
Isabel Giménez ◽  
Cristina Noriega
Keyword(s):  
Older Adults ◽  
Intervention Studies ◽  
Satisfaction With Life ◽  
Meta Analysis ◽  
Specific Treatment ◽  
Community Dwelling ◽  
Group Treatments ◽  
Receive Treatment ◽  
Community Dwelling Older Adults

A meta-analysis of the efficacy of forgiveness interventions in older adults was conducted. International databases (Medline, PsycINFO, Scopus, Web of Science) were searched for studies published from 1990 to 2020 that attempted to promote forgiveness in older adults. Most intervention studies are group treatments targeted towards community-dwelling older adults. Participants in these studies are mainly women. The intervention objectives and contents vary widely and often criteria are not well-defined. Participants that received forgiveness interventions reported significantly higher levels of forgiveness than participants that did not receive treatment. Additionally, forgiveness interventions resulted in more changes in depression, stress and anger than no intervention conditions. Forgiveness treatment also enhances positive states (satisfaction with life, subjective happiness, and psychological wellbeing). The reported effects are moderate. The specific treatment model (e.g., Enright’s, Worthington’s) and format (e.g., group-based interventions and individually delivered programs) do not differentially predict better outcomes. In conclusion, future intervention studies should include more male participants and utilize a broader range of follow-up periods. Caution must be exercised because of the limited number of studies developed to date; researchers must be cautious when generalizing the results.

scholarly journals Effectiveness of Elexacaftor/Tezacaftor/Ivacaftor Therapy in Three Subjects with the Cystic Fibrosis Genotype Phe508del/Unknown and Advanced Lung Disease

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1178
Author(s):  
Vito Terlizzi ◽  
Carmela Colangelo ◽  
Giovanni Marsicovetere ◽  
Michele D’Andria ◽  
Michela Francalanci ◽  
...  
Keyword(s):  
Drug Response ◽  
Ex Vivo ◽  
Forced Expiratory Volume ◽  
Considerable Decrease ◽  
Six Minute Walk Test ◽  
Sweat Chloride ◽  
Access Program ◽  
Minute Walk

We evaluated the effectiveness and safety of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) in three subjects carrying the Phe508del/unknown CFTR genotype. An ex vivo analysis on nasal epithelial cells (NEC) indicated a significant improvement of CFTR gating activity after the treatment. Three patients were enrolled in an ELX/TEZ/IVA managed-access program, including subjects with the highest percent predicted Forced Expiratory Volume in the 1st second (ppFEV1) < 40 in the preceding 3 months. Data were collected at baseline and after 8, 12 and 24 weeks of follow-up during treatment. All patients showed a considerable decrease of sweat chloride (i.e., meanly about 60 mmol/L as compared to baseline), relevant improvement of ppFEV1 (i.e., >8) and six-minute walk test, and an increase in body mass index after the first 8 weeks of treatment. No pulmonary exacerbations occurred during the 24 weeks of treatment and all domains of the CF Questionnaire-Revised improved. No safety concerns related to the treatment occurred. This study demonstrates the benefit from the ELX/TEZ/IVA treatment in patients with CF with the Phe508del and one unidentified CFTR variant. The preliminary ex vivo analysis of the drug response on NEC helps to predict the in vivo therapeutic endpoints.

scholarly journals THU0502 EFFICACY AND SAFETY OF SECUKINUMAB TREATMENT IN JUVENILE IDIOPATHIC ARTHRITIS PATIENTS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 489.3-489
Author(s):  
I. Kriulin ◽  
E. Alexeeva ◽  
T. Dvoryakovskaya ◽  
K. Isaeva ◽  
A. Chomakhidze ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Psoriatic Arthritis ◽  
Response To Therapy ◽  
Inactive Disease ◽  
Hla B27 ◽  
Serious Adverse Events ◽  
National Medical ◽  
Alternative Drug ◽  
Baseline Information

Background:Anti-IL-17A biologic drug secukinumab (SEC) proved to be effective for treatment of psoriatic arthritis. However data about its efficacy in juvenile idiopathic arthritis (JIA) are restricted to off-label experience.Objectives:To evaluate the effectiveness and safety of SEC in JIA patients in the National Medical Research Center of Children`s health, Moscow, Russia.Methods:25 patients started SEC therapy from 12/2017 to 11/2019 in single-center prospective study. 3 patients withdrew treatment: two patients (8%) due to AE (1 - allergy followed by MAS after first injection and 1 – leukopenia) and one patient (4%) – after 10 months of treatment due to secondary inefficacy. Among others, 14 patients which were successfully treated for 6 months or longer were included into analysis. At the baseline, information was collected on the characteristics of the onset of the disease, previous therapy and its success. Patients were monitored at least 1 time per year. At each visit, clinical and laboratory characteristics of JIA severity were assessed. Response to therapy was assessed using the ACRPedi 30/50/70/90 criteria, the C.Wallace criteria for inactive disease (WID) and clinical remission. AEs were assessed at each visit.Results:Among 14 patients received SEC for at least 6 months, 7 (50%) have enthesitis-related arthritis, one (7.1%) – persistent oligoarthritis, 4 (28.6%) – RF-negative polyarthritis, 2 (14.3%) – psoriatic arthritis. 6 patients (42.9%) were HLA-B27 positive. Median age of JIA onset was 8.8 (IQR 5:11), age at SEC initiation – 14 (9.9:16.1), disease duration before SEC start – 3.3 (2.7:5.8). 7 (50%) were biologics-naïve, 2 (14.3%) were previously treated with anti-TNF drug, 5 (35.7%) have 2 or more different biologics in anamnesis.SEC demonstrated high efficacy after the first injection resulting in JADAS-71 decreasing in all patients by median 4.3 (1.6:7.1) points and 7/7/5/2 patients (50%/50%/35.7%/14.3%) achieved ACR Pedi 30/50/70/90 response.After 6 months of treatment, WID was achieved by 7 (50%) patients, JADAS-71 decreased from baseline level 15.2 (12.7:20.5) to 0.8 (0:4.2) points, and 14/13/11/9 patients (100%/92.9%/78.6%/64.3%) achieved ACR Pedi 30/50/70/90 response. One patients who had active uveitis at SEC initiation remained with subactive uveitis; one patient with uveitis remission had not flare episodes during follow-up period. One patient (7.1%) had successfully treated evaluation of transaminases after 4-th injection.Conclusion:Secukinumab showed high effectiveness and safety in children with JIA and can be further used both as a first-line drug in JIA associated with HLA-B27, and as an alternative drug for the ineffectiveness of the standard treatment regimen with biologics. No serious adverse events were registered during follow-up period.Disclosure of Interests:Ivan Kriulin: None declared, Ekaterina Alexeeva Grant/research support from: Roche, Pfizer, Centocor, Novartis, Speakers bureau: Roche, Novartis, Pfizer., Tatyana Dvoryakovskaya: None declared, Ksenia Isaeva: None declared, Aleksandra Chomakhidze: None declared, Evgeniya Chistyakova: None declared, Olga Lomakina: None declared, Rina Denisova: None declared, Anna Mamutova: None declared, Anna Fetisova: None declared, Marina Gautier: None declared, Dariya Vankova: None declared, Elizaveta Krekhova: None declared, Meyri Shingarova: None declared, Alina Alshevskaya: None declared, Andrey Moskalev: None declared

scholarly journals POS0941 IN SPONDYLOARTHRITIS PATIENTS THE PRESENCE OF COMORBIDITIES IS AN INDEPENDENT PREDICTOR OF INSUFFICIENT RESPONSE TO THERAPY WITH BIOLOGIC AGENTS AND TREATMENT DISCONTINUATION

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 733.2-734
Author(s):  
I. Flouri ◽  
N. Kougkas ◽  
N. Avgustidis ◽  
A. Repa ◽  
A. Eskitzis ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Disease Duration ◽  
Cox Regression ◽  
Independent Predictor ◽  
Response To Therapy ◽  
Treatment Discontinuation ◽  
Randomized Controlled Studies ◽  
Insufficient Response ◽  
The Impact

Background:Long-term observational studies of patients under biologic disease-modifying anti-rheumatic drug (bDMARD) therapies in routine clinical practice can provide us with important data regarding patients with comorbidities, who are usually excluded from randomized controlled studies.Objectives:To study the impact of comorbidities in the outcome (response and persistence to therapy) of patients with spondyloarthritis (SpA) receiving bDMARDs in real-world clinical practice.Methods:Prospective study of all patients who start a bDMARD in a tertiary centre University Hospital after their consent. All patient comorbidities [among a list of approximately 100 pre-specified major comorbidities] are registered by treating physicians at baseline and during follow-up.Comorbidities were studied as total Comorbidities Count (CC) and rheumatic disease comorbidity index (RDCI). Statistical analyses were performed using logistic and Cox regression models, adjusting for the potential confounding of age, sex, disease duration, diagnosis (axial vs. peripheral SpA), number of previous conventional synthetic and biologic DMARDs, year of therapy start, and co-administered methotrexate and corticosteroids (yes/no). Analyses of response to therapy also included baseline BASDAI or ASDAS indices as confounding variables.Results:A total of 603 biologic treatments (1st: 298, 2nd: 157, ≥3rd: 148) were analyzed. Half (51%) of the patients were female, 413 patients had axial SpA (AxSpA) and 190 peripheral SpA (perSpA). At baseline, median (IQR) age: 48 (38-57) years, disease duration: 11 (4-19) years, CC: 2 (1-4) and RDCI: 1 (0-2). Both comorbidity indices were significantly higher in perSpA compared to AxSpA (p<0.001).At 6 months of therapy, 31% of patients with AxSpA achieved BASDAI50 and 39% had ASDAS-ESR < 2.1. Higher CC was an independent predictor of insufficient response according to BASDAI50 [OR (95%) = 0.70 (0.52-0.94), p=0.019] and higher RDCI was predicting failure to achieve ASDAS-ESR < 2.1 [OR (95%) = 0.59 (0.37-0.94), p=0.027]. Other independent predictors of non-response were age, longer disease duration and (for ASDAS-ESR<2.1) higher baseline disease activity.During 1405 patient-years of follow-up, 349 (58%) treatments were discontinued. The adjusted hazard ratio for bDMARD discontinuation within the first 2 years of treatment due to insufficient response was doubled in patients with CC ≥2 versus those with CC ≤1 [HR = 2.27 (1.14-4.53), p=0.020] or with RDCI ≥1 (vs. RDCI = 0) [HR = 2.23 (1.22-4.07), p=0.009]. Comorbidities’ indices were not significant predictors of treatment discontinuations due to adverse events.Conclusion:The presence of comorbidities in patients with SpA is an independent predictor for insufficient 6-month response to bDMARDs and resultant treatment discontinuation due to failure.Acknowledgements:This research is co-financed by Greece and the European Union (European Social Fund- ESF) through the Operational Programme «Human Resources Development, Education and Lifelong Learning» in the context of the project “Reinforcement of Postdoctoral Researchers - 2nd Cycle” (MIS-5033021), implemented by the State Scholarships Foundation (ΙΚΥ).Disclosure of Interests:None declared

THE INFLUENCE OF ADRENAL STEROIDS AND CORTICOTROPIN ON MASSIVE MYOCLONIC SEIZURES OF INFANCY

PEDIATRICS ◽  
1963 ◽  
Vol 32 (2) ◽  
pp. 169-174
Author(s):  
Patrick F. Bray
Keyword(s):  
Neurological Deficit ◽  
Prognostic Value ◽  
Rational Expectation ◽  
Initial Response ◽  
Response To Therapy ◽  
Adrenal Steroids ◽  
Focal Neurological Deficit ◽  
Rational Treatment ◽  
Follow Up Study

A 4-year follow-up study is reported on 10 infants whose minor motor seizures were treated intensively with cortisone and/or corticotropin. No correlation was found between the infants' initial clinical and electroencephalographic response to therapy and their follow-up intelligence quotients. The similar initial electroencephalographic findings, contrasted with the marked followup differences in levels of intellectual functioning, illustrate the limited prognostic value of the electroencephalogram in this syndrome. Similarly, no correlation was noted in the patients' initial response to therapy, and the presence or absence of microcephaly or focal neurological deficit. In the absence of any other rational treatment, and despite the dismal prospect suggested by this report and those of others, renewed efforts to treat patients earlier and more intensively with cortisone and corticotropin could be undertaken. However, in the light of 4 years' experience, such an approach might be a reflection more of therapeutic desperation than of rational expectation of good results.

Alpha-1 antitrypsin deficiency: clarifying the role of the putative protective threshold

2021 ◽  
pp. 2101410
Author(s):  
Alessandro N. Franciosi ◽  
Daniel Fraughen ◽  
Tomás P. Carroll ◽  
Noel G. McElvaney
Keyword(s):  
Risk Estimation ◽  
Specific Treatment ◽  
Weekly Administration ◽  
Risk Assessment Models ◽  
Increased Risk ◽  
Antitrypsin Deficiency ◽  
Dosing Regimens ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin ◽  
Protective Threshold

AATD is the only readily identifiable monogenic cause of COPD. To date the only condition-specific treatment for AATD-associated COPD is weekly administration of intravenous purified pooled human AAT (IV-AAT). Uncertainties regarding which AATD genotypes should benefit from IV-AAT persist. IV-AAT is costly and involves weekly administration of a plasma product. Much of the risk stratification has been centred around the long-accepted hypothesis of a “putative protective threshold” of 11 µM (0.57 g·L−1) in serum. This hypothesis has become central to the paradigm of AATD care, though its derivation and accuracy for defining risk of disease remain unclear.We review the literature and examine the association between the 11 µM threshold and clinical outcomes to provide context and insight into the issues surrounding this topic.We found no data which demonstrates an increased risk of COPD dependent on the 11 µM threshold. Moreover, an abundance of recent clinical data examining this threshold refutes the hypothesis. Conversely, the use of 11 µM as a treatment target in appropriate ZZ individuals is supported by clinical evidence, although more refined dosing regimens are being explored.Continued use of the 11 µM threshold as a determinant of clinical risk is questionable, perpetuates inappropriate AAT-augmentation practices, may drive increased healthcare expenditure and should not be used as an indicator for commencing treatment.Genotype represents a more proven indicator of risk, with ZZ and rare ZZ-equivalent genotypes independently associated with COPD. New and better risk assessment models are needed to provide individuals diagnosed with AATD with reliable risk estimation and optimised treatment goals.

Epigenetics In Autoimmune Disease

2018 ◽  
Author(s):  
Matlock A Jeffries
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Autoimmune Disease ◽  
Noncoding Rna ◽  
Specific Treatment ◽  
Cell Types ◽  
Response To Therapy ◽  
Human Immune System ◽  
Treatment Regimens ◽  
New Research

Autoimmunity refers to a pathologic state of immunologic dysregulation in which the human immune system turns inward, attacking healthy tissues. The key step in this process is a break of self-immune tolerance. Recent studies have implicated dysregulation of gene expression via altered epigenetic control as a key mechanism in the development and promotion of autoimmunity. Epigenetics is defined as heritable changes in gene expression as a result of modification of DNA methylation, histone side chains, and noncoding RNA. Studies examining identical twins discordant for lupus, for example, were among the first to identify alterations in DNA methylation leading to lupus. Histone side-chain changes have been studied extensively in rheumatoid arthritis (RA), and many pathogenic cell types in RA exhibit a hyperacetylation phenotype. Finally, new research in the noncoding RNA field has not only uncovered potentially targetable pathways (e.g., miR-155) but may lead to the development of new diagnostic and prognostic biomarkers, helping physicians better tailor specific treatment regimens to improve response to therapy in autoimmune disease.   This review contains 4 figures, 1 table and 47 references Key Words: autoimmunity, big data, biomarkers, computational biology, DNA methylation, epigenetics, histone acetylation, histone methylation, microRNA, noncoding RNA

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