Alpha-1 Antitrypsin Deficiency Detection in a Portuguese Population

Alpha-1 antitrypsin deficiency (AATD) is an autosomal co-dominant disease characterised by low serum levels of this molecule. Its epidemiology remains unknown in many countries, mainly due to its underdiagnosed state and lack of patients’ registries. We aim to evaluate and characterise a sample of Portuguese individuals tested for AATD, between 2006 and 2015, based on a retrospective analysis from the database of a laboratory offering AATD genetic diagnosis service. 1684 individuals were considered, covering almost every region in Portugal. Genetic diagnosis resulted from requests of clinicians from different areas of expertise, mainly pulmonology (35.5%). Most subjects could be distributed into more common genotypes: MZ (25.4%, n = 427), MS (15.5%, n = 261), SZ (11.2%, n = 188), ZZ (9.4%, n = 158) and SS (5.6%, n = 95). 9.5% of the subjects were found to carry at least one rare deleterious allele, including the recently described P_Gaia, Q0_{Oliveira do Douro}, Q0_{Vila Real} and a novel S_Gaia variant. This study comprises 417 subjects (24.7%) with severe to very severe AATD and 761 carriers (45.2%), 22.7% of those identified by familial screening. The present study represents the most complete survey of AATD in Portugal so far and discloses a high rate of severe and very severe deficiency cases, attributed not only to ZZ and SZ genotypes but also to a large number of rare combinations with other null and deficiency alleles. It also uncovers a low awareness to AATD among the medical community, highlighting the need to create a Portuguese national registry and AATD guidelines and increase the awareness about this condition.     

Screening and familial testing of patients for alpha 1-antitrypsin deficiency

alpha(1)-Antitrypsin deficiency (AATD) is an autosomal-codominant genetic disorder that predisposes individuals to the development of liver and lung disease. AATD is greatly underrecognized and underdiagnosed. Early identification allows preventive measures to be taken, the most important of which is the avoidance of smoking (including the inhalation of second-hand smoke) and exposure to environmental pollutants. Early detection also allows careful lung function monitoring and augmentation therapy while the patient still has preserved lung function. Cost factors and controversies have discouraged the initiation of large-scale screening programs of the newborn and adult populations in the United States and Europe (except for Sweden). There are sound medical reasons for targeted screening. Evidence-based recommendations for testing have been published by the American Thoracic Society/European Respiratory Society task force, which take potential social, psychological, and ethical adverse factors into consideration. This review discusses rationales for testing and screening for AATD in asymptomatic individuals, family members, and the general population, weighing benefits against potential psychological, social, and ethical implications of testing. For most, negative issues are outweighed by the benefits of testing. AATD testing should be routine in the management of adults with emphysema, COPD, and asthma with incompletely reversible airflow obstruction.     

Three-dimensional computed tomography for evaluation and management of children with complex chest wall anomalies: useful information or just pretty pictures?

Purpose

Shaded surface display (SSD) technology, with 3-dimensional computed tomography reconstruction, has been reported in a few small series of patients with congenital or acquired chest wall deformities. Shaded surface display images are visually attractive and educational, but many institutions are hesitant to use these secondary to cost and image data storage concerns. This study was designed to assess the true value of SSD to the patient, family, and operating surgeon, in the evaluation and management of these children.

Methods

After institutional review board approval, we performed a retrospective review of records of 82 patients with chest wall deformities, evaluated with SSD, from 2002 to 2009. Shaded surface display usefulness, when compared to routine 2-dimensional computed tomography, was graded on a strict numerical scale from 0 (added no value besides education for the patient/family) to 3 (critical for surgical planning and patient management).

Results

There were 56 males and 26 females. Median age was 15.3 years (range, 0.6-41.1 years). Deformities included 56 pectus excavatum, 19 pectus carinatum, and 8 other/mixed deformities. Six patients also had acquired asphyxiating thoracic dystrophy (AATD). Eleven (13%) had previous chest wall reconstructive surgery. In 25 (30%) patients, SSD was useful or critical. Findings underappreciated on 2-dimensional images included sternal abnormalities (29), rib abnormalities (28), and heterotopic calcifications (7). Shaded surface display changed or influenced operation choice (4), clarified bone vs soft tissue (3), helped clarify AATD (3), and aided in rib graft evaluation (2). Point biserial correlation coefficient analysis (R_pb) displayed significance for SSD usefulness in patients with previous chest repair surgery (R_pb = 0.48, P ≤ .001), AATD (R_pb = 0.34, P = .001), pectus carinatum (R_pb = 0.27, P = .008), and females (R_pb = 0.19, P = .044).

Conclusions

Shaded surface display, when used to evaluate children and young adults with congenital or acquired chest wall deformities, provides useful or critical information for surgical planning and patient management in almost one third of patients, especially in those requiring a second operation, with acquired asphyxiating thoracic dystrophy, pectus carinatum, and females.     

Combined liver-lung transplantation: Indications,outcomes, current experience and ethical Issues

Combined liver-lung transplantation (CLLT) is a rare, life-saving procedure to treat concomitant lung and liver disease. There have been 93 combined lung and liver transplantations performed in the United States since 1994. Techniques include both lung first and liver first sequential transplants with selective extracorporeal circulation of either thoracic or abdominal portions, with either end-to-end or Roux-en-Y choledochojejunostomy for biliary reconstruction. This review evaluates the existing literature regarding combined lung and liver transplantation (CLLT), describing the candidates, operation, perioperative complications, associated management strategies, and recommendations for immunosuppressive therapy and follow up.