Diagnosing α<sub>1</sub>-antitrypsin deficiency: how to improve the current algorithm

McElvaney, Noel G.

doi:10.1183/09059180.10010814

Cited by 52 publications

(46 citation statements)

References 15 publications

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“…For instance, genotyping errors have been reported to range from 0.5% to 30% in some studies [53]. Genotyping errors have been reported during the diagnosis of AAT deficiency [54,55].…”

Section: Complications Of Our Understanding By Common Biases In Genetmentioning

confidence: 99%

COPD in individuals with the PiMZ alpha-1 antitrypsin genotype

Ashry

Strange

2017

Eur Respir Rev

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Since the discovery of severe alpha-1 antitrypsin deficiency as a genetic risk factor for emphysema, there has been ongoing debate over whether individuals with intermediate deficiency with one protease inhibitor Z allele (PiMZ, or MZ) are at some risk for emphysema. This is important, because MZ individuals comprise 2-5% of the general population. In this review we summarise the evidence about the risks of the MZ population to develop emphysema or asthma. We discuss the different study designs that have tried to answer this question. The risk of emphysema is more pronounced in case-control than in population-based studies, perhaps due to inadequate power. Carefully designed family studies show an increased risk of emphysema in MZ smokers. This is supported by the rapid decline in lung function of MZ individuals when compared to the general population after massive environmental exposures. The risk of asthma in MZ subjects is less studied, and more literature is needed before firm conclusions can be made. Augmentation therapy in MZ individuals is not supported by any objective studies. MZ smokers are at increased risk for emphysema that is more pronounced when other environmental challenges are present.

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“…For instance, genotyping errors have been reported to range from 0.5% to 30% in some studies [53]. Genotyping errors have been reported during the diagnosis of AAT deficiency [54,55].…”

Section: Complications Of Our Understanding By Common Biases In Genetmentioning

confidence: 99%

COPD in individuals with the PiMZ alpha-1 antitrypsin genotype

Ashry

Strange

2017

Eur Respir Rev

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“…Lung function in AATD is often characterized by earlier reduction in gas transfer and FEV 1 often declines later in disease progression . However, similar to other lung manifestations there is wide variability between individuals .…”

Section: Diagnosis Of Aatdmentioning

confidence: 99%

“…More than 150 AAT variants have been described . Most have been identified by isoelectric focusing (IEF) and many further characterized by gene sequencing …”

Section: Diagnosis Of Aatdmentioning

confidence: 99%

“…Many remain undiagnosed either because of a lack of clinical manifestation of their deficiency or through being unrecognized by their treating physicians. It has been reported, based upon allelic frequencies, that less than 10% of AATD individuals are diagnosed, while 1% of all patients with chronic obstructive pulmonary disease (COPD) have AATD …”

Section: Introductionmentioning

confidence: 99%

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Diagnosis and treatment of lung disease associated with alpha one‐antitrypsin deficiency: A position statement from the Thoracic Society of Australia and New Zealand*

et al. 2020

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AATD is a common inherited disorder associated with an increased risk of developing pulmonary emphysema and liver disease. Many people with AATD‐associated pulmonary emphysema remain undiagnosed and therefore without access to care and counselling specific to the disease. AAT augmentation therapy is available and consists of i.v. infusions of exogenous AAT protein harvested from pooled blood products. Its clinical efficacy has been the subject of some debate and the use of AAT augmentation therapy was recently permitted by regulators in Australia and New Zealand, although treatment is not presently subsidized by the government in either country. The purpose of this position statement is to review the evidence for diagnosis and treatment of AATD‐related lung disease with reference to the Australian and New Zealand population. The clinical efficacy and adverse events of AAT augmentation therapy were evaluated by a systematic review, and the GRADE process was employed to move from evidence to recommendation. Other sections address the wide range of issues to be considered in the care of the individual with AATD‐related lung disease: when and how to test for AATD, changing diagnostic techniques, monitoring of progression, disease in heterozygous AATD and pharmacological and non‐pharmacological therapy including surgical options for severe disease. Consideration is also given to broader issues in AATD that respiratory healthcare staff may encounter: genetic counselling, patient support groups, monitoring for liver disease and the need to establish national registries for people with AATD in Australia and New Zealand.

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“…Rarer cases occur in patients with α1-antitrypsin deficiency 2. Despite the chest radiograph findings, a CT scan was obtained due to the case’s complexity, helping to identify a possible secondary cause (emphysema and subpleural blebs).…”

Section: Descriptionmentioning

confidence: 99%

Bilateral secondary spontaneous pneumothorax

Pedreira

Silvério

Casimiro³

et al. 2018

BMJ Case Reports

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DescriptionA 40-year-old male patient presented to the emergency department with complaints of shortness of breath associated with bilateral pleuritic chest pain. He denied any history of trauma and had smoked 40 cigarettes daily for the past 22 years.On examination, the patient appeared breathless with a respiratory rate of 25 breaths/min and peripheral capillary oxygen saturation (SpO 2 ) of 92% on room air. Neck examination showed no tracheal deviation and chest examination identified decreased bilateral chest expansion with no intercostal retractions. On chest palpation, there was a slightly diminished tactile fremitus on both sides. Chest percussion revealed a hyper-resonant note heard over the right and left upper and mid zones. On auscultation, there were no audible breath sounds and whispered voice sounds were abolished over the right and left upper and mid zones.The gasometric evaluation revealed the presence of hypoxaemia and hypocapnia. A posteroanterior chest radiograph showed a large bilateral pneumothorax (figure 1). The thoracic CT scan revealed focal areas of emphysema and apical subpleural blebs, which were located predominantly in the peripheral regions of the apex (figure 2).Supplemental high-flow oxygen was given to the patient. After confirmation with needle aspiration, small-bore chest drains were placed on both sides and the patient had complete re-expansion of both lungs. Despite the American College of Chest Physicians Delphi Consensus Statement regarding the management of secondary spontaneous pneumothorax (SSP) and after careful discussion with a chest physician, chemical or surgical pleurodesis was not considered at this point since there was a complete resolution after the use of chest drains. From the aetiological investigation, it stood out a decreased serum level of α1-antitrypsin. Its association with the high smoking load (44 pack years) in this patient was assumed to be the cause of the bilateral SSP episode. He was later discharged, being advised to cease smoking.Several months later, he was again admitted with a new left pneumothorax. This time, after evaluation by a chest physician, he underwent a wedge resection of the left upper lobe and mechanical pleurodesis by video-assisted thoracoscopic surgery. He has remained asymptomatic since then, with no further pneumothorax recurrences.Spontaneous pneumothorax is frequently associated with smoking habits, making smoking cessation

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Diagnosing α₁-antitrypsin deficiency: how to improve the current algorithm

Cited by 52 publications

References 15 publications

COPD in individuals with the PiMZ alpha-1 antitrypsin genotype

COPD in individuals with the PiMZ alpha-1 antitrypsin genotype

Diagnosis and treatment of lung disease associated with alpha one‐antitrypsin deficiency: A position statement from the Thoracic Society of Australia and New Zealand*

Bilateral secondary spontaneous pneumothorax

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Diagnosing α1-antitrypsin deficiency: how to improve the current algorithm

Cited by 52 publications

References 15 publications

COPD in individuals with the PiMZ alpha-1 antitrypsin genotype

COPD in individuals with the PiMZ alpha-1 antitrypsin genotype

Diagnosis and treatment of lung disease associated with alpha one‐antitrypsin deficiency: A position statement from the Thoracic Society of Australia and New Zealand*

Bilateral secondary spontaneous pneumothorax

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Diagnosing α₁-antitrypsin deficiency: how to improve the current algorithm