Screen patients for AATD: position statement from TSANZ


By Sunalie Silva

26 Feb 2020

Respiratory physicians are being urged to screen all patients with chronic airflow obstruction and certain patients with adult onset asthma for the common but underdiagnosed genetic disorder Alpha 1 Antitrypsin Deficiency (AATD), which causes early onset emphysema.

The new screening advice, based on an evidence review conducted by an expert Working Group commissioned by the Thoracic Society of Australia and New Zealand (TSANZ), was released in a position statement on 6 February.

The TSANZ Working Group also gave a conditional recommendation, citing low quality evidence, that newer augmentation therapies could be considered in non-smoking patients with AATD. However that advice was not unanimous with eight of the 14 panel members in favour of the recommendation five against and four abstaining.

Meanwhile, one panel member withdrew authorship maintaining that a strong recommendation in favour of AAT augmentation should have been made.

Treatment not subsidised

As reported previously by the limbic two augmentation therapies, the alpha I proteinase inhibitors Zemaira and Prolastin-C, have been listed on the Australian Register of Therapeutic Goods (ARTG) for the treatment of AATD since February 2017 and November 2016, respectively. But the treatment, which may cost up to $100,000 year, is not yet subsidised by the government.

Speaking to the limbic Dr Jack Dummer, consultant and senior lecturer in respiratory medicine at the University of Otago, New Zealand and chair of the TSANZ Working Group, said while clinical trials haven’t been able to provide conclusive evidence of benefit from augmentation therapy over standard therapy, weakness in the body of evidence means that a benefit can’t be excluded.

“The opinion of the Working Group reflected wider opinion in the medical world on augmentation therapy in that there is no consensus currently on whether it works or not,” says Dr Dummer.

“Some clinical researchers think that the benefits seen in terms of lung density on CT scanning are sufficient evidence that this therapy works and others, equally strongly, believe that we need evidence from trials to show improvement in more traditional clinical outcomes such as mortality, quality of life and functional status. In a binary decision it’s very difficult to bring those two groups to a consensus – both are valid viewpoints,” he adds.

And while in the position paper panel members say there are no ‘important side effects’ of augmentation therapy based on the available evidence, the ‘burden of weekly i.v. infusion and costs of treatment should be considered’.

Dr Dummer says the mainstay of AATD treatment continues to be with measures similar to COPD.

“Most of the evidence would suggest what is good for usual COPD also works for AATD so we suggest for the most part patients with AATD benefit from the same types of treatment.”

No routine testing in asthma patients

Meanwhile other recommendations in the position paper support World Health Organization advice to test for AATD in all patients with COPD – but, unlike the WHO, it does not recommend routine testing in all asthma patients.

“In patients with adult onset asthma, testing for AATD really should be something that’s done when there is some degree of clinical correlation; that’s patients with persistent airflow limitation, emphysema disproportionate to their smoking history or in the presence of liver or skin disease,” says Dr Dummer.

For diagnosing the condition the TSANZ Working Group recommends that AAT and C-reactive protein (CRP) levels be measured at the same time, which Dr Dummer says would identify patients with an inflammatory state that may potentially affect AAT levels.

“Because AAT is an inflammatory protein it will rise in inflammatory conditions and you can be misled into believing a patient doesn’t have an AAT deficiency if you test someone with COPD when, for example, they have an exacerbation,” he notes.

Once a deficiency is picked up, AAT phenotyping or genotyping should be carried out to clarify what type of AATD deficiency the patient has followed by genetic counseling, he adds.

Family screening

Meanwhile TSANZ recommends that the decision to screen family members of patients with an AATD diagnosis should rest with the family members themselves.

“It’s a situation of some complexity in that having alleles related to AATD does not necessarily put you at risk of disease,” explains Dr Dummer.

“So there has to be a balance between testing to provide clinical benefit and not worrying people who would otherwise remain well.”

The full position statement can be viewed here.

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