Speaker's Highlight

• Don Sin University of British Columbia, St. Paul Hospital (Canada)
  Kenneth R. Chapman Toronto General Hospital Research Institute (Canada)
• Parameswaran Nair McMaster University (Canada)
  Carolyn Calfee UCSF (U.S.A.)
• Gregory P. Downey University of Colorado School of Medicine (U.S.A.)
  David A. Schwartz University of Colorado School of Medicine (U.S.A.)
• Neil Schluger Tuberculosis Control Branch, California Department of Public Health (U.S.A.)
  Nick Kim Critical Care & Sleep Medicine, University of California San Diego (U.S.A.)
• Nicola Hananiah Baylor College of Medicine (U.S.A.)
  Jae-Joon Yim Seoul National University College of Medicine (Republic of Korea)
• Koichiro Asano Tokai University School of Medicine (Japan)
  Diahn-Warng Perng Taipei Veterans General Hospital (Taiwan)
• Konstantinos Kostikas University of Ioannina (Greece)
  Karin Klooster University Medical Center Groningen (Kingdom of the Netherlands)

• Screening for Alpha-1 Antitrypsin Deficiency in COPD Patients

  Chronic obstructive pulmonary disease is commonly linked with cigarette smoke, occupational exposure and air pollution, but a genetic condition can also contribute to emphysema and persistent airflow limitation. Alpha-1 antitrypsin deficiency (AATD) is underdiagnosed worldwide, including in Australia, where many people remain unaware that an inherited disorder may be affecting their lungs.

  Identifying AATD can change how clinicians assess risk, counsel families and plan long-term respiratory care. It can also prompt earlier smoking cessation, reduce exposure to respiratory irritants and support testing for relatives. The respiratory focus of the APSR 2022 congress site reflects the importance of recognising less common causes of obstructive lung disease alongside everyday clinical priorities.

  Why Alpha-1 Antitrypsin Matters

  Alpha-1 antitrypsin is a protein produced mainly in the liver. Its role includes protecting lung tissue from enzymes released during inflammation. When levels are very low, the lungs may be more vulnerable to destruction, particularly in people who smoke or work around dust, fumes and chemicals.

  AATD is associated with early-onset emphysema, basal-predominant changes on imaging, unexplained bronchiectasis and liver disease. COPD may develop at a younger age than expected, sometimes before 45, although symptoms can appear later. A family history of emphysema, liver disease or unexplained respiratory illness strengthens the case for investigation.

  Australian clinicians should avoid assuming that a patient’s ethnicity or location rules out the condition. Patients in Sydney, Melbourne, Perth and regional communities can all be affected. AATD is inherited across populations, and a straightforward blood test is more reliable than judging risk from appearance or background.

  Who Should Be Tested

  Many international respiratory guidelines support testing for AATD in every person with COPD, regardless of age, smoking history or family origin. This broad approach is practical because symptoms and spirometry cannot reliably distinguish inherited deficiency from smoking-related disease. Testing is also reasonable in people with unexplained bronchiectasis, persistent airflow obstruction, cryptogenic liver disease or a close relative with confirmed AATD.

  The conversation should be handled sensitively. Genetic findings can affect relatives and may cause anxiety about insurance, employment or family health. Explain why the test is being offered, what the result could mean and whether confirmatory testing may be needed. In Aboriginal and Torres Strait Islander communities, culturally safe communication and appropriate local involvement are essential; the same principle applies when working with culturally diverse families across Australia.

  Testing is particularly valuable when COPD appears disproportionate to the smoking history, when several relatives have respiratory disease or when emphysema is found in a younger adult. A normal or low body mass index, recurrent chest infections and unexplained liver abnormalities can add useful clinical context, but none should replace formal testing.

  How Screening Works

  Initial assessment usually involves a serum alpha-1 antitrypsin concentration. The sample may be affected by acute inflammation because AAT is an acute-phase protein, so a borderline result may need repeating when the patient is clinically stable. C-reactive protein and liver function tests can help clinicians interpret the result.

  A low concentration should lead to confirmatory analysis, commonly phenotype testing and/or SERPINA1 genotyping. These tests identify abnormal protein patterns or disease-associated variants such as the Z and S alleles. Concentration testing alone can miss some clinically important variants, while genetic testing alone may not explain the full biochemical picture.

  Australian general practices can discuss suitable pathology pathways with local laboratories, especially when patients live far from metropolitan respiratory services. In rural and remote areas, reliable specimen handling, telehealth access and clear communication between the GP, pathology provider and specialist are important. The test should be recorded in the medical history so that future clinicians do not repeatedly overlook it.

  Interpreting Results And Family Risk

  A low AAT level does not automatically establish severe deficiency, and a genetic variant does not always predict the same degree of lung damage. Results must be considered alongside spirometry, smoking exposure, symptoms, imaging, liver tests and family history. A respiratory physician or clinical genetic service can clarify uncertain or discordant findings.

  Patients with confirmed deficiency should be offered family-based assessment. Adult first-degree relatives may benefit from testing because early knowledge supports smoking avoidance, occupational protection and timely monitoring. Testing children requires careful discussion of consent, maturity, family circumstances and the potential value of knowing the result.

  The result should be explained in plain language rather than presented as a label alone. People with a carrier state may have different risks from those with severe deficiency, and relatives can have different genotypes within the same family. Written information and an opportunity to revisit the discussion are useful, particularly after a serious diagnosis.

  Practical Steps For Australian Clinics

  A consistent clinic process reduces missed diagnoses and makes screening easier to incorporate into routine COPD care:

  • Offer AATD testing when COPD is diagnosed, and consider it for unexplained bronchiectasis, emphysema, liver disease or a relevant family history.
  • Record smoking status, occupational exposures, age at symptom onset, liver history and affected relatives.
  • Use serum AAT concentration as an initial test, with phenotype or genotype confirmation when the result is low, borderline or clinically unexpected.
  • Refer confirmed cases or complex results to a respiratory physician, genetic counsellor or specialist service.
  • Provide smoking cessation support, vaccination advice, pulmonary rehabilitation and exposure reduction regardless of the genetic result.

  Smoking cessation remains the most important modifiable intervention. Australian services may include a GP-led plan, Quitline support and local respiratory rehabilitation, with access differing between metropolitan centres and remote communities. Influenza, COVID-19 and pneumococcal vaccination should be considered according to current Australian recommendations and individual risk.

  Treatment for COPD caused by AATD generally follows evidence-based COPD care: inhaled medicines when indicated, exercise training, nutrition support and management of exacerbations. Specialist teams can assess advanced emphysema, liver complications and whether any disease-specific therapy or clinical trial is appropriate. Access to advanced services can vary between states and territories, so referral should not be delayed when deficiency is confirmed.

  Building Long-Term Care Around The Diagnosis

  AATD screening has value beyond finding a rare genetic result. It can explain an unexpected clinical pattern, encourage relatives to seek assessment and give patients a clearer reason to avoid tobacco smoke. It may also identify liver risk requiring monitoring, particularly when liver enzymes are abnormal or there is a family history of liver disease.

  Follow-up should include regular symptom review, spirometry and assessment of exacerbations, exercise tolerance and exposure risks. Imaging is guided by the clinical picture rather than performed automatically at every visit. Patients who have never smoked still need practical advice about dust, fumes, vaping and occupational hazards.

  The essential message is simple: COPD should prompt consideration of alpha-1 antitrypsin deficiency, not just a review of smoking history. Early, accurate testing allows Australian patients and their families to make informed decisions, while clinicians can tailor respiratory and liver care to the person’s actual risk.

  Richard Russell Nuffield Department of Clinical Medicine, University of Oxford (United Kingdom)
• Mona Bafadhel King’s College London (United Kingdom)
  David Jackson Guy’s and St Thomas’ Hospital, King’s College London (United Kingdom)
• James Chalmers University of Dundee (United Kingdom)
  David Price University of Aberdeen (United Kingdom)