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)

• Telomere length and the risk of idiopathic pulmonary fibrosis

  Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease in which scar tissue gradually replaces healthy lung tissue. Its causes are not fully understood, yet ageing, inherited susceptibility and environmental exposures all appear to influence who develops the condition. Telomere biology has become an important part of this picture because unusually short telomeres can reduce the lung’s ability to repair repeated epithelial injury.

  Telomeres are protective DNA sequences at the ends of chromosomes. They shorten as cells divide, and their length varies with age, genetics, illness and life exposures. Understanding this relationship may help clinicians recognise patients with familial pulmonary fibrosis, anticipate treatment complications and select appropriate tests, while avoiding the mistake of treating telomere length as a standalone prediction tool.

  What telomeres do in lung health

  Telomeres act like protective caps that help maintain chromosome stability. When they become critically short, cells may enter senescence or die rather than continue dividing. In the lungs, this can affect alveolar type II cells, which help replenish the epithelial lining after injury and produce surfactant.

  Age-related telomere shortening is expected, but some people inherit variants that accelerate the process. Genes associated with telomere maintenance include TERT, TERC, RTEL1 and PARN. These variants may be linked with familial pulmonary fibrosis, bone marrow abnormalities, liver disease or premature greying, although the clinical pattern differs between families.

  How short telomeres may increase IPF susceptibility

  The current model suggests that short telomeres leave the lung with fewer repair reserves. Viral infections, cigarette smoke, air pollution or occupational dust may injure the alveolar lining. If repair cells cannot renew effectively, abnormal wound healing and excess collagen deposition may follow, contributing to pulmonary fibrosis.

  This does not mean that every person with short telomeres will develop IPF. Many other factors matter, including age, smoking history, genetic background and exposure to materials such as silica, metal dust or agricultural particulates. In Australia, clinicians may need to consider farming, mining and construction work when taking an exposure history, especially in regional communities.

  Telomere length and familial pulmonary fibrosis

  A family history of IPF or unexplained lung scarring is a strong reason to explore inherited susceptibility. Some patients present with disease at a younger age, while others develop symptoms later in life after years of apparently normal health. Relatives may also have conditions outside the lungs, such as low blood counts, abnormal liver function or early hair greying.

  Genetic counselling is valuable before testing because results can affect relatives and create uncertainty when a variant has unclear significance. A respiratory physician may combine family history, high-resolution CT findings, pulmonary function tests and blood investigations rather than relying on one laboratory measurement. The APSR 2022 congress provides useful context for how respiratory specialists discuss emerging evidence across the Asia-Pacific region.

  Measuring telomere length in clinical practice

  Telomere length can be measured in peripheral blood using methods such as quantitative polymerase chain reaction, flow-FISH or Southern blot-based testing. These techniques do not produce identical results, and values may vary according to the laboratory, the cell type examined and the reference population used. A result should therefore be interpreted against age-adjusted standards.

  Very short telomeres may support suspicion of a telomere biology disorder, but a borderline result does not exclude one. Testing is most informative when it answers a defined clinical question, such as assessing familial pulmonary fibrosis or evaluating a patient before transplantation. Commercial testing marketed directly to consumers may lack the clinical context needed for safe interpretation.

  Implications for treatment and transplantation

  Telomere dysfunction can influence how a patient responds to medical treatment. People with severe telomere shortening may be more vulnerable to bone marrow suppression, liver toxicity or infection with some therapies. This does not automatically rule out antifibrotic treatment, but it reinforces the need for careful monitoring of blood counts, liver enzymes and overall tolerance.

  Transplant teams may also consider telomere biology when assessing candidates with advanced disease. Short telomeres can be associated with complications after lung transplantation, including cytopenias and infection. Decisions remain individual, balancing disease severity, functional status, comorbidities and available donor options rather than using a single telomere threshold.

  What this means for Australian respiratory care

  Australia’s geography makes access to specialist interstitial lung disease services uneven. A patient in Perth, Darwin or a remote New South Wales town may need telehealth, coordinated local lung function testing and travel to a tertiary centre. Medicare-supported care, public hospital capacity and access to genetic counselling can affect how quickly investigations are completed.

  Aboriginal and Torres Strait Islander patients may face additional barriers linked to distance, health-service access and mistrust created by past experiences. A culturally safe approach, involvement of Aboriginal health workers and clear explanations of genetic information are essential. Clinicians should also avoid assuming that a test developed in overseas populations has precisely the same reference range for every Australian patient.

  Research directions and unanswered questions

  Researchers are examining whether telomere length can help divide IPF into biologically meaningful subgroups. Future studies may combine telomere measurements with genomic data, blood biomarkers, imaging and clinical outcomes. This could improve risk assessment and reveal why some patients progress quickly while others remain stable for longer periods.

  Important uncertainties remain. Telomere length can be a marker of inherited risk, accumulated ageing or both, and it is not yet clear how often testing changes management outside specialist settings. Larger, diverse cohorts are needed, including Australians from metropolitan, rural and remote regions. Until stronger evidence emerges, telomere results should complement—not replace—clinical assessment, family history and multidisciplinary review.

  For patients and families, the practical message is that telomere length is best viewed as one piece of a wider risk profile. A careful history should cover relatives with pulmonary fibrosis, blood disorders or liver disease, along with smoking and workplace exposures. When suspicion is high, referral to an interstitial lung disease service and genetic counsellor can guide appropriate testing, monitoring and family discussions. A sensible clinical approach is to interpret telomere results alongside symptoms, imaging, lung function and treatment risks rather than treating the number as a diagnosis.

  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)