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)

• How Genes Shape Risk From Environmental Lung Disease

  Lung disease develops through an interaction between inherited biology and the air people breathe. Tobacco smoke, silica dust, traffic pollution, mould, infectious agents and bushfire smoke can affect many people, yet only some develop severe asthma, chronic obstructive pulmonary disease, pulmonary fibrosis or occupational lung injury.

  The genetics of susceptibility to environmental lung disease is therefore less about finding one “disease gene” and more about understanding patterns of risk. A person’s genome may influence airway inflammation, immune defence, antioxidant capacity, tissue repair and the way the body processes toxic substances. These factors can alter both the likelihood of illness and its severity after exposure.

  Risk influence	Typical examples	Possible effect on lung health
  Inherited variants	Alpha-1 antitrypsin deficiency, immune-response variants	Greater vulnerability to emphysema, infection or inflammation
  Workplace exposure	Silica, asbestos, coal dust, welding fumes	Silicosis, fibrosis, COPD or lung cancer risk
  Outdoor pollution	Traffic emissions, ozone, smoke haze	Asthma attacks, impaired lung growth and exacerbations
  Household exposure	Tobacco smoke, wood heaters, mould	Airway irritation and recurring respiratory symptoms
  Gene–environment interaction	Genetic risk combined with smoking or dust	Earlier onset or more severe disease
  Epigenetic change	Exposure-related changes in gene regulation	Altered inflammation without changing DNA sequence

  Why Susceptibility Varies

  People with similar exposure histories can have very different outcomes. Some develop persistent airway narrowing after years of smoking, while others retain relatively stable lung function. Differences in detoxification enzymes, mucosal barriers, inflammatory signalling and lung repair may help explain this variation.

  Alpha-1 antitrypsin deficiency is a well-established example. Variants in the SERPINA1 gene can reduce protection against enzymes released during inflammation, increasing the risk of early emphysema, particularly in people who smoke. This example is unusual because the genetic association is strong and clinically actionable; most environmental lung conditions involve many variants, each contributing a small amount of risk.

  Exposure Can Switch Genetic Risk On

  Genes do not operate in isolation. Fine particles from diesel engines, silica dust from engineered stone, cigarette smoke and airborne chemicals can trigger oxidative stress in lung tissue. If inherited antioxidant or repair pathways are less effective, the same exposure may cause greater cellular injury.

  Regulatory marks known as epigenetic changes can also influence how genes are expressed. These changes may follow exposure to air pollution or tobacco smoke and can affect immune activity, airway responsiveness and fibrosis. Some epigenetic patterns may be reversible when exposure falls, although the duration and clinical importance of these changes remain active areas of research.

  Occupational Hazards And Inherited Risk

  Work-related lung disease remains a significant concern in Australia. Engineered stone fabrication has drawn particular attention because respirable crystalline silica can cause rapidly progressive silicosis, including in younger workers. Construction, mining, quarrying, tunnelling and manufacturing can also create harmful dust and fume exposures.

  Genetic testing is not a substitute for workplace controls. Wet cutting, local exhaust ventilation, respiratory protection, health surveillance and safer materials remain central to prevention. However, a family history of unexplained emphysema, pulmonary fibrosis or unusual occupational lung disease may support specialist assessment and a closer review of exposure history.

  Bushfire Smoke And Urban Air

  Australia’s bushfire seasons have made smoke exposure a recurring public health issue in Sydney, Melbourne, Canberra and regional communities. Fine particulate matter can penetrate deep into the lungs, worsening asthma, COPD and cardiovascular disease. People with inherited differences in inflammatory or antioxidant pathways may experience more symptoms during prolonged smoke events.

  Urban exposure also matters. Traffic-related nitrogen dioxide and particulate pollution can contribute to childhood wheeze and reduced lung development, particularly near busy roads. In Perth and other growing cities, local weather patterns, dust and seasonal smoke can combine with traffic emissions. Genetic susceptibility research may eventually help identify people who need more targeted protection, but broad public health advice remains important for everyone.

  Indigenous And Regional Health Contexts

  Respiratory risk in Aboriginal and Torres Strait Islander communities must be considered alongside housing quality, overcrowding, access to care, smoking exposure, socioeconomic conditions and the effects of colonisation. Genetic explanations should never be used to imply that poor outcomes are biologically predetermined. Environmental and structural factors often create the largest preventable burden.

  Distance also affects diagnosis and treatment. A patient in the Pilbara, Far North Queensland or a remote Northern Territory community may have limited access to spirometry, respiratory specialists and genetic counselling. Telehealth, Aboriginal Community Controlled Health Services and culturally safe care can support earlier assessment, provided testing is clinically appropriate and accompanied by clear explanations.

  From Research To Personalised Care

  Genomic studies are examining variants linked with asthma, COPD, pulmonary fibrosis, hypersensitivity pneumonitis and susceptibility to particulate pollution. Researchers increasingly use large biobanks, occupational cohorts and longitudinal lung-function data to separate inherited risk from exposure intensity and social conditions.

  For Australian clinicians, the practical value currently lies in selected testing and careful risk assessment rather than routine genome screening. Testing may be relevant for suspected alpha-1 antitrypsin deficiency, familial pulmonary fibrosis or an unusual pattern of disease. Results should be interpreted with genetic counselling, because a risk variant does not predict a certain diagnosis and a negative result does not make hazardous exposure safe.

  Practical Measures For Risk Reduction

  A prevention plan should combine exposure control, clinical monitoring and family-aware care. The following measures are especially useful:

  • Record occupations, dusty tasks, ventilation conditions, smoking history and major smoke events.
  • Avoid tobacco smoke and reduce indoor exposure to mould, wood smoke and poorly ventilated fumes.
  • Use fit-tested respiratory protection when workplace controls cannot fully remove hazardous dust.
  • Seek assessment for unexplained breathlessness, persistent cough, wheeze or falling exercise tolerance.
  • Consider specialist referral when there is early emphysema, pulmonary fibrosis or a strong family history.
  • Follow local air-quality alerts during bushfires and limit strenuous outdoor activity when smoke is dense.
  • Ensure children and adults with asthma have an up-to-date written management plan.

  Genetic information can improve prevention when it is paired with practical support. In Australia, this includes access through public respiratory services, private laboratories and specialist clinics, with costs and availability varying between metropolitan and regional areas. Genetic data also requires careful handling, including attention to privacy, insurance implications and informed consent.

  The central lesson is that inherited susceptibility changes the response to environmental hazards, but it does not define a person’s future. Safer workplaces, cleaner air, smoking cessation, early diagnosis and equitable respiratory care can reduce risk across the population. What readers should remember is simple: genes may influence vulnerability, while exposure control and timely care remain powerful ways to protect lung health.

  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)