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)

• Microbiome Shifts Driving Bronchiectasis Progression

  The respiratory microbiome has emerged as one of the most fascinating frontiers in chronic lung disease research, and bronchiectasis sits squarely at the centre of this conversation. For decades, clinicians treated the dilated airways of bronchiectasis as a structural problem requiring airway clearance and intermittent antibiotics. Newer culture-independent sequencing techniques have revealed that the bacterial, fungal, and viral communities living within these damaged airways shift in patterns that predict exacerbations, hospitalisations, and quality of life decline.

  The APSR 2022 congress, held in partnership with KATRD, brought together respiratory physicians, microbiologists, and allied health researchers to examine these very patterns. Australia contributes significantly to the global conversation, with high-quality cohort data from the Australian Bronchiectasis Registry and unique insights from remote and Indigenous communities where disease prevalence remains strikingly high. Understanding the trajectory of dysbiosis in these populations helps clarify how microbial imbalance translates into clinical deterioration.

  The Architecture of the Airway Microbiome

  In healthy lungs, microbial communities are sparse but diverse, dominated by organisms such as Prevotella, Veillonella, and Streptococcus at low abundance. The airways of patients with stable bronchiectasis show a different signature, often enriched with potential pathogens even between exacerbations. This baseline composition matters enormously because it determines which species will bloom when the system is challenged by a viral infection or environmental insult.

  Loss of microbial diversity correlates strongly with disease severity. Studies using 16S rRNA sequencing have shown that patients with frequent exacerbations harbour fewer bacterial taxa, dominated instead by Pseudomonas aeruginosa or Haemophilus influenzae. This pattern mirrors findings in chronic obstructive pulmonary disease, though the clinical course in bronchiectasis is often punctuated by purulent sputum and structural progression visible on high-resolution CT.

  Pathogen Dominance and Clinical Worsening

  Pseudomonas aeruginosa colonisation marks a turning point in the natural history of bronchiectasis. Once established in the lower airways, it forms biofilms that resist phagocytosis and penetrate poorly into sputum. Patients with chronic Pseudomonas face steeper lung function decline, more hospital admissions, and reduced survival compared with those colonised by other organisms.

  The transition from a diverse microbiome to a pathogen-dominated one is rarely abrupt. It typically unfolds over months to years, with intermediate states showing co-colonisation by Staphylococcus aureus, Streptococcus pneumoniae, and non-tuberculous mycobacteria. Each shift leaves an imprint on inflammatory markers, radiology, and symptom burden, making longitudinal sampling clinically informative rather than purely academic.

  Antibiotic Pressure and Microbial Resilience

  Frequent antibiotic courses reshape the airway ecosystem in ways clinicians are only beginning to appreciate. While necessary to clear acute infections, repeated exposure to broad-spectrum agents depletes commensal anaerobes that normally keep potential pathogens in check. This ecological vacuum leaves the door open for resistant strains to fill the niche.

  Long-term macrolide protocols, including azithromycin three times weekly, have transformed maintenance therapy for patients with frequent exacerbations. The evidence behind macrolide therapy in bronchiectasis continues to evolve, and conference discussions highlighted both the anti-inflammatory benefits and the risks of resistance emergence. Australian clinicians must balance these trade-offs carefully given rising macrolide resistance across the Asia-Pacific region.

  Inhaled antibiotics add another layer of selective pressure. Agents like tobramycin and colistin target Pseudomonas without significantly disrupting oral and gut flora, but data on long-term microbiome recovery remain limited. Researchers at the Westmead Institute are tracking these patients with serial sputum samples to map community reassembly after inhaled courses.

  Inflammation as the Bridge from Dysbiosis to Damage

  The link between microbial imbalance and lung tissue damage runs through the host immune response. Neutrophil elastase, matrix metalloproteinases, and pro-inflammatory cytokines surge in response to pathogen-derived molecules such as lipopolysaccharide and flagellin. Persistent neutrophilic inflammation drives airway wall destruction, perpetuating the very structural changes that foster further microbial dysbiosis.

  This vicious cycle explains why some patients progress despite apparently adequate infection control. Treating the bacterial insult alone does not break the inflammatory feedback loop. Biological therapies targeting neutrophil chemotaxis, including CXCR2 antagonists and brensocatib, are now in late-phase trials with results expected to reshape treatment paradigms in coming years.

  Australian Research and Indigenous Health Realities

  Bronchiectasis carries a disproportionate burden among Aboriginal and Torres Strait Islander Australians, with prevalence rates among the highest reported globally. The Menzies School of Health Research in Darwin has documented this gap over two decades, linking it to crowded housing, limited access to specialist care in remote communities, and childhood respiratory infections that damage developing airways.

  Research at the Royal Adelaide Hospital and the Alfred in Melbourne has shown that Indigenous patients often present with more advanced radiological disease and carry different microbial profiles, including higher rates of non-tuberculous mycobacteria. Culturally safe, community-led models of care are being trialled across the Northern Territory to address these inequities, with outreach physiotherapists and telehealth reviews making real inroads.

  The Australian Bronchiectasis Registry, coordinated through Lung Foundation Australia, captures longitudinal data on microbiological patterns, treatment responses, and outcomes. Findings from this registry inform local antibiotic protocols and continue to shape national consensus statements, ensuring clinical guidelines reflect real-world Australian practice rather than imported recommendations.

  Emerging Therapeutic Targets and Microbiome Modulation

  Looking beyond antibiotics, researchers are exploring ways to restore a more balanced airway microbiome. Nebulised bacteriophage therapy, probiotic formulations tailored to respiratory niches, and even faecal microbiota transplantation for gut-lung axis modulation are entering early clinical evaluation. None has yet earned a place in standard care, but several show promising signals in phase II work.

  Personalised medicine approaches are also gaining traction, with treatment selection guided by individual microbiome profiles rather than broad disease categories. Molecular diagnostics that return species-level identification within hours are being piloted in Brisbane and Sydney, potentially shortening the path from sputum collection to targeted therapy.

  Vaccination strategies against Pseudomonas and Staphylococcus aureus remain in development, and prevention of initial pathogen acquisition could prove more powerful than treatment of established dysbiosis. Combined with smoking cessation programs and improved indoor air quality standards, such primary prevention measures offer hope for slowing disease progression at its roots.

  Practical Considerations for the Australian Respiratory Clinician

  • Obtain sputum cultures at every clinically stable visit, not only during exacerbations, to track colonisation patterns over time.
  • Consider non-tuberculous mycobacterial screening in patients with refractory symptoms, particularly those with nodular-bronchiectatic disease patterns on imaging.
  • Use macrolide maintenance therapy selectively, weighing exacerbation reduction against resistance risk and drug interactions.
  • Engage local Indigenous health workers when caring for Aboriginal and Torres Strait Islander patients to support culturally safe, community-based management.
  • Refer eligible patients to the Australian Bronchiectasis Registry to strengthen the evidence base and access emerging therapies through clinical trials.
  • Pair antibiotic courses with structured airway clearance to reduce bacterial load and limit reliance on repeated drug exposure.
  • Monitor for Pseudomonas acquisition with regular microbiological surveillance, as early detection may alter long-term outcomes.

  For clinicians across Sydney, Melbourne, Perth, and the regional centres in between, the practical message is straightforward: each sputum sample tells a story about the trajectory of the disease. Documenting the microbiome journey alongside lung function, radiology, and symptom scores turns routine review visits into opportunities for proactive intervention. The Australian respiratory community is well placed to lead this shift, given strong registry data, world-class research institutions, and meaningful engagement with communities most affected by bronchiectasis.

  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)