Precision medicine is changing bronchiectasis care

Inhaled antibiotics can work very well for some people with bronchiectasis, yet provide only modest or inconsistent benefit for others. Emerging research suggests that biologically distinct subgroups, known as endotypes, may help explain this variation.

For many years, bronchiectasis treatment decisions have relied on clinical features such as symptom burden, exacerbation history, sputum culture results and whether Pseudomonas aeruginosa is present.

These factors remain important, but they do not fully explain a familiar problem in clinical practice and research: two apparently similar patients can respond very differently to the same inhaled antibiotic.

One patient may experience fewer exacerbations, improved sputum control and better quality of life. Another may continue to have frequent flare-ups despite apparently appropriate treatment.

The precision-medicine question

Instead of asking only whether inhaled antibiotics work in bronchiectasis, researchers are increasingly asking which patients are biologically most likely to benefit.

Bronchiectasis is not one single disease

Bronchiectasis is the final structural result of many different illnesses and biological processes. It can develop after severe infection, immune deficiency, aspiration, inflammatory disease, primary ciliary dyskinesia or another underlying condition.

Patients may also differ in airway microbiology, inflammatory pattern, mucus characteristics, immune response and speed of disease progression.

Different underlying causes

Post-infectious disease, immune deficiency, allergic disease and genetic disorders may all produce bronchiectasis through different pathways.

Different airway microbiomes

The community of organisms living in the airways may differ substantially even when routine cultures identify the same headline pathogen.

Different inflammatory patterns

Neutrophilic, eosinophilic, mixed and immune-related patterns may influence symptoms, exacerbations and treatment response.

Different rates of progression

Some patients remain relatively stable, while others experience repeated infections, declining lung function or increasing symptom burden.

Two people can therefore have chronic cough, daily sputum, repeated chest infections and positive cultures for Pseudomonas aeruginosa while still having meaningfully different disease biology.

Why might inhaled-antibiotic response vary?

Inhaled antibiotics deliver a high concentration of antibiotic directly to the airways. This can reduce bacterial load while limiting exposure to the rest of the body.

That principle is attractive, especially for chronic Pseudomonas infection. However, successful treatment depends on more than the presence or absence of a single bacterial species.

Measure the disease

Review exacerbations, symptoms, sputum microbiology, lung function and treatment burden.

Identify the biology

Assess airway microbiota, bacterial load, inflammatory markers and host-response features where suitable tools exist.

Match the treatment

Select the therapy most likely to address the dominant infection or inflammatory pathway.

Bacterial load may differ

Some patients have a large and persistent airway bacterial burden, while others have intermittent or lower-level detection. The potential benefit of suppressive antibiotic treatment may therefore differ.

The wider microbiome may matter

Routine culture usually reports selected organisms that grow under laboratory conditions. It does not describe the full community of bacteria within the airway.

Different microbial communities may influence inflammation, pathogen behaviour, antibiotic competition and resilience after treatment.

Inflammation may continue after bacterial suppression

Reducing Pseudomonas bacterial load may not completely control symptoms if another inflammatory pathway, mucus-clearance problem or underlying disease remains active.

Host response may influence benefit

Patients may differ in immune-cell activity, antibody response, airway damage and susceptibility to inflammatory injury. These differences may affect how much clinical benefit follows a reduction in bacterial load.

Phenotypes and endotypes: what is the difference?

Phenotype

What the disease looks like

A phenotype describes visible clinical characteristics, such as frequent exacerbations, chronic infection, daily sputum production or severe radiological disease.

Endotype

What is driving the disease

An endotype describes the biological mechanism underlying a subgroup, such as a particular inflammatory pathway, microbial community or immune-response pattern.

Phenotypes remain useful because they are practical and available during routine assessment. Endotypes aim to go deeper by explaining why patients with the same clinical phenotype may respond differently.

A simple example

“Chronic Pseudomonas infection” is a phenotype. Different microbiota and inflammatory patterns within that group may represent separate endotypes with different responses to inhaled antibiotics.

What do current guidelines recommend?

Current guidelines continue to support inhaled antibiotics for selected patients. Precision medicine does not make these recommendations obsolete.

2025 European guidance

The European Respiratory Society recommends offering long-term inhaled antibiotics to adults at high risk of exacerbations who have chronic Pseudomonas aeruginosa infection despite standard care.

It also conditionally supports inhaled antibiotics for selected high-risk patients chronically infected with other pathogens.

UK specialist practice

British guidance has traditionally recommended inhaled colistin for chronic Pseudomonas infection, with inhaled gentamicin as an alternative in selected patients.

Long-term antibiotic treatment is generally specialist led and considered after airway clearance, sputum testing and treatment of associated conditions have been optimised.

These recommendations use clinical risk and microbiology because validated endotype testing is not yet routinely available.

What does the overall inhaled-antibiotic evidence show?

The clinical-trial record has often appeared mixed. Some studies have shown meaningful reductions in exacerbations or bacterial load, while others have failed to meet their primary endpoint.

A 2024 systematic review and meta-analysis brought together 20 studies involving 3,468 adults with bronchiectasis.

20 studies

Randomised studies of inhaled antibiotics were included in the updated evidence review.

3,468 patients

The analysis combined evidence from a substantial adult bronchiectasis population.

Modest average effect

Exacerbations were reduced slightly overall, with a probable reduction in severe exacerbations.

The average results are encouraging but do not imply that every patient benefits equally. A moderate average effect may combine strong responders, limited responders and patients who gain no meaningful benefit.

Patient group	Possible response	Potential explanation
Strong responder	Fewer exacerbations, reduced sputum burden and improved quality of life	Antibiotic-sensitive dominant pathogen and a treatment- responsive infective endotype
Partial responder	Lower bacterial load but only modest symptom improvement	Infection improves while mucus dysfunction or inflammation remains active
Limited responder	Little change in exacerbations or daily symptoms	Different microbiota, resistant organisms or a non-dominant infective pathway
Poorly tolerant patient	Treatment stopped because of cough, wheeze or treatment burden	Airway reactivity or practical difficulty using regular inhaled therapy

What did the ORBIT endotype research find?

One of the most important recent developments came from a new analysis of samples collected during the ORBIT-3 and ORBIT-4 Phase 3 trials.

The original trials tested inhaled liposomal ciprofloxacin in patients with bronchiectasis and chronic Pseudomonas aeruginosa infection. Their headline results appeared inconsistent, with one trial showing clearer benefit than the other.

Researchers looked beyond routine cultures

The later analysis examined sputum microbiota using genetic sequencing, alongside inflammatory markers, proteomics and geographical differences.

This provided a more detailed biological picture than a standard report stating only that Pseudomonas was present.

Microbiota differences

Patients had different airway bacterial-community structures despite sharing the label of chronic Pseudomonas infection.

Inflammatory differences

Biological inflammatory profiles varied and were associated with differing clinical behaviour.

Exacerbation differences

Microbiota and inflammatory patterns were associated with how frequently patients experienced flare-ups.

Treatment-response differences

These biological patterns were also associated with response to inhaled liposomal ciprofloxacin.

When researchers accounted for microbiota profile and geographical region, the treatment estimates from ORBIT-3 and ORBIT-4 became more similar and aligned more closely with earlier meta-analyses.

Why this matters

Some apparent inconsistency between bronchiectasis trials may reflect meaningful biological differences between enrolled patients rather than random statistical noise.

Why sputum culture may not tell the whole story

Sputum culture remains essential. It identifies important pathogens, helps assess antibiotic susceptibility and guides treatment during exacerbations.

However, culture provides only a partial view of the airway environment.

It may not describe the full bacterial community
It does not routinely quantify every organism present
It provides limited information about host inflammation
It may not distinguish different Pseudomonas biological states
It does not measure immune-response patterns
It cannot reliably predict treatment response alone

Two cultures can look identical on paper

Two sputum samples may both be reported as growing Pseudomonas aeruginosa while differing greatly in total bacterial load, microbial diversity, inflammatory activity and interaction with the host immune system.

Which other bronchiectasis endotypes are being studied?

Precision-medicine research extends beyond chronic Pseudomonas infection. Several candidate endotypes are being explored.

Neutrophilic endotype

Characterised by dominant neutrophil-driven inflammation and potentially suited to treatments targeting neutrophil enzymes or inflammatory pathways.

Eosinophilic endotype

A subgroup with raised eosinophilic inflammation that may have different treatment responses from conventional neutrophilic bronchiectasis.

Infective endotype

Disease in which persistent bacterial burden and infection are dominant drivers of exacerbations and symptoms.

Immune-related endotype

Disease associated with immune deficiency, altered antibody response or another distinct host-defence abnormality.

These categories remain areas of active research. They are not yet universally defined or ready to replace standard clinical assessment.

What does this mean for patients today?

Precision medicine does not mean that inhaled antibiotics should be withheld until complex molecular testing becomes available.

Inhaled antibiotics remain a reasonable, guideline-supported option for selected patients, particularly those with chronic Pseudomonas infection and repeated exacerbations.

Treatment should have a measurable goal

Before treatment begins, the patient and specialist should agree what improvement would make the therapy worthwhile.

This might include fewer exacerbations, fewer rescue antibiotic courses, reduced sputum burden, fewer hospital admissions or improved daily symptoms.

Factors a specialist may currently consider

Number and severity of previous exacerbations
Repeated sputum culture results
Presence of chronic Pseudomonas infection
Previous antibiotic susceptibility results
Daily sputum volume and symptom burden
Airway-clearance adherence
Kidney, hearing and balance health
Airway reactivity and nebuliser tolerance
Previous response to oral or inhaled antibiotics
Practical treatment burden and patient preference

Treatment response should then be reviewed rather than assuming that continued therapy must be beneficial simply because the microbiological indication appeared appropriate.

How could better endotyping improve care?

Avoid ineffective treatment

Patients who are unlikely to benefit could avoid months of nebuliser burden, airway side effects and unnecessary antibiotic exposure.

Identify likely responders

Patients with a treatment-responsive infective endotype could be prioritised for inhaled therapy earlier.

Guide combination treatment

Some people may need inhaled antibiotics combined with macrolides, enhanced airway clearance or targeted anti-inflammatory treatment.

Improve clinical trials

Selecting patients whose biology matches the drug mechanism may reduce trial inconsistency and identify effective treatments more reliably.

Precision medicine beyond inhaled antibiotics

The implications extend beyond traditional antibiotics. Researchers are investigating therapies aimed at specific inflammatory, bacterial and immune pathways.

Anti-Pseudomonas antibody treatment

Research into gremubamab, a monoclonal-antibody strategy directed against Pseudomonas aeruginosa, has provided encouraging proof-of-concept findings.

This approach aims to target the pathogen more specifically than broad antimicrobial treatment, although further research and regulatory assessment are needed.

Biologically targeted anti-inflammatory treatment

As inflammatory endotypes become clearer, future therapies may be matched to neutrophilic, eosinophilic or other dominant pathways.

The long-term aim is a treatment model in which inhaled antibiotics, antibodies, anti-inflammatory medicines and airway-clearance strategies are selected according to each patient’s dominant disease mechanism.

What are the current limitations?

Precision medicine in bronchiectasis remains a developing field. Most advanced endotyping tools are not yet available in routine clinical care.

Many studies remain exploratory
Endotype definitions are not yet standardised
Advanced sequencing is not routinely available
Biomarker tests must be reproducible
Testing must become affordable and practical
Results must lead to clear treatment decisions

A biomarker is not clinically useful simply because it differs between groups. It must reliably predict an outcome or treatment response and improve care when used in real patients.

Fundamentals still matter

Precision medicine cannot replace airway clearance, exercise, vaccination, smoking cessation, treatment of underlying causes, sputum monitoring and careful review of exacerbation history.

What might bronchiectasis care look like in the future?

The most likely development is gradual integration rather than an immediate transformation of routine care.

Better routine clinical stratification Specialists will continue combining exacerbation history, symptoms, imaging and sputum microbiology more systematically.
Practical biomarker panels Selected inflammatory or microbial markers may become available without requiring extensive research-laboratory testing.
More targeted clinical trials Studies may enrol patients according to biological signatures that match the treatment mechanism.
Predictive treatment selection Clinicians may be able to estimate the likelihood of benefit from inhaled antibiotics before committing a patient to long-term treatment.
Combination treatment by endotype Infection-directed, inflammatory and mucus-clearance treatments may be combined according to the patient’s dominant biological drivers.

Chronic Pseudomonas infection may increasingly be viewed not as one uniform end-stage label, but as a family of biological states requiring different treatment strategies.

Conclusion

Inhaled antibiotics remain an important treatment for selected people with bronchiectasis, particularly those with chronic Pseudomonas aeruginosa infection and frequent exacerbations.

However, patients sharing the same clinical label can differ in airway microbiota, bacterial load, inflammation and immune response. These differences may help explain why some patients obtain substantial benefit while others experience little change.

The ORBIT endotype analysis suggests that some inconsistency in previous inhaled-antibiotic trials may reflect meaningful biological variation between study populations.

Precision medicine aims to identify that variation and match the right treatment to the right patient. Endotyping is not yet routine, but it may eventually make inhaled-antibiotic treatment more predictable, efficient and personalised.

Frequently asked questions

What is precision medicine in bronchiectasis?

Precision medicine means tailoring treatment to the biological processes driving an individual patient’s disease, rather than relying only on symptoms, CT appearances or a standard sputum-culture label.

Why do inhaled antibiotics help some patients more than others?

Response may be influenced by bacterial load, antibiotic susceptibility, airway microbiota, inflammatory activity, mucus clearance, immune response and how well the treatment is tolerated and used.

What is a Pseudomonas endotype?

It is a biologically distinct subgroup within the wider population of patients with chronic Pseudomonas aeruginosa infection. Different microbial and inflammatory patterns may be associated with different exacerbation risks and treatment responses.

Are inhaled antibiotics still recommended?

Yes. Current European guidance recommends long-term inhaled antibiotics for adults at high risk of exacerbations who have chronic Pseudomonas infection despite standard care. Treatment should be specialist led and reviewed for benefit.

Which inhaled antibiotics are used for bronchiectasis?

Depending on local practice, licensing, sputum results and the patient’s health, options may include inhaled colistin, gentamicin, tobramycin or other inhaled formulations.

Does growing Pseudomonas mean I will definitely benefit?

No. Chronic Pseudomonas infection is an important treatment indicator, but it does not guarantee a clinically meaningful response. Treatment should have clear goals and be reviewed against exacerbation frequency, symptoms and tolerance.

Is endotype testing available in routine clinics?

Not usually. Most detailed microbiome, proteomic and molecular endotyping methods remain research tools. Routine care still relies on clinical history, sputum cultures, lung function, imaging and treatment response.

What happens if an inhaled antibiotic does not help?

The specialist should reassess adherence, inhaler or nebuliser technique, sputum microbiology, airway clearance, side effects and whether another treatment strategy is more appropriate.

References

Chalmers JD, et al. European Respiratory Society clinical practice guideline for the management of adult bronchiectasis. European Respiratory Journal. 2025. View guideline
Hull RC, et al. Endotypes of Pseudomonas aeruginosa infection in bronchiectasis are associated with inhaled antibiotic response: results from the ORBIT-3 and ORBIT-4 trials. American Journal of Respiratory and Critical Care Medicine. 2025. View publication
Cordeiro R, et al. The efficacy and safety of inhaled antibiotics for the treatment of bronchiectasis in adults: updated systematic review and meta-analysis. Chest. 2024. View publication
University of Dundee. Trial results could herald a major step forward in the treatment of persistent Pseudomonas lung infection. 2025. View research announcement

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