- Bronchiectasis is a long-term airway disease in which the bronchi are widened and damaged. The UK guideline covers non-CF bronchiectasis, and the NHS lists serious childhood infections and conditions such as rheumatoid arthritis among possible causes. For many people no cause is found (NHS causes page; BTS 2019 guideline).
- The strongest independent support is for long-term low-dose macrolide antibiotics. The EMBRACE trial of azithromycin reported roughly a two-thirds cut in exacerbations over six months (141 adults; rate ratio 0.38; funded by the Health Research Council of New Zealand and the Auckland District Health Board Charitable Trust), and the UK guidance gives a strong recommendation for people with three or more exacerbations a year (Wong et al., Lancet 2012; BTS macrolide guideline summary).
- The BLESS erythromycin trial, which many people link with macrolides, names the Mater Adult Respiratory Research Trust Fund as funder in its 2014 follow-up paper. We could not open the original JAMA funding line. Macrolide use also increased macrolide-resistant bacteria (Serisier et al., JAMA 2013; Rogers et al., Lancet Respir Med 2014).
- Brensocatib is the first drug approved for non-CF bronchiectasis in the US (August 2025) and the EU (marketing authorisation 18 November 2025). It cut yearly exacerbations by about 20% in the maker's phase 3 trial, which the maker funded (Chalmers et al., NEJM 2025; EMA EPAR). We could not confirm a UK (MHRA) decision.
- Inhaled antibiotics are the most commercially driven area. Inhaled ciprofloxacin was sponsored by Bayer, and the advisory panel voted against it in 2017. Inhaled colistimethate has a positive first trial (PROMIS 1) and a failed second trial (PROMIS 2), both with authors from the drug company Zambon (RESPIRE 1; PROMIS 1 and 2, Lancet Respir Med 2024).
- Supplement claims are weakly supported. A 2026 systematic review found no significant reduction in exacerbations from mucoactive drugs such as N-acetylcysteine, and vitamin D findings are associations only (McCullough et al., Eur Respir Rev 2026; Moriki et al., 2025).
- Money trail: Brensocatib's pivotal trial was funded by its maker, Insmed, which is headquartered in Bridgewater, New Jersey, and which holds a licence agreement with AstraZeneca for the drug (Insmed press release, August 2025). Both positive macrolide trials are reported as funded by public or charitable bodies, but we could not confirm the EMBRACE funding statement or the BLESS JAMA funding line. The inhaled-antibiotic trials were funded by the makers.
- Evidence grade: Strong for macrolides in adults with frequent exacerbations (with resistance and safety caveats). Moderate for brensocatib in adults with frequent exacerbations (one maker-funded phase 3 trial, plus regulatory decisions). Weak for pulmonary rehabilitation and exercise training. Insufficient for supplements. Risk for antibiotic resistance and for long-term macrolide side effects.
Independent evidence review · Prescription medicine
Long-term low-dose macrolide antibiotics have the best independent evidence for reducing flare-ups in adults with non-CF bronchiectasis who have frequent exacerbations, but they carry a real risk of antibiotic resistance. The newest drug, brensocatib, has regulatory approval in the US and EU and is supported by one large, maker-funded trial. Supplements and most inhaled antibiotics lack trials that are independently funded and clearly positive. Confidence: moderate for macrolides, low to moderate for brensocatib, and low for everything else. Airway clearance and pulmonary rehabilitation are supported mainly by small trials and reviews, with low-quality evidence.
Table of contents
- Evidence summary
- What bronchiectasis is, and its causes
- How the treatments are thought to work
- What works and what does not
- Benefits by claim
- Risks and side effects
- Interactions
- Who needs extra caution
- Doses studied and how the drugs are given
- Follow the money: who makes it and who funded the evidence
- Related research
- Frequently asked questions
- Sources and funding notes
Evidence summary
| Claim | Evidence | Source | Funding / conflict | Strength |
|---|---|---|---|---|
| Long-term azithromycin reduces exacerbations in non-CF bronchiectasis | 141 adults in a 6-month double-blind trial. Exacerbations requiring antibiotics fell by roughly two-thirds versus placebo in the trial report. Rate ratio 0.38 (95% CI 0.26 to 0.54); 0.59 vs 1.57 exacerbations per patient. | Wong et al., Lancet 2012 (EMBRACE) | Health Research Council of New Zealand and Auckland District Health Board Charitable Trust (Lancet 2012 funding statement). | Strong |
| Long-term erythromycin reduces exacerbations | Twelve-month placebo-controlled trial of erythromycin 400 mg twice daily. Annualised exacerbation rate 1.29 vs 1.97 (p=0.003). Macrolide-resistant oropharyngeal streptococci rose sharply on erythromycin. | Serisier et al., JAMA 2013 (BLESS) | Funding statement not opened. Follow-up paper names the Mater Adult Respiratory Research Trust Fund as funder. | Moderate |
| Long-term macrolides increase resistance and change airway bacteria | Follow-up of the BLESS trial: erythromycin did not significantly cut exacerbations in patients without P. aeruginosa infection, and it reduced H. influenzae and increased P. aeruginosa. | Rogers et al., Lancet Respir Med 2014 | Mater Adult Respiratory Research Trust Fund. | Risk |
| Brensocatib reduces pulmonary exacerbations | Phase 3 trial in adults and adolescents. Rate ratio 0.79 (10 mg) and 0.81 (25 mg) vs placebo over 52 weeks. Exacerbation-free at week 52: 48.5% vs 40.3%. | Chalmers et al., NEJM 2025 (ASPEN) | Funded by Insmed, the drug's maker. | Moderate |
| Brensocatib safety | Adverse events were similar across groups, except more hyperkeratosis (skin thickening) on brensocatib. FEV1 decline was smaller on the 25 mg dose than on placebo. | Chalmers et al., NEJM 2025 | Funded by Insmed. | Risk |
| Inhaled ciprofloxacin reduces exacerbations in bacteria-positive bronchiectasis | RESPIRE 1: 416 patients, the 14-day on/off regimen prolonged time to first exacerbation. RESPIRE 2 showed trends that did not reach significance. | De Soyza et al., EJR 2018 (RESPIRE 1); Aksamit et al., EJR 2018 (RESPIRE 2) | Sponsored by Bayer (manufacturer), per trial registry and trade reports. | Weak |
| Inhaled colistimethate reduces exacerbations in P. aeruginosa infection | PROMIS 1 suggested benefit. PROMIS 2 did not replicate it and was stopped early during the COVID-19 pandemic. No deaths were related to study treatment. | Haworth et al., Lancet Respir Med 2024 | Zambon SpA, the drug company; two authors are Zambon SpA research staff. Funding line not opened. | Weak |
| Mucoactive drugs (including N-acetylcysteine) reduce exacerbations | 24 studies. Seven randomised trials (n=1,259) gave a pooled difference of −0.40 exacerbations per year, not significant (95% CI −1.04 to 0.24). Certainty very low. | McCullough et al., Eur Respir Rev 2026 | Funding not verified (full text not opened). | Insufficient |
| Exercise training and pulmonary rehabilitation improve exercise and quality of life | Short-term gains in exercise capacity and quality of life. Outpatient exercise training reduced exacerbations (median 2 vs 1 over 12 months). Certainty low to moderate. | Lee et al., Arch Phys Med Rehabil 2017; Lee et al., Cochrane 2021 | Funding not verified for either review. | Weak |
| Airway clearance techniques are safe and help sputum clearance | Cochrane review of 7 studies (105 participants, mostly cross-over). Safe in stable disease. Effect on acute infection unknown. | Lee et al., Cochrane 2015 | Funding statements conflict across Cochrane pages; could not open the full review to confirm. | Moderate |
| Vitamin D deficiency is linked with worse bronchiectasis | Seven studies, mostly observational. Lower vitamin D in patients than controls, and worse severity in deficient patients. No trial showing benefit from supplements. | Moriki et al., 2025 | Funding not verified. | Insufficient |
Independent evidence and credibility scorecard
Independence tiers: 1 = regulator or government body; 2 = academic, charitable or professional-society source with no declared commercial funding for the work (or funding we could not verify, flagged in the row); 3 = independent authors analysing mostly manufacturer-run trials, or minor declared industry ties; 4 = manufacturer-funded or manufacturer-authored. Credibility runs from A (highest) to D.
| Source | Who funds it | Country | Independence tier (1–4) | Credibility (A–D) | Why it would tell the truth / residual bias |
|---|---|---|---|---|---|
| NHS causes page | Tax-funded NHS (England) | UK | 1 | B | Public health duty and accountability for accuracy. Plain-language summary, so it cannot settle clinical questions. |
| EMA public assessment record for Brinsupri | EU regulator (funding not separately verified) | EU (Amsterdam) | 1 | A | Legal mandate and public accountability. Residual bias: decisions rest on the maker's submitted data. |
| EMBRACE (Wong et al., Lancet 2012) | Health Research Council of New Zealand; Auckland District Health Board Charitable Trust (Lancet 2012 funding statement) | New Zealand | 2 | B | No commercial stake identified; the funders are a government research council and a charitable trust, so it is scored tier 2 rather than tier 1. Single trial of 141 adults, so result needs replication. |
| BLESS (Serisier et al., JAMA 2013) | Mater Adult Respiratory Research Trust Fund (charitable trust), per follow-up paper; JAMA funding line not opened | Australia | 2 | B | Charity-funded university trial with no drug maker. Residual bias: a positive exacerbation result is more publishable, and the mixed resistance findings were reported. |
| BTS adult bronchiectasis guideline (Hill et al., Thorax 2019) | British Thoracic Society (professional society); funding statement not opened | UK | 2 | B | Professional body whose members must declare interests; it benefits from clear, usable guidance. Residual bias: expert consensus can lag behind trials. |
| ERS guideline (Polverino et al., Eur Respir J 2017) | European Respiratory Society (professional society); funding statement not opened | Europe | 2 | B | Systematic review and GRADE method. Residual bias: multi-author panel with unverified declared ties. |
| Cochrane airway clearance review (Lee et al., 2015) | Funding statements conflict across Cochrane pages (NIHR infrastructure support vs "no funding"); not confirmed | UK (Cochrane Airways Group) | 2 | A | Systematic method and public reporting of gaps. Residual bias: the small trial base limits certainty. |
| Pulmonary rehabilitation review (Lee et al., 2017) | Funding not verified | Not verified | 2 | B | Academic review with a clear publication incentive. Residual bias: small, heterogeneous trials. |
| Mucoactive agents meta-analysis (McCullough et al., 2026) | Funding not verified (full text not opened) | Not verified | 2 | B | Systematic review of 24 studies that reports a negative pooled result. Several authors also ran an included trial (CLEAR); independent assessors extracted its data. Residual bias: most trials at high or some risk of bias. |
| ASPEN (Chalmers et al., NEJM 2025) | Insmed (drug maker) | US (Bridgewater, New Jersey) | 4 | C | Peer-reviewed in a top journal, with a registered protocol. Residual bias: the sponsor designed, ran and profits from the trial. |
| PROMIS 1 and 2 (Haworth et al., Lancet Respir Med 2024) | Zambon SpA (drug company), whose staff are co-authors | Italy (Zambon SpA, Bresso, Milan) | 4 | C | Peer-reviewed, with an honest report of the failed second trial. Residual bias: the maker chooses which trial to publish and promote. |
| RESPIRE 1 and 2 (De Soyza; Aksamit, EJR 2018) | Bayer (drug maker), per trial registry and trade reports | Germany (Bayer AG, Leverkusen) | 4 | C | Peer-reviewed and transparent about the mixed second trial. Residual bias: maker-run design; the advisory panel rejected the regimen. |
Sources cluster in the UK, Europe and the US. The most independent evidence (regulatory and public-funded trials) comes mainly from New Zealand, the UK and the EU. The commercial evidence comes from the US and Germany. Convergence is strongest on macrolides, where a New Zealand trial and an Australian trial both show fewer exacerbations (both are reported as public or charity-funded; not fully confirmed here), while both also flag resistance.
What bronchiectasis is, and its causes
Bronchiectasis describes airways that are permanently widened and damaged, so mucus pools and infections recur. The BTS guideline covers non-CF bronchiectasis, which excludes cystic fibrosis (BTS 2019). The ERS guideline sets out the investigation of underlying causes, treatment of exacerbations, pathogen eradication, long-term antibiotics, mucoactive drugs and respiratory physiotherapy (ERS 2017).
The NHS lists several possible causes. These include severe infections such as pneumonia, tuberculosis, measles, whooping cough and COVID-19. Other causes are asthma, COPD, inhaling damaging substances, problems with the immune system, and conditions such as rheumatoid arthritis and inflammatory bowel disease. For many people, the NHS says, no clear cause is found (NHS causes page). Cystic fibrosis is excluded from the BTS guideline, which covers non-CF disease only.
Legal status matters here. Brensocatib is licensed for non-CF bronchiectasis in the EU and US. Macrolides are used off-label for this purpose in the UK, because no macrolide has a UK product licence for long-term immunomodulatory use (BTS macrolide guideline summary).
How the treatments are thought to work
Each class of treatment targets a different part of the cycle of damage, mucus and infection.
- Macrolides (azithromycin, erythromycin) are antibiotics that also reduce airway inflammation. The trials suggest they lower the number of flare-ups. They also change which bacteria live in the airway, which is the main concern for resistance (Rogers et al. 2014).
- Brensocatib is a reversible inhibitor of dipeptidyl peptidase 1 (DPP-1). The enzyme activates neutrophil serine proteases, which the maker and trial authors link to airway inflammation and damage (ASPEN 2025). The link between this pathway and exacerbations is supported by the trial result, not by separate proof.
- Inhaled antibiotics aim to reduce bacteria such as Pseudomonas aeruginosa in the airway, which is linked to more exacerbations and higher mortality (Haworth et al. 2024).
- Airway clearance and exercise help move mucus and improve fitness. They do not treat the damaged airway itself.
What is proven in humans: lower exacerbation rates with macrolides and brensocatib in trials, and short-term fitness gains from exercise programmes. What rests on lab or animal work only: the detailed mechanism of most supplements, and most claims for probiotic inhalers, which are at an early stage.
What works and what does not
| Treatment | Verdict | Basis |
|---|---|---|
| Long-term macrolide (frequent exacerbators) | WORKS | Fewer exacerbations in two trials; UK strong recommendation at three or more a year (EMBRACE; BLESS) |
| Brensocatib (adults and adolescents, 12 and over) | WORKS (modest) | About 20% fewer yearly exacerbations in one maker-funded phase 3 trial (ASPEN) |
| Exercise training and pulmonary rehabilitation | MIXED | Better fitness and quality of life; exercise training reduced exacerbations in one review (Lee 2017) |
| Airway clearance techniques | MIXED | Safe and helpful for sputum in stable disease; unknown in flare-ups (Cochrane 2015) |
| Inhaled ciprofloxacin | MIXED | One trial positive, one trend-only; advisory panel voted against in 2017 (RESPIRE 1; trade report) |
| Inhaled colistimethate (P. aeruginosa infection) | MIXED | Positive in PROMIS 1, not replicated in PROMIS 2 (Haworth 2024) |
| N-acetylcysteine and other mucoactive drugs | DOES NOT SHOW BENEFIT (pooled) | No significant reduction in exacerbations (McCullough 2026) |
| Vitamin D | INSUFFICIENT | Deficiency is associated with worse disease, but no trial of supplements was found in our search (Moriki 2025) |
Benefits by claim
Can a macrolide reduce flare-ups?
Yes, in adults with frequent exacerbations. EMBRACE gave 500 mg azithromycin three times a week for six months to 141 adults with non-CF bronchiectasis. Exacerbations fell by roughly two-thirds compared with placebo in the trial report. The per-patient rates were 0.59 vs 1.57 and the rate ratio was 0.38 (95% CI 0.26 to 0.54) (Wong et al. 2012). The effect is large, but the trial was short and small. BLESS, an Australian trial of twice-daily erythromycin for 12 months in 117 adults, found fewer exacerbations (1.29 vs 1.97 per year), with a rise in macrolide resistance (Serisier et al. 2013).
Does brensocatib help?
It lowered exacerbations modestly. In ASPEN, the annualised exacerbation rate was cut by about 20% (rate ratio 0.79 for 10 mg and 0.81 for 25 mg). The share of patients without an exacerbation at week 52 rose from 40.3% to about 48.5%. The 25 mg dose also reduced the decline in lung function (FEV1) compared with placebo (Chalmers et al. 2025). The trial was funded by Insmed, so the result is one industry-run study that now sits within regulatory decisions.
Do inhaled antibiotics help?
Only in narrow groups, and the evidence is mixed. The RESPIRE 1 trial randomised 416 patients to inhaled ciprofloxacin (32.5 mg twice daily in 14-day or 28-day on/off cycles) and found longer time to first exacerbation on the 14-day regimen. RESPIRE 2 showed trends that did not reach significance (De Soyza et al. 2018; Aksamit et al. 2018). Inhaled colistimethate via the adaptive aerosol nebuliser device gave a clinically important result in PROMIS 1, but PROMIS 2 did not confirm it and stopped early (Haworth et al. 2024). We rate this area as weak and maker-driven.
Does airway clearance help?
It is safe in stable disease and may help bring up sputum. The Cochrane review found seven studies with 105 participants, most of them cross-over trials, and concluded the effect on acute infection is unknown (Lee et al. 2015). A later Cochrane review found too little evidence to rank positive expiratory pressure against other techniques (Lee et al. 2017).
Does exercise or pulmonary rehabilitation help?
It improves fitness and quality of life in the short term. Outpatient exercise training reduced exacerbations over 12 months (median 2 vs 1). Rehabilitation started during an exacerbation did not change exacerbation frequency or mortality (Lee et al. 2017). A 2021 Cochrane review of six studies (275 participants) found low-certainty evidence of better walking distance and quality of life after exercise training (Lee et al. 2021).
Do supplements help?
There is little evidence that they do. A 2026 meta-analysis of mucoactive agents, which include N-acetylcysteine, found no significant reduction in exacerbations and small FEV1 gains of about 3% (95% CI 0.31 to 6.15), with very low certainty (McCullough et al. 2026). A 2025 registry study of 2,461 patients compared two doses of N-acetylcysteine, but it is observational and cannot show cause (Oscullo et al. 2025). A 30-patient trial found that adding a high-protein supplement enriched with beta-hydroxy-beta-methylbutyrate to rehabilitation did not change the results (Doña et al. 2018). Vitamin D deficiency is more common in people with bronchiectasis and goes with worse disease, but the review says this association cannot show that supplements help (Moriki et al. 2025).
Risks and side effects
Brensocatib. Adverse events were similar across groups, except for hyperkeratosis (thickening of the skin) that was more common on brensocatib (ASPEN 2025). We did not open the full safety tables, so we cannot give rates for other effects.
Inhaled antibiotics. The PROMIS authors report no deaths related to study treatment (Haworth 2024). We did not open the full safety tables for the inhaled ciprofloxacin trials. Resistance to the inhaled drug is a recognised concern raised by the FDA panel (trade report).
Macrolides. Beyond resistance, the BTS macrolide guidance covers safety in general and asks clinicians to consider risks for each person (Smith et al. 2020). We could not open the full guideline, so we do not quote its specific monitoring steps.
Interactions
We could not verify a full interaction list for brensocatib, the inhaled antibiotics or the macrolides in the sources we opened. Macrolides interact with a number of other medicines, so a pharmacist should check any new prescription against your full list. Do not add supplements to these treatments without checking with your clinician first.
Who needs extra caution
The trials we reviewed enrolled adults with CT-confirmed bronchiectasis and recent exacerbations. ASPEN included adolescents aged 12 and over, while EMBRACE enrolled adults aged 18 and over (Wong 2012; Chalmers 2025). Specialist teams weigh macrolide resistance and any prior nontuberculous mycobacteria infection before starting a long-term macrolide. Pregnancy, breastfeeding and kidney or liver disease need individual decisions; we did not verify the label warnings in this review.
Doses studied and how the drugs are given
These are the doses used in trials, not personal advice. Do not change a dose without your clinician.
- Azithromycin: 500 mg three times a week for six months (EMBRACE) (Wong 2012).
- Erythromycin ethylsuccinate: 400 mg twice daily for 12 months (BLESS) (Serisier 2013).
- Brensocatib: 10 mg or 25 mg once daily, approved for patients aged 12 and over (FDA approval announcement; EMA EPAR). Check the full label for dosing rules.
- Ciprofloxacin dry powder for inhalation: 32.5 mg twice daily in 14-day or 28-day on/off cycles for 48 weeks (RESPIRE) (De Soyza 2018).
- Colistimethate sodium: inhaled twice daily via the adaptive aerosol nebuliser device for 12 months (PROMIS) (Haworth 2024).
Product quality. Macrolides and brensocatib are prescription medicines made to licensed standards. We found no sourced contamination reports for these products in our search. Supplements are not regulated to the same standard, and we did not check product testing for any named brand.
Research funding at a glance
12 sources graded. The counts below are the independence tiers assigned in the scorecard above. They count sources, not funding amounts or evidence quality.
Public funding alone does not prove independence, and commercial funding alone does not prove a claim false. Named funders, countries and relationships are in the scorecard and source notes.
Follow the money: who makes it and who funded the evidence
Who makes and sells the drugs
Brensocatib is developed by Insmed, which is headquartered in Bridgewater, New Jersey (Insmed press release). Insmed's press release also refers to a licence agreement with AstraZeneca AB for brensocatib, so a second company has a documented commercial tie to the drug. Insmed is a listed company whose shares are held mainly by institutions. We did not find a single controlling owner in the sources we opened. The marketing authorisation holder in the EU is Insmed Netherlands B.V. in Utrecht (EMA EPAR).
Inhaled ciprofloxacin was developed by Bayer, which is headquartered in Leverkusen, Germany (Bayer AG entry (Wikipedia)). Inhaled colistimethate is developed by Zambon SpA, based in Bresso, Milan, Italy (affiliation given in the Lancet Respiratory Medicine paper).
The macrolide trials we cite were funded by public or charitable bodies rather than a drug maker, which is why macrolides form the strongest independent area. Their funders still carry residual interests, such as academic careers that reward positive trials.
Who funded the trials
- EMBRACE (macrolides, New Zealand): Health Research Council of New Zealand and Auckland District Health Board Charitable Trust (Wong 2012).
- BLESS (erythromycin, Australia): the Mater Adult Respiratory Research Trust Fund, a charitable trust, according to the follow-up paper (Rogers 2014). We could not open the JAMA funding line to confirm the wording. Press coverage of the JAMA paper names the same trust.
- ASPEN (brensocatib): funded by Insmed (Chalmers 2025).
- RESPIRE 1 and 2 (inhaled ciprofloxacin): Bayer is named as sponsor in trade reports and the trial registry listing (ClinicalTrials.gov NCT02106832). We could not open the registry sponsor field.
- PROMIS 1 and 2 (inhaled colistimethate): Zambon SpA research staff are co-authors, and the funding line was not opened (Haworth 2024).
- Cochrane and guideline reviews: funding statements are either absent, conflicting or not opened (see the scorecard).
Documented integrity events and regulatory history
The FDA advisory committee voted against the 14-day regimen of inhaled ciprofloxacin by 9 to 6 and against the 28-day regimen by 14 to 1 in November 2017 (the trade report is dated 17 November). Panellists pointed to inconsistent results between the two trials (trade report). We could not confirm the FDA's final decision from the sources we opened, so we treat the inhaled ciprofloxacin US status as unverified. Brensocatib is approved in the US (August 2025) and the EU (18 November 2025), but its UK status is not confirmed here. We did not find a documented recall, ban or warning letter for brensocatib or the macrolides in our search.
Related research
- Asthma Prevention and Management: Evidence and Safety Guide
- Asthma Supplements: Nutritional Roles, Evidence Limits and Safety
- Chronic Rhinosinusitis: Adult Care and Adjunct Evidence
- Eosinophilic granulomatosis with polyangiitis: EGPA symptoms, asthma, ANCA and treatment
- Rheumatoid Arthritis: DMARD Guidance and Supplement Evidence
- Cardiac Rehabilitation: Exercise, Recovery, Home Programmes and Safety
- Pulmonary Hypertension: Types, Diagnosis, Treatment and Evidence Funding
Frequently asked questions
What causes bronchiectasis?
The NHS lists severe infections in childhood or adulthood, inherited conditions, immune problems, and conditions such as rheumatoid arthritis and inflammatory bowel disease. For many people, no clear cause is found (NHS causes page).
Do antibiotics like azithromycin cure bronchiectasis?
No. Long-term macrolides reduce flare-ups in adults with frequent exacerbations, but they do not reverse the damage to the airways. The strongest evidence is the EMBRACE trial, which reported roughly a two-thirds cut in exacerbations over six months (Wong 2012).
Is brensocatib approved, and does it work?
It is approved for adults and adolescents with non-CF bronchiectasis in the US (August 2025) and the EU (18 November 2025), In the maker's phase 3 trial it cut yearly exacerbations by about 20%, and the trial was funded by Insmed (EMA EPAR; Chalmers 2025).
Why are long-term macrolides risky?
They can increase macrolide-resistant bacteria. In the BLESS trial, erythromycin increased resistant oropharyngeal streptococci sharply (Serisier 2013). Specialists decide whether the benefit outweighs this risk for each person.
Do inhaled antibiotics work for bronchiectasis?
Only in narrow groups. Inhaled ciprofloxacin gave mixed results across two trials (De Soyza 2018), and inhaled colistimethate worked in one trial but not in a second (Haworth 2024).
Does N-acetylcysteine help bronchiectasis?
The evidence does not show a reduction in exacerbations. A 2026 meta-analysis of mucoactive agents found a pooled difference that was not significant, with very low certainty (McCullough 2026).
Sources and funding notes
What we could not verify: the full text of the 2019 BTS adult guideline and the 2017 ERS guideline (the publisher pages returned access errors), so we have not quoted their airway-clearance, sputum-culture or Pseudomonas wording; the JAMA funding line for BLESS; the sponsor field for the RESPIRE registry entry; the funding statements for the 2026 mucoactive review, the 2017 and 2021 exercise reviews and the 2025 vitamin D review; the MHRA (UK) decision on brensocatib; and the FDA's final decision on inhaled ciprofloxacin. The BTS and ERS guideline funding statements were not opened.
- NHS: Bronchiectasis causes — UK public health information; tax-funded NHS.
- Hill AT et al. British Thoracic Society guideline for bronchiectasis in adults, Thorax 2019 — UK professional guideline; funding statement not verified.
- Smith D et al. British Thoracic Society guideline for the use of long-term macrolides in adults with respiratory disease, Thorax 2020 — UK professional guideline; funding statement not verified.
- NHS Medicines Resources: BTS macrolide guideline summary — UK NHS summary; off-label status and recommendation for three or more exacerbations a year.
- Polverino E et al. European Respiratory Society guidelines for the management of adult bronchiectasis, Eur Respir J 2017 — European professional guideline; funding statement not verified.
- Wong C et al. Azithromycin for prevention of exacerbations in non-CF bronchiectasis (EMBRACE), Lancet 2012 — randomised trial; funded by the Health Research Council of New Zealand and the Auckland District Health Board Charitable Trust.
- Serisier DJ et al. Effect of long-term, low-dose erythromycin on pulmonary exacerbations (BLESS), JAMA 2013 — randomised trial; funder per follow-up paper is the Mater Adult Respiratory Research Trust Fund.
- Rogers GB et al. Long-term macrolide treatment and respiratory microbiota in non-CF bronchiectasis (BLESS analysis), Lancet Respir Med 2014 — trial analysis; Mater Adult Respiratory Research Trust Fund.
- Lee AL et al. Airway clearance techniques for bronchiectasis, Cochrane Database Syst Rev 2015 — systematic review; funding statements conflict.
- Lee AL et al. Positive expiratory pressure therapy versus other airway clearance techniques, Cochrane 2017 — systematic review; funding not verified.
- Lee AL et al. Pulmonary rehabilitation in non-CF bronchiectasis: a systematic review, Arch Phys Med Rehabil 2017 — systematic review; funding not verified.
- Lee AL et al. Exercise training for bronchiectasis, Cochrane 2021 — systematic review; funding not verified.
- Chalmers JD et al. Phase 3 trial of the DPP-1 inhibitor brensocatib in bronchiectasis (ASPEN), NEJM 2025 — funded by Insmed.
- European Medicines Agency: Brinsupri (brensocatib) EPAR — EU regulator; MAH Insmed Netherlands B.V.; authorisation 18 November 2025 (CHMP opinion adopted 16 October 2025).
- Insmed: FDA approves Brinsupri (press release, 12 August 2025) — maker's announcement; headquarters and AstraZeneca licence reference.
- De Soyza A et al. RESPIRE 1, Eur Respir J 2018 — Bayer-sponsored phase 3 trial.
- Aksamit T et al. RESPIRE 2, Eur Respir J 2018 — Bayer-sponsored phase 3 trial.
- HCPLive: FDA advisory committee advises against ciprofloxacin DPI (2017) — trade press; vote counts.
- Haworth CS et al. Inhaled colistimethate sodium in bronchiectasis (PROMIS 1 and 2), Lancet Respir Med 2024 — phase 3 trials with Zambon SpA-affiliated authors.
- McCullough B et al. Mucoactive agents in bronchiectasis: systematic review and meta-analysis, Eur Respir Rev 2026 — funding not verified.
- Oscullo G et al. Optimal dose of N-acetylcysteine (RIBRON registry), J Thorac Dis 2025 — observational registry; funding not verified.
- Moriki D et al. Vitamin D deficiency and severity of non-CF bronchiectasis, Expert Rev Respir Med 2025 — systematic review; funding not verified.
- Doña E et al. Pulmonary rehabilitation with or without nutritional supplementation in bronchiectasis, J Cardiopulm Rehabil Prev 2018 — 30-patient randomised trial; funding not verified.
- ClinicalTrials.gov: NCT02106832 (inhaled ciprofloxacin DPI, non-CF bronchiectasis) — trial registry; sponsor field not opened.
- Bayer AG (Wikipedia) — encyclopedia entry; used for headquarters only. — commercial data provider; used for headquarters only.
Educational research reviewed 9 October 2026. This article is not medical advice; talk to a qualified clinician or pharmacist before starting, stopping or combining treatments.
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