Highly Symptomatic Patients With Bronchiectasis Face Increased Exacerbation Risk

Highly symptomatic patients with bronchiectasis are at an increased risk of exacerbation, regardless of previous exacerbation history or disease severity, according to a study published in The Lancet Respiratory Medicine.¹

Although prior research has linked highly symptomatic patients with bronchiectasis to an increased exacerbation risk, international guidelines do not currently recommend preventive treatments for these patients. In contrast, for other airway diseases, such as asthma and chronic obstructive pulmonary disease, guidelines recommend that symptomatic patients receive anti-inflammatory treatment to prevent future exacerbations, as early intervention is considered more effective than waiting for worsening episodes.²

Patients with bronchiectasis who are highly symptomatic face an increased risk of future exacerbations, suggesting symptoms should guide preventive treatment strategies. | Image Credit: Jo Panuwat D - stock.adobe.com

To address this gap, the researchers investigated the relationship between symptoms and future exacerbations among patients with bronchiectasis.¹ They also conducted a post hoc analysis of 3 randomized controlled trials (RCTs) using long-term macrolides to determine whether the number-needed-to-treat to prevent future exacerbations depends both on previous exacerbations and symptoms.

The researchers analyzed eligible patients included in the European Bronchiectasis Registry (EMBARC), an observational study of patients with bronchiectasis across 30 countries worldwide. They evaluated their baseline symptoms with the Quality-of-Life Bronchiectasis Questionnaire Respiratory Symptoms Scale (QoL-B-RSS), as well as at 1-year follow-up, and related them to their future exacerbation risk.

Subsequently, the researchers conducted a post hoc pooled analysis of 341 participants with bronchiectasis across 3 RCTs of macrolides: BLESS, BAT, and EMBRACE.^3,4,5 Using a negative binomial regression model, they aimed to determine whether baseline symptoms were associated with long-term macrolide treatment response.¹

Of the 19,324 patients included in the EMBARC registry, 9466 (49.0%) had QoL-B assessment scores at baseline and 1-year follow-up exacerbation data. The median age of the included patients was 68 (IQR, 58-74), and most were female (n = 5763; 60.9%). Also, the median Bronchiectasis Severity Index score was 7 (range, 4-10), with higher scores indicating more severe disease.

Additionally, at baseline, the median (IQR) QoL-B-RSS was 63.0 (44.4-77.8). The researchers divided patients into quartiles (Q) to better understand the QoL-B-RSS distribution, which ranges from 0 to 100, with lower scores indicating more severe symptoms. There were 2277 (24.1%) patients below the Q1 symptoms score, 2446 (25.8%) between Q1 and the median score, 2306 (24.4%) between the median score and Q3, and 2436 (25.7%) patients above Q3.

Preliminary univariate analyses that evaluated the relationship among exacerbations during follow-up determined a significantly increased risk in patients with a higher number of exacerbations in the previous year (P < .0001) and lower QoL-B-RSS (P < .0001).

After adjusting for Bronchiectasis Severity Index scores and previous exacerbations, those with an approximately average QoL-B-RSS (60-70) had an estimated future exacerbation rate ratio (RR) of 1.30 (95% CI, 1.12-1.50) compared with patients with QoL-B-RSS of 90 to 100, which indicated little to no symptoms. Therefore, previous exacerbations (RR for every additional exacerbation, 1.11; 95% CI, 1.10-1.12; P < .0001) and symptoms (RR for every 10 points lower QoL-B-RSS, 1.10; 95% CI, 1.09-1.11; P < .0001) were identified as strong independent risk factors for future exacerbations.

The expected number of exacerbations in 1 year was similar between patients with 3 previous exacerbations and average symptom scores (1.58 exacerbations per year; 95% CI, 1.48-1.69) and patients with no previous exacerbations but worse symptom scores (1.55 exacerbations per year; 95% CI, 1.41-1.70), which supported the researchers’ hypothesis that symptoms independently predict future exacerbations.

This same pattern was observed in the post hoc analysis, both in the macrolide and placebo groups. The number-needed-to-treat to prevent exacerbations with long-term macrolide therapy was also comparable: 1.45 (95% CI, 1.08-2.24) for patients selected based on frequent exacerbations and 1.43 (95% CI, 1.06-2.18) for those with few previous exacerbations but high symptom scores.

The researchers acknowledged their study’s limitations, one being that the quality-of-life scores are based on questionnaires that may be subject to response error or recall bias. Still, they expressed confidence in their findings and their relevance for guiding future bronchiectasis treatment strategies.

“These findings raise the possibility that symptoms should be included in future bronchiectasis treatment algorithms, as is the case for other airway diseases such as asthma and chronic obstructive pulmonary disease,” the authors wrote.

References

1. Sibila O, Stobo J, Perea L, et al. Symptoms, risk of future exacerbations, and response to long-term macrolide treatment in bronchiectasis: an observational study. Lancet Respir Med. Published online August 27, 2025. doi:10.1016/S2213-2600(25)00160-2
2. Pavord ID, Beasley R, Agusti A, et al. After asthma: redefining airways diseases. Lancet. 2018;391(10118):350-400. doi:10.1016/S0140-6736(17)30879-6
3. Serisier DJ, Martin ML, McGuckin MA, et al. Effect of long-term, low-dose erythromycin on pulmonary exacerbations among patients with non–cystic fibrosis bronchiectasis: the BLESS randomized controlled trial. JAMA. 2013;309(12):1260–1267. doi:10.1001/jama.2013.2290
4. Altenburg J, de Graaff CS, Stienstra Y, et al. Effect of azithromycin maintenance treatment on infectious exacerbations among patients with non–cystic fibrosis bronchiectasis: the BAT randomized controlled trial. JAMA. 2013;309(12):1251–1259. doi:10.1001/jama.2013.1937
5. Wong C, Jayaram L, Karalus N, et al. Azithromycin for prevention of exacerbations in non-cystic fibrosis bronchiectasis (EMBRACE): a randomised, double-blind, placebo-controlled trial. Lancet. 2012;380(9842):660-667. doi:10.1016/S0140-6736(12)60953-2