The management of chronic obstructive pulmonary disease (COPD) exacerbations remains largely symptom-based, as guideline recommendations prioritize clinical features—such as sputum purulence, dyspnoea, and the need for ventilatory support—to guide antibiotic use, while systemic corticosteroids are broadly prescribed based on exacerbation severity 1. This paradigm persists despite evidence of heterogeneity in exacerbations 2. This mismatch between underlying mechanisms and treatment exposes patients to unnecessary therapies, increasing the risk of antimicrobial resistance and cumulative corticosteroid toxicity, while also contributing to healthcare costs 3. In a recent publication in Respirology, Wong and colleagues report a prospective observational study evaluating the BioFire FilmArray Pneumonia plus Panel (FAPP) in 74 adults hospitalized with COPD exacerbations 4. Spontaneous sputum obtained on admission was analysed using FAPP, which targets 27 respiratory pathogens (15 common bacteria, 3 atypical bacteria, and 9 viruses), together with standard-of-care testing (culture and nasopharyngeal viral PCR). Patients with radiographic pneumonia were excluded. The authors found that FAPP increased overall pathogen detection by 42% (36% vs. 78%; p 40 mg/L or 20–40 mg/L if purulent sputum) performed only modestly better (59%). Sputum culture performed even less well, with a sensitivity of 32% for the same bacteria that FAPP detected. Building on prior work describing the heterogeneity of exacerbations 5, 6, these were classified by integrating FAPP results with blood eosinophil count (BEC) measured before systemic corticosteroid administration into viral (FAPP detection with or without bacterial co-detection), bacterial-predominant (high-abundance bacterial detection by FAPP, without viral detection), eosinophilic (BEC ≥ 300 cells/μL, without viral detection and no or low-abundance bacterial detection), and unclassified phenotypes. The bacterial-predominant phenotype (37% of exacerbations) was associated with higher blood neutrophil counts and CRP levels, and a greater proportion of moderate-to-severe exacerbations according to the Rome criteria. Length of stay did not differ significantly across phenotypes, although 180-day treatment failure was lower in the eosinophilic than in the unclassified phenotype. These findings support biological stratification of exacerbations but should be interpreted cautiously when considering prognostic conclusions. Although all patients received antibiotics according to local practice, FAPP results were associated with antibiotic modification in 12% (9 patients): de-escalation or cessation in 3, and escalation in 6 after identification of Pseudomonas aeruginosa. Patients with no or low-abundance bacterial detection were more likely to receive shorter antibiotic courses than those with high-abundance detection. Although these findings suggest that rapid molecular diagnostics could influence antibiotic stewardship, the low frequency of antibiotic modifications indicates that more evidence is required to increase prescribers' confidence in de-escalating antibiotherapy. Several limitations deserve emphasis. First, this was a single-centre observational study with a modest sample size, and it was not powered to determine whether FAPP-guided management improves antibiotic use or outcomes across phenotypes. Second, the population was restricted to hospitalized patients able to produce sputum, limiting generalizability to milder outpatient exacerbations. Third, pathogens not included in the panel remained undetected, as illustrated by cultured Corynebacterium, Stenotrophomonas, and Streptococcus species. Finally, in the unclassified phenotype (24% of exacerbations), non-infectious contributors warrant further study. The study extends the findings of two previous investigations. In a secondary analysis of the ResPOC randomized controlled trial, Brendish et al. found that rapid syndromic molecular PCR in adults hospitalized with asthma or COPD exacerbations did not reduce initial antibiotic prescribing but enabled earlier discontinuation when a viral aetiology was identified 7. Similarly, a prospective pilot study of critically ill patients with severe COPD exacerbations demonstrated that adding respiratory multiplex PCR to conventional microbiological testing increased the microbiological yield to 50% with shorter antibiotic duration 8. More importantly, Wong et al. shift attention to the more clinically relevant question of whether exacerbations can be biologically categorized using integrated microbial and host information, a concept that has recently been emphasized in the context of asthma attacks (Figure 1) 9. The next step is clear. As demonstrated by trials of eosinophil-guided corticosteroid therapy in COPD exacerbations 10, 11, interventional studies are now needed to determine whether treatment decisions informed by combined rapid molecular diagnostics and host biomarkers can improve antibiotic use and patient outcomes compared with current symptom-based approaches. This strategy is supported by a recent proof-of-concept trial showing that a diagnostic stewardship intervention that interpreted viral testing and serum procalcitonin results decreased antibiotic use among hospitalized adults with community-acquired pneumonia 12. This work was supported by the Association Pulmonaire du Québec (APQ)'s Research Chair in respiratory medicine and the Fonds de Recherche du Québec—Santé (FRQS). The views expressed are those of the authors and not necessarily those of the sponsors. This work was supported by Fonds de Recherche du Québec-Santé; Association Pulmonaire du Québec. Carlos Andrés Celis-Preciado reports that he has received an education scholarship from the Fonds de Recherche du Québec, within the current work. Outside the current work, he has received scholarships from the Université de Sherbrooke and the Canadian Asthma Allergy and Immunology Foundation, as well as speaker honoraria from AstraZeneca, GlaxoSmithKline, and Sanofi-Regeneron. Simon Couillard reports the following: he has received non-restricted research grants from the NIHR Oxford BRC, the Quebec Respiratory Health Research Network, the Association Pulmonaire du Québec, the Academy of Medical Sciences, AstraZeneca, bioMérieux, Circassia Niox Group, and Sanofi-Genyme-Regeneron; he is the holder of the Association Pulmonaire du Québec's Research Chair in Respiratory medicine and is a Clinical research scholar of the Fonds de recherche du Québec; he received speaker honoraria from AstraZeneca, GlaxoSmithKline, Sanofi-Regeneron, Circassia Niox Group and Valeo Pharma; he received consultancy fees for FirstThought, Apogee Therapeutics, Connect Biopharma, Upstream Bio, AstraZeneca, GlaxoSmithKline, Sanofi-Regeneron, Access Biotechnology and Access Industries; he has received sponsorship to attend/speak at international scientific meetings by/for AstraZeneca and Sanofi-Regeneron. He is an advisory board member and holds stock options in Biometry Inc., a company that is developing a FeNO device (myBiometry); he is a co-inventor of the patent filed as ‘Method for alleviating dyspnea with neuromodulation’. He advised the Institut national d'excellence en santé et services sociaux (INESSS) on an update to the asthma general practice information booklet for general practitioners, as well as on therapeutic indications for Enerzair, and is a member of the asthma steering committee of the Canadian Thoracic Society.
Celis-Preciado et al. (Tue,) studied this question.