Insights into the clinical outcomes of bronchiectasis

To the Editor:

We read with great interest the article by Dhar et al. [1] which, based on data from EMBARC/Respiratory Research Network, thoroughly investigated the clinical outcomes of bronchiectasis in India. The authors have identified important predictors of poor clinical outcomes, some of which represented critical therapeutic targets because these may represent treatable or preventable traits. For instance, identification of the frequent exacerbators who would benefit from intensified airway clearance, macrolide therapy and pulmonary rehabilitation may result in an improved clinical outcome. Their work may also shed light on refining the management strategy for patients with bronchiectasis in many low- and middle-income countries globally. In spite of these promising findings, there are some concerns that merit further discussion.

First, because of the real-world registry study design, in which the inclusion of clinical data among bronchiectasis patients when clinically stable was not mandatory, the final analysis (particularly the sputum microbiology) might have been confounded by the different clinical statuses (e.g. clinical stability versus exacerbation). Patients who have been recruited during an exacerbation of bronchiectasis would be more likely to isolate potentially pathogenic micro-organisms according to the sputum culture, especially among those who were hospitalised due to severe exacerbation with higher risks of being infected with nosocomial pathogens, compared with those recruited when clinically stable [2]. Apart from Pseudomonas aeruginosa (∼11%), the relatively high prevalence of Klebsiella pneumoniae (∼8%) among all potentially pathogenic micro-organisms might have resulted from the high rate of sputum samples obtained from hospitalised patients (36.6–38.8% required at least one hospitalisation due to severe exacerbations). Provision of the sensitivity analysis that only included the clinical data when clinically stable may help further validate the overall findings. Furthermore, the positive rate of potentially pathogenic micro-organisms appeared markedly lower as compared with that in Europe, the USA, Australia and mainland China [3]. Again, it was unclear whether this could be attributable to the inclusion of sputum microbiology data upon hospitalisation, prior to which antibiotics could have already been prescribed.

Second, the analysis pertaining to the annual lung function decline might have been confounded by the inclusion of patients with co-existing COPD or asthma, who were more likely to have a rapid decline in forced expiratory volume in 1 s (FEV₁) compared with the patients who had bronchiectasis alone. According to the supplementary results section, patients with co-existing COPD or asthma were more frequently prescribed inhaled corticosteroids (ICS) and bronchodilators, and would benefit more from treatments such as bronchodilators in terms of FEV₁ improvement [4, 5]. Therefore, the FEV₁ might have been underestimated at baseline among patients with co-existing COPD or asthma, as might have been the decline in FEV₁ during longitudinal follow-up. A sensitivity analysis which included patients with bronchiectasis alone when clinically stable would contribute to a more objective reflection of the annual lung function decline. Perhaps the incorporation of other important spirometry parameters, such as forced vital capacity (FVC) and the ratio of FEV₁ and FVC, is also needed.

Third, co-existing COPD conferred a substantial impact on clinical outcomes such as the rate of mortality, hospitalisation and exacerbation of bronchiectasis in the study. Although this finding has important clinical implications, the definition of COPD should be better clarified. According to a literature report [6], in patients with bronchiectasis there was a highly variable prevalence of COPD, which ranged from 8.8% to 32%, due to the lack of expert consensus. The ROSE criteria [7], proposed in 2021, consisted of the radiological diagnosis of bronchiectasis, airflow obstruction detected by spirometry, respiratory symptoms and exposure to cigarette smoking or other toxic materials (biomass fuel, industrial fumes, etc.). According to the ROSE criteria, cigarette smoking, biomass fuel combustion or industrial noxious material exposures could be considered as eligible exposure criteria for confirming the diagnosis of COPD. In India, the exposure to biomass fuel combustion and industrial toxic fumes has been fairly common and might have played an important role in the development and progression of COPD [8]. We would appreciate if the authors could clarify the following points: Did the study adopt the ROSE criteria to define COPD in patients with bronchiectasis? How did the investigators perform qualitative and quantitative analysis of exposure to biomass fuel combustion and industrial toxic materials? Could recurrent airway infections (e.g. those occurring at childhood) be considered another, as yet to be defined, risk factor of COPD, which is in line with the statements of the Global Initiative for Chronic Obstructive Lung Disease guidelines [9]?

Finally, the use of ICS accounted for up to 53.8% of patients with bronchiectasis without co-existing asthma or COPD. Around 20% of patients with bronchiectasis reportedly had eosinophilic inflammation, as defined by the elevated sputum or blood eosinophil count in the European multinational cohorts [10]. However, no data in direct support of the eosinophil count of blood or sputum were demonstrated in this study, which might help predict the response to ICS treatment [11]. Clarification of the spectrum of eosinophil count in the study population and the reason that justified the use of ICS would be appreciated.

In summary, we further suggest a subgroup analysis based on the disease status and co-existing airway diseases at baseline, provision of the further details regarding the definition of COPD and the eosinophil counts in the study population. This will contribute to our better understanding of the clinical characteristics and outcomes in adults with bronchiectasis who are residing in the rest of the world.

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