Exacerbations of BE and extensive disease significantly increase the risk of a poor QoL. In particular, recurrent yearly exacerbations were found to increase the risk of poor QoL by five-fold. In this study, both effort tolerance (mMRC) and disease severity (BSI) were negatively correlated with physical domain which is formed of the questions assessing physical capability associated with BE in the quality of life questionnaire. However, in clinical practice, the mMRC dyspnoea score is simpler and easier to use than the BSI . The BSI is a complex index that requires lung function parameters, radiological features, exacerbation, hospitalisation and microbiological findings to calculate the score . On the other hand, the mMRC is a four-point grading system for self-reported dyspnoea in everyday life . Although BSI has been shown to accurately predict hospitalisations, exacerbations and mortality of non-cystic fibrosis BE patients, it is more challenging to use and is therefore better suited to scientific purposes than clinical practice . The mMRC and QoL scores have been used to demonstrate the effect of new treatment options for BE .
Health (median score of 41.7), vitality (median score of 50) and respiration (median score of 57) were the domains with the poorest self-reported results in the QoL questionnaire. It has previously been demonstrated that these scores are stable if measured during a stable phase of BE, and that they can be used to differentiate between mild, moderate and severe BE patients . However, in a 2-year follow-up study of 19 BE patients by Magge et al. , physical functioning, role functioning and health perceptions were shown to improve with treatment at a specialised care center. These results are similar to ours for health perceptions (mean score 41.4) and vitality (mean score 45.6), but not for respiration (mean score 62.5).
Our finding of significantly reduced vitality score and mMRC score correlating with the physical domain is in accordance with previous studies that show reduced physical activity of BE patients compared to gender- and age-matched individuals without BE . In our study, the mMRC scale offered practical information on the physical functioning of patients.
The identification of patients at high risk for exacerbations may be valuable to guide clinical decision making with regard to factors such as the frequency and intensity of follow-up and the use of long-term antibiotic therapy. The scoring systems used to assess the severity of BE gave different results for severe disease, as 34.1% of patients were estimated to have severe BE with BSI scoring while only 11.6% of patients were classified as having severe BE with FACED grading. Similar results were described by Visser et al.  in their Australian cohort, as 58% of the cohort had severe disease according to the BSI, whereas 17% had FACED-defined severe disease. Our results are also in good agreement with the observations of a large multidimensional severity assessment conducted by McDonnell et al. , who reported that the BSI is superior to FACED in predicting overall clinically important disease‐related outcomes. The BSI includes parameters for previous hospital admissions and the number of exacerbations in the previous year, whereas FACED includes a parameter for age . Although, they have been shown to have similar capacities for predicting long-term mortality, in our cross-sectional study more patients were classified as having severe BE by BSI scoring than by FACED scoring . This highlights the importance of patients’ previous history of exacerbations.
When phenotyping different BE patients, BE caused by connective tissue disease has been associated with a poor prognosis and rapid disease progression . Immunodeficiency, COPD and allergic bronchopulmonary aspergillosis (ABPA) have been associated with recurrent exacerbations . In the current study, we found poor QoL regardless of background aetiology in BE patients with exacerbations, and especially in those with frequent exacerbations. Furthermore, colonisation of the bronchi with proteobacteria Pseudomonas aeruginosa or Haemophilus influenza is associated with chronic neutrophilic inflammation and exacerbations .
Anti-IL5 and anti-IL5R therapies have been suggested as an add-on therapy for BE . A study that included BE patients with severe asthma, ABPA, idiopathic BE, combined asthma/COPD, EGPA and PCD reported an increase in FEV1 and QoL, as well as a reduction in exacerbations and mMRC scores .
Terpstra et al.  reported significantly worse QoL in BE patients with COPD than in other BE patients. In their study population of 200 BE patients (aged 69.5 years), the mean number of exacerbations was one per year, with zero hospitalisations and a mean mMRC score of 2.68 (SD 1.09). The mean mMRC score in our population was 2.0, but there was a median of two exacerbations per year. Previously, BSI was proposed as a tool for scoring the severity of BE and FACED as a tool for predicting mortality .
The limitations of the current study include the relatively small size of the cohort and the cross-sectional setting of the QoL analysis. The small sample size is due to the limited number of subjects recruited in the original study. A strength of the study is that there were no missing data for QoL questions and mMRC scale results.
An earlier study found that previous severe exacerbations (OR 2.6) or an exacerbation in the past 12 months (OR from 1.38 to 3.90) is predictive of future exacerbations . We found that exacerbations (OR 1.7), frequent yearly exacerbations (OR 4.9) or extensive disease (OR 3.7) increased the risk of poor QoL (Table 4) in the analysis adjusted for age and gender.
Similarly, diminished lung function (analysed as FEV1) has been reported to be a risk factor for future exacerbations . Although those patients with poor QoL had reduced lung function (FEV1 84%) than the others (FEV1 89%), we did not identify lung function as a risk factor for future exacerbations . This may be due to the relatively small study population, together with the relatively well-preserved lung function in our study population.
When estimating the effect of exacerbations and frequent exacerbations on poor QoL, it should be noted that in the study by Brill et al. , the median duration of an exacerbation was 16 days, and 16% of patients had at least one exacerbation with a duration of more than 35 days. Thus, the association of poor QoL with exacerbations is crucial. Despite best practice guidelines, exacerbation will occur at some point, so the secondary treatment goals are to prevent deterioration of lung function and BE radiologic findings and to maintain a good QoL. This should be considered when assessing which BE patients benefit from follow-up at a specialised care center . The current guidelines focus on recommending special care for those with three or more yearly exacerbations and for those on long-term antimicrobial therapy .