Nationwide survey of refractory asthma with bronchiectasis by inflammatory subtypes

Abstract

Rationale: Bronchiectasis and bronchiolitis are differential diagnoses of asthma; moreover, they are factors associated with worse asthma control.

Objective: We determined clinical courses of bronchiectasis/bronchiolitis-complicated asthma by inflammatory subtypes as well as factors affecting them.

Methods: We conducted a survey of refractory asthma with non-cystic fibrosis bronchiectasis/bronchiolitis in Japan. Cases were classified into three groups, based on the latest fractional exhaled NO (FeNO) level (32 ppb for the threshold) and blood eosinophil counts (320/µL for the threshold): high (type 2-high) or low (type 2-low) FeNO and eosinophil and high FeNO or eosinophil (type 2-intermediate). Clinical courses in groups and factors affecting them were analysed.

Results: In total, 216 cases from 81 facilities were reported, and 142 were stratified: 34, 40 and 68 into the type 2-high, -intermediate and -low groups, respectively. The frequency of bronchopneumonia and exacerbations requiring antibiotics and gram-negative bacteria detection rates were highest in the type 2-low group. Eighty-seven cases had paired latest and oldest available data of FeNO and eosinophil counts; they were analysed for inflammatory transition patterns. Among former type 2-high and -intermediate groups, 32% had recently transitioned to the -low group, to which relatively low FeNO in the past and oral corticosteroid use contributed. Lastly, in cases treated with moderate to high doses of inhaled corticosteroids, the frequencies of exacerbations requiring antibiotics were found to be higher in cases with more severe airway lesions and lower FeNO.

Conclusions: Bronchiectasis/bronchiolitis-complicated refractory asthma is heterogeneous. In patients with sputum symptoms and low FeNO, airway colonisation of pathogenic bacteria and infectious episodes are common; thus, corticosteroids should be carefully used.

Keywords: Asthma; Blood eosinophil counts; Bronchiectasis; Bronchiolitis; FeNO.

Fig. 1

Receiver operating characteristic (ROC) curve of the current levels of A exhaled nitric oxide (FeNO) and B blood eosinophil counts that reflected the presence of bronchopneumonia in the last 5 years. C definition of inflammatory type stratified by FeNO and blood eosinophil counts

Fig. 2

Frequencies of A exacerbation requiring systemic corticosteroids (p = 0.30 among the three inflammatory groups by the Kruskal–Wallis test), B exacerbation requiring antibiotics (p = 0.005 among the three groups, p = 0.007 for type 2-low vs type 2-intermedate), C bronchopneumonia (p = 0.01 among the three groups, p = 0.03 for type 2-low vs type 2-high), and D hospitalisation (p = 0.04 among the three groups, p = 0.04 for type 2-low vs type 2-high), in the last 2 years. Boxes and bars indicate upper, lower, and median quartiles

Fig. 3

Transition patterns of inflammatory types in cases followed for 2 years or more (n = 87). Red flow indicates former type 2-high group (n = 31); yellow flow, former type 2-intermediate group (n = 34); blue flow, former type 2-low inflammatory group (n = 22)

Fig. 4

Frequencies of A exacerbation requiring systemic corticosteroids (p = 0.51 among the three transition patterns by the Kruskal–Wallis test), B exacerbation requiring antibiotics (p = 0.02 among the three patterns and p = 0.06 for low-to-low vs high’-to-high’), C bronchopneumonia (p = 0.03 among the three patterns and p = 0.02 for low-to-low vs high’-to-high’), and D hospitalisation (p = 0.08), in the last 2 years. Boxes and bars indicate upper, lower, and median quartiles

Fig. 5

Frequency of exacerbation requiring antibiotics in the last 2 years in cases treated with moderate to high doses of inhaled corticosteroids according to the current degree of A bronchiectasis, i.e., modified Reiff (mReiff) score, B bronchiolitis, and C FeNO level. Boxes and bars indicate upper, lower, and median quartiles