Induced sputum eosinophils and neutrophils and bronchiectasis severity in allergic bronchopulmonary aspergillosis

Abstract

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to the fungus Aspergillus fumigatus that may progress to bronchiectasis. The aim of the present study was to characterize airway inflammation in patients with clinically stable ABPA and asthma, and to correlate this with bronchiectasis severity.Subjects with ABPA and central bronchiectasis (ABPA-CB; n=16) and ABPA with serological evidence alone (ABPA-S; n=10) were studied. Comparison groups were A. fumigatus-sensitized asthma (n=19), non-A. fumigatus-sensitized asthma (n=15) and healthy controls (n=8). Hypertonic saline challenge, sputum induction and highresolution computed tomography (HRCT) of the chest were performed.Sputum eosinophil numbers were markedly elevated in ABPA-CB (median 8.4%) compared to ABPA-S (2.4%), A. fumigatus-sensitized asthma (1.8%), asthma (1.8%) and controls (0.3%) (p<0.01); sputum eosinophil cationic protein levels were higher in ABPA-CB (median 13,706 ng . mL -1 ), compared to ABPA-S (1,633.5 ng . mL -1 ), A. fumigatus-sensitized asthma (1,550.7 ng . mL -1 ), asthma (309.2 ng . mL -1 ), and controls (110 ng . mL -1 ) (p<0.001). ABPA-CB also showed increased sputum neutrophil number (median 60.3%) compared to the other groups (controls 29.3%) (p=0.01). The severity of bronchiectasis on HRCT correlated with sputum neutrophil (r=0.6) and eosinophil number (r=0.5) but not serum immunoglobulin-E levels.In conclusion, clinically stable allergic bronchopulmonary aspergillosis with bronchiectasis is characterized by an intense heterogenous inflammatory infiltrate consisting of eosinophils and neutrophils, which correlates closely with the severity of bronchiectasis on high-resolution computed tomography. Sputum analysis may be useful in monitoring the course of allergic bronchopulmonary aspergillosis.

TNF-α from inflammatory dendritic cells (DCs) regulates lung IL-17A/IL-5 levels and neutrophilia versus eosinophilia during persistent fungal infection

“…1B. The inflammatory pattern in BALB/c mice was reminiscent of the neutrophil-rich inflammation in severe asthma and ABPA (6,20), which persuaded us to investigate the underlying mechanisms.…”

“…Aspergillus fumigatus, which induces allergic bronchopulmonary aspergillosis (ABPA) in 25% of severe asthmatics, is one of the most common fungi involved (1,2). Neutrophilic airway inflammation is now well recognized as being a feature of severe asthma (3)(4)(5) and ABPA (6,7). During acute infection, neutrophils are crucial for antifungal defense (8,9), and lack of neutrophils is the best appreciated risk factor for invasive aspergillosis (10).…”

“…During acute infection, neutrophils are crucial for antifungal defense (8,9), and lack of neutrophils is the best appreciated risk factor for invasive aspergillosis (10). However, uncontrolled neutrophil infiltration in Aspergillus-induced allergic disorders positively correlates with tissue damage and loss of lung function (6,11). Because the control of neutrophils is highly desirable in these diseases, there is considerable interest in understanding the mechanisms that promote and perpetuate pulmonary neutrophilia (12).…”

Induced sputum IL-8 gene expression, neutrophil influx and MMP-9 in allergic bronchopulmonary aspergillosis

“…Adults with stable asthma were recruited from the respiratory clinic of the John Hunter Hospital and classified as ABPA (n=29) or non-A. fumigatus-sensitised asthma (n=9), as previously described [5]. Twenty-one healthy controls were recruited by advertisement.…”

“…ABPA is typically characterised by sputum eosinophilia, however, lung tissue also shows a mixed inflammatory infiltrate with eosinophils and neutrophils [4]. Recently the current authors reported that sputum neutrophils were increased in ABPA and correlated with the severity of bronchiectasis [5].…”