Discussion
AECOPD is often associated with infectious agents, including bacteria, virus and fungi. A previous study was conducted in critically ill patients with isolation of Aspergillus spp. from the respiratory tract, with mortality rates of 50% in the colonization group and 80% in the invasive infection group after 9 months of follow-up.[13] Therefore, clinicians usually focus on infection when a positive Aspergillus spp. culture is obtained from the LRT. However, the significance of a more frequent clinical phenomenon, Aspergillus spp. colonization, has yet to be clarified. In this research, a pair-matched observational study was conducted to investigate the differences in the clinical manifestations and short-term outcomes between COPD patients with and without Aspergillus colonization in LRT.
Cigarette smoking, one of the major risk factors for the development of COPD, induces structural and functional changes in airway epithelium in vitro and in vivo.[14–16] In our study, the number of patients with a history of smoking was higher in the Aspergillus colonization group than in the control group, which indicated that smoking is a potential risk for Aspergillus colonization. Cigarette smoking and repeated airway inflammation could alter the structure and function of lung and injure a profound effect on the host defense against invading pathogens and particulates, thus impairing the airway epithelium[17,18] and mad COPD patients more susceptible to Aspergillus colonization. Meanwhile, most patients in the Aspergillus colonization group received higher doses of ICS during stable stage treatment, in contrast to the control group. Our findings were consistent with a previous study that suggested that high-dose corticosteroids use was a risk for Aspergillus colonization or positive Aspergillus culture.[19,20]
In our study, Aspergillus-colonized patients presented with wheezing and wheezing rales in the acute exacerbation period. More than half of the patients received systemic corticosteroids and/or ICS. The percentage of corticosteroid usage in the two groups was similar, but in the Aspergillus colonization group, patients received higher doses of ICS. This finding suggested that Aspergillus colonization contributed to an increased severity of exacerbations in COPD patients. These phenomena suggested that high-dose ICS treatment was related to Aspergillus colonization and induced similar clinical manifestations to allergic reactions due to Aspergillus colonization. A previous study on the mechanism involved in Aspergillus-related allergic reactions was based on the Aspergillus hyphae and involved antigen-triggered mast cell degranulation and release of histamine and inflammatory factors.[21–24] These data showed that Aspergillus colonization may aggravate airway hyper-responsiveness and worsen airway inflammation and bronchoconstriction. But no cohort study of patients with repeated cultures of Aspergillus have been done in COPD patients, it is unclear whether fungal colonization contributes to lower lung function or is a marker of more severe lung disease and aggressive therapy. In our study, patients with Aspergillus colonization had a longer time to be stable and a longer duration of hospitalization, which indicated that Aspergillus colonization was related with clinical manifestations and short-term outcomes of COPD patients.
After demonstrating the significance of Aspergillus colonization in the airways of COPD patients, we highlighted an essential clinical treatment dilemma: whether to eliminate colonization with anti-fungal therapy or to stabilize wheezing with continuous ICS. Because Aspergillus colonization is clinically significant, the treatment strategy should aim to eliminate colonization. However, a previous study showed that the removal of Aspergillus colonization did not improve lung function in a long-term observation; this finding cast doubt on the value of anti-fungal therapy. Due to the lack of research on the effect of Aspergillus colonization on AECOPD and stable COPD, challenges remain for clinical decision making. The relationship between colonization and invasive infection is unclear. Whether increasing the fungal load of colonization in the airway could result in invasive pulmonary mycosis has not been determined. Aspergillus colonization induces sustainable inflammation in the airway, which leads to worsening lung function. Meanwhile, poorer lung function is significantly associated with Aspergillus colonization. However, in clinical practice, ICS are commonly used to control wheezing and airway inflammation, which could also enhance the risk of Aspergillus colonization in the airway. It is concerning that once Aspergillus colonization in the airways of COPD patients is identified, a vicious cycle is established. Unfortunately, no accurate timing, biomarker, or scoring system exists that could determine the optimal antifungal therapy.
There were some limitations to this study: (1) we could not determine the timing of Aspergillus colonization: the acute exacerbation or stable stage; (2) we only conducted this retrospective study without a long-term observation from the beginning of Aspergillus colonization to its causing symptomatic clinical manifestation. Thus, whether Aspergillus colonization could affect the clinical process was still unknown, including lung function decline, the frequency of acute exacerbation, and daily symptoms; and (3) we performed this research in a single center and recruited a small sample of patients.
BMC Pulm Med. 2018;18(55) © 2018 BioMed Central, Ltd.
