Sensitization to <em>Aspergillus fumigatus</em> as a risk factor for bronchiectasis in COPD

Abstract

BackgroundBronchiectasis–chronic obstructive pulmonary disease (COPD) overlap presents a possible clinical phenotype of COPD, but it is unclear why it develops in a subset of patients. We hypothesized that sensitization to Aspergillus fumigatus (A fum) is associated with bronchiectasis in COPD and occurs more frequently in vitamin D-deficient patients.MethodsThis observational study investigated sensitization to A fum in an outpatient clinical cohort of 300 COPD patients and 50 (ex-) smoking controls. Total IgE, A fum-specific IgE against the crude extract and against the recombinant antigens and A fum IgG were measured using ImmunoCAP fluoroenzyme immunoassay. Vitamin D was measured by radioimmunoassay, and computed tomography images of the lungs were scored using the modified Reiff score.ResultsSensitization to A fum occurred in 18% of COPD patients compared to 4% of controls (P=0.0110). In all, 31 COPD patients (10%) were sensitized to the crude extract and 24 patients (8%) had only IgE against recombinant antigens. A fum IgG levels were significantly higher in the COPD group (P=0.0473). Within COPD, A fum-sensitized patients were more often male (P=0.0293) and more often had bronchiectasis (P=0.0297). Pseudomonas aeruginosa and Serratia marcescens were more prevalent in historical sputum samples of A fum-sensitized COPD patients compared to A fum-non-sensitized COPD patients (P=0.0436). Vitamin D levels were comparable (P=0.2057). Multivariate analysis demonstrated that sensitization to recombinant f1 or f3 had a 2.8-fold increased risk for bronchiectasis (P=0.0030).ConclusionThese results highlight a potential role for sensitization to A fum in COPD-related bronchiectasis.

Aspergillus fumigatus Detection and Risk Factors in Patients with COPD–Bronchiectasis Overlap

“…Although this study does not allow us to attribute causality, our findings support the hypothesis that A. fumigatus contributes to the development and/or progression of bronchiectasis in COPD. We recently showed that the sensitization to specific A. fumigatus allergens was associated with the presence of bronchiectasis in COPD [ 5 ]. Next to an upregulation of the Th2 pathway, Aspergillus proteases may play an important role through enhanced mucus production and airway remodeling [ 24 , 25 ].…”

“…The combined presence of COPD and bronchiectasis in one patient is not rare. In cohorts of COPD patients, bronchiectasis has been described in 30–60% of patients [ 2 , 3 , 4 , 5 ], whereas bronchiectasis cohorts report COPD as the underlying cause in approximately 30% of patients [ 6 , 7 ].The recognition of an overlap is relevant, since these patients not only have a worse prognosis [ 2 , 7 , 8 ], but their diagnostic and therapeutic approach is also different.…”

The global impact of Aspergillus infection on COPD

“…The highest prevalence of sensitisation was in Europe based on studies located in Belgium and the United Kingdom (Table 3). In Belgium, Everaerts et al reported the highest prevalence of 18.3% sensitised to Aspergillus 24 . In contrast, Le Pape et al in Colombia found the lowest prevalence at 7.9% 27 .…”

“…We identified 122 articles via systematic search and an additional three were identified manually ( Fig S1). After 27 duplicates were removed, the remaining 98 were screened by title and abstract; of these papers, 86 were excluded and 12 full text articles were assessed for eligibility and 5 were deemed suitable for inclusion [23][24][25][26][27] . These five papers describe 1028 patients with COPD, 720 (70%) male with a mean age of 68.8 years ( Table 2).…”

Paediatric and adult bronchiectasis: Vaccination in prevention and management

“…Key bacteria associated with bronchiectasis in both stable and exacerbation states are H. influenzae, S. pneumoniae, Moraxella catarrhalis and Staphylococcus aureus, while P. aeruginosa is more commonly detected in adults and those with extensive disease . Detecting multiple respiratory bacterial strains is common amongst patients of all ages, whilst Aspergillus and NTM species can also be a cause and consequence of bronchiectasis in adult patients. Currently available licensed vaccines, while not developed specifically for bronchiectasis, include those for S. pneumoniae (one with an H. influenzae protein (protein D, PD) as a conjugate ), B. pertussis, M. tuberculosis and influenza virus.…”