Putative invasive pulmonary aspergillosis in critically ill patients with chronic obstructive pulmonary disease: a matched cohort study

Abstract

IntroductionPatients with advanced chronic obstructive pulmonary disease (COPD) are at risk for developing invasive pulmonary aspergillosis. A clinical algorithm has been validated to discriminate colonization from putative invasive pulmonary aspergillosis (PIPA) in Aspergillus-positive respiratory tract cultures of critically ill patients. We focused on critically ill patients with COPD who met the criteria for PIPA.MethodsThis matched cohort study included critically ill patients with COPD from two university hospital intensive care units (ICUs). We studied the risk factors for PIPA as well as the impact of PIPA on short- and long-term outcomes. Whether PIPA was associated with a pattern of bacterial colonization and/or infection 6 months before and/or during ICU stay was assessed. In addition, antifungal strategies were reviewed.ResultsFifty cases of PIPA in critically ill patients with COPD in the ICU were matched with one hundred control patients with COPD. The ICU short- and the long-term (at 1 year) mortality were significantly increased in the PIPA group (p < 0.001 for all variables). PIPA was a strong independent risk factor for mortality in the ICU (odds ratio 7.44, 95 % confidence interval 2.93–18.93, p < 0.001) before vasopressor therapy, renal replacement therapy, and duration of mechanical ventilation. Before ICU admission, the use of corticosteroids and antibiotics significantly increased the risk of PIPA (p = 0.004 and p < 0.001, respectively). No significant difference in bacterial etiologic agents responsible for colonization and/or infection was found between the groups. Antifungal treatment was started in 64 % of PIPA cases, with a poor impact on the overall outcome.ConclusionsPIPA was a strong death predictor in critically ill patients with COPD. The use of corticosteroids and antibiotics before ICU admission was a risk factor for PIPA. PIPA was not associated with a specific bacterial pattern of colonization or infection. Prompting antifungal treatment in critically ill patients with COPD who have PIPA may not be the only factor involved in prognosis reversal.

Emergence ofAspergillus fumigatusazole resistance in azole-naïve patients with chronic obstructive pulmonary disease and their homes

“…Patients with chronic obstructive pulmonary disease (COPD) are at risk for Aspergillus colonization and invasive aspergillosis (IA), which has a 1.6%‐3.9% prevalence, and is associated with high mortality . Azole‐resistant Aspergillus fumigatus (ARAF) has been reported in the UK in four itraconazole‐treated COPD patients (3 with chronic pulmonary aspergillosis and one with IA), in one patient with IA who had received voriconazole for 2 days in Denmark, and in two azole‐naïve patients colonized with TR 46 /Y121F/T289A A. fumigatus in the Netherlands .…”

“…Patients with chronic obstructive pulmonary disease (COPD) are at risk for Aspergillus colonization 1,2 and invasive aspergillosis (IA), which has a 1.6%-3.9% prevalence, 3,4 and is associated with high mortality. 5 Azole-resistant Aspergillus fumigatus (ARAF) has been reported in the UK in four itraconazole-treated COPD patients (3 with chronic pulmonary aspergillosis and one with IA 6 ), in one patient with IA who had received voriconazole for 2 days in Denmark, 7 and in two azolenaïve patients colonized with TR 46 /Y121F/T289A A. fumigatus in the Netherlands. 8 However, although the emergence of ARAF is increasingly studied in hematology IA (1%-15.9% prevalence [9][10][11] ), cystic fibrosis (4.5%-8% prevalence [11][12][13] ), or intensive care units (ICU) patients (4.5%-26% prevalence 10,14 ), the epidemiology and potential clinical impact of A. fumigatus azole resistance in patients with COPD have not been specifically assessed so far.…”

Diagnostic Value of Galactomannan Antigen Test in Serum and Bronchoalveolar Lavage Fluid Samples from Patients with Nonneutropenic Invasive Pulmonary Aspergillosis

“…nonneutropenic patients, especially those with chronic obstructive pulmonary disease (COPD), bronchiectasis, or previous tuberculosis, are also prone to pulmonary Aspergillus infections (2,(4)(5)(6)(7). As lung biopsy is invasive and risky and microbiological tests, such as sputum fungal cultures, have very low sensitivities (8), the diagnostic criteria for IPA are based on its characteristic histopathology.…”

The microbiome-metabolome crosstalk in the pathogenesis of respiratory fungal diseases

“…COPD has recently been acknowledged as an important risk factor for IA in critically ill patients. 40,41 Because of the impairment in mucociliary clearance that may influence the balance between persistence and elimination of bacterial communities, 42 understanding the contribution of the lung microbiome to the development of IA in this Figure 2. Bacterial dysbiosis in lung diseases associated with increased risk of infection and allergic reactions caused by Aspergillus spp.…”