RESUMO
Pulmonary infection is a common complication after lung transplantation, and early detection is crucial for outcome. However, the condition can be clinically difficult to diagnose and to distinguish from rejection. The aim of this prospective study was to evaluate heparin-binding protein (HBP), lysozyme, and the cytokines interleukin (IL)-1ß, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF) in bronchoalveolar lavage fluid (BALF) as potential biomarkers for pulmonary infection in lung-transplanted patients. One hundred thirteen BALF samples from 29 lung transplant recipients were collected at routine scheduled bronchoscopies at 3 and 6 months, or on clinical indication. Samples were classified into no, possible, probable, or definite infection at the time of sampling. Rejection was defined by biopsy results. HBP, lysozyme, and cytokines were analyzed in BALF and correlated to likelihood of infection and rejection. All biomarkers were significantly increased in BALF during infection, whereas patients with rejection presented low levels that were comparable to noninfection samples. HBP, IL-1ß, and IL-8 were the best diagnostic markers of infection with area under the receiver-operating characteristic curve values of 0.88, 0.91, and 0.90, respectively. In conclusion, HBP, IL-1ß, and IL-8 could be useful diagnostic markers of pulmonary infection in lung-transplanted patients.
Assuntos
Peptídeos Catiônicos Antimicrobianos/metabolismo , Proteínas Sanguíneas/metabolismo , Líquido da Lavagem Broncoalveolar/química , Proteínas de Transporte/metabolismo , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Transplante de Pulmão/efeitos adversos , Muramidase/metabolismo , Infecções Respiratórias/diagnóstico , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Infecções Respiratórias/etiologia , Infecções Respiratórias/metabolismo , Adulto JovemRESUMO
BACKGROUND: Lung transplant patients experience a high risk of airway infections and microbial colonization of the lung due to constant exposure to the environment through inhaled microorganisms, denervation, reduced ciliary transport, and decreased cough. METHODS: In this nationwide prospective study on Swedish lung transplant patients, we evaluated the microbiological panorama of bacteria, fungi, and virus found in bronchoalveolar lavage fluid (BALF) obtained the first year after lung transplantation (LTx). Differences in microbiological findings depending of concomitant signs of infection and background factors were assessed. RESULTS: A total of 470 bronchoscopies from 126 patients were evaluated. Sixty-two percent (n = 293) of BALF samples had positive microbiological finding(s). Forty-six percent (n = 217) had bacterial growth, 29% (n = 137) fungal growth, and 9% (n = 43) were positive in viral PCR. In 38% of BALF samples (n = 181), a single microbe was found, whereas a combination of bacteria, fungi or virus was found in 24% (n = 112) of bronchoscopies. The most common microbiological findings were Candida albicans, Pseudomonas aeruginosa and coagulase negative Staphylococcus (in 42 (33%), 36 (29%), and 25 (20%) patients, respectively). Microbiological findings were similar in BALF from patients with and without signs of lung infection and the frequency of multidrug resistant (MDR) bacteria was low. No significant association was found between background factors and time to first lung infection. CONCLUSION: This study gives important epidemiologic insights and reinforces that microbiological findings have to be evaluated in the light of clinical symptoms and endobronchial appearance in the assessment of lung infections in lung transplant patients.
Assuntos
Líquido da Lavagem Broncoalveolar/microbiologia , Transplante de Pulmão/efeitos adversos , Pneumonia/microbiologia , Adulto , Idoso , Broncoscopia , Candida albicans/isolamento & purificação , Candida albicans/fisiologia , Farmacorresistência Bacteriana Múltipla , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia/diagnóstico , Pneumonia/epidemiologia , Estudos Prospectivos , Pseudomonas aeruginosa/isolamento & purificação , Pseudomonas aeruginosa/fisiologia , Staphylococcus/isolamento & purificação , Staphylococcus/fisiologia , Suécia/epidemiologia , Adulto JovemRESUMO
We prospectively evaluated a combination of fungal biomarkers in adult haematology patients with focus on their clinical utility at different time points during the course of infection. In total, 135 patients were monitored once to twice weekly for serum (1-3)-ß-d-glucan (BG), galactomannan (GM), bis-methyl-gliotoxin and urinary d-arabinitol/l-arabinitol ratio. In all, 13 cases with proven or probable invasive fungal disease (IFD) were identified. The sensitivity of BG and GM at the time of diagnosis (TOD) was low, but within 2 weeks from the TOD the sensitivity of BG was 92%. BG >800 pg/mL was highly specific for IFD. At a pre-test probability of 12%, both BG and GM had negative predictive values (NPV) >0.9 but low positive predictive values (PPV). In a subgroup analysis of patients with clinically suspected IFD (pre-test probability of 35%), the NPV was lower, but the PPV for BG was 0.86 at cut-off 160 pg/mL. Among IFD patients, 91% had patterns of consecutively positive and increasing BG levels. Bis-methyl-gliotoxin was undetectable in 15 patients with proven, probable and possible IA. To conclude, BG was the superior fungal marker for IFD diagnosis. Quantification above the limit of detection and graphical evaluation of the pattern of dynamics are warranted in the interpretation of BG results.
Assuntos
Biomarcadores/análise , Testes Diagnósticos de Rotina/métodos , Doenças Hematológicas/complicações , Infecções Fúngicas Invasivas/diagnóstico , Adolescente , Adulto , Idoso , Feminino , Galactose/análogos & derivados , Gliotoxina/análogos & derivados , Gliotoxina/sangue , Humanos , Masculino , Mananas/sangue , Pessoa de Meia-Idade , Estudos Prospectivos , Proteoglicanas , Sensibilidade e Especificidade , Soro/química , Álcoois Açúcares/urina , Urinálise , Adulto Jovem , beta-Glucanas/sangueRESUMO
BACKGROUND: The purpose of this study was to prospectively investigate the incidence of influenza-associated pulmonary aspergillosis (IAPA) in influenza patients admitted to intensive care units in Sweden. METHODS: The study included consecutive adult patients with PCR-verified influenza A or B in 12 Swedish intensive care units (ICUs) over four influenza seasons (2019-2023). Patients were screened using serum galactomannan and ß-d-glucan tests and fungal culture of a respiratory sample at inclusion and weekly during the ICU stay. Bronchoalveolar lavage was performed if clinically feasible. IAPA was classified according to recently proposed case definitions. RESULTS: The cohort included 55 patients; 42% were female, and the median age was 59 (IQR 48-71) years. All patients had at least one galactomannan test, ß-d-glucan test and respiratory culture performed. Bronchoalveolar lavage was performed in 24 (44%) of the patients. Five (9%, 95% CI 3.8% - 20.4%) patients were classified as probable IAPA, of which four lacked classical risk factors. The overall ICU mortality was significantly higher among IAPA patients than non-IAPA patients (60% vs 8%, p = 0.01). CONCLUSIONS: The study represents the first prospective investigation of IAPA incidence. The 9% incidence of IAPA confirms the increased risk of invasive pulmonary aspergillosis among influenza patients admitted to the ICU. Therefore, it appears reasonable to implement a screening protocol for the early diagnosis and treatment of IAPA in influenza patients receiving intensive care. TRIAL REGISTRATION: ClinicalTrials.gov NCT04172610, registered November 21, 2019.
Assuntos
Aspergilose , Influenza Humana , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Aspergillus , Glucanos , Influenza Humana/complicações , Influenza Humana/epidemiologia , Unidades de Terapia Intensiva , Estudos Prospectivos , Suécia/epidemiologia , IdosoRESUMO
Fungal tracheobronchitis caused by Aspergillus and Candida spp. is a recognized complication after lung transplantation, but knowledge of the incidence of Candida tracheobronchitis is lacking. The diagnosis relies on fungal cultures in bronchoalveolar lavage fluid (BALF), but cultures have low specificity. We aimed to evaluate the one-year incidence of fungal tracheobronchitis after lung transplantation and to assess the utility of diagnostic markers in serum and BALF to discriminate fungal tracheobronchitis from colonization. Ninety-seven consecutively included adult lung-transplant recipients were prospectively followed. BALF and serum samples were collected at 1, 3 and 12 months after transplantation and analyzed for betaglucan (serum and BALF), neutrophils (BALF) and galactomannan (BALF). Fungal tracheobronchitis was defined according to consensus criteria, modified to include Candida as a mycologic criterion. The cumulative one-year incidence of Candida and Aspergillus tracheobronchitis was 23% and 16%, respectively. Neutrophils of >75% of total leukocytes in BALF had 92% specificity for Candida tracheobronchitis. The area under the ROC curves for betaglucan and galactomannan in BALF to discriminate Aspergillus tracheobronchitis from colonization or no fungal infection were high (0.86 (p < 0.0001) and 0.93 (p < 0.0001), respectively). To conclude, the one-year incidence of fungal tracheobronchitis after lung transplantation was high and dominated by Candida spp. Diagnostic markers in BALF could be useful to discriminate fungal colonization from tracheobronchitis.