The impact of the updated EORTC/MSG criteria on the classification of hematological patients with suspected invasive pulmonary aspergillosis

ObjectivesOur aim was to evaluate the effect of the updated European Organization for Research and Treatment of Cancer (EORTC) and Mycoses Study Group 2019 definitions for invasive pulmonary aspergillosis (IPA) on patient classification and the related all-cause 12-week mortality.MethodsIn this retrospective cohort study from our tertiary care centre, we reclassified patients with haematological malignancy who underwent bronchoalveolar lavage between 2014 and 2019 for suspected IPA using the novel EORTC 2019 criteria. We performed receiver operating characteristic curve analysis to define the optimal cut-off for positive PCR and galactomannan and present survival analyses and their possible association with these diagnostic criteria through post hoc comparisons with log rank and Cox regression.ResultsFrom 323 episodes of suspected IPA in 282 patients, 73 were reclassified: 31 (42.5%) from possible to probable IPA, 5 (6.8%) from EORTC criteria not met to probable IPA, and 37 (50.7%) from EORTC criteria not met to possible IPA. Probable IPA increased therefore 11.1% (64/323, 19.8% to 100/323, 30.9%), mostly due to positive PCR (31/36, 86.1%). There was no difference in mortality between newly defined possible and probable IPA (log rank p = 0.950). Mortality was higher in probable cases with lower cycle thresholds (Ct values) versus higher Ct values (p = 0.004). Receiver operating characteristic curve analysis showed an optimal Ct value cut-off of 36.8 with a sensitivity of 75% (95% CI 64.9%–85.1%) and a specificity of 61.7% (95% CI 53.5–69.9) for 12-week mortality.DiscussionThe new EORTC criteria led to 11.1% more probable IPA diagnoses, mostly due to Aspergillus PCR. Restricting positive PCR to below a certain threshold might improve the discrimination of the new EORTC IPA categories for mortality.     

Resistin is elevated in cystic fibrosis sputum and correlates negatively with lung function

Background

Resistin is an immunometabolic mediator that is elevated in several inflammatory disorders. A ligand for Toll-like receptor 4, resistin modulates the recruitment and activation of myeloid cells, notably neutrophils. Neutrophils are major drivers of cystic fibrosis (CF) lung disease, in part due to the release of human neutrophil elastase- and myeloperoxidase-rich primary granules, leading to tissue damage. Here we assessed the relationship of resistin to CF lung disease.

Gram-negative bacterial pneumonia with secondary aspergillosis in an AIDS patient

Summary A 40-year-old, HIV-infected female patient received antibiotic treatment for a urinary tract infection. After the initial success of therapy and a symptom-free period, she developed pneumonia with septic shock and adult respiratory distress syndrome (ARDS). In spite of intensive care and respirator therapy with positive end-expiratory pressure (PEEP), she died of infectious toxic shock. Autopsy findings showed relapsing, gramnegative, bacterial pneumonia (morphologically compatible with Klebsiella pneumonia) and secondary, invasive aspergillosis. The pathogenesis and epidemiology of these unusual complications of AIDS are discussed.Abbreviations AIDS acquired immunodeficiency syndrome - ARDS adult respiratory distress syndrome - CDC Centers for Disease Control - HIV human immunodeficiency virus - PEEP positive end-expiratory pressure     

Arterial embolization as preoperative treatment for pulmonary aspergillosis with hemoptysis

Pulmonary aspergillosis associated with old tuberculosis is generally resistant to treatment. Thus, if patients are treated only with conservative therapy, their condition continues to deteriorate due to repetitive hemoptysis, and may even become critical. Surgical treatment is required for these patients; however, it is extremely difficult to resect the lesion due to severe adhesions to the chest wall and vascular proliferation surrounding the lesion. We performed preoperative arterial embolization, achieving good results in three patients with hemoptysis caused by pulmonary aspergillosis. The feeding arteries were embolized using microcoils and/or gelatin sponges, and a lobectomy was safely carried out in all patients. We concluded that preoperative arterial embolization is a safe and effective technique to prevent massive hemorrhage occurring at the time of surgery. This work was presented at the 11th Annual Meeting of the Japanese Association for Chest Surgery, held in Kyoto, Japan, May 13–14, 1994     

Pulmonary Sequestration In A Child With Acute Myelold Leukemia

The article describes a relatively rare congenital anomaly that was difficult to diagnose in a 10-year-old child with acute nonlymphoblastic leukemia. Just at diagnosis of leukemia, the patient showed a pathologic chest radiograph because of a parenchymal thickening at the right lung apex. The presence of bronchopneumonia was suspected, and broad-spectrum antibiotic therapy was started with subsequent antifungal treatment for persistent fever and concurrent chemotherapy-induced marrow aplasia, which did not favor pulmonary infiltrate recovery. Continuous culture tests, including bronchial swab, proved negative for Koch-Weeks bacillus, fungal organisms, and other pathogens. Computed tomography, however, was suggestive of Aspergillus lung involvement, and apical sepmentectomy was performed. The anatomic pathologist suggested the diagnosis of intralobar sequestration. In summary, when pulmonary pathology with an excavation is found in a leukemic child, one must consider the possibility of pulmonary sequestration complicated by an infectious disease.     

Transposition of modified latissimus dorsi musculocutaneous flap in the treatment of persistent bronchopleural fistula after posterolateral incision

The condition of a 51-year-old man was complicated with empyema and bronchopleural fistula (BPF) after left upper lobectomy and thoracoplasty for pulmonary aspergillosis. On the postoperative day (POD) 12, the opened bronchial stump was directly closed and covered with a pedicled pectoralis major muscle flap. On POD 66, an open-window thoracostomy was done, because of empyema with Pseudomonas aeruginosa. Two years later, we could fill the empyema cavity, and close the multiple BPFs with the transposition of a modified pedicled musculocutaneous (MC) flap and the additional thoracoplasty to gain good quality of life. Although the MC flap was a proximal part of the latissimus dorsi muscle, which was dissected along the posterolateral incision of the first operation, it could be successfully transplanted to cover the BPFs in the open-window. In some patients with a small open-window on the upper anterior chest wall, the pedicled proximal latissimus dorsi MC flap may be very useful for treating persistent BPFs even after a standard posterolateral incision.     

Allergic bronchopulmonary aspergillosis

Allergic bronchopulmonary aspergillosis (ABPA) occurs in nonimmunocompromised patients and belongs to the hypersensitivity disorders induced by Aspergillus. Genetic factors and activation of bronchial epithelial cells in asthma or cystic fibrosis are responsible for the development of a CD(4)+Th2 lymphocyte activation and IgE, IgG and IgA-AF antibodies production. The diagnosis of ABPA is based on the presence of a combination of clinical, biological and radiological criteria. The severity of the disease is related to corticosteroid-dependant asthma or/and diffuse bronchiectasis with fibrosis. The treatment is based on oral corticosteroids for 6-8 weeks at acute phase or exacerbation and itraconazole is now recommended and validated at a dose of 200 mg/day for a duration of 16 weeks.     

DC-SIGN mediates the binding of Aspergillus fumigatus and keratinophylic fungi by human dendritic cells

Human contact with fungi does not usually lead to pathological consequences, as the immune system manages to defeat the invader pathogens. Nevertheless, under immune suppression, fungi overcome immune defenses and cause diseases that range from nonserious colonizations of keratinizated tissue (Dermatophytosis) to life threatening disseminated infections (Aspergillosis). Host defenses against fungi rely on innate and adaptative responses, with dendritic cell (DC) and macrophage surface receptors having a major role in the recognition of fungal pathogens and in the orchestration of an effective immune response. DC-SIGN is a C-type lectin involved in the recognition of bacterial, viral and parasitic pathogens, as well as in interactions between cells of the immune system. Its expression is restricted to DCs and subsets of macrophages. Here we show that DC-SIGN mediates the binding and capture of Aspergillus fumigatus and keratinophylic fungi, including Chrysosporium tropicum, by human DCs, describe the requirements of these interactions and discuss their potential involvement in the onset and persistence of pulmonary fungal infections.     

Diagnosis of allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis

BACKGROUND: The diagnosis of allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis (CF) patients may be difficult to establish because ABPA shares many characteristics with coexisting atopy or other lung infections in these patients. This study aimed to evaluate the sensitivity and specificity of various paraclinical parameters in the diagnosis of ABPA in patients with CF. METHODS: Accumulated data from a 5-year period in 238 CF patients were used to divide patients into two groups designated the ABPA group (n=26) and the non-ABPA group (n = 35). Patients in both groups were colonized with Aspergillus fumigatus (Af.), but only the ABPA group consistently demonstrated specific IgE antibodies and specific precipitins. Patients without A. fumigatus colonization were not assigned to either of these groups (n = 177). By this selection as the true diagnosis, 10 patients were selected from the ABPA group and 10 patients from the non-ABPA group. RESULTS: The groups were comparable as to age, sex, lung function (P=0.6), and presence of chronic Pseudomonas aeruginosa infection (P>0.1). No significant difference between the groups in unspecific atopic parameters such as eosinophil count (P=0.9) or eosinophil cationic protein (ECP) in sputum, plasma, or serum (P=0.9, P=0.59, and P = 0.9, respectively) was demonstrated. Total IgE was significantly higher in the ABPA group (P<0.01). The groups were comparable in skin prick test (SPT) positivity to a standard panel of aeroallergens (pollen, dander, molds, and mites) (P>0.2). Statistically significantly higher levels in the ABPA group were demonstrated in specific IgE to Af. (P < 0.05), SPT positivity to Af. (P < 0.02), and Af. precipitins (P < 0.05). Histamine release (HR) to Af. tended to be higher (P=0.075) in the ABPA group. Specific IgE to Af. was determined by Magic Lite (ML), CAP, and Maxisorp (in-house RAST). The CAP level was one to two classes higher than the ML level; however, the results were comparable (r=0.66, P<0.005). IgE to Af. measured by CAP was the test which offered the highest positive predictive value (PPV) and negative predictive value (NPV). Optimal diagnostic cutoff levels for the diagnosis of ABPA were determined: class 2 for HR to Af., 200 kIU/l for total IgE, and 3.5 (titer) for precipitating antibodies to Af., and class 2 for IgE to Af. (by CAP System). CONCLUSIONS: Unspecific atopy markers were of limited value for the diagnosis of ABPA. Patients with ABPA do not seem to be more atopic to other aeroallergens than non-ABPA patients. The most valid parameters for the diagnosis of ABPA in CF are SPT to Af., IgE to Af. in combination with precipitating antibodies to Af., and/or total IgE.