Francesco Bini

Pulmonary Cladophialophora boppii Infection in a Lung Transplant Recipient: Case Report and Literature Review

Cladophialophora boppii is a dematiaceous fungus, which has been reported only rarely to be the cause of cutaneous infection. Herein we describe a C boppii parenchymal and bronchial infection in a lung transplant recipient. We also illustrate the clinicoradiologic patterns and review possible treatment options for these difficult infections.

Indoleamine 2,3-Dioxygenase in Lung Allograft Tolerance

BACKGROUND Indoleamine 2,3-dioxygenase (IDO), an enzyme involved in the degradation of tryptophan (Try) to kynurenine (Kyn), is thought to suppress T-cell activity. Although a few experimental studies have suggested a role for IDO in graft acceptance, human data are scarce and inconclusive. We sought to establish whether, in lung transplant recipients (LTRs), plasma IDO activity mirrors the level of graft acceptance. METHODS We measured the plasma Kyn/Try ratio, reflecting IDO activity, by high-performance liquid chromatography (HPLC) in 90 LTRs, including 26 patients who were still functionally/clinically stable for >36 post-transplant months (stable LTRs) and 64 LTRs with bronchiolitis obliterans syndrome (BOS, Grades 0-p to 3). Twenty-four normal healthy controls (NHCs) were also included. RESULTS The Kyn/Try ratio in stable LTRs resembled that observed in NHCs, whereas, unexpectedly, patients with BOS, who had lower counts of peripheral CD4(+) T-regulatory cells and tolerogenic plasmacytoid dendritic cells than stable LTRs, showed an increased plasma Kyn/Try ratio compared with both NHCs and stable LTRs. IDO expression by in vitro-stimulated peripheral blood mononuclear cells (PBMC) did not vary between BOS and stable LTRs. Furthermore, BOS patients displayed signs of chronic systemic inflammation (increased plasma levels of interleukin-8 and tumor necrosis factor-alpha) and higher T-cell activation (increased frequency of peripheral interferon-gamma-producing clones). CONCLUSIONS Our results suggest that, in vivo, in lung transplantation, plasma IDO activity does not reflect the degree of lung graft acceptance, but instead is correlated with the degree of chronic inflammation.

Management of acute respiratory failure in interstitial lung diseases: overview and clinical insights

BackgroundInterstitial lung diseases (ILDs) are a heterogeneous group of diseases characterized by widespread fibrotic and inflammatory abnormalities of the lung. Respiratory failure is a common complication in advanced stages or following acute worsening of the underlying disease. Aim of this review is to evaluate the current evidence in determining the best management of acute respiratory failure (ARF) in ILDs.MethodsA literature search was performed in the Medline/PubMed and EMBASE databases to identify studies that investigated the management of ARF in ILDs (the last search was conducted on November 2017).ResultsIn managing ARF, it is important to establish an adequate diagnostic and therapeutic management depending on whether the patient has an underlying known chronic ILD or ARF is presenting in an unknown or de novo ILD. In the first case both primary causes, such as acute exacerbations of the disease, and secondary causes, including concomitant pulmonary infections, fluid overload and pulmonary embolism need to be investigated. In the second case, a diagnostic work-up that includes investigations in regards to ILD etiology, such as autoimmune screening and bronchoalveolar lavage, should be performed, and possible concomitant causes of ARF have to be ruled out.Oxygen supplementation and ventilatory support need to be titrated according to the severity of ARF and patients’ therapeutic options. High-Flow Nasal oxygen might potentially be an alternative to conventional oxygen therapy in patients requiring both high flows and high oxygen concentrations to correct hypoxemia and control dyspnea, however the evidence is still scarce. Neither Non-Invasive Ventilation (NIV) nor Invasive Mechanical Ventilation (IMV) seem to change the poor outcomes associated to advanced stages of ILDs. However, in selected patients, such as those with less severe ARF, a NIV trial might help in the early recognition of NIV-responder patients, who may present a better short-term prognosis. More invasive techniques, including IMV and Extracorporeal Membrane Oxygenation, should be limited to patients listed for lung transplant or with reversible causes of ARF.ConclusionsDespite the overall poor prognosis of ARF in ILDs, a personalized approach may positively influence patients’ management, possibly leading to improved outcomes. However, further studies are warranted.

Long-term macrolides in diffuse interstitial lung diseases

In the present review we provide currently available evidence for the use of macrolides in the treatment of diffuse interstitial lung diseases (ILDs). Up to now, research on macrolides has mainly focused on three areas. First, macrolides have shown some promising results in cellular models and case reports as antifibrotic agents, by promoting autophagy and clearance of intracellular protein aggregates and acting as regulators of surfactant homeostasis. Secondly, macrolides have an immunomodulatory effect, which has been applied in some organising pneumonia cases. In particular, macrolides have been tested in association with systemic corticosteroids as steroid-sparing agents and alone as either first-line agents in mild cases or second-line agents where steroids were poorly tolerated or had failed. Thirdly, a recent area of research concerns the possible role of macrolides as modulators of lung microbiota and the host–microbiota interaction. This function has been particularly studied in idiopathic pulmonary fibrosis patients, in whom changes in microbiota have been proved to be associated with disease progression. However, the lack of high-quality studies makes the application of macrolide therapy in ILDs a field in which research should be conducted on a large scale. Macrolides may act as microbiota modulators as well as anti-inflammatory and antifibrotic agents in ILDs http://ow.ly/stlc30gB3je

Comparison between anticholinergic and beta-2 agonist treatments by using pletismography and impulse oscillometry

COPD (chronic obstructive pulmonary disease) treatment includes both anticholinergic and beta-2 agonist inhaled bronchodilators which can relieve symptoms and reduce exacerbations. To evaluate the effect of bronchodilator drugs, FEV1 (forced expiratory volume in 1 second) and FVC (forced vital capacity) are routinely measured, even if they don9t often fully identify important mechanical modifications of the lung, e.g. hyperinflation. Body plethysmography and impulse oscillometry (IOS) can better evaluate lung function. We recruited 32 patients: 16 with COPD, 10 with ACOS (asthma COPD overlap syndrome) and 6 with bronchial asthma. Patients underwent spirometry, body pletismography and IOS on 1st day, then they received 100 µg dose of salmeterol on 2nd day and 322 µg dose of aclidinium bromide on 3rd day, repeating functional tests each day. All values bettered, reaching statistical significance, after both salmeterol and aclidinium treatment in bronchial asthma and in ACOS patients, while in COPD patients only sGaw, R5, R20 and AX reached statistical significance, even if all values improved. The percentage of improvement obtained with aclidinium was higher than that obtained with salmeterol in functional tests. Data correlation was then performed. High association was found between FEV1 and R5 and between R5, R20 and VR. Values of ACOS patients showed the strongest association. IOS can adequately measure lung resistance changes caused by inhaled bronchodilators, related to changes in lung volumes. Absolute values of bronchodilation and of reduction of both peripheral and central resistances obtained with aclidinium were greater than those got with salmeterol.