Corticosteroid treatment for persistent pulmonary infiltrates following COVID-19 infection: Clearing the fog?

BACKGROUND: Systemic corticosteroids have been shown to improve outcomes in severe coronavirus disease 2019 (COVID-19) pneumonia; however, their role in post-COVID-19 persistent lung abnormalities is not well defined. Here, we describe our experience with corticosteroids in patients with persistent lung infiltrates following COVID-19 infection. RESEARCH QUESTION: What is the efficacy of systemic corticosteroids in improving lung function and radiological abnormalities in patients following COVID-19 pneumonia? STUDY DESIGN AND METHODS: This is a single-center retrospective study evaluating patients with persistent respiratory symptoms and abnormal chest computed tomography findings. Patients were divided into two groups based on treatment with corticosteroids: "steroid group" and "nonsteroid group." Clinical data were collected from the electronic medical records. RESULTS: Between March 2020 and December 2021, 227 patients were seen in the post-COVID-19 pulmonary clinic, of which 75 were included in this study. The mean age was 56 years, 63% were female, and 75% were white. The main physiologic deficit was reduced Diffusing capacity of the Lungs for Carbon Monoxide (DLCO) at 72% (±22). On chest imaging, the most common findings were ground-glass opacities (91%) and consolidation (29%). Thirty patients received corticosteroid (steroid group) and 45 did not (nonsteroid group). Patients treated with corticosteroids had lower DLCO (DLCO [%]: steroid group 63 ± 17, nonsteroid group 78 ± 23; P = 0.005) and all had ground-glass opacities on imaging compared to 84% in the nonsteroid group (P = 0.04). At follow-up, patients in the steroid group (n = 16) had a significant improvement in spirometry and DLCO. In addition, there was a significant improvement with resolution of ground-glass opacities in both the groups (P < 0.05). CONCLUSION: The use of systemic corticosteroids in patients with persistent respiratory symptoms and radiological abnormalities post-COVID-19 was associated with significant improvement in pulmonary function testing and imaging. Prospective studies are needed to confirm whether these findings are the effect of corticosteroid therapy or disease evolution over time.

Assessment of C-reactive protein levels as an indicator for lung infiltrates in patients with COVID-19 pneumonia.

Lung infiltrates are frequently observed in patients with COVID-19 infection and require specialized management. Identifying reliable laboratory parameters to reduce the need for chest CT scans in non-desaturation patients is of great interest. This study aimed to investigate the potential of C-reactive protein (CRP) as an indicator to identify the presence of lung infiltrates in early COVID-19 infection. The study was conducted at Al-Azhar University hospitals from May 2021 to March 2022 and included 210 patients with COVID-19 infection confirmed by positive PCR, all of whom were previously healthy, non-smokers, and non-hypoxemic. CRP levels were assessed and correlated with lung infiltrates observed in CT chest examinations. The mean value of CRP was 40.3±14.3 mg/L in males and 36.6±15.2 mg/L among females. One hundred sixty-two patients had pneumonic infiltrates, while 48 had no infiltrates. The mean value of CRP was 45.02±10.2 mg/L in patients with radiological infiltrates and 18.8±7.8 mg/L in patients without radiological infiltrates. Based on our findings, a CRP value greater than 29.8 mg/L was suggested as a cut-off value to indicate the presence of lung infiltrates. CRP is a simple laboratory marker that, at certain limits, may point to the presence of pneumonic infiltrates in early non-hypoxemic patients with COVID-19 infection.

Utilidad del lavado broncoalveolar para la detección microbiológica, y factores asociados, en receptores de trasplante de precursores hematopoyéticos: estudio de cohorte retrospectivo / Usefulness of bronchoalveolar lavage for microbiological detection and asssociated factors in hematopoietic stem cell transplant receivers: a retrospective cohort study

INTRODUCCIÓN: Las opacidades pulmonares en receptores de trasplante de precursores hematopoyéticos (TPH) representan un desafío diagnóstico y son una causa de morbimortalidad. Existen grandes discrepancias con respecto a la sensibilidad diagnóstica del lavado broncoalveolar (LBA), sus complicaciones, y los factores asociados a la identificación microbiológica. OBJETIVO: Conocer la utilidad del estudio microbiológico del LBA en el diagnóstico, modificación de la conducta médica y estimar las complicaciones y mortalidad asociada al procedimiento, en receptores de TPH con opacidades pulmonares. PACIENTES Y MÉTODOS: Estudio de cohorte, retrospectivo, en adultos receptores de TPH a los que se les realizó una broncoscopía con LBA por presentar opacidades pulmonares, en el Hospital Italiano de Buenos Aires entre el 01/01/2011 y el 31/12/2020. RESULTADOS: De los 189 procedimientos analizados, en 79 se logró un hallazgo microbiológico (41,8%) y 122 permitieron modificar la conducta médica (64,6%). En 11 casos se observaron complicaciones graves dentro de las 12 horas (5,8%) de efectuado el LBA. La mortalidad intrahospitalaria fue de 16,8% (N = 21/125). El valor de neutrófilos en sangre previo al LBA (p = 0,037) y la presencia de nódulos pulmonares como lesión tomográfica predominante (p = 0,029) se asociaron independientemente al hallazgo microbiològico global. CONCLUSIONES: Nuestra investigación apoya la realización del LBA como herramienta diagnóstica en pacientes que reciben un TPH y presentan opacidades pulmonares.

BACKGROUND: Lung opacities are a cause of morbimortality in bone marrow transplant patients, and represent a diagnostic challenge. There are large discrepancies regarding the diagnostic sensitivity of bronchoalveolar lavage (BAL), its complications, and the factors associated with microbiological detection. AIM: To know the usefulness of the microbiological study of BAL in the diagnosis, in the modification in medical behavior and to estimate the complications and associated mortality of this diagnostic procedure in patients transplanted with hematopoietic progenitor cells with pulmonary opacities. METHODS: Retrospective cohort study in bone marrow transplant adult patients who underwent bronchoscopy with BAL due to lung opacities at Hospital Italiano de Buenos Aires between 01/01/2011 and 12/31/2020. RESULTS: Of the 189 BAL analyzed, 79 presented a microbiological detection (41.8%) and 122 allowed to modify the medical behavior (64.6%). Severe complications were observed within 12 hours after the procedure in11 cases (5.8%). In-hospital mortality was 16,8% (N = 21/125). The value of blood neutrophils prior to bronchoalveolar lavage (p = 0.037) and the presence of pulmonary nodules as the predominant tomographic lesion (p = 0.029) were independently associated with global microbiological detection. CONCLUSION: Our research supports the performance of BAL as a diagnostic tool in bone marrow transplant patients with lung opacities.

Diagnostic Utility of Bronchoalveolar Lavage in Immunocompromised Patients with Lung Infiltrates.

Introduction: Lung infections are associated with a high mortality rate in immunocompromised patients. Achieving an accurate and rapid diagnosis is vital to help guide management, and thus improve survival. Objective: To establish the diagnostic yield, clinical value, and safety of bronchoscopy with bronchoalveolar lavage (BAL) in immunocompromised adult patients with pulmonary infiltrates. Methods: This retrospective study included all immunocompromised adult patients who underwent bronchoscopy with BAL for investigation of radiologically confirmed pulmonary infiltrates at a tertiary care hospital between January 01, 2014, and June 30, 2021. Clinically significant findings of BAL were defined as a positive microbiological result of a potential pathogen determined using routine culture, acid-fast bacilli smear, mycobacterial culture, tuberculosis PCR, fungal culture, Aspergillus antigen, and multiplex PCR panel and/or positive cytology. Results: A total of 103 unique patients were included (mean ± SD age: 44.5 ± 14.1 years), of which the majority were male (60.2%). The BAL diagnostic yield was 52.4% (95% CI: 42.6-62.2%). In the multiple logistic regression model, positive BAL was predicted by symptom of sputum (aOR 4.01, 95% CI: 1.27-12.70, P = 0.018). Almost half of the procedures (43.7%, 95% CI: 33.9-53.4%) resulted in a change in the management plan, with positive BAL findings more than twice as likely to result in a change (OR 2.39, 95% CI: 1.07-5.33, P = 0.033). Only three (2.9%) procedures resulted in complications and required ventilator support and/or oxygen escalation. Conclusions: BAL is a safe clinical tool that can be useful in impacting clinical management in a significant proportion of immunocompromised patients with pulmonary infiltrates.

Lung Ultrasound and High-Resolution Computed Tomography in Suspected COVID-19 Patients Admitted to the Emergency Department: A Comparison.

Objective: To analyze the diagnostic accuracy of lung ultrasonography (LUS) and high-resolution computed tomography (HRCT), to detect COVID-19. Materials and Methods: This study recruited all patients admitted to the emergency medicine unit, due to a suspected COVID-19 infection, during the first wave of the COVID-19 pandemic. These patients also who underwent a standardized LUS examination and a chest HRCT. The signs detected by both LUS and HRCT were reported, as well as the sensitivity, specificity, positive predictive value, and negative predictive value for LUS and HRCT. Results: This cohort included 159 patients, 101 (63%) were diagnosed with COVID-19. COVID-19 patients showed more often confluent subpleural consolidations and parenchymal consolidations in lower lung regions of LUS. They also had "ground glass" opacities and "crazy paving" on HRCT, while pleural effusion and pulmonary consolidations were more common in non-COVID-19 patients. LUS had a sensitivity of 0.97 (95% CI 0.92-0.99) and a specificity of 0.24 (95% CI 0.07-0.5) for COVID-19 lung infections. HRCT abnormalities resulted in a 0.98 sensitivity (95% CI 0.92-0.99) and 0.1 specificity (95% CI 0.04-0.23) for COVID-19 lung infections. Conclusion: In this cohort, LUS proved to be a noninvasive, diagnostic tool with high sensitivity for lung abnormalities that were likewise detected by HRCT. Furthermore, LUS, despite its lower specificity, has a high sensitivity for COVID-19, which could prove to be as effective as HRCT in excluding a COVID-19 lung infection.

Follicular Helper-like T Cells in the Lung Highlight a Novel Role of B Cells in Sarcoidosis.

Rationale: Pulmonary sarcoidosis is generally presumed to be a T-helper cell type 1- and macrophage-driven disease. However, mouse models have recently revealed that chronically inflamed lung tissue can also comprise T follicular helper (Tfh)-like cells and represents a site of active T-cell/B-cell cooperation. Objectives: To assess the role of pulmonary Tfh- and germinal center-like lymphocytes in sarcoidosis. Methods: BAL fluid, lung tissue, and peripheral blood samples from patients with sarcoidosis were analyzed by flow cytometry, immunohistology, RNA sequencing, and in vitro T-cell/B-cell cooperation assays for phenotypic and functional characterization of germinal center-like reactions in inflamed tissue. Measurements and Main Results: We identified a novel population of Tfh-like cells characterized by high expression of the B helper molecules CD40L and IL-21 in BAL of patients with sarcoidosis. Transcriptome analysis further confirmed a phenotype that was both Tfh-like and tissue resident. BAL T cells provided potent help for B cells to differentiate into antibody-producing cells. In lung tissue, we observed large peribronchial infiltrates with T and B cells in close contact, and many IgA+ plasmablasts. Most clusters were nonectopic; that is, they did not contain follicular dendritic cells. Patients with sarcoidosis also showed elevated levels of PD-1high CXCR5- CD40Lhigh ICOShigh Tfh-like cells, but not classical CXCR5+ Tfh cells, in the blood. Conclusions: Active T-cell/B-cell cooperation and local production of potentially pathogenic antibodies in the inflamed lung represents a novel pathomechanism in sarcoidosis and should be considered from both diagnostic and therapeutic perspectives.

EVALI - E-Cigarette or Vaping Product Use-Associated Lung Injury: A Case Report.

The use of electronic cigarettes among the young adult and adolescent population has increased over the past decade. Vaping is the process of inhaling an aerosol that is produced by heating a liquid or wax containing substances, such as nicotine, cannabinoids (e.g., tetrahydrocannabinol (THC), cannabidiol), flavoring, and additives (e.g., glycerol, propylene glycol) using an e-cigarette. A multistate epidemic associated with vaping prompted the Centers for Disease Control and Prevention (CDC) to issue an official health advisory on e-cigarette or vaping product use-associated lung injury (EVALI). EVALI is a diagnosis of exclusion with no specific diagnostic test. We present a case of EVALI before the COVID-19 pandemic time in a 23-year-old immunocompetent male student with an eight-year history of vaping. He presented to the emergency department with fever, shortness of breath, tachypnea, nausea, and diarrhea. The patient had no past medical history. The patient denied illicit drug abuse or known drug allergies. The patient was admitted with a diagnosis of sepsis and pneumonia. The patient's urine drug screen was positive for cannabinoids with a history of vaping. Community-acquired pneumonia due to Legionella, Pneumococcal, Mycoplasma bacteria was ruled out. Influenza A/B, Parainfluenza, Rhino, and Adenoviruses were negative. A computed tomographyscan of the chest showed bilateral infiltrates. He was treated with high dose steroids, empiric antibiotics, high flow oxygen and managed in ICU for seven days. The patient was discharged on tapering doses of steroid and counseled to quit vaping. EVALI outbreak is strongly linked to vitamin E acetate in vaping products. EVALI is a diagnosis of exclusion with a history of vaping and responds well to steroids.

Submassive Pulmonary Embolism in Mild COVID-19 Without Lung Infiltrates.

A 66-year-old man who had been diagnosed with mild coronavirus 2019 (COVID-19) infection nine days prior presented to the emergency room with acute-onset chest pain and shortness of breath. Chest CT angiogram (CTA) revealed pulmonary emboli (PE) in the right and left pulmonary arteries with right heart strain; lung parenchyma showed no infiltrates. Although severe COVID-19 infection is associated with thrombotic complications, data regarding the occurrence of PE in mild cases of COVID-19 is scarce. However, even mild cases of COVID-19 are reported to have revealed lung infiltrates, particularly ground-glass opacities, on imaging. The possibility of the lungs being the primary source of COVID-19-associated coagulopathy has been raised. We report an uncommon case of submassive PE occurring in mild COVID-19, without any associated lung infiltrates. This case indicates that mild COVID-19, without significant lung parenchymal involvement, can also cause a hypercoagulable state, resulting in venous thromboembolism (VTE).

Role of bronchoalveolar lavage in the management of immunocompromised patients with pulmonary infiltrates.

Pulmonary infiltrates are a significant cause of morbidity and mortality in immunocompromised patients and remain a diagnostic challenge due to the broad range of etiologies that include infection and malignancy. Empiric therapy may be sub-optimal and can adversely impact outcome. Therefore, a confirmed diagnosis is necessary and flexible bronchoscopy with bronchoalveolar lavage (BAL) may be a useful diagnostic tool. Samples are obtained for microbiological and cytological testing, but the procedure carries risk of complications including the adverse events related to moderate sedation. A review of published literature on BAL in immunocompromised patients from the year 2000 was undertaken focusing on diagnostic yield, complication rate, mortality as well as factors impacting these outcomes. Studies in which the majority of patients were supported on mechanical ventilation were excluded. A total of 23 studies (7 prospective and 16 retrospective) met inclusion criteria. This covered 3,395 procedures in 3,192 patients with a mean age of 47.4 years; 60.3% male gender. Diagnostic yield ranged from 26% to 69% with no clear association between diagnostic yield and etiology of immunosuppression or clinical/radiological presentation. Post BAL modification of treatment as an indicator for clinical utility ranged from 11% to 84%; and complication rate ranged from 1% to 52%. No specific factors were associated with increased adverse event rate. This review provides a summary of the data on the use of BAL for diagnosis of pulmonary infiltrates in immunocompromised patients, highlighting the heterogeneity of patients, significant variation in findings reported and the need for more data to optimize patient selection.

Utility of bronchoalveolar lavage in the management of immunocompromised patients presenting with lung infiltrates.

BACKGROUND: Bronchoalveolar lavage (BAL) is utilized for diagnosing lung infiltrates in immunocompromised. There is heterogeneity in the data and reported diagnostic yields range from 26 to 69%. Therefore, selection criteria for BAL to maximize yield and minimize complications are unclear. Objectives of this study were to determine the diagnostic yield and complication rate of BAL in immunocompromised patients presenting with lung infiltrates, and identify factors impacting these outcomes. Exploratory aims included characterization of pathogens, rate of treatment modification and mortality. METHODS: Retrospective study from January 2012 to December 2016. Patients on mechanical ventilation were excluded. Positive diagnostic yield was defined as confirmed microbiological or cytological diagnosis. RESULTS: A total of 217 patients were recruited (70.1% male and mean age: 51.7 ± 14.6 years). Diagnostic yield was 60.8% and complication rate 14.7%. Complications (hypoxemia and endobronchial bleeding) were all sell-limiting. Treatment modification based on BAL results was 63.3%. In 97.0% an infectious aetiology was identified. HIV infection (OR 5.304, 95% CI 1.611-17.458, p = 0.006) and severe neutropenia (OR 4.253, 95% CI 1.288-14.045, p = 0.018) were associated with positive yield. Leukemia (OR 0.317, 95% CI 0.102-0.982, p = 0.047) was associated with lower yield. No factors impacted complication rate. Overall mortality (90-day) was 17.5% and in those with hematologic malignancy, it was 28.3%. CONCLUSION: BAL retains utility in diagnosis of immunocompromised patients with lung infiltrates. However, patients with hematologic malignancy have a high mortality and alternative sampling should be considered because of poor results with BAL. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01374542 . Registered June 16, 2011.

Diagnostic Evaluation of Pulmonary Abnormalities in Patients with Hematologic Malignancies and Hematopoietic Cell Transplantation.

Pulmonary complications (PC) of hematologic malignancies and their treatments are common causes of morbidity and mortality. Early diagnosis is challenging due to host risk factors, clinical instability, and provider preference. Delayed diagnosis impairs targeted treatment and may contribute to poor outcomes. An integrated understanding of clinical risk and radiographic patterns informs a timely approach to diagnosis and treatment. There is little prospective evidence guiding optimal modality and timing of minimally invasive lung sampling; however, a low threshold for diagnostic bronchoscopy during the first 24 to 72 hours after presentation should be a guiding principle in high-risk patients.

Lymphocytic Interstitial Pneumonia.

Lymphocytic interstitial pneumonia (LIP) is a rare lung disease on the spectrum of benign pulmonary lymphoproliferative disorders. LIP is frequently associated with connective tissue diseases or infections. Idiopathic LIP is rare; every attempt must be made to diagnose underlying conditions when LIP is diagnosed. Computed tomography of the chest in patients with LIP may reveal ground-glass opacities, centrilobular and subpleural nodules, and randomly distributed thin-walled cysts. Demonstrating polyclonality with immunohistochemistry is the key to differentiating LIP from lymphoma. The 5-year mortality remains between 33% and 50% and is likely to vary based on the underlying disease process.

The Significance of Bronchoalveolar Lavage Fluid Cytology in Diagnosing Lung Infiltrates in Children.

AIM: The aim of this research is to show why is it important in diagnosing children with lung infiltrates. METHODS: Our study included 50 children with lung infiltrates during period 2005-2012, and was conducted on Pediatric Clinic of the University Clinical Center Sarajevo. We sent all cytological BAL analyses to the University Clinical Center Sarajevo. Cytology was performed by direct microscopy. BAL cytology was performed by the principle of sending samples for centrifuging, 12000 revolutions during a 10 min Shandon-cyto spin. Then the centrifuged sample is dried in the air during 1-2 hours, and is then dyed under the May-Grünwald-Giemsa staining, and analyzed under the Olympus BX41 microscope. RESULTS: Nosocomial pneumonia has occurred in 32% children, acquired pneumonia in 38%, and 30% children had a lung infiltrates. 6 (12%) of children were younger then 1 year old, 23 (46%) children were between 1 to 5 years, 14 (28%) of children were between 5 to 10 ages, and 7 (14%) of children were between 10-15 ages. The most of the changes in observed children took place on the right lung, 34%, while 26% occurred on the left side, 22% were normal and 18% changes have affected both lungs, right and left. Percentage of cells in cytological smear in children with BAL were: cylindrical cells 28%, lung macrophage 26%, lymphocytes 17%, detritus 17% and phlegm 12%. Erythrocyte sedimentation rate (ESR) in children with BAL was up to 10-52%, to 50-30%, while ESR after first hour was above 50-18 %. CONCLUSION: Clinical parameters and local inflammation of the affected lobe are associated with positive bronchoalveolar cytology lavage findings.

How to manage lung infiltrates in adults suffering from haematological malignancies outside allogeneic haematopoietic stem cell transplantation.

Pulmonary complications affect up to 40% of patients with severe neutropenia lasting for more than 10 d. As they are frequently associated with fever and elevation of C-reactive protein or other signs of inflammation, they are mostly handled as pneumonia. However, the differential diagnosis is broad, and a causative microbial agent remains undetected in the majority of cases. Pulmonary side effects from cytotoxic treatment or pulmonary involvement by the underlying malignancy must always be taken into account and may provide grounds for invasive diagnostic procedures in selected patients. Pneumocystis jirovecii (in patients not receiving co-trimoxazole as prophylaxis), multi-resistant gram-negative bacilli, mycobacteria or respiratory viruses may be involved. High-risk patients may be infected by filamentous fungi, such as Aspergillus spp., but these infections are seldom proven when treatment is initiated. Microorganisms isolated from cultures of blood, bronchoalveolar lavage or respiratory secretions need careful interpretation as they may be irrelevant for determining the aetiology of pulmonary infiltrates, particularly when cultures yield coagulase-negative staphylococci, enterococci or Candida species. Non-culture based diagnostics for detecting Aspergillus galactomannan, beta-D-glucan or DNA from blood, bronchoalveolar lavage or tissue samples can facilitate the diagnosis, but must always be interpreted in the context of clinical and imaging findings. Systemic antifungal treatment with mould-active agents, given in combination with broad-spectrum antibiotics, improves clinical outcome when given pre-emptively. Co-trimoxazole remains the first-line treatment for Pneumocystis pneumonia, while cytomegalovirus pneumonia will respond to ganciclovir or foscarnet in most cases. The clinical outcome of acute respiratory failure can also be successful with proper intensive care, when indicated.

Idiopathic pulmonary haemosiderosis with celiac disease (Lane-Hamilton syndrome) in an adult - a case report.

Idiopathic pulmonary haemosiderosis (IPH) is a rare disorder of unknown cause characterised by haemoptysis, diffuse alveolar infiltrates and iron-deficiency anaemia. IPH predominantly affects children; it is rare in adults, in whom it usually manifests before 30 years. In adults, course is protracted with a better prognosis, in contrast to children. Even rarer is the Lane-Hamilton syndrome, a condition in which IPH is associated with celiac disease. Only 15 cases of Lane-Hamilton syndrome affecting adults are reported in literature. Treatment of IPH is based on anecdotal case reports and case series because of its rare occurrence. High-dose steroids reportedly reduce morbidity and mortality and delays or stops disease progression; more effectively in adults than children. In Lane-Hamilton syndrome, a gluten-free diet for the celiac disease in addition to steroids for IPH, is the mainstay of therapy. The optimal treatment duration of steroid therapy is not known but anecdotally a more prolonged course results in improved outcome. We report a case of a young woman who presented with exertional dyspnoea, intermittent haemoptysis, severe anaemia and lung infiltrates but no gastrointestinal complaints. After extensive work-up, she was diagnosed with Lane-Hamilton syndrome based on a diagnosis of IPH made from lung biopsy and concomitant celiac disease because of positive anti-gliadin antibody and endomyosial antibody and jejunal biopsy. She was treated with sustained low-dose steroid therapy for a year and a gluten-free diet with resolution of her symptoms, anaemia and lung infiltrates. At 4 years of follow-up, she remains stable, without recurrence.

Distinguishing the Causes of Pulmonary Infiltrates in Patients With Acute Leukemia.

Pulmonary infiltrates are commonly observed in patients with acute leukemia (AL), particularly acute myeloid leukemia, who undergo remission induction therapy. The mortality rate is unacceptably high and depends on 3 factors: the host (performance status, comorbidities, and frailty), the etiology of the infiltrates and the type of response to antileukemic therapy. The approach to the diagnosis of pulmonary infiltrates in patients with AL includes a medical history, thorough physical examination, radiologic pattern of the infiltrates (focal vs. diffuse), and timing of their appearance in relation to the start of antileukemic therapy (early, ie, within the first 2 weeks or late). Localized infiltrates are most commonly caused by bacterial (early) and fungal infections (late). Diffuse early infiltrates might be caused by leukemic infiltration of the lungs, pulmonary hemorrhage and/or edema, diffuse alveolar damage, viral pneumonia, and rarely transfusion-related acute lung injury (TRALI) or the differentiation syndrome. Similar to the early phase, pulmonary edema, viral pneumonia, and rarely TRALI might cause diffuse infiltrates during the late phase, in addition to immune reconstitution and pneumocystosis, particularly among patients with acute lymphoblastic leukemia. Diagnostic tests, invasive and noninvasive, can be particularly useful to establish the diagnosis. Early intervention is critical and is based on the most likely diagnosis with modification when the etiology is confirmed.

Diagnosis and antimicrobial therapy of lung infiltrates in febrile neutropenic patients (allogeneic SCT excluded): updated guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO).

Up to 25% of patients with profound neutropenia lasting for >10 days develop lung infiltrates, which frequently do not respond to broad-spectrum antibacterial therapy. While a causative pathogen remains undetected in the majority of cases, Aspergillus spp., Pneumocystis jirovecii, multi-resistant Gram-negative pathogens, mycobacteria or respiratory viruses may be involved. In at-risk patients who have received trimethoprim-sulfamethoxazole (TMP/SMX) prophylaxis, filamentous fungal pathogens appear to be predominant, yet commonly not proven at the time of treatment initiation. Pathogens isolated from blood cultures, bronchoalveolar lavage (BAL) or respiratory secretions are not always relevant for the etiology of pulmonary infiltrates and should therefore be interpreted critically. Laboratory tests for detecting Aspergillus galactomannan, ß-D-glucan or DNA from blood, BAL or tissue samples may facilitate the diagnosis; however, most polymerase chain reaction assays are not yet standardized and validated. Apart from infectious agents, pulmonary side-effects from cytotoxic drugs, radiotherapy or pulmonary involvement by the underlying malignancy should be included into differential diagnosis and eventually be clarified by invasive diagnostic procedures. Pre-emptive treatment with mold-active systemic antifungal agents improves clinical outcome, while other microorganisms are preferably treated only when microbiologically documented. High-dose TMP/SMX is first choice for treatment of Pneumocystis pneumonia, while cytomegalovirus pneumonia is treated primarily with ganciclovir or foscarnet in most patients. In a considerable number of patients, clinical outcome may be favorable despite respiratory failure, so that intensive care should be unrestrictedly provided in patients whose prognosis is not desperate due to other reasons.