Significance of clinical-immunological patterns and diagnostic yield of biopsies in microscopic polyangiitis and granulomatosis with polyangiitis.

BACKGROUND: Microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are the two major antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). OBJECTIVES: To characterize a homogenous AAV cohort and to assess the impact of clinicopathological profiles and ANCA serotypes on clinical presentation and prognosis. Clinical differences in GPA patients according to ANCA serotype and the diagnostic yield for vasculitis of biopsies in different territories were also investigated. RESULTS: This retrospective study (2000-2021) included 152 patients with AAV (77 MPA/75 GPA). MPA patients (96.1% myeloperoxidase [MPO]-ANCA and 2.6% proteinase 3 [PR3]-ANCA) presented more often with weight loss, myalgia, renal involvement, interstitial lung disease (ILD), cutaneous purpura, and peripheral nerve involvement. Patients with GPA (44% PR3-ANCA, 33.3% MPO, and 22.7% negative/atypical ANCA) presented more commonly with ear, nose, and throat and eye/orbital manifestations, more relapses, and higher survival than patients with MPA. GPA was the only independent risk factor for relapse. Poor survival predictors were older age at diagnosis and peripheral nerve involvement. ANCA serotypes differentiated clinical features in a lesser degree than clinical phenotypes. A mean of 1.5 biopsies were performed in 93.4% of patients in different territories. Overall, vasculitis was identified in 80.3% (97.3% in MPA and 61.8% in GPA) of patients. CONCLUSIONS: The identification of GPA presentations associated with MPO-ANCA and awareness of risk factors for relapse and mortality are important to guide proper therapeutic strategies in AAV patients. Biopsies of different affected territories should be pursued in difficult-to-diagnose patients based on their significant diagnostic yield.

Bronchoscopist's perception of the quality of the single-use bronchoscope (Ambu aScope4™) in selected bronchoscopies: a multicenter study in 21 Spanish pulmonology services.

BACKGROUND: The disposable bronchoscope is an excellent alternative to face the problem of SARS-CoV-2 and other cross infections, but the bronchoscopist's perception of its quality has not been evaluated. METHODS: To evaluate the quality of the Ambu-aScope4 disposable bronchoscope, we carried out a cross-sectional study in 21 Spanish pulmonology services. We use a standardized questionnaire completed by the bronchoscopists at the end of each bronchoscopy. The variables were described with absolute and relative frequencies, measures of central tendency and dispersion depending on their nature. The existence of learning curves was evaluated by CUSUM analysis. RESULTS: The most frequent indications in 300 included bronchoscopies was bronchial aspiration in 69.3% and the median duration of these was 9.1 min. The route of entry was nasal in 47.2% and oral in 34.1%. The average score for ease of use, image, and aspiration quality was 80/100. All the planned techniques were performed in 94.9% and the bronchoscopist was satisfied in 96.6% of the bronchoscopies. They highlighted the portability and immediacy of the aScope4TM to start the procedure in 99.3%, the possibility of taking and storing images in 99.3%. The CUSUM analysis showed average scores > 70/100 from the first procedure and from the 9th procedure more than 80% of the scores exceeded the 80/100 score. CONCLUSIONS: The aScope4™ scored well for ease of use, imaging, and aspiration. We found a learning curve with excellent scores from the 9th procedure. Bronchoscopists highlighted its portability, immediacy of use and the possibility of taking and storing images.

Systemic corticosteroids for community-acquired pneumonia: reasons for use and lack of benefit on outcome.

BACKGROUND AND OBJECTIVE: Although the benefits of systemic corticosteroids in community-acquired pneumonia (CAP) are not clear, their use is frequent in clinical practice. We described the frequency of this practice, patients' characteristics and its clinical impact. METHODS: We investigated all adult CAP patients visited between June 1997 and January 2008 (n = 3257). RESULTS: Two hundred and sixty patients received systemic corticosteroids (8%) with a mean daily dose of 45 (33) mg (median, 36 mg/day). Patients receiving corticosteroids were older (74 (13) vs 65 (19) years), had more comorbidities (respiratory, 59% vs 38%, cardiac, 29% vs 16%, etc.), higher Pneumonia Severity Index (Fine IV-V, 76% vs 50%) and had received inhaled corticosteroids (36% vs 15%) and previous antibiotics (31% vs 23%) more frequently (P < 0.01, each). Significant predictors of corticosteroid administration were: chronic obstructive pulmonary disease (odds ratio (OR), 1.91), fever (OR, 0.59), expectoration (OR, 1.59), creatinine (+1 mg/dL, OR, 0.92), SaO(2) ≥ 92% (OR, 0.46), C-reactive protein (+5 mg/dL; OR, 0.92) and cardiac failure (OR, 1.76). Mortality (6% vs 7%; P = 0.43) and time to clinical stability (4 (3-6) vs 5 (3-7) days; P = 0.11) did not differ between the two groups, while length of hospital stay was longer for the steroid group (9 (6-14) vs 6 (3-9) days; P < 0.01). CONCLUSIONS: The main reasons for administering systemic steroids were the presence of chronic respiratory comorbidity or severe clinical presentation, but therapy did not influence mortality or clinical stability; by contrast, steroid administration was associated with prolonged length of stay. Nevertheless the steroid group did not show an increased mortality as it was expected according to the initial Pneumonia Severity Index score. Influence of steroids on outcomes of CAP need to be further investigated through randomized clinical trial.

Integral mediastinal staging in patients with NON-SMALL cell lung cancer and risk factors for occult N2 disease.

BACKGROUND: In patients with non-small cell lung cancer (NSCLC), the presence of abnormal hiliar lymph nodes (clinical N1; cN1), central tumor location and/or tumor size (diameter >3 cm) increases the risk of occult mediastinal metastasis (OMM). This study investigates prospectively the diagnostic value of an integral mediastinal staging (IMS) strategy that combines EndoBronchial Ultrasound-TransBronchial Needle Aspiration (EBUS-TBNA) and Video-Assisted Mediastinoscopy (VAM) in patients with NSCLC at risk of OMM. METHODS: Patients with NSCLC and radiologically normal mediastinum assessed non-invasively by positron emission tomography and computed tomography of the chest (PET-CT), and OMM risk factors (cN1, central tumor and/or >3 cm) underwent EBUS-TBNA followed by VAM if the former was negative. Those with negative IMS underwent resection surgery of the tumor. RESULTS: EBUS-TBNA identified OMM in 2 out of the 49 patients evaluated (4%) and VAM in 1 of the 47 patients with negative EBUS (2%). Two patients with a negative IMS had OMM at surgery. Overall, the prevalence of OMM was 10%. EBUS-TBNA has a sensitivity of 40%, a negative predictive value (NPV) of 93.6%, and negative likelihood ratio of 0.60 (95%CI:0.30-1.16). The risk of not diagnosing OMM after EBUS was 6% and after IMS was 4.4%. CONCLUSION: Integral mediastinal staging in patients with NSCLC and clinical risk factors for OMM, does not seem to provide added diagnostic value to that of EBUS-TBNA, except perhaps in patients with cN1 disease who deserve further research.

Sputum purulence-guided antibiotic use in hospitalised patients with exacerbations of COPD.

In patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) needing hospitalisation, sputum purulence is associated with bacteria in the lower respiratory tract. We performed a prospective non-randomised interventional pilot study applying a sputum purulence-guided strategy of antibiotic treatment and investigating the relationship between sputum purulence and biomarkers. In hospitalised patients with acute exacerbation of COPD antibiotics were restricted to those with purulent sputum. The primary end-point was rate of therapeutic failure during hospitalisation. Secondary end-points were parameters reflecting short- and long-term outcomes. We included 73 patients, 34 with non-purulent sputum. No differences were observed on therapeutic failure criteria (9% non-purulent versus 10% purulent (p=0.51)). Serum C-reactive protein (CRP) was significantly increased in the purulent group at admission (11.6 versus 5.3, p=0.006) and at day 3 (2.7 versus 1.2, p=0.01). Serum procalcitonin (PCT) was similar between the groups. No differences were found in short-term outcomes. The exacerbation rate at 180 days was higher in the purulent group. These results support the hypothesis of performing a randomised trial using a sputum purulence-guided antibiotic treatment strategy in patients with acute exacerbations of COPD. CRP, but not PCT, may be a useful parameter to increase confidence of the absence of bacterial bronchial infection.

Efficacy predictors of lung volume reduction with Zephyr valves in a European cohort.

The Endobronchial Valve for Emphysema Palliation Trial (VENT) was a multi-centre, prospective, randomised, controlled trial conducted to evaluate the safety and effectiveness of unilateral endobronchial valve (EBV) treatment. The purpose of this analysis was to assess outcomes in the previously unreported European VENT study cohort. Patients with advanced emphysema were randomly assigned (2:1) to receive Zephyr® (Pulmonx Inc., Redwood City, CA, USA) EBV treatment (n = 111) or medical management (n = 60). At 6 months, EBV patients demonstrated a significant improvement compared with the controls for mean ± SD change in forced expiratory volume in 1 s (7 ± 20% versus 0.5 ± 19%; p = 0.067), cycle ergometry (2 ± 14 W versus -3 ± 10 W; p = 0.04) and St George's Respiratory Questionnaire (-5 ± 14 points versus 0.3 ± 13 points; p = 0.047). At 12 months, the magnitude of the difference between groups for change from baseline was of similar magnitude to the differences seen at 6 months. Rates for complications did not differ significantly. EBV patients with computed tomography (CT) scans suggestive of complete fissure and lobar occlusion had a mean ± SD lobar volume reduction of -80 ± 30% and >50% met minimal clinical difference thresholds. The degree of emphysema heterogeneity did not preclude excellent outcomes. Unilateral lobar volume reduction using EBV treatment is safe and superior clinical results correlated with CT suggestive of complete fissures and successful lobar occlusion. Emphysema heterogeneity was not critical for determining positive outcomes.

Efficacy of linezolid compared to vancomycin in an experimental model of pneumonia induced by methicillin-resistant Staphylococcus aureus in ventilated pigs.

OBJECTIVE: To assess the efficacy of linezolid compared with vancomycin in an experimental model of pneumonia induced by methicillin-resistant Staphylococcus aureus (MRSA) in ventilated pigs. METHODS: Forty pigs (30 kg) were intubated and challenged via bronchoscopy with a suspension of 106 colony forming units of MRSA into every lobe. Afterwards, pigs were ventilated up to 96 hours. Twelve hours after bacterial inoculation, the animals were randomized into 4 groups of treatment: group 1, control; group 2, vancomycin twice daily; group 3, continuous infusion of vancomycin; and group 4, linezolid. Clinical and laboratory parameters were monitored throughout the study. Bacterial cultures of bronchoalveolar lavage fluid and lung tissue samples were performed at the end of the study. Measurements of histopathology derangements of lung samples and studies of intrapulmonary drug penetration were performed. RESULTS: A total of 34 animals completed the study. No differences in clinical and laboratory parameters were observed. The percentage of bronchoalveolar lavage fluid and lung tissue samples with positive cultures for MRSA in controls and groups 2, 3, and 4 was respectively 75%, 11%, 11%, and 0% (p < .01); 52%, 9%, 24%, and 2.5% (p < .01). Histopathology studies demonstrated signs of pneumonia in 95%, 69%, 58%, and 57% and signs of severe pneumonia in 48%, 29%, 22%, and 0% of controls and groups 2, 3, and 4, respectively (p < .01). In addition, pharmacokinetics/pharmacodynamics profile in serum and lung tissue showed better results for linezolid compared with both vancomycin treatments. CONCLUSIONS: In this animal model of MRSA pneumonia, linezolid showed a better efficacy than vancomycin showed because of a better pharmacokinetics/pharmacodynamics index.

Linezolid limits burden of methicillin-resistant Staphylococcus aureus in biofilm of tracheal tubes.

OBJECTIVE: To evaluate the effects of systemic treatment with linezolid compared with vancomycin on biofilm formation in mechanically ventilated pigs with severe methicillin-resistant Staphylococcus aureus-induced pneumonia. DESIGN: Prospective randomized animal study. SETTING: Departments of Pneumology, Microbiology, and Pharmacy of the Hospital Clínic, Barcelona, and Scientific and Technological Services of the University of Barcelona. SUBJECTS: We prospectively analyzed 70 endotracheal tube samples. Endotracheal tubes were obtained from pigs either untreated (controls, n=20), or treated with vancomycin (n=32) or linezolid (n=18). INTERVENTIONS: The endotracheal tubes were obtained from a previous randomized study in tracheally intubated pigs with methicillin-resistant Staphylococcus aureus severe pneumonia, and mechanically ventilated for 69±16 hrs. MEASUREMENTS AND MAIN RESULTS: Distal and medial hemisections of the endotracheal tube were assessed to quantify methicillin-resistant Staphylococcus aureus burden, antibiotic biofilm concentration by high-performance liquid chromatography or bioassay, and biofilm thickness through scanning electron microscopy. We found a trend toward a significant variation in biofilm methicillin-resistant Staphylococcus aureus burden (log colony-forming unit/mL) among groups (p=.057), and the lowest bacterial burden was found in endotracheal tubes treated with linezolid (1.98±1.68) in comparison with untreated endotracheal tubes (3.72±2.20, p=.045) or those treated with vancomycin (2.97±2.43, p=.286). Biofilm linezolid concentration was 19-fold above the linezolid minimum inhibitory concentration, whereas biofilm vancomycin concentration (1.60±0.91 µg/mL) was consistently below or close to the vancomycin minimum inhibitory concentration. Biofilm was thicker in the vancomycin group (p=.077). CONCLUSIONS: Systemic treatment with linezolid limits endotracheal tube biofilm development and methicillin-resistant Staphylococcus aureus burden. The potential clinical usefulness of linezolid in decreasing the risk of biofilm-related respiratory infections during prolonged tracheal intubation requires further investigation.

EBUS-TBNA Cytological Samples for Comprehensive Molecular Testing in Non-Small Cell Lung Cancer.

Clinical guidelines promote the identification of several targetable biomarkers to drive treatment decisions in advanced non-small cell lung cancer (NSCLC), but half of all patients do not have a viable biopsy. Specimens from endobronchial-ultrasound transbronchial needle aspiration (EBUS-TBNA) are an alternative source of material for the initial diagnosis of NSCLC, however their usefulness for a complete molecular characterization remains controversial. EBUS-TBNA samples were prospectively tested for several biomarkers by next-generation sequencing (NGS), nCounter, and immunohistochemistry (PD-L1). The primary objectives were to assess the sensitivity of EBUS-TBNA samples for a comprehensive molecular characterization and to compare its performance to the reference standard of biopsy samples. Seventy-two EBUS-TBNA procedures were performed, and 42 NSCLC patients were diagnosed. Among all cytological samples, 92.9% were successfully genotyped by NGS, 95.2% by nCounter, and 100% by immunohistochemistry. There were 29 paired biopsy samples; 79.3% samples had enough tumor material for genomic genotyping, and 96.6% for PD-L1 immunohistochemistry. A good concordance was found between both sources of material: 88.9% for PD-L1, 100% for NGS and nCounter. EBUS-TBNA is a feasible alternative source of material for NSCLC genotyping and allows the identification of patient candidates for personalized therapies with high concordance when compared with biopsy.

Predicting bacteremic pneumonia in HIV-1-infected patients consulting the ED.

INTRODUCTION: HIV-1-infected patients have higher incidence of community-acquired pneumonia (CAP) and risk of complications. Bacteremia has been associated with a higher risk of complications in such patients. We investigated factors associated with bacteremia in HIV-1-infected patients with CAP presenting at the emergency department. METHODS: We included HIV-1-infected patients with CAP for 3 years (March 2005-February 2008). Only patients in whom blood cultures were performed were finally included. Clinical data (age; sex; CD4(+) count; serum HIV viral load; previous or current intravenous drug use and antiretroviral treatment; systolic blood pressure; and cardiac and respiratory rates), analytical data (leukocyte count, arterial oxygen content, C-reactive protein value, and urgent Streptococcus pneumoniae and Legionella spp antigen urine detection), and APACHE-II (Acute Physiology and Chronic Health Evaluation) score were compiled. The need for intensive care unit admission, mechanical ventilation, mortality, and for patients finally discharged, duration of admission were retrospectively obtained from the clinical history. A multivariate analysis using logistic regression was performed to find independent predictors of bacteremia. RESULTS: We diagnosed 129 HIV-1-infected patients with CAP. Blood cultures were performed in 118 cases (91%). Bacteremia was present in 28 (24%). Independent predictors of bacteremia were the detection of S pneumoniae antigen in urine (odds ratio, 9.0; 95% confidence interval, 1.9-42.0) and the absence of current antiretroviral treatment (odds ratio, 7.1; 95% confidence interval, 1.4-33.3). In-hospital mortality was higher in patients with bacteremia (15% vs 0%). CONCLUSION: HIV-1-infected patients with CAP who are not on current antiretroviral therapy and have positive S pneumoniae antigenuria are at increased risk of having bacteremia. Bacteremic patients have a poor outcome.

Impact of a systematic evaluation of connective tissue disease on diagnosis approach in patients with interstitial lung diseases.

To date, there is no clear agreement regarding which is the best method to detect a connective tissue disease (CTD) during the initial diagnosis of interstitial lung diseases (ILD). The aim of our study was to explore the impact of a systematic diagnostic strategy to detect CTD-associated ILD (CTD-ILD) in clinical practice, and to clarify the significance of interstitial pneumonia with autoimmune features (IPAF) diagnosis in ILD patients.Consecutive patients evaluated in an ILD Diagnostic Program were divided in 3 groups: IPAF, CTD-ILD, and other ILD forms. Clinical characteristics, exhaustive serologic testing, high resolution computed tomography (HRCT) images, lung biopsy specimens, and follow-up were prospectively collected and analyzed.Among 139 patients with ILD, CTD was present in 21 (15.1%), 24 (17.3%) fulfilled IPAF criteria, and 94 (67.6%) were classified as other ILD forms. Specific systemic autoimmune symptoms such as Raynaud phenomenon (19%), inflammatory arthropathy (66.7%), and skin manifestations (38.1%) were more frequent in CTD-ILD patients than in the other groups (all P < .001). Among autoantibodies, antinuclear antibody was the most frequently found in IPAF (42%), and CTD-ILD (40%) (P = .04). Nonspecific interstitial pneumonia, detected by HRCT scan, was the most frequently seen pattern in patients with IPAF (63.5%), or CTD-ILD (57.1%) (P < .001). In multivariate analysis, a suggestive radiological pattern by HRCT scan (odds ratio [OR] 15.1, 95% confidence interval [CI] 4.7-48.3, P < .001) was the strongest independent predictor of CTD-ILD or IPAF, followed by the presence of clinical features (OR 14.6, 95% CI 4.3-49.5, P < .001), and serological features (OR 12.4, 95% CI 3.5-44.0, P < .001).This systematic diagnostic strategy was useful in discriminating an underlying CTD in patients with ILD. The defined criteria for IPAF are fulfilled by a considerable proportion of patients referred for ILD.

MicroRNAs expressed during lung cancer development are expressed in human pseudoglandular lung embryogenesis.

BACKGROUND/AIMS: MicroRNAs (miRNAs) play a role during mouse embryonic development and are also important in carcinogenesis. In order to investigate whether there are similar patterns of miRNA expression levels in pseudoglandular human embryonic lung and in human lung tumors, we have analyzed 18 miRNAs (the let-7 family, the miR-17-92 cluster, miR-221 and miR-222) in human embryonic lung samples and in paired lung tumor and normal lung tissue samples and correlated the results with clinicopathological characteristics. METHODS: RNA was obtained from 12 human embryonic lung samples, 33 lung tumor samples and 33 paired normal lung samples. miRNAs were assessed by quantitative real-time PCR. RESULTS: Members of the let-7 family were downregulated and members of the miR-17-92 cluster and miR-221 were overexpressed both in embryonic lung tissue and in lung tumors. Low levels of let-7c were associated with absence of metastases (p = 0.015), early-stage non-small cell lung cancer (NSCLC, p = 0.05), and smokers (p = 0.009). High levels of miR-106a were associated with small-cell lung cancer (p = 0.031), and high levels of miR-19a with advanced NSCLC (p = 0.008). CONCLUSION: Our study lends support to the model of cancer as an alteration of normal development, as many miRNAs were similarly expressed in early human lung development and stage I-II of lung cancer development.

[Transbronchial needle aspiration in the study of mediastinal lymph nodes: yield and cost-effectiveness]. / Punción transbronquial aspirativa en el estudio de las adenopatías mediastínicas: rentabilidad y coste-beneficio.

OBJECTIVE: The role of different techniques for mediastinal staging in patients with suspected lung cancer is a subject of debate. The aim of this study was to analyze the diagnostic yield and cost-effectiveness of transbronchial needle aspiration in the mediastinal staging of lung cancer in patients being evaluated in a tertiary hospital. PATIENTS AND METHODS: This was a retrospective, observational study of the results of transbronchial needle aspiration in patients with suspected lung cancer and mediastinal lymph node involvement. A cost-effectiveness analysis of the systematic use of this technique was also performed. RESULTS: One-hundred ninety-four patients (85% men, 15% women) were evaluated. The diagnosis of lung cancer was confirmed in 157 (81%). Cytology samples obtained by transbronchial needle aspiration were adequate in 147 (76%) of the 194 cases. When only the adequate samples were included in the analysis, transbronchial needle aspiration showed a sensitivity of 88%, specificity of 100%, positive predictive value of 100%, negative predictive value of 64%, and efficiency of 90%. Mediastinoscopy was avoided in 44 (34%) of the 127 patients with localized non-small cell lung cancer, with an estimated saving of euro 119,456. CONCLUSIONS: Transbronchial needle aspiration has a high diagnostic yield and obviates the need for mediastinoscopy in a significant percentage of cases. This finding is of diagnostic and economic significance.

Experimental severe Pseudomonas aeruginosa pneumonia and antibiotic therapy in piglets receiving mechanical ventilation.

BACKGROUND: Little is known about the general and local consequences of severe pneumonia under mechanical ventilation (SPMV) and how these are resolved with antibiotic therapy (ABT). OBJECTIVES: To investigate the physiologic, biological, microbiological, and pathologic changes produced by experimental SPMV in a porcine model, and to evaluate the effect of ABT. METHODS: Pseudomonas aeruginosa was inoculated in 12 large white-Landrace piglets receiving mechanical that were killed after 72 h if death did not occur before. Vital signs, serum and BAL cytokines, serum C-reactive protein (CRP), and graded postmortem lung pathology and cultures (blood and quantitative BAL and lung) were evaluated. Six piglets received inappropriate ABT (no ABT or ceftriaxone), and six piglets received appropriate ABT (ciprofloxacin). MEASUREMENTS AND MAIN RESULTS: Pathologic and microbiological evidence of infection were present in all the animals in both groups. SPMV produced significant oxygenation and lung compliance worsening, increased serum CRP, and reduced BAL fluid tumor necrosis factor (TNF)-alpha. Arterial thrombosis in lung pathology was associated with higher temperature, hypoxemia and low lung compliance, higher initial serum CRP and TNF-alpha concentrations, and increased serum interleukin (IL)-6 and BAL IL-6 and TNF-alpha. Reduced ABT reduced body temperature and culture positivity. CONCLUSIONS: This model resembles VAP and has been used for studying pulmonary infection and inflammation related to mechanical ventilation. ABT reduced fever and bacterial burden in SPMV but had no effect on cytokine or CRP concentrations, oxygenation, or lung mechanics. Pulmonary artery thrombosis was associated with worse response to infection.

Microbiologic features and outcome of pneumonia in transplanted patients.

We prospectively evaluated lower respiratory tract infections in solid organ transplantation (SOT) patients to determine the microbiologic diagnosis and clinical outcomes. We diagnosed 83 cases of pneumonia, 38 of which were community acquired and 45 were nosocomial. Those with bilateral infiltrates or absence of improvement after 3 days of treatment underwent fiberoptic bronchoscopy. Bacterial pneumonia was the most frequent diagnosis and mixed infection predominated in the nosocomial group (11/45 nosocomial versus 1/38 community). Fiberoptic bronchoscopy with bronchoalveolar lavage had higher diagnostic yield in nosocomial pneumonia (77% versus 47%). Mortality differences between the 2 groups were 58% nosocomial versus 8% community-acquired infections (P < 0.001). SOT patients with nosocomial pneumonia, or those who needed mechanical ventilation, had a high mortality rate and benefits from the fiberoptic diagnostic techniques.

Fungal pneumonia, chronic respiratory diseases and glucocorticoids.

Invasive pulmonary aspergillosis (IPA) usually occurs in severely immunocompromised patients. The expanded use of glucocorticoids (GC) in clinical practice accounts for the increasing number of fungal infections reported in mildly or non-immunocompromised hosts. We report a series of 8 patients with fungal pneumonia in whom long term high dose GC treatment was the only risk factor for opportunistic infections. All patients except one had chronic underlying disorders (asthma, idiopathic fibrosis, chronic obstructive pulmonary disease, COPD). Seven patients were diagnosed with pulmonary aspergillosis. Etiological suspicion of fungal infection was obtained during lifetime in six cases and in one case was confirmed only in the post-mortem examination. In most cases bronchoscopic techniques allowed identification of the microorganism. However, delay in establishing the diagnosis (mean 20 days) precluded a prompt initiation of a specific treatment. The course of the fungal infection was ominous. All but one patient experienced progressive respiratory failure requiring ICU admission and mechanical ventilation support. Despite this, all of them died. The only survivor was a patient receiving early empirical antifungal treatment due to a high clinical suspicion of fungal infection. Based on the present and previous findings, antifungal treatment should be considered in chronic respiratory patients requiring high or repetitive doses of GC when there is clinical evidence of pneumonia and isolation of Aspergillus spp. from respiratory secretions.

Cryobiopsy in the diagnosis of diffuse interstitial lung disease: yield and cost-effectiveness analysis.

BACKGROUND: Assessment of patients with suspected interstitial lung disease (ILD) includes surgical lung biopsy (SLB) when clinical and radiological data are inconclusive. However, cryobiopsy is acquiring an important role in the ILD diagnostic process. The objective of this study was to evaluate the diagnostic yield, safety and economic costs of the systematic use of cryobiopsy in the assessment of patients with suspected ILD. METHODS: This was a retrospective observational study of patients who had undergone transbronchial cryobiopsy for evaluation of ILD from January 2011 to January 2014. The procedures were performed with a video bronchoscope using a cryoprobe for the collection of lung parenchyma specimens, which were analyzed by pathologists. Diagnostic yield, complications and economic costs of this technique were analyzed. RESULTS: Criobiopsy specimens from a total of 33 patients were included. A specific diagnosis was obtained in 26, producing a diagnostic yield of 79%. In 5 patients, SLB was required for a histopathological confirmation of disease, but the procedure could not be performed in 4, due to severe comorbidities. The most frequent complications were pneumothorax (12%) and gradei (9%) or gradeii (21%) bleeding. There were no life-threatening complications. The systematic use of cryobiopsy saved up to €59,846. CONCLUSION: Cryobiopsy is a safe and potentially useful technique in the diagnostic assessment of patients with ILD. Furthermore, the systematic use of cryobiopsy has an important economic impact.

Pulmonary infiltrates in patients receiving long-term glucocorticoid treatment: etiology, prognostic factors, and associated inflammatory response.

BACKGROUND: Glucocorticoid treatment alters immunoregulatory defense mechanisms and may therefore favor the development of different pulmonary infections. METHODS: The etiology, prognostic factors, and associated inflammatory response of pulmonary infiltrates in 33 patients receiving long-term glucocorticoid treatment (LTGCT) were prospectively evaluated. RESULTS: Aspergillus spp (n = 9, 31%) and Staphylococcus spp (n = 6, 21%) were the most common causative agents. Using different diagnostic techniques, we obtained a specific diagnosis in 28 of 33 episodes (85%) of pulmonary infiltrates. Bronchoscopic techniques provided the diagnosis in 64% of the cases. Crude mortality was 45%. Variables associated with mortality were as follows: age > 64 years, bilateral radiographic involvement, delay in diagnosis, inappropriate empirical treatment, Simplified Acute Physiology Score (SAPS) II > or = 25, and requirement for mechanical ventilation (MV). SAPS II > or = 25 (odds ratio [OR], 16; 95% confidence interval, 1 to 260) and MV requirement (OR, 50; 95% confidence interval, 2 to 360) were also significant on multivariate analysis. Pulmonary infections were associated with an increase in the concentration of relevant inflammatory cytokines such as tumor necrosis factor-alpha and interleukin-6 both in serum and BAL. This local and systemic inflammatory response was attenuated when compared with the response observed in patients with pulmonary infections but without glucocorticoid treatment or receiving glucocorticoids for a short period of time (< 9 days). CONCLUSIONS: Pulmonary infiltrates in patients receiving LTGCT are often caused by fungi and Gram-positive cocci, and are associated with attenuated local and systemic inflammatory response. Although in most cases, sputum cultures and bronchoscopic techniques are diagnostic, the associated mortality is high, particularly in those requiring MV.

Prognostic factors of non-HIV immunocompromised patients with pulmonary infiltrates.

STUDY OBJECTIVES: To assess the outcome and the prognostic factors in 200 non-HIV immunocompromised patients with pulmonary infiltrates (PIs). DESIGN: Prospective observational study. SETTING: An 800-bed university hospital. PATIENTS: Two hundred non-HIV immunocompromised patients (hematologic malignancies, 79 patients; hematopoietic stem cell transplants [HSCTs], 61 patients; and solid-organ transplants, 60 patients). METHODS: Investigation of prognostic factors related to mortality using a multiple logistic regression model. RESULTS: Specific diagnosis of the PI was obtained in 78% of the cases (infectious origin was determined in 74%). The overall mortality rate was 39% (78 of 200 patients). Patients with HSCT had the highest mortality rate (53%). A requirement for mechanical ventilation (odds ratio [OR], 28; 95% confidence interval [CI], 9 to 93), an APACHE (acute physiology and chronic health evaluation) II score of > 20 (OR, 5.5; 95% CI, 2 to 14.7), and a delay of > 5 days in establishing a specific diagnosis (OR, 3.4; 95% CI, 1.2 to 9.6) were the variables associated with mortality at the multivariate analysis. The subgroup analysis based on underlying disease confirmed the prognostic significance of these variables and the infectious etiology for the PI. CONCLUSIONS: Mortality in immunocompromised patients is high, particularly in patients undergoing HSCT. Achieving an earlier diagnosis potentially may improve the mortality rate of these patients.

Nosocomial pneumonia in immunosuppressed patients.

Nosocomial pneumonia represents a serious challenge for clinicians caring for IC patients. Although there have been advances in prophylactic, preemptive, and therapeutic measures, the implications of an inadequate empirical treatment for survival require a prompt and active attitude. A great diversity of diagnostic and laboratory procedures is currently available. In each case, the clinician must determine the tests that should be performed based on different variables. The proper use of noninvasive and bronchoscopic procedures substantially increases the diagnostic yield causing changes in the empirical treatment in most patients. The authors believe that fiberoptic bronchoscopy must be done early when the pulmonary infiltrates are identified if there is not a rapid (48 hours) and clear response to empiric treatment. This approach allows the establishment of a more specific treatment when the possibilities of full recovery are still high. The potential benefit of treatment modifications for survival in IC patients who require MV and undergo bronchoscopy is most probably minimal, because of the severity and irreversibility of the underlying pulmonary process. It is hoped that the application of molecular tools in diagnosis and the advances in preventive strategies and therapeutic agents will improve the survival of NP in a population of IC patients that is expected to grow over the next years.