Federico Fiorentino

Using the Electronic Nose to Identify Airway Infection during COPD Exacerbations.

Background The electronic nose (e-nose) detects volatile organic compounds (VOCs) in exhaled air. We hypothesized that the exhaled VOCs print is different in stable vs. exacerbated patients with chronic obstructive pulmonary disease (COPD), particularly if the latter is associated with airway bacterial infection, and that the e-nose can distinguish them. Methods Smell-prints of the bacteria most commonly involved in exacerbations of COPD (ECOPD) were identified in vitro. Subsequently, we tested our hypothesis in 93 patients with ECOPD, 19 of them with pneumonia, 50 with stable COPD and 30 healthy controls in a cross-sectional case-controlled study. Secondly, ECOPD patients were re-studied after 2 months if clinically stable. Exhaled air was collected within a Tedlar bag and processed by a Cynarose 320 e-nose. Breath-prints were analyzed by Linear Discriminant Analysis (LDA) with “One Out” technique and Sensor logic Relations (SLR). Sputum samples were collected for culture. Results ECOPD with evidence of infection were significantly distinguishable from non-infected ECOPD (p = 0.018), with better accuracy when ECOPD was associated to pneumonia. The same patients with ECOPD were significantly distinguishable from stable COPD during follow-up (p = 0.018), unless the patient was colonized. Additionally, breath-prints from COPD patients were significantly distinguished from healthy controls. Various bacteria species were identified in culture but the e-nose was unable to identify accurately the bacteria smell-print in infected patients. Conclusion E-nose can identify ECOPD, especially if associated with airway bacterial infection or pneumonia.

Usefulness of Bronchoscopic Probe-Based Confocal Laser Endomicroscopy in the Diagnosis of Pneumocystis jirovecii Pneumonia

Background: Probe-based confocal laser endomicroscopy (pCLE) is a novel technique that provides in vivo microscopic imaging of the distal lung. We hypothesized that the intra-alveolar exudates characterizing Pneumocystis jirovecii pneumonia (PJP) can be identified by pCLE in vivo and help in its diagnosis. Objectives: We aimed to assess the usefulness of pCLE for the in vivo diagnosis of PJP. Methods: Thirty-two human immunodeficiency virus (HIV)-positive patients with new pulmonary infiltrates and fever were studied using pCLE. Real-time alveolar images were recorded during the bronchoscopy for off-line analysis by two independent observers. Bronchoalveolar lavage samples were also obtained and processed for microbiology and cytological evaluation, including Grocott stain for P. jirovecii. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of pCLE for the diagnosis of PJP in these patients were calculated. Results: Fourteen patients (44%) were confirmed to have PJP by cultures/staining. pCLE was well tolerated in all patients. It identified intra-alveolar exudates in 13 of them (41%), where 11 of them (85%) had positive Grocott stain for P. jirovecci, with 93% concordance between observers. Sensitivity, specificity, PPV and NPV of pCLE for the diagnosis of PJP were 79, 89, 85 and 84%, respectively. In smokers, these figures improved to be 92, 88, 85 and 94%. Conclusions: pCLE is a quick and safe procedure for on-site diagnosis of PJP in HIV+ patients with excellent specificity and sensitivity mainly in smokers.

Structure–function relationship in COPD revisited: an in vivo microscopy view

Background Fibred confocal fluorescence microscopy (FCFM) is a novel technology that allows the in vivo assessment and quantification during bronchoscopy of the bronchial wall elastic fibre pattern, alveolar and vessel diameters and thickness of the elastic fibre in the alveolar wall. Aims To relate these structural characteristics with lung function parameters in healthy subjects, smokers with normal spirometry and patients with chronic obstructive pulmonary disease (COPD). Methods We performed FCFM in 20 never smokers, 20 smokers with normal spirometry and 23 patients with COPD who required bronchoscopy for clinical reasons. The bronchial wall elastic fibre pattern was classified as lamellar, loose and mixed pattern, and later confirmed pathologically. Airspace dimensions and extra-alveolar vessel diameters were measured. Lung function measurements and pulmonary CT scans were obtained in all participants. Results Patients with COPD were characterised by a significantly higher prevalence of loose fibre bronchial deposition pattern and larger alveolar diameter which correlated inversely with several lung function parameters (forced expiratory volume in 1 s (FEV1) , FEV1/forced vital capacity ratio, maximum expiratory flow, carbon monoxide transfer factor and carbon monoxide transfer coefficient; p<0.05). Increased alveolar macrophages were demonstrated in active smokers with or without COPD. Conclusions This is the first FCFM study to describe in vivo microscopic changes in the airways and alveoli of patients with COPD that are related to lung function impairment. These findings open the possibility of assessing the in vivo effects of therapeutic interventions for COPD in future studies.

Características de pacientes asmáticos ingresados en una unidad de cuidados respiratorios intermedios

INTRODUCTION Intermediate respiratory care units (IRCU) provide continuous monitoring and non-invasive mechanical ventilation (NIMV) in patients with severe respiratory failure who are usually admitted to intensive care units (ICU). The usefulness of IRCU in managing severe asthma exacerbations has never been evaluated. METHODS Clinical data were prospectively and systematically compiled from patients admitted to the IRCU with a principal diagnosis of bronchial asthma exacerbation. We assessed therapeutic failure (intubation or exitus) and patient evolution up until 6 months after discharge compared with a group of patients admitted to a conventional hospital ward, paired for age and sex, and with the same principal diagnosis. RESULTS A total of 74 asthma patients were included (37 admitted to IRCU and 37 to the hospital ward) with a mean age (±SD) of 58±20, who were predominantly women (67%), with previous diagnosis of asthma and persistent asthma treatment. The main cause of admittance to the IRCU was severe respiratory failure. The patients who were admitted to the IRCU presented more radiological affectation (alveolar infiltrates) and had significantly higher pCO(2). Ten patients admitted to the IRCU required NIMV. There were no differences between the two groups regarding either therapeutic failure or the 6-month follow-up after discharge. CONCLUSIONS Patients with severe asthma exacerbations can be managed in an IRCU while avoiding hospitalization in an ICU and demonstrating a prognosis similar to milder exacerbations treated in conventional hospital wards.

EPOC y asma

Chronic obstructive pulmonary disease and asthma are both highly prevalent inflammatory diseases characterized by airway obstruction with distinct pathogenic mechanisms and different degrees of response to antiinflammatory therapy. However, forms of presentation that show overlap between both diseases and which are not clearly represented in clinical trials are frequently encountered in clinical practice. These patients may show accelerated loss of pulmonary function and have a worse prognosis. Therefore their early identification is essential. Biomarkers such as bronchial hyperreactivity or nitric oxide in exhaled air have yielded discrepant results. Phenotypic characterization will allow treatment with inhaled corticosteroids to be individually tailored and optimized.

Effectiveness of a comprehensive management program of fragile COPD patients

Introduction: The frequent exacerbator phenotype of COPD (fragile COPD) is associated with higher mortality, more exacerbations and greater resource consumption. A comprehensive care management program (CCMP) can be useful for the patient and the healthcare system. Objective: To evaluate the efficacy of a CCMP for patients with fragile COPD. Methods: Case-control study of patients with fragile COPD followed- up for at least 12 months. Cases were included in a CCMP consisting specialized medical evaluation, telephone and onsite monitoring by a case manager nurse and access to specialized care for early treatment of exacerbation. Controls received usual outpatient care. The number of admissions, emergency room (ER) visits, hospital days, number of treatments with steroids or antibiotics and survival rate were evaluated. Results: 36 cases and 36 controls matched for age and sex were studied. At baseline, cases had worse lung function and greater dyspnea than controls (FEV1 0.83 ± 0.26 vs 1.29 ± 0.54, p = 0.0001; mMRC 2.7 ± 0.88 vs 1.91 ± 0.85, p = 0.0018 respectively). However, during follow-up, cases had fewer hospital admissions (0.27 ± 0.57 vs 2.5 ± 1.96, p Conclusion: A CCMP for fragile COPD patients is effective in the prevention of hospitalizations and reduction of moderate exacerbations compared to usual care.

Transbronchial cryobiopsy in the diagnosis of the idiopathic interstitial pneumonias

Background Histology is crucial for the multidisciplinary diagnosis of idiopathic interstitial pneumonias (IIP). Transbronchial cryobiopsy (TBC) has been demonstrated to be useful for obtaining lung parenchyma; however its experience in the diagnosis of IIP is limited. Objectives To describe the diagnostic yield and safety of TBC in the study of IIP. Method Prospective study of 23 outpatients of TBC. All cases had the typical clinical and radiological features of IIP. The endoscopic procedure was performed in the operating theatre using a flexible bronchoscope obtaining 3-5 biopsies of lung parenchyma with radiological control. Biopsies were reviewed by the reference pathologist. Results The patients were 65±10-year-old (57% men). The length range of biopsies was 2-7 mm. The sample was adequate (at least 20 alveolar spaces) in 20 patients (87%). The specific diagnosis (confirmed by Multidisciplinary discussion) was obtained in 12 patients (52%): usual interstitial pneumonia (UIP n=9) and nonspecific interstitial pneumonia (NSIP n=3). The complications were: pneumothorax in 2 patients (both required drainage), 4 patients showed significant bleeding (>100 ml), one of them severe with respiratory failure but the patient recovered 3 days after. In the remaining patients the diagnosis was reached by VATS (9 patients: UIP [n=5], unclassifiable interstitial pneumonia [n=2], NSIP [n=1] and respiratory bronchiolitis associated to interstitial pneumonia [n=1]), or by clinical and radiological parameters (1 organising pneumonia, 1 UIP). Conclusions In patients with suspected IIP, TBC is useful to obtain lung parenchyma with good yield and avoids in 52% of open biopsies in our population.

Predicción en tiempo real de la malignidad de ganglios linfáticos mediastínicos mediante ecografía endobronquial

OBJECTIVE To evaluate the utility of different ultrasonographic (US) features in differentiating benign and malignant lymph node (LN) by endobronchial ultrasound (EBUS) and validate a score for real-time clinical application. METHODS 208 mediastinal LN acquired from 141 patients were analyzed. Six different US criteria were evaluated (short axis ≥10 mm, shape, margin, echogenicity, and central hilar structure [CHS], and presence of hyperechoic density) by two observers independently. A simplified score was generated where the presence of margin distinction, round shape and short axis ≥10 mm were scored as 1 and heterogeneous echogenicity and absence of CHS were scored as 1.5. The score was evaluated prospectively for real-time clinical application in 65 LN during EBUS procedure in 39 patients undertaken by two experienced operators. These criteria were correlated with the histopathological results and the sensitivity, specificity, positive and negative predictive values (PPV and NPV) were calculated. RESULTS Both heterogenicity and absence of CHS had the highest sensitivity and NPV (≥90%) for predicting LN malignancy with acceptable inter-observer agreement (92% and 87% respectively). On real-time application, the sensitivity and specificity of the score >5 were 78% and 86% respectively; only the absence of CHS, round shape and size of LN were significantly associated with malignant LN. CONCLUSIONS Combination of different US criteria can be useful for prediction of mediastinal LN malignancy and valid for real-time clinical application.