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 / Characteristics of Asthma Patients Admitted to an Intermediate Respiratory Care Unit

Introducción: Las unidades de cuidados respiratorios intermedios (UCRI) permiten la monitorización continua y la ventilación mecánica no invasiva (VMNI) en los pacientes con insuficiencia respiratoria grave que habitualmente ingresan en unidades de cuidados intensivos (UCI). La utilidad de las UCRI en el manejo de las agudizaciones graves del asma nunca ha sido evaluada. Métodos: Se recogieron de forma prospectiva y sistemática los datos clínicos de pacientes ingresados en la UCRI con el diagnóstico principal de asma bronquial agudizada, se evaluó el fracaso terapéutico (intubación o fallecimiento) y su evolución hasta 6meses tras el alta, comparada con un grupo de pacientes ingresados en planta de hospitalización convencional pareados por edad y sexo, con el mismo diagnóstico principal. Resultados: Se incluyeron un total de 74 pacientes asmáticos (37 ingresan en la UCRI y 37 en planta) con una edad media (±DE) de 58±20 años, predominantemente mujeres (67%), con diagnóstico previo y tratamiento de asma persistente. La causa principal de ingreso en la UCRI fue insuficiencia respiratoria grave. Los pacientes que ingresaron en la UCRI presentaron más afectación radiológica (infiltrados alveolares) y tenían una pCO2 significativamente mayor. Diez pacientes ingresados en la UCRI precisaron VMNI. No hubo diferencias entre ambos grupos en fracasos terapéuticos, ni en seguimiento a los 6meses del alta. Conclusiones: Los pacientes con agudizaciones graves del asma pueden ser atendidos en una UCRI, evitando ingresos en la UCI y con un pronóstico similar a las agudizaciones más leves que son ingresadas en una planta de hospitalización convencional(AU)

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 (ICUs). 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 pCO2. Ten patients admitted to the IRCU required non-invasive mechanical ventilation (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(AU)

Characteristics of asthma patients admitted to an intermediate respiratory care unit.

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.

Molecular mechanisms of inflammation during exacerbations of chronic obstructive pulmonary disease.

INTRODUCTION: Exacerbations of chronic obstructive pulmonary disease (COPD) are characterised by an inflammatory and systemic response that persists for some time after their clinical resolution. The mechanisms of this inflammatory process are not well known. OBJECTIVES: To explore the inflammatory changes and possible mechanisms during COPD exacerbation. METHODS: We determined the inflammatory cell concentrations in blood and sputum, nitric oxide in exhaled air (FeNO), C-reactive protein (CRP) in plasma, cytokines (IL-6, 8, 1ß, 10, 12, TNF-α) and SLPI (leukocyte protease inhibitor) and total antioxidant status (TAS) in blood and sputum, the activity of nuclear kappa B factor (NF-κ B) and of the histone deacetylase enzyme (HDAC) in 17 patients during COPD exacerbation and in stable phase, as well as in 17 smoker and 11 non-smoker controls. RESULTS: COPD exacerbations are characterised by high levels of FeNO (p<0.05), plasma CRP (p<0.001) and IL-8, IL-1B, IL-10 in sputum (p<0.05) greater activation of NF-κ appaB in sputum macrophages compared with stable COPD and controls. During the stable phase, there continue to be high levels of oxidative stress, SLPI, IL-8, IL-6 and TNF-alfa, with no observed changes in either HDAC activity or in the amount of neutrophils in sputum, despite presenting a significant improvement (p<0.05) in lung function. CONCLUSIONS: Changes were observed in different pulmonary and systemic inflammatory markers during COPD exacerbation, which did not completely resolve during stable phase. However, current treatment does not allow for HDAC activity to be modified, which limits its anti-inflammatory effects.

Mecanismos moleculares de inflamación durante las agudizaciones de la enfermedad pulmonar obstructiva crónica / Molecular Mechanisms of Inflammation During Exacerbations of Chronic Obstructive Pulmonary Disease

Introducción: Las agudizaciones de la enfermedad pulmonar obstructiva crónica (AEPOC) se caracterizanpor una respuesta inflamatoria pulmonar y sistémica, que persiste tiempo después de la resolución clínica.Los mecanismos de este proceso inflamatorio no son bien conocidos.Objetivos: Investigar los cambios inflamatorios y sus mecanismos durante las agudizaciones de la EPOC.Métodos: Se determinaron las concentraciones de células inflamatorias en sangre y esputo, óxido nítricoen aire exhalado (FeNO), proteína C reactiva (PCR) en plasma, citocinas (interleucinas [IL] 6, 8, 1 , 10,12, TNF- ) y SLPI (inhibidor de la leucoproteasa), marcadores de estrés oxidativo, la actividad del factornuclear kappa B (NF- B) y de la enzima histona deacetilasa (HDAC) a 17 pacientes durante una AEPOC,en fase estable y a 17 controles fumadores y 11 no fumadores.Resultados: Las AEPOC se caracterizaron por presentar niveles elevados de FeNO (p < 0,05), PCR en plasma(p < 0,001) e IL-8, IL-1 , IL-10 en esputo (p < 0,05) y mayor activación de NF- B en macrófagos de esputoen comparación con EPOC estable y controles. Durante la fase estable persisten niveles elevados de estrésoxidativo, SLPI, IL-8, IL-6 y TNF-alfa, sin objetivarse cambios en la actividad HDAC ni en la cantidad deneutrófilos en esputo a pesar de presentar una mejoría significativa (p < 0,05) de la función pulmonar.Conclusiones: Durante las AEPOC se observan cambios en marcadores inflamatorios pulmonares y sistémicosque no se resuelven por completo en fase estable. El tratamiento actual no permite modificar laactividad HDAC lo que limita sus efectos antiinflamatorios(AU)

Introduction: Chronic obstructive pulmonary disease (COPD) is characterised by an inflammatory andsystemic response that increases during exacerbations of the disease (ECOPD), although the mechanismsof this inflammatory process are not well known.Objectives: To explore the inflammatory changes and possible mechanisms during ECOPD.Methods: We determined the inflammatory cell concentrations in blood and sputum, nitric oxide inexhaled air (FeNO), reactive C-reactive protein (CRP) in plasma, cytokines (IL-6, 8, 1 , 10, 12, TNF- )and SLPI and total antioxidant activity (TAS) in blood and sputum, the activity of nuclear kappa B factor(NF-kB) and of the histone deacetylase enzymes (HDAC) in 17 patients during ECOPD, in stable phase andin 17 smoking controls and 11 non- smoking.Results: ECOPD is characterised by higher levels of FeNO (P<.05), plasma CRP (P<.001) and IL-8, IL-1B,IL-10 in sputum (P<.05) compared with stable COPD and controls. The TAS levels in sputum were lowerin the exacerbated than in stable phase (P<.05) although significantly higher than the controls (P<.05). These findings were accompanied by a greater activation of NF-kB in sputum macrophages during theECOPD with no changes in the HDAC activity or in the number of neutrophils in sputum, and a statisticallysignificant deterioration (P<.05) of lung function.Conclusions: Changes were observed in different pulmonary and systemic inflammatory markers duringECOPD, that were not completely resolved during stability. However, current treatment does not allowthe modification of HDAC activity, which limits its anti-inflammatory effects(AU)

Control del asma. Posibles “piedras en el camino” / Asthma control. Possible obstacles along the way

Con las pautas terapéuticas actuales, la mayoría de pacientes con asma debería alcanzar un buen control dela enfermedad. Sin embargo, aunque si bien los ingresos y la mortalidad por asma han disminuido, los resultadosrelativos al nivel de control y calidad de vida están lejos de la situación óptima que sería esperablede acuerdo a la eficacia potencial de los tratamientos. Esta discrepancia puede deberse a diferentes factoresy es compleja de analizar. Un mal control del asma puede estar causado por motivos tan diversos como queel paciente no haya entendido como tomar la medicación, u otros como que padezca una comorbilidad notratada que empeore el asma o bien que sufra una forma de asma grave insensible a los glucocorticoides.En el artículo se repasan circunstancias en las que el mal control del asma sucede por razones atribuibles aaspectos humanos, los cuales pueden ser debidos al propio paciente e independientes a la propia enfermedad,o bien a un déficit en la actuación de los profesionales de la salud en aspectos específicos y circunstanciasvinculadas al asma. Además, también se analiza un pequeño pero importante grupo de pacientes conasma en los que la enfermedad en sí misma es grave y refractaria a los tratamientos habituales(AU)

With current therapeutic regimens, asthma should be well controlled in most patients. However, althoughasthma-related hospital admissions and mortality have decreased, the potential efficacy of treatments isnot translating into optimal asthma control and quality of life. This discrepancy may be due to severalfactors and is complex to analyze. Poor asthma control can be caused by diverse reasons such as thepatient’s failure to understand how to take the medication, the presence of an untreated, underlyingcomborbid condition that aggravates the asthma, and the possibility that the patient has a severe form ofglucocorticosteroid-insensitive asthma.The present article reviews the situations in which poor asthma control occurs for human-related reasons.These situations can be due to patients themselves and be independent of the disease or can be due toinadequate intervention by health professionals in specific areas and circumstances linked to asthma. Asmall but important group of patients with asthma is also analyzed; in this group, the asthma per se issevere and is refractory to routine treatments(AU)

[Asthma control. Possible obstacles along the way]. / Control del asma. Posibles "piedras en el camino"

With current therapeutic regimens, asthma should be well controlled in most patients. However, although asthma-related hospital admissions and mortality have decreased, the potential efficacy of treatments is not translating into optimal asthma control and quality of life. This discrepancy may be due to several factors and is complex to analyze. Poor asthma control can be caused by diverse reasons such as the patient's failure to understand how to take the medication, the presence of an untreated, underlying comorbid condition that aggravates the asthma, and the possibility that the patient has a severe form of glucocorticosteroid-insensitive asthma. The present article reviews the situations in which poor asthma control occurs for human-related reasons. These situations can be due to patients themselves and be independent of the disease or can be due to inadequate intervention by health professionals in specific areas and circumstances linked to asthma. A small but important group of patients with asthma is also analyzed; in this group, the asthma per se is severe and is refractory to routine treatments.