The Role of Inflammatory Phenotype in Patients With Exacerbation-prone Asthma and Ongoing Therapy

Introduction: The risk factors for having frequent exacerbations are not well documented in cohort studies of patients with asthma on existing therapy. The objective of the present study was to compare the clinical and inflammatory characteristics of patients with exacerbation-prone asthma (EPA) with a history of two or more exacerbations in the previous year with those who had presented just one or no exacerbation. Methods: An ambispective observational study was conducted in a tertiary hospital. Patients diagnosed with moderate or severe asthma and ongoing therapy, whose inflammatory profile was determined by means of allergy and atopy status, blood eosinophilia and induced sputum were included. Patients were classified according to the number of asthma exacerbations in EPA (≥2 exacerbations in the previous year) vs. non-exacerbators (≤1 exacerbation in the previous year). Clinical, lung function and inflammatory characteristics of the two groups were compared. Results: Three hundred ten patients were visited in the Asthma Unit in 2018 and the combination of atopy and allergy status, blood eosinophilia and induced sputum was obtained in 96 (31%) patients. Of this latter group, 46 patients (47%) presented EPA compared to 50 (53%) non-exacerbators. Airway and blood eosinophilic inflammation did not differ between EPA and non-exacerbators in patients with asthma and ongoing therapy, and it was not a risk factor for EPA in our cohort. Conclusion: Airway or blood type 2 inflammation status is not a valid tool for recognizing EPA or predicting asthma exacerbations in asthma patients following controller therapy. (AU)

The Role of Inflammatory Phenotype in Patients With Exacerbation-prone Asthma and Ongoing Therapy.

INTRODUCTION: The risk factors for having frequent exacerbations are not well documented in cohort studies of patients with asthma on existing therapy. The objective of the present study was to compare the clinical and inflammatory characteristics of patients with exacerbation-prone asthma (EPA) with a history of two or more exacerbations in the previous year with those who had presented just one or no exacerbation. METHODS: An ambispective observational study was conducted in a tertiary hospital. Patients diagnosed with moderate or severe asthma and ongoing therapy, whose inflammatory profile was determined by means of allergy and atopy status, blood eosinophilia and induced sputum were included. Patients were classified according to the number of asthma exacerbations in EPA (≥2 exacerbations in the previous year) vs. non-exacerbators (≤1 exacerbation in the previous year). Clinical, lung function and inflammatory characteristics of the two groups were compared. RESULTS: Three hundred ten patients were visited in the Asthma Unit in 2018 and the combination of atopy and allergy status, blood eosinophilia and induced sputum was obtained in 96 (31%) patients. Of this latter group, 46 patients (47%) presented EPA compared to 50 (53%) non-exacerbators. Airway and blood eosinophilic inflammation did not differ between EPA and non-exacerbators in patients with asthma and ongoing therapy, and it was not a risk factor for EPA in our cohort. CONCLUSION: Airway or blood type 2 inflammation status is not a valid tool for recognizing EPA or predicting asthma exacerbations in asthma patients following controller therapy.

Promotion of physical activity after hospitalization for COPD exacerbation: A randomized control trial.

BACKGROUND AND OBJECTIVE: Physical activity worsens during exacerbations of chronic obstructive pulmonary disease (COPD) and notably after hospitalizations. Pedometer-based interventions are useful to increase physical activity in stable patients with COPD. However, there is little information concerning the implementation of such programs following severe exacerbation. This study assessed the efficacy of a physical activity program after hospitalization for a COPD exacerbation. METHODS: We performed a prospective, 12-week, parallel group, assessor-blinded, randomized control trial in COPD patients hospitalized for an exacerbation. After discharge, physical activity and other secondary variables were assessed. Patients were allocated (1:1) to a physical activity promotion program (intervention group, IG) or usual care (control group, CG). Based on a motivational interview and accelerometer physical activity assessment, a patient-tailored, pedometer-based, progressive and target-driven program was designed. Linear mixed effect models were used to analyse between-group differences. RESULTS: Forty-six out of 61 patients recruited were randomized and 43 (IG = 20, CG = 23) completed the study. In-hospital and baseline characteristics were similar in both groups. After 12 weeks of intervention, the mean steps difference between groups was 2093 steps/day, p = 0.018, 95% CI 376-4012, favouring the IG. Only the IG significantly increased the number of steps/day compared to baseline (mean difference [95% CI] 2932 [1069-4795] steps; p = 0.004). There were no other between-group differences. CONCLUSION: After hospitalization for a COPD exacerbation, a patient-tailored physical activity program based on a motivational interview and the use of pedometers, with progressive and customized targets, improved the number of steps/day.

Discriminant Validity of a Single Clinical Question for the Screening of Inactivity in Individuals Living with COPD.

Introduction: Quantifying physical activity in chronic obstructive pulmonary disease (COPD) with questionnaires and activity monitors in clinical practice is challenging. The aim of the present study was to analyse the discriminant validity of a single clinical question for the screening of inactive individuals living with COPD. Methods: A multicentre study was carried out in stable COPD individuals both in primary and tertiary care. Patients wore the Dynaport accelerometer for 8 days and then answered 5 physical activity questions developed for the study, referring to the week in which their physical activity was monitored. Receiver operating characteristic (ROC) curve analysis with physical activity level (PAL) as the gold standard reference was used to determine the best cut-off point for each of the 5 clinical physical activity questions tested. Results: A total of 86 COPD participants were analysed (males 68.6%; mean (SD) age 66.6 (8.5) years; FEV1 50.9 (17.3)% predicted; mean of 7305 (3906) steps/day). Forty-two (48.8%) participants were considered physically inactive (PAL ≤1.69). Answers to 4 out of 5 questions significantly differed in active vs inactive patients. The Kappa index and ROC curves showed that the answer to the question "On average, how many minutes per day do you walk briskly?" had the best discriminative capacity for inactivity, with an area under the curve (AUC) (95% Confidence interval (CI)) of 0.73 (0.63-0.84) and 30 min/day was identified as the best cut-off value (sensitivity (95% CI): 0.75 (0.60-0.87); specificity: 0.76 (0.61-0.88)). Conclusion: The present results indicate that self-reported brisk walk time lower than 30 min/day may be a valid tool for the screening of inactivity in individuals living with COPD in routine care, if more detailed physical activity measures are not feasible.

Is there a procoagulant state long-term after lung transplantation? A prospective study.

BACKGROUND: Venous thromboembolism (VTE) is a major complication after lung transplantation (LT). However, its pathophysiology remains unknown, and coagulation profiles have yet to be described. OBJECTIVE: The aim of this study was to longitudinally assess coagulation status after LT. METHODS: We performed a prospective study and described the coagulation profiles of 48 patients at 5 different time-points: before LT and at 24-72 h, 2 weeks, 4 months, and 1 year after LT. RESULTS: At baseline, almost all analyzed coagulation factors were within the normal range, except for FVIII, which was above the normal range. Von Willebrand factor (vWF) and FVIII were increased after LT and remained high at 1 year after transplantation. The cumulative incidence of VTE was 22.9%. Patients who developed VTE had higher FVIII activity 2 weeks after LT. CONCLUSIONS: This is the first study to describe coagulation profiles up to 1 year after LT. We show that most markers of a procoagulant state normalize at 2 weeks after LT, but that values of FVIII and vWF remain abnormal at 1 year. This problem has received little attention in the literature. Larger studies are necessary to confirm the results and to design appropriate prophylactic strategies.

Long-term results of sirolimus treatment in lymphangioleiomyomatosis: a single referral centre experience.

There are few published data on long-term treatment with sirolimus in lymphangioleiomyomatosis (LAM). The objective of this study was to describe the long-term effect of sirolimus in a series of LAM patients followed up in a referral centre, focusing on pulmonary function. We retrospectively reviewed a series of 48 patients with LAM diagnosed, followed up and treated with sirolimus in a single centre. Response to sirolimus was evaluated at 1 and 5 years. A negative sirolimus response was defined as an FEV1 decline greater than - 75 ml/year. A mixed-effects model was used to estimate the longitudinal changes in FEV1 (average slope), both as absolute (ml/year) and as predicted values (%predicted/year). From a total of 48 patients, 9 patients underwent lung transplantation and 4 died during the study. Mean (95% CI) FEV1 slope over 5 years was - 0.14 (- 26.13 to 25.85) ml/year in the whole LAM group, 42.55 (14.87 to 70.22) ml/year in the responder group, - 54.00 (- 71.60 to - 36.39) ml/year in the partial responder group and - 84.19 (- 113.5 to - 54.0) ml/year in the non-responder group. After 5 years of sirolimus treatment 59% had a positive response, 30% had a partial response and 11% had a negative response. Our study found that sirolimus treatment had a positive long-term effect on most LAM patients.

Near-normal aerobic capacity in long-term survivors after lung transplantation.

The clinical course of lung transplantation (LT) is diverse: some patients present chronic lung allograft dysfunction (CLAD) and progressive decline in pulmonary function, but others maintain normal spirometric values and active lives. OBJECTIVES: The aim of this study was to elucidate whether long-term LT survivors with normal spirometry achieve normal exercise capacity, and to identify predictive factors of exercise capacity. METHODS: This was a cross-sectional multicentre study, where bilateral LT recipients who survived at least 10 years after LT, with normal spirometry, no diagnosis of CLAD and modified Medical Research Council dyspnoea degree ≤2 underwent cardiopulmonary exercise testing (CPET). RESULTS: 28 LT recipients were included with a mean±sd age of 48.7±13.6 years. Oxygen uptake (V' O2 ) had a mean±sd value of 21.49±6.68 mL·kg-1·min-1 (75.24±15.6%) and the anaerobic threshold was reached at 48.6±10.1% of the V' O2max predicted. The mean±sd heart rate reserve at peak exercise was 17.56±13.6%. The oxygen pulse increased during exercise and was within normal values at 90.5±19.4%. The respiratory exchange ratio exceeded 1.19 at maximum exercise. The median (25-75th percentile) EuroQol-5D score was 1 (0.95-1), indicating a good quality of life. The median (25-75th percentile) International Physical Activity Questionnaire score was 5497 (4007-9832) MET-min·week-1 with 89% of patients reporting more than 1500 MET-min·week-1. In the multivariate regression models, age, sex and diffusing capacity of the lung for carbon monoxide remained significantly associated with V' O2max (mL·kg-1·min-1); haemoglobin and forced expiratory volume in 1 s were significantly associated with maximum work rate (watts), after adjusting for confounders. CONCLUSION: We report for the first time near-normal peak V' O2 values during CPET and normal exercise capacity in long-term LT recipients without CLAD.

Hypersensitivity Pneumonitis and (Idiopathic) Pulmonary Fibrosis Due to Feather Duvets and Pillows / Neumonitis por hipersensibilidad y fibrosis pulmonar (idiopática) debidas a los edredones y las almohadas de plumas

INTRODUCTION: Exposure to feather bedding may be an unnoticed cause of hypersensitivity pneumonitis (HP) and idiopathic pulmonary fibrosis (IPF). Thus, an in-depth clinical study of the diagnosis of patients with suspected HP and IPF is required in order to determine their etiologies. The objective of the present study is to raise awareness of HP and pulmonary fibrosis due to exposure to feather bedding, and to study the prevalence and describe long-term outcomes. METHODS: We describe a series of 33 patients diagnosed with HP and pulmonary fibrosis due to feather bedding exposure and followed over a 10-year period. The patients were from a subgroup of 127 individuals with HP undergoing in-depth evaluation using a diagnostic protocol at a regional referral center. RESULTS: Eleven (33%) patients were clinically diagnosed with acute HP and 22 (67%) with chronic HP. Ten (45%) chronic HP patients showed a high resolution computed tomography (HRCT) pattern of usual interstitial pneumonia (UIP) with suspected IPF. The prevalence of HP was 6.2/100 000 feather bedding users (compared with 54.6 per 100 000 bird-breeders). The survival rates of patients over the 10-year period was 100% for acute HP and 64% for chronic HP. CONCLUSIONS: In a series of HP patients, the diagnosis was attributed to feather bedding exposure in 26%. UIP pattern on HRCT was present in nearly half of the chronic cases. The survival of patients with chronic HP at ten years was 64%, despite avoiding further exposure

INTRODUCCIÓN: La exposición a la ropa de cama rellena de plumas puede ser una causa que pase inadvertida de neumonitis por hipersensibilidad (NH) y fibrosis pulmonar idiopática (FPI). Por lo tanto, se requiere un estudio clínico en profundidad durante el proceso diagnóstico de pacientes con sospecha de NH e FPI para determinar sus etiologías. El objetivo del presente estudio es crear conciencia sobre la NH y la fibrosis pulmonar debidas a la exposición a la ropa de cama rellena de plumas, y estudiar la prevalencia y describir los resultados a largo plazo. MÉTODOS: Describimos una serie de 33 pacientes diagnosticados con NH y fibrosis pulmonar debido a la exposición a la ropa de cama rellena de plumas y en seguimiento durante un período de 10 años. Los pacientes pertenecían a un subgrupo de 127 individuos con NH a los cuales se les estaba realizando una evaluación en profundidad utilizando un protocolo de diagnóstico en un centro de referencia regional. RESULTADOS: A 11 pacientes (33%) se les diagnosticó de NH aguda y a 22 (67%) de NH crónica. Diez de los pacientes con NH crónica (45%) mostraron un patrón de neumonía intersticial usual (NIU) en la tomografía computarizada de alta resolución (TCAR), con sospecha de FPI. La prevalencia de NH fue de 6,2/100.000 usuarios de ropa de cama rellena de plumas (en comparación con el 54,6 por cada 100.000 criadores de aves). Las tasas de supervivencia de los pacientes durante el período de 10 años fueron del 100% para la NH aguda y del 64% para la NH crónica. CONCLUSIONES: En una serie de pacientes con NH, el diagnóstico se atribuyó a la exposición a la ropa de cama rellena de plumas en un 26%. El patrón NIU en el TCAR estaba presente en casi la mitad de los casos crónicos. La supervivencia de los pacientes con NH crónica a los 10 años fue del 64%, a pesar de evitar posteriores exposiciones

Hypersensitivity Pneumonitis and (Idiopathic) Pulmonary Fibrosis Due to Feather Duvets and Pillows.

INTRODUCTION: Exposure to feather bedding may be an unnoticed cause of hypersensitivity pneumonitis (HP) and idiopathic pulmonary fibrosis (IPF). Thus, an in-depth clinical study of the diagnosis of patients with suspected HP and IPF is required in order to determine their etiologies. The objective of the present study is to raise awareness of HP and pulmonary fibrosis due to exposure to feather bedding, and to study the prevalence and describe long-term outcomes. METHODS: We describe a series of 33 patients diagnosed with HP and pulmonary fibrosis due to feather bedding exposure and followed over a 10-year period. The patients were from a subgroup of 127 individuals with HP undergoing in-depth evaluation using a diagnostic protocol at a regional referral center. RESULTS: Eleven (33%) patients were clinically diagnosed with acute HP and 22 (67%) with chronic HP. Ten (45%) chronic HP patients showed a high resolution computed tomography (HRCT) pattern of usual interstitial pneumonia (UIP) with suspected IPF. The prevalence of HP was 6.2/100 000 feather bedding users (compared with 54.6 per 100 000 bird-breeders). The survival rates of patients over the 10-year period was 100% for acute HP and 64% for chronic HP. CONCLUSIONS: In a series of HP patients, the diagnosis was attributed to feather bedding exposure in 26%. UIP pattern on HRCT was present in nearly half of the chronic cases. The survival of patients with chronic HP at ten years was 64%, despite avoiding further exposure.

Addition of Rituximab to Oral Corticosteroids in the Treatment of Chronic Hypersensitivity Pneumonitis / Adición de rituximab a los corticosteroides orales en el tratamiento de la neumonitis por hipersensibilidad crónica

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Use of serum KL-6 level for detecting patients with restrictive allograft syndrome after lung transplantation.

KL-6 is an antigen produced mainly by damaged type II pneumocytes that is involved in interstitial lung disease. Chronic lung allograft dysfunction (CLAD) after lung transplantation (LT) is a major concern for LT clinicians, especially in patients with restrictive allograft syndrome (RAS). We investigated KL-6 levels in serum and bronchoalveolar lavage fluid (BALF) as a potential biomarker of the RAS phenotype. Levels of KL-6 in serum and BALF were measured in 73 bilateral LT recipients, and patients were categorized into 4 groups: stable (ST), infection (LTI), bronchiolitis obliterans syndrome (BOS), and RAS. We also studied a healthy cohort to determine reference values for serum KL-6. The highest levels of KL-6 were found in the serum of patients with RAS (918 [487.8-1638] U/mL). No differences were found for levels of KL-6 in BALF. Using a cut-off value of 465 U/mL serum KL-6 levels was able to differentiate RAS patients from BOS patients with a sensitivity of 100% and a specificity of 75%. Furthermore, higher serum KL-6 levels were associated with a decline in Forced Vital Capacity (FVC) at 6 months after sample collection. Therefore, KL-6 in serum may well be a potential biomarker for differentiating between the BOS and RAS phenotypes of CLAD in LT recipients.

Promoción de la actividad física tras un ingreso hospitalario por exacerbación de la enfermedad pulmonar obstructiva crónica / Promoting Physical Activity After Hospitalization For Chronic Obstructive Pulmonary Disease Exacerbation

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Long-term outcomes in chronic hypersensitivity pneumonitis.

INTRODUCTION: The objective of this study was to analyze mortality, possible predictors of long-term survival, and health-related quality of life of a large chronic hypersensitivity pneumonitis (CHP) patient sample. METHODS: Longitudinal study in patients diagnosed with CHP during 2004-2013, followed for at least 1 year. Patients remaining alive and consenting to participate had a follow-up visit during 2015, including a complete pulmonary function study and the EuroQol-5D and Beck Depression and Anxiety Inventories. RESULTS: Out of the 160 patients finally included, 87 remained alive. Seventy-three had died or underwent lung transplantation at the time of the study with a median survival of 7.0 (4.4-14.5) years. A Cox proportional risk model showed that factors associated with lower survival were as follows: increased age, a low percentage of lymphocytes in bronchoalveolar lavage (BAL), a decreased transfer factor of the lung for carbonmonoxide (DLCO), presence of honeycomb in the high-resolution chest scan (HRCT), and the usual interstitial pneumonia (UIP) histologic pattern. At follow-up, all patients presented an EuroQol-5D score <0.8 and 21(50%) and 9(28.6%) subjects presented a probable anxiety and depressive syndrome, respectively. CONCLUSION: CHP is a severe disease with a bad mid-term prognosis. Lymphocyte values in BAL and DLCO values at baseline, presence of honeycomb in HRCT, and UIP histologic pattern were found to be predictors of survival. Early accurate diagnosis of the disease is fundamental for prompt initiation of antigen avoidance.

Prophylaxis with enoxaparin for prevention of venous thromboembolism after lung transplantation: a retrospective study.

Venous thromboembolism (VTE) is a frequent complication after solid organ transplantation (SOT) and, specifically, after lung transplantation (LT). The objectives of this study were to evaluate prophylaxis with enoxaparin and to describe risk factors for VTE after LT. We retrospectively reviewed the clinical records of 333 patients who underwent LT in our institution between 2009 and 2014. We compared two consecutive cohorts: one that received enoxaparin only during post-transplant hospital admissions and a second cohort that received 90-day extended prophylaxis with enoxaparin. Cumulative incidence function for competing risk analysis was used to determine incidence of VTE during the first year after transplantation. Risk factors were analyzed using a Cox proportional hazards regression model. The cumulative incidence of VTE was 15.3% (95% CI: 11.6-19.4). Median time from transplant to the event was 40 (p25-p75, 14-112) days. Ninety-day extended prophylaxis did not reduce the incidence of VTE. In this study, the risk factors associated with VTE were male gender and interstitial lung disease. VTE is a major complication after LT, and 90-day extended prophylaxis was not able to prevent it. Large, multicenter, randomized clinical trials should be performed to define the best strategy for preventing VTE.

BALF cytokines in different phenotypes of chronic lung allograft dysfunction in lung transplant patients.

The long-term success of lung transplantation (LT) is limited by chronic lung allograft dysfunction (CLAD). Different phenotypes of CLAD have been described, such as bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). The purpose of this study was to investigate the levels of cytokines and chemokines in bronchoalveolar lavage fluid (BALF) as markers of these CLAD phenotypes. BALF was collected from 51 recipients who underwent (bilateral and unilateral) LT. The study population was divided into three groups: stable (ST), BOS, and RAS. Levels of interleukin (IL)-4, IL-5, IL-6, IL-10, IL-13, tumor necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured using the multiplex technology. BALF neutrophilia medians were higher in BOS (38%) and RAS (30%) than in ST (8%) (P=.008; P=.012). Regarding BALF cytokines, BOS and RAS patients showed higher levels of INF-γ than ST (P=.02; P=.008). Only IL-5 presented significant differences between BOS and RAS (P=.001). BALF neutrophilia is as a marker for both CLAD phenotypes, BOS and RAS, and IL-5 seems to be a potential biomarker for the RAS phenotype.

Guía de Practica Clínica sobre la utilización de los dispositivos de avance mandibular (DAM) en el tratamiento de pacientes adultos con Síndrome de Apneas-Hipoapneas del Sueño

Los objetivos de la GPC son: Valorar la eficacia de los dispositivos de avance mandibular en el tratamiento de los pacientes adultos con síndrome de apneas-hipopneas obstructivas del sueño (SAOS); Valorar los factores predictores de buena respuesta al tratamiento con dispositivos de avance mandibular en pacientes adultos diagnosticados de SAOS; Valorar la metodología de implementación y seguimiento del tratamiento con DAM en pacientes adultos diagnosticados de SAOS y, finalmente, pretende aportar información de interés para los pacientes adultos diagnosticados de SAOS.

Guía española de práctica clínica utilización de los dispositivos de avance mandibular (DAM) en el tratamiento de pacientes adultos con síndrome de apneas-hipopneas del sueño / Spanish guide to clinical practice using mandibular advancement devices (MAD) in the treatment of adult patients with sleep apnea-hypopnea syndrome

Objetivos: La GPC se orienta a los profesionales encuadrados en unidades de sueño en el diagnóstico del SAOS y de su tratamiento, especialmente con CPAP nasal. Asimismo el presente documento aspira a ser de utilidad para las distintas especialidades involucradas en el seguimiento de pacientes con SAOS. Objetivos: - Valorar la eficacia de los dispositivos de avance mandibular en el tratamiento de los pacientes adultos con síndrome de apneas-hipopneas obstructivas del sueño (SAOS). - Valorar los factores predictores de buena respuesta al tratamiento con dispositivos de avance mandibular en pacientes adultos diagnosticados de SAOS. - Valorar la metodología de implementación y seguimiento del tratamiento con DAM en pacientes adultos diagnósticados de SAOS. Finalmente, pretende aportar información de interés para los pacientes adultos diagnosticados de SAOS.