Analysis of Immune Cell Subsets in Peripheral Blood from Patients with Engineered Stone Silica-Induced Lung Inflammation.

Silicosis caused by engineered stone (ES-silicosis) is an emerging worldwide issue characterized by inflammation and fibrosis in the lungs. To our knowledge, only a few reports have investigated leukocyte/lymphocyte subsets in ES-silicosis patients. The present study was designed to explore the proportions of the main lymphocyte subsets in ES-silicosis patients stratified into two groups, one with simple silicosis (SS) and the other with a more advanced state of the disease, defined as progressive massive fibrosis (PMF). The proportions of B (memory and plasmablasts) cells, T (helper, cytotoxic, regulatory) cells, and natural killer (NK) (regulatory and cytotoxic) cells were investigated by multiparameter flow cytometry in 91 ES-silicosis patients (53 SS patients and 38 PMF patients) and 22 healthy controls (HC). Although the total number of leukocytes did not differ between the groups studied, lymphopenia was observed in patients compared to healthy controls. Compared with those in healthy controls, the proportions of memory B cells, naïve helper T cells, and the CD4+/CD8+ T cells' ratio in the peripheral blood of patients with silicosis were significantly decreased, while the percentages of plasma cells, memory helper T cells, and regulatory T cells were significantly increased. For the NK cell subsets, no significant differences were found between the groups studied. These results revealed altered cellular immune processes in the peripheral blood of patients with ES-silicosis and provided further insight into silicosis pathogenesis.

Plasma Cytokine Profiling Reveals Differences between Silicotic Patients with Simple Silicosis and Those with Progressive Massive Fibrosis Caused by Engineered Stone.

Engineered stone silicosis has become an occupational epidemic disease that progresses rapidly to progressive massive fibrosis with respiratory failure and death, and there is no effective treatment. Silica deposition in the lung triggers a series of inflammatory reactions with the participation of multiple cytokines and cellular mediators whose role in the development and progression of the disease is largely unknown. We hypothesized that differences in plasma cytokine levels exist between patients diagnosed with simple silicosis (SS) and patients diagnosed with progressive massive fibrosis (PMF). Plasma samples from 91 ES silicosis patients, diagnosed and classified by chest radiography and/or high-resolution computed tomography with SS (n = 53) and PMF (n = 38), were assayed by multiplex assays for levels of 34 cytokines. Additionally, a healthy volunteer control group (n = 22) was included. Plasma levels of a high number of cytokines were significantly higher in subjects with silicosis than in healthy control subjects. Moreover, the levels of IL-1RA, IL-8, IL-10, IL-16, IL-18, TNF-α, MIP-1α, G-CSF and VEGF were significantly elevated in PMF compared to SS patients. This study shows that plasma cytokine levels differ between healthy people and silicosis patients, and some of them are also significantly elevated in patients with PMF compared with patients with SS, which could indicate their involvement in the severity of the disease, be considered as biomarkers and could be explored as future therapeutic targets for the disease.

Demographic, exposure and clinical characteristics in a multinational registry of engineered stone workers with silicosis.

OBJECTIVES: To investigate differences in workplace exposure, demographic and clinical findings in engineered stone (ES) workers from a multinational consortium using the Engineered Stone Silicosis Investigators (ESSI) Global Silicosis Registry. METHODS: With ethics board approval in Israel, Spain, Australia and the USA, ES workers ages 18+ with a physician diagnosis of work-related silicosis were enrolled. Demographic, occupational, radiologic, pulmonary function and silica-related comorbidity data were compared cross-sectionally among countries using analysis of variance, Fisher's exact tests and logistic regression. RESULTS: Among 169 ES workers with silicosis, most were men, with mean age 51.7 (±11.4) years. Mean work tenure in stone fabrication or masonry was 19.9 (±9.8) years. Different methods of case ascertainment explained some inter-country differences, for example, workers in Queensland, Australia with a state-based surveillance program were likely to be identified earlier and with shorter work tenure. Overall, 32.5% of workers had progressive massive fibrosis, the most severe form of dust-related pneumoconiosis, of whom 18.5% reported ≤10 years of work tenure. Lung function impairment including restriction, reduced diffusion capacity and hypoxaemia was common, as was autoimmunity. CONCLUSIONS: Findings from a multinational registry represent a unique effort to compare demographic, exposure and clinical information from ES workers with silicosis, and suggest a substantial emerging population of workers worldwide with severe and irreversible silica-associated diseases. This younger worker population is at high risk for disease progression, multiple comorbidities and severe disability. The ESSI registry provides an ongoing framework for investigating epidemiological trends and developing prospective studies for prevention and treatment of these workers.

Current global perspectives on silicosis-Convergence of old and newly emergent hazards.

Silicosis not a disease of the past. It is an irreversible, fibrotic lung disease specifically caused by exposure to respirable crystalline silica (RCS) dust. Over 20,000 incident cases of silicosis were identified in 2017 and millions of workers continue to be exposed to RCS. Identified case numbers are however a substantial underestimation due to deficiencies in reporting systems and occupational respiratory health surveillance programmes in many countries. Insecure workers, immigrants and workers in small businesses are at particular risk of more intense RCS exposure. Much of the focus of research and prevention activities has been on the mining sector. Hazardous RCS exposure however occurs in a wide range of occupational setting which receive less attention, in particular the construction industry. Recent outbreaks of silicosis associated with the fabrication of domestic kitchen benchtops from high-silica content artificial stone have been particularly notable because of the young age of affected workers, short duration of RCS exposure and often rapid disease progression. Developments in nanotechnology and hydraulic fracking provide further examples of how rapid changes in technology and industrial processes require governments to maintain constant vigilance to identify and control potential sources of RCS exposure. Despite countries around the world dealing with similar issues related to RCS exposure, there is an absence of sustained global public health response including lack of consensus of an occupational exposure limit that would provide protection to workers. Although there are complex challenges, global elimination of silicosis must remain the goal.

Compositional and structural analysis of engineered stones and inorganic particles in silicotic nodules of exposed workers.

BACKGROUND: Engineered stone silicosis is an emerging disease in many countries worldwide produced by the inhalation of respirable dust of engineered stone. This silicosis has a high incidence among young workers, with a short latency period and greater aggressiveness than silicosis caused by natural materials. Although the silica content is very high and this is the key factor, it has been postulated that other constituents in engineered stones can influence the aggressiveness of the disease. Different samples of engineered stone countertops (fabricated by workers during the years prior to their diagnoses), as well as seven lung samples from exposed patients, were analyzed by multiple techniques. RESULTS: The different countertops were composed of SiO2 in percentages between 87.9 and 99.6%, with variable relationships of quartz and cristobalite depending on the sample. The most abundant metals were Al, Na, Fe, Ca and Ti. The most frequent volatile organic compounds were styrene, toluene and m-xylene, and among the polycyclic aromatic hydrocarbons, phenanthrene and naphthalene were detected in all samples. Patients were all males, between 26 and 46 years-old (average age: 36) at the moment of the diagnosis. They were exposed to the engineered stone an average time of 14 years. At diagnosis, only one patient had progressive massive fibrosis. After a follow-up period of 8 ± 3 years, four patients presented progressive massive fibrosis. Samples obtained from lung biopsies most frequently showed well or ill-defined nodules, composed of histiocytic cells and fibroblasts without central hyalinization. All tissue samples showed high proportion of Si and Al at the center of the nodules, becoming sparser at the periphery. Al to Si content ratios turned out to be higher than 1 in two of the studied cases. Correlation between Si and Al was very high (r = 0.93). CONCLUSION: Some of the volatile organic compounds, polycyclic aromatic hydrocarbons and metals detected in the studied countertop samples have been described as causative of lung inflammation and respiratory disease. Among inorganic constituents, aluminum has been a relevant component within the silicotic nodule, reaching atomic concentrations even higher than silicon in some cases. Such concentrations, both for silicon and aluminum showed a decreasing tendency from the center of the nodule towards its frontier.

Automated Home Oxygen Delivery for Patients with COPD and Respiratory Failure: A New Approach.

Long-term oxygen therapy (LTOT) has become standard care for the treatment of patients with chronic obstructive pulmonary disease (COPD) and other severe hypoxemic lung diseases. The use of new portable O2 concentrators (POC) in LTOT is being expanded. However, the issue of oxygen titration is not always properly addressed, since POCs rely on proper use by patients. The robustness of algorithms and the limited reliability of current oximetry sensors are hindering the effectiveness of new approaches to closed-loop POCs based on the feedback of blood oxygen saturation. In this study, a novel intelligent portable oxygen concentrator (iPOC) is described. The presented iPOC is capable of adjusting the O2 flow automatically by real-time classifying the intensity of a patient's physical activity (PA). It was designed with a group of patients with COPD and stable chronic respiratory failure. The technical pilot test showed a weighted accuracy of 91.1% in updating the O2 flow automatically according to medical prescriptions, and a general improvement in oxygenation compared to conventional POCs. In addition, the usability achieved was high, which indicated a significant degree of user satisfaction. This iPOC may have important benefits, including improved oxygenation, increased compliance with therapy recommendations, and the promotion of PA.

Use of predictive algorithms in-home monitoring of chronic obstructive pulmonary disease and asthma: A systematic review.

Major reported factors associated with the limited effectiveness of home telemonitoring interventions in chronic respiratory conditions include the lack of useful early predictors, poor patient compliance and the poor performance of conventional algorithms for detecting deteriorations. This article provides a systematic review of existing algorithms and the factors associated with their performance in detecting exacerbations and supporting clinical decisions in patients with chronic obstructive pulmonary disease (COPD) or asthma. An electronic literature search in Medline, Scopus, Web of Science and Cochrane library was conducted to identify relevant articles published between 2005 and July 2015. A total of 20 studies (16 COPD, 4 asthma) that included research about the use of algorithms in telemonitoring interventions in asthma and COPD were selected. Differences on the applied definition of exacerbation, telemonitoring duration, acquired physiological signals and symptoms, type of technology deployed and algorithms used were found. Predictive models with good clinically reliability have yet to be defined, and are an important goal for the future development of telehealth in chronic respiratory conditions. New predictive models incorporating both symptoms and physiological signals are being tested in telemonitoring interventions with positive outcomes. However, the underpinning algorithms behind these models need be validated in larger samples of patients, for longer periods of time and with well-established protocols. In addition, further research is needed to identify novel predictors that enable the early detection of deteriorations, especially in COPD. Only then will telemonitoring achieve the aim of preventing hospital admissions, contributing to the reduction of health resource utilization and improving the quality of life of patients.

Computerised Analysis of Telemonitored Respiratory Sounds for Predicting Acute Exacerbations of COPD.

Chronic obstructive pulmonary disease (COPD) is one of the commonest causes of death in the world and poses a substantial burden on healthcare systems and patients' quality of life. The largest component of the related healthcare costs is attributable to admissions due to acute exacerbation (AECOPD). The evidence that might support the effectiveness of the telemonitoring interventions in COPD is limited partially due to the lack of useful predictors for the early detection of AECOPD. Electronic stethoscopes and computerised analyses of respiratory sounds (CARS) techniques provide an opportunity for substantial improvement in the management of respiratory diseases. This exploratory study aimed to evaluate the feasibility of using: (a) a respiratory sensor embedded in a self-tailored housing for ageing users; (b) a telehealth framework; (c) CARS and (d) machine learning techniques for the remote early detection of the AECOPD. In a 6-month pilot study, 16 patients with COPD were equipped with a home base-station and a sensor to daily record their respiratory sounds. Principal component analysis (PCA) and a support vector machine (SVM) classifier was designed to predict AECOPD. 75.8% exacerbations were early detected with an average of 5 ± 1.9 days in advance at medical attention. The proposed method could provide support to patients, physicians and healthcare systems.

Inflammatory indices obtained from routine blood tests show an inflammatory state associated with disease progression in engineered stone silicosis patients.

Patients with silicosis caused by occupational exposure to engineered stone (ES) present a rapid progression from simple silicosis (SS) to progressive massive fibrosis (PMF). Patient classification follows international rules based on radiology and high-resolution computed tomography (HRCT), but limited studies, if any, have explored biomarkers from routine clinical tests that can be used as predictors of disease status. Our objective was thus to investigate circulating biomarker levels and systemic inflammatory indices in ES silicosis patients whose exposure to ES dust ended several years ago. Ninety-one adult men, ex-workers in the manufacturing of ES, 53 diagnosed with SS and 38 with PMF, and 22 healthy male volunteers (HC) as controls not exposed to ES dust, were recruited. The following circulating levels of biomarkers like lactate dehydrogenase (LDH), angiotensin-converting-enzyme (ACE), protein C reactive (PCR), rheumatoid factor, alkaline phosphatase and fibrinogen were obtained from clinical reports after being measured from blood samples. As biochemical markers, only LDH (HC = 262 ± 48.1; SS = 315.4 ± 65.4; PMF = 337.6 ± 79.3 U/L), ACE (HC = 43.1 ± 18.4; SS = 78.2 ± 27.2; PMF = 86.1 ± 23.7 U/L) and fibrinogen (HC = 182.3 ± 49.1; SS = 212.2 ± 43.5; PMF = 256 ± 77.3 U/L) levels showed a significant sequential increase, not been observed for the rest of biomarkers, in the HC → SS → PMF direction. Moreover, several systemic inflammation indices neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic inflammation response index (SIRI), systemic immune-inflammation index (SII), aggregate index of systemic inflammation (AISI) derived from whole blood cell counts showed significant differences between the HC, SS and PMF groups. All these biomarkers were analyzed using receiver operating characteristic (ROC) curves, and the results provided moderately high sensitivity and specificity for discriminating between ES silicosis patient groups and healthy controls. Our study reveals that some inflammatory biomarkers, easily available from routine blood analysis, are present in ES silicosis patients even several years after cessation of exposure to ES silica dust and they could help to know the progression of the disease.

Artificial Stone Silicosis: Accumulation of errors in the resurgence of an occupational disease: A qualitative study.

BACKGROUND: Exposure to artificial stone machining, under the conditions in which marble workers work with this new product, can cause silicosis. OBJECTIVE: To examine the experiences of marble workers affected, both in workshop and during home installation of countertops, before diagnosis of silicosis. METHODS: Qualitative study in which 10 open-ended semistructured interviews were conducted with marble workers diagnosed with silicosis after machining artificial stone countertops in Cádiz, Spain. Interviews were recorded, transcribed, and coded using a directed content analysis. Codes were organized into themes. RESULTS: Interviews up to 120 minutes and transcript analysis revealed three themes: 1) Heavy exposure for piecework: construction boom in an environment of labor deregulation and high demand for the novel product; 2) Poor working conditions: dry machining of artificial stone without proper protection in the workshop and greater exposure during home installation of countertops; 3) Concatenated legal transgressions: deficiencies in prevention and health surveillance without safety conditions for the correct handling of artificial stone. CONCLUSIONS: The fight against an emerging occupational disease-artificial stone silicosis-should focus on detecting affected workers and avoiding new cases, forcing joint efforts to achieve rigorous compliance with health surveillance and protecting marble workers to achieve healthy and safe workplaces.

Portable Oxygen Therapy: Is the 6-Minute Walking Test Overestimating the Actual Oxygen Needs?

The appropriate titration for the personalized oxygen needs of patients with chronic obstructive pulmonary disease (COPD) and severe hypoxemia is a determining factor in the success of long-term oxygen therapy. There are no standardized procedures to assist in determining the patient's needs during the physical activities of daily life. Despite that effort tests are a wide broad approach, further research concerning the development of protocols to titrate O2 therapy is needed. The main objective of this study was to assess whether the level of oxygen titrated through the 6-minute walking test (6MWT) for patients with COPD and exertional hypoxemia is adequate to meet the patients' demand during their activities of daily living. Physiological and subjective variables were estimated for a study population during two walking tests: a 6MWT and a 20-minute walking circuit (20MWC), designed ad-hoc to reproduce daily physical activities more truthfully. The results indicate that in a significant proportion of patients, the 6MWT might not accurately predict their oxygen needs at a domiciliary environment. Therefore, the titration of the portable O2 therapy could not be optimal in these cases, with the detrimental impact on the patient's health (hyperoxia episodes), the autonomy of the oxygen device, and the decrease of time out of the home.

Artificial Stone Silicosis: Rapid Progression Following Exposure Cessation.

BACKGROUND: Silicosis is rapidly emerging in high-income countries in relation to the replacement of natural stone with artificial stone, especially in the manufacturing and installation of kitchen and bathroom countertops. Progression of this form of silicosis following the cessation of exposure is unknown. RESEARCH QUESTION: The objective of this study was to determine the radiologic progression and lung function in individuals with artificial stone silicosis. STUDY DESIGN AND METHODS: Between 2009 and 2018, a total of 106 patients were diagnosed with artificial stone silicosis in the Bay of Cádiz area (southern Spain), 14.15% by using biopsy results and the remainder according to chest radiography and high-resolution CT imaging. Follow-up consisted of respiratory function tests and radiographic studies. All patients stopped working in the stone industry following diagnosis. RESULTS: All patients were men; their mean ± SD age at diagnosis was 36.2 ± 7.0 years, and the mean duration of exposure was 12.0 ± 4.3 years. At diagnosis, 99 patients were considered to have simple silicosis (93.4%) and seven to have progressive massive fibrosis (PMF) (6.6%). After a mean follow-up of 4.01 ± 2.1 years, disease in 56% of patients had progressed two or more International Labour Office subcategories, and the number of patients with PMF had increased to 40 (37.7%). Regarding lung function, there was a decrease in FVC and FEV1, with an average decrease of 86.8 and 83.4 mL per year, respectively; in 25% of patients, the annual decrease was > 157 mL in FVC and > 133 mL in FEV1. Multivariable analysis showed that lower FVC at diagnosis and longer duration of exposure to silica were associated with progression to PMF. INTERPRETATION: Artificial stone silicosis rapidly progresses to PMF even following exposure cessation, and a significant percentage of patients experience a very rapid decrease in lung function.

Serum levels of soluble mesothelin-related peptides in malignant and nonmalignant asbestos-related pleural disease: relation with past asbestos exposure.

BACKGROUND: Malignant pleural mesothelioma (MPM) results from malignant transformation of mesothelial cells. Past asbestos exposure represents a major risk factor for MPM and other benign pleural disease. Soluble mesothelin-related peptides (SMRP) have been regarded as a promising serum biomarker for MPM. The aim of this study was to investigate serum levels of SMRP in malignant and nonmalignant asbestos-related pleural disease. PATIENTS: Four groups of patients were investigated: group 1 composed of 48 healthy subjects, group 2 composed of 177 patients with previous asbestos exposure and no pleural disease, group 3 composed of 36 patients with MPM, and group 4 composed of 101 patients with previous asbestos exposure and benign pleural disease. Serum SMRP levels were determined by ELISA. RESULTS: Serum SMRP levels were significantly higher among group 3 than the other three groups. There were no differences in SMRP concentrations between groups 2 and 4. Subjects exposed to asbestos had higher SMRP concentrations than normal control subjects regardless of the presence of pleural disease. The area under the receiver operating characteristic curve for SMRP values was 0.75 (95% confidence interval, 0.68-0.83). The SMRP level at 0.55 nmol/L/L was determined as the most optimal cutoff value with resulting sensitivity and specificity of 72% and 72% for the diagnosis of MPM. CONCLUSIONS: These data attest to good diagnostic sensitivity and specificity of SMRP for the diagnosis of malignant mesothelioma. We have also shown that serum SMRP levels might serve as a marker of asbestos exposure.

Factors related to quality of life in patients receiving home mechanical ventilation.

OBJECTIVES: The objective of this study was to evaluate factors associated with health-related quality of life (HRQOL) among patients receiving home mechanical ventilation (HMV). METHODS: Observational, cross-sectional study. Patients receiving HMV were recruited from hospital outpatients facilities at five participating centers; a single follow-up visit was scheduled. The Spanish version of the Severe Respiratory Insufficiency (SRI) Questionnaire was used and the following variables were collected: socio-demographic status, previous medical history (Charlson-Age Comorbidity Index), current symptoms, administration of questionnaires, pulmonary function tests (PFT), current ventilatory support, and oxygen therapy. RESULTS: One hundred and fifteen patients (57 males and 58 females, mean age 62+/-13 years) were investigated. The reasons for HMV were as follows: thoracic cage abnormalities (33 patients), obesity hypoventilation syndrome (37 patients), neuromuscular disorders (18 patients), sequelae of tuberculosis (12 patients), and chronic obstructive pulmonary disease (15 patients). In a bivariate approach, dyspnea, the number of hospitalizations, and the number of emergency room admissions in last year were the main predictors of each HRQOL dimension. Multivariate analysis showed that dyspnea, FEV(1)/FVC, and the number of hospitalizations in the previous year were independently associated with HRQOL. CONCLUSIONS: HRQOL of patients receiving HMV is influenced by many factors, especially by dyspnea and the number of admissions. An obstructive pattern in the PFT also influences HRQOL. These findings may have therapeutic implications.

CPAP titration: Different methods for similar clinical results.

BACKGROUND: Continuous positive airway pressure (CPAP) is the main treatment for obstructive sleep apnea-hypopnea syndrome (OSAHS). Polysomnography (PSG) is the gold standard for CPAP titration. However, alternative methods have been sought to titrate CPAP at less expense in terms of time and resources. The aim of this study was to analyze CPAP success in controlling OSAHS symptoms and adverse effects by two titration methods. METHODS: This was a retrospective, observational cohort study in which 200 CPAP-naive patients who had been referred to our sleep laboratory and diagnosed with OSAHS were evaluated on two consecutive visits. During the first visit, an initial CPAP pressure was established either by split-night PSG or by using a mathematical formula. On the second visit, 1 month later, symptom persistence and adverse effects of CPAP treatment were assessed. RESULTS: Patients included were 157 males (78.5%) and 43 females (21.5%) aged 56+/-10 years. 87 patients (43.5%) were titrated by PSG and 113 (56.5%) using the formula. At the second visit, symptoms had improved significantly for both groups with no significant differences in the presence of adverse effects. The initial pressure had to be readjusted in five patients. CONCLUSIONS: This study suggests that formula titration can control symptoms as effectively as split-night titration. A prompt evaluation of the patient is advisable in order to ensure compliance with treatment and to correct possible adverse effects.

Physiological closed-loop control in intelligent oxygen therapy: A review.

BACKGROUND AND OBJECTIVE: Oxygen therapy has become a standard care for the treatment of patients with chronic obstructive pulmonary disease and other hypoxemic chronic lung diseases. In current systems, manually continuous adjustment of O2 flow rate is a time-consuming task, often unsuccessful, that requires experienced staff. The primary aim of this systematic review is to collate and report on the principles, algorithms and accuracy of autonomous physiological close-loop controlled oxygen devices as well to present recommendations for future research and studies in this area. METHODS: A literature search was performed on medical database MEDLINE, engineering database IEEE-Xplore and wide-raging scientific databases Scopus and Web of Science. A narrative synthesis of the results was carried out. RESULTS: A summary of the findings of this review suggests that when compared to the conventional manual practice, the closed-loop controllers maintain higher saturation levels, spend less time below the target saturation, and save oxygen resources. Nonetheless, despite of their potential, autonomous oxygen therapy devices are scarce in real clinical applications. CONCLUSIONS: Robustness of control algorithms, fail-safe mechanisms, limited reliability of sensors, usability issues and the need for standardized evaluating methods of assessing risks can be among the reasons for this lack of matureness and need to be addressed before the wide spreading of a new generation of automatic oxygen devices.

[Health-related quality of life of patients receiving home mechanical ventilation: the Spanish version of the severe respiratory insufficiency questionnaire]. / Calidad de vida relacionada con la salud de pacientes en programa de ventilación mecánica domiciliaria. La versión española del cuestionario SRI.

OBJECTIVE: Home mechanical ventilation is used with patients with severe, chronic respiratory failure, a condition that has a serious impact on quality of life. The aim of this study was to produce a translation and cultural adaptation of the Severe Respiratory Insufficiency. Questionnaire for the Spanish population, the first health-related quality of life questionnaire specifically designed for patients receiving home mechanical ventilation. METHODS: Four bilingual German-Spanish translators were used to translate and back-translate the questionnaire. Meetings were held with the translators following each step of the translation process to produce a single version that could be used in the next step. At the end of the process, the questionnaire was piloted to assess its comprehensibility. A scoring system using a scale of 1 (lowest) to 10 (highest) was used to rate both translation difficulty and the naturalness of the language produced. The equivalence of the original and translated items was also evaluated. RESULTS: Three Spanish versions of the questionnaire were produced. Task difficulty was rated as quite low: the mean (SD) ratings were 1.4 (0.6) for translation and 2.2 (1.1) for back translation. The naturalness of the translated items was rated as very high, with scores improving with the successive versions (version 1, 8.4; version 2, 8.7; version 3, 9.1; P< .001). Thirty of the questionnaire items (61.2%) were judged to be fully equivalent, 13 (26.5%) to be similar, and 6 (12.2%) to be non-equivalent. The meaning conveyed by 5 of the items was changed or clarified during piloting. CONCLUSIONS: The translation of the questionnaire using the translation-back-translation procedure has produced a version that is both comparable to the original and accessible to the Spanish population. Its validity is currently being tested in a multicenter study.