RESUMO
Introduction: The patient experience is defined as all the interactions that occur between patients and the healthcare system. The experience of patients with respiratory disease with home respiratory treatments (HRT) is not captured in currently available Patient-Reported Outcome Measures (PROM). We present the psychometric validation of the Patient-Reported Experience Measure (PREM) 'HowRwe' in Spanish and for respiratory patients with HRT. Methods: After translation following ISPOR guidelines (International Society for Pharmacoeconomics and Outcomes Research), the questionnaire was administered to adult respiratory patients who were receiving treatment at Hospital Universitario de La Princesa. The administration was done in two stages with 6 months of difference between the pre- and post-test. Results: We studied 228 respiratory patients, with a mean (SD) age of 64.1 (13.2) years, 52.2% were men, 68.0% were married or coupled, and 56.6% were retired. Reliability coefficients of the scale were adequate, with α = .921 and Ω = .929 for pre-test, and α = .940 and Ω = .958 for post. The confirmatory factor analysis tested for pre- and post-intervention, showed an excellent overall fit: χ2(2) = 49.380 (p < .001), CFI = .941 and SRMR = .072; and χ2(2) = 37.579 (p < .001), CFI = .982 and SRMR = .046, respectively. No statistically significant associations were observed for neither age, adherence nor quality of life, except between HowRwe post-test and quality of life pre-test (r = .14 [.01,.26]; p = .035). No significant differences were found in sociodemographic variables. No differences in pre-test or post-test were found in effect of HRT. 85.6% of patients found the content of HowRwe "Useful", and the preferred channel to respond it were paper, app and email. Conclusions: The Spanish version of the 'HowRwe' questionnaire to measure the experience in respiratory patients with home respiratory treatments (HRT), has adequate psychometric properties and conceptual and semantic equivalence with the original English version.
Introducción: La experiencia del paciente se define como todas las interacciones que ocurren entre los pacientes y el sistema de salud. La experiencia de los pacientes con enfermedades respiratorias con terapias respiratorias domiciliarios (TRD) no se refleja en las Medidas de resultados informados por el paciente (PROM) disponibles actualmente. Presentamos la validación psicométrica de la Medida de Experiencia Reportada por el Paciente (PREM por sus siglas en inglés) 'HowRwe' en español y para pacientes respiratorios con TRD. Métodos: Después de la traducción siguiendo las pautas de ISPOR (Sociedad Internacional de Farmacoeconomía e Investigación de Resultados), el cuestionario se administró a pacientes respiratorios adultos que estaban recibiendo tratamiento en el Hospital Universitario de La Princesa. La administración se realizó en dos etapas con 6 meses de diferencia entre el pre y post test. Resultados: Se estudiaron 228 pacientes respiratorios, con una edad media (DE) de 64,1 ± 13,2 años, el 52,2% eran hombres, el 68,0% estaban casados o en pareja y el 56,6% eran jubilados. Los coeficientes de confiabilidad de la escala fueron adecuados, con α = .921 y Ω = .929 para el pretest, y α = .940 y Ω = .958 para el post. El análisis factorial confirmatorio testado para pre y postintervención, mostró un ajuste global excelente: χ2(2) = 49.380 (p < .001), CFI = .941 y SRMR = .072; y χ2(2) = 37,579 (p < .001), CFI = .982 y SRMR = .046, respectivamente. No se observaron asociaciones estadísticamente significativas ni para la edad, la adherencia ni para la calidad de vida, excepto entre HowRwe postest y calidad de vida pretest (r = .14 [.01,.26];p = .035). No se encontraron diferencias significativas en las variables sociodemográficas. No se encontraron diferencias en el efecto de la TRH en el pretest o postest. El 85,6% de los pacientes encontró "útil" el contenido de HowRwe y el canal preferido para responder fue el papel, la aplicación y el correo electrónico. Conclusiones: La versión española del cuestionario 'HowRwe' para medir la experiencia en pacientes respiratorios con tratamientos respiratorios domiciliarios (TRH), tiene adecuadas propiedades psicométricas y equivalencia conceptual y semántica con la versión original en inglés.
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Smokefree laws are intended to protect against second-hand smoke (SHS) in outdoor areas. We examined if exposure to PM2.5 particles in outdoor smoking areas changed breathing rates in 60 patients with asthma (n = 30) or with COPD (n = 30), in an open, non-randomised, interventional study model in Czechia, Ireland and Spain. The patients wore a PM2.5 particle monitor (AirSpeck) and a breath monitor (RESpeck) for 24 h to determine changes in breathing rates (Br) at rest and during a visit to an outside smoking area. Spirometry and breath CO were measured before and the day after visiting an outdoor smoking area. The PM2.5 levels at the 60 venues were highly variable, ranging from ≥2000 µg/m3 (in 4 premises) to ≤10 µg/m3 (in 3 premises, which had only a single wall in the structure). At 39 venues, the mean PM 2.5 levels were ≥25 µg/m3. The breathing rate changed significantly in 57 of the 60 patients, resulting in an increase in some patients and a decrease in others. Comprehensive smokefree laws were ineffective in protecting asthma and COPD patients from exposure to high levels of SHS in outside areas of pubs and terraces, which should be avoided by these patients. These findings also support the extension of smokefree laws to outside areas.
Assuntos
Poluição do Ar em Ambientes Fechados , Asma , Doença Pulmonar Obstrutiva Crônica , Poluição por Fumaça de Tabaco , Humanos , Poluição por Fumaça de Tabaco/análise , Espanha , Asma/epidemiologia , Fumar , Doença Pulmonar Obstrutiva Crônica/epidemiologiaRESUMO
BACKGROUND: An association of ABO blood group and COVID-19 remains controversial. METHODS: Following STROBE guidance for observational research, we explored the distribution of ABO blood group in patients hospitalized for acute COVID-19 and in those with Long COVID. Contingency tables were made and risk factors were explored using crude and adjusted Mantle-Haentzel odds ratios (OR and 95% CI). RESULTS: Up to September 2022, there were a total of 5,832 acute COVID-19 hospitalizations in our hospital, corresponding to 5,503 individual patients, of whom blood group determination was available for 1,513 (27.5%). Their distribution by ABO was: 653 (43.2%) group 0, 690 (45.6%) A, 113 (7.5%) B, and 57 (3.8%) AB, which corresponds to the expected frequencies in the general population. In parallel, of 676 patients with Long COVID, blood group determination was available for 135 (20.0%). Their distribution was: 60 (44.4%) from group 0, 61 (45.2%) A, 9 (6.7%) B, and 5 (3.7%) AB. The distribution of the ABO system of Long COVID patients did not show significant differences with respect to that of the total group (p ≥ 0.843). In a multivariate analysis adjusting for age, sex, ethnicity, and severity of acute COVID-19 infection, subgroups A, AB, and B were not significantly associated with developing Long COVID with an OR of 1.015 [0.669-1.541], 1.327 [0.490-3.594] and 0.965 [0.453-2.058], respectively. The effect of the Rh+ factor was also not significant 1,423 [0.772-2,622] regarding Long COVID. CONCLUSIONS: No association of any ABO blood subgroup with COVID-19 or developing Long COVID was identified.
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COVID-19 , Humanos , COVID-19/epidemiologia , Sistema ABO de Grupos Sanguíneos , Síndrome de COVID-19 Pós-Aguda , Fatores de Risco , Estudos Longitudinais , Sistema do Grupo Sanguíneo Rh-HrRESUMO
Inhibition of mTOR is the standard of care for lymphangioleiomyomatosis (LAM). However, this therapy has variable tolerability and some patients show progressive decline of lung function despite treatment. LAM diagnosis and monitoring can also be challenging due to the heterogeneity of symptoms and insufficiency of non-invasive tests. Here, we propose monoamine-derived biomarkers that provide preclinical evidence for novel therapeutic approaches. The major histamine-derived metabolite methylimidazoleacetic acid (MIAA) is relatively more abundant in LAM plasma, and MIAA values are independent of VEGF-D. Higher levels of histamine are associated with poorer lung function and greater disease burden. Molecular and cellular analyses, and metabolic profiling confirmed active histamine signaling and metabolism. LAM tumorigenesis is reduced using approved drugs targeting monoamine oxidases A/B (clorgyline and rasagiline) or histamine H1 receptor (loratadine), and loratadine synergizes with rapamycin. Depletion of Maoa or Hrh1 expression, and administration of an L-histidine analog, or a low L-histidine diet, also reduce LAM tumorigenesis. These findings extend our knowledge of LAM biology and suggest possible ways of improving disease management.
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Neoplasias Pulmonares , Linfangioleiomiomatose , Biomarcadores , Histamina , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Linfangioleiomiomatose/tratamento farmacológico , Transdução de SinaisRESUMO
BACKGROUND: Further evidence is needed on the effects that short- and long-term exposure to secondhand smoke (SHS) have on the respiratory health of patients with lung disease. Within the TackSHS project we aimed to assess the acute respiratory effects in lung function that result from short-term SHS exposure among patients with asthma and chronic obstructive pulmonary disease (COPD). METHODS: The study design was an intervention trial with measurements before/after exposure to SHS in legal outdoor smoking areas. We studied patients with asthma or COPD from Czechia, Ireland, and Spain. Forced spirometry, peak flow and carbon monoxide (CO) measurements were performed pre- and 24 h post- exposure. RESULTS: Overall, 60 patients were studied, 30 with asthma, and 30 with COPD; 35 (58.3%) were female. There were no significant differences observed in exhaled CO between pre- and 24 h post-exposure neither in women (p = 0.210), nor in men (p = 0.169).A statistically significant decrease in forced vital capacity (FVC) was seen, overall, in asthma participants (p = 0.02) and in forced expiratory volume in the first second (FEV1), (p = 0.02), FVC (p = 0.04) and peak expiratory flow rate (PEFR) (p = 0.04) in female asthmatic participants. The observed decreases in respiratory measurements in COPD were not significant. There were no reported increases in symptoms, respiratory medication, or use of health services 24 h after the exposure. CONCLUSION: We conclude that acute, short-term SHS exposure had a statistically significant effect on spirometry in female asthma patients but did not significantly modify spirometric indices 24 h later in COPD patients.
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Poluentes Atmosféricos/efeitos adversos , Asma/fisiopatologia , Pulmão/fisiopatologia , Poluição por Fumaça de Tabaco/efeitos adversos , Adulto , Idoso , Asma/metabolismo , Monóxido de Carbono/metabolismo , Feminino , Fluxo Expiratório Forçado , Volume Expiratório Forçado , Humanos , Pulmão/metabolismo , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Caracteres Sexuais , Espirometria , Capacidade VitalRESUMO
BACKGROUND: Patients with coronavirus disaese 2019 (COVID-19) can develop a cytokine release syndrome that eventually leads to acute respiratory distress syndrome requiring invasive mechanical ventilation (IMV). Because IL-6 is a relevant cytokine in acute respiratory distress syndrome, the blockade of its receptor with tocilizumab (TCZ) could reduce mortality and/or morbidity in severe COVID-19. OBJECTIVE: We sought to determine whether baseline IL-6 serum levels can predict the need for IMV and the response to TCZ. METHODS: A retrospective observational study was performed in hospitalized patients diagnosed with COVID-19. Clinical information and laboratory findings, including IL-6 levels, were collected approximately 3 and 9 days after admission to be matched with preadministration and postadministration of TCZ. Multivariable logistic and linear regressions and survival analysis were performed depending on outcomes: need for IMV, evolution of arterial oxygen tension/fraction of inspired oxygen ratio, or mortality. RESULTS: One hundred forty-six patients were studied, predominantly males (66%); median age was 63 years. Forty-four patients (30%) required IMV, and 58 patients (40%) received treatment with TCZ. IL-6 levels greater than 30 pg/mL was the best predictor for IMV (odds ratio, 7.1; P < .001). Early administration of TCZ was associated with improvement in oxygenation (arterial oxygen tension/fraction of inspired oxygen ratio) in patients with high IL-6 (P = .048). Patients with high IL-6 not treated with TCZ showed high mortality (hazard ratio, 4.6; P = .003), as well as those with low IL-6 treated with TCZ (hazard ratio, 3.6; P = .016). No relevant serious adverse events were observed in TCZ-treated patients. CONCLUSIONS: Baseline IL-6 greater than 30 pg/mL predicts IMV requirement in patients with COVID-19 and contributes to establish an adequate indication for TCZ administration.
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Anticorpos Monoclonais Humanizados/administração & dosagem , Tratamento Farmacológico da COVID-19 , COVID-19 , Síndrome da Liberação de Citocina , Interleucina-6/sangue , SARS-CoV-2 , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/sangue , COVID-19/mortalidade , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: Nocturnal desaturation in cystic fibrosis (CF) may have prognostic implications because a significant and maintained nocturnal desaturation can contribute to the development and progression of pulmonary hypertension with cor pulmonale. Its relation with the desaturation in exercise has not been sufficiently studied. We aimed to determine whether desaturation during 6MWT can be an indicator of nocturnal desaturation in adult subjects with CF. METHODS: 57 subjects were included: 50.9% male, 27.5 ± 7.7 y old, mean FEV1 = 2.37 ± 0.74 L, and %FEV1 67 ± 18.1%. Desaturation during 6MWT was defined as oxygen saturation (SpO2 ) ≤ 90% or a decline of > 4 points in SpO2 from baseline, and nocturnal desaturation as a desaturation index > 4 or > 5% of sleep time with SpO2 ≤ 90%. RESULTS: Desaturation observed during 6MWT in adult subjects with CF did not correlate with nocturnal desaturation (P = .27). Subjects with %FEV1 ≤ 55% and diffusion capacity of carbon monoxide (DLCO) ≤ 50 mmol/min/mm Hg were at higher risk of 6MWT desaturation. Nocturnal desaturation was more frequent in males, with PaO2 ≤ 71 mm Hg in blood gas analysis. CONCLUSIONS: Desaturation observed in 6MWT cannot predict desaturation at night in adults with CF. Other parameters were identified as predictors of desaturation.
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Gasometria/estatística & dados numéricos , Fibrose Cística/fisiopatologia , Exercício Físico/fisiologia , Consumo de Oxigênio/fisiologia , Sono/fisiologia , Adulto , Ritmo Circadiano , Fibrose Cística/complicações , Feminino , Volume Expiratório Forçado , Humanos , Hipertensão Pulmonar/etiologia , Masculino , Valor Preditivo dos Testes , Capacidade de Difusão Pulmonar , Teste de Caminhada , Adulto JovemAssuntos
Doença Pulmonar Obstrutiva Crônica , Fatores Sexuais , Fumar/efeitos adversos , Fatores Etários , Comorbidade , Suscetibilidade a Doenças , Dispneia/etiologia , Poluição Ambiental/efeitos adversos , Feminino , Humanos , Prognóstico , Doença Pulmonar Obstrutiva Crônica/etiologia , Doença Pulmonar Obstrutiva Crônica/terapia , Enfisema Pulmonar/epidemiologia , Fatores de Risco , Abandono do Hábito de FumarRESUMO
Nowadays engineered nanomaterials (ENMs) are increasingly used in a wide range of commercial products and biomedical applications. Despite this, the knowledge of human potential health risk as well as comprehensive biological and toxicological information is still limited. We have investigated the capacity of two frequently used metallic ENMs, nanosilver and magnetite nanoparticles (MNPs), to induce thymidine kinase (Tk +/-) mutations in L5178Y mouse lymphoma cells and transformed foci in Bhas 42 cells. Two types of nanosilver, spherical nanoparticles (AgNM300) and fibrous (AgNM302) nanorods/wires, and MNPs differing in surface modifications [MNPs coated with sodium oleate (SO-MNPs), MNPs coated with SO + polyethylene glycol (SO-PEG-MNPs) and MNPs coated with SO + PEG + poly(lactide-co-glycolic acid) SO-PEG-PLGA-MNPs] were included in this study. Spherical AgNM300 showed neither mutagenic nor carcinogenic potential. In contrast, silver nanorods/wires (AgNM302) increased significantly the number of both gene mutations and transformed foci compared with the control (untreated) cells. Under the same treatment conditions, neither SO-MNPs nor SO-PEG-PLGA-MNPs increased the mutant frequency compared with control cells though an equivocal mutagenic effect was estimated for SO-PEG-MNPs. Although SO-MNPs and SO-PEG-MNPs did not show any carcinogenic potential, SO-PEG-PLGA-MNPs increased concentration dependently the number of transformed foci in Bhas 42 cells compared with the control cells. Our results revealed that fibrous shape underlies the mutagenic and carcinogenic potential of nanosilver while surface chemistry affects the biosafety of MNPs. Considering that both nanosilver and MNPs are prospective ENMs for biomedical applications, further toxicological evaluations are warranted to assess comprehensively the biosafety of these nanomaterials.
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Nanopartículas Metálicas/toxicidade , Mutação , Prata/toxicidade , Timidina Quinase/efeitos dos fármacos , Animais , Carcinógenos/farmacologia , Carcinógenos/toxicidade , Compostos Férricos/farmacologia , Compostos Férricos/toxicidade , Nanopartículas Metálicas/química , Camundongos , Testes de Mutagenicidade , Mutagênicos/farmacologia , Mutagênicos/toxicidade , Prata/farmacologia , Timidina Quinase/genéticaRESUMO
Oxygen-sensing pathways executed by the hypoxia-inducible factors (HIFs) induce a cellular adaptive program when oxygen supply becomes limited. However, the role of the HIF oxygen-sensing pathway in the airway response to hypoxic stress in adulthood remains poorly understood. Here we found that in vivo exposure to hypoxia led to a profound increase in bronchial epithelial cell proliferation mainly confined to Club (Clara) cells. Interestingly, this response was executed by hypoxia-inducible factor 2α (HIF2α), which controls the expression of FoxM1, a recognized proliferative factor of Club cells. Furthermore, HIF2α induced the expression of the resistin-like molecules α and ß (RELMα and ß), previously considered bronchial epithelial growth factors. Importantly, despite the central role of HIF2α, this proliferative response was not initiated by in vivo Vhl gene inactivation or pharmacological inhibition of prolyl hydroxylase oxygen sensors, indicating the molecular complexity of this response and the possible participation of other oxygen-sensing pathways. Club cells are principally involved in protection and maintenance of bronchial epithelium. Thus, our findings identify a novel molecular link between HIF2α and Club cell biology that can be regarded as a new HIF2α-dependent mechanism involved in bronchial epithelium adaptation to oxygen fluctuations.