[Asthma]. / Asma.

Asthma is a chronic inflammatory disease that affects about 5% of the world's population and generates high health and social costs. Proper management of the disease requires a correct diagnosis, based on objective measures of functional impairment, as well as symptom control and assessment of the future risk of exacerbations.It has been estimated that 18% of asthma patients in Western Europe have severe asthma and approximately 50% of them have poor control. The severity of asthma is established based on the minimum maintenance treatment needs to achieve control. Asthma clinical practice guidelines recommend classifying severe patients into allergic asthma (T2); eosinophilic asthma (T2) and non-T2 asthma in order to establish the most appropriate treatment.In recent decades, new biological therapies have been developed that can be applied according to the phenotype and endotype of asthma, allowing for selective and personalized treatment. These phenotypes and endotypes can change over time and therefore, the identification of biomarkers capable of predicting the severity, the course of the disease and the response to a given treatment seems essential. A large number of biomarkers have been studied in asthma, but so far only a few can be readily used in routine clinical practice. The application of omics technologies (epigenomics, genomics, transcriptomics, proteomics, metabolomics, lipidomics, etc.) for this purpose is still in the research phase.

Patient-reported outcome measures in severe asthma: an expert consensus.

OBJECTIVE: The study aimed to reach a consensus on the most relevant patient-reported outcomes (PROs), the corresponding measures (PROMs), and measurement frequency during severe asthma patient follow-up. METHODS: Two Delphi rounds were conducted. The questionnaire was developed based on a systematic literature review, a focus group with patients, and a nominal group with experts. It assessed PROs' relevance and the appropriateness (A) and feasibility (F) of PROMs using a Likert scale (1=totally agree; 9=totally disagree). The consensus was established when ≥75% of participants agreed (1-3) or disagreed (7-9). RESULTS: Sixty-three professionals (25 hospital pharmacists, 14 allergists, 13 pulmonologists, and 11 nurses) and 5 patients answered the Delphi questionnaire. A consensus was reached on all PROs regarding their relevance. Experts agreed on the use of ACT (A:95.24%; F:95.24%), mini AQLQ (A:93.65; F:79.37%), mMRC dyspnea scale (A:85.71%; F:85.71%), TAI (A:92.06%; F:85.71%), MMAS (A:75.40%; F:82%), and the dispensing register (A:96.83%; F:92.06%). Also considered suitable were: SNOT-22 (A:90.48%; F:73.80%), PSQI (A:82.54; F:63.90%), HADS (A:82.54; F:64%), WPAI (A:77.78%; F:49.20%), TSQM-9 (A:79.37; F:70.50%) and knowledge of asthma questionnaire (A:77%; F:68.80%); however, their use in clinical practice was considered unfeasible. Panelists also agreed on the appropriateness of EQ-5D, which was finally included despite being considered unfeasible (A: 84.13%; F:67.20%) in clinical practice. Agreement was reached on using ACT, TAI, mMRC, and a dispensing register every three months; mini-AQLQ and MMAS every six months; and EQ-5D every twelve months. CONCLUSION: This consensus paves the way toward patient-centered care, promoting the development of strategies supporting routine assessment of PROs in severe asthma management.

Age-dependent effect of the IFIH1/MDA5 gene variants on the risk of critical COVID-19.

MDA5, encoded by the IFIH1gene, is a cytoplasmic sensor of viral RNAs that triggers interferon (IFN) antiviral responses. Common and rare IFIH1 variants have been associated with the risk of type 1 diabetes and other immune-mediated disorders, and with the outcome of viral diseases. Variants associated with reduced IFN expression would increase the risk for severe viral disease. The MDA5/IFN pathway would play a critical role in the response to SARS-CoV-2 infection mediating the extent and severity of COVID-19. Here, we genotyped a cohort of 477 patients with critical ICU COVID-19 (109 death) for three IFIH1 functional variants: rs1990760 (p.Ala946Thr), rs35337543 (splicing variant, intron 8 + 1G > C), and rs35744605 (p.Glu627Stop). The main finding of our study was a significant increased frequency of rs1990760 C-carriers in early-onset patients (< 65 years) (p = 0.01; OR = 1.64, 95%CI = 1.18-2.43). This variant was also increased in critical vs. no-ICU patients and in critical vs. asymptomatic controls. The rs35744605 C variant was associated with increased blood IL6 levels at ICU admission. The rare rs35337543 splicing variant showed a trend toward protection from early-onset critical COVID-19. In conclusion, IFIH1 variants associated with reduced gene expression and lower IFN response might contribute to develop critical COVID-19 with an age-dependent effect.

IGHG3 hinge length variation was associated with the risk of critical disease and death in a Spanish COVID-19 cohort.

IgG3 would play an important role in the immune adaptive response against SARS-CoV-2, and low plasma levels might increase the risk of COVID-19 severity and mortality. The IgG3 hinge sequence has a variable repeat of a 15 amino acid exon with common 4-repeats (M) and 3-repeats (S). This length IGHG3 polymorphism might affect the IgG3 effector functions. The short hinge length would reduce the IgG3 flexibility and impairs the neutralization and phagocytosis compared to larger length-isoforms. We genotyped the IGHG3 length polymorphism in patients with critical COVID-19 (N = 516; 107 death) and 152 moderate-severe but no-critical cases. Carriers of the S allele had an increased risk of critical ICU and mortality (p < 0.001, OR = 2.79, 95% CI = 1.66-4.65). This adverse effect might be explained by a less flexibility and reduced ability to induce phagocytosis or viral neutralization for the short length allele. We concluded that the IgG3 hinge length polymorphism could be a predictor of critical COVID-19 and the risk of death. This study was based on a limited number of patients from a single population, and requires validation in larger cohorts.

Results in clinical practice in the treatment of severe eosinophilic asthma with mepolizumab: a real-life study.

OBJECTIVE: Add-on therapy with monoclonal antibodies is the recommended therapy for severe asthmatic patients refractory to maintenance treatment. In randomized control trials, mepolizumab reduced the number of exacerbations, the need of oral corticosteroids (OCS), increased asthma control, and lung function in a population of uncontrolled severe eosinophilic asthmatic patients. In this piece of work, we aimed to assess mepolizumab efficacy and safety in a cohort of patients with severe eosinophilic asthma in real-life conditions. METHODS: A retrospective study was carried out at eight hospitals from Asturias (Spain). The sample included patients treated with mepolizumab from 1 January 2016 to 31 March 2019. Demographic and clinical variables were collected, including OCS use, asthma control, lung function, and exacerbation rate. RESULTS: Sixty-nine patients (72% women) with mean age 56 ± 13 years were included. Annual exacerbation rate decreased from 4.7 (SD 3.7) to 1.3 (SD 2.5) (p < 0.001). The number of patients requiring OCS treatment decreased from 25 patients (36%, mean prednisone dose = 18 mg/day) to 13 patients (19%, mean prednisone dose = 9 mg/day) (p < 0.001). Twelve patients (48%) stopped OCS treatment. Forced expired volume in one second (FEV1) as percentage increased from 68% (SD 20) to 76% (SD 21) (p < 0.001). Fifty-six patients (81%) were considered responders to mepolizumab. No serious adverse events were detected during the study period. CONCLUSIONS: Overall, this study demonstrates mepolizumab efficacy and safety in a cohort of patients with uncontrolled severe eosinophilic asthma in routine clinical practice.

Association between the interferon-induced transmembrane protein 3 gene (IFITM3) rs34481144 / rs12252 haplotypes and COVID-19.

The interferon induced transmembrane-protein 3 (IFITM3) plays an important role in the defence against viral infection. IFITM3 gene variants have been linked to differences in expression and associated with the risk of severe influenza by some authors. More recently, these variants have been associated with the risk of COVID-19 after SARS-CoV-2 infection. We determined the effect of two common IFITM3 polymorphisms (rs34481144 â€‹C/T and rs12252 A/G) on the risk of hospitalization due to COVID-19 by comparing 484 patients (152 required support in thr intensive care unit, ICU) and 182 age and sex matched controls (no disease symptoms). We found significantly higher frequencies of rs34481144 â€‹T and rs12252 â€‹G carriers among the patients (OR â€‹= â€‹2.02 and OR â€‹= â€‹1.51, respectively). None of the two variants were associated with ICU-admission or death. We found a significantly higher frequency of rs34481144 CC â€‹+ â€‹rs12252 AA genotype carriers among the controls, suggesting a protective effect (p = 0.001, OR = 0.56, 95%CI = 0.40-0.80). Moreover, haplotype rs34481144 â€‹C - rs12252 A was significantly increased in the controls (p â€‹= â€‹0.008, OR â€‹= â€‹0.71, 95%CI â€‹= â€‹0.55-0.91). Our results showed a significant effect of the IFITM3 variants in the risk for hospitalization after SARS-CoV-2 infection.

Biopsy of Intrapulmonary Lesions in Lungs with Atelectasis and Pleural Effusion / Biopsia de lesiones intrapulmonares en pulmones con atelectasia y derrame pleural

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¿Puede ser la infección por SARS-CoV-2 un factor de riesgo de aspergilosis pulmonar? / Can SARS-CoV-2 be a Risk Factor for Pulmonary Aspergillosis?

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Assessment of risk scores in Covid-19.

OBJECTIVE: To analyse the accuracy of commonly used risk scores (PSI and CURB-65) in predicting mortality and need for ICU admission in Covid-19. MATERIAL AND METHODS: Prospective study of patients diagnosed with Covid-19 pneumonia. Patients were followed until home discharge or death. PSI, CURB-65, SMART-COP and MuLBSTA severity scores were assessed on admission. Risk scores were related to mortality and ICU admission. RESULTS: About 249 patients, 143 males (57.4%) were included. The mean age was 65.6 + 16.1 years. Factors associates with mortality in the multivariate analysis were age > 80 years (OR: 13.9; 95% CI 3.8-51.1) (P = .000), lymphocytes < 800 (OR: 2.9; CI 95% 1.1-7-9) (P = .040), confusion (OR: 6.3; 95% CI 1.6-24.7) (P = .008) and NT-proBNP > 500 pg/mL (OR: 10.1; 95% CI 1.1-63.1) (P = .039). In predicting mortality, the PSI score: AUC 0.874 (95% CI 0.808-0.939) and the CURB-65 score: AUC 0.852 (95% CI 0.794-0.909) were the ones that obtained the best results. In the need for ICU admission, the SMART-COP score: AUC 0.749 (95% CI 0.695-0.820) and the MuLBSTA score: AUC 0.777 (95% CI 0.713-0.840) were the ones that obtained better results, with significant differences with PSI and CURB-65. The scores with the lowest value for ICU admission prediction were PSI with AUC of 0.620 (95% CI 0.549-0.690) and CURB-65 with AUC of 0.604 (95% CI 0.528-0.680). CONCLUSIONS: Prognosis scores routinely used for CAP (PSI and CURB-65) were good predictors for mortality in patients with Covid-19 CAP but not for need of hospitalisation or ICU admission. In the evaluation of Covid-19 pneumonia, we need scores that allow to decide the appropriate level of care.

Impacto clínico de una unidad de patología pleural en un hospital de tercer nivel / Clinical Impact of a Pleural Unit in a Tertiary Level Hospital

INTRODUCCIÓN: La enfermedad pleural conlleva un gran número de ingresos y elevadas estancias hospitalarias. Con el fin de mejorar esto, se creó en nuestro hospital una unidad de patología pleural (UPP). Nuestro objetivo es analizar el impacto clínico de dicha unidad. MATERIAL Y MÉTODOS: Estudio prospectivo en el que incluimos a los pacientes ingresados en la UPP del Hospital Universitario Central de Asturias por neumotórax espontáneo primario (NEP), secundario (NES), derrame pleural paraneumónico complicado (DPPC) y derrame pleural maligno (DPM), entre enero de 2015 y diciembre de 2018. Analizamos parámetros descriptivos, estancias medias, reingresos al mes, necesidad de cirugía y, en los DPPC, también la mortalidad hospitalaria. Los datos se compararon con los de los pacientes ingresados por la misma enfermedad en neumología durante los 2 años previos (2013-2014). Describimos además todos los procedimientos realizados en la UPP, tanto ambulatorios como en pacientes ingresados. RESULTADOS: Se incluyeron 741 pacientes. Objetivamos una disminución progresiva de los ingresos totales por enfermedad pleural y de la estancia media (días) en dichas afecciones, excepto en el DPM: NEP de 6,2 a 4,2 (p = 0,004), NES de 13,2 a 8,6 (p = 0,005), DPM de 10,3 a 12,3 (p = 0,05) y DPPC de 18,3 a 11,3 (p = 0,001). Existió una reducción de los reingresos al mes y de la mortalidad hospitalaria por DPPC en el periodo de la UPP (14,9% al 5,5%) (p = 0,021). CONCLUSIONES: La creación de una UPP podría disminuir el número de ingresos innecesarios, favoreciendo una reducción de las estancias medias y, en los DPPC, también la mortalidad hospitalaria

INTRODUCTION: Pleural disease involves a large number of admissions and long hospital stays. In order to improve this situation, a Pleural Unit (PU) was created in our hospital. Our aim was to analyze the clinical impact of this unit. MATERIAL AND METHODS: In this prospective study, we included patients admitted to the PU of the Hospital Universitario Central de Asturias for primary spontaneous pneumothorax (PSP), secondary spontaneous pneumothorax (SSP), complicated parapneumonic pleural effusion (CPPE), and malignant pleural effusion (MPE) between January 2015 and December 2018. We analyzed descriptive parameters, mean length of stay, readmissions at 1 month, need for surgery, and in the CPPE group, in-hospital mortality. The data were compared with those of patients admitted to the respiratory medicine department for the same diseases during the previous two years (2013-2014). We also describe all procedures performed in the PU, in both inpatients and outpatients. RESULTS: A total of 741 patients were included, We observed a progressive decrease in total admissions for pleural diseases and mean length of stay (days) (with the exception of MPE), as follows: PSP: from 6.2 to 4.2 (P = .004); SSP: 13.2 to 8.6 (P = .005), MPE: 10.3 to 12.3 (P = .05); and CPPE: 18.3 to 11.3 (P = .001) There was a reduction in hospital readmissions at 1 month and in in-hospital mortality due to CPPE in the PU period (14.9% to 5.5%) (P = .021). CONCLUSIONS: The creation of a PU could decrease the number of unnecessary admissions, and reduce mean lengths of stay and, in the case of CPPE, in-hospital mortality

Clinical Impact of a Pleural Unit in a Tertiary Level Hospital. / Impacto clínico de una unidad de patología pleural en un hospital de tercer nivel.

INTRODUCTION: Pleural disease involves a large number of admissions and long hospital stays. In order to improve this situation, a Pleural Unit (PU) was created in our hospital. Our aim was to analyze the clinical impact of this unit. MATERIAL AND METHODS: In this prospective study, we included patients admitted to the PU of the Hospital Universitario Central de Asturias for primary spontaneous pneumothorax (PSP), secondary spontaneous pneumothorax (SSP), complicated parapneumonic pleural effusion (CPPE), and malignant pleural effusion (MPE) between January 2015 and December 2018. We analyzed descriptive parameters, mean length of stay, readmissions at 1 month, need for surgery, and in the CPPE group, in-hospital mortality. The data were compared with those of patients admitted to the respiratory medicine department for the same diseases during the previous two years (2013-2014). We also describe all procedures performed in the PU, in both inpatients and outpatients. RESULTS: A total of 741 patients were included, We observed a progressive decrease in total admissions for pleural diseases and mean length of stay (days) (with the exception of MPE), as follows: PSP: from 6.2 to 4.2 (P=.004); SSP: 13.2 to 8.6 (P=.005), MPE: 10.3 to 12.3 (P=.05); and CPPE: 18.3 to 11.3 (P=.001) There was a reduction in hospital readmissions at 1 month and in in-hospital mortality due to CPPE in the PU period (14.9% to 5.5%) (P=.021). CONCLUSIONS: The creation of a PU could decrease the number of unnecessary admissions, and reduce mean lengths of stay and, in the case of CPPE, in-hospital mortality.

Respuesta a la hipercapnia en pacientes con síndrome obesidad-hipoventilación en tratamiento con ventilación no invasiva en domicilio / Hypercapnia Response in Patients with Obesity-Hypoventilation Syndrome Treated with Non-Invasive Ventilation at Home

Introducción: En la patogenia del síndrome de obesidad-hipoventilación (SOH) se ha postulado una disfunción del centro respiratorio, que muchas veces precisa la utilización de ventilación no invasiva (VNI) en domicilio para el tratamiento. Nuestro objetivo fue medir el efecto de la VNI en la función del CR en pacientes con SOH y los factores que lo determinan. Métodos: Con un diseño prospectivo de mediciones repetidas se estudió la respuesta a la hipercapnia (RHC) midiendo la pendiente de la relación p01/pEtCO2 en situación basal y tras 6meses de tratamiento con VNI en un grupo de pacientes con SOH. Previamente en un grupo control se estableció un umbral en 0,22cmH2O/mmHg para diferenciar la respuesta óptima (RO) de la respuesta subóptima (RSO) del CR. Resultados: Se incluyeron 36 casos, 19 varones (52%), de 65 (DE: 9) años de edad; un 63% de ellos tenían un p01/pEtCO2 por debajo del valor de referencia. El valor basal de p01/pEtCO2 fue de 0,17 (DE: 0,14) cmH2O/mmHg y tras 6meses de VNI fue de 0,30 (DE: 0,22) cmH2O/mmHg (p=0,011). Tras 6meses de tratamiento con VNI, 12 casos (33%) mantienen una función deprimida de su CR. Conclusión: Un 63% de los pacientes con SOH mostraron disfunción de su CR. La aplicación de VNI mejora la función del CR, aunque no en todos los casos

Introduction: Respiratory center (RC) dysfunction has been implicated in the pathogenesis of obesity-hypoventilation syndrome (OHS), and often requires treatment with home non-invasive ventilation (NIV). Our objective was to measure the effect of NIV on RC function in patients with OHS, and the factors that determine such an effect. Methods: We performed a prospective, repeated measures study to evaluate hypercapnia response (HR) by determining the p01/pEtCO2 ratio slope at baseline and after 6months of treatment with NIV in a group of OHS patients. A threshold of 0.22cmH2O/mmHg had previously been established in a control group, in order to differentiate optimal RC response from suboptimal RC response. Results: A total of 36 cases were included, 19 men (52%) aged 65 (SD 9) years, 63% of whom had p01/pEtCO2 below the reference value. Baseline p01/pEtCO2 was 0.17 (SD: 0.14) cmH2O/mmHg and, after 6 months of NIV, 0.30 (SD: 0.22) cmH2O/mmHg (p=0.011). After 6months of treatment with NIV, depressed RC function persisted in 12 cases (33%). Conclusion: In total, 63% of OHS patients had RC dysfunction. The application of NIV improves RC function but not in all cases

Hypercapnia Response in Patients with Obesity-Hypoventilation Syndrome Treated with Non-Invasive Ventilation at Home. / Respuesta a la hipercapnia en pacientes con síndrome obesidad-hipoventilación en tratamiento con ventilación no invasiva en domicilio.

INTRODUCTION: Respiratory center (RC) dysfunction has been implicated in the pathogenesis of obesity-hypoventilation syndrome (OHS), and often requires treatment with home non-invasive ventilation (NIV). Our objective was to measure the effect of NIV on RC function in patients with OHS, and the factors that determine such an effect. METHODS: We performed a prospective, repeated measures study to evaluate hypercapnia response (HR) by determining the p01/pEtCO2 ratio slope at baseline and after 6months of treatment with NIV in a group of OHS patients. A threshold of 0.22cmH2O/mmHg had previously been established in a control group, in order to differentiate optimal RC response from suboptimal RC response. RESULTS: A total of 36 cases were included, 19 men (52%) aged 65 (SD 9) years, 63% of whom had p01/pEtCO2 below the reference value. Baseline p01/pEtCO2 was 0.17 (SD: 0.14) cmH2O/mmHg and, after 6 months of NIV, 0.30 (SD: 0.22) cmH2O/mmHg (p=0.011). After 6months of treatment with NIV, depressed RC function persisted in 12 cases (33%). CONCLUSION: In total, 63% of OHS patients had RC dysfunction. The application of NIV improves RC function but not in all cases.