Documento de consenso de expertos para el control del asma en personas mayores / Expert consensus recommendations for the management of asthma in older adults

El asma constituye un problema de salud pública presente en pacientes de cualquier edad, aunque continúa existiendo cierta tendencia a asumir de forma errónea que dicha entidad resulta casi siempre exclusiva de la infancia y de gente joven. Los estudios epidemiológicos señalan que, a partir de la sexta década de la vida, la prevalencia de esta enfermedad en países como España alcanza el 6-10%, con mayor predominio entre las mujeres de 64 a 75 años. Asimismo, dos tercios de las muertes debidas al asma acontecen en esta etapa de la vida, llegando a ocasionar un número de ingresos sustancial, estancias hospitalarias más prolongadas y, desde el punto de vista del financiador, unos costes económicos directos notables. En la actualidad el asma en las personas mayores (65 años o más) constituye un tema de enorme preocupación, cuya realidad se encuentra infravalorada e infratratada, por lo que resulta del todo necesario establecer unas recomendaciones adecuadas para el diagnóstico y tratamiento de la enfermedad en esta población de edad. Con este objetivo nació este consenso que recoge la evidencia disponible más actualizada. Las recomendaciones/conclusiones que se proponen son el resultado de un consenso de tipo nominal desarrollado a lo largo del año 2019 y que han sido validadas por los panelistas en sucesivas rondas de votación. (AU)

Asthma is a public health problem in patients of any age, although there is still a tendency to erroneously assume that it is almost always confined to children and young people. Epidemiological studies indicate that, from the sixth decade of life, the prevalence of this disease in countries such as Spain reaches 6-10%, with a higher prevalence among women aged 64 to 75 years. In addition, two-thirds of asthma deaths occur at this stage of life, resulting in a substantial number of hospital admissions, longer hospital stays and, from a finance point of view, significant direct economic costs. Asthma in older adults (65 years or older) is now a matter of great concern, the reality of which is underestimated and undertreated. It is therefore essential to establish appropriate recommendations for the diagnosis and treatment of asthma in the aging population. This consensus, which brings together the latest evidence available, was conceived with this objective. The proposed recommendations/conclusions are the result of a nominal consensus developed throughout 2019 and validated by panellists in successive rounds of voting. (AU)

Expert consensus recommendations for the management of asthma in older adults. / Documento de consenso de expertos para el control del asma en personas mayores.

Asthma is a public health problem in patients of any age, although there is still a tendency to erroneously assume that it is almost always confined to children and young people. Epidemiological studies indicate that, from the sixth decade of life, the prevalence of this disease in countries such as Spain reaches 6-10%, with a higher prevalence among women aged 64 to 75 years. In addition, two-thirds of asthma deaths occur at this stage of life, resulting in a substantial number of hospital admissions, longer hospital stays and, from a finance point of view, significant direct economic costs. Asthma in older adults (65 years or older) is now a matter of great concern, the reality of which is underestimated and undertreated. It is therefore essential to establish appropriate recommendations for the diagnosis and treatment of asthma in the aging population. This consensus, which brings together the latest evidence available, was conceived with this objective. The proposed recommendations/conclusions are the result of a nominal consensus developed throughout 2019 and validated by panellists in successive rounds of voting.

Double-blind, randomized, controlled, trial to assess the efficacy of allogenic mesenchymal stromal cells in patients with acute respiratory distress syndrome due to COVID-19 (COVID-AT): A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: 1. To assess the efficacy of Mesenchymal Stromal Cells (MSC) versus a control arm as described in the primary endpoint. 2. To evaluate the effects of MSC on the secondary efficacy endpoints. 3. To evaluate the safety and tolerability profiles of MSC. 4. To study soluble and cellular biomarkers that might be involved in the course of the disease and the response to the investigational product. TRIAL DESIGN: A double-blind, randomized, controlled, trial to evaluate the efficacy and safety of MSC intravenous administration in patients with COVID-induced Acute Respiratory Distress Syndrome (ARDS) compared to a control arm. PARTICIPANTS: The trial is being conducted at a third level hospital, Hospital Universitario Puerta de Hierro, in Majadahonda, Madrid (Spain). Inclusion criteria 1. Informed consent prior to performing study procedures (witnessed oral consent with written consent by representatives will be accepted to avoid paper handling). Written consent by patient or representatives will be obtained whenever possible. 2. Adult patients ≥18 years of age at the time of enrolment. 3. Laboratory-confirmed SARS-CoV-2 infection as determined by Polymerase Chain Reaction (PCR), in oropharyngeal swabs or any other relevant specimen obtained during the course of the disease. Alternative tests (e.g., rapid antigen tests) are also acceptable as laboratory confirmation if their specificity has been accepted by the Sponsor. 4. Moderate to severe ARDS (PaO2/FiO2 ratio equal or less than 200 mmHg) for less than 96 hours at the time of randomization. 5. Patients requiring invasive ventilation are eligible within 72 hours from intubation. 6. Eligible for ICU admission, according to the clinical team. Exclusion criteria 1. Imminent and unavoidable progression to death within 24 hours, irrespective of the provision of treatments (in the opinion of the clinical team). 2. "Do Not Attempt Resuscitation" order in place. 3. Any end-stage organ disease or condition, which in the investigator's opinion, makes the patient an unsuitable candidate for treatment. 4. History of a moderate/severe lung disorder requiring home-based oxygen therapy. 5. Patient requiring Extracorporeal Membrane Oxygenation (ECMO), haemodialysis or hemofiltration at the time of treatment administration. 6. Current diagnosis of pulmonary embolism. 7. Active neoplasm, except carcinoma in situ or basalioma. 8. Known allergy to the products involved in the allogeneic MSC production process. 9. Current pregnancy or lactation (women with childbearing potential should have a negative pregnancy test result at the time of study enrolment). 10. Current participation in a clinical trial with an experimental treatment for COVID-19 (the use of any off-label medicine according to local treatment protocols is not an exclusion criteria). 11. Any circumstances that in the investigator's opinion compromises the patient's ability to participate in the clinical trial. INTERVENTION AND COMPARATOR: - Experimental treatment arm: Allogeneic MSC (approximately 1 x 106 cells/kg). - Control arm: placebo solution (same composition as the experimental treatment, without the MSC). One single intravenous dose of the assigned treatment will be administered on Day 0 of the study. All trial participants will receive standard of care (SOC). In the context of the current worldwide pandemic, SOC can include medicines that are being used in clinical practice (e.g. lopinavir/ritonavir; hydroxy/chloroquine, tocilizumab, etc.), as well as those authorised for COVID (e.g., remdesivir). MAIN OUTCOMES: Primary endpoint: Change in the PaO2/FiO2 ratio from baseline to day 7 of treatment administration, or to the last available PaO2/FiO2 ratio if death occurs before day 7. Secondary endpoints: - All-cause mortality on days 7, 14, and 28 after treatment. - PaO2/FiO2 ratio at baseline and days 2, 4, 7, 14 and 28 after treatment. - Oxygen saturation (by standardized measurement) at baseline, daily until day 14, and on day 28 after treatment. - Time to PaO2/FiO2 ratio greater than 200 mmHg. - Subjects' clinical status on the WHO 7-point ordinal scale at baseline, daily until day 14, and on day 28 after treatment. - Time to an improvement of one category from admission on the WHO 7-point ordinal scale. - Percentage of patients that worsen at least one category on the WHO 7-point ordinal scale. - Percentage of patients that improve at least one category (maintained 48h) on the WHO 7-point ordinal scale. - Sequential Organ Failure Assessment (SOFA) scale at baseline and days 2, 4, 7, 14 and 28 after treatment. - Duration of hospitalization (days). - Duration of ICU stay (days). - Oxygen therapy-free days in the first 28 days after treatment. - Duration of supplemental oxygen. - Incidence of and duration of non-invasive and invasive mechanical ventilation in the first 28 days after treatment. - Mechanical ventilation-free days in the first 28 days after treatment. - Ventilation parameters. - Incidence of new onset pulmonary fibrosis at 3 and 12 months after treatment, based on CT scan and pulmonary function tests. - Survival at 3 and 12 months. - Cumulative incidence of Serious Adverse events (SAEs) and Grade 3 and 4 Adverse Events (AEs). - Cumulative incidence of Adverse Drug Reactions (ADR) in the experimental treatment arm. - Cumulative incidence of AEs of special interest. - Levels of analytical markers (C-Reactive Protein, lymphocyte and neutrophil counts, lymphocyte subpopulations, LDH, ferritin, D-dimer, coagulation tests and cytokines...) at baseline and days 2, 4, 7, 14 and 28 after treatment. - Other soluble and cellular biomarkers that might be involved in the course of the disease and the response to MSC. RANDOMISATION: The assignment to treatment will be carried out randomly and blinded, with a 1:1 allocation. Randomization will be done through a centralized system embedded in the electronic Case Report Form (CRF). BLINDING (MASKING): To ensure blinding, treatments will be prepared for administration at the Cell Production Unit and the administration of the treatment will be masked, not allowing the identification of the Investigational Medicinal Product (IMP). NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 20 participants are planned to be randomized, 10 to each treatment group. TRIAL STATUS: Protocol version: 1.2, dated October 14th, 2020 Start of recruitment: 01/10/2020 End of recruitment (estimated): December 2020. TRIAL REGISTRATION: EudraCT Number: 2020-002193-27 , registered on July 14th, 2020. NCT number: NCT04615429 , registered on November 4th, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Accreditation of specialized asthma units for adults in Spain: an applicable experience for the management of difficult-to-control asthma.

This paper, developed by consensus of staff physicians of accredited asthma units for the management of severe asthma, presents information on the process and requirements for already-existing asthma units to achieve official accreditation by the Spanish Society of Pneumology and Thoracic Surgery (SEPAR). Three levels of specialized asthma care have been established based on available resources, which include specialized units for highly complex asthma, specialized asthma units, and basic asthma units. Regardless of the level of accreditation obtained, the distinction of "excellence" could be granted when more requirements in the areas of provision of care, technical and human resources, training in asthma, and teaching and research activities were met at each level. The Spanish experience in the process of accreditation of specialized asthma units, particularly for the care of patients with difficult-to-control asthma, may be applicable to other health care settings.