Analysis of comorbidities and multimorbidity in adult patients in the International Severe Asthma Registry.

BACKGROUND: Investigation for the presence of asthma comorbidities is recommended by the Global Initiative for Asthma because their presence can complicate asthma management. OBJECTIVE: To understand the prevalence and pattern of comorbidities and multimorbidity in adults with severe asthma and their association with asthma-related outcomes. METHODS: This was a cross-sectional study using data from the International Severe Asthma Registry from 22 countries. A total of 30 comorbidities were identified and categorized a priori as any of the following: (1) potentially type 2-related comorbidities, (2) potentially oral corticosteroid (OCS)-related comorbidities, or (3) comorbidities mimicking or aggravating asthma. The association between comorbidities and asthma-related outcomes was investigated using multivariable models adjusted for country, age at enrollment, and sex (ie male or female). RESULTS: Of the 11,821 patients, 69%, 67%, and 55% had at least 1 potentially type 2-related, potentially OCS-related, or mimicking or aggravating comorbidities, respectively; 57% had 3 or more comorbidities, and 33% had comorbidities in all 3 categories. Patients with allergic rhinitis, nasal polyposis, and chronic rhinosinusitis experienced 1.12 (P = .003), 1.16 (P < .001), and 1.29 times (P < .001) more exacerbations per year, respectively, than those without. Patients with nasal polyposis and chronic rhinosinusitis were 40% and 46% more likely (P < .001), respectively, to have received long-term (LT) OCS. All assessed potential OCS-related comorbidities (except obesity) were associated with a greater likelihood of LTOCS use (odds ratios [ORs]: 1.23-2.77) and, except for dyslipidemia, with a greater likelihood of uncontrolled asthma (ORs: 1.29-1.68). All mimicking or aggravating comorbidities assessed were associated with more exacerbations (1.24-1.68 times more), all (except bronchiectasis) with increased likelihood of uncontrolled asthma (ORs: 1.57-1.81), and all (except chronic obstructive pulmonary disease) with increased likelihood of LTOCS use (ORs: 1.37-1.57). A greater number of comorbidities was associated with worse outcomes. CONCLUSION: In a global study, comorbidity or multimorbidity is reported in most adults with severe asthma and is associated with poorer asthma-related outcomes. CLINICAL TRIAL REGISTRATION: The International Severe Asthma Registry database has ethical approval from the Anonymous Data Ethics Protocols and Transparency (ADEPT) committee (ADEPT0218) and is registered with the European Union Electronic Register of Post-Authorization Studies (European Network Centres for Pharmacoepidemiology and Pharmacovigilance [ENCEPP]/DSPP/23720). The study was designed, implemented, and reported in compliance with the European Network Centres for Pharmacoepidemiology and Pharmacovigilance (ENCEPP) Code of Conduct (EMA 2014; EUPAS44024) and with all applicable local and international laws and regulations, and registered with ENCEPP (https://www.encepp.eu/encepp/viewResource.htm?id=48848). Governance was provided by ADEPT (registration number: ADEPT1121).

Association Between T2-related Comorbidities and Effectiveness of Biologics in Severe Asthma.

Rationale: Previous studies investigating the impact of comorbidities on the effectiveness of biologic agents have been relatively small and of short duration and have not compared classes of biologic agents. Objectives: To determine the association between type 2-related comorbidities and biologic agent effectiveness in adults with severe asthma (SA). Methods: This cohort study used International Severe Asthma Registry data from 21 countries (2017-2022) to quantify changes in four outcomes before and after biologic therapy-annual asthma exacerbation rate, FEV1% predicted, asthma control, and long-term oral corticosteroid daily dose-in patients with or without allergic rhinitis, chronic rhinosinusitis (CRS) with or without nasal polyps (NPs), NPs, or eczema/atopic dermatitis. Measurements and Main Results: Of 1,765 patients, 1,257, 421, and 87 initiated anti-IL-5/5 receptor, anti-IgE, and anti-IL-4/13 therapies, respectively. In general, pre- versus post-biologic therapy improvements were noted in all four asthma outcomes assessed, irrespective of comorbidity status. However, patients with comorbid CRS with or without NPs experienced 23% fewer exacerbations per year (95% CI, 10-35%; P < 0.001) and had 59% higher odds of better post-biologic therapy asthma control (95% CI, 26-102%; P < 0.001) than those without CRS with or without NPs. Similar estimates were noted for those with comorbid NPs: 22% fewer exacerbations and 56% higher odds of better post-biologic therapy control. Patients with SA and CRS with or without NPs had an additional FEV1% predicted improvement of 3.2% (95% CI, 1.0-5.3; P = 0.004), a trend that was also noted in those with comorbid NPs. The presence of allergic rhinitis or atopic dermatitis was not associated with post-biologic therapy effect for any outcome assessed. Conclusions: These findings highlight the importance of systematic comorbidity evaluation. The presence of CRS with or without NPs or NPs alone may be considered a predictor of the effectiveness of biologic agents in patients with SA.

Phenotyping the Responses to Systemic Corticosteroids in the Management of Asthma Attacks (PRISMA): protocol for an observational and translational pilot study.

INTRODUCTION: Asthma and its associated exacerbation are heterogeneous. Although severe asthma attacks are systematically prescribed corticosteroids and often antibiotics, little is known about the variability of response to these therapies. Blood eosinophils and fractional exhaled nitric oxide (FeNO) are type 2 inflammation biomarkers that have established mechanistic, prognostic and theragnostic values in chronic asthma, but their utility in acute asthma is unclear. We speculate that the clinical and biological response to those treatments varies according to inflammometry and microbiological test results. METHODS AND ANALYSIS: An observational longitudinal pilot study with multimodal clinical and translational assessments will be performed on 50 physician-diagnosed ≥12-year-old asthmatics presenting with an asthma attack and 12 healthy controls, including blood eosinophil count (venous and point-of-care (POC) capillary blood), FeNO and testing for airway infection (sputum cultures and POC nasopharyngeal swabs). People with asthma will be assessed on day 0 and after a 7-day corticosteroid course, with home monitoring performed in between. The primary analysis will be the change in the forced expiratory volume in 1 s according to type 2 inflammatory status (blood eosinophils ≥0.15×109/L and/or FeNO ≥25 ppb) after treatment. Key secondary analyses will compare changes in symptom scores and the proportion of patients achieving a minimal clinically important difference. Exploratory analyses will assess the relationship between clinical, lung function, inflammatory and microbiome parameters; satisfaction plus reliability indices of POC tests; and sex-gender variability in treatment response. Ultimately, this pilot study will serve to plan a larger trial comparing the clinical and biological response to systemic corticosteroids according to inflammatory biomarkers, offering valuable guidance for more personalised therapeutic strategies in asthma attacks. ETHICS AND DISSEMINATION: The protocol has been approved by the Research Ethics Committee of the CIUSSS de l'Estrie-CHUS, Sherbrooke, Quebec, Canada (#2023-4687). Results will be communicated in an international meeting and submitted to a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT05870215).

[Tezepelumab: a new option for the treatment of severe asthma]. / Tezepelumab: una nueva opción para el tratamiento del asma grave.

In Latin America, asthma is a public health problem with a significant impact on both patients and health systems. The greater understanding of the pathophysiology and the recognition of the central role that inflammation has in the severity of asthma has favored the development of monoclonal antibodies that have IL-5, IL-4, IL-13 and IgE as therapeutic targets. Although these therapeutic alternatives promote better control of the disease, not all patients respond favorably to these treatments. Therefore, it is of particular interest to explore monoclonal antibodies such as Tezepelumab, directed against thymic stromal lymphopoietin (TSLP), an alarmin (epithelial cytokine) that participates in the initiation and perpetuation of inflammation in Asthma. Therefore, in this review, we will show the clinical efficacy of tezepelumab in reducing the annual rate of exacerbations, improving lung function, and reducing bronchial hyperreactivity, regardless of the patient's baseline biomarker levels. Therefore, this new molecule is a highly effective therapeutic option for patients with severe asthma.

En Latinoamérica, el asma es un problema de salud pública con un impacto importante tanto para los pacientes como para los sistemas de salud. El mayor entendimiento de la fisiopatología y el reconocimiento del papel central que tiene la inflamación en la severidad del asma ha favorecido el desarrollo de anticuerpos monoclonales que tienen como blancos terapéuticos a la IL-5, IL-4, IL-13 y la IgE. Si bien estas alternativas terapéuticas favorecen un mejor control de la enfermedad, no todos los pacientes responden favorablemente a esos tratamientos. Por lo que resulta de particular interés explorar anticuerpos monoclonales como el Tezepelumab, dirigido contra la linfopoyetina estromal tímica (TSLP) una alarmina (citocina epitelial) que participa en el inicio y la perpetuación de la inflamación en el Asma. Por lo que, en esta revisión, mostraremos la eficacia clínica del tezepelumab en la disminución de la tasa anual de exacerbaciones, mejora en la función pulmonar y en la disminución en la hiperreactividad bronquial, independientemente de los niveles de biomarcadores basales que el paciente presente. Por lo que esta nueva molécula es una opción terapéutica altamente eficaz para el paciente con asma grave.

Estrategias de Reperfusión en el tratamiento de la embolia pulmonar aguda: Una revisión narrativa de la literatura / Reperfusion strategies in acute pulmonary embolism: A narrative review

La embolia pulmonar (EP) es una patología con gran carga de morbimortalidad, que amerita un diagnóstico y tratamiento oportunos, para mejorar los desenlaces de los pacientes. En el escenario agudo la trombólisis, bien sea por vía sistémica o dirigida por catéter, constituye una de las opciones de tratamiento que debe ser considerada. En este artículo se revisa la evidencia existente con respecto a las indicaciones de la terapia trombolítica, su eficacia y riesgos asociados.

Pulmonary embolism (PE) is an entity that still carries a high burden of morbidity and mortality. Timely diagnosis and treatment are required in order to improve the outcomes of patients. Either systemic or catheter-directed, thrombolysis is a treatment option that must be considered in the acute setting. In this article we review the evidence regarding indications, effectiveness and risks associated with thrombolytic therapy.

Sarcopenia, lung disease and mortality: a secondary analysis of the CRELES study / Sarcopenia, doença pulmonar e mortalidade: uma análise secundária do estudo CRELES

AIM: Chronic obstructive pulmonary disease (COPD) is a pro-inflammatory condition leading to wasting states such as sarcopenia. We aimed to describe the effect of COPD and sarcopenia on mortality in Costa Rican older adults in the Costa Rican Longevity and Healthy Aging Study (CRELES). METHOD: This is a secondary analysis of the CRELES, a cohort study consisting of three waves of interviews. For the current study, data from the first and third waves were used. The dependent variable was survival status. COPD and sarcopenia were independent variables. Bivariate analyses were used to compare mortality curves for each group. Association with 3-year mortality was tested with Cox regression models, and hazard ratios (HR) with 95% confidence intervals (CI) were estimated as a measure of the strength of association. RESULTS: Of a total of 2704 participants, 54.29% (n = 1468) were women. Overall mortality was 9.05%. Sarcopenic older adults had the strongest association with mortality (HR = 2.65; 95%CI, 1.81­3.90; p < 0.001), followed by those with both COPD and sarcopenia (HR = 2.59; 95%CI, 1.37­4.92; p = 0.003). The weakest association with mortality was found in patients with neither COPD nor sarcopenia. CONCLUSIONS: The synergistic effect of sarcopenia and COPD has been shown to independently increase mortality in older patients. Our results may be applicable to both Latin American residents and subjects of Hispanic descent living in developed countries. Sarcopenia should be assessed in all patients with COPD since the latter is not a disease limited to the lungs, but rather a systemic disease.

OBJETIVO: A doença pulmonar obstrutiva crônica (DPOC) é uma condição pró-inflamatória que conduz a estados de perda como a sarcopenia. Nosso objetivo foi descrever o efeito da DPOC e da sarcopenia sobre a mortalidade em idosos costa-riquenhos do estudo Costa Rican Longevity and Healthy Aging Study (CRELES). MÉTODO: Esta é uma análise secundária do CRELES, um estudo de coorte composto por três ondas de entrevistas. Para o presente estudo, foram utilizados dados da primeira e terceira ondas. A variável dependente foi o status de sobrevida. DPOC e sarcopenia foram variáveis independentes. Foram realizadas análises bivariadas para comparar as curvas de mortalidade para cada grupo. Testou-se a associação à mortalidade em 3 anos com modelos de regressão de Cox, e razões de risco (HR) com intervalos de confiança (IC) de 95% foram estimadas como medida da força da associação. RESULTADOS: De um total de 2704 participantes, 54,29% (n = 1468) eram mulheres. A mortalidade geral foi 9,05%. Idosos sarcopênicos apresentaram a associação mais forte à mortalidade (HR = 2,65; IC95%, 1,81­3,90; p < 0,001), seguidos por aqueles com DPOC e sarcopenia (HR = 2,59; IC95%, 1,37­4,92; p = 0,003). A associação mais fraca à mortalidade foi encontrada em pacientes sem DPOC e sarcopenia. CONCLUSÕES: Demonstrou-se que o efeito sinérgico da sarcopenia e da DPOC aumenta de forma independente a mortalidade em pacientes idosos. Nossos resultados podem ser aplicáveis a residentes latino-americanos e a descendentes de hispânicos que vivem em países desenvolvidos. A sarcopenia deve ser avaliada em todos os pacientes com DPOC, visto que esta não é uma doença limitada aos pulmões, mas sim uma doença sistêmica.

Social networks and traditional metrics of impact in pulmonary medicine journals: a correlation study.

INTRODUCTION: The Scimago Journal Rank (SJR) impact factor is extensively used. However, as the Internet has become widely available, new metrics are coming into play. Our research aims to determine whether a correlation between the SJR impact factor and metrics reflecting social media activity does exist. MATERIALS AND METHODS: We have used pulmonary medicine journals indexed in the SJR. Variables of social network usage have been extracted from verified accounts. Bivariate analyses have been performed with the Mann-Whitney U tests, the correlation between social media-derived variables and the SJR impact factor have been assessed with the Spearman correlation coefficient. Results are presented before and after adjustment for the years since the creation of the accounts. RESULTS: From 130 journals, 38 had at least one social network account, Twitter being the most commonly used (22.85%). The H index was higher in journals with social network accounts (Median 60 vs 17; p < 0.01). The global correlation between the SJR and the number of followers on Twitter revealed moderate agreement (r = 0.46; p < 0.01), which was excellent in open access journals (rs = 0.90; p < 0.05). CONCLUSIONS: The use of social networks is directly correlated with traditional indicators of scientific impact. The joint use of alternative and traditional metrics may be useful for journals in order to generate strategies aiming to increase their audience, as well as for researchers when deciding about the best option of disseminating their articles.

Regla de predicción PERC y dímero D ajustado por edad: dos nuevas estrategias en el diagnóstico de embolia pulmonar aguda / PERC prediction rule and D-dimer adjusted for age: two new strategies in the diagnosis of acute pulmonary embolism

Resumen: La embolia pulmonar es una enfermedad de alta incidencia a pesar del subdiagnóstico y acarrea alto riesgo de morbilidad y mortalidad. Las herramientas preprueba actuales (clínica, escalas de probabilidad y dímero D) han permitido optimizar la precisión diagnóstica con miras a seleccionar al subgrupo de pacientes que obtendrán el mayor beneficio de la práctica de una angiotomografía para establecer el diagnóstico de embolia pulmonar. Este artículo revisa críticamente la evidencia publicada de la escala de predicción clínica PERC y el ajuste del dímero D por edad para el diagnóstico de embolia pulmonar aguda. Se hizo una revisión estructurada de la bibliografía médica en las bases de datos PubMed, TripDatabase y Epistemonikos. La búsqueda se limitó a metanálisis, estudios aleatorios, estudios de cohorte y guías de manejo, sin límites en idioma o fecha de publicación, utilizando los términos MESH d-dimer, pulmonary embolism, diagnosis y Pulmonary Embolism Rule-Out Criteria. Se hizo la lectura del título y el resumen de 1512 referencias de las que se seleccionaron 50 que fueron representativas para el tema de esta revisión; después de una clasificación y extracción de los datos se procedió a la redacción del texto. La escala PERC y el dímero D ajustado por edad son estrategias recomendadas en el abordaje diagnóstico del paciente con embolia pulmonar.

Abstract: Pulmonary embolism is a high incidence disease despite underdiagnosis and carries a high risk of morbidity and mortality. The current pre-test tools (clinical, probability scales and D-dimer) have allowed to optimize the diagnostic accuracy, since it is problematic to select the subgroup of patients who will obtain a greater benefit from the practice of an angiotomography to establish the diagnosis of pulmonary embolism. This paper reviews critically the published evidence on the PERC scale and the adjusting of the D-dimer with age for the diagnosis of acute pulmonary embolism. As structured review of the medical literature on PubMed, Tripdatabase and Epistemonikos databases was made. Search was limited to meta-analysis, randomized studies, cohort studies, review articles and treatment guidelines without limits on language or date of publication, using MESH terms: d-dimer, pulmonary embolism, diagnosis. It was performed the reading of the title and abstract of 1512 references of which 50 were selected as representative for the subject of this review. We wrote the manuscript after classification and data extraction. The use of the PERC scale and age-adjusted D-dimer are recommended in the diagnostic approach of the patient with pulmonary embolism.

Compromiso pulmonar en pacientes con infección por el virus de inmunodeficiencia humana (VIH) / Pulmonary Manifestations in Patients with Human Immunodeficiency Virus (HIV) Infection

El virus de la inmunodeficiencia humana (VIH) continúa siendo un problema de salud pública mundial, a pesar de la introducción de la terapia antirretroviral y la profilaxis frente a patógenos oportunistas. El pulmón es uno de los órganos más afectados por condiciones tanto infecciosas como no infecciosas en el contexto de la enfermedad retroviral; sin embargo, la prevalencia de las enfermedades de las vías respiratorias ha cambiado en las últimas dos décadas, tanto local como globalmente, por lo que se decidió realizar una búsqueda de la literatura más reciente en las bases de datos Medline y SciELO, incluyendo revisiones de tema y estudios originales, con el objetivo de elaborar una descripción actualizada de las principales enfermedades pulmonares descritas en pacientes con VIH, desde los puntos de vista clínico, paraclínico, radiológico y broncoscópico.

Human immunodeficiency virus (HIV) remains a public health problem worldwide, despite the introduction of antiretroviral therapy and prophylaxis against opportunistic pathogens. The lung is one of the most affected organs by both infectious and non-infectious diseases in the context of HIV, however, the prevalence of respiratory tract diseases has changed over the past two decades, both locally and globally, therefore, the authors decided to conduct a search of the most recent literature on Medline and SciELO databases, including reviews and original studies, with the aim of elaborating an updated description of the main pulmonary diseases in patients with HIV, taking into account clinical, paraclinical, radiological and bronchoscopic aspects.

[Sarcopenia in the elderly with a history of COPD/asthma: Results of the SABE-Bogotá study]. / Sarcopenia en ancianos con antecedente de EPOC/asma: resultados del estudio SABE - Bogotá.

INTRODUCTION: It has been reported that sarcopenia frequently co-exists with COPD/asthma, and can significantly affect quality of life and the control of chronic diseases. The aim of this study is to describe the association between COPD/asthma and sarcopenia. MATERIAL AND METHODS: Data was used from the SABE-Bogotá study, which included 2,000 older adults aged 60 years or more. It is a cross-probabilistic cluster sample with 81.9% coverage. The dependent variable was COPD/asthma. An analysis was performed to determine the association with sarcopenia and the other variables using univariate and bivariate analysis and logistic regression adjusted to confusion variables. RESULTS: The self-reported prevalence of COPD/asthma in the total sample was 16.7%, and Sarcopenia was estimated as 6,96%, but in COPD/asthma patients it was 11.2% (P=.004). In the multivariate analysis an association was found between COPD/asthma and sarcopenia (2.01, 95% CI: 1,21-3,35). CONCLUSIONS: Screening of sarcopenia in older adults with COPD/asthma, as well as interventions such as nutrition and exercise, are important, and ideally in the context of pulmonary rehabilitation programs, due the significant independent association that was found between COPD/asthma and sarcopenia.

Derrame pleural eosinofílico: una presentación no común de tuberculosis pleural / Eosinophilic pleural effusion: an uncommon presentation of pleural tuberculosis

De forma característica, la tuberculosis pleural se manifiesta como un exudado linfocitario con valores elevados de adenosín deaminasa (ADA) pleural. Se presenta el caso de una paciente con exudado eosinofílico, ADA alta y biopsia pleural compatible con tuberculosis. Se revisa la literatura sobre el significado clínico y las diferentes posibilidades diagnósticas del derrame pleural eosinofílico, y su asociación con tuberculosis.