Inflammasome-Related Genetic Polymorphisms as Severity Biomarkers of COVID-19.

The most critical forms of coronavirus disease 2019 (COVID-19) are associated with excessive activation of the inflammasome. Despite the COVID-19 impact on public health, we still do not fully understand the mechanisms by which the inflammatory response influences disease prognosis. Accordingly, we aimed to elucidate the role of polymorphisms in the key genes of the formation and signaling of the inflammasome as biomarkers of COVID-19 severity. For this purpose, a large and well-defined cohort of 377 COVID-19 patients with mild (n = 72), moderate (n = 84), severe (n = 100), and critical (n = 121) infections were included. A total of 24 polymorphisms located in inflammasome-related genes (NLRP3, NLRC4, NLRP1, CARD8, CASP1, IL1B, IL18, NFKB1, ATG16L1, and MIF) were genotyped in all of the patients and in the 192 healthy controls (HCs) (who were without COVID-19 at the time of and before the study) by RT-qPCR. Our results showed that patients with mild, moderate, severe, and critical COVID-19 presented similar allelic and genotypic distribution in all the variants studied. No statistically significant differences in the haplotypic distribution of NLRP3, NLRC4, NLRP1, CARD8, CASP1, IL1B, and ATG16L1 were observed between COVID-19 patients, who were stratified by disease severity. Each stratified group of patients presented a similar genetic distribution to the HCs. In conclusion, our results suggest that the inflammasome polymorphisms studied are not associated with the worsening of COVID-19.

Inercia clínica o terapéutica en neumología: una reflexión sobre su definición y actores principales / Clinical or therapeutic inertia in pneumology: critical reflection on its definition and main actors

La inercia clínica se define como los fallos del médico en el inicio o la intensificación del tratamiento cuando están indicados. Nuestro objetivo es reflexionar sobre este concepto aplicado en enfermedad pulmonar obstructiva crónica y asma, y el papel del profesional sanitario y del sistema de salud como actores implicados. Dejamos aparte la inercia del paciente para otro ámbito de estudio e intervención. Proponemos definir la inercia clínica para procesos durante el diagnóstico y el tratamiento cuando no se inicia o modifica (intensifica o disminuye) una terapia. También se identifican los factores que contribuyen a la inercia clínica o terapéutica y se plantean estrategias de mejora. (AU)

Clinical inertia is defined as the physician’s failure to initiate or intensify treatment when it is indicated. Our objective is to reflect on this concept applied to chronic obstructive pulmonary disease and asthma, and the role of health professional and health system as stakeholders. We leave patient inertia aside for another area of study and intervention. We propose to define clinical inertia for diagnosis and therapeutic processes when a treatment is not started or modified (intensifies or decreases). Factors that contribute to clinical and/or therapeutic inertia are also identified and improvement strategies are proposed. (AU)

Association of Kinesiophobia with Catastrophism and Sensitization-Associated Symptoms in COVID-19 Survivors with Post-COVID Pain.

Pain symptoms after the acute phase of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are present in almost 50% of COVID-19 survivors. The presence of kinesiophobia is a risk factor which may promote and perpetuate pain. This study aimed to investigate variables associated with the presence of kinesiophobia in a sample of previously hospitalized COVID-19 survivors exhibiting post-COVID pain. An observational study was conducted in three urban hospitals in Spain, including one hundred and forty-six COVID-19 survivors with post-COVID pain. Demographic (age, weight, height), clinical (intensity and duration of pain), psychological (anxiety level, depressive level, sleep quality), cognitive (catastrophizing), sensitization-associated symptoms, and health-related quality of life variables were collected in 146 survivors with post-COVID pain, as well as whether they exhibited kinesiophobia. Stepwise multiple linear regression models were conducted to identify variables significantly associated with kinesiophobia. Patients were assessed a mean of 18.8 (SD 1.8) months after hospital discharge. Kinesiophobia levels were positively associated with anxiety levels (r: 0.356, p < 0.001), depression levels (r: 0.306, p < 0.001), sleep quality (r: 0.288, p < 0.001), catastrophism (r: 0.578, p < 0.001), and sensitization-associated symptoms (r: 0.450, p < 0.001). The stepwise regression analysis revealed that 38.1% of kinesiophobia variance was explained by catastrophism (r2 adj: 0.329, B = 0.416, t = 8.377, p < 0.001) and sensitization-associated symptoms (r2 adj: 0.381, B = 0.130, t = 3.585, p < 0.001). Kinesiophobia levels were associated with catastrophism and sensitization-associated symptoms in previously hospitalized COVID-19 survivors with post-COVID pain. Identification of patients at a higher risk of developing a higher level of kinesiophobia, associated with post-COVID pain symptoms, could lead to better therapeutic strategies.

Relationship Between Clinical Control, Respiratory Symptoms and Quality of Life for Patients with COPD.

Background: The concept of clinical control has been proposed as an instrument for evaluating patients with COPD. However, the possible association between clinical control, reduced symptom severity and HRQoL has yet to be confirmed. Methods: This multicentre, prospective and observational study was carried out in 15 pulmonology clinics in Spain. The patients were followed up for six months, with a baseline visit (V0), followed by visits at three months (V1) and six months (V2). Clinical control was determined at V1, with the application of both clinical criteria and the COPD assessment test (CAT). All patients reported their symptoms by a validated symptom diary (E-RS) using a portable device, and their HRQoL was assessed using the EQ5D questionnaire. The relationship between clinical control and E-RS and HRQoL during follow-up was assessed with t-test. Results: A total of 126 patients were screened. After application of the inclusion/exclusion criteria, 93 were finally included (mean age 66 ± 8 years, 84.9% male), with a mean FEV1 predicted of 49.8% ± 16.5%. Of these patients, 44 (47.3%) achieved clinical control at V1, according to CAT criteria, and 50 (53.8%), according to clinical criteria. The E-RS scores differed between controlled and uncontrolled patients at all time points, both according to CAT (mean differences of -4.6, -5.6 and -6.2 units at V0, V1 and V2, respectively, p<0.005 for all comparisons) and to clinical criteria (mean differences of -3.3, -5-6 and -4.99 units, respectively, p<0.005 for all comparisons). The controlled patients also presented a significantly better HRQoL, measured by the EQ5D questionnaire (mean difference 0.13 and 0.10 at V2 by CAT or clinical criteria, respectively, p<0.05). Conclusion: Clinical control in patients with COPD, whether measured by CAT or by clinical criteria, is associated with a lower symptom load and a better HRQoL.

Traducción y validación del cuestionario multidimensional Disnea-12 / Translation and Validation of the Multidimensional Dyspnea-12 Questionnaire

Introducción: La disnea es un síntoma con un componente multidimensional, aunque las herramientas que se utilizan habitualmente para evaluarla no tienen en cuenta esta faceta. El cuestionario Disnea-12 valora la multidimensionalidad de la disnea, específicamente las dimensiones afectiva y sensorial. El objetivo de este estudio es validar el cuestionario Disnea-12 al español. Métodos: Se realizó una traducción del original en inglés al español y del español al inglés para verificar la equivalencia del texto. Posteriormente se verificó la comprensión del texto tras pasárselo a 10 pacientes. La fiabilidad y la validez del cuestionario se estudiaron en un grupo independiente de EPOC diagnosticados y clasificados por las guías GOLD de las consultas externas de neumología del Hospital Universitario Marqués de Valdecilla. Resultados: El grupo (n = 51) tenía una media de edad de 65 años y un FEV1 medio del 50%. Todos los pacientes entendieron las preguntas del cuestionario. El instrumento presentó consistencia interna de alfa = 0,937 y un coeficiente de correlación intraclase: 0,969; p<0,001. Se encontraron correlaciones estadísticamente significativas con las puntuaciones del HAD (HADansiedad r = 0,608 y HADdepresión r = 0,615), disnea de la mMRC (r = 0,592), T6MM (r = -0,445), FEV1 (r = -0,312), las 4 dimensiones de CRQ-SAS (disnea r = -0,626; fatiga r = -0,718; función emocional r = -0,663; control de enfermedad r = -0,740), el CAT (r = 0,669) y el índice de disnea basal (r = -0,615). Los grupos GOLD más sintomáticos (B y D) presentaron una puntuación 10,32 puntos mayor en el Disnea-12 (p < 0,001). Conclusión: El cuestionario Disnea-12 es un instrumento válido y fiable para evaluar la disnea de forma multidimensional (AU)

Introduction: Dyspnea is a multidimensional symptom, but this multidimensionality is not considered in most dyspnea questionnaires. The Dyspnea-12 takes a multidimensional approach to the assessment of dyspnea, specifically the sensory and the affective response. The objective of this study was to translate into Spanish and validate the Dyspnea-12 questionnaire. Methods: The original English version of the Dyspnea-12 questionnaire was translated into Spanish and backtranslated to analyze its equivalence. Comprehension of the text was verified by analyzing the responses of 10 patients. Reliability and validation of the questionnaire were studied in an independent group of COPD patients attending the pulmonology clinics of Hospital Universitario Marqués de Valdecilla, diagnosed and categorized according to GOLD guidelines. Results: The mean age of the group (n = 51) was 65 years and mean FEV1 was 50%. All patients understood all questions of the translated version of Dyspnea-12. Internal consistency of the questionnaire was alfa=0.937 and intraclass correlation coefficient was = .969; P < .001. Statistically significant correlations were found with HADS (anxiety r = .608 and depression r = .615), mMRC dyspnea (r = .592), 6MWT (r = -0.445), FEV1 (r = -0.312), all dimensions of CRQ-SAS (dyspnea r = -0.626; fatigue r = -0.718; emotional function r = -0.663; mastery r = -0.740), CAT (r = 0.669), and baseline dyspnea index (r = -0.615). Dyspnea-12 scores were 10.32 points higher in symptomatic GOLD groups (B and D) (P < .001). Conclusion: The Spanish version of Dyspnea-12 is a valid and reliable instrument to study the multidimensional nature of dyspnea (AU)

Translation and Validation of the Multidimensional Dyspnea-12 Questionnaire. / Traducción y validación del cuestionario multidimensional Disnea-12.

INTRODUCTION: Dyspnea is a multidimensional symptom, but this multidimensionality is not considered in most dyspnea questionnaires. The Dyspnea-12 takes a multidimensional approach to the assessment of dyspnea, specifically the sensory and the affective response. The objective of this study was to translate into Spanish and validate the Dyspnea-12 questionnaire. METHODS: The original English version of the Dyspnea-12 questionnaire was translated into Spanish and backtranslated to analyze its equivalence. Comprehension of the text was verified by analyzing the responses of 10 patients. Reliability and validation of the questionnaire were studied in an independent group of COPD patients attending the pulmonology clinics of Hospital Universitario Marqués de Valdecilla, diagnosed and categorized according to GOLD guidelines. RESULTS: The mean age of the group (n=51) was 65 years and mean FEV1 was 50%. All patients understood all questions of the translated version of Dyspnea-12. Internal consistency of the questionnaire was α=0.937 and intraclass correlation coefficient was=.969; P<.001. Statistically significant correlations were found with HADS (anxiety r=.608 and depression r=.615), mMRC dyspnea (r=.592), 6MWT (r=-0.445), FEV1 (r=-0.312), all dimensions of CRQ-SAS (dyspnea r=-0.626; fatigue r=-0.718; emotional function r=-0.663; mastery r=-0.740), CAT (r=0.669), and baseline dyspnea index (r=-0.615). Dyspnea-12 scores were 10.32 points higher in symptomatic GOLD groups (B and D) (P<.001). CONCLUSION: The Spanish version of Dyspnea-12 is a valid and reliable instrument to study the multidimensional nature of dyspnea.

Physical activity patterns and clusters in 1001 patients with COPD.

We described physical activity measures and hourly patterns in patients with chronic obstructive pulmonary disease (COPD) after stratification for generic and COPD-specific characteristics and, based on multiple physical activity measures, we identified clusters of patients. In total, 1001 patients with COPD (65% men; age, 67 years; forced expiratory volume in the first second [FEV1], 49% predicted) were studied cross-sectionally. Demographics, anthropometrics, lung function and clinical data were assessed. Daily physical activity measures and hourly patterns were analysed based on data from a multisensor armband. Principal component analysis (PCA) and cluster analysis were applied to physical activity measures to identify clusters. Age, body mass index (BMI), dyspnoea grade and ADO index (including age, dyspnoea and airflow obstruction) were associated with physical activity measures and hourly patterns. Five clusters were identified based on three PCA components, which accounted for 60% of variance of the data. Importantly, couch potatoes (i.e. the most inactive cluster) were characterised by higher BMI, lower FEV1, worse dyspnoea and higher ADO index compared to other clusters ( p < 0.05 for all). Daily physical activity measures and hourly patterns are heterogeneous in COPD. Clusters of patients were identified solely based on physical activity data. These findings may be useful to develop interventions aiming to promote physical activity in COPD.

Clinical features and outcomes of interstitial lung disease in anti-Jo-1 positive antisynthetase syndrome.

BACKGROUND: Interstitial lung disease (ILD) is a common extra-muscular manifestation of antisynthetase (AS) syndrome. ILD prevalence is higher with anti-Jo-1 antibody positivity. Data on long-term outcomes in these patients are lacking. METHODS: Over 15 years, we identified subjects with anti-Jo-1 positive AS syndrome and ILD. Demographics, pulmonary function testing (PFT), high-resolution computed tomography (HRCT), histopathology, and long-term survival were analyzed. RESULTS: We identified 103 subjects (mean age 49.2 years, female predominance [70%]). The predominant myopathy was polymyositis (64%) followed by dermatomyositis (24%). In approximately half of studied subjects, AS syndrome and ILD were diagnosed within 6 months of each other. The majority had restriction on PFTs (98%). Non-specific interstitial pneumonia (NSIP) was the most common HRCT pattern (52%), followed by NSIP overlapping with organizing pneumonia (OP) (22%). Thirty-nine subjects had biopsy data. Ten-year survival was 68%. Multivariable analysis adjusted for age at ILD diagnosis, gender, FVC and DLCO, revealed that male gender (HR = 2.60, p = 0.04) and DLCO at presentation (HR = 0.94, p = 0.05) significantly predicted mortality. CONCLUSIONS: We present a large cohort of anti-Jo-1 positive AS syndrome with ILD and note good overall survival.

Self-management and quality of life in chronic obstructive pulmonary disease (COPD): The mediating effects of positive affect.

OBJECTIVE: This study aimed to increase our understanding of general self-management (SM) abilities in COPD by determining if SM can predict disease specific quality of life (QoL), by investigating whether specific SM domains are significant in COPD and by exploring the mediating effect of the positive/negative affect in the association between SM and QoL. METHODS: Cross-sectional study based on 292 patients with COPD. Measures included demographics, lung function, gait speed, health care utilization, positive/negative affect, SM abilities, breathlessness and disease specific QoL. We performed, correlation, multiple regression models and mediation analysis (positive/negative affect being mediator between SM and QoL association). RESULTS: After controlling for breathlessness, living alone, marital status, hospitalization history, age and lung function, SM related to QoL (p<0.0001). Investment in behaviors (hobbies and social relationships) and self-efficacy are SM domains independently related to QoL in COPD. Positivity measured by the positive/negative affect ratio completely mediates the relationship of SM with QoL. CONCLUSION: SM is independently associated with disease specific QoL in COPD after adjustment significant covariates but positive/negative affect ratio completely mediates the relationship of SM with QoL. PRACTICE IMPLICATIONS: Measuring positive/negative affect and addressing investment behavior and self-efficacy are important in implementing COPD-SM programs.

Respiratory training in Spain.

Respiratory medicine is a varied specialty that encompasses a broad spectrum of diseases, specific diagnostic and treatment techniques, and both critical and chronic care patients. However, while in some countries is one of the most competitive specialties to get into, in Spain is one of the less popular options.

Emotional Intelligence: A Novel Outcome Associated with Wellbeing and Self-Management in Chronic Obstructive Pulmonary Disease.

RATIONALE: Individuals with chronic obstructive pulmonary disease (COPD) often struggle with diminished autonomy and quality of life. Emotional factors play a crucial role in the well-being of patients with COPD; they are independently associated with critical outcomes such as dyspnea, quality of life, and health care use. Emotional intelligence is the capacity to understand and manage personal thoughts and feelings, as well as to positively influence interpersonal communication and social well-being. Emotional intelligence is a trainable skill that is extensively used in corporate business to improve well-being and performance, and it may also be significant in the self-management of emotions in patients with chronic disease. Importantly, research supports the proposition that emotional intelligence may be developed and learned at any time or any age, and training programs have been associated with increased well-being and better emotional regulation in patients with chronic disease. However, to date, no research has been done to investigate its value in patients with COPD. OBJECTIVES: We aimed to investigate the association between emotional intelligence and two meaningful outcomes in COPD: quality of life and self-management abilities. METHODS: Participants with moderate to severe COPD completed a disease-specific quality of life tool (Chronic Respiratory Questionnaire), the Trait Emotional Intelligence Questionnaire, the Self-Management Abilities Scale, the modified Medical Research Council Dyspnea Scale, and pulmonary function tests, and also provided information about living conditions and self-reported health care use. MEASUREMENTS AND MAIN RESULTS: A total of 310 patients with COPD (mean age, 69 ± 9 yr; 40% female; mean FEV1%, 42.4 ± 15.8) participated in the study. Emotional intelligence was significantly and independently associated with self-management abilities (P < 0.0001) and all domains of quality of life assessed (dyspnea, fatigue, emotions, and mastery; P < 0.0001) after adjusting for age, degree of bronchial obstruction, breathlessness, and other significant confounders. CONCLUSIONS: Emotional intelligence may represent an important attribute in COPD, as it is associated with self-management abilities and all domains of quality of life, regardless of age or disease severity. Emotional intelligence can be learned and may complement existing rehabilitation efforts. Attention to it may address the current gap that exists in the treatment of emotional components of COPD responsible for decreased quality of life and increased health care use.

Forecasting COPD hospitalization in the clinic: optimizing the chronic respiratory questionnaire.

PURPOSE: Forecasting hospitalization in patients with COPD has gained significant interest in the field of COPD care. There is a need to find simple tools that can help clinicians to stratify the risk of hospitalization in these patients at the time of care. The perception of quality of life has been reported to be independently associated with hospitalizations, but questionnaires are impractical for daily clinical use. Individual questions from valid questionnaires can have robust predictive abilities, as has been suggested in previous reports, as a way to use patient-reported outcomes to forecast important events like hospitalizations in COPD. Our primary aim was to assess the predictive value of individual questions from the Chronic Respiratory Questionnaire Self-Assessment Survey (CRQ-SAS) on the risk of hospitalization and to develop a clinically relevant and simple algorithm that clinicians can use in routine practice to identify patients with an increased risk of hospitalization. PATIENTS AND METHODS: A total of 493 patients with COPD prospectively recruited from an outpatient pulmonary clinic completed the CRQ-SAS, demographic information, pulmonary function testing, and clinical outcomes. The cohort had a mean age of 70 years, was 54% male, with forced expiratory volume in 1 second percentage predicted 42.8±16.7, and modified Medical Research Council dyspnea scale score of 2±1.13. RESULTS: Our analysis validated the original CRQ-SAS domains. Importantly, recursive partitioning analysis identified three CRQ-SAS items regarding fear or panic of breathlessness, dyspnea with basic activities of daily living, and depressive symptoms that were highly predictive of hospitalization. We propose a robust (area under the curve =0.70) but short and easy algorithm for daily clinical care to forecast hospitalizations in patients with COPD. CONCLUSION: We identified three themes - fear of breathlessness, dyspnea with basic activities of daily living, and depressive symptoms - as important patient-reported outcomes to predict hospitalizations, and propose a short and easy algorithm to forecast hospitalizations in patients with COPD.