Impact of Air Pollution on Asthma: A Scoping Review.

Asthma is the most common chronic respiratory disease and a major public health problem. Although the causal relationship between air pollution and asthma remains controversial, a large number of studies have provided increasingly consistent evidence of the involvement of air pollutants in asthma onset and exacerbations. We conducted a keyword search-based literature review using PubMed, Scopus and Web of Science databases for studies with titles or abstracts containing predefined terms. This narrative review discusses the current evidence on the pathological effects of pollution throughout life and the mechanisms involved in the onset, development, and exacerbation of asthma, and presents current measures and interventions for pollution damage control. Further global efforts are still needed to improve air quality.

El asma es la enfermedad respiratoria crónica más común, y un importante problema de salud pública. Aunque la relación causal entre la contaminación del aire y el asma sigue siendo controvertida, una gran cantidad de estudios han proporcionado evidencia cada vez más consistente de la participación de los contaminantes del aire en el inicio y las exacerbaciones del asma. Realizamos una revisión de la literatura basada en búsqueda de palabras clave utilizando las bases de datos PubMed, Scopus y Web of Science para estudios con títulos o resúmenes que contienen términos predefinidos. Esta revisión narrativa analiza la evidencia actual sobre los efectos patológicos de la contaminación a lo largo de la vida y los mecanismos involucrados en el inicio, desarrollo y exacerbación del asma, y presenta las medidas e intervenciones actuales para el control de daños por contaminación. Todavía se necesitan más esfuerzos globales para mejorar la calidad del aire.

PTGDR2 Expression in Peripheral Blood as a Potential Biomarker in Adult Patients with Asthma.

BACKGROUND: Precision medicine is a promising strategy to identify biomarkers, stratify asthmatic patients according to different endotypes, and match them with the appropriate therapy. This proof-of-concept study aimed to investigate whether gene expression in peripheral blood could provide a valuable noninvasive approach for the molecular phenotyping of asthma. METHODS: We performed whole-transcriptome RNA sequencing on peripheral blood of 30 non-atopic non-asthmatic controls and 30 asthmatic patients. A quantitative PCR (qPCR) validation study of PTGDR2 that encodes for CRTH2 receptor, expressed in cells involved in T2 inflammation, was developed in a cohort of 361 independent subjects: 94 non-asthmatic non-atopic controls, 187 asthmatic patients [including 82 with chronic rhinosinusitis with nasal polyposis (CRSwNP) and 24 with aspirin-exacerbated respiratory disease (AERD)], 52 with allergic rhinitis, and 28 with CRSwNP without asthma. RESULTS: PTGDR2 was one of the most differentially overexpressed genes in asthmatic patients' peripheral blood (p-value 2.64 × 106). These results were confirmed by qPCR in the validation study, where PTGDR2 transcripts were significantly upregulated in asthmatic patients (p < 0.001). This upregulation was mainly detected in some subgroups such as allergic asthma, asthma with CRSwNP, AERD, eosinophilic asthma, and severe persistent asthma. PTGDR2 expression was detected in different blood cell types, and its correlation with eosinophil counts showed differences in some groups of asthmatic patients. CONCLUSIONS: We found that PTGDR2 expression levels could identify asthma patients, introduce a minimally invasive biomarker for adult asthma molecular phenotyping, and add additional information to blood eosinophils. Although further studies are required, analyzing PTGDR2 expression levels in peripheral blood of asthmatics might assist in selecting patients for treatment with specific antagonists.

Molecular Analysis of IL-5 Receptor Subunit Alpha as a Possible Pharmacogenetic Biomarker in Asthma.

Background: Asthma is a heterogeneous syndrome with a broad clinical spectrum and high drug response variability. The inflammatory response in asthma involves multiple effector cells and mediator molecules. Based on asthma immunopathogenesis, precision medicine can be a promising strategy for identifying biomarkers. Biologic therapies acting on the IL-5/IL-5 receptor axis have been developed. IL-5 promotes proliferation, differentiation and activation of eosinophils by binding to the IL-5 receptor, located on the surface of eosinophils and basophils. This study aimed to investigate the expression of IL5RA in patients with several types of asthma and its expression after treatment with benralizumab, a biologic directed against IL-5 receptor subunit alpha. Methods: Sixty peripheral blood samples, 30 from healthy controls and 30 from asthmatic patients, were selected for a transcriptomic RNAseq study. Differential expression analysis was performed by statistical assessment of fold changes and P-values. A validation study of IL5RA expression was developed using qPCR in 100 controls and 187 asthmatic patients. The effect of benralizumab on IL5RA expression was evaluated in five patients by comparing expression levels between pretreatment and after 3 months of treatment. The IL5RA mRNA levels were normalized to GAPDH and TBP expression values for each sample. Calculations were made by the comparative ΔΔCt method. All procedures followed the MIQE guidelines. Results: IL5RA was one of the most differentially overexpressed coding transcripts in the peripheral blood of asthmatic patients (P = 8.63E-08 and fold change of 2.22). In the qPCR validation study, IL5RA expression levels were significantly higher in asthmatic patients than in controls (P < 0.001). Significant expression differences were present in different asthmatic types. In the biological drug study, patients treated with benralizumab showed a significant decrease in IL5RA expression and blood eosinophil counts. A notable improvement in ACT and lung function was also observed in these patients. Conclusions: These results indicate that IL5RA is overexpressed in patients with different types of asthma. It could help identify which asthmatic patients will respond more efficiently to benralizumab, moving toward a more personalized asthma management. Although further studies are required, IL5RA could play a role as a biomarker and pharmacogenetic factor in asthma.

Clinical benefits of home-based pulmonary rehabilitation in patients with chronic obstructive pulmonary disease.

PURPOSE: To evaluate the benefits of home-based pulmonary rehabilitation (PR) in patients with severe and very severe chronic obstructive pulmonary disease (COPD). METHODS: Randomized clinical trial involving 58 patients. Pulmonary function, quality of life evaluated by the Saint George Respiratory Questionnaire, breathlessness evaluated by the London Chest Activity of Daily Living Scale, and exercise tolerance evaluated by 6-minute walk distance were assessed at baseline and at 12 weeks. The program consisted of 2 weekly visits by a physiotherapist in the first 2 weeks, followed by visits twice a month, as well as weekly telephone calls. Training included breathing and stretching exercises and strength exercises (upper and lower limbs), along with endurance training, including walking, stair climbing, cycling, and treadmill walking, depending on available patient resources. RESULTS: The treatment group (TG; n = 23) and control group (CG; n = 18) completed the study. Following the intervention, no statistically significant differences were found in pulmonary function in the TG and CG. The TG exhibited statistically significant differences in the activity domain (P = .008), impact domain (P < .001), and total scores of the Saint George Respiratory Questionnaire (P < .001). In addition, the TG demonstrated statistically significant differences in all domains of the London Chest Activity of Daily Living Scale and no differences were observed in the CG after 12 weeks. There was a statistically significant difference in the 6-Minute Walk Distance in the TG after rehabilitation (P = .008). CONCLUSIONS: This study offers evidence that home-based PR promotes benefits in the quality of life, breathlessness in activities of daily living, and exercise capacity in patients with severe and very severe COPD. Home-based PR must be considered as part of the treatment for patients who live far from hospitals even in severe COPD.

Un método alternativo para la predicción del riesgo de complicaciones postoperatorias en la resección pulmonar / An Alternative Method for Predicting the Risk of Postoperative Complications in Lung Resection

Objetivos: Los objetivos de este trabajo son rediseñar un modelo de regresión lineal para estimar el valor de VO2max (VO2 estimado) ya publicado y comparar la capacidad predictiva de los valores VO2 medido y VO2 estimado en la aparición de complicaciones cardiorrespiratorias en una serie de pacientes sometidos a resección pulmonar por cáncer de pulmón. Método: Estudio prospectivo y observacional en 83 pacientes. Variables analizadas: demográficas, comorbilidad, IMC, FEV1%, FVC%, DLCO%, distancia recorrida media diaria (km), VO2max medido en el test de ejercicio cardiopulmonar (CPET) y complicación postoperatoria. Estadística descriptiva y comparativa de variables usando Mann-Whitney test para categóricas y t de Student para continuas normales. Se diseña un modelo de regresión lineal donde VO2max, la variable dependiente, se estima desde la distancia recorrida, DLCO% y edad del paciente y su resultado es la VO2 estimada. Se compara la capacidad predictiva de los VO2max medido y estimado mediante t de Student, agrupando por ocurrencia o no de complicaciones cardiorrespiratorias. Resultados: Los 2 grupos son homogéneos en edad, distribución de sexos, IMC, FEV1%, DLCO%, comorbilidad, cirugía realizada y distancia media recorrida/día. VO2 medida y VO2 estimada tienen distribución normal (K-Smirnov p > 0,32). En la predicción de complicaciones, las medias del VO2 estimado a partir del modelo son significativamente diferentes entre los pacientes con/sin complicación (t de Student p = 0,037); frente a los valores de VO2 medido que no distinguen grupos (t de Student p = 0,42). Conclusiones: El VO2max estimado por el modelo es más predictivo en esta serie de casos que el VO2max medido en una CPET

Objectives: The aims of this study were to design a best fit linear regression model to estimate VO2max (estimated VO2) and to compare the ability of VO2 values (measured and estimated) predicting cardiorespiratory complications in a series of patients undergoing lung resection for lung cancer. Method: This was a prospective, observational study performed in 83 patients. Variables analyzed were: demographic characteristics, comorbidity, body mass index (BMI), FEV1%, FVC%, diffusion capacity (DLCO%), mean daily distance walked in kilometers, VO2max measured by cardio-pulmonary exercise test(CPET) and postoperative complications. Descriptive and comparative statistical analysis of the variables was performed using the Mann-Whitney test for categorical variables and the Student’s t-test for continuous variables. A new linear regression model was designed, where the dependent variable (measured VO2max) was estimated by the distance, DLCO% and age, resulting in the estimated VO2. The predictive power of the measured and estimated consumption was analyzed using the Student’s t-test, grouping by the occurrence or absence of cardiorespiratory complications. Results: Both groups were homogeneous for age, sex, BMI, FEV1%, DLCO%, comorbidity, type of resection performed and mean distance walked per day. Estimated VO2 and measured VO2 were normally distributed (K-Smirnov test, P > 0.32). VO2 means estimated by the model (age, DLCO% and mean distance walked per day) were significantly different between patients with and without complications (Student’s t test, P = 0.037) compared with measured VO2 values, which did not differentiate groups (Student's t test , P = 0.42). Conclusion: The VO2max estimated by the model is more predictive in this case series than the VO2max measured during a standard exercise test

An alternative method for predicting the risk of postoperative complications in lung resection.

OBJECTIVES: The aims of this study were to design a best fit linear regression model to estimate VO2max (estimated VO2) and to compare the ability of VO2 values (measured and estimated) predicting cardiorespiratory complications in a series of patients undergoing lung resection for lung cancer. METHOD: This was a prospective, observational study performed in 83 patients. Variables analyzed were: demographic characteristics, comorbidity, body mass index (BMI), FEV1%, FVC%, diffusion capacity (DLCO%), mean daily distance walked in kilometers, VO2max measured by cardio-pulmonary exercise test (CPET) and postoperative complications. Descriptive and comparative statistical analysis of the variables was performed using the Mann-Whitney test for categorical variables and the Student's t-test for continuous variables. A new linear regression model was designed, where the dependent variable (measured VO2max) was estimated by the distance, DLCO% and age, resulting in the estimated VO2. The predictive power of the measured and estimated consumption was analyzed using the Student's t-test, grouping by the occurrence or absence of cardiorespiratory complications. RESULTS: Both groups were homogeneous for age, sex, BMI, FEV1%, DLCO%, comorbidity, type of resection performed and mean distance walked per day. Estimated VO2 and measured VO2 were normally distributed (K-Smirnov test, P>.32). VO2 means estimated by the model (age, DLCO% and mean distance walked per day) were significantly different between patients with and without complications (Student's t test, P=.037) compared with measured VO2 values, which did not differentiate groups (Student's t test, P=.42). CONCLUSION: The VO2max estimated by the model is more predictive in this case series than the VO2max measured during a standard exercise test.

The health-related quality of life of patients with chronic obstructive pulmonary disease and asthma evaluated by the SGRQ.

AIMS: To compare the effects of asthma and chronic obstructive pulmonary disease (COPD) on the quality of life of patients evaluated using the Saint George Respiratory Questionnaire (SGRQ) through correlating the variables, domains and total score. METHODS: A cross-sectional study from October 2008 to March 2009 with 75 adult outpatients at the University Hospital of Salamanca, Spain. Patients provided their clinical and socio-demographical data after being informed of the study's aims and ethical aspects. The Spanish version of the SGRQ and the statistical packa ge Statistics SPSS version 17.0 were used for statistical analysis. RESULTS: 65.3% were male and 34.7% female with mean age 60.4 years. 68% had a diagnosis of asthma and 30.7% COPD. Statistically significant differences (p<0.05) between diagnosis and the 'activity' domain were found. None were found between gender, smoking, ex-smoking or hypertension and the domains. The income levels were inversely related (p=0.038) with the total score. Statistically significant differences between age and the 'activity' (p<0.01) and 'impact' (p<0.05) domains and the SGRQ total score were found (p<0.01). The forced expiratory volume in one second (FEV1%pred) only correlated with the 'activity' domain (p<0.01) and with the total score (p<0.01). CONCLUSIONS: No variable correlated with all domains and the total score of the instrument. Some presented no statistically significant difference.