Alpha-1 antitrypsin deficiency and Pi*S and Pi*Z SERPINA1 variants are associated with asthma exacerbations.

INTRODUCTION AND OBJECTIVES: Asthma is a chronic inflammatory disease of the airways. Asthma patients may experience potentially life-threatening episodic flare-ups, known as exacerbations, which may significantly contribute to the asthma burden. The Pi*S and Pi*Z variants of the SERPINA1 gene, which usually involve alpha-1 antitrypsin (AAT) deficiency, had previously been associated with asthma. The link between AAT deficiency and asthma might be represented by the elastase/antielastase imbalance. However, their role in asthma exacerbations remains unknown. Our objective was to assess whether SERPINA1 genetic variants and reduced AAT protein levels are associated with asthma exacerbations. MATERIALS AND METHODS: In the discovery analysis, SERPINA1 Pi*S and Pi*Z variants and serum AAT levels were analyzed in 369 subjects from La Palma (Canary Islands, Spain). As replication, genomic data from two studies focused on 525 Spaniards and publicly available data from UK Biobank, FinnGen, and GWAS Catalog (Open Targets Genetics) were analyzed. The associations between SERPINA1 Pi*S and Pi*Z variants and AAT deficiency with asthma exacerbations were analyzed with logistic regression models, including age, sex, and genotype principal components as covariates. RESULTS: In the discovery, a significant association with asthma exacerbations was found for both Pi*S (odds ratio [OR]=2.38, 95% confidence interval [CI]= 1.40-4.04, p-value=0.001) and Pi*Z (OR=3.49, 95%CI=1.55-7.85, p-value=0.003)Likewise, AAT deficiency was associated with a higher risk for asthma exacerbations (OR=5.18, 95%CI=1.58-16.92, p-value=0.007) as well as AAT protein levels (OR= 0.72, 95%CI=0.57-0.91, p-value=0.005). The Pi*Z association with exacerbations was replicated in samples from Spaniards with two generations of Canary Islander origin (OR=3.79, p-value=0.028), and a significant association with asthma hospitalizations was found in the Finnish population (OR=1.12, p-value=0.007). CONCLUSIONS: AAT deficiency could be a potential therapeutic target for asthma exacerbations in specific populations.

Allergic rhinitis and dental caries: A systematic review.

OBJECTIVE: Dental caries is one of the most common chronic diseases affecting millions of people globally. Some studies revealed the presence of bidirectional relationship between allergic rhinitis (AR) and oral diseases, with each disease having a potential impact on the other. In this study we aimed to systematically review the literature and analyze the available evidence regarding whether AR contributes to the development of dental caries. METHODS: Three authors, members of the YO-IFOS rhinology study group, independently analyzed the data sources (Pubmed, the Cochrane Library, EMBASE, SciELO) for papers assessing the relationship between rhinitis and caries, in adult and pediatric patients. RESULTS: Eight studies met the inclusion criteria (87612 participants). Six studies were performed in children. A total of three studies found an association between AR and dental caries. Only two studies had adjusted the measure of effect for potentially confounding variables. Regarding the quality of the selected studies according to the NICE classification, the most observed methodological limitations detected were: (1) the cross-sectional design of the included studies which could have introduced a simultaneity bias, and (2) not clearly reporting the inclusion and exclusion criteria. CONCLUSION: This systematic review can neither confirm nor deny the presence of an association between AR and caries. Despite the evidence is very scarce to conclude a relationship between AR and caries, the option for examining patients with repetitive caries by an otolaryngologist and those with AR by odontologist should be considered, as these examinations do not possess any risk for the patient.

Allergic rhinitis and dental caries: A systematic review

Objective: Dental caries is one of the most common chronic diseases affecting millions of people globally. Some studies revealed the presence of bidirectional relationship between allergic rhinitis (AR) and oral diseases, with each disease having a potential impact on the other. In this study we aimed to systematically review the literature and analyze the available evidence regarding whether AR contributes to the development of dental caries. Methods: Three authors, members of the YO-IFOS rhinology study group, independently analyzed the data sources (Pubmed, the Cochrane Library, EMBASE, SciELO) for papers assessing the relationship between rhinitis and caries, in adult and pediatric patients. Results: Eight studies met the inclusion criteria (87612 participants). Six studies were performed in children. A total of three studies found an association between AR and dental caries. Only two studies had adjusted the measure of effect for potentially confounding variables. Regarding the quality of the selected studies according to the NICE classification, the most observed methodological limitations detected were: (1) the cross-sectional design of the included studies which could have introduced a simultaneity bias, and (2) not clearly reporting the inclusion and exclusion criteria. Conclusion: This systematic review can neither confirm nor deny the presence of an association between AR and caries. Despite the evidence is very scarce to conclude a relationship between AR and caries, the option for examining patients with repetitive caries by an otolaryngologist and those with AR by odontologist should be considered, as these examinations do not possess any risk for the patient (AU)

Analysis of Differentially Expressed MicroRNAs in Serum and Lung Tissues from Individuals with Severe Asthma Treated with Oral Glucocorticoids.

Nowadays, microRNAs (miRNAs) are increasingly used as biomarkers due to their potential contribution to the diagnosis and targeted treatment of a range of diseases. The aim of the study was to analyze the miRNA expression profiles in serum and lung tissue from patients with severe asthma treated with oral corticosteroids (OCS) and those without OCS treatment. For this purpose, serum and lung tissue miRNAs of OCS and non-OCS asthmatic individuals were evaluated by miRNAs-Seq, and subsequently miRNA validation was performed using RT-qPCR. Additionally, pathway enrichment analysis of deregulated miRNAs was conducted. We observed altered expression by the next-generation sequencing (NGS) of 11 miRNAs in serum, of which five (hsa-miR-148b-3p, hsa-miR-221-5p, hsa-miR-618, hsa-miR-941, and hsa-miR-769-5p) were validated by RT-qPCR, and three miRNAs in lung tissue (hsa-miR-144-3p, hsa-miR-144-5p, and hsa-miR-451a). The best multivariate logistic regression model to differentiate individuals with severe asthma, treated and untreated with OCS, was to combine the serum miRNAs hsa-miR-221-5p and hsa-miR-769-5p. Expression of hsa-miR-148b-3p and hsa-miR-221-5p correlated with FEV1/FVC (%) and these altered miRNAs act in key signaling pathways for asthma disease and the regulated expression of some genes (FOXO3, PTEN, and MAPK3) involved in these pathways. In conclusion, there are miRNA profiles differentially expressed in OCS-treated individuals with asthma and could be used as biomarkers of OCS treatment.

Correction: Alfaro-Arnedo et al. IGF1R as a Potential Pharmacological Target in Allergic Asthma. Biomedicines 2021, 9, 912.

In the original article [...].

The Recumbent Position Affects Nasal Resistance: A Systematic Review and Meta-Analysis.

OBJECTIVE: Nasal diseases are among the main motives for the early discontinuation of continuous positive airway pressure therapy and for long-term therapeutic compliance with mandibular advancement device. Although our clinical experience leads us to the belief that recumbency impacts nasal airflow in some patient populations, there is no consensus regarding the magnitude of this effect and the specific group of patients who are the most affected by this condition. In this study, we conducted a meta-analysis to assess the effect of the recumbent position on nasal resistance and nasal airflow. REVIEW METHODS: PubMed (Medline), Cochrane Library, EMBASE, Scopus, and SciELO databases were checked for relevant studies by two members of the YO-IFOS study group. The two authors extracted the data. The main outcome was expressed as the difference between nasal resistance and nasal airflow before and after recumbency. RESULTS: Nine studies with a total population of 291 individuals were included in the meta-analysis for nasal resistance after recumbency. We found a statistically significant difference in nasal airway resistance of -0.18 Pa sec/cm3 as compared to before and after recumbency through rhinomanometry (RMM) analysis. A subgroup analysis revealed a variation of -0.20 Pa sec/cm3 for patients with snoring or sleep apnea and - 0.10 Pa sec/cm3 for healthy individuals. Regarding nasal airflow measured with RMM, three studies (n = 32) in asymptomatic controls revealed a statistically significant difference of 47.33 ml/sec. CONCLUSIONS: Recumbency increases nasal resistance and diminishes nasal airflow. This finding is of utmost importance in snorers and sleep apnea patients. Laryngoscope, 132:6-16, 2022.

IGF1R as a Potential Pharmacological Target in Allergic Asthma.

BACKGROUND: Asthma is a chronic lung disease characterized by reversible airflow obstruction, airway hyperresponsiveness (AHR), mucus overproduction and inflammation. Although Insulin-like growth factor 1 receptor (IGF1R) was found to be involved in asthma, its pharmacological inhibition has not previously been investigated in this pathology. We aimed to determine if therapeutic targeting of IGF1R ameliorates allergic airway inflammation in a murine model of asthma. METHODS: C57BL/6J mice were challenged by house dust mite (HDM) extract or PBS for four weeks and therapeutically treated with the IGF1R tyrosine kinase inhibitor (TKI) NVP-ADW742 (NVP) once allergic phenotype was established. RESULTS: Lungs of HDM-challenged mice exhibited a significant increase in phospho-IGF1R levels, incremented AHR, airway remodeling, eosinophilia and allergic inflammation, as well as altered pulmonary surfactant expression, all of being these parameters counteracted by NVP treatment. HDM-challenged lungs also displayed augmented expression of the IGF1R signaling mediator p-ERK1/2, which was greatly reduced upon treatment with NVP. CONCLUSIONS: Our results demonstrate that IGF1R could be considered a potential pharmacological target in murine HDM-induced asthma and a candidate biomarker in allergic asthma.

Impacto del síndrome de apnea-hipopnea del sueño en la neuropatía diabética. Revisión sistemática / Impact of sleep apnoea-hypopnoea syndrome on diabetic neuropathy. A systematic review

Introducción: La diabetes mellitus y el síndrome de apnea-hipopnea del sueño parecen estar relacionados, pero no está bien definido si en los pacientes con ambas enfermedades existe un mayor riesgo de neuropatía periférica. Para ello, realizamos una revisión sistemática.MétodosBúsqueda bibliográfica en 3 bases de datos electrónicas usando una estrategia predefinida y la metodología PRISMA. Solamente se incluyeron estudios originales (cualquier tipo de diseño) y publicados a partir del año 2000 en inglés, francés, portugués o español. Se estableció una escala de calidad de los estudios.ResultadosSe seleccionaron 12 artículos, de los que 6 estudiaban pacientes diabéticos tipo 2. La prevalencia global de síndrome de apnea-hipopnea del sueño fue del 43,7% (1.559/3.564 pacientes). La neuropatía diabética fue más frecuente en los pacientes con síndrome de apnea-hipopnea del sueño en 9 estudios, aunque solo en 4 de manera significativa (60 vs. 27%, p<0,001; 64,5 vs. 36%, p=0,03; 37 vs. 23,4%, p<0,02; 66,6 vs. 0%, p=0,007). En un estudio, la neuropatía diabética fue más frecuente en los pacientes sin síndrome de apnea-hipopnea del sueño (aunque sin significación estadística) y en 2 no se hizo la comparación entre pacientes con/sin síndrome de apnea-hipopnea del sueño.ConclusionesLos resultados observados indican una relación entre diabetes mellitus y síndrome de apnea-hipopnea del sueño en la aparición de neuropatía diabética.

Introduction: Diabetes mellitus and sleep apnoea-hypopnoea syndrome appear to be related, but it is not well defined whether there is an increased risk of peripheral neuropathy in patients with both diseases. For this reason, we conducted a systematic review.MethodsBibliographic search in 3 electronic databases using a predefined strategy and the PRISMA methodology. Only original studies (any type of design) published from 2000 onwards in English, French, Portuguese or Spanish were included. A study quality scale was established.ResultsTwelve articles were selected, of which six studied type 2 diabetic patients. The overall prevalence of sleep apnoea-hypopnoea syndrome was 43.7% (1,559/3,564 patients). Diabetic neuropathy was more frequent in patients with sleep apnoea-hypopnoea syndrome in nine studies, although significantly only in four (60% vs 27%, P<.001; 64.5% vs 36%, P=.03; 37% vs 23.4%, P<.02; 66.6% vs 0%, P=.007). In one study, diabetic neuropathy was more frequent in patients without sleep apnoea-hypopnoea syndrome (although not statistically significant) and in 2 no comparison was made between patients with/without sleep apnoea/hypopnoea syndrome.ConclusionsThe observed results suggest a relationship between diabetes mellitus and sleep apnoea-hypopnoea syndrome in the occurrence of diabetic neuropathy. (AU)

Clinical and inflammatory characteristics of patients with asthma in the Spanish MEGA project cohort.

INTRODUCTION: The MEGA (MEchanism underlying the Genesis and evolution of Asthma) project is a multicenter cohort study carried out in eight Spanish hospitals, gathering clinical, physiological, and molecular data from patients with asthma and multimorbidities in order to gain insight into the different physiopathological mechanisms involved in this disorder. MATERIAL AND METHODS: We report the baseline clinical and physiological characteristics and biomarker measures of adult participants in the project with the aim of better understanding the natural history and underlying mechanisms of asthma as well as the associated multimorbidities across different levels of severity. We carried out a detailed clinical examination, pulmonary function testing, measurement of fractional exhaled nitric oxide (FeNO), blood counts, induced sputum, skin prick tests, chest computed tomography scan, asthma questionnaires, and multimorbidity assessment in 512 asthmatic patients. RESULTS: When compared to patients with milder disease, severe asthmatic patients showed greater presence of symptoms, more exacerbations, lower asthma control, increased airflow obstruction, and higher frequency of chronic rhinosinusitis with nasal polyps, severe rhinitis, anxiety and depression, gastroesophageal reflux, and bronchiectasis. CONCLUSION: The MEGA project succeeded in recruiting a high number of asthma patients, especially those with severe disease, who showed lower control and higher frequency of multimorbidities.

Impact of sleep apnoea-hypopnoea syndrome on diabetic neuropathy. A systematic review. / Impacto del síndrome de apnea-hipopnea del sueño en la neuropatía diabética. Revisión sistemática.

INTRODUCTION: Diabetes mellitus and sleep apnoea-hypopnoea syndrome appear to be related, but it is not well defined whether there is an increased risk of peripheral neuropathy in patients with both diseases. For this reason, we conducted a systematic review. METHODS: Bibliographic search in 3 electronic databases using a predefined strategy and the PRISMA methodology. Only original studies (any type of design) published from 2000 onwards in English, French, Portuguese or Spanish were included. A study quality scale was established. RESULTS: Twelve articles were selected, of which six studied type 2 diabetic patients. The overall prevalence of sleep apnoea-hypopnoea syndrome was 43.7% (1,559/3,564 patients). Diabetic neuropathy was more frequent in patients with sleep apnoea-hypopnoea syndrome in nine studies, although significantly only in four (60% vs 27%, P<.001; 64.5% vs 36%, P=.03; 37% vs 23.4%, P<.02; 66.6% vs 0%, P=.007). In one study, diabetic neuropathy was more frequent in patients without sleep apnoea-hypopnoea syndrome (although not statistically significant) and in 2 no comparison was made between patients with/without sleep apnoea/hypopnoea syndrome. CONCLUSIONS: The observed results suggest a relationship between diabetes mellitus and sleep apnoea-hypopnoea syndrome in the occurrence of diabetic neuropathy.

Identification of Pleural Response Patterns: A Cluster Analysis / Identificación de patrones de respuesta pleural: un análisis de conglomerados

BACKGROUND: Pleural effusion occurs as a response of the pleura to aggressions. The pleura reacts differently according to the type of injury. However, pleural reactions have not yet been characterized. The objective of this study was to identify homogeneous clusters of patients based on the analytical characteristics of their pleural fluid and identify pleural response patterns. METHODS: A prospective study was conducted of consecutive patients seen in our unit for pleural effusion. Principal component and cluster analyses were carried out to identify pleural response patterns based on a combination of pleural fluid biomarkers. RESULTS: A total of 1613 patients were grouped into six clusters, namely: cluster 1 (10.5% of the cohort, primarily composed of patients with malignant pleural effusions); cluster 2 (17.4%, pleural effusions with inflammatory biomarkers); cluster 3 (16.1%, primarily composed of patients with infectious pleural effusions); cluster 4 (2.5%, a subcluster of cluster 3, superinfectious effusions); cluster 5 (23.4%, paucicellular pleural effusions); and cluster 6 (30.1%, miscellaneous). Significant differences were observed across clusters in terms of the analytical characteristics of PF (p < 0.001 for all), age (p < 0.001), and gender (p = 0.016). A direct relationship was found between the type of cluster and the etiology of pleural effusion. CONCLUSION: Pleural response is heterogeneous. The pleura may respond differently to the same etiology or similarly to different etiologies, which hinders diagnosis of pleural effusion

INTRODUCCIÓN: El derrame pleural ocurre como una respuesta de la pleura a las agresiones. La pleura reacciona de manera diferente según el tipo de lesión. Sin embargo, las reacciones pleurales aún no se han clasificado. El objetivo de este estudio fue identificar grupos homogéneos de pacientes basados en las características analíticas de su líquido pleural e identificar patrones de respuesta pleural. MÉTODOS: Se realizó un estudio prospectivo de pacientes consecutivos ingresados en nuestra unidad por presentar derrame pleural. Se llevaron a cabo análisis de componentes principales y análisis de conglomerados para identificar los patrones de respuesta pleural basados en las combinaciones de biomarcadores del líquido pleural. RESULTADOS: Un total de 1.613 pacientes se agruparon en 6 grupos: conglomerado 1 (10,5% de la cohorte, compuesto principalmente por pacientes con derrames pleurales malignos); conglomerado 2 (17,4%, derrames pleurales con biomarcadores inflamatorios); conglomerado 3 (16,1%, compuesto principalmente por pacientes con derrames pleurales infecciosos); conglomerado 4 (2,5%, un subgrupo del conglomerado 3, derrames superinfecciosos); conglomerado 5 (23,4%, derrames pleurales paucicelulares), y el conglomerado 6 (30,1%, miscelánea). Se observaron diferencias significativas entre los grupos en las características analíticas del líquido pleural (p < 0,001 para todos), la edad (p < 0,001) y el género (p = 0,016). Se encontró una relación directa entre el tipo de conglomerado y la etiología del derrame pleural. CONCLUSIONES: La respuesta pleural es heterogénea. La pleura puede responder de manera diferente a una misma etiología o de manera similar en diferentes etiologías, lo que dificulta el diagnóstico de derrame pleural

Identification of Pleural Response Patterns: A Cluster Analysis.

BACKGROUND: Pleural effusion occurs as a response of the pleura to aggressions. The pleura reacts differently according to the type of injury. However, pleural reactions have not yet been characterized. The objective of this study was to identify homogeneous clusters of patients based on the analytical characteristics of their pleural fluid and identify pleural response patterns. METHODS: A prospective study was conducted of consecutive patients seen in our unit for pleural effusion. Principal component and cluster analyses were carried out to identify pleural response patterns based on a combination of pleural fluid biomarkers. RESULTS: A total of 1613 patients were grouped into six clusters, namely: cluster 1 (10.5% of the cohort, primarily composed of patients with malignant pleural effusions); cluster 2 (17.4%, pleural effusions with inflammatory biomarkers); cluster 3 (16.1%, primarily composed of patients with infectious pleural effusions); cluster 4 (2.5%, a subcluster of cluster 3, superinfectious effusions); cluster 5 (23.4%, paucicellular pleural effusions); and cluster 6 (30.1%, miscellaneous). Significant differences were observed across clusters in terms of the analytical characteristics of PF (p<0.001 for all), age (p<0.001), and gender (p=0.016). A direct relationship was found between the type of cluster and the etiology of pleural effusion. CONCLUSION: Pleural response is heterogeneous. The pleura may respond differently to the same etiology or similarly to different etiologies, which hinders diagnosis of pleural effusion.

Evolución tras la retirada de la oxigenoterapia domiciliaria. Perfil del paciente en el que hay que reintroducirla / Progress After the Withdrawal of Home Oxygen Therapy. The Profile of Patients Requiring Reintroduction

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La combinación de la determinación de parámetros bioquímicos del líquido pleural mejora la predicción diagnóstica de la infección pleural complicada/empiema / The Combined Use of Pleural Fluid Parameters Improves Diagnostic Accuracy in Complicated Pleural Infection/Empyema

Introducción: Predecir cuándo un derrame pleural infeccioso puede evolucionar hacia una infección complicada/empiema es difícil de establecer. Nuestro propósito es analizar si un modelo predictivo construido con parámetros bioquímicos del líquido pleural puede ayudar a identificar estos derrames. Métodos: Se estudió de forma prospectiva a todos los pacientes diagnosticados de derrame pleural infeccioso y se clasificaron en no complicados y complicados/empiemas. Se realizó un análisis de regresión logística para estimar la probabilidad de infección pleural complicada/empiema. Con base en parámetros bioquímicos del líquido pleural, se construyó un modelo predictivo y se determinaron su discriminación (áreas bajo la curva ROC), calibración y precisión diagnóstica. Resultados: Se incluyó a 177 pacientes (74 infecciones pleurales no complicadas y 103 complicadas/empiemas). El área bajo la curva del modelo construido (pH, lactato deshidrogenasa e interleucina 6) fue 0,9783, significativamente mejor que cualquiera de las variables bioquímicas utilizadas de forma individual (0,921, 0,949 y 0,837, respectivamente; p < 0,001 usando todos los parámetros). La tasa de clasificación correcta fue del 96% de los derrames (170/177; 72/74 [97,3%] de los no complicados y 98/103 [95,1%] de los complicados/empiemas). Conclusión: El modelo predictivo analizado tiene una buena rentabilidad para el diagnóstico de las infecciones pleurales complicadas/empiemas, superior a la de cualquiera de las variables individuales que lo componen

Introduction: Identifying infectious pleural effusions (IPE) that will progress to complicated infection or empyema is challenging. The purpose of this study was to determine whether a model based on multiple biochemical parameters in pleural fluid can predict which IPEs will produce empyema. Methods: A prospective study was performed of all cases of IPEs treated in our unit. IPEs were classified as uncomplicated or complicated (empyema). Logistic regression was used to estimate the risk for complicated pleural infection (empyema). A predictive model was developed using biochemical parameters in pleural fluid. Discriminatory power (areas under the ROC curve), calibration, and diagnostic accuracy of the model were assessed. Results: A total of 177 patients were included in the study (74 with uncomplicated infectious pleural effusion, and 103 with complicated pleural effusion/empyema). The area under the curve (AUC) for the model (pH, lactate dehydrogenase and interleukin 6) was 0.9783, which is significantly superior to the AUC of the individual biochemical parameters alone (0.921, 0.949, and 0.837, respectively; P <.001 using all parameters). The rate of correct classification of infectious pleural effusions was 96% [170/177: 72/74 (97.3%) for uncomplicated and 98/103 (95.1%) for complicated effusion (empyema)]. Conclusion: The multiple-marker model showed better diagnostic performance for predicting complicated infectious pleural effusion (empyema) compared to individual parameters alone