MicroRNA-26a in respiratory diseases: mechanisms and therapeutic potential.

MicroRNAs (miRNAs) are short, non-coding single-stranded RNA molecules approximately 22 nucleotides in length, intricately involved in post-transcriptional gene expression regulation. Over recent years, researchers have focused keenly on miRNAs, delving into their mechanisms in various diseases such as cancers. Among these, miR-26a emerges as a pivotal player in respiratory ailments such as pneumonia, idiopathic pulmonary fibrosis, lung cancer, asthma, and chronic obstructive pulmonary disease. Studies have underscored the significance of miR-26a in the pathogenesis and progression of respiratory diseases, positioning it as a promising therapeutic target. Nevertheless, several challenges persist in devising medical strategies for clinical trials involving miR-26a. In this review, we summarize the regulatory role and significance of miR-26a in respiratory diseases, and we analyze and elucidate the challenges related to miR-26a druggability, encompassing issues such as the efficiency of miR-26a, delivery, RNA modification, off-target effects, and the envisioned therapeutic potential of miR-26a in clinical settings.

Pulmonology for the rhinologist.

PURPOSE OF REVIEW: The upper and lower airways are inter-related despite serving different functions and can no longer be considered separately. Rhinologists are becoming increasingly aware of the role the lower airway plays in optimizing outcomes for their patients. This review highlights recent developments in pulmonology that impact rhinologic conditions. RECENT FINDINGS: The unified airway concept now supports the multidisciplinary management of respiratory and rhinologic pathologies. Biomarkers, biologics and the concept of treatable traits have permitted the development of personalized and precise treatment of the entire respiratory tract. The concept of corticosteroid stewardship, the introduction of steroid sparing agents for the treatment of respiratory diseases and the development of biomarkers, now forces us to be more considerate and precise with oral corticosteroid (OCS) prescribing and to consider reduction regimens. Finally, current research on climate change and vaping will allow us to better educate and prepare our patients to improve adherence and avoid exacerbations to maintain optimal global respiratory health. SUMMARY: The inter-relatedness of the upper and lower airway has encouraged a multidisciplinary focus in respiratory medicine. More research is required to improve the precision respiratory medicine model, particularly in the realm of biomarkers and endotyping. These developments must also consider the impact of climate change, pollution and toxins for us to provide optimum care for our patients.

Treatable traits models of care.

Treatable traits is a personalized approach to the management of respiratory disease. The approach involves a multidimensional assessment to understand the traits present in individual patients. Traits are phenotypic and endotypic characteristics that can be identified, are clinically relevant and can be successfully treated by therapy to improve clinical outcomes. Identification of traits is followed by individualized and targeted treatment to those traits. First proposed for the management of asthma and chronic obstructive pulmonary disease (COPD) the approach is recommended in many other areas of respiratory and now immunology medicine. Models of care for treatable traits have been proposed in different diseases and health care setting. In asthma and COPD traits are identified in three domains including pulmonary, extrapulmonary and behavioural/lifestyle/risk-factors. In bronchiectasis and interstitial lung disease, a fourth domain of aetiological traits has been proposed. As the core of treatable traits is personalized and individualized medicine; there are several key aspects to treatable traits models of care that should be considered in the delivery of care. These include person centredness, consideration of patients' values, needs and preferences, health literacy and engagement. We review the models of care that have been proposed and provide guidance on the engagement of patients in this approach to care.

Abordaje paliativo en enfermedades respiratorias avanzadas / Palliative Approach in Advanced Respiratory Diseases

Las enfermedades respiratorias crónicas avanzadas son prevalentes y producen deterioro de la calidad de vida, en particular la enfermedad pulmonar obstructiva crónica (EPOC), las enfermedades pulmonares intersticiales difusas (EPID) y las enfermedades neuromusculares progresivas con compromiso diafragmático (ENM). Quienes las padecen presentan síntomas persistentes que no son siempre adecuada-mente controlados por los tratamientos recomendados por las guías clínicas de mane-jo. El tratamiento paliativo de los síntomas persistentes es un punto relevante y suelen presentarse barreras para su implementación.Este artículo ofrece una revisión narrativa sobre una perspectiva latinoamericana acerca del rol de los cuidados paliativos en enfermedades respiratorias avanzadas.

Advanced chronic respiratory diseases are prevalent and cause deterioration in qual-ity of life, particularly chronic obstructive pulmonary disease (COPD), diffuse intersti-tial lung diseases (ILD) and progressive neuromuscular diseases with diaphragmatic involvement (NMD). Those who suffer from them usually present persistent symptoms that are not always adequately controlled by the treatments recommended by the clinical management guidelines. Palliative treatment of persistent symptoms is a relevant point, but the pal-liative approach usually presents barriers to its implementation.This article offers a narrative review over Latin American perspective on the role of pal-liative care in advanced respiratory diseases.

Perceptions of the effectiveness of non-pharmacological management of respiratory disorders among CRD patients.

Chronic respiratory diseases (CRDs) are among the leading cause of mortality worldwide. While pharmacological approaches are commonly used to manage symptoms, non-pharmacological management of CRDs is considered crucial in preventing disease progression and improving patient self-efficacy. To describe the perceived effectiveness of non-pharmacological management of CRDs among CRD patients and determine whether the CRD patients perceptions of the effectiveness of non-pharmacological management are associated with their demographic characteristics. An analytic cross-sectional study design was utilized. The non-pharmacological management practices of CRD patients and their perception of the effectiveness of these therapeutic measures were assessed using a researcher-developed questionnaire. Data collection took place in primary healthcare centers in Al Ahsa, Saudi Arabia from October 2021 to March 2022. The proportion of CRD patients who perceived that non-pharmacological interventions were effective was computed. Binary logistic regression was performed to determine the association between the demographic characteristics of the respondents and their perception of the effectiveness of non-pharmacological management. Among the 390 respondents, 42% perceived that non-pharmacological measures were effective. Half of the respondents believed that smoking cessation, influenza vaccination, improving physical activity, and nutrition support helped alleviate CRD symptoms, while less than half of the respondents considered pulmonary rehabilitation, educational programs, and oxygen therapy effective measures to control symptoms. Women were found to be 3.24 times more likely to perceive non-pharmacological interventions as effective (P < .0000) compared to men. Those with university-level education were 66.6% less likely to consider non-pharmacological interventions to be effective (P < .0000) than those who completed preuniversity-level education. Age and marital status did not significantly influence perceptions of effectiveness. Differences in the perceptions of the effectiveness of various non-pharmacological measures to alleviate CRD symptoms existed among the CRD patients of Al Ahsa. The perception of effectiveness was significantly associated with the patient's gender and educational attainment.

Consultas por enfermedades respiratorias agudas en la población pediátrica y su relación con el material particulado atmosférico en Bahía Blanca: un estudio ecológico / Consultations for acute respiratory diseases in the pediatric population and their relationship with atmospheric particulate matter in Bahía Blanca: an ecological study

Introducción. El material particulado (PM) es uno de los contaminantes del aire que mayor implicación tienen en la aparición o exacerbación de cuadros respiratorios en niños. Objetivo. Describir las características de las consultas por enfermedades respiratorias agudas en menores de 15 años, los niveles de PM en el aire, y analizar la asociación existente entre ellos en un sector de Bahía Blanca entre abril de 2019 y marzo de 2020. Población y métodos. Estudio ecológico de series temporales y grupos múltiples. Análisis descriptivo de consultas totales, por área, diagnóstico, y del PM. Modelo de correlación y regresión lineal generalizado para determinar la relación entre las variables. Se utilizó el programa SPSS®. Resultados. Se recopilaron 4787 consultas. Un 38,6 % (1846) correspondieron a rinitis y un 21,1 % (1011) a broncoespasmo. El PM de 10 nm (PM10) superó su valor límite el 31 % (115) de los días de estudio y el de 2,5 nm (PM2,5) un 3 % (8). Un aumento del 10 % del PM2,5 demostró incrementos de 1,3 % en las consultas totales; el incremento llegó al 2,1 % en el área más cercana al sector industrial (p <0,05). En esta última, el aumento del 10 % de los valores de PM10 se asoció al aumento del 1,8 % de las consultas (p <0,05). Conclusión. Se demostró asociación positiva entre las consultas por enfermedad respiratoria aguda y los niveles de PM del aire, sobre todo con el PM2,5 y en el área más cercana al sector industrial.

Introduction. Particulate matter (PM) is one of the air pollutants most involved in the onset or exacerbation of respiratory conditions in children. Objective. To describe the characteristics of consultations for acute respiratory diseases in children younger than 15 years and the levels of PM in the air and to analyze their association in a sector of Bahía Blanca between April 2019 and March 2020. Population and methods. Ecological, time-series study with multiple groups. Descriptive analysis of total number of consultations, by area, diagnosis, and PM. Generalized linear correlation and regression model to determine the relationship among variables. The SPSS® software was used. Results. Data from 4787 consultations were collected. Of these, 38.6% (1846) were related to rhinitis and 21.1% (1011), to bronchospasm. PM of 10 nm (PM10) exceeded its limit value on 31% (115) of the study days, and PM of 2.5 nm (PM2.5), on 3% (8). A 10% increase in PM2.5 showed increases of 1.3% in total consultations; the increase reached 2.1% in the area closest to the industrial sector (p < 0.05). In the latter, a 10% increase in PM10 was associated with an increase of 1.8% in consultations (p < 0.05). Conclusion. A positive association was evidenced between consultations for acute respiratory diseases and PM levels in the air, especially with PM2.5 and in the area closest to the industrial sector.

Uso prolongado de cánula nasal de alto flujo en niños con problemas respiratorios / Prolonged use of high flow nasal cannula in children with respiratory problems

La cánula nasal de alto flujo (CNAF) es una modalidad ventilatoria no invasiva segura y efectiva, usada ampliamente en patología respiratoria aguda en adultos y niños. Objetivo: presentar casos clínicos pediátricos que utilizaron CNAF por tiempo prolongado por problemas respiratorios crónicos. Descripción de casos clínicos, revisión de fichas clínicas de 5 pacientes que utilizaron CNAF por más de 1 mes, entre los años 2017-2020 en el Complejo Asistencial Dr. Sótero del Río. Aprobado por Comité de Ética. Resultados: 5 pacientes varones de mediana 61 (44 a 212) días de edad al inicio del uso de CNAF. Diagnóstico de base: displasia broncopulmonar (2/5), síndrome de Treacher Collins (1/5), síndrome de cimitarra con hipoplasia pulmonar derecha (1/5) y traqueobroncomalacia severa (1/5). Todos requirieron previamente uso de ventilación invasiva o no invasiva con mediana de 59 (4 a 78) días. A todos se les realizó broncoscopia, saturometría contínua o poligrafía para diagnóstico y titulación de CNAF y oxígeno. Todos mejoraron clínicamente, la SpO2 y el número de apneas. Dos pacientes se enviaron a domicilio con uso de Airvo2 nocturno. La mediana de uso de CNAF fue 165 (34 a 445) días. Conclusiones: el uso prolongado de CNAF es útil en pacientes pediátricos seleccionados, bien tolerado y factible de utilizar en domicilio.

The high-flow nasal cannula (HFNC) is a safe and effective non-invasive ventilation support widely used in acute respiratory pathology in adults and children. Objective: To present pediatric clinical cases that used HFNC for an extended period due to chronic respiratory disease. Description of clinical cases, review of medical records of 5 patients who used HFNC for more than 1 month, between the years 2017-2020 at Complejo Asistencial Dr. Sótero del Río. Approved by the Ethics Committee. Results: 5 male patients with a median age of 61 (44 to 212) days at the start of HFNC use. Underlying diagnoses: bronchopulmonary dysplasia (2/5), Treacher Collins syndrome (1/5), Scimitar syndrome with right pulmonary hypoplasia (1/5), and severe tracheobronchomalacia (1/5). All of them previously required invasive or non-invasive ventilation for a median of 59 (4 to 78) days. All patients underwent bronchoscopy, continuous pulse oximetry or polygraphy for diagnosis and titration of HFNC and oxygen. All showed clinical improvement, including SpO2 levels and the number of apneas. Two patients were discharged with nocturnal use of Airvo 2 at home. The median duration of HFNC use was 165 (34 to 445) days. Conclusions: Prolonged use of HFNC is useful in selected pediatric patients, well tolerated, and feasible for home use.

Atividade física para usuários de serviços de saúde com doenças respiratórias / Physical activity for health service users with respiratory diseases

Contexto: A respiração é regulada por um complexo processo fisiológico que pode ser afetado em algumas patologias. No Brasil, a mortalidade por doenças respiratórias em relação ao total de mortes foi de 6%, no ano de 2016. Dados do período de 1995 a 2005 indicam que as doenças do aparelho respiratório estiveram entre as principais causas de internação do Sistema Único de Saúde (SUS) em todas as regiões brasileiras. A atividade física (AF) pode beneficiar a saúde de indivíduos com diagnóstico de problemas respiratórios, já que a prática regular permite a manutenção dos volumes e das capacidades respiratórias, diminuindo a restrição do movimento pela rigidez da caixa torácica e da coluna vertebral, além de manter a capacidade funcional e promover o bem-estar geral. Pergunta de pesquisa: A prática de atividade física é efetiva para a melhoria da capacidade respiratória e do desempenho das atividades de vida diária de usuários de serviços de saúde com diagnóstico de patologias respiratórias? Método: As buscas foram realizadas em quatro bases de literatura científica para identificar revisões sistemáticas (RS) sobre os efeitos da prática de AF na saúde de pessoas com doenças respiratórias. A qualidade metodológica das RS foi avaliada com a ferramenta AMSTAR 2. Resultados: De 1.045 registros recuperados nas bases, 21 revisões sistemáticas foram selecionadas para esta revisão rápida. Com relação à qualidade metodológica, três RS foram classificadas como de confiança alta, uma de confiança moderada, cinco de confiança baixa e doze de confiança criticamente baixa. Os dados extraídos das RS são apresentados conforme a condição da doença respiratória avaliada. Efeito de AF em pessoas com doença pulmonar obstrutiva crônica (DPOC): Onze RS analisaram AF em pessoas com DPOC ou obstrução crônica das vias aéreas. Oito indicaram que a maioria dos desfechos avaliados não apresentaram diferenças significativas ou foram incertos entre os grupos com AF combinando exercícios aeróbicos e anaeróbicos e o comparador. Três RS analisando apenas exercícios aeróbicos apontaram maioria de efeitos positivos dessa modalidade de AF em alguns desfechos de saúde dessas pessoas. Efeito de AF em pessoas com hipertensão pulmonar: Três RS utilizando exercícios combinados indicaram efeitos benéficos. Uma RS apresentou resultados incertos em relação à qualidade de vida. Efeito de AF em pessoas com fibrose pulmonar: Duas RS combinaram exercícios aeróbicos e anaeróbicos indicaram efeito positivo ou incerto para qualidade de vida. Houve efeitos positivos nos desfechos de distância de caminhada (DTC6), capacidade de exercício e dispneia, e efeitos incertos no pico de volume de oxigênio (pico de VO2) e no volume expiratório forçado no primeiro segundo e nenhuma diferença na participação em AF. Efeito de AF em pessoas com bronquiectasia: Uma RS apontou efeitos positivos de exercícios combinados para DTC6, qualidade de vida, distância incremental da caminhada, exacerbação de bronquiectasia, dispneia e fadiga. Indicou que não houve diferença de efeito entre os grupos para tosse. Efeito de AF em pessoas com câncer de pulmão de células não pequenas: Três RS apontaram que os efeitos foram em sua maioria positivos para pico de VO2 e DTC6. Houve efeitos inconclusivos para a melhora na qualidade de vida. Efeito de AF em pessoas com sarcoidose pulmonar: Uma RS indicou efeitos positivos para fadiga, força muscular e DTC6 de programas de tratamentos de reabilitação para pessoas com sarcoidose pulmonar. Segurança de AF para pessoas com doenças respiratórias: Cinco RS apresentaram resultados de eventos adversos. De modo geral, elas indicaram que as intervenções de AF foram seguras para pessoas com patologias respiratórias. Considerações finais: A atividade física mostrou relação com a melhoria da capacidade respiratória e física de pessoas com doenças respiratórias. Deve-se considerar, no entanto, as limitações metodológicas da maioria das RS incluídas, a heterogeneidade de intervenções e comparadores, além da escassez de estudos para algumas das condições de saúde.

Context: Breathing is regulated by a complex physiological process that can be affected in some pathologies. In Brazil, mortality from respiratory diseases in relation to total deaths was 6% in 2016. Data from 1995 to 2005 indicate that respiratory diseases were among the main causes of hospitalization in the Unified Health System (SUS) in all Brazilian regions. Physical activity (PA) can benefit the health of individuals diagnosed with respiratory problems, since regular practice allows for the maintenance of respiratory volumes and capacities, reducing movement restriction due to the rigidity of the rib cage and spine, in addition to maintain functional capacity and promote general well-being. Research question: Is the practice of physical activity effective for improving respiratory capacity and the performance of activities of daily living of users of health services diagnosed with respiratory pathologies? Method: Searches were carried out in four scientific literature databases to identify systematic reviews (SR) on the effects of PA practice on the health of people with respiratory diseases. The methodological quality of the SRs was evaluated using the AMSTAR 2 tool. Results: Of 1045 records retrieved from the databases, 21 systematic reviews were selected for this rapid review. Regarding methodological quality, three RS were classified as high confidence, one as moderate confidence, five as low confidence and twelve as critically low confidence. The data extracted from the RS are presented according to the condition of the respiratory disease evaluated. Effect of PA in people with chronic obstructive pulmonary disease (COPD): Eleven RS analyzed PA in people with COPD or chronic airway obstruction. Eight indicated that most of the outcomes evaluated did not show significant differences or were uncertain between the groups with PA combining aerobic and anaerobic exercises and the comparator. Three SRs analyzing only aerobic exercises showed the majority of positive effects of this PA modality on some health outcomes of these people. Effect of PA in people with pulmonary hypertension: Three RS using combined exercises indicated beneficial effects. One SR presented uncertain results in relation to quality of life. Effect of PA in people with pulmonary fibrosis: Two RS combined aerobic and anaerobic exercise indicated a positive or uncertain effect for quality of life. There were positive effects on outcomes of walking distance (6MWD), exercise capacity and dyspnea, and uncertain effects on peak oxygen volume (peak VO2) and forced expiratory volume in one second and no difference in PA participation. Effect of PA in people with bronchiectasis: An RS showed positive effects of combined exercise for 6MWD, quality of life, incremental walking distance, exacerbation of bronchiectasis, dyspnea and fatigue. It indicated that there was no difference in effect between the cough groups. Effect of AF in people with non-small cell lung cancer: Three RS showed that the effects were mostly positive for peak VO2 and 6MWD. There were inconclusive effects for improvement in quality of life. Effect of AF in people with pulmonary sarcoidosis: An RS indicated positive effects for fatigue, muscle strength and 6MWD of rehabilitation treatment programs for people with pulmonary sarcoidosis. Safety of PA for people with respiratory diseases: Five RS showed adverse event results. Overall, they indicated that PA interventions were safe for people with respiratory conditions. Final considerations: Physical activity showed a relationship with the improvement of respiratory and physical capacity of people with respiratory diseases. However, one should consider the methodological limitations of most of the SRs included, the heterogeneity of interventions and comparators, in addition to the scarcity of studies for some of the health conditions.

Therapeutic role of mesenchymal stem cell-derived exosomes in respiratory disease.

Exosomes are extracellular vesicles found in various tissues, blood circulation, and tissue fluids, secreted into the extracellular environment by fusing a multivesicular body with a plasma membrane. Various cell types release these vesicles to contribute to many cellular functions, including intercellular communication, cell proliferation, differentiation, angiogenesis, response to stress, and immune system signaling. These natural nanoparticles have therapeutic effects in various diseases and exhibit a behavior similar to the cell from which they originated. In the meantime, exosomes derived from mesenchymal stem cells have attracted the attention of many researchers and physicians due to their unique ability to modulate the immune system, repair tissue and reduce inflammation. Numerous clinical and preclinical studies have examined the effect of MSC-derived exosomes in various diseases, and their results have been published in prestigious journals. This review article discusses the biogenesis and sources of exosomes, MSC-derived exosomes, the use of these exosomes in regenerative medicine, and treatments based on exosomes derived from stem cells in respiratory diseases.

Prioritising primary care respiratory research needs: results from the 2020 International Primary Care Respiratory Group (IPCRG) global e-Delphi exercise.

Respiratory diseases remain a significant cause of global morbidity and mortality and primary care plays a central role in their prevention, diagnosis and management. An e-Delphi process was employed to identify and prioritise the current respiratory research needs of primary care health professionals worldwide. One hundred and twelve community-based physicians, nurses and other healthcare professionals from 27 high-, middle- and low-income countries suggested 608 initial research questions, reduced after evidence review by 27 academic experts to 176 questions covering diagnosis, management, monitoring, self-management and prognosis of asthma, COPD and other respiratory conditions (including infections, lung cancer, tobacco control, sleep apnoea). Forty-nine questions reached 80% consensus for importance. Cross-cutting themes identified were: a need for more effective training of primary care clinicians; evidence and guidelines specifically relevant to primary care, adaption for local and low-resource settings; empowerment of patients to improve self-management; and the role of the multidisciplinary healthcare team.

Outpatient Respiratory Management of Infants, Children, and Adolescents with Post-Prematurity Respiratory Disease: An Official American Thoracic Society Clinical Practice Guideline.

Background: Premature birth affects millions of neonates each year, placing them at risk for respiratory disease due to prematurity. Bronchopulmonary dysplasia is the most common chronic lung disease of infancy, but recent data suggest that even premature infants who do not meet the strict definition of bronchopulmonary dysplasia can develop adverse pulmonary outcomes later in life. This post-prematurity respiratory disease (PPRD) manifests as chronic respiratory symptoms, including cough, recurrent wheezing, exercise limitation, and reduced pulmonary function. This document provides an evidence-based clinical practice guideline on the outpatient management of infants, children, and adolescents with PPRD. Methods: A multidisciplinary panel of experts posed questions regarding the outpatient management of PPRD. We conducted a systematic review of the relevant literature. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to rate the quality of evidence and the strength of the clinical recommendations. Results: The panel members considered the strength of each recommendation and evaluated the benefits and risks of applying the intervention. In formulating the recommendations, the panel considered patient and caregiver values, the cost of care, and feasibility. Recommendations were developed for or against three common medical therapies and four diagnostic evaluations in the context of the outpatient management of PPRD. Conclusions: The panel developed recommendations for the outpatient management of patients with PPRD on the basis of limited evidence and expert opinion. Important areas for future research were identified.

Results of the home mechanical ventilation national program among adults in Chile between 2008 and 2017.

BACKGROUND: Home mechanical ventilation (HMV) is a viable and effective strategy for patients with chronic respiratory failure (CRF). The Chilean Ministry of Health started a program for adults in 2008. METHODS: This study examined the following data from a prospective cohort of patients with CRF admitted to the national HMV program: characteristics, mode of admission, quality of life, time in the program and survival. RESULTS: A total of 1105 patients were included. The median age was 59 years (44-58). Women accounted for 58.1% of the sample. The average body mass index (BMI) was 34.9 (26-46) kg/m2. A total of 76.2% of patients started HMV in the stable chronic mode, while 23.8% initiated HMV in the acute mode. A total of 99 patients were transferred from the children's program. There were 1047 patients on non-invasive ventilation and 58 patients on invasive ventilation. The median baseline PaCO2 level was 58.2 (52-65) mmHg. The device usage time was 7.3 h/d (5.8-8.8), and the time in HMV was 21.6 (12.2-49.5) months. The diagnoses were COPD (35%), obesity hypoventilation syndrome (OHS; 23.9%), neuromuscular disease (NMD; 16.3%), non-cystic fibrosis bronchiectasis or tuberculosis (non-CF BC or TBC; 8.3%), scoliosis (5.9%) and amyotrophic lateral sclerosis (ALS; 5.24%). The baseline score on the Severe Respiratory Insufficiency questionnaire (SRI) was 47 (± 17.9) points and significantly improved over time. The lowest 1- and 3-year survival rates were observed in the ALS group, and the lowest 9-year survival rate was observed in the non-CF BC or TB and COPD groups. The best survival rates at 9 years were OHS, scoliosis and NMD. In 2017, there were 701 patients in the children's program and 722 in the adult´s program, with a prevalence of 10.4 per 100,000 inhabitants. CONCLUSION: The most common diagnoses were COPD and OHS. The best survival was observed in patients with OHS, scoliosis and NMD. The SRI score improved significantly in the follow-up of patients with HMV. The prevalence of HMV was 10.4 per 100,000 inhabitants. Trial registration This study was approved by and registered at the ethics committee of North Metropolitan Health Service of Santiago, Chile (N° 018/2021).

Chronic respiratory diseases other than asthma in children: the COVID-19 tsunami.

Coronavirus disease 2019 (COVID-19) affects all components of the respiratory system, including the neuromuscular breathing apparatus, conducting and respiratory airways, pulmonary vascular endothelium, and pulmonary blood flow. In contrast to other respiratory viruses, children have less severe symptoms when infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A minority of children experience a post-infectious inflammatory syndrome, the pathology and long-term outcomes of which are poorly understood. The reason for the lower burden of symptomatic disease in children is not yet clear, but several pathophysiological characteristics are postulated. The SARS-CoV-2 pandemic has brought distinct challenges to the care of children globally. Proper recommendations have been proposed for a range of non-asthmatic respiratory disorders in children, including primary ciliary dyskinesia and cystic fibrosis. These recommendations involve the continuation of the treatment during this period and ways to maintain stability. School closures, loss of follow-up visit attendance, and loss of other protective systems for children are the indirect outcomes of measures to mitigate the COVID-19 pandemic. Moreover, COVID-19 has reshaped the delivery of respiratory care in children, with non-urgent and elective procedures being postponed, and distancing imperatives have led to rapid scaling of telemedicine. The pandemic has seen an unprecedented reorientation in clinical trial research towards COVID-19 and a disruption in other trials worldwide, which will have long-lasting effects on medical science. In this narrative review, we sought to outline the most recent findings on the direct and indirect effects of SARS-CoV-2 pandemic on pediatric respiratory chronic diseases other than asthma, by critically revising the most recent literature on the subject.

Involvement of epithelia-derived exosomes in chronic respiratory diseases.

Exosomes are tiny membrane lipid bilayer vesicles (φ40-100 nm) formed by the fusion of multivesicular bodies with plasma membrane, which are released extracellular by exocytosis. As natural nanocarriers, exosomes contain a variety of signal substances of the mother cell: nucleic acids, proteins and lipids, etc., which always play a vital role in the transmission of signal molecules between different cells. Epithelial cells are the first-line defense system against various inhaled allergens causing chronic respiratory diseases (CRD), such as asthma and chronic obstructive pulmonary disease (COPD). It's noted that increasing literature shows the exosomes derived from epithelial cells are involved in the pathogenesis of CRD. Moreover, the correlations between exosome cargo and the disease phenotypes show a high potential of using exosomes as biomarkers of CRD. In this review, we mainly focus on the physiological functions of epithelial-derived exosomes and illustrate the involved mechanism of epithelial-derived exosomes in common CRD.

Cellular Therapy for the Treatment of Paediatric Respiratory Disease.

Respiratory disease is the leading cause of death in children under the age of 5 years old. Currently available treatments for paediatric respiratory diseases including bronchopulmonary dysplasia, asthma, cystic fibrosis and interstitial lung disease may ameliorate symptoms but do not offer a cure. Cellular therapy may offer a potential cure for these diseases, preventing disease progression into adulthood. Induced pluripotent stem cells, mesenchymal stromal cells and their secretome have shown great potential in preclinical models of lung disease, targeting the major pathological features of the disease. Current research and clinical trials are focused on the adult population. For cellular therapies to progress from preclinical studies to use in the clinic, optimal cell type dosage and delivery methods need to be established and confirmed. Direct delivery of these therapies to the lung as aerosols would allow for lower doses with a higher target efficiency whilst avoiding potential effect of systemic delivery. There is a clear need for research to progress into the clinic for the treatment of paediatric respiratory disease. Whilst research in the adult population forms a basis for the paediatric population, varying disease pathology and anatomical differences in paediatric patients means a paediatric-centric approach must be taken.

Physiological functions and therapeutic applications of neutral sphingomyelinase and acid sphingomyelinase.

Sphingomyelin (SM) can be converted into ceramide (Cer) by neutral sphingomyelinase (NSM) and acid sphingomyelinase (ASM). Cer is a second messenger of lipids and can regulate cell growth and apoptosis. Increasing evidence shows that NSM and ASM play key roles in many processes, such as apoptosis, immune function and inflammation. Therefore, NSM and ASM have broad prospects in clinical treatments, especially in cancer, cardiovascular diseases (such as atherosclerosis), nervous system diseases (such as Alzheimer's disease), respiratory diseases (such as chronic obstructive pulmonary disease) and the phenotype of dwarfisms in adolescents, playing a complex regulatory role. This review focuses on the physiological functions of NSM and ASM and summarizes their roles in certain diseases and their potential applications in therapy.

Optimization of PEGylated KL4 Peptide for siRNA Delivery with Improved Pulmonary Tolerance.

Pulmonary delivery of small interfering RNA (siRNA) is a promising therapeutic strategy for treating various respiratory diseases but an effective carrier for the delivery of siRNA into the cells of the lungs and a robust gene-silencing effect is still lacking. Previously, we reported that the KL4 peptide, a synthetic cationic peptide with a repeating KLLLL sequence, can mediate effective siRNA transfection in lung epithelial cells but its high hydrophobic leucine content, and hence poor water solubility, limits its application as a delivery vector. Here, we show that the covalent attachment of monodisperse poly(ethylene glycol) (PEG) improves the solubility of KL4 and the uptake of its complex with siRNA into lung epithelial cells, such that very robust silencing is produced. All PEGylated KL4 peptides, with PEG length varying between 6 and 24 monomers, could bind and form nanosized complexes with siRNA, but the interaction between siRNA and peptides became weaker as the PEG chain length increased. All PEGylated KL4 peptides exhibited satisfactory siRNA transfection efficiency on three human lung epithelial cell lines, including A549 cells, Calu-3 cells, and BEAS-2B cells. The PEG12KL4 peptide, which contains 12 monomers of PEG, was optimal for siRNA delivery and also demonstrated a low risk of inflammatory response and toxicity in vivo following pulmonary administration.

Respiratory Disorders in Ferrets.

Ferrets are susceptible to many disorders affecting the respiratory tract including both primary diseases and diseases of other body systems secondarily affecting the respiratory tract. Some primary respiratory diseases are shared with other mammal species including humans; potentially zoonotic diseases include important pathogens such as influenza and SARS-CoV-2. Other diseases include infections (bacterial, parasitic, and fungal) and neoplasia. A thorough workup is important to identify exact causes in order to formulate a treatment plan. Infectious diseases include bacterial, fungal, parasitic, and viral.