BRACETS: Bimodal repository of auscultation coupled with electrical impedance thoracic signals.

BACKGROUND AND OBJECTIVE: Respiratory diseases are among the most significant causes of morbidity and mortality worldwide, causing substantial strain on society and health systems. Over the last few decades, there has been increasing interest in the automatic analysis of respiratory sounds and electrical impedance tomography (EIT). Nevertheless, no publicly available databases with both respiratory sound and EIT data are available. METHODS: In this work, we have assembled the first open-access bimodal database focusing on the differential diagnosis of respiratory diseases (BRACETS: Bimodal Repository of Auscultation Coupled with Electrical Impedance Thoracic Signals). It includes simultaneous recordings of single and multi-channel respiratory sounds and EIT. Furthermore, we have proposed several machine learning-based baseline systems for automatically classifying respiratory diseases in six distinct evaluation tasks using respiratory sound and EIT (A1, A2, A3, B1, B2, B3). These tasks included classifying respiratory diseases at sample and subject levels. The performance of the classification models was evaluated using a 5-fold cross-validation scheme (with subject isolation between folds). RESULTS: The resulting database consists of 1097 respiratory sounds and 795 EIT recordings acquired from 78 adult subjects in two countries (Portugal and Greece). In the task of automatically classifying respiratory diseases, the baseline classification models have achieved the following average balanced accuracy: Task A1 - 77.9±13.1%; Task A2 - 51.6±9.7%; Task A3 - 38.6±13.1%; Task B1 - 90.0±22.4%; Task B2 - 61.4±11.8%; Task B3 - 50.8±10.6%. CONCLUSION: The creation of this database and its public release will aid the research community in developing automated methodologies to assess and monitor respiratory function, and it might serve as a benchmark in the field of digital medicine for managing respiratory diseases. Moreover, it could pave the way for creating multi-modal robust approaches for that same purpose.

Dry response and acclimated characteristics of people ascending the Tibetan Plateau.

Due to a long period of low humidity, exposure to the dry environment of the Tibetan Plateau can cause skin and respiratory diseases and threaten human health. To examine the characteristics of acclimatization response to humidity comfort in visitors to the Tibetan Plateau based on an examination of the targeted effect and mechanism of the dry environment. A scale corresponding to local dryness symptoms was proposed. Eight participants were selected to conduct a two-week plateau experiment and a one-week plain experiment under six humidity ratios, respectively, to explore the characteristics of dry response and acclimatization of people entering the plateau. The results indicate that duration has a significant effect on human dry response. On the sixth day after entering Tibet, the degree of dryness reached the maximum, and acclimatization to the plateau environment began on the 12th day. The sensitivity of different body parts to the change in a dry environment was different. When the indoor humidity ratio increased from 9.04 g/kg to 21.77 g/kg, the symptoms of dry skin were most significantly relieved by 0.5 units of scale. After de-acclimatization, the degree of dryness in the eyes was most significantly alleviated, reducing by nearly one scale. The analysis of human symptom indicators in a dry environment shows that subjective and physiological indices are influential and essential in measuring human comfort in a dry environment. This study extends our understanding of dry environment responses and cognition of human comfort and lays a solid foundation for humid built environments in the plateau.

A systematic review and meta-analysis of respiratory dysfunction in Parkinson's disease.

INTRODUCTION: Respiratory dysfunction in Parkinson's disease (PD) is common and associated with increased hospital admission and mortality rates. Central and peripheral mechanisms have been proposed in PD. To date no systematic review identifies the extent and type of respiratory impairments in PD compared with healthy controls. METHODS: PubMed, EMBASE, CINAHL, Web of Science, Pedro, MEDLINE, Cochrane Library and OpenGrey were searched from inception to December 2021 to identify case-control studies reporting respiratory measures in PD and matched controls. RESULTS: Thirty-nine studies met inclusion criteria, the majority with low risk of bias across Risk of Bias Assessment tool for Non-randomized Studies (RoBANS) domains. Data permitted pooled analysis for 26 distinct respiratory measures. High-to-moderate certainty evidence of impairment in PD was identified for vital capacity (standardised mean difference [SMD] 0.75; 95% CI 0.45-1.05; p < 0.00001; I2  = 10%), total chest wall volume (SMD 0.38; 95% CI 0.09-0.68; p = 0.01; I2  = 0%), maximum inspiratory pressure (SMD 0.91; 95% CI 0.64-1.19; p < 0.00001; I2  = 43%) and sniff nasal inspiratory pressure (SMD 0.58; 95% CI 0.30-0.87; p < 0.00001; I2  = 0%). Sensitivity analysis provided high-moderate certainty evidence of impairment for forced vital capacity and forced expiratory volume in 1 s during medication ON phases and increased respiratory rate during OFF phases. Lower certainty evidence identified impairments in PD for maximum expiratory pressure, tidal volume, maximum voluntary ventilation and peak cough flow. CONCLUSIONS: Strong evidence supports a restrictive pattern with inspiratory muscle weakness in PD compared with healthy controls. Limited data for central impairment were identified with inconclusive findings.

Función pulmonar: ¿Debemos cambiar la forma de calcular la respuesta broncodilatadora en la espirometría en niños? / Should we change the way we calculate the bronchodilator response in children's spirometry?

Tradicionalmente se ha definido la respuesta broncodilatadora (RB) positiva como una mejoría ≥ de 12 % del VEF1. En el año 2022 se publica una Guía sobre la interpretación de función la pulmonar de la Sociedad Americana de Tórax y la Sociedad Europea de Enfermedades Respiratorias, donde se propone que la RB debe expresarse como el cambio porcentual del VEF1 en relación con el VEF1 predicho y que un cambio ≥ 10 % indica una RB positiva. Las sociedades científicas en Chile están evaluando estas recomendaciones para decidir su adecuada implementación en pediatría.

Traditionally, a positive bronchodilator (BR) response has been defined as a ≥ 12% improvement in FEV1. In the year 2022, a Guide on the interpretation of pulmonary function of the American Thoracic Society and the European Society of Respiratory Diseases was published, where it was proposed that BR should be expressed as the percent change in FEV1 relative to predicted FEV1 and that a change ≥ 10% indicates a positive BR. Scientific societies in Chile are evaluating these recommendations to decide their proper implementation in pediatrics.

Effect of Early vs Standard Approach to Tracheostomy on Functional Outcome at 6 Months Among Patients With Severe Stroke Receiving Mechanical Ventilation: The SETPOINT2 Randomized Clinical Trial.

Importance: Many patients with severe stroke have impaired airway protective reflexes, resulting in prolonged invasive mechanical ventilation. Objective: To test whether early vs standard tracheostomy improved functional outcome among patients with stroke receiving mechanical ventilation. Design, Setting, and Participants: In this randomized clinical trial, 382 patients with severe acute ischemic or hemorrhagic stroke receiving invasive ventilation were randomly assigned (1:1) to early tracheostomy (≤5 days of intubation) or ongoing ventilator weaning with standard tracheostomy if needed from day 10. Patients were randomized between July 28, 2015, and January 24, 2020, at 26 US and German neurocritical care centers. The final date of follow-up was August 9, 2020. Interventions: Patients were assigned to an early tracheostomy strategy (n = 188) or to a standard tracheostomy (control group) strategy (n = 194). Main Outcomes and Measures: The primary outcome was functional outcome at 6 months, based on the modified Rankin Scale score (range, 0 [best] to 6 [worst]) dichotomized to a score of 0 (no disability) to 4 (moderately severe disability) vs 5 (severe disability) or 6 (death). Results: Among 382 patients randomized (median age, 59 years; 49.8% women), 366 (95.8%) completed the trial with available follow-up data on the primary outcome (177 patients [94.1%] in the early group; 189 patients [97.4%] in the standard group). A tracheostomy (predominantly percutaneously) was performed in 95.2% of the early tracheostomy group in a median of 4 days after intubation (IQR, 3-4 days) and in 67% of the control group in a median of 11 days after intubation (IQR, 10-12 days). The proportion without severe disability (modified Rankin Scale score, 0-4) at 6 months was not significantly different in the early tracheostomy vs the control group (43.5% vs 47.1%; difference, -3.6% [95% CI, -14.3% to 7.2%]; adjusted odds ratio, 0.93 [95% CI, 0.60-1.42]; P = .73). Of the serious adverse events, 5.0% (6 of 121 reported events) in the early tracheostomy group vs 3.4% (4 of 118 reported events) were related to tracheostomy. Conclusions and Relevance: Among patients with severe stroke receiving mechanical ventilation, a strategy of early tracheostomy, compared with a standard approach to tracheostomy, did not significantly improve the rate of survival without severe disability at 6 months. However, the wide confidence intervals around the effect estimate may include a clinically important difference, so a clinically relevant benefit or harm from a strategy of early tracheostomy cannot be excluded. Trial Registration: ClinicalTrials.gov Identifier: NCT02377167.

Función pulmonar oscilometría de impulso en pediatría: procedimiento y aplicación clínica / Pulmonary function impulse oscillometry in pediatrics: procedure and clinical application

La Oscilometría de Impulso (IOS) es una técnica no invasiva que evalúa las propiedades mecánicas de todo el sistema respiratorio durante la respiración tranquila. Mide la impedancia total del sistema respiratorio, evaluando la resistencia total de la vía aérea, la resistencia de la vía aérea alta y las propiedades elásticas del pulmón. Detecta el compromiso de la vía aérea periférica en forma muy precoz, antes que la espirometría, y es útil en niños pequeños porque no requiere maniobras de espiración forzada. Permite evaluar la respuesta broncodilatadora y broncoconstrictora a través de pruebas de provocación bronquial para el diagnóstico de hiperreactividad bronquial. La IOS tiene un rol en la evaluación temprana y seguimiento de la función pulmonar en niños con enfermedades respiratorias crónicas, principalmente asma bronquial, displasia broncopulmonar y fibrosis quística. Este artículo revisa los aspectos fisiológicos, técnicos y aplicación clínica de la IOS, considerando las últimas recomendaciones para la estandarización del examen y las limitaciones que dificultan su interpretación .

Impulse Oscillometry (IOS) is a non-invasive technique that assesses the mechanical properties of the entire respiratory system during quiet breathing. It measures the total impedance of the respiratory system by evaluating total airway resistance, upper airway resistance, and elastic properties of the lung. It detects peripheral airway compromise very early, before spirometry, and is useful in young children because it does not require forced expiration maneuvers. It allows evaluating the bronchodilator and bronchoconstrictor response through bronchial provocation tests for the diagnosis of bronchial hyperreactivity. The IOS has a role in the early evaluation and monitoring of lung function in children with chronic respiratory diseases, mainly bronchial asthma, bronchopulmonary dysplasia and cystic fibrosis. This article reviews the physiological, technical, and clinical application aspects, considering the latest recommendations for the standardization of the test and the limitations that hinder its interpretation.

Human microphysiological models of airway and alveolar epithelia.

Human organ-on-a-chip models are powerful tools for preclinical research that can be used to study the mechanisms of disease and evaluate new targets for therapeutic intervention. Lung-on-a-chip models have been one of the most well-characterized designs in this field and can be altered to evaluate various types of respiratory disease and to assess treatment candidates prior to clinical testing. These systems are capable of overcoming the flaws of conventional two-dimensional (2-D) cell culture and in vivo animal testing due to their ability to accurately recapitulate the in vivo microenvironment of human tissue with tunable material properties, microfluidic integration, delivery of precise mechanical and biochemical cues, and designs with organ-specific architecture. In this review, we first describe an overview of currently available lung-on-a-chip designs. We then present how recent innovations in human stem cell biology, tissue engineering, and microfabrication can be used to create more predictive human lung-on-a-chip models for studying respiratory disease. Finally, we discuss the current challenges and future directions of lung-on-a-chip designs for in vitro disease modeling with a particular focus on immune and multiorgan interactions.

Exosomes in chronic respiratory diseases.

Exosomes are nano-sized vesicles released by almost all cell types, with a central role as mediators of intercellular communication. In addition to physiological conditions, these extracellular vesicles seem to play a pivotal role in inflammatory processes. This assumption offers the opportunity to study exosomes as promising biomarkers and therapeutic tools for chronic respiratory disorders. Indeed, although it is well-known that at the basis of conditions like asthma, chronic obstructive pulmonary disease, alpha-1 antitrypsin deficiency and idiopathic pulmonary fibrosis there is a dysregulated inflammatory process, an unequivocal correlation between different phenotypes and their pathophysiological mechanisms has not been established yet. In this review, we report and discuss some of the most significant studies on exosomes from body fluids of subjects affected by airway diseases. Furthermore, the most widespread techniques for exosome isolation and characterization are described. Further studies are needed to answer the unresolved questions about the functional link between exosomes and chronic respiratory diseases.

Targeting the Angiopoietin/Tie Pathway: Prospects for Treatment of Retinal and Respiratory Disorders.

Anti-angiogenic approaches have significantly advanced the treatment of vascular-related pathologies. The ephemeral outcome and known side effects of the current vascular endothelial growth factor (VEGF)-based anti-angiogenic treatments have intensified research on other growth factors. The angiopoietin/Tie (Ang/Tie) family has an established role in vascular physiology and regulates angiogenesis, vascular permeability, and inflammatory responses. The Ang/Tie family consists of angiopoietins 1-4, their receptors, tie1 and 2 and the vascular endothelial-protein tyrosine phosphatase (VE-PTP). Modulation of Tie2 activation has provided a promising outcome in preclinical models and has led to clinical trials of Ang/Tie-targeting drug candidates for retinal disorders. Although less is known about the role of Ang/Tie in pulmonary disorders, several studies have revealed great potential of the Ang/Tie family members as drug targets for pulmonary vascular disorders as well. In this review, we summarize the functions of the Ang/Tie pathway in retinal and pulmonary vascular physiology and relevant disorders and highlight promising drug candidates targeting this pathway currently being or expected to be under clinical evaluation for retinal and pulmonary vascular disorders.

Aerodigestive Clinics as Emerging Pediatric Care Model: The First 100 Patients in Israel.

BACKGROUND: Aerodigestive clinics are run by interdisciplinary medical and surgical teams, and provide complex care coordination and combined endoscopies. OBJECTIVES: To describe the design and patient population of the first pediatric aerodigestive center in Israel. METHODS: A retrospective single-center cohort study was conducted describing patients followed in the aerodigestive clinic of Schneider Children's Medical Center of Israel, a tertiary pediatric hospital, between its inception in January 2017 and June 2020. RESULTS: During the study period, 100 patients were seen at the combined respiratory and digestive (NoAM) clinic, with a total of 271 visits. Median age at first assessment was 29.5 months (range 3-216). Fifty-six patients (56%) had esophageal atresia and tracheoesophageal fistula. Thirty-nine patients had an identified genetic disorder, 28 had a primary airway abnormality, 28 were oxygen dependent, and 21 were born premature. Fifty-two patients underwent triple endoscopy, consisting of flexible bronchoscopy, rigid bronchoscopy, and gastroscopy. In 33 patients, esophageal dilatation was necessary. Six patients underwent posterior tracheopexy at a median of 6 months of age (range 5 days to 8 years) all with ensuing symptom improvement. The total mean parental satisfaction score on a Likert-type scale of 1-5 (5 = highest satisfaction) was 4.5. CONCLUSIONS: A coordinated approach is required to provide effective care to the growing population of children with aerodigestive disorders. The cross fertilization between multiple disciplines offers a unique opportunity to develop high quality and innovative care. Outcome measures must be defined to objectively measure clinical benefit.

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.

Small airway function in Finnish COVID-19 survivors.

Follow-up studies of COVID-19 patients have found lung function impairment up to six months after initial infection, but small airway function has not previously been studied. Patients (n = 20) hospitalised for a severe SARS-CoV-2 infection underwent spirometry, impulse oscillometry, and multiple measurements of alveolar nitric oxide three to six months after acute infection. None of the patients had small airway obstruction, nor increased nitric oxide concentration in the alveolar level. None of the patients had a reduced FEV1/FVC or significant bronchodilator responses in IOS or spirometry. In conclusion, we found no evidence of inflammation or dysfunction in the small airways.

Modelling the links between farm characteristics, respiratory health and pig production traits.

Sustainable livestock production requires links between farm characteristics, animal performance and animal health to be recognised and understood. In the pig industry, respiratory disease is prevalent, and has negative health, welfare and economic consequences. We used national-level carcass inspection data from the Food Standards Agency to identify associations between pig respiratory disease, farm characteristics (housing type and number of source farms), and pig performance (mortality, average daily weight gain, back fat and carcass weight) from 49 all in/all out grow-to-finish farms. We took a confirmatory approach by pre-registering our hypotheses and used Bayesian multi-level modelling to quantify the uncertainty in our estimates. The study findings showed that acquiring growing pigs from multiple sources was associated with higher respiratory condition prevalence. Higher prevalence of respiratory conditions was linked with higher mortality, and lower average daily weight gain, back fat and pig carcass weight. Our results support previous literature using a range of data sources. In conclusion, we find that meat inspection data are more valuable at a finer resolution than has been previously indicated and could be a useful tool in monitoring batch-level pig health in the future.

Effects of pain on depression, sleep, exercise tolerance, and quality of life in patients with nontuberculous mycobacterial pulmonary disease.

ABSTRACT: The experience and causes of pain in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) have not been clarified.This study aimed to determine the prevalence and severity of bodily pain (BP) in patients with NTM-PD. We also investigated the clinical indicators that contribute to pain.We used a retrospective cross-sectional study design. The participants were 114 NTM-PD patients (109 women) with a mean age of 65 years. The prevalence and severity of pain were measured using 2 items from the 36-Item Short Form Survey version 2 (SF-36), and the BP score was calculated. Functional limitation due to dyspnea was quantified using the Modified Medical Research Council Dyspnea Scale (mMRC), depression was assessed using the Center for Epidemiological Studies Depression Scale (CES-D), sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI); health-related quality of life was assessed using the Leicester Cough Questionnaire (LCQ), and exercise tolerance was measured using the Incremental Shuttle Walk Test (ISWT).Pain was reported by 70.2% of the patients (n = 80), and of these, 35.7% (n = 25) reported moderate to very severe pain. NTM-PD patients with high levels of pain had significantly higher scores on the mMRC, CES-D, and PSQI scores, and significantly lower performance on the ISWT and LCQ. Multiple regression analysis identified ISWT, CES-D, and PSQI as independent factors that affected BP scores.Our findings suggest that pain significantly impacts daily life associated with reduced exercise tolerance, the presence of depressive symptoms, and poor sleep quality in patients with NTM-PD.

Correlaciones entre el test de velocidad en 4 metros y el test de caminata en 6 min en enfermos respiratorios crónicos / Correlations between the 4 meter speed test and the 6-minute walking test in chronic respiratory patients

Resumen La prueba de velocidad de marcha en 4 metros (T4M) es considerada sustituto de la caminata en 6 min (TC6M) en EPOC. Sin embargo, no ha sido bien investigada en otras enfermedades respiratorias. Durante un año estudiamos pacientes que concurrieron a nuestra Unidad para realizar el TC6M midiendo la velocidad alcanzada en 4 metros, 2 h previo a realizar el TC6M. De 162 pacientes 99 eran mujeres. La edad media fue de 65 años, peso de 73 kg, talla de 158 cm, IMC 29,4 kg/m2. 36% tenían fibrosis pulmonar idiopática, 17% EPOC, GOLD IV,11% EPOC, GOLD III, 12% apnea de sueño y 12% otras enfermedades. No hubo diferencia para los distintos diagnósticos en ambos tests. La distancia media en TC6Mfue 368,5 m la velocidad: 1,01 m/s en T4M.Hubo una correlación positiva significativa entre ambos test: alto rendimiento en T4M es equivalente a un alto rendimiento en el TC6M. Hubo correlación negativa con la edad y positiva con la estatura. Al año de seguimiento 16 pacientes habían fallecido, siendo estos los que habían obtenido los más bajos rendimientos en ambos tests (T4M: 0,69 m/s y 248,1 m en TC6M) La posibilidad de sobrevida cayó a 20% en aquellos individuos que alcanzaron una velocidad inferior a 0,69 m/s. Es posible sustituir el TC6M por el T4M en pacientes con diferentes patologías respiratoria, podemos predecir la muerte por cualquier causa si un sujeto camina a una velocidad ≤ 0,69 m/s, T4M es barato y fácil de realizar en atención primaria, sirviendo como evaluación de riesgo para referir a un centro más complejo.

4-Meter Gait Speed Test (4MGST) a frailty test, is considered a surrogate for the 6-Minute Walk Test (6MWT) in COPD. However, it has not been investigated in other respiratory conditions. Over a year, we studied patients attending our Unit for evaluation with 6MWT, measuring the speed they achieved walking 4 m, 2 h before performing 6MWT. 162 patients (99 women) were studied; series' mean values were: age 65 years-old; body weight, 73 kg; height, 158 cm and BMI, 29.4 kg/m2. 36% of them had idiopathic pulmonary fibrosis, 17% GOLD IV COPD, 11% GOLD III COPD, 12% pulmonary arterial hypertension, 12% obstructive apnea-hypopnea syndrome, and 12% other conditions. ANOVA showed no difference between diagnostic categories for both test. Average score in 6MWT was 368.5 m and 1.01 m/s in 4MGST. Pearson correlation coefficient revealed significant positive correlation between results of both tests: high score in 4MGST is equivalent to high score in 6MWT. There was negative correlation with age and positive correlation with height. At one year follow-up, 16 patients had died. They obtained significantly lower scores in both tests (4MGST: 0.69 m/s and 6MWT: 248.1 m) Survival chance fell to 20% for patients walking slower than 0.69 m/s. It is possible to replace TC6M with T4M in patients with different respiratory pathologies, we can predict death for any cause if a subject walked at ≤ speed at 0.69 m/s. T4M is cheap and easy to perform in primary care, serving as a risk assessment to refer to a more complex center.

The use of a mobile spirometry with a feedback quality assessment in primary care setting - A nationwide cross-sectional feasibility study.

OBJECTIVES: Mobile phone-linked portable spirometers are light-weight, easy to use and low cost, with new software to facilitate data collection. In this study we investigated the feasibility of the AioCare® mobile spirometry in primary care. METHODS: In this nationwide, cross-sectional study, AioCare® spirometers (HealthUp, Poland) were distributed among primary healthcare centres across Poland. Operators (primary care professionals) received a 2-h training session, after which spirometry was performed in patients attending routine visits with respiratory symptoms or risk factors for obstructive airway diseases. Spirometry was considered technically correct when at least three manoeuvres met ERS/ATS acceptability and repeatability criteria. The most common spirometry errors were assessed and stepwise logistic regression was applied to identify factors associated with technically correct spirometry. Airway obstruction was defined as FEV1/FVC below the lower limit of normal. A restrictive pattern was defined as FVC below the lower limit of normal. RESULTS: Between 1 September 2018 and 1 September 2019, 10,936 spirometry examinations were performed in 9855 patients by 673 operators. 5347 (49%) spirometry examinations met both acceptability and repeatability criteria. The most common error was plateau error (17.7%). Operator age >40 years (OR 1.49, 95% CI 1.35-1.64) and repetition of the examination at the same visit (OR 1.90, 95% CI 1.66-2.16) increased the likelihood of a technically correct examination. Airway obstruction was found in 17% of correctly performed spirometry examinations. CONCLUSIONS: Our nationwide study suggests that use of the AioCare® mobile spirometer in primary care could be feasible. More intensive and continual training should be implemented to improve the quality of spirometry examinations.

Ca2+ Signaling by TRPV4 Channels in Respiratory Function and Disease.

Members of the transient receptor potential (TRP) superfamily are broadly expressed in our body and contribute to multiple cellular functions. Most interestingly, the fourth member of the vanilloid family of TRP channels (TRPV4) serves different partially antagonistic functions in the respiratory system. This review highlights the role of TRPV4 channels in lung fibroblasts, the lung endothelium, as well as the alveolar and bronchial epithelium, during physiological and pathophysiological mechanisms. Data available from animal models and human tissues confirm the importance of this ion channel in cellular signal transduction complexes with Ca2+ ions as a second messenger. Moreover, TRPV4 is an excellent therapeutic target with numerous specific compounds regulating its activity in diseases, like asthma, lung fibrosis, edema, and infections.

Aspirin desensitization in NSAID-exacerbated respiratory disease and its outcomes in the clinical course of asthma: A systematic review of the literature and meta-analysis.

BACKGROUND: Nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (NERD) might benefit from aspirin desensitization (AD) as an alternative treatment to standard care. However, there is conflicting evidence regarding its role in bronchial symptoms and asthma exacerbations. OBJECTIVE: To analyze the clinical effects of AD in terms of lung function, systemic and inhaled steroid use, the frequency of acute asthma exacerbations, and adverse effects in patients with NERD and asthma. METHODOLOGY: We identified randomized clinical trials (RCTs) from PubMed, EMBASE, SCOPUS, and EBSCO. We also searched the RCT references for additional studies. Studies comparing AD to placebo in patients with a previous history of pulmonary symptoms triggered by ASA or other NSAIDs or with a positive provocation test to ASA were included. PRIMARY RESULTS: Five studies with 210 participants with NERD were included in this review. The study duration ranged from 3 to 6 months. Overall, the risk of bias across the included RCTs was low. We identified 3 studies evaluating lung function, 2 of which reported a significant improvement in FEV1 in the AD group after 6 months, while the other reported no difference among the treatments. Due to high heterogeneity, we did not pool the results. The remaining primary outcomes were reported only in a single study each, hindering their interpretation. Secondary outcomes revealed reduced symptom and medication scores in patients with AD. CONCLUSIONS: Due to the small number of studies included in this systematic review, conclusions should be made with caution. AD shows a trend towards improving lung function (FEV1) following 6 months of treatment, although no conclusions can be made regarding the use of corticosteroids or the frequency of acute exacerbations. AD appears to reduce both symptom and medication scores. Additional RCTs are needed to fully assess the efficacy of AD in reducing bronchial symptoms in patients with NERD.

The melatonergic pathway and its interactions in modulating respiratory system disorders.

Melatonin is a key intracellular neuroimmune-endocrine regulator and coordinator of multiple complex and interrelated biological processes. The main functions of melatonin include the regulation of neuroendocrine and antioxidant system activity, blood pressure, rhythms of the sleep-wake cycle, the retardation of ageing processes, as well as reseting and optimizing mitochondria and thereby the cells of the immune system. Melatonin and its agonists have therefore been mooted as a treatment option across a wide array of medical disorders. This article reviews the role of melatonin in the regulation of respiratory system functions under normal and pathological conditions. Melatonin can normalize the structural and functional organization of damaged lung tissues, by a number of mechanisms, including the regulation of signaling molecules, oxidant status, lipid raft function, optimized mitochondrial function and reseting of the immune response over the circadian rhythm. Consequently, melatonin has potential clinical utility for bronchial asthma, chronic obstructive pulmonary disease, lung cancer, lung vascular diseases, as well as pulmonary and viral infections. The integration of melatonin's effects with the alpha 7 nicotinic receptor and the aryl hydrocarbon receptor in the regulation of mitochondrial function are proposed as a wider framework for understanding the role of melatonin across a wide array of diverse pulmonary disorders.

Aspirin exacerbated respiratory disease (AERD): molecular and cellular diagnostic & prognostic approaches.

Aspirin-exacerbated respiratory disease (AERD) is characterized by immune cells dysfunction. This study aimed to investigate the molecular mechanisms involved in AERD pathogenesis. Relevant literatures were identified by a PubMed search (2005-2019) of english language papers using the terms "Aspirin-exacerbated respiratory disease", "Allergic inflammation", "molecular mechanism" and "mutation". According to the significant role of inflammation in AERD development, ILC-2 is known as the most important cell in disease progression. ILC-2 produces cytokines that induce allergic reactions and also cause lipid mediators production, which activates mast cells and basophils, ultimately. Finally, Monoclonal antibody and Aspirin desensitization in patients can be a useful treatment strategy for prevention and treatment.