Exhaled breath condensate (EBC) in respiratory diseases: recent advances and future perspectives in the age of omic sciences.

Exhaled breath condensate (EBC) is used as a promising noninvasive diagnostic tool in the field of respiratory medicine. EBC is achieved by cooling exhaled air, which contains aerosolized particles and volatile compounds present in the breath. This method provides useful information on the biochemical and inflammatory state of the airways. In respiratory diseases such as asthma, chronic obstructive pulmonary disease and cystic fibrosis, EBC analysis can reveal elevated levels of biomarkers such as hydrogen peroxide, nitric oxide and various cytokines, which correlate with oxidative stress and inflammation. Furthermore, the presence of certain volatile organic compounds in EBC has been linked to specific respiratory conditions, potentially serving as disease-specific fingerprints. The noninvasive nature of EBC sampling makes it particularly useful for repeated measures and for use in vulnerable populations, including children and the elderly. Despite its potential, the standardization of collection methods, analytical techniques and interpretation of results currently limits its use in clinical practice. Nonetheless, EBC holds significant promise for improving the diagnosis, monitoring and therapy of respiratory diseases. In this tutorial we will present the latest advances in EBC research in airway diseases and future prospects for clinical applications of EBC analysis, including the application of the Omic sciences for its analysis.

Clinical application of flexible fiberoptic bronchoscopy in neonatal respiratory diseases.

BACKGROUND: Respiratory disease is a predominantly observed problem in neonates. Moreover, the application of flexible bronchoscopy in newborns is gradually increasing. This study aimed to investigate the value of bronchoscopy in neonates respiratory abnormalities and evaluate the safety of bronchoscopy application. METHODS: Clinical data and outcomes of 56 neonates who underwent flexible bronchoscopy were retrospectively analyzed. Correlations among indications for bronchoscopy, findings, and clinical diseases were assessed. RESULTS: A total of 56 neonates had a minimum weight of 1200 g at the time of bronchoscopy, while the minimum gestational age at birth was 26 + 1 weeks. A total of 22 cases (39.3%) had two or more clinical indications; the five most common indications were respiratory distress in 24 (42.9%), stridor in 22 (39.3%), pulmonary atelectasis in 10 (17.6%), feeding difficulty in 10 (17.6%), and difficult weaning from mechanical ventilation in 6 (10.7%) cases. A total of 13 types of abnormalities were detected in the respiratory tract. The most common abnormalities were laryngomalacia in 29 (59.2%), tracheobroncomalacia in 8 (16.3%), and vocal cord paralysis in 6 (12.2%) cases. Bronchoalveolar lavage was performed in 39 cases. Eight cases were diagnosed by bronchoscopy and then treated with surgery in the Thoracic Surgery/Otolaryngology Department; all of them were cured and discharged from the hospital after surgery. No serious complications, such as pneumothorax or shock, occurred in any of the children, of whom none died. CONCLUSIONS: Flexible bronchoscopy could play an important role in diagnosing and identifying respiratory disorders in neonates and be safely used with few serious complications.

The Role of Exhaled Breath Condensate in Chronic Inflammatory and Neoplastic Diseases of the Respiratory Tract.

Asthma and chronic obstructive pulmonary disease (COPD) are among the most common chronic respiratory diseases. Chronic inflammation of the airways leads to an increased production of inflammatory markers by the effector cells of the respiratory tract and lung tissue. These biomarkers allow the assessment of physiological and pathological processes and responses to therapeutic interventions. Lung cancer, which is characterized by high mortality, is one of the most frequently diagnosed cancers worldwide. Current screening methods and tissue biopsies have limitations that highlight the need for rapid diagnosis, patient differentiation, and effective management and monitoring. One promising non-invasive diagnostic method for respiratory diseases is the assessment of exhaled breath condensate (EBC). EBC contains a mixture of volatile and non-volatile biomarkers such as cytokines, leukotrienes, oxidative stress markers, and molecular biomarkers, providing significant information about inflammatory and neoplastic states in the lungs. This article summarizes the research on the application and development of EBC assessment in diagnosing and monitoring respiratory diseases, focusing on asthma, COPD, and lung cancer. The process of collecting condensate, potential issues, and selected groups of markers for detailed disease assessment in the future are discussed. Further research may contribute to the development of more precise and personalized diagnostic and treatment methods.

Medical and legal diagnoses comparison of the occupational diseases: A nationwide study in Turkey.

OBJECTIVES: The underreporting of occupational diseases in many countries significantly hampers the development of intervention programs, posing a significant public health problem. Our study aimed to contribute to the occupational diseases surveillance by examining the data of hospitals authorized to issue reports throughout Turkey. MATERIAL AND METHODS: This cross-sectional study was conducted using medical diagnoses of occupational diseases reported to the General Directorate of Public Health from 81 provinces in Turkey between 1 January 2018 and 31 December 2022. The study evaluated hospitals that made medical diagnoses of occupational diseases and compared age groups, genders, occupational disease diagnosis groups and provinces of work regarding legal and medical diagnoses. RESULTS: The top three disease groups in terms of medical diagnosis are musculoskeletal disorders with 38.8%, respiratory diseases with 14.4% and hearing defects with 10.9%. Regarding legal diagnoses, respiratory system diseases ranked first with 26.4%, followed by musculoskeletal disorders with 8.2% and hearing defects with 5.5%. While the provinces where most cases of medical occupational diseases are diagnosed share similarities, the majority of affected individuals in Karabük and Batman have not received a legal recognition of the occupational disease. Two-thirds of Turkey's medical occupational disease diagnoses were made in two hospitals. CONCLUSION: This study is reflecting national data in Turkey and is the country's first nationwide study. The number of occupational diseases in Turkey is lower than expected. It would be more accurate to express the data in a way that includes medical diagnoses instead of using the number of compensated files corresponding to legal diagnoses.

Imaging of Large Airway Disorders.

Large airway disorders encompass a large variety of diseases and pathology, with broad categories including anatomic variants, congenital abnormalities, acquired abnormalities, inflammatory/infiltrative causes, infection, and tumors. The most common diseases in each category are discussed with a focus on the salient imaging findings. Pitfalls to beware of are discussed through the article, and concludes with a general method to approaching large airways pathology that should provide the reader with a basic framework and understanding of this complex topic.

Research progress of KL-6 in respiratory system diseases.

This article comprehensively elucidates the discovery of Krebs von den Lungen-6 (KL-6), its structural features, functional mechanisms, and the current research status in various respiratory system diseases. Discovered in 1985, KL-6 was initially considered a tumor marker, but its elevated levels in interstitial lung disease (ILD) led to its recognition as a relevant serum marker for ILD. KL-6 is primarily produced by type 2 alveolar epithelial cell regeneration. Over the past 30 years since the discovery of KL-6, the number of related research papers has steadily increased annually. Following the coronavirus disease 2019 (COVID-19) pandemic, there has been a sudden surge in relevant literature. Despite KL-6's potential as a biomarker, its value in the diagnosis, treatment, and prognosis varies across different respiratory diseases, including ILD, idiopathic pulmonary fibrosis (IPF), COVID-19, and lung cancer. Therefore, as an important serum biomarker in respiratory system diseases, the value of KL-6 still requires further investigation.

Gasotransmitter Research Advances in Respiratory Diseases.

Significance: Gasotransmitters are small gas molecules that are endogenously generated and have well-defined physiological functions. The most well-defined gasotransmitters currently are nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S), while other potent gasotransmitters include ammonia, methane, cyanide, hydrogen gas, and sulfur dioxide. Gasotransmitters play a role in various respiratory diseases such as asthma, chronic obstructive pulmonary disease, obstructive sleep apnea, lung infection, bronchiectasis, cystic fibrosis, primary ciliary dyskinesia, and COVID-19. Recent Advances: Gasotransmitters can act as biomarkers that facilitate disease diagnosis, indicate disease severity, predict disease exacerbation, and evaluate disease outcomes. They also have cell-protective properties, and many studies have been conducted to explore their pharmacological applications. Innovative drug donors and drug delivery methods have been invented to amplify their therapeutic effects. Critical Issues: In this article, we briefly reviewed the physiological and pathophysiological functions of some gasotransmitters in the respiratory system, the progress in detecting exhaled gasotransmitters, as well as innovative drugs derived from these molecules. Future Directions: The current challenge for gasotransmitter research includes further exploring their physiological and pathological functions, clarifying their complicated interactions, exploring suitable drug donors and delivery devices, and characterizing new members of gasotransmitters. Antioxid. Redox Signal. 40, 168-185.

Role of Nasal Nitric Oxide in Primary Ciliary Dyskinesia and Other Respiratory Conditions in Children.

Nitric oxide (NO) is produced within the airways and released with exhalation. Nasal NO (nNO) can be measured in a non-invasive way, with different devices and techniques according to the age and cooperation of the patients. Here, we conducted a narrative review of the literature to examine the relationship between nNO and some respiratory diseases with a particular focus on primary ciliary dyskinesia (PCD). A total of 115 papers were assessed, and 50 were eventually included in the review. nNO in PCD is low (below 77 nL/min), and its measurement has a clear diagnostic value when evaluated in a clinically suggestive phenotype. Many studies have evaluated the role of NO as a molecular mediator as well as the association between nNO values and genotype or ciliary function. As far as other respiratory diseases are concerned, nNO is low in chronic rhinosinusitis and cystic fibrosis, while increased values have been found in allergic rhinitis. Nonetheless, the role in the diagnosis and prognosis of these conditions has not been fully clarified.

The role of oxylipins in NSAID-exacerbated respiratory disease (N-ERD).

Nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) is characterized by nasal polyp formation, adult-onset asthma, and hypersensitivity to all cyclooxygenase-1 (COX-1) inhibitors. Oxygenated lipids are collectively known as oxylipins and are polyunsaturated fatty acids (PUFA) oxidation products. The most extensively researched oxylipins being the eicosanoids formed from arachidonic acid (AA). There are four major classes of eicosanoids including leukotrienes, prostaglandins, thromboxanes, and lipoxins. In N-ERD, the underlying inflammatory process of the upper and lower respiratory systems begins and occurs independently of NSAID consumption and is due to the overproduction of cysteinyl leukotrienes. Leukotriene mediators all induce edema, bronchoconstriction, and airway mucous secretion. Thromboxane A2 is a potent bronchoconstrictor and induces endothelial adhesion molecule expression. Elevated Prostaglandin D2 metabolites lead to vasoconstriction, additionally impaired up-regulation of prostaglandin E2 leads to symptoms seen in N-ERD as it is essential for maintaining homeostasis of inflammatory responses in the airway and has bronchoprotective and anti-inflammatory effects. A characteristic feature of N-ERD is diminished lipoxin levels, this decreased capacity to form endogenous mediators with anti-inflammatory properties could facilitate local inflammatory response and expose bronchial smooth muscle to relatively unopposed actions of broncho-constricting substances. Treatment options, such as leukotriene modifying agents, aspirin desensitization, biologic agents and ESS, appear to influence eicosanoid pathways, however more studies need to be done to further understand the role of oxylipins. Besides AA-derived eicosanoids, other oxylipins may also pay a role but have not been sufficiently studied. Identifying pathogenic N-ERD mechanism is likely to define more effective treatment targets.

Validity of diagnoses of respiratory diseases recorded in a Japanese administrative database.

BACKGROUND: Validating the information recorded in administrative databases is essential. However, no study has comprehensively validated the accuracy of Japanese Diagnosis Procedure Combination (DPC) data on various respiratory diseases. Therefore, this study aimed to evaluate the validity of diagnoses of respiratory diseases in the DPC database. METHODS: We conducted chart reviews of 400 patients hospitalized in the departments of respiratory medicine in two acute-care hospitals in Tokyo, between April 1, 2019 and March 31, 2021, and used them as reference standards. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of DPC data on 25 respiratory diseases were determined. RESULTS: Sensitivity ranged from 22.2% (aspiration pneumonia) to 100% (chronic eosinophilic pneumonia and malignant pleural mesothelioma) and was <50% for eight diseases, while specificity was >90% for all diseases. PPV ranged from 40.0% (aspiration pneumonia) to 100% (coronavirus disease 2019, bronchiectasis, chronic eosinophilic pneumonia, pulmonary hypertension, squamous cell carcinoma, small cell carcinoma, lung cancer of other histological types, and malignant pleural mesothelioma) and was >80% for 16 diseases. Except for chronic obstructive pulmonary disease (82.9%) and interstitial pneumonia (other than idiopathic pulmonary fibrosis) (85.4%), NPV was >90% for all diseases. These validity indices were similar in both hospitals. CONCLUSIONS: The validity of diagnoses of respiratory diseases in the DPC database was high in general, thereby providing an important basis for future studies.

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.

Protocolo clínico de atendimento de pneumonia adquirida na comunidade para Pronto-Socorro Infantil do Hospital do Servidor Público Municipal de São Paulo / Clinical protocol for community-acquired pneumonia care for the Children's Emergency Room of the Hospital do Servidor Público Municipal de São Paulo

A pneumonia adquirida na comunidade (PAC) é a infecção aguda do parênquima pulmonar que ocorre no meio comunitário. A PAC representa a maior causa de morbidade e mortalidade em todo o mundo em crianças abaixo de cinco anos. Nesta faixa etária, a etiologia viral é a mais comum; porém, dentre as causas bacterianas, o Streptoccocus pneumoniae é o mais prevalente. As manifestações clínicas variam de acordo com o patógeno, hospedeiro e da gravidade da doença, sendo geralmente descrita com tosse, febre e desconforto respiratório. A PAC complicada é a pneumonia que, apesar do uso de antibióticos, evolui com complicações locais ou sistêmicas. Nos pacientes hospitalizados, as hemoculturas devem ser consideradas para auxiliar no diagnóstico etiológico e planejamento terapêutico. O tratamento inicial deve ser iniciado empiricamente com antibióticos. Caso haja necessidade de hospitalização, hemoculturas devem ser consideradas para auxiliar na propedêutica. Após implementação das vacinas pneumocócicas, principalmente após introdução da vacina pneumocócica 13 valente (PCV 13), houve redução significativa dos casos de pneumonia bacteriana e também da necessidade hospitalização. Diante de tal realidade, a elaboração do trabalho possui como objetivo a melhora dos procedimentos e a padronização dos atendimentos da população pediátrica com um quadro clínico sugestivo pneumonia adquirida na comunidade, que procura o serviço de Pronto Atendimento Infantil do Hospital do Servidor Público Municipal de São Paulo (HSPM), ao construir um protocolo clínico de atendimento específico para a doença. O presente trabalho objetiva elaborar um protocolo clínico de atendimento de pneumonia adquirida na comunidade no Hospital do Servidor Público Municipal de São Paulo, contribuindo na assistência médica dos pacientes pediátricos. Apesar do grande avanço com a introdução das vacinas pneumocócicas, a PAC ainda representa uma importante causa de mortalidade na população infantil, sendo fundamental a elaboração de protocolos clínicos para abordar corretamente os pacientes que recorrem a um Pronto Socorro Infantil. Protocolos clínicos são diretrizes fundamentadas nas melhores práticas para a abordagem e tratamento de determinadas doenças, baseadas em evidência científica. O presente trabalho objetiva a melhora dos procedimentos e a uniformização dos atendimentos da população pediátrica com pneumonia, que procura o serviço de Pronto Atendimento Infantil do Hospital do Servidor Público Municipal de São Paulo (HSPM), com a construção de um protocolo clínico de atendimento específico para a doença, a partir da revisão de literatura atualizada, cujo período de vigência seguirá os progressos científicos sobre o tema. Palavras-chave: Pneumonia Adquirida da Comunidade. Protocolos clínicos. Pediatria. Serviços Médicos de Emergência. Vacinas Pneumocócicas

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.

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.

Evaluation of airway inflammation in mechanically ventilated patients using cell count and protein concentration.

Mechanically ventilated (MV) patients may present airway inflammation and elevated secretion production. However, it is unknown whether cell and/or protein counts in bronchial samples may be useful to evaluate their clinical condition. Our aim was to standardize sampling and propose a new mechanical mucus dissolution in Tracheal-Bronchial secretions. In all patients, bronchial lining fluid aspiration (BLF), Bronchoalveolar lavage (BAL) and Bronchial Washings (BW40, BW5) were performed, while visible bronchial secretions were obtained via bronchoscopy (VBS) and blinded, via a common catheter for tracheobronchial aspiration (AC). Mucus was mechanically or DTT dissolved and cell number was count. Protein, albumin and TNF-α levels were measured, in mucus dissolved samples from control and MV patients. Cell number and protein levels were elevated in mucus dissolved compared to non-dissolved, or DTT dissolved. Cell number and TNF-α levels were elevated in MV patients compared to controls, while protein levels were lower in MV patients. Differences in cell and protein levels were observed in samples acquired using different sampling technics. Therefore, mechanical mucus dissolution provides a proper sample for evaluation, and the sampling technic used can influence the sample's characteristics.

Abdominal Pain in the Emergency Department: Missed Diagnoses.

Abdominal pain is the most common chief complaint in the Emergency Department. Abdominal pain is caused by a variety of gastrointestinal and nongastrointestinal disorders. Some frequently missed conditions include biliary pathology, appendicitis, diverticulitis, and urogenital pathology. The Emergency Medicine clinician must consider all aspects of the patient's presentation including history, physical examination, laboratory testing, and imaging. If no diagnosis is identified, close reassessment of pain, vital signs, and physical examination are necessary to ensure safe discharge. Strict verbal and written return precautions should be provided to the patient.

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.