Associations between long-term ozone exposure and small airways function in Chinese young adults: a longitudinal cohort study.

BACKGROUND: Increasing evidence is appearing that ozone has adverse effects on health. However, the association between long-term ozone exposure and lung function is still inconclusive. OBJECTIVES: To investigate the associations between long-term exposure to ozone and lung function in Chinese young adults. METHODS: We conducted a prospective cohort study among 1594 college students with a mean age of 19.2 years at baseline in Shandong, China from September 2020 to September 2021. Lung function indicators were measured in September 2020 and September 2021, including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), forced expiratory flow at the 25th, 50th, and 75th percentile of the FVC (FEF25, FEF50, and FEF75) and mean flow rate between 25% and 75% of the FVC (FEF25-75) were measured. Daily 10 km×10 km ozone concentrations come from a well-validated data-fusion approach. The time-weighted average concentrations in 12 months before the lung function test were defined as the long-term ozone exposure. The associations between long-term ozone exposure and lung function indicators in Chinese young adults were investigated using a linear mixed effects model, followed by stratified analyses regarding sex, BMI and history of respiratory diseases. RESULTS: Each interquartile range (IQR) (8.9 µg/m3) increase in long-term ozone exposure were associated with a -204.3 (95% confidence interval (CI): -361.6, -47.0) ml/s, -146.3 (95% CI: -264.1, -28.4) ml/s, and - 132.8 (95% CI: -239.2, -26.4) ml/s change in FEF25, FEF50, and FEF25-75, respectively. Stronger adverse associations were found in female participants or those with BMI ≥ 24 kg/m2 and history of respiratory diseases. CONCLUSION: Long-term exposure to ambient ozone is associated with impaired small airway indicators in Chinese young adults. Females, participants with BMI ≥ 24 kg/m2 and a history of respiratory disease have stronger associations.

Air pollution and childhood respiratory consultations in primary care: a systematic review.

BACKGROUND: Outdoor air pollution is a known risk factor for respiratory morbidity worldwide. Compared with the adult population, there are fewer studies that analyse the association between short-term exposure to air pollution and respiratory morbidity in children in primary care. OBJECTIVE: To evaluate whether children in a primary care setting exposed to outdoor air pollutants during short-term intervals are at increased risk of respiratory diagnoses. METHODS: A search in Medline, the Cochrane Library, Web of Science and Embase databases throughout March 2023. Percentage change or risk ratios with corresponding 95% CI for the association between air pollutants and respiratory diseases were retrieved from individual studies. Risk of bias assessment was conducted with the Newcastle-Ottawa Scale (NOS) for cohort or case-control studies and an adjusted NOS for time series studies. RESULTS: From 1366 studies, 14 were identified as meeting the inclusion criteria. Most studies had intermediate or high quality. A meta-analysis was not conducted due to heterogeneity in exposure and health outcome. Overall, studies on short-term exposure to air pollutants (carbon monoxide (CO), sulfur dioxide (SO2), nitrogen dioxide (NO2) and particulate matter ≤10 µm (PM10)) were associated with increased childhood respiratory consultations in primary care. In general, exposure to ozone was associated with a reduction in respiratory consultations. CONCLUSIONS: The evidence suggests CO, SO2, NO2, PM10 and PM2.5 are risk factors for respiratory diseases in children in primary care in the short term. However, given the heterogeneity of the studies, interpretation of these findings must be done with caution. PROSPERO REGISTRATION NUMBER: CRD42022259279.

Comparison and interobserver reliability between a visual analog scale and the Wisconsin Calf Health Scoring Chart for detection of respiratory disease in dairy calves.

Respiratory disease is an ongoing challenge for calves in the dairy sector with a relatively high prevalence and impact on welfare and economics. Applying scoring protocols for detecting respiratory disease requires that they are easily implemented, consistent between observers and fast to use in daily management. This study was conducted in one Danish dairy farm from September 2020 through January 2021. The study included 126 heifer calves enrolled in the age of 17 to 24 d. All calves were observed every second day for a period of 46 d. At each visit all calves were scored with a new visual analog scale (VAS) and the Wisconsin Calf Health Scoring Chart (WCHSC). We calculated agreement between the 2 scoring systems based on conditional probability to score higher or lower than a cutoff in the VAS compared with a specified cutoff in WCHSC used as reference test. A generalized mixed effects regression model was developed to estimate the prevalence of respiratory disease and the overall agreement between the 2 scoring systems. The overall agreement between the VAS and WCHSC was 89.6%. The second part of the study assessed interobserver reliability between 2 experienced observers and between an experienced observer and veterinary students. The interobserver reliability was calculated by intraclass correlation coefficient and was 0.58 between experienced observers and was 0.34 between an experienced observer and veterinary students indicating a moderate to poor reliability between the observers. It was possible to use VAS as an alternative clinical scoring method, which primarily focuses on the general condition of the individual calf rather than specific categories of clinical signs. Our study set up lacked a comparison to other diagnostic tools i.e., thoracic ultrasound to confirm the findings which should be considered in future studies when exploring VAS as a screening tool for detection of respiratory disease in dairy calves.

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.

Efficacy and Safety of an mRNA-Based RSV PreF Vaccine in Older Adults.

BACKGROUND: Respiratory syncytial virus (RSV) can cause substantial morbidity and mortality among older adults. An mRNA-based RSV vaccine, mRNA-1345, encoding the stabilized RSV prefusion F glycoprotein, is under clinical investigation. METHODS: In this ongoing, randomized, double-blind, placebo-controlled, phase 2-3 trial, we randomly assigned, in a 1:1 ratio, adults 60 years of age or older to receive one dose of mRNA-1345 (50 µg) or placebo. The two primary efficacy end points were the prevention of RSV-associated lower respiratory tract disease with at least two signs or symptoms and with at least three signs or symptoms. A key secondary efficacy end point was the prevention of RSV-associated acute respiratory disease. Safety was also assessed. RESULTS: Overall, 35,541 participants were assigned to receive the mRNA-1345 vaccine (17,793 participants) or placebo (17,748). The median follow-up was 112 days (range, 1 to 379). The primary analyses were conducted when at least 50% of the anticipated cases of RSV-associated lower respiratory tract disease had occurred. Vaccine efficacy was 83.7% (95.88% confidence interval [CI], 66.0 to 92.2) against RSV-associated lower respiratory tract disease with at least two signs or symptoms and 82.4% (96.36% CI, 34.8 to 95.3) against the disease with at least three signs or symptoms. Vaccine efficacy was 68.4% (95% CI, 50.9 to 79.7) against RSV-associated acute respiratory disease. Protection was observed against both RSV subtypes (A and B) and was generally consistent across subgroups defined according to age and coexisting conditions. Participants in the mRNA-1345 group had a higher incidence than those in the placebo group of solicited local adverse reactions (58.7% vs. 16.2%) and of systemic adverse reactions (47.7% vs. 32.9%); most reactions were mild to moderate in severity and were transient. Serious adverse events occurred in 2.8% of the participants in each trial group. CONCLUSIONS: A single dose of the mRNA-1345 vaccine resulted in no evident safety concerns and led to a lower incidence of RSV-associated lower respiratory tract disease and of RSV-associated acute respiratory disease than placebo among adults 60 years of age or older. (Funded by Moderna; ConquerRSV ClinicalTrials.gov number, NCT05127434.).

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.

Low-cost air quality portable sensors and their potential use in respiratory health.

Air pollution is an environmental risk for the general population and for patients with various diseases, particularly respiratory diseases. Little data are available on personal exposure, but the recent emergence of low-cost air quality sensors (LCSs) should enable a better understanding of the health impacts of air pollution at the individual level. However, the reliability and accuracy of most sensors in the market have not been established, and a thorough understanding of their strengths and limitations is needed. We therefore conducted a review to address the following questions: 1) What is an LCS and what is the extent of its possible application? 2) Is the data obtained a reliable indicator of exposure? 3) What are the advantages and disadvantages of LCSs? 4) Could LCSs be useful in investigating the impact of air pollution on respiratory health? Further studies are needed to promote the use of LCS in research settings and among respiratory patients. This will allow us to monitor exposure levels, provide alerts and study the respiratory effects of individual-level air pollution.

Oral meloxicam given as an ancillary treatment at respiratory disease diagnosis was not associated with growth, clinical scores, or ultrasound scores in preweaned dairy calves.

Objective: To assess the efficacy of a single dose of oral meloxicam as an ancillary therapy to an antibiotic given at the time of respiratory disease identification on average daily gain (ADG), behavioral attitude, clinical respiratory, and lung ultrasound scores in preweaned dairy calves. Animals: 215 male and female Holstein, Jersey, and crossbred preweaned calves enrolled between 1 and 14 days of age at study enrollment on a single commercial dairy in the western US. Methods: The study took place from March 4, 2021, to November 21, 2021. In this double-blind placebo-controlled study, calves were given an antibiotic (1.1 mL of tulathromycin/kg, SC, once) and either a placebo (1 mg of lactose monohydrate/kg, in a gelatin capsule) or oral meloxicam (1 mg/kg) at the time of respiratory disease identification. Behavioral attitude, clinical respiratory, and lung ultrasound scores and ADG were assessed in preweaned dairy calves at different time points including the next health examination, 1 week later, or at weaning. Results: There was no association between treatment (placebo vs meloxicam) on ADG or respiratory disease status at weaning (P > .05). There was no effect of treatment on behavioral attitude, clinical respiratory, or lung ultrasound scores at the next health examination or 1 week later (P > .05). Clinical Relevance: The present study did not provide evidence that oral meloxicam given once is beneficial for growth, behavioral attitude, or clinical or lung ultrasound scores.

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.

Advances and perspectives of nanozymes in respiratory diseases.

Respiratory diseases, some of the most common human diseases, have become a prominent public health and medical problem. Feasible treatment and prevention strategies are still required to prepare for respiratory emergencies. Nanotechnology has provided new technological conceptions in respiratory disease-related applications and inspired the exploration of various multifunctional nanomaterials. Among them, "nanozymes" with enzyme-like activities and nanomaterials' physicochemical properties may propel the development in this field. Over the past few decades, nanozymes have distinguished themselves in the fields of biosensing, biomedicine, imaging, and environmental protection due to their outstanding enzymatic properties, reactive oxygen species-regulating mechanism, high stability, modifiability, mass production, and others. Herein, this article reviews the research progress of nanozymes in diagnosing, treating, and preventing respiratory diseases, hoping to bring new ideas for promoting nanozymes and their beneficial applications in respiratory diseases.

A simplified scoring system for the diagnosis of diarrhea and respiratory diseases in dairy calves.

Objective: To compare the capacity of a simplified calf health scoring chart (SIM score) with the University of Wisconsin's calf health scoring chart (WIN score) for the diagnosis of calf diarrhea and calf respiratory disease (RD). Animals and procedures: Holstein calves (N = 222) were clinically evaluated for diarrhea and RD diagnosis using the WIN and SIM scores. The WIN score was based on fecal consistency for diagnosis of diarrhea (0 = feces of normal consistency to 3 = watery feces; score ≥ 2 = positive diagnosis); and on nasal discharge, ocular discharge, coughing, ear position, and rectal temperature for diagnosis of RD (each clinical sign receives a score of 0 to 3; aggregate score ≥ 5 = positive diagnosis). The SIM score was based on a hide cleanliness score for diagnosis of diarrhea [0 = negative (calf was clean) and 1 = positive (tail head region, thighs, and/or legs were soiled)]; and on nasal discharge, ocular discharge, coughing, and ear position for diagnosis of RD (rectal temperature measurement was not required and each clinical sign had 2 levels of severity; aggregate score ≥ 5 = positive diagnosis). Results: In the RD diagnosis, the SIM score had a sensitivity of 88.24%, a specificity of 95.01%, a positive predictive value (PPV) of 55.56%, and a negative predictive value (NPV) of 99.13%. In the diarrhea diagnosis, the SIM score had a sensitivity of 94.62%, a specificity of 49.64%, a PPV of 18.22%, and an NPV of 98.73%. Conclusion: Compared with the WIN score, the SIM score is a reliable test for diagnosing RD but not for diagnosing diarrhea.

Un système de notation simplifié pour le diagnostic de la diarrhée et des maladies respiratoires chez les veaux laitiers. Objectif: Comparer la capacité d'un tableau de notation simplifié de la santé du veau (score SIM) avec le tableau de notation de la santé du veau (score WIN) de l'University of Wisconsin pour le diagnostic de la diarrhée du veau et de la maladie respiratoire du veau (RD). Animaux et procédures: Des veaux Holstein (N = 222) ont été évalués cliniquement pour le diagnostic de diarrhée et de RD à l'aide des scores WIN et SIM. Le score WIN était basé sur la consistance fécale pour le diagnostic de diarrhée (0 = fèces de consistance normale à 3 = fèces aqueuses; score ≥ 2 = diagnostic positif ); et sur l'écoulement nasal, l'écoulement oculaire, la toux, la position des oreilles et la température rectale pour le diagnostic de RD (chaque signe clinique reçoit un score de 0 à 3; score global ≥ 5 = diagnostic positif ). Le score SIM était basé sur un score de propreté de la peau pour le diagnostic de diarrhée [0 = négatif (le mollet était propre) et 1 = positif (la région de la tête de la queue, les cuisses et/ou les pattes étaient souillées); et sur l'écoulement nasal, l'écoulement oculaire, la toux et la position des oreilles pour le diagnostic de RD (la mesure de la température rectale n'était pas requise et chaque signe clinique avait 2 niveaux de gravité; score global ≥ 5 = diagnostic positif ). Résultats: Dans le diagnostic de RD, le score SIM avait une sensibilité de 88,24 %, une spécificité de 95,01 %, une valeur prédictive positive (VPP) de 55,56 % et une valeur prédictive négative (VPN) de 99,13 %. Dans le diagnostic de diarrhée, le score SIM avait une sensibilité de 94,62 %, une spécificité de 49,64 %, une VPP de 18,22 % et une VPN de 98,73 %. Conclusion: Comparé au score WIN, le score SIM est un test fiable pour diagnostiquer le RD mais pas pour diagnostiquer la diarrhée.(Traduit par Dr Serge Messier).

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.

Evaluating Listening Performance for COVID-19 Detection by Clinicians and Machine Learning: Comparative Study.

BACKGROUND: To date, performance comparisons between men and machines have been carried out in many health domains. Yet machine learning (ML) models and human performance comparisons in audio-based respiratory diagnosis remain largely unexplored. OBJECTIVE: The primary objective of this study was to compare human clinicians and an ML model in predicting COVID-19 from respiratory sound recordings. METHODS: In this study, we compared human clinicians and an ML model in predicting COVID-19 from respiratory sound recordings. Prediction performance on 24 audio samples (12 tested positive) made by 36 clinicians with experience in treating COVID-19 or other respiratory illnesses was compared with predictions made by an ML model trained on 1162 samples. Each sample consisted of voice, cough, and breathing sound recordings from 1 subject, and the length of each sample was around 20 seconds. We also investigated whether combining the predictions of the model and human experts could further enhance the performance in terms of both accuracy and confidence. RESULTS: The ML model outperformed the clinicians, yielding a sensitivity of 0.75 and a specificity of 0.83, whereas the best performance achieved by the clinicians was 0.67 in terms of sensitivity and 0.75 in terms of specificity. Integrating the clinicians' and the model's predictions, however, could enhance performance further, achieving a sensitivity of 0.83 and a specificity of 0.92. CONCLUSIONS: Our findings suggest that the clinicians and the ML model could make better clinical decisions via a cooperative approach and achieve higher confidence in audio-based respiratory diagnosis.

Deployment-Related Respiratory Disease: Where Are We?

Military personnel and veterans who have deployed to Afghanistan, Iraq, and parts of Southwest Asia (SWA) since 1990 are at risk of developing a host of respiratory symptoms and deployment-related respiratory diseases (DRRDs). This review aims to summarize our current understanding of DRRD and inform pulmonary practitioners of recent updates to DRRD screening, diagnosis, evaluation, and management. The most common respiratory diseases in these patients include asthma, chronic sinonasal disease, laryngeal disease/dysfunction, and distal lung disease. Pulmonary function testing and chest imaging are the most commonly used diagnostic tools, but techniques such as lung clearance index testing via multiple breath washout, forced oscillation testing/impulse oscillometry, and quantitative chest computed tomography (CT) assessment appear promising as noninvasive modalities to aid in lung disease detection in this population. We also summarize guidance on conducting an occupational and deployment exposure history as well as recommendations for testing. Finally, we discuss the Sergeant First Class Heath Robinson Honoring our Promise to Address Comprehensive Toxics Act of 2022 (PACT Act) that includes a list of health conditions that are "presumptively" considered to be related to SWA military deployment toxic exposures, and provide resources for clinicians who evaluate and treat patients with DRRD.

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.