Respiratory Disease Research Research Articles

3D Bioprinitng technologies for the enhancement and application of functional lung organoid models

Respiratory diseases, ranging from minor infections to serious chronic diseases and malignancies, negatively affect the respiratory system and are influenced by various environmental factors such as air pollution, occupational hazards, and tobacco smoke, as well as lifestyle, genetic causes, and infectious agents. The prevalence and severity of respiratory diseases requires the development of advanced models to better understand their pathophysiology and develop effective treatments. In this context, 3D bioprinting technology is emerging as an innovative tool to create functional lung organoid models. The use of induced pluripotent stem cells (iPSCs) and extracellular matrix (ECM) in bioprinting enables the development of organoids that closely mimic human lung tissue. Bioprinting-based organoids can better replicate the dynamic environment of the human lung, facilitating more accurate disease modeling and drug testing. In this review, we highlight the potential of bioprinted lung organoids in understanding the mechanisms of chronic respiratory diseases, testing the efficacy and safety of new drugs, and exploring regenerative medicine approaches. The integration of advanced bioprinting and organoid technologies is a promising field in respiratory disease research and treatment, offering new hope for patients suffering from lung diseases.

Design, manufacture, and control of a low-cost positive airway pressure device

Current positive airway pressure devices cost NZ$800-$2500, posing a financial barrier for the estimated 1 billion individuals worldwide with sleep apnea and those researching respiratory diseases. Increasing diagnoses and research interest in the area necessitate a low-cost, easily accessible alternative. Thus, the mePAP, a high-quality, multipurpose, low-cost (∼NZ$250) positive airway pressure device, was designed and prototyped specifically for respiratory disease research, particularly for sleep apnea. The mePAP allows user customization and provides researchers with an affordable tool for testing positive airway pressure algorithms. Unlike typical commercial devices, the mePAP offers adaptability with open-source data collection and easily modifiable software for implementing and analysing different control and diagnostic algorithms. It features three control modes: constant; bilevel; and automatic; and provides pressures from 4 to 20 cmH2O, controlled via a phone app through Wi-Fi, with a mini-sensor added at the mask for increased accuracy. Validation tests showed the mePAP’s performance is comparable to a gold-standard Fisher & Paykel device, with extremely similar output pressures. The mePAP’s low cost enhances accessibility and equity, allowing researchers to test ventilation algorithms for sleep apnea and other respiratory conditions, with all data openly available for analysis. Its adaptability and multiple applications increase its usability and usefulness across various research and clinical settings.

Testing pulmonary physiology in ventilated non-human primates.

Animal models of respiratory viral infections are essential for investigating disease pathogenesis and the efficacy of antivirals and vaccine candidates. A major limitation in the research of respiratory diseases in animal models is correlating clinically relevant changes in pulmonary physiology with cellular and molecular mechanistic studies. Few animal models have captured and correlated physiologic changes in lung function and immune response within same experiment, which is critical given the heterogeneous nature of lung disease due to viral infections. In ventilated human patients, pulmonary physiology testing can be used to not only capture oxygenation, ventilation, but also pulmonary mechanics to yield quantitative measures of lung function and scalar tracings of flow-volume and pressure-volume loops. Application of this protocol during mechanical ventilation in non-human (NHP) models would represent a major advance in respiratory viral disease research. We have applied and optimized a human pulmonary physiology testing protocol to ventilated pigtail macaques (Macaca nemestrina) at baseline and 5 days after influenza A (IAV) viral inoculation. The NHPs manifested clinical disease with hypothermia and loss of body weight. Declines in lung function were striking with a 66%-81% decline in P/F ratio, a measure of oxygenation reflecting the ratio of partial pressure of oxygen in arterial blood (PaO2 ) to the fraction of inspiratory oxygen concentration (FiO2 ). There was also a 16%-45% decline in lung compliance. We describe a new approach to performing pulmonary physiology testing protocol in non-human primates to better capture quantitative correlates of respiratory disease and demonstrate protection by therapeutics and vaccines.

МЕТАБОЛОМІЧНИЙ ПІДХІД ДО ПРОГНОЗУВАННЯ ПЕРЕБІГУ ХРОНІЧНОГО ОБСТРУКТИВНОГО ЗАХВОРЮВАННЯ ЛЕГЕНЬ: НОВЕ СЛОВО У РОЗУМІННІ ЗАХВОРЮВАННЯ

Metabolomics is the branch of science that investigates various metabolites (both intermediate and terminal metabolic products) and their role in biomatrices. In respiratory diseases, metabolomics studies focus mainly on identified metabolites, which can predict the onset and progression of severe illnesses, which can be fatal for many patients (COPD, asthma, interstitial lung diseases, malignancy, etc.). In this article, we review the current development of metabolic changes in COPD, mainly at the time of exacerbation. The aim of the study is to make a comprehensive review of the relevant literature related to metabolomic markers of COPD and its exacerbations, as well as to investigate the potential clinical benefit of the metabolomic profile of this disease. The review describes the technological tools and methods currently used in metabolomic research in respiratory diseases. Our team conducted a non-systematic review of relevant literature. PubMed and Scopus were the main databases of scientific information for collecting relevant publications from the international literature.

Progress and Gaps in Respiratory Disease Research and Treatment: Highlights of the IRM 2024 in Shanghai

Progress and Gaps in Respiratory Disease Research and Treatment: Highlights of the IRM 2024 in Shanghai

Public involvement in chronic respiratory diseases research: A qualitative study of patients', carers' and citizens' perspectives.

Patient and public involvement (PPI) initiatives involving patients with chronic respiratory disease (CRD) are rare. Therefore, this study aimed to explore the perspectives of patients with CRD, carers and interested citizens regarding the relevance and need for a PPI network and suggestions for its implementation. A qualitative study based on focus groups was conducted. Recruitment occurred through invitations on social media platforms and to patients who have participated in previous asthma studies of the team. Three focus groups were conducted, via video conference, using a semi-structured guide. Thematic analysis was performed by two independent researchers and discussed with the extended team. Fifteen patients with CRD, one carer and one interested citizen (13 females, median 36 (range: 18-72) years) participated. All participants acknowledged the importance of implementing a collaborative network and demonstrated interest in being integrated. Participants acknowledged the importance of their involvement in several phases of the research cycle. The main aim identified for this network was to facilitate communication between patients and researchers. Participants regarded the integration of patients, carers, researchers and healthcare professionals from different scientific areas as relevant. The use of digital platforms to attract members and support the work, together with group dynamics and regular meetings, were some of the most relevant practical considerations for implementing the network. The identified facilitators for their engagement were sharing experiences, researchers' and healthcare professionals' support and feedback and schedule flexibility. The identified barriers included the amount of time dedicated, low health/digital literacy and the potential detachment of nondiagnosed patients or those with low symptom impact in daily life. Patients, carers and citizens acknowledged the relevance of implementing a collaborative network and demonstrated interest in active participation in every stage of the health research cycle. A deeper knowledge of the barriers and facilitators identified in this study could support implementing these initiatives in Portugal. This study was designed by a research team that included one patient with asthma and one carer. They were specifically involved in building the study protocol and the interview guide. They also gave feedback regarding the electronic consent form and the short sociodemographic questionnaire created, namely by removing noncontributing words or phrases and rewording expressions. The lay summary was written by another patient with asthma. All participants of this study were invited to implement and integrate the ConectAR network-a collaborative network of research in respiratory health. In Portugal, chronic respiratory patients do not have an active role as 'coinvestigators'. This study aimed to acknowledge if patients and citizens considered a patient and public involvement network useful, whose main purpose would be to facilitate communication between patients and researchers. A study based on online group interviews was carried out with patients with chronic respiratory diseases and interested citizens, both recruited on social media platforms. Participants considered that bringing together patients, carers, researchers and healthcare professionals is valuable because sharing different experiences and perspectives may help patients to improve their daily lives and increase research quality. In conclusion, patients agree that implementing a collaborative network with researchers and healthcare professionals and participating in the health research cycle is quite preponderant. Acknowledging what can help and deter this network may be beneficial to implementing this type of initiative in Portugal.

Evaluation value and mechanism of ADRB2 and FCER1B gene polymorphisms in preterm infants with congenital respiratory diseases.

In this study, we observed the value of ADRB2 and FCER1B gene polymorphisms in evaluating congenital respiratory diseases in preterm infants (PTIs), analyzed their effects on airway smooth muscle cells (ASMCs), and preliminarily discussed the underlying mechanism. First, we placed 64 healthy PTIs (control group) and 45 PTIs with congenital respiratory diseases (research group) born at our hospital from April 2021 to June 2023 were selected as the research subjects. Through testing, we found that the carriers of AA genotype of the polymorphic marker rs1042713 of the ADRB2 gene and that of the rs569108 locus of the FCER1B gene were less in the research group compared with the control group (P<0.05). Preterm infants carrying the GG genotype had a 2.887-fold (P<0.05) increased risk of developing congenital respiratory disease under the recessive model at the rs1042713 locus of the ADRB2 gene. Under the dominant model, preterm infants who did not carry the AA genotype had a 3.070-fold (P<0.05) increased risk of developing congenital respiratory disease. Subsequently, the constructed abnormal expression vectors of ADRB2 and FCER1B were transfected into ASMCs to examine changes in cell activity and pyroptosis. We found that up-regulating ADRB2 and FCERIB expression promoted ASMC proliferation and inflammatory reactions, inhibited apoptosis, and accelerated pyroptosis (P<0.05); silencing their expression, however, led to the opposite effect. In conclusion, the ADRB2 and FCERIB gene polymorphisms are strongly correlated with congenital respiratory diseases, which can provide a reference for clinical evaluation of congenital respiratory diseases in PTIs.

Assessing shared respiratory pathogens between domestic (Ovis aries) and bighorn (Ovis canadensis) sheep; methods for multiplex PCR, amplicon sequencing, and bioinformatics to characterize respiratory flora.

Respiratory disease is responsible for dramatic population declines in bighorn sheep (Ovis canadensis), and respiratory pathogen diagnostics contribute to the management of bighorn populations. To create a comprehensive and consistent approach to bighorn sheep respiratory diagnostics, we created a culture-independent assay to detect and strain type Mannheimia haemolytica, Bibersteinia trehalosi, Pasteurella multocida, and Mycoplasma ovipneumoniae. The assay also detects and characterizes the Pasteurellaceae leukotoxin A gene, and broadly assesses the bacterial composition of each sample based on 16S rRNA sequences. The assay is based on a three-step approach: 1) Multiplex PCR to amplify targets including eight loci for each bacterial species, the Pasteurellaceae lktA gene, and the 16S rRNA gene 2) Library preparation, barcoding, and short-read Illumina sequencing to determine the genetic sequences of each target, and 3) Bioinformatics in the form of automated software to analyze genetic sequences. The assay was designed to assess shared pathogens between domestic and bighorn sheep, but could be useful for many applications in bighorn sheep respiratory disease research and management.

Different volatile organic compounds in local point source air pollution pose distinctive elevated risks for respiratory disease-associated emergency room visits

Air pollution increases risk of respiratory disease but prior research has focused on particulate matter and criteria air pollutants, and there are few studies on respiratory effects of volatile organic compounds (VOC). We examined zip code level relationships between emergency room (ER) visits for respiratory illness and VOC pollution in New York State from 2010 to 2018. Detailed information on VOC pollution was derived from the National Emissions Inventory, which provides point source information on VOC emissions at the zip code level. We considered four respiratory diseases: asthma, acute upper respiratory infections, chronic obstructive pulmonary disease (COPD), and lower respiratory disease, using mixed effects regression with a random intercept to account for county level variability in single pollutant models, and Random Forest Regression (RFR) to assess relative importance of VOC exposures when considered together in multipollutant models.Single pollutant models show associations between respiratory-related ER visits with all pollutants of interest across all study years, even after adjusting for poverty and smoking by zip code. The largest relative single pollutant effect sizes considered included benzene, ethylbenzene, and total (summed) VOCs. Results from RFR including all VOC exposures indicate that ethylbenzene has the greatest variable importance for asthma, acute upper respiratory infections, and COPD, with toluene and benzene most important for lower respiratory ailments. RFR results also demonstrate presence of pairwise interactive effects between VOC pollutants. Our findings show that local VOC pollution may offer a significant contribution to the risk of respiratory disease-related ER visits, and that effects vary by illness and by VOC compound. ER visit rates for respiratory illness were elevated in high poverty zip codes, although this may be attributable to the fact that the poor lack basic access to health care and use ERs more frequently for routine care.

The Application of New Approach Methodologies in Respiratory Disease Research: Their Role in Improving Translational Medicine from Bench to Bedside.

The SARS-CoV-2 outbreak focused global attention on the shortcomings of the drug discovery process. It led to its acceleration in several areas, particularly in the processes associated with the development and approval of COVID-19 vaccines. This situation contrasts with the low approval rates of new drugs for respiratory system diseases (e.g. asthma, chronic obstructive pulmonary disease, cancer, tuberculosis), which are leading causes of morbidity and mortality worldwide. In this context, innovation in respiratory system drug discovery is surely needed, and it is most likely to succeed through the use of preclinical models that are cost-effective, high-throughput and generate predictive human-relevant outcomes. Here, we highlight several non-animal new approach methodologies (NAMs) and their applications in respiratory research. We describe their potential uses for efficacy and toxicity assessments, to optimise the drug development process and reduce the high failure rates in clinical trials.

Anti-Oxidant and Pro-Oxidant Effects of Peroxiredoxin 6: A Potential Target in Respiratory Diseases.

Peroxiredoxin 6 (PRDX6) is widely distributed in several organs, especially the lungs. The role of PRDX6 in oxidative stress is controversial and even contradictory, as indicated by research conducted over the past 20 years. PRDX6 has anti-oxidant or pro-oxidant effects on oxidative stress in different diseases. It can even exhibit both anti-oxidant and pro-oxidant effects in the same disease. These findings are attributed to the fact that PRDX6 is a multifunctional enzyme. The peroxidase and phospholipase A2 activity of PRDX6 is closely related to its anti-oxidant and pro-oxidant effects, which leads to the conflicting regulatory effects of PRDX6 on oxidative stress in respiratory diseases. Moreover, PRDX6 interacts with multiple redox signaling pathways to interfere with cell proliferation and apoptosis. PRDX6 has become a new target in respiratory disease research due to its important regulatory role in oxidative stress. In this paper, the role of PRDX6 in oxidative stress in respiratory diseases and the research progress in targeting PRDX6 are reviewed.

National Plan for Chronic Respiratory Diseases Prevention and Control in Iran.

Lower respiratory tract infections, chronic obstructive pulmonary disease (COPD), tuberculosis, and lung cancer are among the leading 10 causes of death worldwide. The Board of Respiratory Diseases Research Network (RDRN), a sub-committee of the Iranian Non-Communicable Diseases Committee (INCDC) is particularly concerned that there should be a coordinated National strategy to address the burden caused by chronic respiratory diseases. Iranian Ministry of Health and Medical Education (MoHME) has decided to give promotion to the establishment of research networks and use them as the milestones for research management, particularly for the national health priorities. National Service Framework (NSF), which was designed for Chronic Respiratory Diseases, is one of the main outcomes of the chronic respiratory diseases sub-committee of INCDC. The main seven strategies were represented by the Steering Committee in 2010 for a period of 10 years. Successful development and implementation of our goals provide the CRDs sub-committee of INCDC with the opportunity to develop a paradigm to prevent chronic respiratory diseases. A stronger national plan for controlling chronic respiratory diseases will ensure stronger advocacy to support respiratory health at national, sub-national, and regional levels.

A scientometrics study of the nanomedicines assisted in respiratory diseases.

Nanomedicine has been extensively studied for its versatility and broad-spectrum applications of theranostics in the research of respiratory disease. However, to the best of our knowledge, a scientometrics study based on the scientific knowledge assay of the overall situation on nanomedicine applied in the research of respiratory disease has not been reported so far, which would be of major importance to relevant researchers. To explore and exhibit the research status and developing trend of nanomedicines deployed in basic or clinical research in respiratory disease, the research ecosystem and exciting subareas were profiled based on the massive data mining and visualization from the relevant works reported from 2006 to 2021. Data were collected from the Web of Science database. Data statistics software and bibliometric analysis software were employed to visualize the research trend and the relationship between respiratory diseases and nanomedicines in each representative direction. The cluster analysis and burst detections indicated that the improvement of drug delivery and vaccine developments are the up-to-date key directions in nanomedicines for respiratory disease research and treatments. Furthermore, we emphatically studied four branch areas in this field including COVID-19, nanotube, respiratory syncytial virus, and mRNA vaccine those are selected for in-depth mining and bibliometric coupling analysis. Research trends signify the future focuses will center on preventing respiratory diseases with mRNA vaccines using nanoparticle-based approaches. We anticipate our study will enable researchers to have the panorama and deep insights in this area, thus inspiriting further exploitations especially the nanobiomaterial-based systems for theranostic applications in respiratory disease treatment.

Lung Organoids in Smoking Research: Current Advances and Future Promises.

Tobacco smoking has been established to contribute to the pathogenesis of various respiratory diseases including chronic obstructive pulmonary disease (COPD), lung cancer, and asthma. However, major hurdles in mechanistic studies on the role of smoking in human lungs remain in part due to the lack of ex vivo experimental models and ambiguous data from animal models that can best recapitulate the architecture and pathophysiology of the human lung. Recent development of the lung organoid culture system has opened new avenues for respiratory disease research as organoids are proving to be a sophisticated ex vivo model that functionally and structurally mimics the human lungs better than other traditionally used models. This review will discuss how recent advances in lung organoid systems may help us better determine the injurious and immunological effect of smoking on human lungs and will provide some suggestions for future research directions.

Transparency in Non-Technical Project Summaries to Promote the Three Rs in Respiratory Disease Research.

Non-Technical Project Summaries (NTS) are legal documents that were first introduced by the Directive 2010/63/EU to enhance transparency within scientific animal experimentation. Researchers intending to conduct biological research on animal models must fulfil the NTS requirements by outlining their proposed use of animals and how they plan to implement the Three Rs (replacement, reduction and refinement of animal use) in their experiments. This study outlines a novel systematic analysis approach that enables the assessment of NTS transparency based on the accuracy of reporting of certain Three Rs-specific information. This potentially customisable strategy could help toward the development of practical guidelines for use by Animal Welfare and Ethical Review Bodies (AWERBs) in establishments conducting animal research, in the process of scrutinising NTS during their pre-submission review of proposed licence applications. This could help to identify gaps in reporting of Three Rs-specific information relating to the planned animal experiments, which represents a remarkable step toward achieving greater openness in scientific communication. This study supports the concept that NTS transparency can promote the implementation of non-animal alternatives in fields where this is currently lacking, such as respiratory disease research. Although NTS were originally conceived as informative documents for a lay audience, we can conclude that data in NTS can be successfully used as a basis for systematic analysis. By reviewing the NTS, the experimental limitations of the currently available replacement strategies can also be highlighted, potentially pinpointing where there is a need for future method development.

Determining relevant risk factors associated with mid- and late-feeding-stage bovine respiratory disease morbidity in cohorts of beef feedlot cattle

Previous bovine respiratory disease (BRD) research has focused on events early in the feeding phase, but the objective of this study was to determine characteristics and risk factors associated with cohort-level BRD morbidity in the middle and late portions of the feeding phase.

Intratracheal administration of solutions in mice; development and validation of an optimized method with improved efficacy, reproducibility and accuracy

Animal models are still vital in the field of respiratory disease research. To improve the accuracy and consistency of the dose of specific compounds administered specifically in the respiratory tract, it is important to optimize and to compare the technique to currently available techniques. In this study, an optimized intubation-mediated intratracheal administration (IMIT) technique is described and compared to oropharyngeal aspiration (OA).Adult female Balb/c mice were treated with Evans Blue using IMIT or OA and sacrificed after a short recovery to observe the distribution of solutions throughout the lungs. Additionally, mice were treated with increasing doses of lipopolysaccharide (LPS) or saline to compare efficacy of both techniques. Inflammatory cell numbers in bronchoalveolar lavage were quantified 24 h post-administration.Evans Blue staining revealed a more homogeneous distribution and less variability among animals treated using IMIT as compared to OA. Higher inflammatory cell numbers were observed in IMIT mice compared to OA mice after exposure to vehicle or the lowest LPS concentration.This study shows that the optimized IMIT is superior to OA with regards to efficacy, reproducibility and accuracy. This IMIT method can be deployed to refine 3R animal welfare aspects of the experimental design and improve the reproducibility of respiratory disease mouse models.

Action Report of Chronic Respiratory Diseases Research sub-committee of INCDC, an Experience from Iran

Action Report of Chronic Respiratory Diseases Research sub-committee of INCDC, an Experience from Iran

Controlling the polarity of human gastrointestinal organoids to investigate epithelial biology and infectious diseases.

Human epithelial organoids-3D spheroids derived from adult tissue stem cells-enable investigation of epithelial physiology and disease and host interactions with microorganisms, viruses and bioactive molecules. One challenge in using organoids is the difficulty in accessing the apical, or luminal, surface of the epithelium, which is enclosed within the organoid interior. This protocol describes a method we previously developed to control human and mouse organoid polarity in suspension culture such that the apical surface faces outward to the medium (apical-out organoids). Our protocol establishes apical-out polarity rapidly (24-48 h), preserves epithelial integrity, maintains secretory and absorptive functions and allows regulation of differentiation. Here, we provide a detailed description of the organoid polarity reversal method, compatible characterization assays and an example of an application of the technology-specifically the impact of host-microbe interactions on epithelial function. Control of organoid polarity expands the possibilities of organoid use in gastrointestinal and respiratory health and disease research.

Exploring the 175-year history of spirometry and the vital lessons it can teach us today.

175 years have elapsed since John Hutchinson introduced the world to his version of an apparatus that had been in development for nearly two centuries, the spirometer. Though he was not the first to build a device that sought to measure breathing and quantify the impact of disease and occupation on lung function, Hutchison coined the terms spirometer and vital capacity that are still in use today, securing his place in medical history. As Hutchinson envisioned, spirometry would become crucial to our growing knowledge of respiratory pathophysiology, from Tiffeneau and Pinelli's work on forced expiratory volumes, to Fry and Hyatt's description of the flow-volume curve. In the 20th century, standardization of spirometry further broadened its reach and prognostic potential. Today, spirometry is recognized as essential to respiratory disease diagnosis, management and research. However, controversy exists in some of its applications, uptake in primary care remains sub-optimal and there are concerns related to the way in which race is factored into interpretation. Moving forward, these failings must be addressed, and innovations like Internet-enabled portable spirometers may present novel opportunities. We must also consider the physiologic and practical limitations inherent to spirometry and further investigate complementary technologies such as respiratory oscillometry and other emerging technologies that assess lung function. Through an exploration of the storied history of spirometry, we can better contextualize its current landscape and appreciate the trends that have repeatedly arisen over time. This may help to improve our current use of spirometry and may allow us to anticipate the obstacles confronting emerging pulmonary function technologies.