Treatment Of Chronic Respiratory Diseases Research Articles

Chronic Respiratory Diseases: Innovations in Treatment and Management

Chronic Respiratory Diseases (CRDs) include diseases of the airways and the lung and are among the major causes of morbidity and mortality worldwide. The major CRDs include asthma, chronic obstructive pulmonary disease (COPD), pulmonary sarcoidosis, pneumoconiosis and interstitial lung diseases (ILDs). The common symptoms of CRDs include wheezing, chest tightness, shortness of breath and cough [1]. These diseases affect millions of people across the globe and have significant impacts on patients’ quality of life and healthcare. Over the past few decades, however, improvement in the pharmacotherapy has provided a considerable progress. For example, biologics have given a new insight in the management of severe asthma by modulating certain inflammatory processes. Medications like omalizumab, dupilumab, and Mepolizumab are aimed at adjusting the immune response and significantly decrease the frequency of exacerbations and increase overall lung function. In addition, innovations in the field of stem cell therapy and tissue engineering are targeted to repair or replace diseased lung tissue, thus, being aimed at treating the origin of the diseases rather than simply alleviating the symptoms. Furthermore, Nanoparticles can be orally given, intravenously injected or inhaled using nanoparticle aerosols. Nanoparticles can also be used in the molecular imaging of chronic lung diseases such as COPD. Advanced inhalers, developed with sensors, can monitor the usage of medication and provide feedback in real-time to ensure compliance to prescriptions and other salient treatment plans. COPD pulmonary rehabilitation programs of exercise and education together with psychological support for individuals have been documented to enhance quality of life. The use of AI and a machine learning system has now moved to the ability to forecast disease exacerbations and provide individualized recommendations for treatment of CRDs. As a result, people with COPD receive care through various healthcare professions like doctors, nurses, and physiotherapists, which may have diverse roles, such as prescribing medications, supporting their self‐management or patient education, or delivering exercise training. The aim of an Integrated Disease Management (IDM) programme is that various aspects of care through which healthcare providers are working in coordination to deliver improved and optimum care to patients. Similarly Advancements in the treatment of ILD are being conducted, and recently, some new FDA-approved drugs have been advised for the management of patients. Among these are Nintedanib is a tyrosine kinase inhibitor, Pirfenidone an anti-fibrotic and anti-thrombotic agent and Treprostinil is an analogue of prostacyclin. These drugs have opened a new path for the treatment of ILD and have improved the recovery outcomes of patients [2]. Rituximab has also been found to be effective in more than half of patients treated in a small prospective open-label trial of refractory pulmonary disease in sarcoidosis[3]. Overall, there is a renewed emphasis on CRD management as a burgeoning field. With the advancement in the research in the personalized, proactive and integrative strategy the efforts made will lay down new avenues of better health outcomes for millions of people suffering from the CRDs. The future of respiratory health is bright as it is a growing field that has no sign of discontinuing its steady development and pushing for the comforts and breakthroughs for many patients across the globe.

Digital voice-based biomarker for monitoring respiratory quality of life: findings from the colive voice study

Regular monitoring of respiratory quality of life (RQoL) is essential in respiratory healthcare, facilitating prompt diagnosis and tailored treatment for chronic respiratory diseases. Voice alterations resulting from respiratory conditions create unique audio signatures that can potentially be utilized for disease screening or monitoring. Analyzing data from 1908 participants from the Colive Voice study, which collects standardized voice recordings alongside comprehensive demographic, epidemiological, and patient-reported outcome data, we evaluated various strategies to estimate RQoL from voice, including handcrafted acoustic features, standard acoustic feature sets, and advanced deep audio embeddings derived from pretrained convolutional neural networks. We compared models using clinical features alone, voice features alone, and a combination of both. The multimodal model combining clinical and voice features demonstrated the best performance, achieving an accuracy of 70.8% and an area under the receiver operating characteristic curve (AUROC) of 0.77; an improvement of over 5% in terms of accuracy and 7% in terms of AUROC compared to model utilizing voice features alone. Incorporating vocal biomarkers significantly enhanced the predictive capacity of clinical variables across all acoustic feature types, with a net classification improvement (NRI) of up to 0.19. Our digital voice-based biomarker is capable of accurately predicting RQoL, either as an alternative to or in conjunction with clinical measures, and could be used to facilitate rapid screening and remote monitoring of respiratory health status.

Microbiota of the upper respiratory tract in children with chronic adenoiditis

Background. Routine application of the GC-MS method to assess the URT microbiota can potentially improve the efficacy and safety of treatment for chronic respiratory diseases.
 Aim. To perform a comparative analysis of the microbiota from the surface of the pharyngeal tonsil, from the deep parts of the nose, and saliva in children with chronic adenoiditis.
 Materials and methods. The study included 90 patients with chronic adenoiditis (CA) and/or pharyngeal tonsil hypertrophy (PTH). All study participants had swabs taken from the surface of the pharyngeal tonsil, from the deep parts of the nasal cavity, and saliva as a biological fluid of the oral cavity. Microorganisms were identified by specific fatty acids using GC-MS to assess the composition of the microbial community on the surface of the pharyngeal tonsil.
 Results. The study showed that the microbiota of the nasopharynx is identical in its qualitative composition to microorganisms from the deep parts of the nose. However, according to the results of the analysis of microbial markers of saliva, the oral microbiota showed significant differences in the quantitative and qualitative composition of microorganisms compared with the nasopharyngeal microbiota.
 Conclusion. The introduction of the GC-MS method for assessing the URT microbiota enables its monitoring in clinical practice for the treatment of chronic respiratory system diseases without disturbing the ecology of the mucous membranes and the whole body.

Role of the Fungus Pneumocystis in IL1β Pathway Activation and Airways Collagen Deposition in Elastase-Induced COPD Animals.

Inflammation and mucus production are prevalent characteristics of chronic respiratory conditions, such as asthma and chronic chronic obstructive pulmonary disease (COPD). Biological co-factors, including bacteria, viruses, and fungi, may exacerbate these diseases by activating various pathways associated with airway diseases. An example is the fungus Pneumocystis, which is linked to severe COPD in human patients. Recent evidence has demonstrated that Pneumocystis significantly enhanced inflammation and mucus hypersecretion in a rat model of elastase-induced COPD. The present study specifically aims to investigate two additional aspects associated with the pathology induced by Pneumocystis infection: inflammation and collagen deposition around airways. To this end, the focus was to investigate the role of the IL-1β pro-inflammatory pathway during Pneumocystis infection in COPD rats. Several airway pathology-related features, such as inflammation, mucus hypersecretion, and fibrosis, were evaluated using histological and molecular techniques. COPD animals infected with Pneumocystis exhibited elevated inflammation levels, including a synergistic increase in IL-1β and Cox-2. Furthermore, protein levels of the IL-1β-dependent transcription factor cAMP response element-binding (CREB) showed a synergistic elevation of their phosphorylated version in the lungs of COPD animals infected with Pneumocystis, while mucus levels were notably higher in the airways of COPD-infected animals. Interestingly, a CREB responsive element (CRE) was identified in the Muc5b promoter. The presence of CREB in the Muc5b promoter was synergistically increased in COPD animals infected with Pneumocystis compared to other experimental groups. Finally, an increment of deposited collagen was identified surrounding the airways of COPD animals infected with Pneumocystis compared with the other experimental animal groups and correlated with the increase of Tgfβ1 mRNA levels. These findings emphasize the role of Pneumocystis as a potential biological co-factor in chronic respiratory diseases like COPD or asthma, warranting new perspectives in the treatment of chronic respiratory diseases.

New perspectives on advances in diagnosis through imaging in chronic respiratory diseases: a systematic literature review

Background: Chronic respiratory diseases, such as asthma, chronic obstructive pulmonary disease (COPD), interstitial lung disease, and cystic fibrosis, present substantial global health challenges. This systematic review explores recent advances in imaging-based diagnostic methods for these conditions, emphasizing high-resolution computed tomography (HRCT), magnetic resonance imaging (MRI), positron emission tomography (PET), and artificial intelligence (AI). Methodology: A systematic search of databases identified studies published in the last five years, focusing on innovative imaging techniques for chronic respiratory diseases. Inclusion criteria emphasized diagnostic accuracy and advancements in imaging modalities. Results: Seven studies were included, covering interventions in intensive care, mesenchymal stem cell therapy for COVID-19-induced acute respiratory distress syndrome (ARDS), endovascular treatment for aortic arch aneurysms, and lung cancer screening. MSC therapy demonstrated positive outcomes in ARDS patients, while endovascular repair showed technical success. LungSEARCH highlighted the effectiveness of lung cancer screening in high-risk populations. Discussion: Recent imaging technologies, including HRCT, MRI, PET, and AI, have revolutionized chronic respiratory disease diagnosis. The review emphasizes their clinical applications, impact on patient outcomes, and potential for personalized medicine. AI enhances image analysis accuracy, yet challenges like cost and interpretation discrepancies persist. Conclusion: Imaging technologies, particularly HRCT, MRI, PET, and AI, show promise in improving diagnostic accuracy and personalized treatment for chronic respiratory diseases. Collaboration among healthcare professionals, researchers, and industry stakeholders is crucial for addressing challenges and ensuring widespread access to advanced diagnostic tools. Future directions involve refining imaging methods for routine clinical integration, advancing patient care, and reducing the burden of respiratory diseases.

Discovery and Identification of Novel 5-Hydroxy-4H-benzo[1,4]oxazin-3-one Derivatives as Potent β2-Adrenoceptor Agonists through Structure-Based Design, Synthesis, and Biological Evaluation.

Although β2-agonists are crucial for treatment of chronic respiratory diseases, optimizing β2-agonistic activity and selectivity remains essential for achieving favorable therapeutic outcomes. A structure-based molecular design workflow was employed to discover a novel class of β2 agonists featuring a 5-hydroxy-4H-benzo[1,4]oxazin-3-one scaffold, which potently stimulated β2 adrenoceptors (β2-ARs). Screening for the β2-agonistic activity and selectivity led to the identification of compound A19 (EC50 = 3.7 pM), which functioned as a partial β2-agonist in HEK-293 cells containing endogenous β2-ARs. Compound A19 exhibited significant relaxant effects, rapid onset time (Ot50 = 2.14 min), and long duration of action (>12 h) on isolated guinea pig tracheal strips, as well as advantageous pharmacokinetic characteristics in vivo, rendering A19 suitable for inhalation administration. Moreover, A19 suppressed the upregulation of inflammatory cytokines and leukocytes and improved lung function in a rat model of COPD, thereby indicating that A19 is a potential β2 agonist candidate for further study.

Emerging Role of Precision Medicine in Diagnosis and Treatment of Chronic Respiratory Disease

Precision medicine is the current approach to managing chronic respiratory diseases, especially asthma and chronic obstructive pulmonary disease (COPD). It involves the evaluation of genetic, environmental, and lifestyle variations for each patient. It requires valid and specific biomarkers obtained through genetic studies, biomolecular technology, and omics-based technology to determine targeted therapies. Asthma and COPD have heterogeneous clinical phenotype variations, and giving one standard treatment for asthma and COPD may not necessarily provide the same effectiveness to other patients. The endotype, a specific molecular mechanism in disease pathogenesis, is essential in phenotype variation. The role of precision medicine in asthma and COPD is to determine endotypes through specific biomarkers and to provide specific targeted therapy for achieving personalized treatment in each patient. The application of precision medicine not only provides precise diagnosis and treatment but also enables early detection in individuals at risk and prevention of progression and exacerbation in asthma and COPD.

Zang Siwei Qingfei Mixture Alleviates Pulmonary Arterial Hypertension in Rats: Integrated Network Pharmacology and Metabolomics

Purpose: Pulmonary arterial hypertension (PAH) is a fatal condition characterized by poor control of pulmonary hemodynamics and vascular development. Zang Siwei Qingfei mixture (ZSQM) is a traditional Chinese medicine formula used for the treatment of chronic respiratory diseases. However, the underlying mechanism of ZSQM for treating PAH remains unclear.Methods: A PAH rat model was established after monocrotaline (MCT) injection, and pulmonary hemodynamic features and pathological changes were evaluated. The candidate targets of ZSQM against PAH were discovered using network pharmacology. Then, molecular docking was used to validate the discovered key targets. Moreover, serum metabolomics was used to identify differential metabolites. The metabolomics and network pharmacology integrated network was constructed.Results: ZSQM alleviated MCT‐induced pulmonary vascular injury and vascular remodeling. We found ZSQM core component chrysin and six hub genes according to network pharmacology, including CYP2C19, CASP8, PTK2, VEGFA, FLT4, and TNNI3. Molecular docking revealed strong binding affinities between key targets and chrysin. Meanwhile, western blotting results validated significant changes in the expression of these key targets. Subsequently, we confirmed that chrysin existed in the ZSQM by HPLC–MS. In addition, a total of 19 metabolites with potential significance were identified to be implicated in the therapeutic mechanisms of ZSQM. The further integrated analysis indicated an interconnection between these key targets, their related core metabolites (12(S)HETE, ascorbate, succinate, vitamin C, and L‐arginine), and metabolic pathways.Conclusion: The study, employing metabolomics and network pharmacology, has concluded that ZSQM has the potential to enhance the treatment of PAH by targeting multiple pathways and molecular targets. This finding suggests that ZSQM could serve as a promising alternative therapy for PAH.

Berberine-loaded engineered nanoparticles attenuate TGF-β-induced remodelling in human bronchial epithelial cells

Airway remodelling occurs in chronic respiratory diseases (CRDs) such as asthma and chronic obstructive pulmonary disease (COPD). It is characterized by aberrant activation of epithelial reparation, excessive extracellular matrix (ECM) deposition, epithelial-to-mesenchymal transition (EMT), and airway obstruction. The master regulator is Transforming Growth Factor-β (TGF-β), which activates tissue repair, release of growth factors, EMT, increased cell proliferation, and reduced nitric oxide (NO) secretion. Due to its fundamental role in remodelling, TGF-β is an emerging target in the treatment of CRDs. Berberine is a benzylisoquinoline alkaloid with antioxidant, anti-inflammatory, and anti-fibrotic activities whose clinical application is hampered by poor permeability. To overcome these limitations, in this study, berberine was encapsulated in monoolein-based liquid crystalline nanoparticles (BM-LCNs). The potential of BM-LCNs in inhibiting TGF-β-induced remodelling features in human bronchial epithelial cells (BEAS-2B) was tested. BM-LCNs significantly inhibited TGF-β-induced migration, reducing the levels of proteins upregulated by TGF-β including endoglin, thrombospondin-1, basic fibroblast growth factor, vascular-endothelial growth factor, and myeloperoxidase, and increasing the levels of cystatin C, a protein whose expression was downregulated by TGF-β. Furthermore, BM-LCNs restored baseline NO levels downregulated by TGF-β. The results prove the in vitro therapeutic efficacy of BM-LCNs in counteracting TGF-β-induced remodelling features. This study supports the suitability of berberine-loaded drug delivery systems to counteract airway remodelling, with potential application as a treatment strategy against CRDs.

Disease burden and risk factors of chronic respiratory diseases in Jiangsu Province from 1990 to 2019

Objective: To analyze the prevalence and the trend of the disease burden of chronic respiratory diseases and relevant risk factors in Jiangsu province from 1990 to 2019 and provide evidence for the prevention and treatment of chronic respiratory diseases. Methods: The data from the 2019 Global Burden of Disease Study (GBD2019) were used to calculate the prevalence rate, mortality rate and disability-adjusted life year (DALY) rate. Software Joinpoint was used to calculate the annual percent change (APC) and average annual percent change (AAPC) of the standardized prevalence rate, standardized mortality rate and standardized DALY rate. The population attributable fractions (PAF) were used to estimate the proportion of chronic respiratory disease caused by different risk factors. Results: In 1990 and 2019, the prevalence rates of chronic respiratory diseases were 4.83% and 5.45%. The mortality rates were 134.91/100 000 and 80.99/100 000 respectively, and the DALY rates were 2 678.52/100 000 and 1 534.31/100 000 respectively. From 1990 to 2019, the age-standardized prevalence rate, mortality rate and DALY rate in Jiangsu showed a significant downward trend (AAPC values were -0.90%, -5.28% and -4.70% respectively, P<0.05). Tobacco use was the leading cause of chronic respiratory diseases, followed by air pollution, occupational exposure, suboptimal temperature and high BMI. Compared with 1990, the proportion of DALYs of chronic respiratory diseases attributable to tobacco use and high BMI increased in 2019. Conclusion: The overall burden of chronic respiratory diseases in Jiangsu shows a downward trend. Prevention and health education should be focused on the population with a smoking history and high BMI. At the same time, environmental management, attention to suboptimal temperature and control of occupational exposure factors should also be adopted as important means to prevent and control chronic respiratory diseases.

The Impact of Long-Term Macrolide Exposure on the Gut Microbiome and Its Implications for Metabolic Control.

Long-term low-dose macrolide therapy is now widely used in the treatment of chronic respiratory diseases for its immune-modulating effects, although the antimicrobial properties of macrolides can also have collateral impacts on the gut microbiome. We investigated whether such treatment altered intestinal commensal microbiology and whether any such changes affected systemic immune and metabolic regulation. In healthy adults exposed to 4 weeks of low-dose erythromycin or azithromycin, as used clinically, we observed consistent shifts in gut microbiome composition, with a reduction in microbial capacity related to carbohydrate metabolism and short-chain fatty acid biosynthesis. These changes were accompanied by alterations in systemic biomarkers relating to immune (interleukin 5 [IL-5], IL-10, monocyte chemoattractant protein 1 [MCP-1]) and metabolic (serotonin [5-HT], C-peptide) homeostasis. Transplantation of erythromycin-exposed murine microbiota into germ-free mice demonstrated that changes in metabolic homeostasis and gastrointestinal motility, but not systemic immune regulation, resulted from changes in intestinal microbiology caused by macrolide treatment. Our findings highlight the potential for long-term low-dose macrolide therapy to influence host physiology via alteration of the gut microbiome. IMPORTANCE Long-term macrolide therapy is widely used in chronic respiratory diseases although its antibacterial activity can also affect the gut microbiota, a key regulator of host physiology. Macrolide-associated studies on the gut microbiota have been limited to short antibiotic courses and have not examined its consequences for host immune and metabolic regulation. This study revealed that long-term macrolides depleted keystone bacteria and impacted host regulation, mediated directly by macrolide activity or indirectly by alterations to the gut microbiota. Understanding these macrolide-associated mechanisms will contribute to identifying the risk of long-term exposure and highlights the importance of targeted therapy for maintenance of the gut microbiota.

Targeting protein glycosylation to regulate inflammation in the respiratory tract: novel diagnostic and therapeutic candidates for chronic respiratory diseases.

Protein glycosylation is a widespread posttranslational modification that can impact the function of proteins. Dysregulated protein glycosylation has been linked to several diseases, including chronic respiratory diseases (CRDs). CRDs pose a significant public health threat globally, affecting the airways and other lung structures. Emerging researches suggest that glycosylation plays a significant role in regulating inflammation associated with CRDs. This review offers an overview of the abnormal glycoenzyme activity and corresponding glycosylation changes involved in various CRDs, including chronic obstructive pulmonary disease, asthma, cystic fibrosis, idiopathic pulmonary fibrosis, pulmonary arterial hypertension, non-cystic fibrosis bronchiectasis, and lung cancer. Additionally, this review summarizes recent advances in glycomics and glycoproteomics-based protein glycosylation analysis of CRDs. The potential of glycoenzymes and glycoproteins for clinical use in the diagnosis and treatment of CRDs is also discussed.

Compatibility and aerosol characteristics of beclomethasone mixed with N-acetylcysteine

Mixing different kind inhalation medications for simultaneous inhalation is widely used in the treatment of chronic respiratory diseases, and it can minimize the administration time and improve patient adherence. To our knowledge, it is unclear whether beclomethasone (BDP, Clenil®) can bemixed with acetylcysteine (NAC, Fluimucil®), because the in vitro physico-chemical compatibility and aerosol characteristics of the mixture are unknown. In this study, we investigated physical compatibility, including the appearance, pH, osmotic pressure and chemical stability, as well as aerosol characteristics, including particle size corresponding to 10%/50%/90% of the cumulative percentage of total particle volume (X10/X50/X90), volume median droplet diameter (VMD), mass median aerodynamic diameter (MMAD), fine particle fraction (FPF), fine particle dose (FPD) and geometric standard deviation (GSD), delivery rate, and total delivery of the above solutions. After mixing, there were no significant changes in visual appearance, pH, osmolality and drug content of the mixtures at room temperature for 12 h. The FDP of BDP in the mixture decreased by 16.49%, whereas the NAC increased by 10.85%. The delivery rates of BDP and NAC in the mixture decreased by 66.05% and 45.54%, and total delivery increased by 13.20% and 25.29%, respectively. However, the MMAD, FPF, particle size and GSD of the mixture were almost unchanged. We demonstrated that these admixtures are physico-chemically compatible but that coadministration of beclomethasone with acetylcysteine can markedly affect output and aerosol characteristics.

Progress of researches on anti-inflammatory mechanism of acupuncture underlying amelioration of chronic respiratory diseases

In recent years, acupuncture has gained great progress in the treatment of chronic respiratory diseases (CRD), and the clinical effect is remarkable, but its underlying mechanisms are relatively complex, with the anti-inflammatory effect being the primary aspect. Based on the literature both at home and abroad, we found that the anti-inflammatory mechanism of acupuncture mainly involves chemokines, kinase-related pathways, helper T cells, epigenetic modification, autophagy, vagal-mediated cholinergic anti-inflammatory pathway, etc. The researches on some anti-inflammatory mechanisms are still in the initial stage, the relationship among various pathways, and the key factors affecting the effect of acupuncture, such as acupoint selection, stimulation intensity and needling depth, etc. warrant further exploration in the future.

Bacterial Contamination of Inhalation Chambers Used for Cats and Dogs with Chronic Airway Diseases.

Inhalation chambers (ICs) are regularly used in veterinary medicine for the inhalative treatment of chronic respiratory diseases in dogs and cats. Since therapy is usually required lifelong and daily, devices are frequently in use. The aim of this study was to identify bacterial contamination of ICs used for cats and dogs in relation to the applied cleaning measures. Swabs from ICs of 66 cats and 19 dogs with chronic airway diseases were obtained using a standardized protocol and subsequently cultured. A questionnaire was completed by the pet owners regarding the history of their pet's illness and applied device cleaning measures. Overall, 64% (54/86) of the ICs were found to be contaminated; the mask was significantly (p < 0.001) more often contaminated than other device parts. Most cultured bacteria were environmental contaminants; however, some harbored pathogenic potential. Cleaning frequency and method did not significantly influence the presence of contamination. Bacterial contamination of ICs, used for cats and dogs, is common but is not significantly influenced by the type or frequency of cleaning. To avoid potential infection by opportunistic bacteria, the instruction of pet owners regarding the maintenance of the ICs is recommended.

Development of Approaches to the Prevention and Treatment of Chronic Respiratory Diseases

The article investigates measures in the field of prevention and treatment of chronic respiratory diseases. The author notes that preventive measures in the field of reducing the incidence of chronic respiratory diseases, as well as preventive measures in this area will significantly reduce their spread, which will improve the level of efficiency and quality of life of people and will positively affect labor productivity, which is undoubtedly extremely important for the economy of any state. In addition, the social results of the above measures will have a positive impact on the overall public health and indirectly make a significant contribution to the country’s GDP

In silico and in vitro ADME-Tox analysis and in vivo pharmacokinetic study of representative pan-PDE inhibitors from the group of 7,8-disubstituted derivatives of 1,3-dimethyl-7H-purine-2,6-dione

Phosphodiesterase (PDE) inhibitors represent a wide class of chemically different compounds that have been extensively studied in recent years. Their anti-inflammatory and anti-fibrotic effects are particularly desirable in the treatment of chronic respiratory diseases, including asthma and chronic obstructive pulmonary disease (COPD). Due to diversified expression of individual PDEs within cells and/or tissues as well as PDE signaling compartmentalization, pan-PDE inhibitors (compounds capable of simultaneously blocking various PDE subtypes) are of particular interest. Recently, a large group of 7,8-disubstituted derivatives of 1,3-dimethyl-7H-purine-2,6-dione (theophylline) was designed and synthesized. These compounds were characterized as potent pan-PDE inhibitors and their prominent anti-inflammatory and anti-fibrotic activity in vitro has been proved. Herein, we investigated a general in vitro safety profile and pharmacokinetic characteristics of two leading compounds from this group: a representative compound with N′-benzylidenebutanehydrazide moiety (38) and a representative derivative containing N-phenylbutanamide fragment (145). Both tested pan-PDE inhibitors revealed no cytotoxic, mutagenic, and genotoxic activity in vitro, showed moderate metabolic stability in mouse and human liver microsomes, as well as fell into the low or medium permeation category. Additionally, 38 and 145 revealed a lack of interaction with adenosine receptors, including A1, A2A, and A2B. Pharmacokinetic analysis revealed that both tested 7,8-disubstituted derivatives of 1,3-dimethyl-7H-purine-2,6-dione were effectively absorbed from the peritoneal cavity. Simultaneously, they were extensively distributed to mouse lungs and after intraperitoneal (i.p.) administration were detected in bronchoalveolar lavage fluid. These findings provide evidence that investigated compounds represent a new drug candidates with a favorable in vitro safety profile and satisfactory pharmacokinetic properties after a single i.p. administration. As the next step, further pharmacokinetic studies after multiple i.p. and p.o. doses will be conducted to ensure effective 38 and 145 serum and lung concentrations for a longer period of time. In summary, 7,8-disubstituted derivatives of 1,3-dimethyl-7H-purine-2,6-dione represent a promising compounds worth testing in animal models of chronic respiratory diseases, the etiology of which involves various PDE subtypes.

Acupuncture for dyspnea and breathing physiology in chronic respiratory diseases: A protocol of a systematic review and meta-analysis of randomized controlled trials.

Background:Dyspnea is one of the most common symptoms of chronic respiratory disease (CRD) and is closely related to increased functional disability and mortality, resulting in substantial adverse outcomes on patients and imposing great social and economic burden. Although multiple clinical trials and systematic reviews have suggested that acupuncture could be effective in treating COPD and lung cancer, little is known about its effects on dyspnea relief in patients with CRD. The present study aimed to use a systematic review approach to evaluate the effectiveness and safety of acupuncture in the treatment of dyspnea in patients with CRD.Methods:We will search the following 9 databases from inception to June 30, 2022, PubMed, Web of Science, EMBASE, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, WANFANG Database, Chinses Scientific and Technological Periodical Database, and Chinese Biomedical Database, and the Cochrane Library Database. Clinical randomized controlled trials in English or Chinese that evaluate invasive acupuncture versus control group in treatment of CRD with dyspnea will be included. The primary outcome will be dyspnea scores, breathing physiological function, and the secondary outcomes include exercise tolerance by six-minute walk distance quality of life, quality of life and adverse events. Two reviewers will independently conduct study selection, data extraction and quality assessment. The Review Manager software will be used for meta-analysis. This protocol will be carried out in accordance with the PRISMA-P guidance.Conclusion:This systematic review and meta-analysis will provide the evidence of whether acupuncture is an effective and safe intervention for CRD with dyspnea. The results will be disseminated through peer-reviewed publication.

Unravelling the Therapeutic Potential of Nano-Delivered Functional Foods in Chronic Respiratory Diseases.

Chronic inflammation of the respiratory tract is one of the most concerning public health issues, as it can lead to chronic respiratory diseases (CRDs), some of which are more detrimental than others. Chronic respiratory diseases include chronic obstructive pulmonary disease (COPD), asthma, lung cancer, and pulmonary fibrosis. The conventional drug therapies for the management and treatment of CRDs only address the symptoms and fail to reverse or recover the chronic-inflammation-mediated structural and functional damage of the respiratory tract. In addition, the low efficacy and adverse effects of these drugs have directed the attention of researchers towards nutraceuticals in search of potential treatment strategies that can not only ameliorate CRD symptoms but also can repair and reverse inflammatory damage. Hence, there is a growing interest toward investigating the medicinal benefits of nutraceuticals, such as rutin, curcumin, zerumbone, and others. Nutraceuticals carry many nutritional and therapeutic properties, including anti-inflammatory, antioxidant, anticancer, antidiabetic, and anti-obesity properties, and usually do not have as many adverse effects, as they are naturally sourced. Recently, the use of nanoparticles has also been increasingly studied for the nano drug delivery of these nutraceuticals. The discrete size of nanoparticles holds great potential for the level of permeability that can be achieved when transporting these nutraceutical compounds. This review is aimed to provide an understanding of the use of nutraceuticals in combination with nanoparticles against CRDs and their mechanisms involved in slowing down or reversing the progression of CRDs by inhibiting pro-inflammatory signaling pathways.

Extracellular HMGB1 as Inflammatory Mediator in the Progression of Mycoplasma Gallisepticum Infection.

High-mobility group box 1 (HMGB1), a member of damage-associated molecular patterns (DAMPs), is involved in the immune regulation of several infectious diseases. Mycoplasma gallisepticum (MG) infection is proved to cause an abnormal immune response, but the role of HMGB1 in MG-induced chronic respiratory disease (CRD) is unclear. In this study, we found that HMGB1 was released from the nucleus to the extracellular in macrophages upon infection with MG. Extracellular HMGB1 bound to TLR2 activating the NF-κB pathway triggering a severe inflammatory storm and promoting the progression of MG infection. More importantly, TLR4 could be activated by HMGB1 to trigger immune disorders after TLR2 was silenced. This disease process could be interrupted by ethyl pyruvate (EP) inhibition of HMGB1 release or glycyrrhizic acid (GA). Furthermore, treatment of MG-infected chickens with GA significantly alleviated immune organ damage. In conclusion, we demonstrate that HMGB1 is secreted extracellularly to form an inflammatory environment upon MG infection, triggering a further cellular inflammatory storm in a positive feedback approach. Blocking MG-induced HMGB1 release or suppression downstream of the HMGB1-TLR2/TLR4 axis may be a promising novel strategy for the treatment of CRD. Furthermore, this study may provide a theoretical reference for understanding non-LPS-activated TLR4 events.