CLINICAL MANAGEMENT OF CHRONIC ORANGUTAN RESPIRATORY DISEASE SYNDROME IN THREE ADULT MALE BORNEAN ORANGUTANS (PONGO PYGMAEUS).

Orangutan respiratory disease syndrome (ORDS) is a disease unique to orangutans (Pongo sp), characterized by chronic bacterial infection and inflammation of any region or combination of regions of the respiratory tract, including the sinuses, air sacs, cranial bones, airways, and lung parenchyma. Aggressive early intervention during a first episode may prevent progression to chronic disease. However, in the setting of an established chronic disease, intermittent acute exacerbations are associated with worsening symptoms and increased infection and inflammation. ORDS is ultimately fatal due to loss of respiratory function resulting from chronic structural damage. Utilizing potentially lifelong medications to slow the progression of chronic, destructive inflammation in the respiratory tract, chronic treatment is aimed at stabilizing the animals' respiratory function, decreasing the frequency of recurrent exacerbations, and improving their general well-being. Three adult male Bornean orangutans (Pongo pygmaeus) housed at an orangutan rehabilitation and reintroduction center in Indonesia have long histories of recurrent respiratory disease. Each underwent CT scans confirming ORDS with chronic airway disease prior to initiation of a long-term treatment protocol. Based on data-driven medical management of bronchiectasis in humans, the three orangutans have been treated with long-term combination regimens of oral azithromycin, nebulized salbutamol, and nebulized hypertonic saline. Follow-up CT scans in all three animals at least 1 yr following treatment initiation showed improvements throughout their respiratory tracts. The duration of each exacerbation period decreased, and the orangutans have longer symptom-free periods compared to before the start of treatment. At an average of 5 yr into the long-term treatment protocol, all three orangutans are thriving. Chronic medical management of ORDS modeled after human treatment of bronchiectasis has been efficacious in these three orangutans and encourages further study of this approach.

Exploring the Potential of Asl-us-Soos (Glycyrrhiza glabra L.) in the Treatment of Respiratory Diseases-An Ethnomedicinal and Pharmacological Review.

Background: Asl-us-Soos (Glycyrrhiza glabra L.) has been used as a therapeutic agent in the treatment of respiratory, digestive, and neurological disorders since ancient times in Unani Medicine. Its therapeutic uses have been documented in Unani pharmacopeia, classical textbooks, and manuscripts based on experience in clinical practices. Asl-us-Soos (AS) and its compound preparations are recommended in the treatment of respiratory diseases such as Dhat al-Janb (pleurisy), Dhat al-Ri'a (pneumonia), Jamod us Sadr (pulmonary apoplexy), Diq al-Nafas (asthma), Sil (thiasis), and Diq (pulmonary tuberculosis). Objectives: This review aimed to provide insight into ethno-medicinal uses, pharmacological activities, and phytochemical profile of AS. The review also highlights the prospects in the development of potential drug molecules for various respiratory ailments. Methods: This review is based on a search of authentic Unani classical literature and major databases such as Science Direct, Medline (via PubMed), Google Scholar, Scopus, and Web of Science. The studies published between January 2001 and February 2022 were included in this study. Results: This review found that AS had medicinal uses in various respiratory disorders. Its roots are used as single drug and compound formulations for the treatment of dry cough, bronchial asthma, bronchitis, and pneumonia. In addition, AS contains active phytoconstituents such as glycyrrhizin (glycyrrhizic acid), isoliquiritigenin, glabridin, and licochalcone A. They have been extensively studied using in vitro and in vivo models and were found to exhibit pharmacological effects in pulmonary tuberculosis, pulmonary carcinoma, emphysema, bronchial asthma, pneumonia, and upper respiratory tract infections. Moreover, glycyrrhizin has been found to possess therapeutic potential against COVID-19. Conclusion: This review concludes that AS is a potent anti-tumor, anti-inflammatory, anti-microbial, anti-oxidant, expectorant, and antitussive drug. This plant could be an important source for the development of new drug compounds for various respiratory diseases.

The role of histone deacetylases in inflammatory respiratory diseases: an update.

INTRODUCTION: Histone deacetylases (HDACs) catalyze the removal of acetyl groups from lysine residues of histones and other proteins, generally leading to a closed chromosomal configuration and transcriptional repression. Different HDACs have distinct substrate specificities and functions in different biological processes. Accumulating evidence indicates that HDACs play a key role in the pathogenesis of multiple respiratory diseases. AREAS COVERED: After an extensive search of the PubMed database, Web of Science and ClinicalTrials.gov, covering the period from 1992 to 2024, this review summarizes recent advances in understanding the role of HDACs in inflammatory respiratory diseases, including allergic rhinitis (AR), chronic rhinosinusitis (CRS), asthma and chronic obstructive pulmonary disease (COPD). We also examine recent progress on the efficacy and potential use of histone deacetylase inhibitors (HDACi) for the treatment of these diseases. EXPERT OPINION: Available data indicate that HDACs play an important role in the development of common inflammatory respiratory diseases, and HDACi have shown promise as treatments for these diseases. However, the exact roles and underlying mechanisms of specific HDACs in disease pathogenesis require further study. Additional work is necessary to develop novel potent HDACi with high isoform selectivity.

Targeting ferroptosis using Chinese herbal compounds to treat respiratory diseases.

BACKGROUND: Respiratory diseases pose a grave threat to human life. Therefore, understanding their pathogenesis and therapeutic strategy is important. Ferroptosis is a novel type of iron-dependent programmed cell death, distinct from apoptosis, necroptosis, and autophagy, characterised by iron, reactive oxygen species, and lipid peroxide accumulation, as well as glutathione (GSH) depletion and GSH peroxidase 4 (GPX4) inactivation. A close association between ferroptosis and the onset and progression of respiratory diseases, including chronic obstructive pulmonary disease, acute lung injury, bronchial asthma, pulmonary fibrosis, and lung cancer, has been reported. Recent studies have shown that traditional Chinese medicine (TCM) compounds exhibit unique advantages in the treatment of respiratory diseases owing to their natural properties and potential efficacy. These compounds can effectively regulate ferroptosis by modulating several key signalling pathways such as system Xc- -GSH-GPX4, NCOA4-mediated ferritinophagy, Nrf2-GPX4, and Nrf2/HO-1, thus playing a positive role in improving respiratory diseases. PURPOSE: This comprehensive review systematically outlines the regulatory role of ferroptosis in the onset and progression of respiratory diseases and provides evidence for treating respiratory diseases by targeting ferroptosis with TCM compounds. These insights aim to offer potential remedies for the clinical prevention and treatment of respiratory diseases. STUDY DESIGN AND METHODS: We searched scientific databases PubMed, Web of Science, Scopus, and CNKI using keywords such as "ferroptosis","respiratory diseases","chronic obstructive pulmonary disease","bronchial asthma","acute lung injury","pulmonary fibrosis","lung cancer","traditional Chinese medicine","traditional Chinese medicine compound","monomer", and "natural product" to retrieve studies on the therapeutic potential of TCM compounds in ameliorating respiratory diseases by targeting ferroptosis. The retrieved data followed PRISMA criteria (preferred reporting items for systematic review). RESULTS: TCM compounds possess unique advantages in treating respiratory diseases, stemming from their natural origins and proven clinical effectiveness. TCM compounds can exert therapeutic effects on respiratory diseases by regulating ferroptosis, which mainly involves modulation of pathways such as system Xc- -GSH-GPX4,NCOA4-mediated ferritinophagy, Nrf2-GPX4, and Nrf2/HO-1. CONCLUSION: TCM compounds have demonstrated promising potential in improving respiratory diseases through the regulation of ferroptosis. The identification of specific TCM-related inducers and inhibitors of ferroptosis holds great significance in developing more effective strategies. However, current research remains confined to animal and cellular studies, emphasizing the imperative for further verifications through high-quality clinical data.

Exploring the Role of Lactoferrin in Managing Allergic Airway Diseases among Children: Unrevealing a Potential Breakthrough.

The prevalence of allergic diseases has dramatically increased among children in recent decades. These conditions significantly impact the quality of life of allergic children and their families. Lactoferrin, a multifunctional glycoprotein found in various biological fluids, is emerging as a promising immunomodulatory agent that can potentially alleviate allergic diseases in children. Lactoferrin's multifaceted properties make it a compelling candidate for managing these conditions. Firstly, lactoferrin exhibits potent anti-inflammatory and antioxidant activities, which can mitigate the chronic inflammation characteristic of allergic diseases. Secondly, its iron-binding capabilities may help regulate the iron balance in allergic children, potentially influencing the severity of their symptoms. Lactoferrin also demonstrates antimicrobial properties, making it beneficial in preventing secondary infections often associated with respiratory allergies. Furthermore, its ability to modulate the immune response and regulate inflammatory pathways suggests its potential as an immune-balancing agent. This review of the current literature emphasises the need for further research to elucidate the precise roles of lactoferrin in allergic diseases. Harnessing the immunomodulatory potential of lactoferrin could provide a novel add-on approach to managing allergic diseases in children, offering hope for improved outcomes and an enhanced quality of life for paediatric patients and their families. As lactoferrin continues to capture the attention of researchers, its properties and diverse applications make it an intriguing subject of study with a rich history and a promising future.

Thymic Stromal Lymphopoietin and Tezepelumab in Airway Diseases: From Physiological Role to Target Therapy.

Thymic stromal lymphopoietin (TSLP), is a protein belonging to a class of epithelial cytokines commonly called alarmins, which also includes IL-25 and IL-33. Functionally, TSLP is a key player in the immune response to environmental insults, initiating a number of downstream inflammatory pathways. TSLP performs its role by binding to a high-affinity heteromeric complex composed of the thymic stromal lymphopoietin receptor (TSLPR) chain and IL-7Rα. In recent years, the important role of proinflammatory cytokines in the etiopathogenesis of various chronic diseases such as asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), chronic obstructive pulmonary diseases (COPDs), and chronic spontaneous urticaria has been studied. Although alarmins have been found to be mainly implicated in the mechanisms of type 2 inflammation, studies on monoclonal antibodies against TSLP demonstrate partial efficacy even in patients whose inflammation is not definable as T2 and the so-called low T2. Tezepelumab is a human anti-TSLP antibody that prevents TSLP-TSLPR interactions. Several clinical trials are evaluating the safety and efficacy of Tezepelumab in various inflammatory disorders. In this review, we will highlight major recent advances in understanding the functional role of TSLP, its involvement in Th2-related diseases, and its suitability as a target for biological therapies.

CRISPR/Cas9 gene editing: a novel strategy for fighting drug resistance in respiratory disorders.

Respiratory disorders are among the conditions that affect the respiratory system. The healthcare sector faces challenges due to the emergence of drug resistance to prescribed medications for these illnesses. However, there is a technology called CRISPR/Cas9, which uses RNA to guide DNA targeting. This technology has revolutionized our ability to manipulate and visualize the genome, leading to advancements in research and treatment development. It can effectively reverse epigenetic alterations that contribute to drug resistance. Some studies focused on health have shown that targeting genes using CRISPR/Cas9 can be challenging when it comes to reducing drug resistance in patients with respiratory disorders. Nevertheless, it is important to acknowledge the limitations of this technology, such as off-target effects, immune system reactions to Cas9, and challenges associated with delivery methods. Despite these limitations, this review aims to provide knowledge about CRISPR/Cas9 genome editing tools and explore how they can help overcome resistance in patients with respiratory disorders. Additionally, this study discusses concerns related to applications of CRISPR and provides an overview of successful clinical trial studies.

Polyphenols as Therapeutics in Respiratory Diseases: Moving from Preclinical Evidence to Potential Clinical Applications.

Respiratory diseases are the most common and severe health complication and a leading cause of death worldwide. Despite breakthroughs in diagnosis and treatment, few safe and effective therapeutics have been reported. Phytochemicals are gaining popularity due to their beneficial effects and low toxicity. Polyphenols are secondary metabolites with high molecular weights found at high levels in natural food sources such as fruits, vegetables, grains, and citrus seeds. Over recent decades, polyphenols and their beneficial effects on human health have been the subject of intense research, with notable successes in preventing major chronic non-communicable diseases. Many respiratory syndromes can be treated effectively with polyphenolic supplements, including acute lung damage, pulmonary fibrosis, asthma, pulmonary hypertension, and lung cancer. This review summarizes the role of polyphenols in respiratory conditions with sufficient experimental data, highlights polyphenols with beneficial effects for each, and identifies those with therapeutic potential and their underlying mechanisms. Moreover, clinical studies and future research opportunities in this area are discussed.

[Translated article] Pharmaceutical care in respiratory diseases: Current situation and opportunities for hospital pharmacy in Spain.

OBJECTIVE: Respiratory diseases present a challenge for the healthcare system due to their prevalence and clinical impact. The aim of this study was to explore the current situation of hospital pharmacy in the field of respiratory diseases. METHOD: Observational, cross-sectional study, with a national scope, divided into 2 parts. In an initial phase, the activity and level of pharmaceutical care in respiratory diseases was evaluated through an online questionnaire using REDCap. The survey was addressed to department chiefs and consisted of 17 items, divided into 2 modules: general data and general activity. The second phase was open to hospital pharmacists, with the aim of exploring their opinion on care, training, and improvement needs. The number of items in this phase was 19, divided into 5 modules: general data, pharmaceutical care, competencies, training, and degree of satisfaction. RESULTS: In the first phase, 23 hospitals were included. Most of them (n=20) had a pharmacist in charge of respiratory diseases. However, a large proportion of them dedicated less than 40% of their working day to this activity. The pharmacist's activity occurred at the level of external patients (n=21), hospitalised patients (n=16), and secondarily in management (n=8). Integration is greater in pathologies such as asthma, IPF, pulmonary hypertension, and bronchiectasis. Participation in committees was present in 15 hospitals, with variability in pathologies and degree of involvement. In the second phase, 164 pharmacists participated, who considered pharmaceutical care in cystic fibrosis, asthma, and lung transplant as a priority. 51% considered integration to be adequate and 91% considered it necessary to implement prioritisation criteria. Professional competencies ranged from 6.5 to 6.9 out of 10 points. Only 45% of participants had received specific training in the last 4 years, indicating greater priority for asthma, pulmonary hypertension, and IPF. CONCLUSIONS: Most centers have pharmacists specialised in respiratory diseases. However, there is room for improvement in terms of subspecialisation, participation in multidisciplinary committees, implementation of prioritisation criteria, diversification in pathologies treated, as well as greater specific training in this area.

Availability, cost and affordability of essential medicines for chronic respiratory diseases in low-income and middle-income countries: a cross-sectional study.

Contemporary data on the availability, cost and affordability of essential medicines for chronic respiratory diseases (CRDs) across low-income and middle-income countries (LMICs) are missing, despite most people with CRDs living in LMICs. Cross-sectional data for seven CRD medicines in pharmacies, healthcare facilities and central medicine stores were collected from 60 LMICs in 2022-2023. Medicines for symptomatic relief were widely available and affordable, while preventative treatments varied widely in cost, were less available and largely unaffordable. There is an urgent need to address these issues if the Sustainable Development Goal 3 is to be achieved for people with asthma by 2030.

Targeting reprogrammed metabolism as a therapeutic approach for respiratory diseases.

Metabolic reprogramming underlies the etiology and pathophysiology of respiratory diseases such as asthma, idiopathic pulmonary fibrosis (IPF), and chronic obstructive pulmonary disease (COPD). The dysregulated cellular activities driving airway inflammation and remodelling in these diseases have reportedly been linked to aberrant shifts in energy-producing metabolic pathways: glycolysis and oxidative phosphorylation (OXPHOS). The rewiring of glycolysis and OXPHOS accompanying the therapeutic effects of many clinical compounds and natural products in asthma, IPF, and COPD, supports targeting metabolism as a therapeutic approach for respiratory diseases. Correspondingly, inhibiting glycolysis has largely attested effective against experimental asthma, IPF, and COPD. However, modulating OXPHOS and its supporting catabolic pathways like mitochondrial pyruvate catabolism, fatty acid ß-oxidation (FAO), and glutaminolysis for these respiratory diseases remain inconclusive. An emerging repertoire of metabolic enzymes are also interconnected to these canonical metabolic pathways that similarly possess therapeutic potential for respiratory diseases. Taken together, this review highlights the urgent demand for future studies to ascertain the role of OXPHOS in different respiratory diseases, under different stimulatory conditions, and in different cell types. While this review provides strong experimental evidence in support of the inhibition of glycolysis for asthma, IPF, and COPD, further verification by clinical trials is definitely required.

Pharmaceutical care in respiratory diseases: Current situation and opportunities for Hospital Pharmacy in Spain. / Atención farmacéutica en enfermedades respiratorias: situación y oportunidades de la farmacia hospitalaria en España.

OBJECTIVE: Respiratory diseases present a challenge for the healthcare system due to their prevalence and clinical impact. The aim of this study was to explore the current situation of hospital pharmacy in the field of respiratory diseases. METHOD: Observational, cross-sectional study, with a national scope, divided into 2 parts. In an initial phase, the activity and level of pharmaceutical care in respiratory diseases was evaluated through an online questionnaire using REDCap. The survey was addressed to department chiefs and consisted of 17 items, divided into 2 modules: general data and general activity. The second phase was open to hospital pharmacists, with the aim of exploring their opinion on care, training, and improvement needs. The number of items in this phase was 19, divided into 5 modules: general data, pharmaceutical care, competencies, training and degree of satisfaction. RESULTS: In the first phase, 23 hospitals were included. Most of them (n=20) had a pharmacist in charge of respiratory diseases. However, a large proportion of them dedicated less than 40% of their working day to this activity. The pharmacist's activity occurred at the level of external patients (n=20), hospitalized patients (n=16), and secondarily in management (n=8). Integration is greater in pathologies such as asthma, IPF, pulmonary hypertension, and bronchiectasis. Participation in committees was present in 15 hospitals, with variability in pathologies and degree of involvement. In the second phase, 164 pharmacists participated, who considered pharmaceutical care in cystic fibrosis, asthma and lung transplant as a priority. Fifty-one percent considered integration to be adequate and 91% considered it necessary to implement prioritization criteria. Professional competencies ranged from 6.5-6.9 out of 10 points. Only 45% of participants had received specific training in the last four years, indicating greater priority for asthma, pulmonary hypertension and IPF. CONCLUSIONS: Most centers have pharmacists specialized in respiratory diseases. However, there is room for improvement in terms of sub specialization, participation in multidisciplinary committees, implementation of prioritization criteria, diversification in pathologies treated, as well as greater specific training in this area.

Human Rhinovirus: Molecular and Clinical Overview / Rinovirus humano: descripción molecular y clínica

Human rhinoviruses (HRVs) are associated with a wide spectrum of clinical manifestations, ranging from mild cold symptoms to more severe respiratory illnesses, significantly burdening global healthcare systems. At the molecular level, HRVs belong to the Picornaviridae family and are classified into three species: HRV-A, HRV-B, and HRV-C. Advances in genomic sequencing and phylogenetic analysis have revealed a remarkable genetic diversity within HRV species, with over 160 serotypes identified. This genetic variability contributes to the ability of HRVs to evade host immune responses and facilitates their continuous circulation in the population. This review provides an overview of the molecular and clinical aspects of HRV infections.(AU)

Recent advances in the therapeutic potential of nobiletin against respiratory diseases.

BACKGROUND: Nobiletin is a natural polymethoxylated flavonoid widely present in citrus fruit peels. It has been demonstrated to exert the effects of anti-tumor, anti-inflammation, anti-oxidative, anti-apoptotic and improve cardiovascular function. Increasing evidences suggest that nobiletin plays an important role in respiratory diseases (RDs) treatment. OBJECTIVE: This review aimed to investigate the therapeutic potential of nobiletin against RDs, such as lung cancer, COPD, pulmonary fibrosis, asthma, pulmonary infection, acute lung injury, coronavirus disease 2019, and pulmonary arterial hypertension. METHODS: We retrieved extensive literature of relevant literatures in English until June 26, 2023 from the database of PubMed, Web of Science, and Scopus databases. The keywords of "nobiletin and lung", "nobiletin and respiratory disease", "nobiletin and chronic respiratory diseases", "nobiletin and metabolites", "nobiletin and pharmacokinetics", "nobiletin and toxicity" were searched in pairs. A total of 298 literatures were retrieved from the above database. After excluding the duplicates and reviews, 53 were included in the current review. RESULTS: We found that the therapeutic mechanisms are based on different signaling pathways. Firstly, nobiletin inhibited the proliferation and suppressed the invasion and migration of cancer cells by regulating the related pathway or key target, like Bcl-2, PD-L1, PARP, and Akt/GSK3ß/ß-catenin in lung cancer treatment. Secondly, nobiletin treats COPD and ALI by targeting classical signaling pathway mediating inflammation. Besides, the available findings show that nobiletin exerts the effect of PF treatment via regulating mTOR pathway. CONCLUSIONS: With the wide range of pharmacological activities, high efficiency and low toxicity, nobiletin can be used as a potential agent for preventing and treating RDs. These findings will contribute to further research on the molecular mechanisms of nobiletin and facilitate in-depth studies on nobiletin at both preclinical and clinical levels for the treatment of RDs.

Medicaciones inhaladas y cámaras de inhalación para el asma infantil. Red española de grupos de trabajo sobre asma en pediatría (REGAP) / Inhaled medications and inhalation chambers for childhood asthma. Spanish network of working groups on asthma in pediatrics (REGAP)

El asma, la enfermedad crónica más prevalente en la edad pediátrica, continúa planteando desafíos en su manejo y tratamiento1. Guías nacionales e internacionales destacan la importancia de la educación terapéutica (ET) para lograr el control de esta enfermedad2,3. Esta educación implica la transmisión de conocimientos y habilidades al paciente y su familia, mejorando la adherencia a la medicación, corrigiendo errores en la técnica de inhalación y ajustando el tratamiento según las características individuales de cada paciente4,5. Es esencial que la ET sea progresiva, gradual e individualizada, y que esté presente en todos los niveles asistenciales. La formación en ET de profesionales sanitarios es crucial, especialmente para los pediatras, quienes además deben conocer la extensa variabilidad de medicamentos e inhaladores disponibles y sus indicaciones para cada edad6. Para abordar esta necesidad, el Grupo red española de grupos de trabajo sobre asma en pediatría (REGAP) ha revisado exhaustivamente los inhaladores actualmente disponibles en España para el tratamiento del asma en la edad pediátrica. La revisión incluye una revisión de los distintos sistemas de inhalación y los distintos fármacos inhalados, utilizados para el tratamiento del asma en la edad pediátrica. Esta revisión se actualizará anualmente, incluyendo información sobre fármacos, dispositivos, cámaras de inhalación, indicaciones y financiación. El Grupo REGAP espera que estas tablas sean una valiosa ayuda para los pediatras en su práctica clínica diaria y constituyen una eficaz herramienta de ET.(AU)

Asthma, the most prevalent chronic disease in pediatric age, continues to pose challenges in its management and treatment. National and international guidelines emphasize the importance of therapeutic education (TE) to achieve disease control. TE involves imparting knowledge and skills to the patient and their family, enhancing medication adherence, rectifying errors in inhalation technique, and tailoring treatment based on individual patient characteristics. It is essential for TE to be progressive, gradual, and personalized, spanning all levels of care. Training healthcare professionals in TE is crucial, particularly for pediatricians, who must also be aware of the extensive variability of available meds and inhalers and their respective age-specific indications. Addressing this need, the REGAP Group extensively reviewed inhalers currently available in Spain for pediatric asthma treatment. The review encompassed different inhalation systems and inhaled drugs used for pediatric asthma treatment. This review will be updated annually, providing information on medications, devices, inhalation chambers, indications, and financiation. The REGAP Group hopes that these tables will be a valuable help for pediatricians in their daily clinical practice and serve as an effective TE tool.(AU)

Designing inhaled small molecule drugs for severe respiratory diseases: an overview of the challenges and opportunities.

INTRODUCTION: Inhaled drugs offer advantages for the treatment of respiratory diseases over oral drugs by delivering the drug directly to the lung, thus improving the therapeutic index. There is an unmet medical need for novel therapies for lung diseases, exacerbated by a multitude of challenges for the design of inhaled small molecule drugs. AREAS COVERED: The authors review the challenges and opportunities for the design of inhaled drugs for respiratory diseases with a focus on new target discovery, medicinal chemistry, and pharmacokinetic, pharmacodynamic, and toxicological evaluation of drug candidates. EXPERT OPINION: Inhaled drug discovery is facing multiple unique challenges. Novel biological targets are scarce, as is the guidance for medicinal chemistry teams to design compounds with inhalation-compatible features. It is exceedingly difficult to establish a PK/PD relationship given the complexity of pulmonary PK and the impact of physical properties of the drug substance on PK. PK, PD and toxicology studies are technically challenging and require large amounts of drug substance. Despite the current challenges, the authors foresee that the design of inhaled drugs will be facilitated in the future by our increasing understanding of pathobiology, emerging medicinal chemistry guidelines, advances in drug formulation, PBPK models, and in vitro toxicology assays.

Opportunities and Challenges for Inhalable Nanomedicine Formulations in Respiratory Diseases: A Review.

Lungs experience frequent interactions with the external environment and have an abundant supply of blood; therefore, they are susceptible to invasion by pathogenic microorganisms and tumor cells. However, the limited pharmacokinetics of conventional drugs in the lungs poses a clinical challenge. The emergence of different nano-formulations has been facilitated by advancements in nanotechnology. Inhaled nanomedicines exhibit better targeting and prolonged therapeutic effects. Although nano-formulations have great potential, they still present several unknown risks. Herein, we review the (1) physiological anatomy of the lungs and their biological barriers, (2) pharmacokinetics and toxicology of nanomaterial formulations in the lungs; (3) current nanomaterials that can be applied to the respiratory system and related design strategies, and (4) current applications of inhaled nanomaterials in treating respiratory disorders, vaccine design, and imaging detection based on the characteristics of different nanomaterials. Finally, (5) we analyze and summarize the challenges and prospects of nanomaterials for respiratory disease applications. We believe that nanomaterials, particularly inhaled nano-formulations, have excellent prospects for application in respiratory diseases. However, we emphasize that the simultaneous toxic side effects of biological nanomaterials must be considered during the application of these emerging medicines. This study aims to offer comprehensive guidelines and valuable insights for conducting research on nanomaterials in the domain of the respiratory system.