Comparative Analysis of Laboratory and Radiation Methods of Studies with the Degree of Severity of Patients with COVID-19

The study is devoted to a comparative analysis and retrospective evaluation of laboratory and instrumental data with the severity of lung tissue damage in COVID-19 of patients with COVID-19. An improvement was made in the methodology for interpreting and analyzing dynamic changes associated with COVID-19 on CT images of the lungs. The technique includes the following steps: pre-processing, segmentation with color coding, calculation and evaluation of signs to highlight areas with probable pathology (including combined evaluation of signs). Analysis and interpretation is carried out on the emerging database of patients. At the same time the following indicators are distinguished: the results of the analysis of CT images of the lungs in dynamics;the results of the analysis of clinical and laboratory data (severity course of the disease, temperature, saturation, etc.). The results of laboratory studies are analyzed with an emphasis on the values of the main indicator - interleukin-6. This indicator is a marker of significant and serious changes characterizing the severity of the patient's condition. © 2023 IEEE.

The Relationship between COVID-19 and Pulmonary Fibrosis After of Infection in AL-Najaf Province, Iraq

Background and Purpose: A significant part of the "post-acute COVID-19 syndrome" that may significantly aggravate patients' clinical history is pulmonary fibrosis (PF), a pathological result of chronic and acute interstitial lung illnesses linked to impaired wound repair. Despite being inconclusive, the information that is currently available suggests that more than a third of COVID-19 hospital patients experience aberrant lung fibrosis after leaving the hospital. The current study's goal is to ascertain if pulmonary fibrosis and COVID-19 susceptibility are related. Material(s) and Method(s): The Al-Amal Hospital provided data on coronavirus infections. Regarding Pulmonary Fibrosis, Age, and Gender in the Najaf Province in 2022. The results were evaluated using the Statistical Analysis System application's Chi-squared test (SPSS). Result(s): In the study results of our study were as follows, where it was found that (11.21%) of the total patients in the age group 18-25 are prone to suffering from pulmonary fibrosis, while (20%) of the age group were 25-36, and also found that (29.08%, 45.74% and 31.19%) for the following age groups, respectively: 36-47y, 47-57y and 57-67y. Finally, it was found that 117 (26.77%) patients out of 320 suffer from pulmonary fibrosis symptoms of the age group 67-77 years, where it formed a significant difference compared with the rest of the age groups. Conclusion(s): There is a link between infection with COVID 19 and pulmonary fibrosis, among other conditions. However, our study shows that severe COVID-19 is linked with considerable respiratory symptoms and morbidity, in-cluding dyspnea, which was reported by many survivors. There is an urgent need for more research to understand the connection more generally and to identify therapies that might help prevent similar lung infections in the future.Copyright © 2023, Colegio de Farmaceuticos de la Provincia de Buenos Aires. All rights reserved.

Trends and Outcomes in Lung Transplantation in Patients with and without Idiopathic Pulmonary Fibrosis in Spain during the Period 2016-2020.

(1) Background: This paper aims to assess temporal trends (2016-2020) in incidence, patient's characteristics, complications, length of hospital stay (LOHS) and in-hospital mortality (IHM) among patients with and without idiopathic pulmonary fibrosis (IPF) undergoing lung transplantation (LTx). We also analyse the effect of the COVID-19 pandemic on LTx in these populations. (2) Methods: A retrospective, population-based observational study was conducted using the Spanish National Hospital Discharge Database. Multivariable adjustment was conducted with logistic regression to analyse the IHM. (3) Results: We identified 1777 admissions for LTx during the study period, of which 573 (32.2%) were performed in patients with IPF. The number of hospital admissions for LTx rose from 2016 to 2020, both in patients with and without IPF, but a marked reduction was observed from year 2019 to year 2020. Over time, the proportion of single LTx decreased and bilateral LTx increased significantly in both groups. The incidence of LTx complications increased significantly over time along with the increase in the incidence of IPF. No significant differences in the incidence of complications or in the IHM between patients with and without IPF were found. Suffering any complication of the LTx and pulmonary hypertension were conditions positively associated with IHM in patients with and without IPF. The IHM remained stable from 2016 to 2020 in both study populations and was not affected by the COVID pandemic. (4) Conclusions: Patients with IPF account for almost a third of all lung transplants. The number of LTx increased over time in patients with and without IPF, but a marked reduction was observed from 2019 to 2020. Although the proportion of LTx complications increased significantly over time in both groups, the IHM did not change. IPF was not associated with increased complications or IHM after LTx.

Diagnostic Dilemma: A Patient With Pulmonary Fibrosis Who Presented for Severe Tracheal Stenosis After COVID-19 Pneumonia.

A 44-year-old man with pulmonary fibrosis presented to our pulmonary hypertension clinic with biphasic stridor and dyspnea. He was sent to the emergency department, where he was found to have 90% subglottic tracheal stenosis and was successfully treated with balloon dilation. Seven months prior to the presentation, he required intubation for coronavirus disease 2019 (COVID-19) pneumonia complicated by hemorrhagic stroke. He was discharged after percutaneous dilatational tracheostomy, which was decannulated after three months. Our patient possessed several risk factors for tracheal stenosis, including endotracheal intubation, tracheostomy, and airway infection. Furthermore, our case is of great importance given the developing literature on COVID-19 pneumonia and its subsequent complications. Additionally, his history of interstitial lung disease may have confounded his presentation. Therefore, it is important to understand stridor, as it is an important exam finding that clinically distinguishes upper and lower airway disease. Our patient's biphasic stridor is consistent with the diagnosis of severe tracheal stenosis.

[Pulmonary fibrosis in patients with COVID-19: A review].

The viral infectious disease pandemic caused by SARS-CoV-2 has affected over 500 million people and killed over 6 million. This is the official data provided by the WHO as of the end of May 2022. Among people who have recovered from COVID-19, post-COVID syndrome is quite common. Scattered epidemiological studies on post-COVID syndrome, however, indicate its high relevance. One of the manifestations of post-COVID syndrome is the development of pulmonary fibrosis (PF). This article is devoted to the analysis of literature data on epidemiology, immunomorphology, as well as X-ray morphological and functional characteristics of PF in patients with post-COVID syndrome. Attention is drawn to the various phenotypes of the post-COVID syndrome and the incidence of PF, which, as clinical practice shows, is most common in people who have had severe COVID-19. This article discusses in detail the molecular biological and immunological mechanisms of PF development. The fibrotic process of the lung parenchyma is not an early manifestation of the disease; as a rule, radiomorphological signs of this pathological process develop after four weeks from the onset of acute manifestations of a viral infection. The characteristic signs of PF include those that indicate the process of remodulation of the lung tissue: volumetric decrease in the lungs, "cellular" degeneration of the lung parenchyma, bronchiectasis and traction bronchiolectasis. The process of remodulating the lung tissue, in the process of fibrosis, is accompanied by a violation of the lung function; a particularly sensitive test of functional disorders is a decrease in the diffusion capacity of the lung tissue. Therefore, in the process of monitoring patients with post-COVID syndrome, a dynamic study of the ventilation function of the lungs is recommended. The main clinical manifestation of PF is dyspnea that occurs with minimal exertion. Shortness of breath also reflects another important aspect of fibrous remodulation of the lung parenchyma - oxygen dissociation is disturbed, which reflects a violation of the gas exchange function of the lungs. There are no generally accepted treatments for PF in post-COVID syndrome. The literature considers such approaches as the possibility of prescribing antifibrotic therapy, hyaluronidase, and medical gases: thermal helium, nitric oxide, and atomic hydrogen. The article draws attention to the unresolved issues of post-covid PF in people who have had COVID-19.

Radiological Findings as Predictors of COVID-19 Lung Sequelae: A Systematic Review and Meta-Analysis

Background This systematic review and meta-analysis aimed to investigate the radiological predictors of post- coronavirus disease 19 (COVID-19) pulmonary fibrosis and incomplete absorption of pulmonary lesions. Method We systematically searched PubMed, EMBASE, and Web of Science for studies reporting the predictive value of radiological findings in patients with post-COVID-19 lung residuals published through November 11, 2022. The pooled odds ratios with a 95% confidence interval (CI) were assessed. The random-effects model was used due to the heterogeneity of the true effect sizes. Results We included 11 studies. There were 1777 COVID-19-positive patients, and 1014 (57 %) were male. All studies used chest computed tomography (CT) as a radiologic tool. Moreover, chest X-ray (CXR) and lung ultrasound were used in two studies, along with a CT scan. CT severity score, Radiographic Assessment of Lung Edema score (RALE), interstitial score, lung ultrasound score (LUS), patchy opacities, abnormal CXR, pleural traction, and subpleural abnormalities were found to be predictors of post-COVID-19 sequels. CT severity score (CTSS) and consolidations were the most common predictors among included studies. Pooled analysis revealed that pulmonary residuals in patients with initial consolidation are about four times more likely than in patients without this finding (OR: 3.830;95% CI: 1.811-8.102, I2: 4.640). Conclusion Radiological findings can predict the long-term pulmonary sequelae of COVID-19 patients. CTSS is an important predictor of lung fibrosis and COVID-19 mortality. Lung fibrosis can be diagnosed and tracked using the LUS. Changes in RALE score during hospitalization can be used as an independent predictor of mortality.

Pneumopathie sévère a SARS-CoV-2: aspects TDM à 6 mois

RÉSUMÉ Introduction – Depuis le début de la pandémie Covid-19, la TDM thoracique a joué un rôle clé dans le diagnostic, l'évaluation pronostique et le suivi de la pneumonie virale à SARS-CoV-2. Données récentes – La persistance de lésions pulmonaires sur la TDM de suivi d'une pneumopathie à Covid-19 grave concerne environ 60 % des patients. L'aspect TDM à 6 mois peut varier d'une résolution radiologique complète à des lésions fibrosantes pouvant imiter des pathologies interstitielles connues. Conclusion – Cet article illustre, à partir des images TDM de la cohorte Recovery from Covid-19 ardS (RECOVIDS) les aspects caractéristiques observés au suivi à 6 mois d'une pneumopathie sévère à SARS-CoV-2. En s'appuyant sur la présence de fibrose et le profil lésionnel prédominant, les radiologues peuvent reconnaître et intégrer ces images dans le diagnostic différentiel d'autres pneumopathies de présentations cliniques et TDM proches. SUMMARY Introduction- Since the beginning of the COVID-19 pandemic, chest computed tomography (CT) has played a key role in the diagnosis, prognostic evaluation, and follow-up of severe SARS-COVD-2 viral pneumonia. Recent Findings- Approximately 60 % of patients with severe COVID-19 exhibit persistent lung lesions on follow-up chest CT. The chest CT appearance at 6-month follow-up can range from complete resolution to severe fibrotic changes that may mimic known interstitial lung diseases. Conclusion- This article illustrates the typical appearance at 6-month using Chest-CT images from the "Recovery from COVID-19 ARDS” (RECOVIDS) cohort. An approach based on the presence of fibrosis and the predominant pattern will enable radiologists to recognize and incorporate these aspects into the differential diagnosis of other interstitial lung diseases that may present with similar clinical and CT features.

Exploring the mechanism of action of three agents white powder in the care for pulmonary diseases based on network pharmacology and technology for molecular docking

Based on the international concern about COVID-19 and pulmonary diseases, the number of cases of lung injury caused by COVID-19 pneumonia and its complications has increased dramatically in recent years, and the complexity of the situation makes the combination of single drugs a major problem in respiratory diseases. Therefore, it would be feasible to replace single drug combinations with compounded formulations for the treatment of a diverse array of pulmonary diseases. At the same time, the visualization of the chemical composition of herbal formulations and the study of molecular interactions to reveal the mechanism of action will be of practical significance. This paper introduced the therapeutic mechanisms of the traditional Chinese medicine formula Three Agents White Powder. Three major pulmonary diseases, COVID-19, pulmonary fibrosis, and lung abscess, were investigated using molecular docking and network pharmacology approaches. Mainly using TCMSP, DAVID, STRING, Genecard database screening, and autodock molecular docking methods, this paper verified that this drug applies its healing benefits to pulmonary diseases through multiple components, multiple targets, and multiple pathways, and illustrated the effectiveness of this formula in the adjuvant treatment of extensive pulmonary diseases. © 2023 SPIE.

Brave New Lungs: Aging in the Shadow of COVID-19.

As the COVID-19 pandemic continues to affect communities worldwide, this novel disease is leaving many survivors with severe lung damage. Among older patients, advanced lung damage is more likely. Survivors of all ages who have extensive lung impacts are likely to be new to managing those issues. Supporting healthy aging for these patients will require both gathering data about their unique experiences and using the existing evidence basis about adapting to managing obstructive lung disease. This article outlines key priorities for research with COVID-19 survivors aging with permanent lung damage and highlights unique considerations for people older at age of onset. It also outlines the relevance of findings from this research for clinical care supporting people newly aging with advanced lung disease from COVID-19. In the process, it summarizes lessons from established patient populations aging with progressive lung disease-using cystic fibrosis as a prominent example from the author's lived experience-that may enhance the experiences of older COVID-19 survivors.

Nanotherapeutic Approaches to Treat COVID-19-Induced Pulmonary Fibrosis.

There have been significant collaborative efforts over the past three years to develop therapies against COVID-19. During this journey, there has also been a lot of focus on understanding at-risk groups of patients who either have pre-existing conditions or have developed concomitant health conditions due to the impact of COVID-19 on the immune system. There was a high incidence of COVID-19-induced pulmonary fibrosis (PF) observed in patients. PF can cause significant morbidity and long-term disability and lead to death in the long run. Additionally, being a progressive disease, PF can also impact the patient for a long time after COVID infection and affect the overall quality of life. Although current therapies are being used as the mainstay for treating PF, there is no therapy specifically for COVID-induced PF. As observed in the treatment of other diseases, nanomedicine can show significant promise in overcoming the limitations of current anti-PF therapies. In this review, we summarize the efforts reported by various groups to develop nanomedicine therapeutics to treat COVID-induced PF. These therapies can potentially offer benefits in terms of targeted drug delivery to lungs, reduced toxicity, and ease of administration. Some of the nanotherapeutic approaches may provide benefits in terms of reduced immunogenicity owing to the tailored biological composition of the carrier as per the patient needs. In this review, we discuss cellular membrane-based nanodecoys, extracellular vesicles such as exosomes, and other nanoparticle-based approaches for potential treatment of COVID-induced PF.

Post-COVID-19 Pulmonary Fibrosis: Facts-Challenges and Futures: A Narrative Review.

Patients with coronavirus disease 2019 (COVID-19) usually suffer from post-acute sequelae of coronavirus disease 2019 (PASC). Pulmonary fibrosis (PF) has the most significant long-term impact on patients' respiratory health, called post-COVID-19 pulmonary fibrosis (PC19-PF). PC19- PF can be caused by acute respiratory distress syndrome (ARDS) or pneumonia due to COVID-19. The risk factors of PC19-PF, such as older age, chronic comorbidities, the use of mechanical ventilation during the acute phase, and female sex, should be considered. Individuals with COVID-19 pneumonia symptoms lasting at least 12 weeks following diagnosis, including cough, dyspnea, exertional dyspnea, and poor saturation, accounted for nearly all disease occurrences. PC19-PF is characterized by persistent fibrotic tomographic sequelae associated with functional impairment throughout follow-up. Thus, clinical examination, radiology, pulmonary function tests, and pathological findings should be done to diagnose PC19-PF patients. PFT indicated persistent limitations in diffusion capacity and restrictive physiology, despite the absence of previous testing and inconsistency in the timeliness of assessments following acute illness. It has been hypothesized that PC19-PF patients may benefit from idiopathic pulmonary fibrosis treatment to prevent continued infection-related disorders, enhance the healing phase, and manage fibroproliferative processes. Immunomodulatory agents might reduce inflammation and the length of mechanical ventilation during the acute phase of COVID-19 infection, and the risk of the PC19-PF stage. Pulmonary rehabilitation, incorporating exercise training, physical education, and behavioral modifications, can improve the physical and psychological conditions of patients with PC19-PF.

Safety and persistence of anti-fibrotic drugs in interstitial lung diseases

Background and ImportanceInterstitial lung diseases (ILD) is a group of rare diseases with bad prognosis, being Idiopathic pulmonary fibrosis (IPF) the most frequent of them. They can be treated with antifibrotic drugs: nintedanib or pirfenidone. However, these drugs have a high rate of adverse effects, which has a significant impact on treatment persistence.Aim and ObjectivesTo analyse the safety of pirfenidone and nintedanib in patients with ILD as well as treatment's persistence, in a third-level hospital.Material and MethodsRetrospective observational study of patients with ILD treated with antifibrotic drugs from January 2016 to August 2022. Variables: sex, age, drug, duration of antifibrotic treatment, associated drug, switch to another antifibrotic drug, side effects, discontinuations, deaths. Information was collected from the hospital's information systems.Results66 patients, 67% men, mean age 67 (47–86).44 patients with nintedanib: 23 IPF, 14 progressive pulmonary fibrosis (PPF), 2 ILD associated with systemic sclerosis, 4 fibroemphysema and 1 ILD not classified. 5 of them were treated with an associated immunosuppressive drug: mycophenolate mofetil. 12 patients needed a dose reduction due to gastrointestinal effects: 100% diarrhea, 80% nausea. 1 patient needed temporary discontinuation due to increased transaminases, which were finally stabilised, being able to return to a higher dose. 2 patients needed discontinuation of treatment due to bleeding: 1 patient was on antiplatelet therapy and the other had a background of epistaxis. These two patients switched to pirfenidone.22 patients with pirfenidone: all of them IPF. 2 patients needed dose reduction due to diarrhoea and 2 needed treatment discontinuation due to severe sunburns. These patients switched to nintedanib.Persistence until progression18 months with nintedanib and 24 months with pirfenidone. 8 patients died during treatment, 4 of them because of COVID-19 infection.Conclusion and RelevanceThanks to a close follow-up in patients with ILD, it is possible to modify the dose and to achieve greater tolerance to treatments. The pandemic affected negatively during the year 2020, not only because of the impossibility of receiving medical appointments, but also due to the acceleration of their death. The rapid establishment of anti-fibrotic treatment and the adequate control of adverse effects are the key for this type of patients.References and/or AcknowledgementsConflict of InterestNo conflict of interest

Contemporary Concise Review 2022: Interstitial lung disease.

Novel genetic associations for idiopathic pulmonary fibrosis (IPF) risk have been identified. Common genetic variants associated with IPF are also associated with chronic hypersensitivity pneumonitis. The characterization of underlying mechanisms, such as pathways involved in myofibroblast differentiation, may reveal targets for future treatments. Newly identified circulating biomarkers are associated with disease progression and mortality. Deep learning and machine learning may increase accuracy in the interpretation of CT scans. Novel treatments have shown benefit in phase 2 clinical trials. Hospitalization with COVID-19 is associated with residual lung abnormalities in a substantial number of patients. Inequalities exist in delivering and accessing interstitial lung disease specialist care.

Biomarkers of Fibrosis in Patients with COVID-19 One Year After Hospital Discharge: A Prospective Cohort Study.

Beyond the acute infection of coronavirus disease (COVID-19), concern has arisen about long-term effects of SARS-CoV-2 infection. The aim of our study was to analyze if there is any biomarker of fibrogenesis in COVID-19 pneumonia patients capable of predicting post-COVID pulmonary sequelae. We conducted a multicenter, prospective, observational cohort study of patients admitted to hospital with bilateral COVID-19 pneumonia. We classified patients in two groups according to severity, and blood samples to measure MMP1, MMP7, periostin and VEGF, respiratory function tests and HRCT imaging were obtained at 2 and 12 months after hospital discharge. A total of 135 patients were evaluated at 12 months. Median age was 61 (IQR: 19) years and 58.5% were men. We found between-group differences in age, radiological involvement, length of hospital stay and inflammatory laboratory parameters. Differences were found between 2 and 12 months in all functional tests, including improvements in FVC% (98.0 vs. 103.9; p=0.001) and DLCO<80% (60.9% vs. 39.7%; p=0.001). At 12 months, 63% of patients had complete HRTC resolution, but fibrotic changes persisted in 29.4%. Biomarker analysis demonstrated differences at 2 months in periostin (ng/mL) (0.8893 vs. 1.437; p<0.001) and MMP-7 (ng/mL) (8.7249 vs. 15.2181; p<0.001). No differences were found at 12 months. In multivariable analysis, only 2-month periostin was associated with 12-month fibrotic changes (OR: 1.0013 95% CI: 1.0006-1.00231; p=0.003) and 12-month DLCO impairment (OR: 1.0006 95% CI: 1.0000-1.0013; p=0.047). Our data suggest that early periostin post-discharge could predict the presence of fibrotic pulmonary changes.

[Post-COVID-19 syndrome]. / Syndrome post-COVID-19.

In the aftermath of acute infection with the severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), a large number of symptoms persist or appear, constituting a real syndrome called "long COVID-19" or "post-COVID- 19" or "post-acute COVID-19 syndrome". Its incidence is very high, half of patients showing at least one symptom at 4-6 months after Coronarovirus infectious disease 2019 (COVID-19). They can affect many organs. The most common symptom is persistent fatigue, similar to that seen after other viral infections. Radiological pulmonary sequelae are relatively rare and not extensive. On the other hand, functional respiratory symptoms, primarily dyspnoea, are much more frequent. Dysfunctional breathing is a significant cause of dyspnoea. Cognitive disorders and psychological symptoms are also very common, with anxiety, depression and post-traumatic stress symptoms being widely described. On the other hand, cardiac, endocrine, cutaneous, digestive or renal sequelae are rarer. The symptoms generally improve after several months, even if their prevalence at two years remains significant. Most of the symptoms are favored by the severity of the initial illness, and the psychic symptoms by the female sex. The pathophysiology of most symptoms is poorly understood. The influence of the treatments used in the acute phase is also important. Vaccination, on the other hand, seems to reduce their incidence. The sheer number of affected patients makes long-term COVID-19 syndrome a public health challenge.

Pulmonary function abnormality in patients recovered from Covid 19 pneumonia, in a tertiary care hospital in India.

Background: One of the most dreaded complications of COVID pneumonia is post-COVID residual lung fibrosis and lung function impairment. Objectives: To find out the extent and type of pulmonary function abnormality using spirometry, diffusion capacity, and 6-minute walk test and to co-relate with the clinical severity at the time of infection, in patients who have recovered from COVID19 pneumonia, in a tertiary care hospital in India. Materials and Methods: This is a prospective, cross-sectional study with a total 100 patients. Patients who have recovered from COVID pneumonia after one month of onset of symptoms and before 3 months who come for follow-up and have respiratory complaints undergo pulmonary function test will be recruited in the study. Results: In our study, the most common lung function abnormality detected was restrictive pattern in 55% of the patients (N = 55) followed by mixed pattern in 9% of patients (N = 9), obstructive in 5% of patients (N = 5), and normal in 31% of patients (N = 31). In our study, total lung capacity was reduced in 62% of the patients and normal in 38% of the patients and diffusion capacity of lung was reduced in 52% of the patients recovered from 52% of the individuals. Also, a 6-minute walk test was reduced in 15% of the patients and normal in 85% of the patients. Conclusion: Pulmonary function test can serve as an important tool in both diagnosis and follow-up of post-COVID lung fibrosis and pulmonary sequalae.

New therapeutic approaches against pulmonary fibrosis.

Pulmonary fibrosis is the end-stage change of a large class of lung diseases characterized by the proliferation of fibroblasts and the accumulation of a large amount of extracellular matrix, accompanied by inflammatory damage and tissue structure destruction, which also shows the normal alveolar tissue is damaged and then abnormally repaired resulting in structural abnormalities (scarring). Pulmonary fibrosis has a serious impact on the respiratory function of the human body, and the clinical manifestation is progressive dyspnea. The incidence of pulmonary fibrosis-related diseases is increasing year by year, and no curative drugs have appeared so far. Nevertheless, research on pulmonary fibrosis have also increased in recent years, but there are no breakthrough results. Pathological changes of pulmonary fibrosis appear in the lungs of patients with coronavirus disease 2019 (COVID-19) that have not yet ended, and whether to improve the condition of patients with COVID-19 by means of the anti-fibrosis therapy, which are the questions we need to address now. This review systematically sheds light on the current state of research on fibrosis from multiple perspectives, hoping to provide some references for design and optimization of subsequent drugs and the selection of anti-fibrosis treatment plans and strategies.

The mechanism of Qingwen Gupi decoction on pulmonary fibrosis based on metabolomics and intestinal flora.

AIMS: To evaluate the effects of the Qingwen Gupi decoction (QGT) in a rat model of bleomycin-induced pulmonary fibrosis (PF), and explore the underlying mechanisms by integrating UPLC-Q-TOF/MS metabolomics and 16S rDNA sequencing of gut microbiota. METHODS AND RESULTS: The animals were randomly divided into the control, PF model, pirfenidone-treated, and low-, medium-, and high-dose QGT groups. The lung tissues were examined and the expression of TGF-ß, SMAD-3, and SMAD-7 mRNAs in the lung tissues were analyzed. Metabolomic profiles were analyzed by UPLC-QTOF/MS, and the intestinal flora were examined by prokaryotic 16 rDNA sequencing. Pathological examination and biochemical indices revealed that QGT treatment improved the symptoms of PF by varying degrees. Furthermore, QGT significantly downregulated TGF-ß1 and Smad-3 mRNAs and increased the expression levels of Smad-7. QGT-L in particular increased the levels of 18 key metabolic biomarkers that were associated with nine gut microbial species and may exert antifibrosis effects through arachidonic acid metabolism, glycerophospholipid metabolism, and phenylalanine metabolism. CONCLUSIONS: QGT alleviated PF in a rat model through its anti-inflammatory, antioxidant, and anti-fibrotic effects, and by reversing bleomycin-induced gut dysbiosis.This study lays the foundation for further research on the pathological mechanisms of PF and the development of new drug candidates.

Adverse Effects of Air Pollution on Pulmonary Diseases.

Environmental exposure to air pollution is known to have adverse effects on various organs. Air pollution has greater effects on the pulmonary system as the lungs are directly exposed to contaminants in the air. Here, we review the associations of air pollution with the development, morbidity, and mortality of pulmonary diseases. Short- and long-term exposure to air pollution have been shown to increase mortality risk even at concentrations below the current national guidelines. Ambient air pollution has been shown to be associated with lung cancer. Particularly long-term exposure to particulate matter with a diameter <2.5 µm (PM2.5) has been reported to be associated with lung cancer even at low concentrations. In addition, exposure to air pollution has been shown to increase the incidence risk of chronic obstructive pulmonary disease (COPD) and has been correlated with exacerbation and mortality of COPD. Air pollution has also been linked to exacerbation, mortality, and development of asthma. Exposure to nitrogen dioxide (NO2) has been demonstrated to be related to increased mortality in patients with idiopathic pulmonary fibrosis. Additionally, air pollution increases the incidence of infectious diseases, such as pneumonia, bronchitis, and tuberculosis. Furthermore, emerging evidence supports a link between air pollution and coronavirus disease 2019 transmission, susceptibility, severity and mortality. In conclusion, the stringency of air quality guidelines should be increased and further therapeutic trials are required in patients at high risk of adverse health effects of air pollution.

Inhaled Lipid Nanoparticles Alleviate Established Pulmonary Fibrosis.

Pulmonary fibrosis, a sequela of lung injury resulting from severe infection such as severe acute respiratory syndrome-like coronavirus (SARS-CoV-2) infection, is a kind of life-threatening lung disease with limited therapeutic options. Herein, inhalable liposomes encapsulating metformin, a first-line antidiabetic drug that has been reported to effectively reverse pulmonary fibrosis by modulating multiple metabolic pathways, and nintedanib, a well-known antifibrotic drug that has been widely used in the clinic, are developed for pulmonary fibrosis treatment. The composition of liposomes made of neutral, cationic or anionic lipids, and poly(ethylene glycol) (PEG) is optimized by evaluating their retention in the lung after inhalation. Neutral liposomes with suitable PEG shielding are found to be ideal delivery carriers for metformin and nintedanib with significantly prolonged retention in the lung. Moreover, repeated noninvasive aerosol inhalation delivery of metformin and nintedanib loaded liposomes can effectively diminish the development of fibrosis and improve pulmonary function in bleomycin-induced pulmonary fibrosis by promoting myofibroblast deactivation and apoptosis, inhibiting transforming growth factor 1 (TGFß1) action, suppressing collagen formation, and inducing lipogenic differentiation. Therefore, this work presents a versatile platform with promising clinical translation potential for the noninvasive inhalation delivery of drugs for respiratory disease treatment.