Loss Of Lung Function Research Articles

Exploration of the unmet needs of patients diagnosed with idiopathic pulmonary fibrosis: a scoping review protocol

IntroductionInterstitial lung diseases consist of a range of lung disorders, the most prevalent being idiopathic pulmonary fibrosis (IPF). IPF is a chronic, progressive disease, resulting in loss of lung function...

Idiopathic pulmonary fibrosis and the role of genetics in the era of precision medicine.

Idiopathic pulmonary fibrosis (IPF) is a chronic, rare progressive lung disease, characterized by lung scarring and the irreversible loss of lung function. Two anti-fibrotic drugs, nintedanib and pirfenidone, have been demonstrated to slow down disease progression, although IPF mortality remains a challenge and the patients die after a few years from diagnosis. Rare pathogenic variants in genes that are involved in the surfactant metabolism and telomere maintenance, among others, have a high penetrance and tend to co-segregate with the disease in families. Common recurrent variants in the population with modest effect sizes have been also associated with the disease risk and progression. Genome-wide association studies (GWAS) support at least 23 genetic risk loci, linking the disease pathogenesis with unexpected molecular pathways including cellular adhesion and signaling, wound healing, barrier function, airway clearance, and innate immunity and host defense, besides the surfactant metabolism and telomere biology. As the cost of high-throughput genomic technologies continuously decreases and new technologies and approaches arise, their widespread use by clinicians and researchers is efficiently contributing to a better understanding of the pathogenesis of progressive pulmonary fibrosis. Here we provide an overview of the genetic factors known to be involved in IPF pathogenesis and discuss how they will continue to further advance in this field. We also discuss how genomic technologies could help to further improve IPF diagnosis and prognosis as well as for assessing genetic risk in unaffected relatives. The development and validation of evidence-based guidelines for genetic-based screening of IPF will allow redefining and classifying this disease relying on molecular characteristics and contribute to the implementation of precision medicine approaches.

Fourteen immunomodulatory alkaloids and two prenylated phenylpropanoids with dual therapeutic approach for COVID-19: molecular docking and dynamics studies

The pandemic outbreak of COVID-19 caused by the new severe acute respiratory syndrome coronavirus (SARS-CoV-2) is a global health burden. To date, there is no highly effective antiviral therapy to eradicate the virus; as a result, researchers are racing to introduce new potential therapeutic agents. Alternatively, traditional immunity boosters and symptomatic treatment based on natural bioactive compounds are also an option. The 3-chymotrypsin-like protease (3CLpro) crystal structure, the main proteolytic enzyme of SARS-CoV-2, has been unraveled, allowing the development of effective protease inhibitors via in silico and biological studies. In COVID-19 infected patients, the loss of lung function, and mortality are reported to be linked to several inflammatory mediators and cytokines. In this context, the approach of introducing immunomodulatory agents may be considered a dual lifesaving strategy in combination with antiviral drugs. This study aims to provide immunomodulatory natural products exhibiting potential protease inhibitory activities. Selected groups of alkaloids of different classes and two prenylated phenylpropanoids from the Brazilian green propolis were in silico screened for their ability to inhibit COVID-19 3CLpro protease. Results showed that compounds exhibited binding energy scores with values ranging from −6.96 to −3.70 compared to the reference synthetic protease inhibitor O6K with a binding energy score of −7.57. O6K binding energy was found comparable with lead phytochemicals in our study, while their toxicity and drug-likeness criteria are better than that of O6K. The activities of these molecules are mainly ascribed to their ability to form hydrogen bonding with 3CLpro crucial amino acid residues of the catalytic site. In addition, the molecular dynamics simulations further showed that some of these compounds formed stable complexes as evidenced by the occupancy fraction measurements. The study suggested that the major immunomodulators 3β, 20α-diacetamido-5α-pregnane, (20S)-(benzamido)-3β-(N,N-dimethyamino)-pregnane, and baccharin are 3CLpro inhibitors. Biological screenings of these phytochemicals will be valuable to experimentally validate and consolidate the results of this study before a rigid conclusion is reached, which may pave the way for the development of efficient modulatory bioactive compounds with dual bioactions in COVID-19 intervention. Communicated by Ramaswamy H. Sarma

Gaps in Cystic Fibrosis Care Are Associated with Reduced Lung Function in the U.S. Cystic Fibrosis Foundation Patient Registry.

Rationale: Cystic fibrosis (CF) is a genetic disease leading to progressive lung function loss and early mortality. Many clinical and demographic variables are associated with lung function decline, but little is known about the effects of prolonged periods of missed care. Objectives: To determine if missed care in the Cystic Fibrosis Foundation Patient Registry (CFFPR) is associated with decreased lung function at follow-up visits. Methods: Deidentified CFFPR data for 2004-2016 were analyzed, with the exposure of interest being ⩾12-month gap in CFFPR data. We modeled percentage predicted forced expiratory volume in 1 second using longitudinal semiparametric modeling with natural cubic splines for age (knots at quantiles) and with subject-specific random effects, adjusted for sex and CFTR (cysticfibrosis transmembrane conductance regulator) genotype, race, and ethnicity and included time-varying covariates for gaps in care, insurance type, underweight body mass index, CF-related diabetes status, and chronic infections. Results: A total of 24,328 individuals with 1,082,899 encounters in the CFFPR met inclusion criteria. In the cohort, 8,413 (35%) individuals had at least a single ⩾12-month episode of discontinuity, whereas 15,915 (65%) had continuous care. Of the encounters preceded by a 12-month gap, 75.8% occurred in patients 18 years and older. Compared with those with continuous care, those with a discontinuous care episode had a lower follow-up percentage predicted forced expiratory volume in 1 second at the index visit (-0.81%; 95% confidence interval, -1.00, -0.61) after adjustment for other variables. The magnitude of this difference was much greater (-2.1%; 95% confidence interval, -1.5, -2.7) in young adult F508del homozygotes. Conclusions: There was a high rate of ⩾12-month gap in care, especially in adults, documented in the CFFPR. Discontinuous care identified in the CFFPR was strongly associated with decreased lung function, especially in adolescents and young adults homozygous for the F508del CFTR mutation. This may have implications for identifying and treating people with lengthy gaps in care and may have implications for CFF care recommendations.

Dopamine Receptor D1 Is Exempt from Transforming Growth Factor β-Mediated Antifibrotic G Protein-Coupled Receptor Landscape Tampering in Lung Fibroblasts.

Pulmonary fibroblasts are the primary producers of extracellular matrix (ECM) in the lungs, and their pathogenic activation drives scarring and loss of lung function in idiopathic pulmonary fibrosis (IPF). This uncontrolled production of ECM is stimulated by mechanosignaling and transforming growth factor beta 1 (TGF-β1) signaling that together promote transcriptional programs including Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ). G protein-coupled receptors (GPCRs) that couple to G α s have emerged as pharmacological targets to inactivate YAP/TAZ signaling and promote lung fibrosis resolution. Previous studies have shown a loss of expression of "antifibrotic GPCRs"-receptors that couple to G α s, in IPF patient-derived fibroblasts compared with non-IPF samples. Of the 14 G α s GPCRs we found to be expressed in lung fibroblasts, the dopamine receptor D1 (DRD1) was one of only two not repressed by TGF-β1 signaling, with the β2-adrenergic receptor being the most repressed. We compared the potency and efficacy of multiple D1 and β2 receptor agonists +/- TGF-β1 treatment in vitro for their ability to elevate cAMP, inhibit nuclear localization of YAP/TAZ, regulate expression of profibrotic and antifibrotic genes, and inhibit cellular proliferation and collagen deposition. Consistently, the activity of β2 receptor agonists was lost, whereas D1 receptor agonists was maintained, after stimulating cultured lung fibroblasts with TGF-β1. These data further support the therapeutic potential of the dopamine receptor D1 and highlight an orchestrated and pervasive loss of antifibrotic GPCRs mediated by TGF-β1 signaling. SIGNIFICANCE STATEMENT: Idiopathic pulmonary fibrosis (IPF) is a deadly lung disease with limited therapies. GPCRs have emerged as a primary target for the development of novel antifibrotic drugs; however, a challenge to this approach is the dramatic changes in GPCR expression in response to profibrotic stimuli. Here, we investigate the impact of TGF-β1 on the expression of antifibrotic GPCRs and show the D1 dopamine receptor expression is uniquely maintained in response to TGF-β1, further implicating it as a compelling target to treat IPF.

Collagen type I alters the proteomic signature of macrophages in a collagen morphology-dependent manner

Idiopathic pulmonary fibrosis is a progressive lung disease that causes scarring and loss of lung function. Macrophages play a key role in fibrosis, but their responses to altered morphological and mechanical properties of the extracellular matrix in fibrosis is relatively unexplored. Our previous work showed functional changes in murine fetal liver-derived alveolar macrophages on fibrous or globular collagen morphologies. In this study, we applied differential proteomics to further investigate molecular mechanisms underlying the observed functional changes. Macrophages cultured on uncoated, fibrous, or globular collagen-coated plastic were analyzed by liquid chromatography-mass spectrometry. The presence of collagen affected expression of 77 proteins, while 142 were differentially expressed between macrophages grown on fibrous or globular collagen. Biological process and pathway enrichment analysis revealed that culturing on any type of collagen induced higher expression of enzymes involved in glycolysis. However, this did not lead to a higher rate of glycolysis, probably because of a concomitant decrease in activity of these enzymes. Our data suggest that macrophages sense collagen morphologies and can respond with changes in expression and activity of metabolism-related proteins. These findings suggest intimate interactions between macrophages and their surroundings that may be important in repair or fibrosis of lung tissue.

Revisiting the COVID-19 Pandemic: An Insight into Long-Term Post-COVID Complications and Repurposing of Drugs

SARS-CoV-2 is a highly contagious and dangerous coronavirus that has been spreading around the world since late December 2019. Severe COVID-19 has been observed to induce severe damage to the alveoli, and the slow loss of lung function led to the deaths of many patients. Scientists from all over the world are now saying that SARS-CoV-2 can spread through the air, which is a very frightening prospect for humans. Many scientists thought that this virus would evolve during the first wave of the pandemic and that the second wave of reinfection with the coronavirus would also be very dangerous. In late 2020 and early 2021, researchers found different genetic versions of the SARS-CoV-2 virus in many places around the world. Patients with different types of viruses had different symptoms. It is now evident from numerous case studies that many COVID-19 patients who are released from nursing homes or hospitals are more prone to developing multi-organ dysfunction than the general population. Understanding the pathophysiology of COVID-19 and its impact on various organ systems is crucial for developing effective treatment strategies and managing long-term health consequences. The case studies highlighted in this review provide valuable insights into the ongoing health concerns of individuals affected by COVID-19.

Adaptation of Nontypeable Haemophilus influenzae in Human Airways in COPD: Genome Rearrangements and Modulation of Expression of HMW1 and HMW2.

Chronic obstructive pulmonary disease (COPD) is a common debilitating disorder that is the third most common cause of death globally. Chronic lower airway infection by nontypeable Haemophilus influenzae (NTHi) in adults with COPD increases airway inflammation, causes increased symptoms, and accelerates progressive loss of lung function. Little is known about the mechanisms by which NTHi survives in COPD airways. To explore this question, the present study analyzes, in detail, 14 prospectively collected, serial isolates of a strain that persisted for 543 days in a patient with COPD, including analysis of four gap-free complete genomes. The NTHi genome underwent inversion of a ~400-kb segment three times during persistence. This inversion event resulted in switching of expression of the HMW1A and HMW2A adhesins as the inversion sites are in the promoter regions of HMW1 and HMW2. Regulation of the level of expression of HMW 1 and HMW2 in the human airways was controlled by the ~400-kb inversion and by 7-bp repeats in the HMW promoters. Analysis of knockout mutants of the persistent strain demonstrated that HMW1 and HMW2 proteins both function in the adherence of NTHi to human respiratory epithelial cells during persistence and that HMW1 also facilitates invasion of epithelial cells. An inverse relationship between biofilm formation and HMW1 expression was observed during persistence. This work advances understanding of the mechanisms of persistence of NTHi in COPD airways, which can inform the development of novel interventions to treat and prevent chronic NTHi infection in COPD. IMPORTANCE Nontypeable Haemophilus influenzae (NTHi) persists in the lower airways of adults with chronic obstructive pulmonary disease (COPD) for months to years, increasing airway inflammation that accelerates the progressive loss of lung function. Understanding the mechanisms of persistence in human airways by NTHi is critical in developing novel interventions. Here, in detail, we studied longitudinally collected sequential isolates of a strain of NTHi that persisted in an adult with COPD, including analysis of four gap-free genomes and knockout mutants to elucidate how the genome adapts in human airways. The NTHi genome underwent a genome rearrangement during persistence and this inversion impacted regulation of expression of key virulence phenotypes, including adherence to respiratory epithelial cells, invasion of epithelial cells and biofilm formation. These novel observations advance our understanding of the mechanisms of persistence of NTHi in the airways of adults with COPD.

Interleukin-1 as a Predictor Cytokine SARS-CoV: Article Review

Severe acute respiratory syndrome coronavirus (SARS-CoV) is an etiologic agent of respiratory disease that has a mortality rate of 10%. IL-1 actively participates in the inflammatory response to infection. SARS-CoV-2 appears to act on the activation and maturation of IL-1?, which in turn activates other proinflammatory cytokines, such as IL-6 and TNF-. Therefore, IL-1? is part of the cytokine storm generated by coronavirus infection. Elevated levels of the IL-1 receptor antagonist (IL-1Ra) in severe cases of COVID-19, and this marker have been associated with increased viral load, loss of lung function, lung damage, and risk of death. In addition, there is an increase in IL-1? levels in patients with severe COVID-19, and this is strongly associated with lung injury. IL-1 levels are associated with the virulence of the process, and significantly higher serum levels have been observed in severe symptomatic SARS-CoV-2 cases than in mild cases or in those infected with the 2003 SARS-CoV coronavirus or 2012 MERS coronavirus.

Exacerbations in COPD: a personalised approach to care

Patients with chronic obstructive pulmonary disease (COPD) can have acute episodes of worsening symptoms, known generically as exacerbations, which are clinically relevant because they involve an acute deterioration of the patient's health status, worsen the patient's prognosis, and are the main cause of economic expenditure associated with COPD. 1 Seemungal TAR Donaldson GC Paul EA Bestall JC Jeffries DJ Wedzicha JA Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1998; 157: 1418-1422 Crossref PubMed Scopus (1786) Google Scholar , 2 Wilkinson TMA Patel IS Wilks M Donaldson GC Wedzicha JA Airway bacterial load and FEV1 decline in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2003; 167: 1090-1095 Crossref PubMed Scopus (303) Google Scholar , 3 Dransfield MT Kunisaki KM Strand MJ et al. Acute exacerbations and lung function loss in smokers with and without chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2017; 195: 324-330 Crossref PubMed Scopus (170) Google Scholar , 4 Soler-Cataluña JJ Martínez-García MA Román Sánchez P Salcedo E Navarro M Ochando R Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease. Thorax. 2005; 60: 925-931 Crossref PubMed Scopus (1401) Google Scholar , 5 Iheanacho I Zhang S King D Rizzo M Ismaila AS Economic burden of chronic obstructive pulmonary disease (COPD): a systematic literature review. Int J Chron Obstruct Pulmon Dis. 2020; 15: 439-460 Crossref PubMed Scopus (93) Google Scholar However, whether these episodes are truly due to an exacerbation of the underlying disease or correspond to worsening symptoms due to any of the diseases that commonly coexist with COPD is difficult to ascertain. In fact, both possibilities can occur separately or in combination. In this context, it is worth noting that effective management of COPD reduces the incidence of exacerbations by around 25–30%, but that most episodes remain (70–75%). 6 Lipson DA Barnhart F Brealey N et al. Once-daily single-inhaler triple versus dual therapy in patients with COPD. N Engl J Med. 2018; 378: 1671-1680 Crossref PubMed Scopus (622) Google Scholar To what extent are these remaining exacerbations due to other factors (ie, are patients misdiagnosed) or mechanisms of COPD not targeted by current preventive treatments? Addressing this question in future research is important to reduce or prevent the incidence and consequences of these exacerbations.

Caveolin-1-Related Intervention for Fibrotic Lung Diseases.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease (ILD) for which there are no effective treatments. Lung transplantation is the only viable option for patients with end-stage PF but is only available to a minority of patients. Lung lesions in ILDs, including IPF, are characterized by alveolar epithelial cell (AEC) senescence and apoptosis and accumulation of activated myofibroblasts and/or fibrotic lung (fL) fibroblasts (fLfs). These composite populations of fLfs show a high rate of basal proliferation, resist apoptosis and senescence, and have increased migration and invasiveness. They also more readily deposit ECM proteins. These features eventuate in progressive destruction of alveolar architecture and loss of lung function in patients with PF. The identification of new, safer, and more effective therapy is therefore mandatory for patients with IPF or related ILDs. We found that increased caveolin-1 and tumor suppressor protein, p53 expression, and apoptosis in AECs occur prior to and then with the proliferation of fLfs in fibrotic lungs. AECs with elevated p53 typically undergo apoptosis. fLfs alternatively demonstrate strikingly low basal levels of caveolin-1 and p53, while mouse double minute 2 homolog (mdm2) levels and mdm2-mediated degradation of p53 protein are markedly increased. The disparities in the expression of p53 in injured AECs and fLfs appear to be due to increased basal expression of caveolin-1 in apoptotic AECs with a relative paucity of caveolin-1 and increased mdm2 in fLfs. Therefore, targeting caveolin-1 using a caveolin 1 scaffolding domain peptide, CSP7, represents a new and promising approach for patients with IPF, perhaps other forms of progressive ILD or even other forms of organ injury characterized by fibrotic repair. The mechanisms of action differ in the injured AECs and in fLfs, in which differential signaling enables the preservation of AEC viability with concurrent limitation of fLf expansion and collagen secretion. The findings in three models of PF indicate that lung scarring can be nearly abrogated by airway delivery of the peptide. Phase 1 clinical trial testing of this approach in healthy volunteers has been successfully completed; Phase 1b in IPF patients is soon to be initiated and, if successful, will be followed by phase 2 testing in short order. Apart from the treatment of IPF, this intervention may be applicable to other forms of tissue injury characterized by fibrotic repair.

Dysregulated lipid metabolism in lymphangioleiomyomatosis pathogenesis as a paradigm of chronic lung diseases.

A chronic inflammatory condition characterizes various lung diseases. Interestingly, a great contribution to inflammation is made by altered lipids metabolism, that can be caused by the deregulation of the mammalian target of rapamycin complex-1 (mTORC1) activity. There is evidence that one of mTOR downstream effectors, the sterol regulatory element-binding protein (SREBP), regulates the transcription of enzymes involved in the de novo fatty acid synthesis. Given its central role in cell metabolism, mTOR is involved in several biological processes. Among those, mTOR is a driver of senescence, a process that might contribute to the establishment of chronic lung disease because the characteristic irreversible inhibition of cell proliferation, associated to the acquisition of a pro-inflammatory senescence-associated secretory phenotype (SASP) supports the loss of lung parenchyma. The deregulation of mTORC1 is a hallmark of lymphangioleiomyomatosis (LAM), a rare pulmonary disease predominantly affecting women which causes cystic remodeling of the lung and progressive loss of lung function. LAM cells have senescent features and secrete SASP components, such as growth factors and pro-inflammatory molecules, like cancer cells. Using LAM as a paradigm of chronic and metastatic lung disease, here we review the published data that point out the role of dysregulated lipid metabolism in LAM pathogenesis. We will discuss lipids' role in the development and progression of the disease, to hypothesize novel LAM biomarkers and to propose the pharmacological regulation of lipids metabolism as an innovative approach for the treatment of the disease.

Comparative Study of Ectopic Lymphoid Aggregates in Sheep and Murine Models of Bleomycin-Induced Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic disease characterized by excessive deposition of extracellular matrix in the interstitial lung parenchyma, often manifested by dyspnea and progressive loss of lung function. The role of inflammation in the pathogenesis of IPF is not well understood. This study evaluated the histopathological and inflammatory components of bleomycin-induced pulmonary fibrosis in mouse and sheep models, in terms of their ability to translate to the human IPF. Merino sheep (n = 8) were bronchoscopically administered with two bleomycin infusions, two weeks apart, into a caudal lung segment, with a saline (control) administered into a caudal segment in the opposite lung. Balb/c mice were twice intranasally instilled, one week apart, with either bleomycin (n = 7); or saline (control, n = 7). Lung samples were taken for the histopathological assessment 28 days in sheep and 21 days in mice after the first bleomycin administration. We observed tertiary lymphoid aggregates, in the fibrotic lung parenchyma of sheep, but not in mouse lung tissues exposed to bleomycin. B-cell and T-cell infiltration significantly increased in sheep lung tissues compared to mouse lung tissues due to bleomycin injury. Statistical analysis showed that the fibrotic score, fibrotic fraction, and tissue fraction significantly increased in sheep lung tissues compared to murine lung tissues. The presence of tertiary lymphoid aggregates in the lung parenchyma and increased infiltration of T-cells and B-cells, in the sheep model, may be useful for the future study of the underlying inflammatory disease mechanisms in the lung parenchyma of IPF patients.

Toxic effect of carpet dust on the biochemical indices and histological structure of the lung in rats: the potential role of cytochrome P450 2E1 and extracellular signal-regulated kinase/mitogen-activated protein kinase pathways

Background: Carpet dust exposure in the carpet industry causes various respiratory hazards that lead to permanent loss of lung function. This study investigated the potentially toxic effects of knotted and tufted carpet dust on rat lungs and the possible involvement of cytochrome P450 2E1 (CYP2E1) and extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) pathways in the induced toxicity, as well as histological changes in the lung induced by carpet dust. Methods: This study divided 48 adult rats into six groups: group I was the control group, group II (vehicle group) received phosphate buffer saline (50 µL/rat), groups III and IV received knotted dust (2.5 and 5 mg/kg, respectively), and groups V and VI received tufted dust (2.5 and 5 mg/kg, respectively). All treatments were intranasally administered once a day for 7 days. Results: Both dust types significantly decreased the lung content of GSH compared with the control. Significantly elevated malondialdehyde (MDA) and nitric oxide (NO) lung contents were observed with an increased CYP2E1, interleukin (IL)-6, nuclear factor kappa B (NF-κβ), and ERK/MAPK. The histological lung structure was moderately affected with a moderately increased number of CD68-positive macrophages in the lung parenchyma of knotted dust-exposed rats, whereas tufted dust exposure severely affected the lung tissue with significantly increased CD68-positive macrophages. Conclusions: Carpet dust exposure could induce oxidative stress and inflammatory response in the lung tissue via induction of CYP2E1 that stimulates ERK/MAPK signalling pathway proteins, resulting in elevated MDA, NO and IL-6 levels in the lung tissue with suppressed GSH content. Tufted dust could possess a more toxic response than knotted ones.

Sirtuin3 confers protection against acute pulmonary embolism through anti-inflammation, and anti-oxidative stress, and anti-apoptosis properties: participation of the AMP-activated protein kinase/mammalian target of rapamycin pathway.

An increasing number of studies have suggested that oxidative stress and inflammation play momentous roles in acute pulmonary embolism (APE). Honokiol, a bioactive biphenolic phytochemical substance, is known for its strong anti-oxidative and anti-inflammatory effects, and it served as an activator of sirtuin3 (SIRT3) in the present study. The purposes of the study were to explore the effects of honokiol on APE rats and investigate whether the function of honokiol is mediated by SIRT3 activation. In the study, the rats received a right femoral vein injection of dextran gel G-50 particles (12 mg/kg) to establish the APE model and were subsequently administered honokiol and/or a selective SIRT3 inhibitor 3-(1H-1,2,3-triazol-4-yl)pyridine (3-TYP; 5 mg/kg) intraperitoneally. The results showed that SIRT3 activation by honokiol attenuated the loss in lung function, ameliorated the inflammatory response and oxidative damage, and inhibited apoptosis in lung tissues of the rats with APE but that this was reversed by 3-TYP. In addition, we found that the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway might be activated by honokiol but restrained by 3-TYP. These results indicated that honokiol was capable of suppressing the adverse effects of APE and that this was diminished by SIRT3 suppression, implying that activation of SIRT3 might serve as a therapeutic method for APE.

Lung Function Loss in Relation to Silica Dust Exposure at a Gold Mine

Lung Function Loss in Relation to Silica Dust Exposure at a Gold Mine

Chronic Obstructive Pulmonary Disease among non-Smokers

Since tobacco use has been linked to COPD for more than 50 years, this population has served as the foundation for almost all of our knowledge regarding the clinical, physiological, pathological, and radiological aspects of the disease as well as the rates of lung function loss and the effectiveness of various treatments. We stated in 1990 that 25 to 45% of COPD cases among never smokers. According to the 2017 Global Burden of Disease report, smoking is only responsible for 35% of the burden of COPD worldwide, with the majority of cases occurring in high-income nations. Most of the world's remaining 65% of nonsmokers with COPD live in low- and middle-income nations. Other non-smoking risk factors for COPD include exposure to biomass smoke while cooking in poorly ventilated homes, high ambient air pollution levels, occupational exposures to dust and gases, ambient ozone exposure, poverty, recurrent respiratory tract infections in childhood, poorly controlled chronic persistent asthma, and prior tubercular lung disease. Worldwide, non-tobacco-related risk factors, which vary by geographic region, are to blame for around half of all instances of COPD. Inflammation, oxidative stress, airway remodelling, and accelerated lung ageing are potential factors for the development of COPD in never-smokers. Never-smokers with COPD had less severe chronic respiratory symptoms, little to no emphysema, less airflow limitation, and fewer comorbidities than smokers who acquire COPD; however, exacerbations can still happen often. More research- including epidemiological, translational, clinical, and implementation studies- is required to fill in knowledge gaps and promote viable solutions to lessen the burden of COPD in never-smokers. Clinical history and spirometry can be used to diagnose Chronic Obstructive Pulmonary Disease (COPD), but identifying its risk factors is time-consuming and crucial because doing so can stop the disease's progression. Contrary to popular belief, smoking cigarettes is only one of the numerous risk factors for COPD. We have examined the etiology of nonsmoker COPD through this review in an effort to identify the causative risk factor and reduce the disease's morbidity and mortality.

Chronic Expression of a Clinical SFTPC Mutation Causes Murine Lung Fibrosis with Idiopathic Pulmonary Fibrosis Features.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic interstitial lung disease. A barrier to developing more effective therapies for IPF is the dearth of preclinical models that recapitulate the early pathobiology of this disease. Intratracheal bleomycin, the conventional preclinical murine model of IPF, fails to reproduce the intrinsic dysfunction to the alveolar epithelial type 2 cell (AEC2) that is believed to be a proximal event in the pathogenesis of IPF. Murine fibrosis models based on SFTPC (Surfactant Protein C gene) mutations identified in patients with interstitial lung disease cause activation of the AEC2 unfolded protein response and endoplasmic reticulum stress-an AEC2 dysfunction phenotype observed in IPF. Although these models achieve spontaneous fibrosis, they do so with precedent lung injury and thus are challenged to phenocopy the general clinical course of patients with IPF-gradual progressive fibrosis and loss of lung function. Here, we report a refinement of a murine Sftpc mutation model to recapitulate the clinical course, physiological impairment, parenchymal cellular composition, and biomarkers associated with IPF. This platform provides the field with an innovative model to understand IPF pathogenesis and index preclinical therapeutic candidates.

Pulmonary function test results and radiological findings 90-120 days after COVID-19 pneumonia: a single-center retrospective study

Background: Survivors of Coronavirus Disease 2019 (COVID-19) pneumonia may have permanent loss of lung function and radiological sequelae. There is a need for markers that predict patients for whom follow-up is required. Aim of the study: To identify the risk factors associated with post-COVID-19 radiological and functional findings. Material and Methods: This is a single-center retrospective study performed in a university hospital. We obtained the data from all hospitalized patients with COVID-19 pneumonia. We included those who underwent pulmonary function tests (PFT) and chest computerized tomography (CT) 90-120 days later. We analyzed initial and peak laboratory results (C-reactive protein (CRP), d-dimer, ferritin, and fibrinogen), and the length of hospital and intensive care unit (ICU) stay. We examined the relationship between baseline data and radiological findings and PFT. Results: Fifty-six patients were included in this study. Of these, 31 (55.4%) were women. The mean age of the patients was 55.05 ± 13.29 years. The mean peak ferritin, fibrinogen, d-dimer, and CRP values recorded during hospitalization follow-up were 285.56 ± 339.82, 518.59 ± 186.93, 1.99 ± 5.69, and 98.94 ± 80.77, respectively. The mean length of hospital and ICU stay were 10.21 ± 8.01 and 8.38 ± 8.90 days, respectively. In 18 (32.1%) patients, we observed a restrictive pattern on PFT, and 22 (39.3%) patients had an abnormal diffusion test. In 21 (37.5%) patients we observed ground glass opacities and in 4 (7.1%) patients reticulation was seen on their chest CT. A multivariate logistic regression analysis revealed that the first visit and peak fibrinogen values were significantly associated with abnormal PFT (p = 0.049, R2 = 0.272), while ferritin and CRP levels at the first visit and peak levels were significantly associated with an abnormality on chest CT (p < 0.001, p = 0.05, respectively). Conclusions: High initial and peak ferritin, fibrinogen, and CRP levels were associated with persistent radiological findings on chest CT and abnormal PFT at 90–120 follow-up after COVID-19 pneumonia.

Exposure to Crude Oil-Related Volatile Organic Compounds Associated with Lung Function Decline in a Longitudinal Panel of Children.

Children in the affected area were exposed to large amounts of volatile organic compounds (VOCs) from the Hebei Spirit oil spill accident. We investigated the lung function loss from the exposure to VOCs in a longitudinal panel of 224 children 1, 3, and 5 years after the VOC exposure event. Atmospheric estimated concentration of total VOCs (TVOCs), benzene, toluene, ethylbenzene, and xylene for 4 days immediately after the accident were calculated for each village (n = 83) using a modeling technique. Forced expiratory volume in 1 s (FEV1) as an indicator of airway status was measured 1, 3, and 5 years after the exposure in 224 children 4~9 years of age at the exposure to the oil spill. Multiple linear regression and linear mixed models were used to evaluate the associations, with adjustment for smoking and second-hand smoke at home. Among the TVOCs (geometric mean: 1319.5 mg/m3·4 d), xylene (9.4), toluene (8.5), ethylbenzene (5.2), and benzene (2.0) were dominant in the order of air concentration level. In 224 children, percent predicted FEV1 (ppFEV1), adjusted for smoking and second-hand smoke at home, was 100.7% after 1 year, 96.2% after 3 years, and 94.6% after 5 years, and the loss over the period was significant (p < 0.0001). After 1 and 3 years, TVOCs, xylene, toluene, and ethylbenzene were significantly associated with ppFEV1. After 5 years, the associations were not significant. Throughout the 5 years' repeated measurements in the panel, TVOCs, xylene, toluene, and ethylbenzene were significantly associated with ppFEV1. Exposure to VOCs from the oil spill resulted in lung function loss among children, which remained significant up to 5 years after the exposure.