scholarly journals Collagen Biosynthesis, Processing, and Maturation in Lung Ageing

2021 ◽  
Vol 8 ◽  
Author(s):  
Ceylan Onursal ◽  
Elisabeth Dick ◽  
Ilias Angelidis ◽  
Herbert B. Schiller ◽  
Claudia A. Staab-Weijnitz
Keyword(s):  
Lung Disease ◽  
Cell Function ◽  
Lysyl Oxidase ◽  
Advanced Glycation Endproducts ◽  
Mouse Lung ◽  
Chronic Obstructive ◽  
Collagen Biosynthesis ◽  
Collagen Crosslinks ◽  
Collagen Crosslinking ◽  
Chronic Lung Diseases

In addition to providing a macromolecular scaffold, the extracellular matrix (ECM) is a critical regulator of cell function by virtue of specific physical, biochemical, and mechanical properties. Collagen is the main ECM component and hence plays an essential role in the pathogenesis and progression of chronic lung disease. It is well-established that many chronic lung diseases, e.g., chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) primarily manifest in the elderly, suggesting increased susceptibility of the aged lung or accumulated alterations in lung structure over time that favour disease. Here, we review the main steps of collagen biosynthesis, processing, and turnover and summarise what is currently known about alterations upon lung ageing, including changes in collagen composition, modification, and crosslinking. Recent proteomic data on mouse lung ageing indicates that, while the ER-resident machinery of collagen biosynthesis, modification and triple helix formation appears largely unchanged, there are specific changes in levels of type IV and type VI as well as the two fibril-associated collagens with interrupted triple helices (FACIT), namely type XIV and type XVI collagens. In addition, levels of the extracellular collagen crosslinking enzyme lysyl oxidase are decreased, indicating less enzymatically mediated collagen crosslinking upon ageing. The latter contrasts with the ageing-associated increase in collagen crosslinking by advanced glycation endproducts (AGEs), a result of spontaneous reactions of protein amino groups with reactive carbonyls, e.g., from monosaccharides or reactive dicarbonyls like methylglyoxal. Given the slow turnover of extracellular collagen such modifications accumulate even more in ageing tissues. In summary, the collective evidence points mainly toward age-induced alterations in collagen composition and drastic changes in the molecular nature of collagen crosslinks. Future work addressing the consequences of these changes may provide important clues for prevention of lung disease and for lung bioengineering and ultimately pave the way to novel targeted approaches in lung regenerative medicine.

scholarly journals The instructive extracellular matrix of the lung: basic composition and alterations in chronic lung disease

2017 ◽  
Vol 50 (1) ◽  
pp. 1601805 ◽  
Author(s):  
Gerald Burgstaller ◽  
Bettina Oehrle ◽  
Michael Gerckens ◽  
Eric S. White ◽  
Herbert B. Schiller ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Lung Disease ◽  
Chronic Lung Disease ◽  
Cell Function ◽  
Mechanical Stability ◽  
Solid Phase ◽  
Chronic Obstructive ◽  
Chronic Lung Diseases ◽  
Binding Interface ◽  
Ecm Proteins

The pulmonary extracellular matrix (ECM) determines the tissue architecture of the lung, and provides mechanical stability and elastic recoil, which are essential for physiological lung function. Biochemical and biomechanical signals initiated by the ECM direct cellular function and differentiation, and thus play a decisive role in lung development, tissue remodelling processes and maintenance of adult homeostasis. Recent proteomic studies have demonstrated that at least 150 different ECM proteins, glycosaminoglycans and modifying enzymes are expressed in the lung, and these assemble into intricate composite biomaterials. These highly insoluble assemblies of interacting ECM proteins and their glycan modifications can act as a solid phase-binding interface for hundreds of secreted proteins, which creates an information-rich signalling template for cell function and differentiation. Dynamic changes within the ECM that occur upon injury or with ageing are associated with several chronic lung diseases. In this review, we summarise the available data about the structure and function of the pulmonary ECM, and highlight changes that occur in idiopathic pulmonary fibrosis (IPF), pulmonary arterial hypertension (PAH), chronic obstructive pulmonary disease (COPD), asthma and lung cancer. We discuss potential mechanisms of ECM remodelling and modification, which we believe are relevant for future diagnosis and treatment of chronic lung disease.

824 Case Series on the Use of Volume Assured Pressure Support in Patients with Chronic Pulmonary Disease and Progressive Hypercapnia

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A321-A322
Author(s):  
William LeMaster ◽  
Dale Jun ◽  
Sharon De Cruz ◽  
Michelle Zeidler ◽  
Rajan Saggar
Keyword(s):  
Respiratory Failure ◽  
Lung Disease ◽  
Pulmonary Disease ◽  
Lung Diseases ◽  
Lung Transplant ◽  
Pressure Support ◽  
Case Series ◽  
Chronic Obstructive ◽  
Hypoxemic Respiratory Failure ◽  
Chronic Lung Diseases

Abstract Introduction Chronic hypercapnia results from destruction of lung parenchyma which occurs in chronic lung diseases including interstitial lung disease (ILD), bronchiectasis, and chronic lung transplant rejection. Many patients with these diseases will experience progressive respiratory failure eventually requiring consideration of transplantation or re-transplantation. Due to physiologic changes in sleep including reduction in tidal volume, worsening air tapping, and REM atonia, hypoventilation can be exacerbated during the sleeping hours. We present four patients who were prescribed nocturnal Volume Assured Pressure Support VAPS for their progressive hypercapnia. Report of case(s) Subject 1 is a 72 year old female with severe bronchiectasis and restrictive lung disease due to TB pneumonia at a young age. Subject 2 is a 45 year old male with history of pulmonary cavitation due to extensive TB disease when he was younger. Subject 3 is a 45-year-old woman with rheumatoid arthritis related ILD with associated pulmonary arterial hypertension. Subject 4 is a 74 year old patient with a bilateral lung transplant for IPF complicated by bronchiolitis obliterans syndrome who presented with progressive dyspnea and hypercapnia. Despite optimal therapy, all of these patients were admitted for hypercapnic and hypoxemic respiratory failure requiring treatment with BPAP then transitioned to nocturnal VAPS on discharge. For all patients, dyspnea and pCO2 improved as outpatients although all patients did eventually experience an exacerbation of their lung disease requiring repeat admission. Conclusion Due to the physiologic changes that occur with sleep, patients with severe lung disease may experience worsening CO2 retention while sleeping. There is little data assessing the use of chronic nocturnal non-invasive ventilation (NIV) to treat the hypercapnia of chronic lung diseases other than chronic obstructive pulmonary disease, extra-thoracic restriction, and neuromuscular disease. In this case series, nocturnal VAPS stabilized and/or reduced pCO2 in patients with pulmonary parenchymal disease of various etiologies. Additional studies are needed to assess long term effects of VAPS in these patients, including exacerbations, symptoms, and overall mortality. Support (if any):

Attitude and Barriers in Palliative Care and Advance Care Planning in Nonmalignant Chronic Lung Disease: Results From a Danish National Survey

2020 ◽  
Vol 35 (4) ◽  
pp. 232-235
Author(s):  
Anita Rath Sørensen ◽  
Kristoffer Marsaa ◽  
Thomas Skovhus Prior ◽  
Elisabeth Bendstrup
Keyword(s):  
Palliative Care ◽  
Lung Disease ◽  
Advance Care Planning ◽  
Clinical Skills ◽  
University Hospital ◽  
Organizational Level ◽  
Chronic Obstructive ◽  
Care Planning ◽  
Chronic Lung Diseases ◽  
Advance Care

Introduction: Patients with chronic obstructive pulmonary disease and interstitial lung disease have a significant burden of symptoms. Many are not offered palliative care (PC). Our aim was to investigate the attitudes to and barriers for PC among physicians. Method: A web-based survey was conducted among members of the Danish Respiratory Society. The questionnaire included contextual (gender, age, clinical experience, type of center, patient caseload) and outcome questions (knowledge and use of statements for PC and advance care planning [ACP], practice of communication about end-of-life decisions, practice for referral to PC, barriers regarding structural surroundings, clinical skills, and organization). Results: One hundred fifty-six (45%) physicians responded. Median age was 40 - 49 years and 55% were female. Fifty-two percent were specialists; 71% worked at a university hospital. The majority of physicians (60%) reported barriers for discussions about PC and ACP; 63% reported lack of time, 52% lack of multidisciplinary staff settings, 63% reported the unpredictability of the prognosis, and 20% insufficient awareness of patient’s culture, religion, or spirituality. Fewer specialists than nonspecialists reported barriers toward ACP. The majority had knowledge of guidelines in PC and ACP, but only a minority used these in daily clinical practice. Conclusion: The attitude toward PC and ACP conversations was positive and implementation was regarded as important, but only a minority performed these conversations in practice. Main barriers were lack of time and staff. Palliative care guidelines were known but only scarcely used. Structural changes at the organizational level to improve access to palliation for patients with nonmalignant chronic lung diseases are needed.

scholarly journals Vitamin D Deficiency and Chronic Lung Disease

2009 ◽  
Vol 16 (3) ◽  
pp. 75-80 ◽  
Author(s):  
Christopher R Gilbert ◽  
Seth M Arum ◽  
Cecilia M Smith
Keyword(s):  
Vitamin D ◽  
Pulmonary Function ◽  
Lung Disease ◽  
Vitamin D Deficiency ◽  
Chronic Lung Disease ◽  
Obstructive Lung Disease ◽  
Lung Diseases ◽  
Chronic Obstructive Lung Disease ◽  
Chronic Obstructive ◽  
Chronic Lung Diseases

Vitamin D deficiency is increasingly being recognized as a prevalent problem in the general population. Patients with chronic lung diseases such as asthma, cystic fibrosis, chronic obstructive lung disease and interstitial pneumonia appear to be at increased risk for vitamin D deficiency for reasons that are not clear.Several studies indicate that vitamin D possesses a range of anti-inflammatory properties and may be involved in processes other than the previously believed functions of calcium and phosphate homeostasis. Various cytokines, cellular elements, oxidative stress and protease/antiprotease levels appear to affect lung fibroproliferation, remodelling and function, which may be influenced by vitamin D levels. Chronic lung diseases such as asthma and chronic obstructive lung disease have also been linked to vitamin D on a genetic basis. This immune and genetic influence of vitamin D may influence the pathogenesis of chronic lung diseases. A recent observational study notes a significant association between vitamin D deficiency and decreased pulmonary function tests in a large ambulatory population.The present review will examine the current literature regarding vitamin D deficiency, its prevalence in patients with chronic lung disease, vitamin D anti-inflammatory properties and the role of vitamin D in pulmonary function.

scholarly journals COVID-19 and restrictive lung disease: A deadly combo to trip off the fine balance

2020 ◽  
Vol 90 (2) ◽  
Author(s):  
Kamal Kant Sahu ◽  
Ajay Kumar Mishra ◽  
Kevin Martin ◽  
Iryna Chastain
Keyword(s):  
Risk Factors ◽  
Chronic Obstructive Pulmonary Disease ◽  
Risk Factor ◽  
Lung Disease ◽  
Lung Diseases ◽  
Chronic Obstructive ◽  
Immunocompromised Patients ◽  
Obstructive Pulmonary Disease ◽  
Restrictive Lung Disease ◽  
Chronic Lung Diseases

Coronavirus Disease (COVID-19) pandemic has so far led to innumerable deaths worldwide. The risk factors so far that have been most studied as poor prognostic factors are old age, individuals with multiple comorbidities and immunocompromised patients. Amongst the chronic lung diseases, most patients with COVID-19 reported so far had asthma, chronic obstructive pulmonary disease (COPD), and interstitial lung disease. Herein, we discuss the significance of restrictive lung disease during the COVID-19 pandemic as a potential risk factor via an example of a patient with kyphoscoliosis who succumbed to death due to COVID-19 pneumonia.

scholarly journals Role of macrophage migration inhibitory factor in age-related lung disease

2015 ◽  
Vol 309 (1) ◽  
pp. L1-L10 ◽  
Author(s):  
Maor Sauler ◽  
Richard Bucala ◽  
Patty J. Lee
Keyword(s):  
Lung Disease ◽  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Clinical Manifestations ◽  
Biological Properties ◽  
Inhibitory Factor ◽  
Chronic Obstructive ◽  
Macrophage Migration ◽  
Chronic Lung Diseases ◽  
Age Related

The prevalence of many common respiratory disorders, including pneumonia, chronic obstructive lung disease, pulmonary fibrosis, and lung cancer, increases with age. Little is known of the host factors that may predispose individuals to such diseases. Macrophage migration inhibitory factor (MIF) is a potent upstream regulator of the immune system. MIF is encoded by variant alleles that occur commonly in the population. In addition to its role as a proinflammatory cytokine, a growing body of literature demonstrates that MIF influences diverse molecular processes important for the maintenance of cellular homeostasis and may influence the incidence or clinical manifestations of a variety of chronic lung diseases. This review highlights the biological properties of MIF and its implication in age-related lung disease.

scholarly journals The burden of chronic respiratory diseases in adults in Nepal: A systematic review

2021 ◽  
Vol 18 ◽  
pp. 147997312199457
Author(s):  
Winifred Ekezie ◽  
Alex Robert Jenkins ◽  
Ian Philip Hall ◽  
Catrin Evans ◽  
Rajendra Koju ◽  
...  
Keyword(s):  
Lung Disease ◽  
Low Income ◽  
Lung Diseases ◽  
Disease Burden ◽  
Airflow Obstruction ◽  
Chronic Respiratory Disease ◽  
Low Income Countries ◽  
Chronic Obstructive ◽  
Cross Sectional ◽  
Chronic Lung Diseases

While chronic lung disease causes substantial global morbidity and mortality, global estimates have primarily been based on broad assumptions. Specific country data from low-income countries such as Nepal are limited. This review assessed primary evidence on chronic respiratory disease burden among adults in Nepal. A systematic search was performed in June 2019 (updated May 2020) for studies through nine databases. High levels of heterogeneity deemed a narrative synthesis appropriate. Among 27 eligible studies identified, most were low-moderate quality with cross-sectional and retrospective study design. Chronic lung diseases identified were chronic obstructive pulmonary disease (COPD), asthma, bronchiectasis and restrictive lung diseases. Studies were categorised as: (i) community-based, (ii) hospital-based and (iii) comorbidity-related and disease burden. Reported disease prevalence varied widely (COPD, 1.67–14.3%; asthma, 4.2–8.9%). The prevalence of airflow obstruction was higher among rural dwellers (15.8%) and those exposed to household air pollution from domestic biomass burning as opposed to liquid petroleum gas users (Odds Ratio: 2.06). Several comorbidities, including hypertension and diabetes mellitus added to the disease burden. The review shows limited literature on lung disease burden in Nepal. Publications varied in terms of overall quality. Good quality research studies with prospective cohorts related to respiratory conditions are required.

scholarly journals The Role of miRNAs in Extracellular Matrix Repair and Chronic Fibrotic Lung Diseases

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1706
Author(s):  
Kauna Usman ◽  
Aileen Hsieh ◽  
Tillie-Louise Hackett
Keyword(s):  
Extracellular Matrix ◽  
Pulmonary Disease ◽  
Lung Diseases ◽  
Cell Function ◽  
Mechanical Stability ◽  
Current Knowledge ◽  
Chronic Obstructive ◽  
Elastic Recoil ◽  
Gene Expressions ◽  
Chronic Lung Diseases

The lung extracellular matrix (ECM) plays a key role in the normal architecture of the lung, from embryonic lung development to mechanical stability and elastic recoil of the breathing adult lung. The lung ECM can modulate the biophysical environment of cells through ECM stiffness, porosity, topography and insolubility. In a reciprocal interaction, lung ECM dynamics result from the synthesis, degradation and organization of ECM components by the surrounding structural and immune cells. Repeated lung injury and repair can trigger a vicious cycle of aberrant ECM protein deposition, accompanied by elevated ECM stiffness, which has a lasting effect on cell and tissue function. The processes governing the resolution of injury repair are regulated by several pathways; however, in chronic lung diseases such as asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary disease (IPF) these processes are compromised, resulting in impaired cell function and ECM remodeling. Current estimates show that more than 60% of the human coding transcripts are regulated by miRNAs. miRNAs are small non-coding RNAs that regulate gene expressions and modulate cellular functions. This review is focused on the current knowledge of miRNAs in regulating ECM synthesis, degradation and topography by cells and their dysregulation in asthma, COPD and IPF.

scholarly journals Proteases, Mucus, and Mucosal Immunity in Chronic Lung Disease

2021 ◽  
Vol 22 (9) ◽  
pp. 5018
Author(s):  
Michael C. McKelvey ◽  
Ryan Brown ◽  
Sinéad Ryan ◽  
Marcus A. Mall ◽  
Sinéad Weldon ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Disease ◽  
Lung Diseases ◽  
Lung Damage ◽  
Chronic Obstructive ◽  
Lung Function Decline ◽  
Obstructive Pulmonary Disease ◽  
Chronic Lung Diseases ◽  
Multifunctional Enzymes ◽  
Disease Experience

Dysregulated protease activity has long been implicated in the pathogenesis of chronic lung diseases and especially in conditions that display mucus obstruction, such as chronic obstructive pulmonary disease, cystic fibrosis, and non-cystic fibrosis bronchiectasis. However, our appreciation of the roles of proteases in various aspects of such diseases continues to grow. Patients with muco-obstructive lung disease experience progressive spirals of inflammation, mucostasis, airway infection and lung function decline. Some therapies exist for the treatment of these symptoms, but they are unable to halt disease progression and patients may benefit from novel adjunct therapies. In this review, we highlight how proteases act as multifunctional enzymes that are vital for normal airway homeostasis but, when their activity becomes immoderate, also directly contribute to airway dysfunction, and impair the processes that could resolve disease. We focus on how proteases regulate the state of mucus at the airway surface, impair mucociliary clearance and ultimately, promote mucostasis. We discuss how, in parallel, proteases are able to promote an inflammatory environment in the airways by mediating proinflammatory signalling, compromising host defence mechanisms and perpetuating their own proteolytic activity causing structural lung damage. Finally, we discuss some possible reasons for the clinical inefficacy of protease inhibitors to date and propose that, especially in a combination therapy approach, proteases represent attractive therapeutic targets for muco-obstructive lung diseases.

scholarly journals Optimization of combined measures of airway physiology and cardiovascular hemodynamics in mice

2020 ◽  
Vol 10 (1) ◽  
pp. 204589402091293 ◽  
Author(s):  
Katrina W. Kopf ◽  
Julie W. Harral ◽  
Emily A. Staker ◽  
Megan E. Summers ◽  
Irina Petrache ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Lung Disease ◽  
Chronic Lung Disease ◽  
Chronic Obstructive ◽  
Murine Models ◽  
Comprehensive Overview ◽  
Cardiovascular Hemodynamics ◽  
Chronic Lung Diseases ◽  
Group 3 ◽  
Airway Physiology

Pulmonary hypertension may arise as a complication of chronic lung disease typically associated with tissue hypoxia, as well as infectious agents or injury eliciting a type 2 immune response. The onset of pulmonary hypertension in this setting (classified as Group 3) often complicates treatment and worsens prognosis of chronic lung disease. Chronic lung diseases such as chronic obstructive lung disease (COPD), emphysema, and interstitial lung fibrosis impair airflow and alter lung elastance in addition to affecting pulmonary vascular hemodynamics that may culminate in right ventricle dysfunction. To date, functional endpoints in murine models of chronic lung disease have typically been limited to separately measuring airway and lung parenchyma physiology. These approaches may be lengthy and require a large number of animals per experiment. Here, we provide a detailed protocol for combined assessment of airway physiology with cardiovascular hemodynamics in mice. Ultimately, a comprehensive overview of pulmonary function in murine models of injury and disease will facilitate the integration of studies of the airway and vascular biology necessary to understand underlying pathophysiology of Group 3 pulmonary hypertension.

Sign in / Sign up

Export Citation Format

Share Document