scholarly journals Cystic Fibrosis Lung Disease in the Aging Population

2021 ◽  
Vol 12 ◽  
Author(s):  
Lisa Künzi ◽  
Molly Easter ◽  
Meghan June Hirsch ◽  
Stefanie Krick
Keyword(s):  
Cystic Fibrosis ◽  
Lung Disease ◽  
Airway Inflammation ◽  
Chronic Inflammation ◽  
Accelerated Aging ◽  
Aging Population ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Repair Mechanisms ◽  
Inflammatory State

The demographics of the population with cystic fibrosis (CF) is continuously changing, with nowadays adults outnumbering children and a median predicted survival of over 40 years. This leads to the challenge of treating an aging CF population, while previous research has largely focused on pediatric and adolescent patients. Chronic inflammation is not only a hallmark of CF lung disease, but also of the aging process. However, very little is known about the effects of an accelerated aging pathology in CF lungs. Several chronic lung disease pathologies show signs of chronic inflammation with accelerated aging, also termed “inflammaging”; the most notable being chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). In these disease entities, accelerated aging has been implicated in the pathogenesis via interference with tissue repair mechanisms, alterations of the immune system leading to impaired defense against pulmonary infections and induction of a chronic pro-inflammatory state. In addition, CF lungs have been shown to exhibit increased expression of senescence markers. Sustained airway inflammation also leads to the degradation and increased turnover of cystic fibrosis transmembrane regulator (CFTR). This further reduces CFTR function and may prevent the novel CFTR modulator therapies from developing their full efficacy. Therefore, novel therapies targeting aging processes in CF lungs could be promising. This review summarizes the current research on CF in an aging population focusing on accelerated aging in the context of chronic airway inflammation and therapy implications.

Pulmonary Evaluation

2016 ◽  
pp. 747-766
Author(s):  
Vivek N. Iyer
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Cystic Fibrosis ◽  
Lung Disease ◽  
Lung Diseases ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Airway Stenosis ◽  
Obstructive Lung Diseases ◽  
Diffuse Panbronchiolitis ◽  
Antitrypsin Deficiency

Obstructive lung diseases include chronic obstructive pulmonary disease (COPD) (eg, chronic bronchitis and emphysema), asthma, bronchiectasis, cystic fibrosis, obliterative bronchiolitis, and diffuse panbronchiolitis (eg, bullous lung disease, α‎1-antitrypsin deficiency, and airway stenosis). The 2 most prevalent obstructive lung diseases are COPD and asthma.

Respiratory issues in rehabilitation

2019 ◽  
pp. 233-250
Author(s):  
Manoj Sivan ◽  
Margaret Phillips ◽  
Ian Baguley ◽  
Melissa Nott
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Cystic Fibrosis ◽  
Lung Disease ◽  
Pulmonary Rehabilitation ◽  
The Other ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Respiratory Impairment ◽  
Neurological Conditions ◽  
Respiratory Conditions

Respiratory aspects of rehabilitation fall into two broad and overlapping categories. One is that of pulmonary rehabilitation which traditionally has focused on exercise, behaviour change, and educational-based intervention for those with chronic lung disease, predominantly chronic obstructive pulmonary disease, but its efficacy has since been proven in other chronic respiratory conditions (e.g. asthma, interstitial lung disease, cystic fibrosis, bronchiectasis, lung transplantation, and pulmonary hypertension). The other is rehabilitation in the context of neurogenic respiratory impairment, which is relevant to persons with both degenerative and monophasic-onset neurological conditions. These categories are overlapping as techniques from one may have relevance to the other. This chapter describes these aspects, investigations, and interventions.

scholarly journals CFTR: cystic fibrosis and beyond

2014 ◽  
Vol 44 (4) ◽  
pp. 1042-1054 ◽  
Author(s):  
Marcus A. Mall ◽  
Dominik Hartl
Keyword(s):  
Cystic Fibrosis ◽  
Lung Disease ◽  
Lessons Learned ◽  
Chronic Obstructive ◽  
Common Mutation ◽  
Transmembrane Conductance Regulator ◽  
Obstructive Pulmonary Disease ◽  
Airway Diseases ◽  
Δf508 Cftr

Cystic fibrosis (CF) remains the most common fatal hereditary lung disease. The discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene 25 years ago set the stage for: 1) unravelling the molecular and cellular basis of CF lung disease; 2) the generation of animal models to study in vivo pathogenesis; and 3) the development of mutation-specific therapies that are now becoming available for a subgroup of patients with CF. This article highlights major advances in our understanding of how CFTR dysfunction causes chronic mucus obstruction, neutrophilic inflammation and bacterial infection in CF airways. Furthermore, we focus on recent breakthroughs and remaining challenges of novel therapies targeting the basic CF defect, and discuss the next steps to be taken to make disease-modifying therapies available to a larger group of patients with CF, including those carrying the most common mutation ΔF508-CFTR. Finally, we will summarise emerging evidence indicating that acquired CFTR dysfunction may be implicated in the pathogenesis of chronic obstructive pulmonary disease, suggesting that lessons learned from CF may be applicable to common airway diseases associated with mucus plugging.

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.

Lung Disease and Genomics

2018 ◽  
Vol 29 (1) ◽  
pp. 74-83 ◽  
Author(s):  
Kenneth Wysocki
Keyword(s):  
Lung Cancer ◽  
Chronic Obstructive Pulmonary Disease ◽  
Cystic Fibrosis ◽  
Lung Disease ◽  
Precision Medicine ◽  
Pulmonary Disease ◽  
The Body ◽  
Chronic Obstructive ◽  
Past Century ◽  
Obstructive Pulmonary Disease

Research and application of genomic medicine in lung disease during the past century has clarified our understanding and focus on specific phenotypes, helping clinicians tailor treatment for individual patients. Cystic fibrosis and lung cancer have been researched extensively; specific genotypes have been instrumental in precision medicine to treat these lung diseases. Asthma and chronic obstructive pulmonary disease are more complex and heterogeneous in their pathogenesis, genotypic profile, and phenotypic expression, making treatment more difficult with increasing disease severity. This article focuses on the evolving state of the science of precision medicine in lung cancer, chronic obstructive pulmonary disease, asthma, and cystic fibrosis. The body of knowledge in lung disease is growing related to pharmacogenomics, clinical guidelines, genome editing, and approaches to genomic health that will guide clinical treatment options, reduce risk, and promote health.

scholarly journals The Ability of Metabolomics to Discriminate Non-Small-Cell Lung Cancer Subtypes Depends on the Stage of the Disease and the Type of Material Studied

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3314
Author(s):  
Tomasz Kowalczyk ◽  
Joanna Kisluk ◽  
Karolina Pietrowska ◽  
Joanna Godzien ◽  
Miroslaw Kozlowski ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Early Stage ◽  
Chronic Obstructive ◽  
Liquid Chromatography Mass Spectrometry ◽  
Obstructive Pulmonary Disease ◽  
Cell Lung Carcinoma ◽  
Cancer Subtypes ◽  
Inflammatory State ◽  
Nsclc Patients

Identification of the NSCLC subtype at an early stage is still quite sophisticated. Metabolomics analysis of tissue and plasma of NSCLC patients may indicate new, and yet unknown, metabolic pathways active in the NSCLC. Our research characterized the metabolomics profile of tissue and plasma of patients with early and advanced NSCLC stage. Samples were subjected to thorough metabolomics analyses using liquid chromatography-mass spectrometry (LC-MS) technique. Tissue and/or plasma samples from 137 NSCLC patients were analyzed. Based on the early stage tissue analysis, more than 200 metabolites differentiating adenocarcinoma (ADC) and squamous cell lung carcinoma (SCC) subtypes as well as normal tissue, were identified. Most of the identified metabolites were amino acids, fatty acids, carnitines, lysoglycerophospholipids, sphingomyelins, plasmalogens and glycerophospholipids. Moreover, metabolites related to N-acyl ethanolamine (NAE) biosynthesis, namely glycerophospho (N-acyl) ethanolamines (GP-NAE), which discriminated early-stage SCC from ADC, have also been identified. On the other hand, the analysis of plasma of chronic obstructive pulmonary disease (COPD) and NSCLC patients allowed exclusion of the metabolites related to the inflammatory state in lungs and the identification of compounds (lysoglycerophospholipids, glycerophospholipids and sphingomyelins) truly characteristic to cancer. Our results, among already known, showed novel, thus far not described, metabolites discriminating NSCLC subtypes, especially in the early stage of cancer. Moreover, the presented results also indicated the activity of new metabolic pathways in NSCLC. Further investigations on the role of NAE biosynthesis pathways in the early stage of NSCLC may reveal new prognostic and diagnostic targets.

scholarly journals Allergic Diseases Caused by Aspergillus Species in Patients with Cystic Fibrosis

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 357
Author(s):  
Aidan K. Curran ◽  
David L. Hava
Keyword(s):  
Cystic Fibrosis ◽  
Fungal Infections ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Hyphal Growth ◽  
Allergic Diseases ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Th2 Immune Response ◽  
Difficulty Breathing ◽  
Oral Corticosteroids

Aspergillus spp. are spore forming molds; a subset of which are clinically relevant to humans and can cause significant morbidity and mortality. A. fumigatus causes chronic infection in patients with chronic lung disease such as asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF). In patients with CF, A. fumigatus infection can lead to allergic disease, such as allergic bronchopulmonary aspergillosis (ABPA) which is associated with high rates of hospitalizations for acute exacerbations and lower lung function. ABPA results from TH2 immune response to Aspergillus antigens produced during hyphal growth, marked by high levels of IgE and eosinophil activation. Clinically, patients with ABPA experience difficulty breathing; exacerbations of disease and are at high risk for bronchiectasis and lung fibrosis. Oral corticosteroids are used to manage aspects of the inflammatory response and antifungal agents are used to reduce fungal burden and lower the exposure to fungal antigens. As the appreciation for the severity of fungal infections has grown, new therapies have emerged that aim to improve treatment and outcomes for patients with CF.

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