Pirfenidone (PFD) is a pharmacological compound with therapeutic efficacy in idiopathic pulmonary fibrosis. It has been chiefly characterized as an antifibrotic agent, although it was initially ...developed as an antiinflammatory compound because of its ability to diminish the accumulation of inflammatory cells and cytokines. Despite recent studies that have elucidated key mechanisms, the precise molecular activities of PFD remain incompletely understood. PFD modulates fibrogenic growth factors, thereby attenuating fibroblast proliferation, myofibroblast differentiation, collagen and fibronectin synthesis, and deposition of extracellular matrix. This effect is mediated by suppression of TGF-β1 (transforming growth factor-β1) and other growth factors. Here, we appraise the impact of PFD on TGF-β1 production and its downstream pathways. Accumulating evidence indicates that PFD also downregulates inflammatory pathways and therefore has considerable potential as a viable and innovative antiinflammatory compound. We examine the effects of PFD on inflammatory cells and the production of pro- and antiinflammatory cytokines in the lung. In this context, recent evidence that PFD can target inflammasome pathways and ensuing lung inflammation is highlighted. Finally, the antioxidant properties of PFD, such as its ability to inhibit redox reactions and regulate oxidative stress-related genes and enzymes, are detailed. In summary, this narrative review examines molecular mechanisms underpinning PFD and its recognized benefits in lung fibrosis. We highlight preclinical data that demonstrate the potential of PFD as a nonsteroidal antiinflammatory agent and outline areas for future research.
Swallowing is a complex biomechanical process synchronized with breathing to protect the airway. However, this finely tuned process may not work well in older individuals and in diseases such as ...chronic obstructive pulmonary disease (COPD). Swallow-breathing dysfunction can have serious detrimental consequences. Individuals with laryngeal penetration are up to 4 times more likely to develop pneumonia and, if pulmonary aspiration occurs, pneumonia is 10 times more likely (1). In COPD, aspiration may occur as a result of dysfunctional upper airway-protective mechanisms, reduced coordination of swallow with breathing, and changes in breathing habits induced by COPD itself (2, 3). Problems with swallow followed by aspiration have long been recognized in COPD, but, to date, research has been limited. Studies have been characterized by small sample sizes, variations in study methods, diagnostic disparities, and poorly defined patient populations (4-9). The prevalence of aspiration in individuals with stable COPD has been reported to be as high as 25% (4, 5), with a trend toward increased hospitalizations and mortality over 36 months (5). Only one exacerbation study has been conducted reporting aspiration in 17% of patients (10). To date, the overall prevalence of aspiration in patients with COPD remains unknown, and associations with adverse respiratory outcomes have not been prospectively examined. This Pulmonary Perspective outlines normal mechanisms of swallow and breathing, explores potential mechanisms of penetration-aspiration, examines evidence for penetration-aspiration in COPD and considers therapeutic strategies. Limitations in current knowledge of this field and research priorities are highlighted.
Contemporary Concise Review 2023: Asthma Politis, John; Bardin, Philip G.; Leong, Paul
Respirology,
August 2024, 2024-08-00, 20240801, Letnik:
29, Številka:
8
Journal Article
Recenzirano
Odprti dostop
SUMMARY OF KEY POINTS
Asthma research and management needs to meet the priorities of the end user—patients, carers and clinicians.
A better understanding of the natural history of asthma and the ...progression of disease has highlighted the importance of early identification of patients with asthma and the potential role of early intervention.
Management of mild asthma requires a consistent approach with the same detail and consideration used when managing severe disease.
Evidence around treatable traits approaches continues to evolve, supporting the role of a personalized medicine in asthma.
Oral corticosteroid (OCS) stewardship continues to be an urgent issue in asthma management. Strategies to taper OCS doses and the implementation of biologic therapies for their steroid sparing benefits will be important steps to address this problem.
The concept of remission in asthma provides an ambitious target and treatment outcome.
ABSTRACT
OCS play an important role in the management of asthma. However, steroid‐related AE are common and represent a leading cause of morbidity. Limited published studies suggest OCS usage varies ...across countries and recent registry data indicate that at least 25–60% of patients with severe asthma in developed countries may at some stage be prescribed OCS. Recent evidence indicate that many patients do not receive optimal therapy for asthma and are often prescribed maintenance OCS or repeated steroid bursts to treat exacerbations. Given the recent progress in adult severe asthma and new treatment options, judicious appraisal of steroid use is merited. A number of strategies and add‐on therapies are now available to treat severe asthma. These include increasing specialist referral for multidisciplinary assessments and implementing OCS‐sparing interventions, such as improving guideline adherence and add‐on tiotropium and macrolides. Biologics have recently become available for severe asthma; these agents reduce asthma exacerbations and lower OCS exposure. Further research, collaboration and consensus are necessary to develop a structured stewardship approach including realistic OCS‐weaning programmes for patients with severe asthma on regular OCS; education and public health campaigns to improve timely access to specialized severe asthma services for treatment optimization; and implementing targeted strategies to identify patients who warrant OCS use using objective biomarker‐based strategies.
Inhaled glucocorticoids are pivotal to achieve asthma control and disease stability in both children and adults; despite their use, with or without other treatments, many patients with asthma have ...ongoing episodic disease exacerbations.
1
Often, these are linked to provocative factors such as viral or bacterial infections, nonadherence to treatment, allergen exposure, and environmental air pollution.
2
Although the clinical presentation varies widely, exacerbations are frequently heralded by slowly declining lung function and increasing asthma symptoms. These acute flares of asthma are detrimental because they adversely affect quality of life, lung function, and health care costs and have the potential to end . . .
"Treatable traits" have been proposed as a new paradigm for the management of airway diseases, particularly complex disease, which aims to apply personalised medicine to each individual to improve ...outcomes. Moving new treatment approaches from concepts to practice is challenging, but necessary. In an effort to accelerate progress in research and practice relating to the treatable traits approach, the Treatable Traits Down Under International Workshop was convened in Melbourne, Australia in May 2018. Here, we report the key concepts and research questions that emerged in discussions during the meeting. We propose a programme of research that involves gaining international consensus on candidate traits, recognising the prevalence of traits, and identifying a potential hierarchy of traits based on their clinical impact and responsiveness to treatment. We also reflect on research methods and designs that can generate new knowledge related to efficacy of the treatable traits approach and consider multidisciplinary models of care that may aid its implementation into practice.
Currently there is no consistent and widely accepted approach to the diagnosis of vocal cord dysfunction/inducible laryngeal obstruction (VCD/ILO). Harmonised diagnostic methods are vital to enable ...optimal diagnosis, advance management and enable research. We aim to obtain consensus on how expert clinicians recognise and diagnose VCD/ILO.
Two-round modified Delphi, with workshop validation.
Institutional Board Review was obtained from the Monash Health Human Research Ethics Committee. The dissemination plan is for presentation and publication.
Registered at Australia and New Zealand Clinical Trials Registry ACTRN12621001520820p.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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