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Matrix Biology : Journal of the... Dec 2023Elastin is a long-lived fibrous protein that is abundant in the extracellular matrix of the lung. Elastic fibers provide the lung the characteristic elasticity during... (Review)
Review
Elastin is a long-lived fibrous protein that is abundant in the extracellular matrix of the lung. Elastic fibers provide the lung the characteristic elasticity during inhalation with recoil during exhalation thereby ensuring efficient gas exchange. Excessive deposition of elastin and other extracellular matrix proteins reduces lung compliance by impairing ventilation and compromising gas exchange. Notably, the degree of elastosis is associated with the progressive decline in lung function and survival in patients with interstitial lung diseases. Currently there are no proven therapies which effectively reduce the elastin burden in the lung nor prevent dysregulated elastosis. This review describes elastin's role in the healthy lung, summarizes elastosis in pulmonary diseases, and evaluates the current understanding of elastin regulation and dysregulation with the goal of guiding future research efforts to develop novel and effective therapies.
Topics: Humans; Lung; Lung Diseases, Interstitial; Fibrosis; Elastin; Elastic Tissue
PubMed: 37922998
DOI: 10.1016/j.matbio.2023.10.003 -
International Journal of Molecular... Jun 2023Pulmonary hypertension (PH) is a disease which affects the cardiopulmonary system; it is defined as a mean pulmonary artery pressure (mPAP) > 20 mmHg as measured by... (Review)
Review
Pulmonary hypertension (PH) is a disease which affects the cardiopulmonary system; it is defined as a mean pulmonary artery pressure (mPAP) > 20 mmHg as measured by right heart catheterization at rest, and is caused by complex and diverse mechanisms. In response to stimuli such as hypoxia and ischemia, the expression and synthesis of endothelin (ET) increase, leading to the activation of various signaling pathways downstream of it and producing effects such as the induction of abnormal vascular proliferation during the development of the disease. This paper reviews the regulation of endothelin receptors and their pathways in normal physiological processes and disease processes, and describes the mechanistic roles of ET receptor antagonists that are currently approved and used in clinical studies. Current clinical researches on ET are focused on the development of multi-target combinations and novel delivery methods to improve efficacy and patient compliance while reducing side effects. In this review, future research directions and trends of ET targets are described, including monotherapy and precision medicine.
Topics: Humans; Hypertension, Pulmonary; Receptors, Endothelin; Endothelin Receptor Antagonists; Lung; Endothelins; Endothelin-1
PubMed: 37373355
DOI: 10.3390/ijms241210206 -
BMJ (Clinical Research Ed.) Apr 2021To test whether StandingTall, a home based, e-health balance exercise programme delivered through an app, could provide an effective, self-managed fall prevention... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To test whether StandingTall, a home based, e-health balance exercise programme delivered through an app, could provide an effective, self-managed fall prevention programme for community dwelling older people.
DESIGN
Assessor blinded, randomised controlled trial.
SETTING
Older people living independently in the community in Sydney, Australia.
PARTICIPANTS
503 people aged 70 years and older who were independent in activities of daily living, without cognitive impairment, progressive neurological disease, or any other unstable or acute medical condition precluding exercise.
INTERVENTIONS
Participants were block randomised to an intervention group (two hours of StandingTall per week and health education; n=254) or a control group (health education; n=249) for two years.
MAIN OUTCOME MEASURES
The primary outcomes were the rate of falls (number of falls per person year) and the proportion of people who had a fall over 12 months. Secondary outcomes were the number of people who had a fall and the number who had an injurious fall (resulting in any injury or requiring medical care), adherence, mood, health related quality of life, and activity levels over 24 months; and balance and mobility outcomes over 12 months.
RESULTS
The fall rates were not statistically different in the two groups after the first 12 months (0.60 falls per year (standard deviation 1.05) in the intervention group; 0.76 (1.25) in the control group; incidence rate ratio 0.84, 95% confidence interval 0.62 to 1.13, P=0.071). Additionally, the proportion of people who fell was not statistically different at 12 months (34.6% in intervention group, 40.2% in control group; relative risk 0.90, 95% confidence interval 0.67 to 1.20, P=0.461). However, the intervention group had a 16% lower rate of falls over 24 months compared with the control group (incidence rate ratio 0.84, 95% confidence interval 0.72 to 0.98, P=0.027). Both groups had a similar proportion of people who fell over 24 months (relative risk 0.87, 95% confidence interval 0.68 to 1.10, P=0.239), but the proportion of people who had an injurious fall over 24 months was 20% lower in the intervention group compared with the control group (relative risk 0.80, 95% confidence interval 0.66 to 0.98, P=0.031). In the intervention group, 68.1% and 52.0% of participants exercised for a median of 114.0 min/week (interquartile range 53.5) after 12 months and 120.4 min/week (38.6) after 24 months, respectively. Groups remained similar in mood and activity levels. The intervention group had a 0.03 (95% confidence interval 0.01 to 0.06) improvement on the EQ-5D-5L (EuroQol five dimension five level) utility score at six months, and an improvement in standing balance of 11 s (95% confidence interval 2 to 19 s) at six months and 10 s (1 to 19 s) at 12 months. No serious training related adverse events occurred.
CONCLUSIONS
The StandingTall balance exercise programme did not significantly affect the primary outcomes of this study. However, the programme significantly reduced the rate of falls and the number of injurious falls over two years, with similar but not statistically significant effects at 12 months. E-health exercise programmes could provide promising scalable fall prevention strategies.
TRIAL REGISTRATION
ACTRN12615000138583.
Topics: Accidental Falls; Aged; Aged, 80 and over; Exercise Therapy; Female; Follow-Up Studies; Humans; Independent Living; Male; Patient Compliance; Prospective Studies; Quality of Life; Single-Blind Method; Telemedicine; Treatment Outcome; Wounds and Injuries
PubMed: 33824131
DOI: 10.1136/bmj.n740 -
Respiratory Care Sep 2022Blunt pulmonary contusions are associated with severe chest injuries and are independently associated with worse outcomes. Previous preclinical studies suggest that...
BACKGROUND
Blunt pulmonary contusions are associated with severe chest injuries and are independently associated with worse outcomes. Previous preclinical studies suggest that contusion progression precipitates poor pulmonary function; however, there are few current clinical data to corroborate this hypothesis. We examined pulmonary dynamics and oxygenation in subjects with pulmonary contusions to evaluate for impaired respiratory function.
METHODS
A chest injury database was reviewed for pulmonary contusions over 5 years at an urban trauma center. This database was expanded to capture mechanical ventilation parameters for the first 7 days on all patients with pulmonary contusion and who were intubated. Daily [Formula: see text]:[Formula: see text], oxygenation indexes (OI), and dynamic compliances were calculated. Pulmonary contusions were stratified by severity. The Fisher exact and chi square tests were performed on categorical variables, and Mann-Whitney U-tests were performed on continuous variables. Significance was assessed at a level of 0.05.
RESULTS A TOTAL OF
1,176 patients presented with pulmonary contusions, of whom, 301 subjects (25.6%) required intubation and had available invasive mechanical ventilation data. Of these, 144 (47.8%) had mild-moderate pulmonary contusion and 157 (52.2%) had severe pulmonary contusion. Overall injury severity score was high, with a median injury severity score of 29 (interquartile range, 22-38). The median duration of mechanical ventilation for mild-moderate pulmonary contusion was 7 d versus 10 d for severe pulmonary contusion ( = .048). All the subjects displayed moderate hypoxemia, which worsened until day 4-5 after intubation. Severe pulmonary contusion was associated with significantly worse early hypoxia on day 1 and day 2 versus mild-moderate pulmonary contusion. Severe pulmonary contusion also had a higher oxygenation index than mild-moderate pulmonary contusion. This trend persisted after adjustment for other factors, including transfusion and fluid administration.
CONCLUSIONS
Pulmonary contusions played an important role in the course of subjects who were acutely injured and required mechanical ventilation. Contusions were associated with hypoxemia not fully characterized by [Formula: see text]: [Formula: see text], and severe contusions had durable elevations in the oxygenation index despite confounders.
Topics: Contusions; Humans; Hypoxia; Lung; Lung Injury; Thoracic Injuries; Wounds, Nonpenetrating
PubMed: 35728821
DOI: 10.4187/respcare.09913 -
Advanced Drug Delivery Reviews Jan 2024Inhaled medicines continue to be an essential part of treatment for respiratory diseases such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis. In... (Review)
Review
Inhaled medicines continue to be an essential part of treatment for respiratory diseases such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis. In addition, inhalation technology, which is an active area of research and innovation to deliver medications via the lung to the bloodstream, offers potential advantages such as rapid onset of action, enhanced bioavailability, and reduced side effects for local treatments. Certain inhaled macromolecules and particles can also end up in different organs via lymphatic transport from the respiratory epithelium. While the majority of research on inhaled medicines is focused on the delivery technology, particle engineering, combination therapies, innovations in inhaler devices, and digital health technologies, researchers are also exploring new pharmaceutical technologies and strategies to prolong the duration of action of inhaled drugs. This is because, in contrast to most inhaled medicines that exert a rapid onset and short duration of action, long-acting inhaled medicines (LAIM) improve not only the patient compliance by reducing the dosing frequency, but also the effectiveness and convenience of inhaled therapies to better manage patients' conditions. This paper reviews the advances in LAIM, the pharmaceutical technologies and strategies for developing LAIM, and emerging new inhaled modalities that possess a long-acting nature and potential in the treatment and prevention of various diseases. The challenges in the development of the future LAIM are also discussed where active research and innovations are taking place.
Topics: Humans; Asthma; Pulmonary Disease, Chronic Obstructive; Pharmaceutical Preparations; Administration, Inhalation; Lung
PubMed: 38040120
DOI: 10.1016/j.addr.2023.115146 -
Best Practice & Research. Clinical... 2020The majority of children who undergo liver transplantation now survive into adulthood and their requirement for life-long follow-up means that they will need to... (Review)
Review
The majority of children who undergo liver transplantation now survive into adulthood and their requirement for life-long follow-up means that they will need to transition from paediatric to adult services. Poor transition is a risk factor for poor clinical and psychosocial outcomes and one of the barriers to effective transition is vulnerability to risk-taking behaviours, and specifically non-adherence. This chapter focuses on practical considerations for transitioning young people from paediatric to adult services, with a particular focus on the risk factors associated with non-adherence and examples of interventions for managing it.
Topics: Hospitals; Humans; Liver Transplantation; Patient Compliance; Survival Analysis
PubMed: 33158474
DOI: 10.1016/j.bpg.2020.101687 -
Respiratory Medicine Sep 2020A sarcoidosis patient may be refractory to corticosteroid therapy. This may be because corticosteroids are ineffective in relieving the sarcoidosis patient's... (Review)
Review
A sarcoidosis patient may be refractory to corticosteroid therapy. This may be because corticosteroids are ineffective in relieving the sarcoidosis patient's symptoms/dysfunction or because the clinician has determined that the risks of corticosteroids outweigh their benefits. Interestingly, when corticosteroids truly fail to improve a sarcoidosis patient's condition, it is very rarely because of failure of the drug as an anti-granulomatous agent; rather, it is usually because the patient's symptoms were unrelated to active sarcoid granulomas. In this manuscript, we review the causes of corticosteroid refractory sarcoidosis. The clinician should consider these causes when confronted with a sarcoidosis patient who is either not responding to corticosteroids, developing corticosteroid side-effects, or is at significant risk of developing such side-effects. We believe that determining the cause of corticosteroid refractory sarcoidosis may aid the clinicians in optimizing the care of sarcoidosis patients and clinical researchers in appropriately stratifying patients for clinical trials.
Topics: Adrenal Cortex Hormones; Humans; Patient Compliance; Sarcoidosis, Pulmonary; Treatment Failure
PubMed: 32658838
DOI: 10.1016/j.rmed.2020.106081 -
Frontiers in Immunology 2023Chronic inflammatory diseases of the lung are some of the leading causes of mortality and significant morbidity worldwide. Despite the tremendous burden these conditions... (Review)
Review
Chronic inflammatory diseases of the lung are some of the leading causes of mortality and significant morbidity worldwide. Despite the tremendous burden these conditions put on global healthcare, treatment options for most of these diseases remain scarce. Inhaled corticosteroids and beta-adrenergic agonists, while effective for symptom control and widely available, are linked to severe and progressive side effects, affecting long-term patient compliance. Biologic drugs, in particular peptide inhibitors and monoclonal antibodies show promise as therapeutics for chronic pulmonary diseases. Peptide inhibitor-based treatments have already been proposed for a range of diseases, including infectious disease, cancers and even Alzheimer disease, while monoclonal antibodies have already been implemented as therapeutics for a range of conditions. Several biologic agents are currently being developed for the treatment of asthma, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis and pulmonary sarcoidosis. This article is a review of the biologics already employed in the treatment of chronic inflammatory pulmonary diseases and recent progress in the development of the most promising of those treatments, with particular focus on randomised clinical trial outcomes.
Topics: Humans; Biological Products; Administration, Inhalation; Pulmonary Disease, Chronic Obstructive; Chronic Disease; Lung; Antibodies, Monoclonal
PubMed: 37334374
DOI: 10.3389/fimmu.2023.1207641 -
Annals of Cardiac Anaesthesia 2021Incentive spirometer (IS) is a popular choice for chest physiotherapy. It is used to optimize preoperative respiratory status and prevent postoperative pulmonary...
Incentive spirometer (IS) is a popular choice for chest physiotherapy. It is used to optimize preoperative respiratory status and prevent postoperative pulmonary complications. However, the use of conventional forms of IS pose a challenging task in children due to the lack of cooperation, compliance, and submaximal effort on the part of pediatric patients. To tackle this problem, we describe an innovative and fascinating technique of spirometry. It employs a toy as a better acceptable incentive spirometry device in pediatric population. This toy has a mouthpiece and a long inflatable plastic strip at the other end. As the child blows into the mouthpiece, a captivating sound from the toy keeps buzzing progressively till the air is being blown during exhalation and is accompanied with inflation of the strip in an elongated fashion. Hence, this device incorporates the two best enjoyed incentives for children, namely, visual and audio to ensure patient compliance and participation.
Topics: Child; Humans; Lung; Motivation; Physical Therapy Modalities; Postoperative Complications; Respiratory Function Tests; Spirometry
PubMed: 33884984
DOI: 10.4103/aca.ACA_188_19 -
Respiratory Research Apr 2023Cellular senescence is a cell fate in response to diverse forms of age-related damage and stress that has been implicated in the pathogenesis of idiopathic pulmonary...
BACKGROUND
Cellular senescence is a cell fate in response to diverse forms of age-related damage and stress that has been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). The associations between circulating levels of candidate senescence biomarkers and disease outcomes have not been specifically studied in IPF. In this study we assessed the circulating levels of candidate senescence biomarkers in individuals affected by IPF and controls and evaluated their ability to predict disease outcomes.
METHODS
We measured the plasma concentrations of 32 proteins associated with senescence in Lung Tissue Research Consortium participants and studied their relationship with the diagnosis of IPF, parameters of pulmonary and physical function, health-related quality of life, mortality, and lung tissue expression of P16, a prototypical marker of cellular senescence. A machine learning approach was used to evaluate the ability of combinatorial biomarker signatures to predict disease outcomes.
RESULTS
The circulating levels of several senescence biomarkers were significantly elevated in persons affected by IPF compared to controls. A subset of biomarkers accurately classified participants as having or not having the disease and was significantly correlated with measures of pulmonary function, health-related quality of life and, to an extent, physical function. An exploratory analysis revealed senescence biomarkers were also associated with mortality in IPF participants. Finally, the plasma concentrations of several biomarkers were associated with their expression levels in lung tissue as well as the expression of P16.
CONCLUSIONS
Our results suggest that circulating levels of candidate senescence biomarkers are informative of disease status, pulmonary and physical function, and health-related quality of life. Additional studies are needed to validate the combinatorial biomarkers signatures that emerged using a machine learning approach.
Topics: Humans; Quality of Life; Idiopathic Pulmonary Fibrosis; Cellular Senescence; Lung; Biomarkers
PubMed: 37029417
DOI: 10.1186/s12931-023-02403-8