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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 -
Thorax Mar 2020Chronic non-invasive ventilation (NIV) has become evidence-based care for stable hypercapnic COPD patients. While the number of patients increases, home initiation of... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Chronic non-invasive ventilation (NIV) has become evidence-based care for stable hypercapnic COPD patients. While the number of patients increases, home initiation of NIV would greatly alleviate the healthcare burden. We hypothesise that home initiation of NIV with the use of telemedicine in stable hypercapnic COPD is non-inferior to in-hospital NIV initiation.
METHODS
Sixty-seven stable hypercapnic COPD patients were randomised to initiation of NIV in the hospital or at home using telemedicine. Primary outcome was daytime arterial carbon dioxide pressure (PaCO) reduction after 6 months NIV, with a non-inferiority margin of 0.4 kPa. Secondary outcomes were health-related quality of life (HRQoL) and costs.
RESULTS
Home NIV initiation was non-inferior to in-hospital initiation (adjusted mean difference in PaCO change home vs in-hospital: 0.04 kPa (95% CI -0.31 to 0.38 kPa), with both groups showing a PaCO reduction at 6 months compared with baseline (home: from 7.3±0.9 to 6.4±0.8 kPa (p<0.001) and in-hospital: from 7.4±1.0 to 6.4±0.6 kPa (p<0.001)). In both groups, HRQoL improved without a difference in change between groups (Clinical COPD Questionnaire total score-adjusted mean difference 0.0 (95% CI -0.4 to 0.5)). Furthermore, home NIV initiation was significantly cheaper (home: median €3768 (IQR €3546-€4163) vs in-hospital: median €8537 (IQR €7540-€9175); p<0.001).
DISCUSSION
This is the first study showing that home initiation of chronic NIV in stable hypercapnic COPD patients, with the use of telemedicine, is non-inferior to in-hospital initiation, safe and reduces costs by over 50%.
TRIAL REGISTRATION NUMBER
NCT02652559.
Topics: Aged; Carbon Dioxide; Chronic Disease; Female; Forced Expiratory Volume; Hospitalization; Hospitals; Humans; Hypercapnia; Male; Middle Aged; Noninvasive Ventilation; Partial Pressure; Patient Compliance; Pulmonary Disease, Chronic Obstructive; Pulmonary Gas Exchange; Quality of Life; Respiratory Insufficiency; Telemedicine; Vital Capacity
PubMed: 31484786
DOI: 10.1136/thoraxjnl-2019-213303 -
Lung Aug 2022Few international studies have investigated factors affecting domiciliary non-invasive ventilation (D-NIV) compliance, and data from the UK are limited. We assessed...
Few international studies have investigated factors affecting domiciliary non-invasive ventilation (D-NIV) compliance, and data from the UK are limited. We assessed compliance (defined as ≥ 4 h/night for at least 70% of the time) in a retrospective UK population study, at three time points (0-1 month, 3-4 months and 11-12 months), for all patients commenced on D-NIV over a 5-year period. A total of 359 patients were included. Non-compliant vs. compliant patients were significantly younger (median age 64 (IQR 52-72) vs. 67 (58-75) years, p = 0.032) and more likely to have schizophrenia, consistent at both 3-4 months (5% vs. 1%, p = 0.033) and 11-12 months (5% vs. 2%, p = 0.049). Repeated measures ANOVA demonstrated that the minutes [median (IQR)] of D-NIV used significantly increased at the three time points (0-1 month, 3-4 months and 11-12 months) for patients with hypertension [310 (147.5-431) vs. 341 (89-450) vs. 378 (224.5-477.5), p = 0.003]; diabetes [296.5 (132.5-417.5) vs. 342.5 (94.5-438.5) vs. 382 (247.5-476.25), p = 0.002] and heart failure [293 (177-403) vs. 326 (123-398) vs. 365 (212-493), p = 0.04]. In conclusion, younger and comorbid schizophrenic patients have lower D-NIV compliance rates, and our data suggest that persistence with D-NIV over a year may improve overall use.
Topics: Humans; Middle Aged; Noninvasive Ventilation; Patient Compliance; Respiration, Artificial; Respiratory Insufficiency; Retrospective Studies
PubMed: 35871430
DOI: 10.1007/s00408-022-00557-8 -
The European Respiratory Journal Aug 2021https://bit.ly/3e2GajO
https://bit.ly/3e2GajO
Topics: Bronchi; COVID-19; Humans; Pulmonary Circulation; Respiratory Insufficiency; SARS-CoV-2
PubMed: 33863743
DOI: 10.1183/13993003.04397-2020 -
Journal of Cellular and Molecular... Apr 2022Nitrogen mustard (NM) is an alkylating vesicant that causes severe pulmonary injury. Currently, there are no effective means to counteract vesicant-induced lung injury....
Nitrogen mustard (NM) is an alkylating vesicant that causes severe pulmonary injury. Currently, there are no effective means to counteract vesicant-induced lung injury. MG53 is a vital component of cell membrane repair and lung protection. Here, we show that mice with ablation of MG53 are more susceptible to NM-induced lung injury than the wild-type mice. Treatment of wild-type mice with exogenous recombinant human MG53 (rhMG53) protein ameliorates NM-induced lung injury by restoring arterial blood oxygen level, by improving dynamic lung compliance and by reducing airway resistance. Exposure of lung epithelial and endothelial cells to NM leads to intracellular oxidative stress that compromises the intrinsic cell membrane repair function of MG53. Exogenous rhMG53 protein applied to the culture medium protects lung epithelial and endothelial cells from NM-induced membrane injury and oxidative stress, and enhances survival of the cells. Additionally, we show that loss of MG53 leads to increased vulnerability of macrophages to vesicant-induced cell death. Overall, these findings support the therapeutic potential of rhMG53 to counteract vesicant-induced lung injury.
Topics: Acute Lung Injury; Animals; Endothelial Cells; Lung; Mechlorethamine; Membrane Proteins; Mice; Recombinant Proteins
PubMed: 35199443
DOI: 10.1111/jcmm.16917 -
Journal of Applied Physiology... Aug 2021Obesity alters chest wall mechanics, reduces lung volumes, and increases airway resistance. In addition, the luminal area of the larger conducting airways is smaller in...
Obesity alters chest wall mechanics, reduces lung volumes, and increases airway resistance. In addition, the luminal area of the larger conducting airways is smaller in women than in men when matched for lung size. We examined whether differences in pulmonary mechanics with obesity and sex were associated with the dysanapsis ratio (DR), an estimate of airway size when the expiratory flow is maximal, in men and women with and without obesity. In addition, we examined the ability to estimate DR using predicted versus measured static recoil pressure at 50% forced vital capacity (FVC; Pst). Participants completed pulmonary function testing and measurements of pulmonary mechanics. Flow, volume, and transpulmonary pressure were recorded while completing forced vital capacity (FVC) maneuvers in a body plethysmograph. Static compliance curves were collected using the occlusion technique. DR was calculated using measured values of forced midexpiratory flow and Pst. DR was also calculated using Pst predicted from previously reported data. There was no significant group (lean vs. obese) by sex interaction or main effect of group on DR. However, women displayed significantly larger DR compared with men. Predicted Pst was significantly greater than measured Pst. DR calculated from measured Pst was significantly greater than when using predicted Pst. In conclusion, although obesity does not appear to alter airway size, women may have larger airways compared with men when midexpiratory flow is maximal. In addition, DR estimated using predicted Pst should be used with caution. It is unclear whether obesity in combination with sex influences the dysanapsis ratio (DR). These data indicate that DR is unaltered in adults with obesity and is greater in women than in men but similar between sexes when matched for lung volume. We also report a significant difference between predicted and measured static recoil pressure. Thus, we caution against predicting static recoil pressure in the calculation of DR.
Topics: Adult; Airway Resistance; Female; Forced Expiratory Volume; Humans; Lung; Lung Volume Measurements; Male; Obesity; Vital Capacity
PubMed: 34166096
DOI: 10.1152/japplphysiol.00133.2021 -
Journal of Mathematical Biology Oct 2022All schoolchildren know how often they breathe, but even experts don't know exactly why. The aim of this publication is to develop a model of the resting spontaneous...
All schoolchildren know how often they breathe, but even experts don't know exactly why. The aim of this publication is to develop a model of the resting spontaneous breathing rate using physiological, physical and mathematical methods with the aid of the principle that evolution pushes physiology in a direction that is as economical as possible. The respiratory rate then follows from an equation with the parameters [Formula: see text]-production rate of the organism, resistance, static compliance and dead space of the lungs, the inspiration duration: expiration duration - ratio and the end-expiratory [Formula: see text] fraction. The derivation requires exclusively secondary school mathematics. Using the example of an adult human or a newborn child, data from the literature then result in normal values for their breathing rate at rest. The reason for the higher respiratory rate of a newborn human compared to an adult is the relatively high [Formula: see text]-production rate together with the comparatively low compliance of the lungs. A side result is the fact that the common alveolar pressure throughout the lungs and the common time constant is a consequence of the economical principle as well. Since the above parameters are not human-specific, there is no reason to assume that the above equation could not also be applicable to many animals breathing through lungs within a thorax, especially mammals. Not only physiology and biology, but also medicine, could benefit: Applicability is being discussed in pulmonary function diagnostics, including pathophysiology. However, the present publication only claims to be a theoretical concept of the spontaneous quiet breathing rate. In the absence of comparable animal data, this publication is intended to encourage further scientific tests.
Topics: Humans; Adult; Animals; Infant, Newborn; Child; Respiratory Rate; Lung; Mammals
PubMed: 36282355
DOI: 10.1007/s00285-022-01790-8 -
Nature Mar 2024Airway integrity must be continuously maintained throughout life. Sensory neurons guard against airway obstruction and, on a moment-by-moment basis, enact vital reflexes...
Airway integrity must be continuously maintained throughout life. Sensory neurons guard against airway obstruction and, on a moment-by-moment basis, enact vital reflexes to maintain respiratory function. Decreased lung capacity is common and life-threatening across many respiratory diseases, and lung collapse can be acutely evoked by chest wall trauma, pneumothorax or airway compression. Here we characterize a neuronal reflex of the vagus nerve evoked by airway closure that leads to gasping. In vivo vagal ganglion imaging revealed dedicated sensory neurons that detect airway compression but not airway stretch. Vagal neurons expressing PVALB mediate airway closure responses and innervate clusters of lung epithelial cells called neuroepithelial bodies (NEBs). Stimulating NEBs or vagal PVALB neurons evoked gasping in the absence of airway threats, whereas ablating NEBs or vagal PVALB neurons eliminated gasping in response to airway closure. Single-cell RNA sequencing revealed that NEBs uniformly express the mechanoreceptor PIEZO2, and targeted knockout of Piezo2 in NEBs eliminated responses to airway closure. NEBs were dispensable for the Hering-Breuer inspiratory reflex, which indicated that discrete terminal structures detect airway closure and inflation. Similar to the involvement of Merkel cells in touch sensation, NEBs are PIEZO2-expressing epithelial cells and, moreover, are crucial for an aspect of lung mechanosensation. These findings expand our understanding of neuronal diversity in the airways and reveal a dedicated vagal pathway that detects airway closure to help preserve respiratory function.
Topics: Animals; Female; Male; Mice; Epithelial Cells; Lung; Mechanoreceptors; Parvalbumins; Reflex; Respiration; Sensory Receptor Cells; Vagus Nerve; Lung Compliance; Respiratory Mechanics
PubMed: 38448588
DOI: 10.1038/s41586-024-07144-2