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Seminars in Fetal & Neonatal Medicine Dec 2023Drug delivery using a surfactant vehicle has the potential to prevent systemic side effects by delivering therapeutic agents directly to the respiratory system. The... (Review)
Review
Drug delivery using a surfactant vehicle has the potential to prevent systemic side effects by delivering therapeutic agents directly to the respiratory system. The inherent chemical properties of surfactant allows it to readily distribute throughout the respiratory system. Therapeutic agents delivered by surfactant can primarily confer additional benefits but have potential to improve surfactant function. It is critically important that additional agents do not interefere with the innate surface tension lowering function of surfactant. Systemic evaluation through benchtop, translational and human trials are required to translate this potential technique into clinical practice.
Topics: Humans; Infant, Newborn; Surface-Active Agents; Drug Carriers; Pulmonary Surfactants; Drug Delivery Systems; Lipoproteins; Respiratory Distress Syndrome, Newborn
PubMed: 38040583
DOI: 10.1016/j.siny.2023.101499 -
Nature Feb 2024An ideal vaccine both attenuates virus growth and disease in infected individuals and reduces the spread of infections in the population, thereby generating herd...
An ideal vaccine both attenuates virus growth and disease in infected individuals and reduces the spread of infections in the population, thereby generating herd immunity. Although this strategy has proved successful by generating humoral immunity to measles, yellow fever and polio, many respiratory viruses evolve to evade pre-existing antibodies. One approach for improving the breadth of antiviral immunity against escape variants is through the generation of memory T cells in the respiratory tract, which are positioned to respond rapidly to respiratory virus infections. However, it is unknown whether memory T cells alone can effectively surveil the respiratory tract to the extent that they eliminate or greatly reduce viral transmission following exposure of an individual to infection. Here we use a mouse model of natural parainfluenza virus transmission to quantify the extent to which memory CD8 T cells resident in the respiratory tract can provide herd immunity by reducing both the susceptibility of acquiring infection and the extent of transmission, even in the absence of virus-specific antibodies. We demonstrate that protection by resident memory CD8 T cells requires the antiviral cytokine interferon-γ (IFNγ) and leads to altered transcriptional programming of epithelial cells within the respiratory tract. These results suggest that tissue-resident CD8 T cells in the respiratory tract can have important roles in protecting the host against viral disease and limiting viral spread throughout the population.
Topics: Animals; Mice; CD8-Positive T-Lymphocytes; Disease Models, Animal; Epithelial Cells; Immunity, Herd; Immunologic Memory; Interferon-gamma; Memory T Cells; Paramyxoviridae; Paramyxoviridae Infections; Respiratory System; Transcription, Genetic; Humans
PubMed: 38086420
DOI: 10.1038/s41586-023-06937-1 -
JAMA Sep 2023The long-term effects of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
The long-term effects of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome remain to be definitively clarified.
OBJECTIVE
To examine the effect of MIST on death or neurodevelopmental disability (NDD) at 2 years' corrected age.
DESIGN, SETTING, AND PARTICIPANTS
Follow-up study of a randomized clinical trial with blinding of clinicians and outcome assessors conducted in 33 tertiary-level neonatal intensive care units in 11 countries. The trial included 486 infants with a gestational age of 25 to 28 weeks supported with continuous positive airway pressure (CPAP). Collection of follow-up data at 2 years' corrected age was completed on December 9, 2022.
INTERVENTIONS
Infants assigned to MIST (n = 242) received exogenous surfactant (200 mg/kg poractant alfa) via a thin catheter; those assigned to the control group (n = 244) received sham treatment.
MAIN OUTCOMES AND MEASURES
The key secondary outcome of death or moderate to severe NDD was assessed at 2 years' corrected age. Other secondary outcomes included components of this composite outcome, as well as hospitalizations for respiratory illness and parent-reported wheezing or breathing difficulty in the first 2 years.
RESULTS
Among the 486 infants randomized, 453 had follow-up data available (median gestation, 27.3 weeks; 228 females [50.3%]); data on the key secondary outcome were available in 434 infants. Death or NDD occurred in 78 infants (36.3%) in the MIST group and 79 (36.1%) in the control group (risk difference, 0% [95% CI, -7.6% to 7.7%]; relative risk [RR], 1.0 [95% CI, 0.81-1.24]); components of this outcome did not differ significantly between groups. Secondary respiratory outcomes favored the MIST group. Hospitalization with respiratory illness occurred in 49 infants (25.1%) in the MIST group vs 78 (38.2%) in the control group (RR, 0.66 [95% CI, 0.54-0.81]) and parent-reported wheezing or breathing difficulty in 73 (40.6%) vs 104 (53.6%), respectively (RR, 0.76 [95% CI, 0.63-0.90]).
CONCLUSIONS AND RELEVANCE
In this follow-up study of a randomized clinical trial of preterm infants with respiratory distress syndrome supported with CPAP, MIST compared with sham treatment did not reduce the incidence of death or NDD by 2 years of age. However, infants who received MIST had lower rates of adverse respiratory outcomes during their first 2 years of life.
TRIAL REGISTRATION
anzctr.org.au Identifier: ACTRN12611000916943.
Topics: Female; Humans; Infant; Infant, Newborn; Dyspnea; Follow-Up Studies; Infant, Premature; Lipoproteins; Pulmonary Surfactants; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Respiratory Sounds; Surface-Active Agents; Catheterization; Minimally Invasive Surgical Procedures; Continuous Positive Airway Pressure; Male; Child, Preschool
PubMed: 37695601
DOI: 10.1001/jama.2023.15694 -
Current Opinion in Critical Care Jun 2024This review explores lung recruitment monitoring, covering techniques, challenges, and future perspectives. (Review)
Review
PURPOSE OF REVIEW
This review explores lung recruitment monitoring, covering techniques, challenges, and future perspectives.
RECENT FINDINGS
Various methodologies, including respiratory system mechanics evaluation, arterial bold gases (ABGs) analysis, lung imaging, and esophageal pressure (Pes) measurement are employed to assess lung recruitment. In support to ABGs analysis, the assessment of respiratory mechanics with hysteresis and recruitment-to-inflation ratio has the potential to evaluate lung recruitment and enhance mechanical ventilation setting. Lung imaging tools, such as computed tomography scanning, lung ultrasound, and electrical impedance tomography (EIT) confirm their utility in following lung recruitment with the advantage of radiation-free and repeatable application at the bedside for sonography and EIT. Pes enables the assessment of dorsal lung tendency to collapse through end-expiratory transpulmonary pressure. Despite their value, these methodologies may require an elevated expertise in their application and data interpretation. However, the information obtained by these methods may be conveyed to build machine learning and artificial intelligence algorithms aimed at improving the clinical decision-making process.
SUMMARY
Monitoring lung recruitment is a crucial component of managing patients with severe lung conditions, within the framework of a personalized ventilatory strategy. Although challenges persist, emerging technologies offer promise for a personalized approach to care in the future.
Topics: Humans; Monitoring, Physiologic; Respiration, Artificial; Respiratory Mechanics; Lung; Electric Impedance; Tomography, X-Ray Computed; Blood Gas Analysis; Ultrasonography
PubMed: 38690956
DOI: 10.1097/MCC.0000000000001157 -
Allergy Feb 2024Asthma remission has emerged as a potential treatment goal. This study evaluated the effectiveness of two biologics (mepolizumab/omalizumab) in achieving asthma... (Observational Study)
Observational Study
BACKGROUND
Asthma remission has emerged as a potential treatment goal. This study evaluated the effectiveness of two biologics (mepolizumab/omalizumab) in achieving asthma remission.
METHODS
This observational study included 453 severe asthma patients (41% male; mean age ± SD 55.7 ± 14.7 years) from two real-world drug registries: the Australian Mepolizumab Registry and the Australian Xolair Registry. The composite outcome clinical remission was defined as zero exacerbations and zero oral corticosteroids during the previous 6 months assessed at 12 months and 5-item Asthma Control Questionnaire (ACQ-5) ≤1 at 12 months. We also assessed clinical remission plus optimization (post-bronchodilator FEV1 ≥80%) or stabilization (post-bronchodilator FEV1 not greater than 5% decline from baseline) of lung function at 12 months. Sensitivity analyses explored various cut-offs of ACQ-5/FEV1 scores. The predictors of clinical remission were identified.
RESULTS
29.3% (73/249) of AMR and 22.8% (37/162) of AXR cohort met the criteria for clinical remission. When lung function criteria were added, the remission rates were reduced to 25.2% and 19.1%, respectively. Sensitivity analyses identified that the remission rate ranged between 18.1% and 34.9% in the AMR cohort and 10.6% and 27.2% in the AXR cohort. Better lung function, lower body mass index, mild disease and absence of comorbidities such as obesity, depression and osteoporosis predicted the odds of achieving clinical remission.
CONCLUSION
Biologic treatment with mepolizumab or omalizumab for severe asthma-induced asthma remission in a subgroup of patients. Remission on treatment may be an achievable treatment target and future studies should consider remission as an outcome measure.
Topics: Humans; Male; Female; Omalizumab; Anti-Asthmatic Agents; Bronchodilator Agents; Australia; Asthma; Biological Products; Antibodies, Monoclonal, Humanized
PubMed: 37632144
DOI: 10.1111/all.15867 -
Actas Dermo-sifiliograficas 2023
Topics: Humans; Omalizumab; Antibodies, Monoclonal, Humanized; Fatty Liver; Treatment Outcome; Anti-Asthmatic Agents
PubMed: 37301476
DOI: 10.1016/j.ad.2021.10.029 -
Actas Dermo-sifiliograficas 2023
Topics: Humans; Omalizumab; Antibodies, Monoclonal, Humanized; Fatty Liver; Treatment Outcome; Anti-Asthmatic Agents
PubMed: 36243139
DOI: 10.1016/j.ad.2021.10.023 -
Trends in Microbiology Sep 2023A thriving multi-kingdom microbial ecosystem inhabits the respiratory tract: the respiratory tract microbiome (RTM). In recent years, the contribution of the RTM to... (Review)
Review
A thriving multi-kingdom microbial ecosystem inhabits the respiratory tract: the respiratory tract microbiome (RTM). In recent years, the contribution of the RTM to human health has become a crucial research aspect. However, research into the key ecological processes, such as robustness, resilience, and microbial interaction networks, has only recently started. This review leans on an ecological framework to interpret the human RTM and determine how the ecosystem functions and assembles. Specifically, the review illustrates the ecological RTM models and discusses microbiome establishment, community structure, diversity stability, and critical microbial interactions. Lastly, the review outlines the RTM responses to ecological disturbances, as well as the promising approaches for restoring ecological balance.
Topics: Humans; Ecosystem; Ecology; Microbiota; Microbial Interactions; Models, Theoretical; Respiratory System
PubMed: 37173205
DOI: 10.1016/j.tim.2023.04.006 -
Frontiers in Immunology 2023The respiratory system exposed to microorganisms continuously, and the pathogenicity of these microbes not only contingent on their virulence factors, but also the... (Review)
Review
The respiratory system exposed to microorganisms continuously, and the pathogenicity of these microbes not only contingent on their virulence factors, but also the host's immunity. A multifaceted innate immune mechanism exists in the respiratory tract to cope with microbial infections and to decrease tissue damage. The key cell types of the innate immune response are macrophages, neutrophils, dendritic cells, epithelial cells, and endothelial cells. Both the myeloid and structural cells of the respiratory system sense invading microorganisms through binding or activation of pathogen-associated molecular patterns (PAMPs) to pattern recognition receptors (PRRs), including Toll-like receptors (TLRs) and NOD-like receptors (NLRs). The recognition of microbes and subsequent activation of PRRs triggers a signaling cascade that leads to the activation of transcription factors, induction of cytokines/5chemokines, upregulation of cell adhesion molecules, recruitment of immune cells, and subsequent microbe clearance. Since numerous microbes resist antimicrobial agents and escape innate immune defenses, in the future, a comprehensive strategy consisting of newer vaccines and novel antimicrobials will be required to control microbial infections. This review summarizes key findings in the area of innate immune defense in response to acute microbial infections in the lung. Understanding the innate immune mechanisms is critical to design host-targeted immunotherapies to mitigate excessive inflammation while controlling microbial burden in tissues following lung infection.
Topics: Humans; NLR Proteins; Endothelial Cells; Pneumonia; Toll-Like Receptors; Pathogen-Associated Molecular Pattern Molecules; Lung
PubMed: 37662905
DOI: 10.3389/fimmu.2023.1249098 -
MMW Fortschritte Der Medizin May 2024
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Asthma; Germany; National Health Programs; Anti-Asthmatic Agents; Drug Costs; Bronchodilator Agents
PubMed: 38693401
DOI: 10.1007/s15006-024-3900-9