-
The International Journal of... Aug 2023Literature Highlights is a digest of notable papers recently published in the leading respiratory journals. Coverage includes shorter regimen for TB treatment; mapping...
Literature Highlights is a digest of notable papers recently published in the leading respiratory journals. Coverage includes shorter regimen for TB treatment; mapping the geographical evolution of TB incidence; diagnostic packages for active case finding for TB; TB burden estimation in settings with high levels of HIV; and digital approaches for TB treatment adherence.
Topics: Humans; Tuberculosis; Incidence; Antitubercular Agents; Medication Adherence; HIV Infections
PubMed: 37491752
DOI: 10.5588/ijtld.23.9908 -
Frontiers in Physiology 2023The primary impact of ventilation and ventilatory efforts on left ventricular (LV) function in left ventricular dysfunction relate to how changes in intrathoracic... (Review)
Review
The primary impact of ventilation and ventilatory efforts on left ventricular (LV) function in left ventricular dysfunction relate to how changes in intrathoracic pressure (ITP) alter the pressure gradients for venous return into the chest and LV ejection out of the chest. Spontaneous inspiratory efforts by decreasing ITP increase both of these pressure gradients increasing venous blood flow and impeding LV ejection resulting in increased intrathoracic blood volume. In severe heart failure states when lung compliance is reduced, or airway resistance is increased these negative swings in ITP can be exacerbated leading to LV failure and acute cardiogenic pulmonary edema. By merely reversing these negative swings in ITP by the use of non-invasive continuous positive airway pressure (CPAP), these profoundly detrimental forces can be immediately reversed, and cardiovascular stability can be restored in moments. This forms the clinical rationale for the immediate use of CPAP for the treatment of acute cardiogenic pulmonary edema. Increasing ITP during positive pressure ventilation decreases the pressure gradients for venous return and LV ejection decreasing intrathoracic blood volume. In a hypovolemic patient even with LV dysfunction this can result in hypotension due to inadequate LV preload. Minor increases in ITP as occur using pressure-limited positive-pressure ventilation primarily reverse the increased LV afterload of negative swings in ITP and if fluid overload was already present, minimally alter cardiac output. The effect of changes in lung volume on LV function are related primarily to its effects on right ventricular (RV) function through changes in pulmonary vascular resistance and overdistention (hyperinflation). In acute lung injury with alveolar collapse, positive pressure ventilation may reduce pulmonary vascular resistance if alveolar recruitment predominates. Hyperinflation, however, impedes diastolic filling while simultaneously increasing pulmonary vascular resistance. Thus, increasing lung volume can reduce RV afterload by reversing hypoxic pulmonary vasoconstriction or increase afterload by overdistention. Hyperinflation can also impede RV filling. All of these processes can be readily identified at the bedside using echocardiography.
PubMed: 37614756
DOI: 10.3389/fphys.2023.1237741 -
Critical Care (London, England) Aug 2023The effects of awake prone position on the breathing pattern of hypoxemic patients need to be better understood. We conducted a crossover trial to assess the... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The effects of awake prone position on the breathing pattern of hypoxemic patients need to be better understood. We conducted a crossover trial to assess the physiological effects of awake prone position in patients with acute hypoxemic respiratory failure.
METHODS
Fifteen patients with acute hypoxemic respiratory failure and PaO/FiO < 200 mmHg underwent high-flow nasal oxygen for 1 h in supine position and 2 h in prone position, followed by a final 1-h supine phase. At the end of each study phase, the following parameters were measured: arterial blood gases, inspiratory effort (ΔP), transpulmonary driving pressure (ΔP), respiratory rate and esophageal pressure simplified pressure-time product per minute (sPTP) by esophageal manometry, tidal volume (V), end-expiratory lung impedance (EELI), lung compliance, airway resistance, time constant, dynamic strain (V/EELI) and pendelluft extent through electrical impedance tomography.
RESULTS
Compared to supine position, prone position increased PaO/FiO (median [Interquartile range] 104 mmHg [76-129] vs. 74 [69-93], p < 0.001), reduced respiratory rate (24 breaths/min [22-26] vs. 27 [26-30], p = 0.05) and increased ΔP (12 cmHO [11-13] vs. 9 [8-12], p = 0.04) with similar sPTP (131 [75-154] cmHO s min vs. 105 [81-129], p > 0.99) and ΔP (9 [7-11] cmHO vs. 8 [5-9], p = 0.17). Airway resistance and time constant were higher in prone vs. supine position (9 cmHO s arbitrary units [4-11] vs. 6 [4-9], p = 0.05; 0.53 s [0.32-61] vs. 0.40 [0.37-0.44], p = 0.03). Prone position increased EELI (3887 arbitrary units [3414-8547] vs. 1456 [959-2420], p = 0.002) and promoted V distribution towards dorsal lung regions without affecting V size and lung compliance: this generated lower dynamic strain (0.21 [0.16-0.24] vs. 0.38 [0.30-0.49], p = 0.004). The magnitude of pendelluft phenomenon was not different between study phases (55% [7-57] of V in prone vs. 31% [14-55] in supine position, p > 0.99).
CONCLUSIONS
Prone position improves oxygenation, increases EELI and promotes V distribution towards dependent lung regions without affecting V size, ΔP, lung compliance and pendelluft magnitude. Prone position reduces respiratory rate and increases ΔP because of positional increases in airway resistance and prolonged expiratory time. Because high ΔP is the main mechanistic determinant of self-inflicted lung injury, caution may be needed in using awake prone position in patients exhibiting intense ΔP. Clinical trail registeration: The study was registered on clinicaltrials.gov (NCT03095300) on March 29, 2017.
Topics: Humans; Prone Position; Respiration; Respiratory Insufficiency; Tidal Volume; Wakefulness; Cross-Over Studies
PubMed: 37592288
DOI: 10.1186/s13054-023-04600-9 -
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 -
Clinical and Experimental Hypertension... Dec 2023To explore the correlation between pulmonary vascular performance and hemodynamics in patients with pulmonary arterial hypertension (PAH), using right heart...
OBJECTIVE
To explore the correlation between pulmonary vascular performance and hemodynamics in patients with pulmonary arterial hypertension (PAH), using right heart catheterization (RHC) and intravascular ultrasound (IVUS).
METHOD
A total of 60 patients underwent RHC and IVUS examinations. Of these, 27 patients were diagnosed with PAH associated with connective tissue diseases (PAH-CTD group), 18 patients were diagnosed with other types of PAH (other-types-PAH group), and 15 patients were without PAH (control group). The hemodynamics and morphological parameters of pulmonary vessels in PAH patients were assessed using RHC and IVUS.
RESULTS
There were statistically significant differences in right atrial pressure (RAP), pulmonary artery systolic pressure (sPAP), pulmonary artery diastolic pressure (dPAP), mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) values between the PAH-CTD group, other-types-PAH group, and the control group (P < .05). No statistically significant difference was noticed in pulmonary artery wedge pressure (PAWP) and cardiac output (CO) values between these three groups (P > .05). The mean wall thickness (MWT), wall thickness percentage (WTP), pulmonary vascular compliance, dilation, elasticity modulus, stiffness index β, and other indicators were significantly different between these three groups (P < .05). Pairwise comparison showed that the average levels of pulmonary vascular compliance and dilation in PAH-CTD group and other-types-PAH group were lower than those in control group, while the average levels of elastic modulus and stiffness index β were higher than those in control group.
CONCLUSION
Pulmonary vascular performance deteriorates in PAH patients, and the performance is better in PAH-CTD patients than in other types of PAH.
Topics: Humans; Pulmonary Arterial Hypertension; Hypertension, Pulmonary; Hemodynamics; Pulmonary Artery; Lung
PubMed: 36906960
DOI: 10.1080/10641963.2023.2185253 -
Pulmonary Pharmacology & Therapeutics Dec 2023Tyvaso DPI is a drug-device combination therapy comprised of a small, portable, reusable, breath-powered, dry powder inhaler (DPI) for the delivery of treprostinil. It... (Review)
Review
Tyvaso DPI is a drug-device combination therapy comprised of a small, portable, reusable, breath-powered, dry powder inhaler (DPI) for the delivery of treprostinil. It is approved for the treatment of pulmonary arterial hypertension and pulmonary hypertension associated with interstitial lung disease. Tyvaso DPI utilizes single-use prefilled cartridges to ensure proper dosing. Unlike nebulizer devices, administration of Tyvaso DPI is passive and does not require coordination with the device. The low-flow rate design results in targeted delivery to the peripheral lungs due to minimal drug loss from impaction in the oropharynx. The inert fumaryl diketopiperazine (FDKP) excipient forms microparticles that carry treprostinil into the airways, with a high fraction of the particles in the respirable range. In a clinical study in patients with pulmonary arterial hypertension, Tyvaso DPI had similar exposure and pharmacokinetics, low incidence of adverse events, and high patient satisfaction compared with nebulized treprostinil solution. Tyvaso DPI may be considered as a first prostacyclin agent or for those that do not tolerate other prostacyclin formulations, patients with pulmonary comorbidities, patients with mixed Group 1 and Group 3 pulmonary hypertension, or those that prefer an active lifestyle and need a portable, non-invasive treatment. Tyvaso DPI is a patient-preferred, maintenance-free, safe delivery option that may improve patient compliance and adherence.
Topics: Humans; Dry Powder Inhalers; Hypertension, Pulmonary; Pharmaceutical Preparations; Pulmonary Arterial Hypertension; Epoprostenol; Administration, Inhalation; Familial Primary Pulmonary Hypertension
PubMed: 37967762
DOI: 10.1016/j.pupt.2023.102266 -
Diagnostics (Basel, Switzerland) Sep 2023Acute respiratory distress syndrome (ARDS) is a major cause of hypoxemic respiratory failure in adults, leading to the requirement for mechanical ventilation and poorer... (Review)
Review
Acute respiratory distress syndrome (ARDS) is a major cause of hypoxemic respiratory failure in adults, leading to the requirement for mechanical ventilation and poorer outcomes. Dysregulated surfactant metabolism and function are characteristic of ARDS. A combination of alveolar epithelial damage leading to altered surfactant synthesis, secretion, and breakdown with increased functional inhibition from overt alveolar inflammation contributes to the clinical features of poor alveolar compliance and alveolar collapse. Quantitative and qualitative alterations in the bronchoalveolar lavage and tracheal aspirate surfactant composition contribute to ARDS pathogenesis. Compared to neonatal respiratory distress syndrome (nRDS), replacement studies of exogenous surfactants in adult ARDS suggest no survival benefit. However, these studies are limited by disease heterogeneity, variations in surfactant preparations, doses, and delivery methods. More importantly, the lack of mechanistic understanding of the exact reasons for dysregulated surfactant remains a significant issue. Moreover, studies suggest an extremely short half-life of replaced surfactant, implying increased catabolism. Refining surfactant preparations and delivery methods with additional co-interventions to counteract surfactant inhibition and degradation has the potential to enhance the biophysical characteristics of surfactant in vivo.
PubMed: 37761330
DOI: 10.3390/diagnostics13182964 -
BMJ Open Respiratory Research Aug 2023IntroductionThere is an unmet need for new treatments for idiopathic pulmonary fibrosis (IPF). The oral preferential phosphodiesterase 4B inhibitor, BI 1015550,... (Randomized Controlled Trial)
Randomized Controlled Trial
UNLABELLED
IntroductionThere is an unmet need for new treatments for idiopathic pulmonary fibrosis (IPF). The oral preferential phosphodiesterase 4B inhibitor, BI 1015550, prevented a decline in forced vital capacity (FVC) in a phase II study in patients with IPF. This study design describes the subsequent pivotal phase III study of BI 1015550 in patients with IPF (FIBRONEER-IPF).
METHODS AND ANALYSIS
In this placebo-controlled, double-blind, phase III trial, patients are being randomised in a 1:1:1 ratio to receive 9 mg or 18 mg of BI 1015550 or placebo two times per day over at least 52 weeks, stratified by use of background antifibrotics (nintedanib/pirfenidone vs neither). The primary endpoint is the absolute change in FVC at week 52. The key secondary endpoint is a composite of time to first acute IPF exacerbation, hospitalisation due to respiratory cause or death over the duration of the trial.
ETHICS AND DISSEMINATION
The trial is being carried out in compliance with the ethical principles of the Declaration of Helsinki, in accordance with the International Council on Harmonisation Guideline for Good Clinical Practice and other local ethics committees. The results of the study will be disseminated at scientific congresses and in peer-reviewed publications.
TRIAL REGISTRATION NUMBER
NCT05321069.
Topics: Humans; Double-Blind Method; Hospitalization; Idiopathic Pulmonary Fibrosis; Patients
PubMed: 37597969
DOI: 10.1136/bmjresp-2022-001563